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Erdogan B, Usturalı Keskin FE, Özcan E, Küçükarda A, Güren AK, Köstek O, Hacioglu BM, Kodaz H. Assessment of new pathological markers in early stage colon cancer: Insights and limitations. World J Gastrointest Oncol 2025; 17:101325. [DOI: 10.4251/wjgo.v17.i3.101325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/09/2024] [Accepted: 12/12/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage, presence of perineural invasion, lymphovascular invasion, poorly differentiated tumor histology, inadequate lymph node sampling (fewer than 12 lymph nodes), and evidence of tumor perforation or obstruction. Tumor-stroma ratio, tumor infiltrating lymphocytes (TIL), Crohn-like reaction (CLR), desmoid reaction, poorly differentiated clusters (PDC) are new pathological markers that are being studied.
AIM To examine the relationship between new pathological markers and defined high risk factors, in early stage colorectal cancer.
METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital, Department of Medical Oncology. We divided those with and without high-risk factors into two groups. We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.
RESULTS There was no statistically significant correlation between presence of TIL, presence of PDC, presence of tumor budding, presence of CLR, presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC (P = 0.82, P = 0.51, P = 0.77, P = 0.37, P = 0.83, respectively). In addition, no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups (P = 0.80). We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage (P = 0.001, P = 0.001, respectively). It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.
CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups. When we examined the relationship between new and old pathological markers, only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.
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Affiliation(s)
- Bulent Erdogan
- Department of Medical Oncology, Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22000, Türkiye
| | | | - Erkan Özcan
- Division of Medical Oncology, Trakya University School of Medicine, Edirne 22000, Türkiye
| | - Ahmet Küçükarda
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22000, Türkiye
| | - Ali Kaan Güren
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Marmara University, Istanbul 34000, Türkiye
| | - Osman Köstek
- Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul 34000, Türkiye
| | - Bekir Muhammet Hacioglu
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22000, Türkiye
| | - Hilmi Kodaz
- Department of Medical Oncology, Acibadem Eskisehir Hospital, Eskisehir 26130, Türkiye
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Romero-Zoghbi SE, Krumina E, López-Campos F, Couñago F. Current and future perspectives in the management and treatment of colorectal cancer. World J Clin Oncol 2025; 16:100807. [DOI: 10.5306/wjco.v16.i2.100807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/30/2024] [Accepted: 10/23/2024] [Indexed: 12/11/2024] Open
Abstract
In this editorial, we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology. The article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer (CRC), one of the leading causes of cancer-related morbidity and mortality worldwide. The article analyzed the therapeutic modalities and their sequencing, focusing on total neoadjuvant therapy for locally advanced rectal cancer. It highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair, addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic CRC. Innovations in surgical techniques, advanced radiotherapy, and systemic agents targeting specific mutational profiles are also discussed, reflecting on how they revolutionized clinical management. Circulating tumor DNA has emerged as a promising tool for detecting minimal residual disease, prognosis, and therapeutic monitoring, solidifying its role in precision oncology. This review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.
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Affiliation(s)
| | - Evita Krumina
- Department of Radiation Oncology, GenesisCare Guadalajara, Guadalajara 19004, Spain
| | - Fernando López-Campos
- Department of Radiation Oncology, Hospital Universitario Ramón Y Cajal, Madrid 28034, Spain
- Department of Radiation Oncology, GenesisCare-Hospital Universitario Vithas Madrid La Milagrosa, Madrid 28010, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, GenesisCare-San Francisco de Asís University Hospital, Madrid 28002, Spain
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Yan X, Wang Y, Ma A, Li H. The role of health economic evidence in clinical practice guidelines for colorectal cancer: a comparative analysis across countries. J Comp Eff Res 2025:e240226. [PMID: 39969114 DOI: 10.57264/cer-2024-0226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2025] Open
Abstract
Aim: Colorectal cancer (CRC) is among the most prevalent malignancies globally and causes massive resource consumption and economic burden. Health economic evidence (HEE) has been used in clinical practice guidelines (CPGs) for cancer to facilitate the rational allocation of health resources. However, in certain guideline development organizations, HEE is not yet utilized as a formal decision-making criterion. This study aimed to compare the discrepancies in the utilization of health economics as evidence in CRC CPGs across different countries and review specific features of economic evidence concerning the guidelines' applicability. Materials & methods: A systematic review was conducted using databases including Medline, Embase, CNKI, WanFang, and other guidelines databases to identify CPGs for CRC published in English or Chinese from January 2017 to September 2023. Data on the incorporation and application of HEE were extracted, and the method and quality of cost-effectiveness analysis (CEA) studies were evaluated. Descriptive analyses were used to summarize the results. Results: Out of 53 CPGs from 14 countries, most originated from the USA (n = 17 of 53 [32%]) and Canada (n = 9 of 53 [17%]). Sixty-eight percent (36/53) considered cost justification, and 57% (30/53) incorporated health economics studies as evidence. The included HEE cited in CPGs ranged from 1990 to 2021 and were not aligned with the countries in which the guidelines were issued. Among these CEA studies, 52% (26/50) were related to screening strategies, and 32% (16/50) pertained to treatment measures. The Markov model was the most frequently used (n = 27 of 50 [54%]). Based on the CHEQUE tool, the methodological quality of these CEA studies was inadequate in areas such as multiple data sources, approaches to select data sources, assessing the quality of data, and relevant equity or distribution. Conclusion: In summary, 57% of guidelines incorporated health economics studies as evidence, with a variation between different countries. The included HEE still had deficiencies in methodology and reporting quality. In the future, it is suggested that health economics research should use a standardized methodology and reporting approach to assist in clinical decision making.
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Affiliation(s)
- Xiaoyu Yan
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| | - Yue Wang
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| | - Aixia Ma
- School of International Pharmaceutical Business & Center for Pharmacoeconomics & Outcomes Research, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| | - Hongchao Li
- School of International Pharmaceutical Business & Center for Pharmacoeconomics & Outcomes Research, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
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Huang H, Xu W, Feng L, Zhong ME, Ye Y, Liu Y, Ye H, Li Z, Cui Y, Liu Z, Zhao K, Yan L, Liang C. Development and evaluation of the mrTE scoring system for MRI-detected tumor deposits and extramural venous invasion in rectal cancer. Abdom Radiol (NY) 2025:10.1007/s00261-025-04840-z. [PMID: 39954064 DOI: 10.1007/s00261-025-04840-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/03/2025] [Accepted: 02/07/2025] [Indexed: 02/17/2025]
Abstract
PURPOSE Tumor deposits (TDs) and extramural venous invasion (EMVI) in locally advanced rectal cancer (LARC) are MRI-detectable markers that reflect the invasive and metastatic potential of tumors. However, both mrTDs and mrEMVI are closely associated with peritumoral vascular signals, and they show a high degree of statistical correlation. We developed a novel scoring system that integrates mrTDs and mrEMVI into a single parameter, simplifying the assessment process and capturing the prognostic value of both factors simultaneously. METHODS We retrospectively included LARC patients who received neoadjuvant chemoradiotherapy at five centers and proposed a novel MRI-based scoring system, mrTE (derived from mrTDs and mrEMVI), to integrate the prognostic significance of mrEMVI and mrTDs in rectal cancer. The prognostic value of different mrTE scores was evaluated using Kaplan-Meier curves and the Cox model. The predictive accuracy of the new scoring system was evaluated using the integrated area under the ROC curve (iAUC). RESULTS A total of 1188 patients with LARC were included in the evaluation cohort to assess the reliability of the novel imaging scoring system. Based on the mrTE scores ranging from 0 to 2, the patients were categorized into three groups. The 3-year disease-free survival rates for the groups were 88.1%, 78.1%, and 51.9% (score 1 vs 0: HR 2.00, 95% CI 1.36-2.93, p < 0.001; score 2 vs 0: HR 4.75, 95% CI 3.61-6.26, p < 0.001). The mrTE scoring system demonstrated superior performance in predicting DFS compared to other clinical and imaging markers, with a higher predictive accuracy (iAUC = 0.707). CONCLUSIONS The mrTE scoring system simplifies the clinical assessment of relevant MR markers and has proven to be an effective tool for predicting the prognosis of LARC patients.
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Affiliation(s)
- Haitao Huang
- School of Medicine, South China University of Technology, Guangzhou, China
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
| | - Weixiong Xu
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Lili Feng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Min-Er Zhong
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, PR China
| | - Yunrui Ye
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yulin Liu
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huifen Ye
- Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical SciencesFudan University Shanghai Cancer Center, Shanghai, China
| | - Zhenhui Li
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Yanfen Cui
- Department of Radiology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan, China
| | - Zaiyi Liu
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
| | - Ke Zhao
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China.
- Medical Research Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
| | - Lifen Yan
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
| | - Changhong Liang
- School of Medicine, South China University of Technology, Guangzhou, China.
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China.
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Li Z, Aihemaiti Y, Yang Q, Ahemai Y, Li Z, Du Q, Wang Y, Zhang H, Cai Y. Survival machine learning model of T1 colorectal postoperative recurrence after endoscopic resection and surgical operation: a retrospective cohort study. BMC Cancer 2025; 25:262. [PMID: 39953493 PMCID: PMC11827358 DOI: 10.1186/s12885-025-13663-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 02/05/2025] [Indexed: 02/17/2025] Open
Abstract
OBJECTIVE To construct a postoperative recurrence prediction model for patients with T1 colorectal cancer after endoscopic resection and surgical operation via survival machine learning algorithms. METHODS Based on two tertiary-level affiliated hospitals, case data of 580 patients with T1 colorectal cancer treated by endoscopic resection and surgery were obtained, and patients' personal information, treatment modalities, and pathology-related information were extracted. After Boruta's algorithmic feature selection, predictors with significant contributions were identified. The patients were divided into a train set and a test set at a ratio of 7:3, and five survival machine learning models were subsequently built, namely, Randomized Survival Forest (RSF), Gradient Boosting (GB), Survival Tree (ST), CoxPH and Coxnet. Interpretability analysis of the model is based on the SHAP algorithm. RESULTS Patients at high risk of lymph node metastasis have a poor prognosis, but different treatment modalities do not significantly affect the prognosis of patients with recurrence. The Random Survival Forest model shows better performance, with a C-index and Integrated Brier Score of 0.848 and 0.098 in the test set, respectively, and its time-dependent AUC is 0.918. The interpretability analysis of the model revealed that submucosal invasion depth < 1000 μm, tumor budding grade of BD1, lymphovascular invasion and perineural invasion are absent, well differentiated cancer cells, and tumor size < 20 mm have positive effects on the model, lts negative gain characteristics are a contributing factor to patient relapse. CONCLUSIONS The prognostic model constructed via survival machine learning for patients with T1 colorectal cancer has good performance, and can provide accurate individualized predictions.
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Affiliation(s)
- Zhihong Li
- School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Yiliyaer Aihemaiti
- School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Qianqian Yang
- School of Nursing, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Yiliminuer Ahemai
- The Third Clinical School of Medicine, Xinjiang Medical University, Urumqi, 83000, China
| | - Zimei Li
- The Third Clinical School of Medicine, Xinjiang Medical University, Urumqi, 83000, China
| | - Qianqian Du
- The Third Clinical School of Medicine, Xinjiang Medical University, Urumqi, 83000, China
| | - Yan Wang
- Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Hanxiang Zhang
- Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Yingbin Cai
- Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
- Xinjiang Regional Center for Research on Population Disease and Health Care, Urumqi, Xinjiang, 830011, China.
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Platt JR, Pennycook S, Muthoo CE, Westwood AC, Frood R, Beggs AD, Scarsbrook A, Seligmann JF, Tolan DJM. Colon cancer biology and treatment in the era of precision oncology: A primer for Radiologists. Eur J Radiol 2025; 185:112000. [PMID: 39978239 DOI: 10.1016/j.ejrad.2025.112000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/07/2025] [Accepted: 02/12/2025] [Indexed: 02/22/2025]
Abstract
In the era of precision oncology, systemic therapies for colon cancer are becoming increasingly biomarker-led, with implications for patients in the neoadjuvant, adjuvant and metastatic settings. As the landscape for colon cancer treatment evolves and becomes more complex, it is important that all members of the multidisciplinary team keep abreast of developments to ensure the most effective care is delivered to patients. As core members of the colorectal multidisciplinary team, Radiologists play a central role throughout the patient journey. This review serves as an educational summary of current and emerging treatment pathways in colon cancer, standards for biomarker testing, mechanisms of action for key drugs, important treatment-related complications, relevant tumour biology that underpins patterns of disease and treatment response, and the specific implications systemic therapies have for cancer imaging and Radiologists. We also highlight the increasing role for radiology in patient stratification and the importance of imaging biomarkers. It is crucial that Radiologists understand the current landscape of colon cancer treatment and emerging strategies on the horizon in clinical trials. Only through engagement across the wider multidisciplinary team will we deliver true personalised medicine for patients with colon cancer.
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Affiliation(s)
- James R Platt
- Division of Oncology, Leeds Institute of Medical Research at St James's, School of Medicine, University of Leeds, Leeds, UK.
| | - Stephanie Pennycook
- Department of Medical Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
| | - Chand E Muthoo
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
| | - Alice C Westwood
- Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St. James's, School of Medicine, University of Leeds, Leeds, UK.
| | - Russell Frood
- Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds, Leeds, UK.
| | - Andrew D Beggs
- Department of Cancer and Genomics, University of Birmingham, Birmingham, UK.
| | - Andrew Scarsbrook
- Leeds Institute of Medical Research at St James's, School of Medicine, University of Leeds, Leeds, UK.
| | - Jenny F Seligmann
- Division of Oncology, Leeds Institute of Medical Research at St James's, School of Medicine, University of Leeds, Leeds, UK.
| | - Damian J M Tolan
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
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Kramer A, van Schaik LF, van den Broek D, Meijer GA, Gutierrez Ibarluzea I, Galnares Cordero L, Fijneman RJA, Ligtenberg MJL, Schuuring E, van Harten WH, Coupé VMH, Retèl VP. Towards Recommendations for Cost-Effectiveness Analysis of Predictive, Prognostic, and Serial Biomarker Tests in Oncology. PHARMACOECONOMICS 2025:10.1007/s40273-025-01470-7. [PMID: 39920559 DOI: 10.1007/s40273-025-01470-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/19/2025] [Indexed: 02/09/2025]
Abstract
BACKGROUND Cost-effectiveness analysis (CEA) of biomarkers is challenging due to the indirect impact on health outcomes and the lack of sufficient fit-for-purpose data. Hands-on guidance is lacking. OBJECTIVE We aimed firstly to explore how CEAs in the context of three different types of biomarker applications have addressed these challenges, and secondly to develop recommendations for future CEAs. METHODS A scoping review was performed for three biomarker applications: predictive, prognostic, and serial testing, in advanced non-small cell lung cancer, early-stage colorectal cancer, and all-stage colorectal cancer, respectively. Information was extracted on the model assumptions and uncertainty, and the reported outcomes. An in-depth analysis of the literature was performed describing the impact of model assumptions in the included studies. RESULTS A total of 43 CEAs were included (31 predictive, 6 prognostic, and 6 serial testing). Of these, 40 utilized different sources for test and treatment parameters, and three studies utilized a single source. Test performance was included in 78% of these studies utilizing different sources, but this parameter was differently expressed across biomarker applications. Sensitivity analyses for test performance was only performed in half of these studies. For the linkage of test results to treatments outcomes, a minority of the studies explored the impact of suboptimal adherence to test results, and/or explored potential differences in treatment effects for different biomarker subgroups. Intermediate outcomes were reported by 67% of studies. CONCLUSIONS We identified various approaches for dealing with challenges in CEAs of biomarker tests for three different biomarker applications. Recommendations on assumptions, handling uncertainty, and reported outcomes were drafted to enhance modeling practices for future biomarker cost-effectiveness evaluations.
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Affiliation(s)
- Astrid Kramer
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Lucas F van Schaik
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Daan van den Broek
- Department for Laboratory Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | | | - Remond J A Fijneman
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marjolijn J L Ligtenberg
- Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands
- Department of Pathology, Radboudumc, Nijmegen, The Netherlands
| | - Ed Schuuring
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Wim H van Harten
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Health technology and Services Research, University of Twente, Enschede, The Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Valesca P Retèl
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.
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Dunn C, Tie J, Gibbs P. A Call for Improved Guidance to Integrate Modern Biomarkers Into Routine Clinical Care-Piecing the Puzzle Together. JAMA Oncol 2025:2829927. [PMID: 39913167 DOI: 10.1001/jamaoncol.2024.6479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2025]
Abstract
This Viewpoint describes the optimal approach to therapy selection for patients with cancer using biomarkers.
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Affiliation(s)
- Catherine Dunn
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Jeanne Tie
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Western Health, Melbourne, Australia
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Sassun R, Sileo A, Ng JC, Violante T, Gomaa I, Mandrekar J, Rumer KK, McKenna NP, Larson DW. Validated Integration of Tumor Deposits in N Staging for Prognostication in Colon Cancer. JAMA Surg 2025:2829924. [PMID: 39908058 PMCID: PMC11800120 DOI: 10.1001/jamasurg.2024.6729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 11/07/2024] [Indexed: 02/06/2025]
Abstract
Importance Tumor deposits have prognostic value in colon cancer, but the current American Joint Committee on Cancer (AJCC) staging only considers them if there are no concurrent positive lymph nodes. Objective To devise a staging system for colon cancer by integrating counts of tumor deposits with positive lymph nodes while retaining the current AJCC staging framework. Design, Setting, and Participants This retrospective cohort study examines data from a large-volume, tertiary care center database (January 2010 through March 2023 with follow-up until December 2023) and the population-based National Cancer Database (January 2010 through December 2020 with follow-up until December 2021). Participants were adults (age 18-75 years) with stage III colon adenocarcinoma who underwent chemotherapy, and had a specified positive lymph node count and tumor deposit count were selected. Exposure A real positive lymph nodes count was developed and used to derive Sassun-Mayo N/tumor, lymph node, and metastasis (TNM) stages that were compared with the AJCC N/TNM stages. Main Outcomes and Measures Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses for 3-year overall survival were performed to assess the efficiency of the 2 staging systems. The concordance index was used for validation using the National Cancer Database. Results From a total patient number of 11 162 (institutional) and 848 704 (national), the final patient numbers were 788 and 77 790, respectively. The institutional database patients had a mean (SD) age of 58.5 (11.5) years; there were 433 male patients (54.9%) and 355 female (45.1%). The national database patients had a mean (SD) age of 59.3 (10.6) years; there were 40 315 male patients (51.8%) and 37 475 female (48.2%). ROC curve areas were improved using the Sassun-Mayo stages (3-year death for AJCC TMN, 0.63 [95% CI, 0.57-0.69] vs 0.66 [95% CI, for 0.60-0.72] for Sassun-Mayo TNM). Kaplan-Meier curves revealed visible overlaps among AJCC N stages, which were absent in the Sassun-Mayo N stages. The concordance index in the Sassun-Mayo N/TNM stages was 0.611 and 0.616, respectively, while in the AJCC N/TNM stages, it was 0.598 and 0.606, respectively. Patients upstaged from N1 to N2 (n = 10 307; 13.2%) had a 3-year overall survival rate nearly identical to that of AJCC N2a patients. Additionally, 3001 patients (3.9%) were upstaged from N2a to N2b, indicating that 13 308 patients (17.1%) with stage III colon cancer across cohorts were understaged. Conclusions and Relevance This study found that Sassun-Mayo N/TNM staging provided superior overall survival stratification compared with the current AJCC staging, suggesting that their implementation could improve prognostication in colon cancer.
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Affiliation(s)
- Richard Sassun
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Annaclara Sileo
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Jyi Cheng Ng
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Tommaso Violante
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Ibrahim Gomaa
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Jay Mandrekar
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Kristen K. Rumer
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | | | - David W. Larson
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
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Taieb J, Souglakos J, Boukovinas I, Falcoz A, Pages F, Messaritakis I, Bennouna J, Artru P, Louvet C, Lepere C, Emile JF, Bouche O, Mazard T, Vernerey D, Vogiatzoglou K, Tzardi M, Sharma S, Liu MC, Sethi H, André T, Galon J, Laurent-Puig P. Combined Analyses of Circulating Tumor DNA and Immunoscore in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France/HORG-IDEA-Greece Trials. J Clin Oncol 2025:JCO2400648. [PMID: 39903903 DOI: 10.1200/jco.24.00648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 10/08/2024] [Accepted: 12/02/2024] [Indexed: 02/06/2025] Open
Abstract
PURPOSE Immunoscore (IS) and circulating tumor DNA (ctDNA) are two emerging technologies in improving prognostication and tailoring adjuvant treatments in patients resected from a stage III colon cancer (CC). Here, we analyzed the prognostic value of the two biomarkers in patients who participated in the randomized phase III IDEA-France and HORG trials. METHODS Plasma samples were collected after surgery and before adjuvant chemotherapy. ctDNA analysis was performed using a clinically validated, personalized, tumor-informed 16-plex protein chain reaction assay. Multivariable analyses for time to recurrence (TTR; patients without recurrence or death due to CC) and overall survival (OS) were performed using ctDNA and IS results, along with other parameters including treatment duration and disease risk group. RESULTS Of the 554 patients with available ctDNA results, 445 were ctDNA-negative (80.3%) and 109 were ctDNA-positive (19.7%); baseline characteristics showed more T4/N2 and venous embolism/lymphatic invasion/perineural invasion+ in ctDNA-positive patients. With a median follow-up of 6.7 years, the 2-year TTR rate was 43.5% (95% CI, 34.1 to 52.6) for ctDNA-positive patients and 88.1% (95% CI, 84.7 to 90.8) for ctDNA-negative patients (P < .0001). ctDNA was confirmed as an independent prognostic marker for both TTR (adjusted hazard ratio [adjHR], 5.21 [95% CI, 3.59 to 7.58]; P < .001) and OS (adjHR, 4.84 [95% CI, 3.40 to 6.89]; P < .001). ctDNA remained the most significant prognostic factor irrespective of disease stage, treatment duration, and IS results. IS was not prognostic in ctDNA-positive patients but remained a significant prognostic tool for ctDNA-negative patients. CONCLUSION In this combined analysis of two adjuvant trials dedicated to patients with stage III CC after surgery, ctDNA was detectable in 19.7% of the patients and was confirmed as a major independent prognostic biomarker. IS seems to bring additional prognostic information in the 80.3% of patients who are ctDNA-negative.
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Affiliation(s)
- Julien Taieb
- Department of Gastroenterology and Gastrointestinal Oncology, CARPEM Comprehensive Cancer Center, Georges-Pompidou European Hospital, AP-HP, Paris, France
- SIRIC CARPEM, Université Paris-Cité, Paris, France
- Centre de Recherche des Cordeliers, INSERM, CNRS, Université Paris-Cité, Sorbonne Université, USPC, Equipe labellisée Ligue Nationale Contre le Cancer, Paris, France
| | - John Souglakos
- Department of Medical Oncology, University Hospital of Heraklion, Crete, Greece
- Laboratory of Translational Oncology, Medical School, University of Crete, Heraklion, Greece
| | | | - Antoine Falcoz
- Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
- INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Bourgogne Franche-Comté University, Besançon, France
| | - Franck Pages
- Department of Immunology, Georges-Pompidou European Hospital, AP-HP, INSERM, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, SIRIC CARPEM, Université Paris-Cité, Paris, France
| | - Ippokratis Messaritakis
- Laboratory of Translational Oncology, Medical School, University of Crete, Heraklion, Greece
| | - Jaafar Bennouna
- Department of Medical Oncology, Hospital Foch, Suresnes, France
| | - Pascal Artru
- Department of Medical Oncology, Private Hospital Jean Mermoz-Ramsay Santé, Lyon, France
| | - Christophe Louvet
- Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France
| | - Celine Lepere
- Department of Gastroenterology and Gastrointestinal Oncology, CARPEM Comprehensive Cancer Center, Georges-Pompidou European Hospital, AP-HP, Paris, France
- SIRIC CARPEM, Université Paris-Cité, Paris, France
| | - Jean Francois Emile
- Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France
| | - Olivier Bouche
- Department of Digestive Oncology, Hospital Robert Debré, Reims, France
| | - Thibault Mazard
- Department of Medical Oncology, Montpellier Cancer Institute (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, University of Montpellier, Montpellier, France
| | - Dewi Vernerey
- Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
- INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Bourgogne Franche-Comté University, Besançon, France
| | | | - Maria Tzardi
- Laboratory of Pathology, University Hospital of Heraklion, Crete, Greece
| | | | | | | | - Thierry André
- Sorbonne Université, Paris, France
- Department of Medical Oncology, Hôpital Saint Antoine, Paris, France
| | - Jérome Galon
- Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, INSERM, SIRIC CARPEM, Sorbonne Université, Université Paris Cité, Paris, France
| | - Pierre Laurent-Puig
- Centre de Recherche des Cordeliers, INSERM, CNRS, Université Paris-Cité, Sorbonne Université, USPC, Equipe labellisée Ligue Nationale Contre le Cancer, Paris, France
- Department of Biology, Assistance Publique-Hôpitaux de Paris, European Georges Pompidou Hospital, Paris, France
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11
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Fan S, Wang J, Hou Y, Cui X, Feng Z, Qi L, Liu J, Bian K, Liang J, Ye Z, Zheng S, Ma W. MRI-based multiregional radiomics for desmoplastic reaction classification and prognosis stratification in stage II rectal cancer: A bicenter study. Eur J Radiol 2025; 183:111888. [PMID: 39705910 DOI: 10.1016/j.ejrad.2024.111888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/22/2024] [Accepted: 12/11/2024] [Indexed: 12/23/2024]
Abstract
PURPOSE To develop an MRI-based multiregional radiomics model for the noninvasive desmoplastic reaction (DR) classification and prognosis stratification in stage II rectal cancer (RC) patients. MATERIALS AND METHODS This study retrospectively involved 336 patients with RC from two centers, with 239 from Center 1 divided into training (n = 191) and internal validation (n = 48) datasets at an 8:2 ratio, and 97 from Center 2 serving as external validation dataset. Radiomics features were extracted, and a multiregional radiomics DR (M-RDR) signature was established using multi-level feature selection procedure. The cut-off value for M-RDR was determined using Youden's index. We further evaluated the predictive values of M-RDR on prognosis and adjuvant chemotherapy stratification. The primary outcome was 3-year disease-free survival (DFS), and cox model performance was assessed using AUCs and 95 % confidence intervals. RESULTS M-RDR demonstrated a high accuracy in DR classification with AUCs of 0.778 and 0.798 in the training and internal validation datasets. Multivariable analysis confirmed M-RDR as an independent prognostic factor after adjusting for clinicopathological factors.The combined model incorporating M-RDR and clinicopathological factors showed good performance in predicting 3-year DFS, with AUCs of 0.923, 0.908, and 0.891 in the training, internal validation and external validation datasets, respectively. Additionally, patients in the M-RDR-high group who received adjuvant chemotherapy had significantly better DFS compared with those who did not (P < 0.05). CONCLUSION The MRI-based multiregional radiomics model could effectively improve non-invasive DR classification, and was able to enhance postoperative risk stratification and treatment decision-making in stage II RC patients.
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Affiliation(s)
- Shuxuan Fan
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Jing Wang
- School of Public Health, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yan Hou
- Department of Radiology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Precise Imaging of Inflammation - Related Tumors, Hebei, China
| | - Xiaonan Cui
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Ziwei Feng
- Department of Epidemiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Lisha Qi
- Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Jiaxin Liu
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Keyi Bian
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Jing Liang
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Zhaoxiang Ye
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Sunyi Zheng
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
| | - Wenjuan Ma
- Department of Breast Imaging, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China.
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12
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Zhang C, Chen J, Liu Y, Yang Y, Xu Y, You R, Li Y, Liu L, Yang L, Li H, Wang G, Li W, Li Z. Amide proton transfer-weighted MRI for assessing rectal adenocarcinoma T-staging and perineural invasion: a prospective study. Eur Radiol 2025; 35:968-978. [PMID: 39122854 DOI: 10.1007/s00330-024-11000-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 06/19/2024] [Accepted: 07/20/2024] [Indexed: 08/12/2024]
Abstract
OBJECTIVE To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA). METHODS This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values. RESULTS A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively. CONCLUSION Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA. CLINICAL RELEVANCE STATEMENT Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning. KEY POINTS The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA.
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Affiliation(s)
- Caixia Zhang
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Jianyou Chen
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Yifan Liu
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Yinrui Yang
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | | | - Ruimin You
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Yanli Li
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Lizhu Liu
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Ling Yang
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Huaxiu Li
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China
| | - Guanshun Wang
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China.
| | - Wenliang Li
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China.
| | - Zhenhui Li
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China.
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13
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Sakamoto T, Mukai T, Noguchi T, Matsui S, Yamaguchi T, Akiyoshi T, Kawachi H, Fukunaga Y. Patterns of lymph node metastasis and long-term outcomes of splenic flexure colon cancer: a descriptive study from a Japanese high-volume center. Surg Today 2025:10.1007/s00595-025-02999-y. [PMID: 39888401 DOI: 10.1007/s00595-025-02999-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 01/06/2025] [Indexed: 02/01/2025]
Abstract
PURPOSE The pattern of lymph node metastasis and the appropriate extent of lymph node dissection in splenic flexure colon cancer remain unclear. This study aimed to describe the clinical characteristics, lymph node metastasis patterns, and oncological outcomes of patients with splenic flexure colon cancer. METHODS The data of patients with splenic flexure cancer diagnosed with pathological stages I-III were extracted from a hospital database. Lymph nodes were mapped and numbered according to the guidelines of the Japanese Society for Cancer of the Colon and Rectum. Five-year disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. RESULTS Among 151 patients, 37.1% had lymph node metastasis. The proportion of lymph node metastasis were 30.1% at station 221, 5.1% at station 222, 2.8% at station 223, 19.8% at station 231, 2.7% at station 232, and 0% at station 253. Among the 59 patients with an accessory middle colic artery, 19 had lymph node metastasis only at stations 221 (14/47) and 231 (5/47). The 5-year estimated DFS rates were 100% for stage I, 94.4% (95% CI, 83.6-98.2) for stage II, and 79.9% (95% CI, 65.6-88.8) for stage III. Ten patients experienced distant recurrence: liver (n = 5), peritoneum (n = 2), para-aortic lymph node (n = 2), and lung metastasis (n = 1). No local recurrence was observed. CONCLUSION In splenic flexure colon cancer, lymph node dissection around the IMA route may be omitted. Similarly, dissection along the left branch of the middle colic artery or the left colic artery may be unnecessary in the presence of an accessory middle colic artery.
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Affiliation(s)
- Takashi Sakamoto
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Toshiki Mukai
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan.
| | - Tatsuki Noguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Shimpei Matsui
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Tomohiro Yamaguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Takashi Akiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Hiroshi Kawachi
- Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-Ku, Tokyo, 135-8550, Japan
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14
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Gallois C, Sroussi M, André T, Mouillet-Richard S, Agueeff N, Mulot C, Vernerey D, Louvet C, Bachet JB, Dourthe LM, Mazard T, Jary M, Coutzac C, Lecaille C, Tabernero J, Van Laethem JL, Lepage C, Emile JF, de Reyniès A, Taieb J, Laurent-Puig P. Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials. J Clin Oncol 2025:JCO2302262. [PMID: 39889251 DOI: 10.1200/jco.23.02262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/08/2024] [Accepted: 12/23/2024] [Indexed: 02/02/2025] Open
Abstract
PURPOSE The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials. PATIENTS AND METHODS 3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first. RESULTS High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile (P < .0001). The IPS score was significantly associated with TTR in multivariable analysis. CONCLUSION Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence.
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Affiliation(s)
- Claire Gallois
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
- Digestive Oncology Department, Institut du Cancer Paris CARPEM, APHP, APHP Centre, Hôpital Européen G. Pompidou, Université Paris Cité, Paris, France
| | - Marine Sroussi
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
- Institut Chimie Biologie Innovation-Laboratoire de BioChimie, ESPCI, UMR8231 CNRS, Université PSL, Paris, France
| | - Thierry André
- Department of Medical Oncology, Hôpital Saint Antoine, Sorbonne Université, Paris, France
| | - Sophie Mouillet-Richard
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
| | - Natacha Agueeff
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
| | - Claire Mulot
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
| | - Dewi Vernerey
- Methodology and Quality of Life Unit in Oncology, University of Besançon, Besançon, France
- Etablissement Français du Sang Bourgogne Franche-Comté, INSERM, Unité Mixte de Recherche 1098, RIGHT Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Franche-Comté University, Besançon University Hospital, Besançon, France
| | - Christophe Louvet
- Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France
| | - Jean-Baptiste Bachet
- Department of Hepato-Gastroenterology and Digestive Oncology, Pitié-Salpêtriére Hospital, APHP, Sorbonne Université, Paris, France
| | | | - Thibault Mazard
- Department of Medical Oncology, IRCM, INSERM, ICM, University of Montpellier, Montpellier, France
| | - Marine Jary
- Department of Digestive and Hepatobiliary Surgery, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
| | - Clélia Coutzac
- Department of Medical Oncology, Centre Leon Berard, University Claude Bernard Lyon, Lyon, France
| | - Cédric Lecaille
- Cancerology Department, Bordeaux Nord Polyclinic, Bordeaux, France
| | - Josep Tabernero
- Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain
| | - Jean-Luc Van Laethem
- Department of Digestive Oncology, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Côme Lepage
- Hepatogastroenterology and Digestive Oncology Department, Dijon Bourgogne Hospital, University of Burgundy and Franche Comté, Dijon, France
| | - Jean-François Emile
- EA4340 BECCOH, Service de Pathologie, Hôpital Ambroise Paré, AP-HP, Université de Versailles SQY, Boulogne, France
| | - Aurélien de Reyniès
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
- Laboratoire SeqOIA, Paris, France
| | - Julien Taieb
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
- Digestive Oncology Department, Institut du Cancer Paris CARPEM, APHP, APHP Centre, Hôpital Européen G. Pompidou, Université Paris Cité, Paris, France
| | - Pierre Laurent-Puig
- Centre de Recherche des Cordeliers, INSERM, Université Paris Cité, Sorbonne Université, Paris, France
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15
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Emile SH, Horesh N, Garoufalia Z, Gefen R, Dourado J, Wexner SD. Survival benefit of adjuvant chemotherapy in stage II large (≥5 cm) colonic adenocarcinomas: A propensity-score matched analysis. Surg Oncol 2025; 58:102190. [PMID: 39923350 DOI: 10.1016/j.suronc.2025.102190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 01/15/2025] [Accepted: 01/28/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Current guidelines recommend selective adjuvant chemotherapy for stage II colon cancer with high-risk features. This study aimed to assess survival benefit of adjuvant chemotherapy in patients with stage II colon adenocarcinomas ≥5 cm without high-risk features. METHODS The National Cancer Database was retrospectively reviewed (2010-2019) for all patients with pathologic stage II colonic adenocarcinomas ≥5 cm who underwent colectomy. Patients were divided into adjuvant and control groups that were propensity-score matched for baseline and treatment confounders. The primary outcome was 5-year overall survival (OS). RESULTS Of 23,937 included patients, adjuvant chemotherapy was given to 2581 (10.8 %). Patient given adjuvant chemotherapy were younger, more often male, Black, had a Charlson score of 0 and private insurance, presented with left-sided cancers and microsatellite stable (MSS) tumors, and more frequently underwent segmental resections and open surgery. 796 patients in the adjuvant group were matched to 1592 patients in the control group. Adjuvant chemotherapy was associated with lower mortality (HR: 0.79; p = 0.022), however, it was not independently associated with improved OS when adjusted for other confounders (HR: 0.84; p = 0.157). The adjuvant group had significantly longer restricted mean OS than the control group (104.9 vs. 100.8 months; p = 0.007). The survival benefit was only noted in patients >50 years, female, White, with non-mucinous adenocarcinomas, MSS tumors, normal CEA levels, and had undergone open and emergency surgery. CONCLUSIONS The study did not demonstrate a clear survival benefit from adjuvant chemotherapy in patients with stage II adenocarcinoma ≥5 cm. A possible potential survival benefit was observed only in a subgroup of patients.
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Affiliation(s)
- Sameh Hany Emile
- Colorectal Surgery Department, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura, Egypt
| | - Nir Horesh
- Colorectal Surgery Department, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Zoe Garoufalia
- Colorectal Surgery Department, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Rachel Gefen
- Colorectal Surgery Department, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of General Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Justin Dourado
- Colorectal Surgery Department, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Steven D Wexner
- Colorectal Surgery Department, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA.
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Negro S, Perissinotto E, Mammi I, Crivellari G, Schiavi F, Cappello F, Spolverato G, Ferrari D, Rausa E, Vitellaro M, Fassan M, Cavestro GM, Mannucci A, Lonardi S, Bergamo F, Urso EDL. Emerging therapeutic strategies in Lynch syndrome-associated colorectal cancer and the role of MMR testing. TUMORI JOURNAL 2025:3008916241310706. [PMID: 39882759 DOI: 10.1177/03008916241310706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Lynch syndrome is the most common hereditary cancer predisposition, accounting for 1-5% of colorectal cancer cases, and is driven by germline mutations in DNA mismatch repair genes. Despite established diagnostic criteria, such as the Amsterdam guidelines, Lynch syndrome remains largely underdiagnosed. To address this gap, universal tumour screening has been introduced for all newly diagnosed cases of colorectal cancer and endometrial cancer, significantly improving early detection. The surgical management of colorectal cancer in patients with Lynch syndrome remains controversial. While extended colectomy reduces the risk of metachronous colorectal cancer, surgical strategies must be carefully individualised based on patient-specific factors. Chemoprevention with aspirin has shown promise in reducing the risk of colorectal cancer, with ongoing trials investigating optimal dosing. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionised the treatment of Microsatellite Instability-High/deficient Mismatch Repair colorectal cancer, offering durable responses and significant survival benefits. In addition, the neoadjuvant use of immune checkpoint inhibitors is paving the way for non-surgical interventions, potentially transforming the management of colorectal cancer in patients with Lynch syndrome. A multidisciplinary approach and continued research are essential to optimise cancer prevention, treatment and quality of life for people with Lynch syndrome.
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Affiliation(s)
- Silvia Negro
- 3rd Surgical Unit, Department of Surgical, Gastroenterological and Oncological Sciences, University of Padua, Padua, Italy
| | - Eleonora Perissinotto
- Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Isabella Mammi
- Unità Tumori Ereditari, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Gino Crivellari
- Unità Tumori Ereditari, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Francesca Schiavi
- Unità Tumori Ereditari, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Filippo Cappello
- Pathological Anatomy Unit, University Hospital of Padova, Padova, Italy
| | - Gaya Spolverato
- 3rd Surgical Unit, Department of Surgical, Gastroenterological and Oncological Sciences, University of Padua, Padua, Italy
| | - Davide Ferrari
- Department of Surgery, IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Emanuele Rausa
- Department of Surgery, IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marco Vitellaro
- Department of Surgery, IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy; Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso
| | - Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sara Lonardi
- Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Francesca Bergamo
- Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Emanuele D L Urso
- 3rd Surgical Unit, Department of Surgical, Gastroenterological and Oncological Sciences, University of Padua, Padua, Italy
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Gueiderikh A, Faivre JC, Golfier C, Escande A, Thureau S. Efficacy of innovative systemic treatments in combination with radiotherapy for bone metastases: a GEMO (the European Study Group of Bone Metastases) state of the art. Cancer Metastasis Rev 2025; 44:28. [PMID: 39875680 PMCID: PMC11775081 DOI: 10.1007/s10555-024-10236-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 12/18/2024] [Indexed: 01/30/2025]
Abstract
The management of bone metastases (BoM) requires a multidisciplinary approach to prevent complications, necessitating updated knowledge in light of the rapid advancements in systemic treatments and surgical, interventional radiology or radiation techniques. This review aims to discuss efficacy of new systemic treatments on BoM, the benefits of radiotherapy adjunction, and the optimal methods for combining them. Preliminary evidence suggesting reduced efficacy of immune checkpoint inhibitors (ICI), and several multi-kinase inhibitors regarding BoM may encourage early use of radiotherapy (RT). Systemic treatment efficacy modulation by RT and ablative RT strategies are explored. Concerns for increased side effects for several kinase inhibitors and double ICI in combination with RT imply suspending those systemic treatments during RT. Various timing strategies to combine prostate hormone therapies and RT are developed. Emerging internal vectorized radiotherapy molecules necessitate developing new combination strategies with RT. Further prospective data collection and comparative trials should be encouraged.
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Affiliation(s)
- Anna Gueiderikh
- Département de Radiothérapie, Gustave Roussy, Villejuif, France
- Université Paris-Saclay, Orsay, France
| | - Jean-Christophe Faivre
- Radiation Oncology Department, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, 54519, France
| | - Constance Golfier
- Radiation Oncology Department, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, 54519, France
| | - Alexandre Escande
- Service de Radiothérapie, Centre Léonard de Vinci, Dechy, France
- Laboratoire CRIStAL, UMR 9186, Université de Lille, Lille, France
- Faculté de Médecine H.Warembourg, Université de Lille, Lille, France
| | - Sébastien Thureau
- Département de Radiothérapie et de Physique Médicale, Centre Henri Becquerel Rouen QuantiF, LITIS EA4108 Université Rouen, Rouen, France.
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18
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Lee JG, Park I, Lee H, Nam S, Kim J, Lee WS, Kang M, Kim JH. Integrating E-cadherin expression levels with TNM staging for enhanced prognostic prediction in colorectal cancer patients. BMC Cancer 2025; 25:150. [PMID: 39871234 PMCID: PMC11770905 DOI: 10.1186/s12885-025-13539-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/16/2025] [Indexed: 01/29/2025] Open
Abstract
PURPOSE This study aimed to investigate the clinical significance of E-cadherin expression levels in colorectal cancer tissues and explore the relationship between E-cadherin expression and tumor node metastasis (TNM) stage. The goal was to establish a more accurate prognostic prediction for colorectal cancer patients by analyzing E-cadherin expression levels alongside TNM staging. METHODS The study examined colorectal cancer patients by dividing them into groups based on E-cadherin expression levels. It then assessed their 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs). Additionally, the prognosis of patients was analyzed by combining E-cadherin expression levels with TNM staging, particularly focusing on patients in stages III and IV. RESULTS The E-cadherinLow group had significantly worse outcomes, with HRs of 2.30 for EFS and 2.76 for DSS compared to the E-cadherinHigh group. When combined with TNM stage III/IV, patients with E-cadherinLow expression showed a poor prognosis, with HRs of 1.93 for EFS and 2.35 for DSS compared to those with E-cadherinHigh expression at the same TNM stage. CONCLUSIONS Low levels of E-cadherin expression are associated with a poor prognosis and decreased survival in colorectal cancer patients. Combining E-cadherin expression levels with TNM staging provides a more precise prediction of patient prognosis and survival, potentially guiding personalized treatment strategies.
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Affiliation(s)
- Jae-Ghi Lee
- Gachon Medical Research Institute, Gachon Biomedical Convergence Institute, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea
| | - Ilkyu Park
- Gachon Medical Research Institute, Gachon Biomedical Convergence Institute, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea
| | - Hannah Lee
- Department of Internal Medicine, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea
| | - Seungyoon Nam
- AI Convergence Center for Medical Science, Department of Genome Medicine and Science, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, 21565, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon, 21999, Republic of Korea
| | - Jisup Kim
- Department of Pathology, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea
| | - Won-Suk Lee
- Department of Surgery, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea
| | - Myunghee Kang
- Department of Pathology, Dongkang Medical Center, Ulsan, 44455, Korea.
| | - Jung Ho Kim
- Gachon Medical Research Institute, Gachon Biomedical Convergence Institute, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea.
- Department of Internal Medicine, College of Medicine, Gachon University Gil Medical Center, Gachon University, Incheon, 21565, Republic of Korea.
- Department of Translational-Clinical Medicine, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon, 21999, Republic of Korea.
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19
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Tsukamoto R, Sugimoto K, Ii Y, Irie T, Kawaguchi M, Kobari A, Tsuchiya Y, Honjo K, Kawai M, Ishiyama S, Takahashi M, Sakamoto K. Prognostic Impact of the Postoperative Carcinoembryonic Antigen Level after Curative Resection of Locally Advanced Rectal Cancer. J Anus Rectum Colon 2025; 9:69-78. [PMID: 39882227 PMCID: PMC11772802 DOI: 10.23922/jarc.2024-035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 10/03/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives This study was conducted to investigate whether preoperative or postoperative carcinoembryonic antigen (CEA) with a new cut-off value is more optimal for predicting long-term outcomes in patients with Stage II/III rectal cancer, and to investigate the effectiveness of postoperative adjuvant chemotherapy (POAC) based on the CEA values. Methods Serum CEA levels were measured preoperatively (pre-CEA) and postoperatively (post-CEA). The area under the receiver operating curve (AUROC) was used to determine a cut-off for CEA. The cut-off for CEA relative to recurrence-free survival (RFS) was established as that giving the highest AUROC. In comparison of superiority between pre- and post- CEA levels, Akaike's information criterion (AIC) was used in the Cox proportional-hazard regression model. Results The subjects were 323 patients who underwent curative surgical treatment for Stage II/III rectal cancer. AIC values indicated that RFS was better stratified by a post-CEA level with a cut-off of 2.3 ng/ml compared with other classifications of pre- or post- CEA. In Stage III or high-risk Stage II cases, there was no effect of POAC on RFS in those with post-CEA <2.3 ng/ml (p=0.39), but in those with post-CEA ≥2.3 ng/ml there was a trend for better RFS in patients who received POAC compared to those without POAC (p=0.06). Conclusions Patients with post-CEA ≥2.3 ng/ml had worse long-term outcomes compared with those with post-CEA <2.3 ng/ml. Post-CEA with a cut-off of 2.3 ng/ml may be useful in determining the indication for POAC for in Stage III or high-risk Stage II cases.
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Affiliation(s)
- Ryoichi Tsukamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kiichi Sugimoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuki Ii
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Takahiro Irie
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Megumi Kawaguchi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Aya Kobari
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuki Tsuchiya
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kumpei Honjo
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Masaya Kawai
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Shun Ishiyama
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Makoto Takahashi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
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20
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Hanevelt J, Brohet RM, Moons LMG, Laclé MM, Vleggaar FP, van Westreenen HL, de Vos Tot Nederveen Cappel WH. Risk of Lymph Node Metastasis in T2 Colon Cancer: A Nationwide Population-Based Cohort Study. Ann Surg Oncol 2025:10.1245/s10434-025-16921-w. [PMID: 39847281 DOI: 10.1245/s10434-025-16921-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 01/04/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Similar to T1 colon cancer (CC), risk stratification may guide T2 CC treatment and reduce unnecessary major surgery. In this study, prediction models were developed that could identify T2 CC patients with a lower risk of lymph node metastasis (LNM) for whom (intensive) follow-up after local treatment could be considered. METHODS A nationwide cohort study was performed involving pT2 CC patients who underwent surgery between 2012 and 2020, using data from the Dutch ColoRectal Audit, which were linked to the Nationwide Pathology Databank. Four machine learning models were evaluated to predict LNM. RESULTS LNMs were found in 1877/9803 patients (19.1%). Independent risk factors included (younger) age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.979-0.990), left-sided CC (OR 1.5, 95% CI 1.4-1.7), poor differentiation (OR 1.7, 95% CI 1.4-2.2), and lymphovascular invasion (LVI; OR 4.1, 95% CI 3.6-4.7). A deficient mismatch repair (MMR) status significantly lowered the risk of LNM (OR 0.3, 95% CI 0.2-0.5). The general linear model demonstrated the highest prediction accuracy, achieving area under the receiver operating characteristic curves of 0.67 and 0.68, with good calibration. In the absence of risk factors, elderly patients (≥74 years of age) had a predicted risk of LNM of 10.7%, yet up to 30% experienced postoperative complications, with mortality rates reaching up to 3.5%. Patients with a deficient MMR status had a predicted risk of LNM of 6.1% if LVI was absent and the tumor was well-differentiated. CONCLUSIONS The risk of LNM should be weighed against surgical risks. The findings of this study will enable clinicians to make more deliberate considerations about these competing risks before making a shared decision.
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Affiliation(s)
- Julia Hanevelt
- Department of Gastroenterology and Hepatology, Isala, Zwolle, The Netherlands.
| | - Richard M Brohet
- Department of Epidemiology and Statistics, Isala, Zwolle, The Netherlands
| | - Leon M G Moons
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Miangela M Laclé
- Department of Pathology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
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Lucarini A, Guida AM, Panis Y. Laparoscopic approach for rectal cancer surgery: triumph of reason or necessity of evolution? Cir Esp 2025:S2173-5077(25)00013-4. [PMID: 39855554 DOI: 10.1016/j.cireng.2024.11.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 11/21/2024] [Indexed: 01/27/2025]
Abstract
The role of laparoscopy in rectal cancer surgery has evolved considerably since the early 2000s. Initial randomized trials, such as COLOR II and COREAN, indicated that laparoscopic approaches offered similar pathological outcomes with better postoperative recovery than open surgery. In contrast, trials like ACOSOG Z6051 and ALaCaRT suggested noninferiority could not be established. Variability in trial outcomes, focusing on either disease-free survival or pathological measures, initially hindered consensus. Long-term analyses have shown no significant difference in disease-free survival between laparoscopic and open approaches. Meta-analyses have reinforced the benefits of laparoscopic surgery, with reduced mortality and similar oncologic effectiveness to open surgery. However, new techniques like transanal TME (TaTME) and robotic approaches have introduced alternatives, though each presents unique challenges, from recurrence rates in TaTME to costs in robotics. While laparoscopy remains the preferred method due to accessibility and outcomes, robotic surgery is expected to gain traction in high-volume centers.
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Affiliation(s)
- Alessio Lucarini
- Colorectal Surgery Center, Groupe Hospitalier Privé Ambroise Paré-Hartmann, Neuilly sur Seine, France; Surgical and Medical Department of Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035, 00189 Rome, Italy
| | - Andrea Martina Guida
- Colorectal Surgery Center, Groupe Hospitalier Privé Ambroise Paré-Hartmann, Neuilly sur Seine, France; Department of Surgical Science, University Tor Vergata, Viale Oxford 81, 00133, Rome, Italy
| | - Yves Panis
- Colorectal Surgery Center, Groupe Hospitalier Privé Ambroise Paré-Hartmann, Neuilly sur Seine, France.
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22
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Wu T, Fang L, Ruan Y, Shi M, Su D, Ma Y, Ma M, Wang B, Liao Y, Han S, Lu X, Zhang C, Liu C, Zhang Y. Tumor aggression-defense index-a novel indicator to predicts recurrence and survival in stage II-III colorectal cancer. J Transl Med 2025; 23:107. [PMID: 39844178 PMCID: PMC11755833 DOI: 10.1186/s12967-025-06141-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/13/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Although the TNM staging system plays a critical role in guiding adjuvant chemotherapy for colorectal cancer (CRC), its precision for risk stratification in stage II and III CRC patients with proficient DNA mismatch repair (pMMR) remains limited. Therefore, precise predictive models and research on postoperative treatments are crucial for enhancing patient survival and improving quality of life. METHODS This retrospective study analyzed 1051 pMMR CRC patients who underwent radical resection and were randomly assigned to training (n = 736) and validation (n = 315) groups. Immunohistochemistry and hematoxylin and eosin staining were utilized to evaluate regulatory-Immunoscore (RIS), tertiary lymphoid structures (TLS), and tumor budding (TB). The Tumor Aggression-Defense Index (TADI) was derived through a multi-factor COX regression model. Subgroup analysis demonstrated potential of TADI in guiding personalized adjuvant therapy for stage II and III CRC. RESULTS Univariate and multivariate Cox analysis indicated that TADI was an independent prognostic indicator. Among stage II CRC, chemotherapy was significantly correlated with improved recurrence times in individuals with intermediate (95% CI 0.19-0.59, P < 0.001) and high (95% CI 0.36-0.95, P = 0.031) TADI. In stage III CRC receiving adjuvant chemotherapy, a duration of 3 months or longer was notably associated with a prolonged time to recurrence in those with high TADI (95% CI 0.40-0.98, P = 0.041) compared to durations of less than 3 months. CONCLUSION The TADI serves as an effective parameter for predicting the survival outcomes of stage I-III pMMR CRC patients and guiding precision treatment strategies.
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Affiliation(s)
- Tong Wu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China
| | - Lin Fang
- Phase I Clinical Research Center, The Affiliated Hospital of Qingdao University in Shandong, Qingdao, China
| | - Yuli Ruan
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China
| | - Mengde Shi
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China
| | - Dan Su
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China
| | - Yue Ma
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China
| | - Ming Ma
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China
| | - Bojun Wang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China
| | - Yuanyu Liao
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China
| | - Shuling Han
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China
| | - Xiaolin Lu
- Department of Orthopedic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Chunhui Zhang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China.
| | - Chao Liu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China.
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China.
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China.
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China.
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China.
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China.
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Popęda M, Żok J, Tomasik B, Duchnowska R, Bieńkowski M. Complete blood counts as potential risk factors of early dissemination to liver and lungs in resected colorectal cancer: a retrospective cohort study. Int J Colorectal Dis 2025; 40:21. [PMID: 39836241 PMCID: PMC11750913 DOI: 10.1007/s00384-024-04802-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/30/2024] [Indexed: 01/22/2025]
Abstract
PURPOSE Liver and lung metastases demonstrate distinct biological, particularly immunological, characteristics. We investigated whether preoperative complete blood count (CBC) parameters, which may reflect the immune system condition, predict early dissemination to the liver and lungs in colorectal cancer (CRC). METHODS In this retrospective single-centre study, we included 268 resected CRC cases with complete 2-year follow-up and analysed preoperative CBC for association with early liver or lung metastasis development. Next, selected CBC and clinicopathological parameters were analysed with uni- and multivariable Cox regression. Independent factors affecting liver or lung metastasis-free survival were incorporated into composite scores, which were further evaluated with receiver operating characteristic (ROC) curves and dichotomised using a modified, specificity-focused, Youden approach to identify particularly high-risk patients. RESULTS Compared to metastasis-free patients, early liver metastases were related to decreases in red blood cells, haematocrit, lymphocytes and elevated monocyte-to-lymphocyte ratio, while lung metastases to lower eosinophil counts. A composite score of independent factors (erythrocytopenia, lower lymphocyte count and pN) yielded HR of 8.01 (95% CI 3.45-18.57, p < 0.001) for liver-specific metastasis-free survival (MFS). For lung-specific MFS, the combination of eosinopenia, pN and primary tumour location showed HR of 13.69 (95% CI 4.34-43.20, p < 0.001). CONCLUSION Early CRC metastases to the liver and lungs are associated with partially divergent clinicopathological and peripheral blood features. We propose simple, clinically implementable scores, based on routinely assessed parameters, to identify patients with an increased risk of early dissemination to the liver or lungs. After validation in independent cohorts, these scores may provide easily available prognostic information.
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Affiliation(s)
- Marta Popęda
- Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
| | - Jolanta Żok
- Department of Oncology, Military Institute of Medicine, Warsaw, Poland
| | - Bartłomiej Tomasik
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
| | - Renata Duchnowska
- Department of Oncology, Military Institute of Medicine, Warsaw, Poland
| | - Michał Bieńkowski
- Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland
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24
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Liu G, Liu K, Ji L, Li Y. Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma. Sci Rep 2025; 15:2568. [PMID: 39833403 PMCID: PMC11747563 DOI: 10.1038/s41598-025-87194-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/16/2025] [Indexed: 01/22/2025] Open
Abstract
The intratumoral microbiota, fatty acid metabolism (FAM), and tumor microenvironment (TME) all provide insights into the management of colon adenocarcinoma (COAD). But the biological link among the three remains unclear. Here, we analyzed intratumoral microbiome samples and matched host transcriptome samples from 420 patients with COAD in The Cancer Genome Atlas (TCGA). All patients were divided into two subtypes (FAM_high and FAM_low) based on the Gene set variation analysis (GSVA) score of FAM pathway. Furthermore, we found significant difference in the intratumoral microbiota signatures between the two subtypes. In-depth analysis suggested that specific microbes in tumors may indirectly modify the TME, particularly stromal cell populations, by modulating the FAM process. More importantly, the crosstalk between the three can have a significant impact on prognosis, response to immunotherapy, and drug sensitivity of patients. Pathological image profiling showed that changes in the TME originating from intratumoral microbiota disturbance could be reflected in pathological image features. In summary, our study provides novel insights into the biological links among the intratumoral microbiota, FAM, and the TME in COAD, and offer guidance for the therapeutic opportunities that target intratumoral microbes.
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Affiliation(s)
- Guangyi Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kun Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lei Ji
- Geneis Beijing Co., Ltd., Beijing, 100102, China
| | - Yang Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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25
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González-Flores E, Garcia-Carbonero R, Élez E, Redondo-Cerezo E, Safont MJ, Vera García R. Gender and sex differences in colorectal cancer screening, diagnosis and treatment. Clin Transl Oncol 2025:10.1007/s12094-024-03801-0. [PMID: 39821481 DOI: 10.1007/s12094-024-03801-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 11/18/2024] [Indexed: 01/19/2025]
Abstract
Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes. However, gender differences also play a role, affecting risk factors, access to or participation in screening and treatment, and patients' experience of treatment (e.g. adverse events and sequelae). Sex and gender issues warrant further investigation in CRC to optimise treatment outcomes for patients.
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Affiliation(s)
- Encarnación González-Flores
- Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas, 2, Beiro, 18014, Granada, Spain.
- Instituto de Investigación biosanitaria.ibs.granada, Granada, Spain.
| | - Rocio Garcia-Carbonero
- Department of Medical Oncology, Hospital Universitario 12 de Octubre, Imas12, Medicine Faculty, Universidad Complutense Madrid (UCM), Madrid, Spain
| | - Elena Élez
- Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Eduardo Redondo-Cerezo
- Instituto de Investigación biosanitaria.ibs.granada, Granada, Spain
- Department of Gastroenterology, Hospital Universitario Virgen de las Nieves, Granada, Spain
- Department of Medicine, The University of Granada, Granada, Spain
| | - María José Safont
- Department of Medical Oncology, University General Hospital of Valencia, Valencia University, CIBERONC, Valencia, Spain
| | - Ruth Vera García
- Department of Medical Oncology, University Hospital of Navarra, Instituto de Investigación Sanitaria de Navarra, IdISNA, Navarra, Spain
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26
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Zimmermann M, Abdalla TSA, Schlüter KU, Thomaschewski M, Keck T, Schlöricke E. Clinical and economic effects of the transformation from an open to a laparoscopic center for colorectal surgery. Langenbecks Arch Surg 2025; 410:38. [PMID: 39810015 PMCID: PMC11732922 DOI: 10.1007/s00423-024-03590-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 12/19/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE The purpose of this study was to assess the feasibility of transitioning from open to laparoscopic surgery for colorectal carcinoma in a primary care hospital setting. Despite the recognized benefits of laparoscopic surgery in postoperative recovery and its demonstrated oncological equivalence, only a minority of patients (30-40%) in Germany undergo laparoscopic procedures, primarily due to concerns which, in addition to the perioperative quality data and economic aspects, focus on patient safety. METHODS Over a three-year period (2012-2014), the transformation process was observed in a colorectal cancer center. Data from 237 patients (115 laparoscopic; 122 open) were collected prospectively and analyzed retrospectively. Short-term outcomes, including demographic data, perioperative complications, and quality metrics, as well as long-term survival data, were included. RESULTS Laparoscopic surgery demonstrated several advantages. Postoperative intensive care needs decreased significantly (average length of stay: laparoscopic 1.2 days vs. open 2.5 days; p = 0.032). Hospital stays were also shorter following laparoscopic surgery (median laparoscopic 10 days vs. median open 14 days; p = 0.011). Quality of specimens, particularly lymph node retrieval, remained comparable (median laparoscopic = 18 vs. median open = 19). Survival data showed non- inferiority of the laparoscopic approach. Despite higher initial costs, laparoscopic surgery yielded cost savings of approximately 3150 € per case due to reduced intensive care and shorter hospital stays. CONCLUSION In conclusion, this study demonstrates the feasibility of transitioning from open to laparoscopic oncologic colorectal surgery in a primary care hospital setting. The findings suggest that such a transition can be accomplished without compromising the quality of specimens, while also realizing cost savings and maintaining patient safety.
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Affiliation(s)
- Markus Zimmermann
- Department of General Surgery, University Medical Center Schleswig Holstein, Campus Lübeck, Ratzeburger Alle 160, 23564, Lübeck, Germany.
| | - Thaer S A Abdalla
- Department of General Surgery, University Medical Center Schleswig Holstein, Campus Lübeck, Ratzeburger Alle 160, 23564, Lübeck, Germany
| | - Kai-Uwe Schlüter
- Department of General Surgery, Westküstenklinikum Heide, Esmarchstraße 50, 25746, Heide, Germany
| | - Michael Thomaschewski
- Department of General Surgery, University Medical Center Schleswig Holstein, Campus Lübeck, Ratzeburger Alle 160, 23564, Lübeck, Germany
| | - Tobias Keck
- Department of General Surgery, University Medical Center Schleswig Holstein, Campus Lübeck, Ratzeburger Alle 160, 23564, Lübeck, Germany
| | - Erik Schlöricke
- Department of General Surgery, Westküstenklinikum Heide, Esmarchstraße 50, 25746, Heide, Germany
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27
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Yavuz R, Aras O, Çiyiltepe H, Dinçer Oİ, Alparslan AŞ, Çakır T. Effects of Microsatellite Instability on the Clinical and Pathological Characteristics of Colon Cancer and the Diagnostic Accuracy of Preoperative Abdominal CT Scans. Diagnostics (Basel) 2025; 15:190. [PMID: 39857073 PMCID: PMC11765182 DOI: 10.3390/diagnostics15020190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/02/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Microsatellite-stable (MSS) and microsatellite-instable (MSI) colon cancer (CC) cases have different characteristics. These characteristics may impact the accuracy of abdominal computed tomography (CT) scan examinations in MSI CC. Methods: A retrospective analysis was conducted to examine the effects of MSI CC on patients' clinical and tumor characteristics. We determined the accuracy of radiological T and N staging compared to pathological T and N staging in CC patients and evaluated the influence of tumor- and patient-related factors on this accuracy. Results: A total of 131 CC patients who had undergone surgical resection were analyzed. Mismatch repair-deficient (dMMR) CC was predominantly found in the right hemicolon (p = 0.023); it was more likely to exhibit moderate (80.8%) or low-grade differentiation (p = 0.01) and had higher rates of mucinous differentiation (p = 0.001). The median neutrophil and platelet counts and C-reactive protein (CRP) levels at diagnosis were significantly higher in patients with dMMR CC (p = 0.022, p = 0.022, and p = 0.018). The depth of invasion influenced the CRP levels in dMMR CC cases (p = 0.015). The abdominal CT exam was accurate regarding the depth of colonic wall invasion in 58.1% and 38.5% of patients with mismatch repair-proficient (pMMR) and dMMR CC, respectively. The assessment of lymph node invasion was accurate in 44.8% of those with pMMR and 50.0% of those with dMMR CC. There was no significant difference in the accuracy in predicting the T and N statuses between the two groups. The accuracy in the determination of the T and N statuses was not affected by the parameters examined. Conclusions: dMMR CC has specific characteristic features. MSI does not affect the accuracy of preoperative abdominal CT.
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Affiliation(s)
- Rıdvan Yavuz
- Gastroenterology Surgery Department, Antalya Training and Research Hospital, Varlık, Kazım Karabekir Cd., Muratpaşa 07100, Antalya, Turkey; (O.A.); (H.Ç.); (O.İ.D.); (T.Ç.)
| | - Orhan Aras
- Gastroenterology Surgery Department, Antalya Training and Research Hospital, Varlık, Kazım Karabekir Cd., Muratpaşa 07100, Antalya, Turkey; (O.A.); (H.Ç.); (O.İ.D.); (T.Ç.)
| | - Hüseyin Çiyiltepe
- Gastroenterology Surgery Department, Antalya Training and Research Hospital, Varlık, Kazım Karabekir Cd., Muratpaşa 07100, Antalya, Turkey; (O.A.); (H.Ç.); (O.İ.D.); (T.Ç.)
| | - Onur İlkay Dinçer
- Gastroenterology Surgery Department, Antalya Training and Research Hospital, Varlık, Kazım Karabekir Cd., Muratpaşa 07100, Antalya, Turkey; (O.A.); (H.Ç.); (O.İ.D.); (T.Ç.)
| | - Ahmet Şükrü Alparslan
- Radiology Department, Antalya Training and Research Hospital, Varlık, Kazım Karabekir Cd., Muratpaşa 07100, Antalya, Turkey;
| | - Tebessüm Çakır
- Gastroenterology Surgery Department, Antalya Training and Research Hospital, Varlık, Kazım Karabekir Cd., Muratpaşa 07100, Antalya, Turkey; (O.A.); (H.Ç.); (O.İ.D.); (T.Ç.)
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28
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Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025; 10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
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Affiliation(s)
- Tianzuo Zhan
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johannes Betge
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nadine Schulte
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lena Dreikhausen
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moying Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Antonia Leipertz
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
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Kawazoe T, Nakanishi R, Ando K, Zaitsu Y, Kudou K, Nakashima Y, Oki E, Yoshizumi T. Preoperative CT lymph node size as a predictor of nodal metastasis in resectable Colon cancer: a retrospective study of 694 patients. BMC Gastroenterol 2025; 25:18. [PMID: 39815179 PMCID: PMC11734230 DOI: 10.1186/s12876-025-03602-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/09/2025] [Indexed: 01/18/2025] Open
Abstract
PURPOSE This study aimed to investigate the efficacy of measuring lymph node size on preoperative CT imaging to predict pathological lymph node metastasis in patients with colon cancer to enhance diagnostic accuracy and improve treatment planning by establishing more reliable assessment methods for lymph node metastasis. METHODS We retrospectively analyzed 1,056 patients who underwent colorectal resection at our institution between January 2004 and March 2020. From this cohort, 694 patients with resectable colon cancer were included in the study. We analyzed the relationship between lymph node size on preoperative CT imaging and lymph node metastasis identified on postoperative pathological examination. RESULTS The optimal cutoff values for the maximum long diameter and short diameter of regional lymph nodes on preoperative CT were identified as 6.5 mm and 5.5 mm, respectively, with an AUC of 0.7794 and 0.7755, respectively. Notably, the predictive accuracy varied by tumor location. Higher cutoff values were observed in the right-sided colon (maximum long diameter: 7.7 mm, maximum short diameter: 5.9 mm) compared to the left-sided colon (maximum long diameter: 5.8 mm, maximum short diameter: 5.2 mm). CONCLUSION Lymph node size on preoperative CT is a significant predictor of pathological lymph node metastasis in colon cancer. Notably, the optimal cutoff values for predicting lymph node metastasis vary depending on the specific region within the colon.
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Affiliation(s)
- Tetsuro Kawazoe
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Ryota Nakanishi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koji Ando
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoko Zaitsu
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kensuke Kudou
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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30
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Tan Y, Hu B, Li Q, Cao W. Prognostic value and clinicopathological significance of pre-and post-treatment systemic immune-inflammation index in colorectal cancer patients: a meta-analysis. World J Surg Oncol 2025; 23:11. [PMID: 39806457 PMCID: PMC11731527 DOI: 10.1186/s12957-025-03662-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 01/07/2025] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND In recent years, the association between systemic immune-inflammation index (SII) and the prognosis of patients with colorectal cancer (CRC) has remained a topic of considerable debate. To address this, the present study was carried out to investigate the prognostic significance of SII in CRC. METHODS Databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science were scrutinized up to March 27, 2024. The relationship between pre- and post-treatment SII levels and the prognosis of CRC was evaluated. Following literature screening, quality assessment, and extraction of outcome measures, a meta-analysis was conducted using Stata. Publication bias was assessed by funnel plots and Egger's test. RESULTS A total of 27 studies were included in the analysis. Pooled results demonstrated that a high SII level was associated with poor overall survival (OS, HR = 1.78, 95% CI = 1.40-2.26), progression-free survival (PFS, HR = 1.80, 95% CI = 1.26-2.56), disease-free survival (DFS, HR = 1.91, 95% CI = 1.43-2.56), and recurrence-free survival (RFS, HR = 3.29, 95% CI = 1.58-6.88). Notably, the association between pre-treatment SII and OS, PFS, and DFS was stronger than that observed for post-treatment SII, indicating that treatment may attenuate the predictive valueof SII for survival outcomes. Additionally, elevated SII was correlated with poor tumor differentiation, tumor location in the rectum, and larger tumor size ≥ 5 cm. CONCLUSION Our meta-analysis suggested that a high SII is a predictor of poor prognosis in CRC patients. High SII levels were strongly correlated with inferior OS, PFS, DFS, and RFS. The relationship between SII and survival outcomes was attenuated post-treatment compared to pre-treatment. Additionally, elevated SII was correlated with clinicopathological factors in CRC patients. These findings suggest that SII can serve as an independent prognostic indicator for CRC.
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Affiliation(s)
- Yueting Tan
- Hunan University of Traditional Chinese Medicine, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No. 233, Cai'e North Road, Kaifu District, Changsha, Hunan, 410005, China
| | - Bei'er Hu
- Hunan University of Traditional Chinese Medicine, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No. 233, Cai'e North Road, Kaifu District, Changsha, Hunan, 410005, China
| | - Qian Li
- Hunan University of Traditional Chinese Medicine, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No. 233, Cai'e North Road, Kaifu District, Changsha, Hunan, 410005, China
| | - Wen Cao
- Hunan University of Traditional Chinese Medicine, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, No. 233, Cai'e North Road, Kaifu District, Changsha, Hunan, 410005, China.
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31
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Seligmann JF, Morton D, Elliott F, Handley K, Gray R, Seymour M, Glimelius B, Magill L, Williams CJM, Quirke P, Bottomley D, Wood HM, Murakami K, Beggs AD, West NP. Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT Trial embedded phase II population. Ann Oncol 2025:S0923-7534(25)00002-X. [PMID: 39805350 DOI: 10.1016/j.annonc.2024.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/19/2024] [Accepted: 12/20/2024] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND The FOxTROT trial has reported advantages of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). Here we present results of the embedded randomized phase II trial testing the addition of panitumumab to neoadjuvant FOLFOX compared with FOLFOX alone in RAS and BRAF-wild-type patients and with biomarker hyperselction. PATIENTS AND METHODS Patients had operable, CT-predicted stage T3-4, N0-2, M0 colon adenocarcinoma. KRAS-wt pts allocated to NAC could optionally be sub-randomized 1:1 to FOLFOX ± panitumumab during the pre-operative phase. RAS/BRAF were tested by NGS; EREG/AREG by RNAseq. Primary endpoint is time to recurrence (TTR) in RAS/BRAF-wt patients; secondary endpoints include safety, histological downstaging, disease-free survival (DFS), colon cancer-specific survival (CCSS), overall survival (OS), and impact of primary tumor location and EREG/AREG. RESULTS In total 269 KRAS-wt patients were enrolled into the embedded phase II trial. Extended RAS/BRAF data were available for 232 (83%) patients; 22/232(9.5%) were RAS-mutant; 41/210(20%) were BRAF-mutant. Median follow up was 42 months. In 169 RAS/BRAF-wt patients there was a trend towards reduced recurrences with FOLFOX plus panitumumab compared with FOLFOX (12% vs 21%, HR=0.51, p=0.09); significant improvements were seen for DFS, CCSS and OS. Within the hyperselected EREG/AREG high group, there was significant reduction in recurrences with panitumumab. Panitumumab was not associated with increased pathological regression of the primary tumor (TRG 1-3 16% vs 22%,p=0.27). FOLFOX plus panitumumab was associated with higher rates of grade 3 diarrhoea (8% vs 3%,) and rash (22% vs 2%). CONCLUSION This exploratory analysis from a randomized phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to peri-operative FOLFOX in RAS/BRAF-wt LACC. Hyperselection with EREG/AREG status was associated with increased efficacy. A dedicated prospective trial within a biomarker selected population is under development. CLINICAL TRIALS REGISTRATION ISRCTN87163246.
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Affiliation(s)
- J F Seligmann
- Division of Oncology, Leeds Institute of Medical Research, University of Leeds, UK.
| | - D Morton
- University Hospital Birmingham, Birmingham, UK
| | - F Elliott
- Division of Oncology, Leeds Institute of Medical Research, University of Leeds, UK
| | - K Handley
- University of Birmingham Clinical Trials Unit, Birmingham, UK
| | - R Gray
- Clinical Trials Service Unit, University of Oxford, Oxford, UK
| | - M Seymour
- Division of Oncology, Leeds Institute of Medical Research, University of Leeds, UK
| | | | - L Magill
- University of Birmingham Clinical Trials Unit, Birmingham, UK
| | - C J M Williams
- Division of Oncology, Leeds Institute of Medical Research, University of Leeds, UK
| | - P Quirke
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research, University of Leeds, UK
| | - D Bottomley
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research, University of Leeds, UK
| | - H M Wood
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research, University of Leeds, UK
| | - K Murakami
- Department of Pathology, Tohoku University, Sendai, Japan
| | - A D Beggs
- Institute of Cancer & Genomic Sciences, University of Birmingham, UK
| | - N P West
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research, University of Leeds, UK
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Pompeu BF, de Souza Pinto Guedes LS, Sobrinho CMCC, Brunini JH, Borges L, de Figueiredo SMP, Junior SA, Formiga FB. Partial versus radical cystectomy in localized colorectal cancer: a systematic review and meta-analysis. Int Urol Nephrol 2025:10.1007/s11255-025-04367-8. [PMID: 39798047 DOI: 10.1007/s11255-025-04367-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 01/04/2025] [Indexed: 01/13/2025]
Abstract
PURPOSE Locally advanced colorectal tumors frequently invade adjacent organs, particularly the urinary bladder in the sigmoid colon and upper rectum, complicating multivisceral resections. This study compared postoperative outcomes of partial cystectomy (PC) and total cystectomy (TC) in patients with locally advanced colorectal cancer. METHODS A systematic review was conducted in PubMed, Scopus, Central Register of Clinical Trials, and Web of Science for studies published up to November 2024. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with I2 statistics. Statistical analyses were performed in R Software 4.4.1. RESULTS Nine retrospective studies including 894 patients were analyzed. Among them, 433 (48.43%) underwent PC, and 461 (51.57%) underwent TC. Compared to TC, PC was associated with significantly lower rates of surgical site infection (OR 0.33; 95% CI 0.13-0.80; p = 0.015), shorter operative time (MD - 169.7 min; 95% CI - 214.1 to - 125.3; p < 0.01), reduced blood loss (MD - 1005.9 ml; 95% CI - 1362.1 to - 649.8; p < 0.01), and shorter hospital stay (MD - 6.6 days; 95% CI - 9.4 to - 3.9; p < 0.01). No significant differences were observed between groups in local or distant recurrence, urinary and intestinal leaks, pelvic abscess, ileus, urinary tract infection, or 90-day mortality. CONCLUSION Partial cystectomy demonstrated superior postoperative outcomes, including fewer surgical site infections, reduced operative time, less blood loss, and shorter hospitalization. Oncological outcomes and other postoperative complications were comparable between PC and TC, supporting PC as a safe and effective option in selected patients.
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Affiliation(s)
- Bernardo Fontel Pompeu
- Department of Colorectal Surgery, Heliopolis Hospital, São Paulo, SP, Brazil.
- University of São Caetano do Sul, Rua Santo Antônio, 50-Centro, São Caetano do Sul, SP, 09521-160, Brazil.
| | | | | | - Julia Hoici Brunini
- Department of Colorectal Surgery, Heliopolis Hospital, São Paulo, SP, Brazil
| | - Leonardo Borges
- Department of Urology, Albert Einstein Hospital, São Paulo, Brazil
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Crisafulli G. Liquid Biopsy and Challenge of Assay Heterogeneity for Minimal Residual Disease Assessment in Colon Cancer Treatment. Genes (Basel) 2025; 16:71. [PMID: 39858618 PMCID: PMC11765229 DOI: 10.3390/genes16010071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/07/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
This review provides a comprehensive overview of the evolving role of minimal residual disease (MRD) for patients with Colon Cancer (CC). Currently, the standard of care for patients with non-metastatic CC is adjuvant chemotherapy (ACT) for all patients with stage III and high-risk stage II CC following surgical intervention. Despite a 5-20% improvement in long-term survival outcomes, this approach also results in a significant proportion of patients receiving ACT without any therapeutic benefit and being unnecessarily exposed to the risks of secondary side effects. This underscores an unmet clinical need for more precise stratification to distinguish patients who necessitate ACT from those who can be treated with surgery alone. By employing liquid biopsy, it is possible to discern MRD enabling the categorization of patients as MRD-positive or MRD-negative, potentially revolutionizing the management of ACT. This review aimed to examine the heterogeneity of methodologies currently available for MRD detection, encompassing the state-of-the-art technologies, their respective advantages, limitations, and the technological challenges and multi-omic approaches that can be utilized to enhance assay performance. Furthermore, a discussion was held regarding the clinical trials that employ an MRD assay focusing on the heterogeneity of the assays used. These differences in methodology, target selection, and performance risk producing inconsistent results that may not solely reflect biological/clinical differences but may be the consequence of the preferential use of particular products in studies conducted in different countries. Standardization and harmonization of MRD assays will be crucial to ensure the liquid revolution delivers reliable and clinically actionable outcomes for patients.
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Zhou J, Huang J, Zhou Z, Fan R, Deng X, Qiu M, Wu Q, Wang Z. Value of ctDNA in surveillance of adjuvant chemosensitivity and regimen adjustment in stage III colon cancer: a protocol for phase II multicentre randomised controlled trial (REVISE trial). BMJ Open 2025; 15:e090394. [PMID: 39753246 PMCID: PMC11749494 DOI: 10.1136/bmjopen-2024-090394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION The standard of care for stage III colon cancer is 3 or 6 months of double-drug regimen chemotherapy following radical surgery. However, patients with positive circulating tumour DNA (ctDNA) exhibit a high risk of recurrence risk even if they receive standard adjuvant chemotherapy. The potential benefit of intensified adjuvant chemotherapy, oxaliplatin, irinotecan, leucovorin and fluoropyrimidine (FOLFOXIRI), for ctDNA-positive patients remains to be elucidated. METHODS AND ANALYSIS This multicentre phase II randomised controlled trial aims to investigate the utility of ctDNA in monitoring chemosensitivity and to preliminarily assess whether intensified chemotherapy with FOLFOXIRI can increase ctDNA clearance and improve survival outcomes. A total of 60 eligible patients with stage III colon cancer exhibiting postoperatively positive ctDNA before and after two cycles of oxaliplatin and capecitabine (XELOX) will be randomly assigned to continue five additional cycles of XELOX (control arm) or switch to eight cycles of FOLFOXIRI (experimental arm). This sequential approach is designed to escalate treatment for patients with persistent ctDNA positivity while avoiding overtreatment in those who may respond well to standard chemotherapy. The primary endpoint is the change in ctDNA concentration, defined as the difference between the ctDNA concentration measured after two cycles of XELOX and after the completion or termination of chemotherapy. Secondary endpoints include the ctDNA clearance rate, 2-year disease-free survival, distant metastasis-free survival, chemotherapy-related side effects and quality of life. ETHICS AND DISSEMINATION This trial has been approved by the Ethics Committee of the West China Hospital, Sichuan University (approval number: 20231998). The findings will be disseminated through peer-reviewed publications and presentations at scientific conferences. TRIAL REGISTRATION NUMBER ClinicalTrials.gov (NCT06242418, registered on 27 January 2024).
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Affiliation(s)
- Jiahao Zhou
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jun Huang
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Zikai Zhou
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Rui Fan
- Genecast Biotechnology Co Ltd, Jiangsu, China
| | - Xiangbing Deng
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Meng Qiu
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Qingbin Wu
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Ziqiang Wang
- Colorectal Cancer Center, Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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Ferkel SAM, Holman EA, Sojwal RS, Rubin SJS, Rogalla S. Tumor-Infiltrating Immune Cells in Colorectal Cancer. Neoplasia 2025; 59:101091. [PMID: 39642846 DOI: 10.1016/j.neo.2024.101091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 11/18/2024] [Indexed: 12/09/2024]
Abstract
Colorectal cancer encompasses a heterogeneous group of malignancies that differ in pathophysiological mechanisms, immune response and infiltration, therapeutic response, and clinical prognosis. Numerous studies have highlighted the clinical relevance of tumor-infiltrating immune cells among different types of colorectal tumors yet vary in cell type definitions and cell identification strategies. The distinction of immune signatures is particularly challenging when several immune subtypes are involved but crucial to identify novel intercellular mechanisms within the tumor microenvironment. In this review, we compile human and non-human studies on tumor-infiltrating immune cells and provide an overview of immune subtypes, their pathophysiological functions, and their prognostic role in colorectal cancer. We discuss how differentiating immune signatures can guide the development of immunotherapeutic targets and personalized treatment regimens. We analyzed comprehensive human protein biomarker profiles across the entire immune spectrum to improve interpretability and application of tumor studies and to ultimately enhance immunotherapy and advance precision medicine for colorectal cancer patients.
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Affiliation(s)
- Sonia A M Ferkel
- Stanford University, School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, USA
| | - Elizabeth A Holman
- Stanford University, School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, USA
| | - Raoul S Sojwal
- Stanford University, School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, USA
| | - Samuel J S Rubin
- Stanford University, School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, USA
| | - Stephan Rogalla
- Stanford University, School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Stanford, USA.
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Inoue H, Shimizu H, Kuriu Y, Arita T, Nanishi K, Kiuchi J, Ohashi T, Yamamoto Y, Konishi H, Morimura R, Shiozaki A, Ikoma H, Kubota T, Fujiwara H, Otsuji E. Patients with T4N0 and T1‑3N1 colon cancer and a high preoperative carcinoembryonic antigen level benefit from adjuvant chemotherapy with oxaliplatin for 6 months. Oncol Lett 2025; 29:13. [PMID: 39526306 PMCID: PMC11544698 DOI: 10.3892/ol.2024.14759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 09/20/2024] [Indexed: 11/16/2024] Open
Abstract
A shorter duration of oxaliplatin adjuvant chemotherapy has recently emerged as a potential option for patients with high-risk stage II and low-risk stage III (T1-3N1) colon cancer (CC). The present study aimed to elucidate the risk factors for recurrence in these patient populations and to identify the appropriate indications for shortened treatment durations. The present study retrospectively analyzed 396 patients who underwent curative surgery for pathological T4N0 or stage III CC, followed by adjuvant chemotherapy, at two institutes. Overall, 234 patients with T4N0 and low-risk stage III CC were categorized into the low-risk group and 162 patients with high-risk stage III CC into the high-risk group. The 3-year relapse-free survival rate was significantly higher in the low-risk group than in the high-risk group. Multivariate Cox model analysis of the low-risk group revealed that high preoperative serum levels of carcinoembryonic antigen (CEA) and incomplete 6-month adjuvant chemotherapy with oxaliplatin were independent poor prognostic factors. The prognosis of patients in the low-risk group who had abnormal CEA levels and did not complete the 6-month adjuvant treatment with oxaliplatin was similar to that of patients in the high-risk group. However, the prognosis of patients in the low-risk group with high CEA levels improved with a 6-month adjuvant treatment with oxaliplatin to a similar level to that of all patients with low CEA levels in the low-risk group. In conclusion, the present study suggested that the duration of adjuvant chemotherapy with oxaliplatin should not be shortened in patients with high preoperative CEA levels, even in the low-risk group.
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Affiliation(s)
- Hiroyuki Inoue
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
- Department of Digestive Surgery, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto 605-0981, Japan
| | - Hiroki Shimizu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Yoshiaki Kuriu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Kenji Nanishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Jun Kiuchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Takuma Ohashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Yusuke Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Ryo Morimura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Leonhardi J, Mehdorn M, Stelzner S, Scheuermann U, Höhn AK, Seehofer D, Schnarkowski B, Denecke T, Meyer HJ. Diagnostic accuracy and reliability of CT-based Node-RADS for colon cancer. Abdom Radiol (NY) 2025; 50:1-7. [PMID: 38976057 PMCID: PMC11711253 DOI: 10.1007/s00261-024-04485-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/24/2024] [Accepted: 06/30/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVE The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of the Node-RADS classification of staging computed tomography (CT) images to categorize and stage lymph nodes in patients with colon cancer. MATERIALS AND METHODS All patients were surgically resected and the lymph nodes were histopathological analyzed. All investigated lymph nodes were scored in accordance to the Node-RADS classification by two experienced radiologists. Interreader variability was assessed with Cohen's kappa analysis, discrimination analysis was performed with Mann-Whitney-U test and diagnostic accuracy was assessed with receiver-operating characteristics (ROC) curve analysis. RESULTS Overall, 108 patients (n = 49 females, 45.3%) with a mean age of 70.08 ± 14.34 years were included. In discrimination analysis, the total Node-RADS score showed statistically significant differences between N- and N + stage (for reader 1: mean 1.89 ± 1.09 score for N- versus 2.93 ± 1.62 score for N+, for reader 2: 1.33 ± 0.48 score for N- versus 3.65 ± 0.94 score for N+, p = 0.001, respectively). ROC curve analysis for lymph node discrimination showed an area under the curve of 0.68. A threshold value of 2 resulted in a sensitivity of 0.62 and a specificity of 0.71. CONCLUSION Node-RADS score derived from staging CT shows only limited diagnostic accuracy to correctly predict nodal positivity in colon cancer. The interreader variability seems to be high and should question the clinical translation for this tumour entity.
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Affiliation(s)
- Jakob Leonhardi
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
| | - Matthias Mehdorn
- Department of Visceral and Transplantation Surgery, University Hospital Leipzig, University of Leipzig, Leipzig, Germany
| | - Sigmar Stelzner
- Department of Visceral and Transplantation Surgery, University Hospital Leipzig, University of Leipzig, Leipzig, Germany
| | - Uwe Scheuermann
- Department of Visceral and Transplantation Surgery, University Hospital Leipzig, University of Leipzig, Leipzig, Germany
| | - Anne-Kathrin Höhn
- Department of Pathology, University Hospital Leipzig, University of Leipzig, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral and Transplantation Surgery, University Hospital Leipzig, University of Leipzig, Leipzig, Germany
| | - Benedikt Schnarkowski
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
| | - Timm Denecke
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
| | - Hans-Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany.
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Giuliani O, Baldacchini F, Bucchi L, Mancini S, Ravaioli A, Vattiato R, Zamagni F, Sassatelli R, Triossi O, Trande P, Palmonari C, Mussetto A, Fabbri C, Giovanardi M, de Padova A, Falcini F. Factors affecting treatment decisions for endoscopically resected low- and high-risk malignant colorectal polyps in a screening setting. Dig Liver Dis 2025; 57:282-289. [PMID: 39327146 DOI: 10.1016/j.dld.2024.08.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 08/22/2024] [Accepted: 08/30/2024] [Indexed: 09/28/2024]
Abstract
INTRODUCTION The European Guidelines for colorectal cancer screening of 2006 state that only high-risk endoscopically resected malignant colorectal polyps (MCPs), defined as poor/no differentiation or positive resection margins or lymphovascular invasion, require colonic resection. METHODS A multicentre series of 954 patients with screen-detected MCP (northern Italy, 2005-2016, age 50-69) was studied to identify (1) the factors affecting the choice of colonic resection, and (2) the factors associated with deviation from the European Guidelines for low- and high-risk patients. Data analysis was based on multilevel logistic regression models. RESULTS Five hundred sixty-four (59.1 %) patients underwent colonic resection. The factors significantly associated with surgical referral included: distal and rectal versus proximal tumour site (inverse association); sessile and flat versus pedunculated morphology (direct association); tumour size (direct); moderate/poor versus good differentiation (direct); adenocarcinoma of not otherwise specified type versus adenocarcinoma with a residual adenoma component (direct); positive versus negative resection margins (direct); lymphovascular invasion (direct); and high-grade versus low-grade/absent tumour budding (direct). In low-risk MCPs, tumour budding encouraged strongly the decision for surgery. In high-risk MCPs, a distal/rectal tumour site encouraged the follow-up option. CONCLUSION The identification of factors associated with treatment choices other than those currently recommended may help prioritise the clinical questions in the development of future guidelines.
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Affiliation(s)
- Orietta Giuliani
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy
| | - Flavia Baldacchini
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy
| | - Lauro Bucchi
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy.
| | - Silvia Mancini
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy
| | - Alessandra Ravaioli
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy
| | - Rosa Vattiato
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy
| | - Federica Zamagni
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy
| | - Romano Sassatelli
- Unit of Gastroenterology and Digestive Endoscopy, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Omero Triossi
- Gastroenterology Unit, Local Health Authority, Santa Maria delle Croci Hospital, Ravenna, Italy
| | - Paolo Trande
- Struttura Semplice Dipartimentale Screening del Colon-Retto, AUSL di Modena, Modena, Italy
| | - Caterina Palmonari
- Western Health District and UOSD Management, Epidemiology, Oncologic screening, Health promotion programmes, AUSL Ferrara, Ferrara, Italy
| | - Alessandro Mussetto
- Gastroenterology Unit, Local Health Authority, Santa Maria delle Croci Hospital, Ravenna, Italy
| | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Local Health Authority, Forlì-Cesena, Italy
| | - Mauro Giovanardi
- Gastroenterology and Digestive Endoscopy Unit, Local Health Authority, Rimini, Italy
| | - Angelo de Padova
- Gastroenterology and Digestive Endoscopy Unit, Local Health Authority, Rimini, Italy
| | - Fabio Falcini
- Emilia-Romagna Cancer Registry, Romagna Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Forlì, Italy; Cancer Prevention Unit, Local Health Authority, Forlì, Italy
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Palkovsky M, Modrackova N, Neuzil-Bunesova V, Liberko M, Soumarova R. The Bidirectional Impact of Cancer Radiotherapy and Human Microbiome: Microbiome as Potential Anti-tumor Treatment Efficacy and Toxicity Modulator. In Vivo 2025; 39:37-54. [PMID: 39740900 PMCID: PMC11705129 DOI: 10.21873/invivo.13803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/02/2024] [Accepted: 10/14/2024] [Indexed: 01/02/2025]
Abstract
Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapy-induced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects.
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Affiliation(s)
- Martin Palkovsky
- Department of Oncology, University Hospital Kralovske Vinohrady, Prague, Czech Republic;
- Charles University, Third Faculty of Medicine, Department of Oncology, Prague, Czech Republic
| | - Nikol Modrackova
- Czech University of Life Sciences Prague, Department of Microbiology, Nutrition and Dietetics, Faculty of Agrobiology, Food and Natural Resources, Prague, Czech Republic
| | - Vera Neuzil-Bunesova
- Czech University of Life Sciences Prague, Department of Microbiology, Nutrition and Dietetics, Faculty of Agrobiology, Food and Natural Resources, Prague, Czech Republic
| | - Marian Liberko
- Department of Oncology, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Charles University, Third Faculty of Medicine, Department of Oncology, Prague, Czech Republic
| | - Renata Soumarova
- Department of Oncology, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Charles University, Third Faculty of Medicine, Department of Oncology, Prague, Czech Republic
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Berner AM, Murugaesu N. The Evolving Role of Genomics in Colorectal Cancer. Clin Oncol (R Coll Radiol) 2025; 37:103661. [PMID: 39536702 DOI: 10.1016/j.clon.2024.10.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 08/08/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024]
Abstract
Approximately 75% of colorectal cancers (CRCs) harbour an identifiable driver mutation, 5% of which are heritable. These drivers have recognised implications for prognosis and therapy selection. In addition, potential germline mutations require investigations to inform testing of relatives, as well as surveillance for other malignancies. With increasing numbers of targeted drugs being approved, judicious testing is required to ensure sufficient tumour sample is available for testing and at the right point in the cancer pathway. Liquid biopsy with circulating tumour DNA (ctDNA) in the blood presents an exciting adjunct to tumour tissue testing for molecular drivers, as well as escalation and de-escalation of therapy. Here, we review the most frequent molecular alterations in CRC, how genomic testing should be integrated into the treatment pathway for CRC, and sources of further education.
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Affiliation(s)
- A M Berner
- Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6AU, UK
| | - N Murugaesu
- Guy's & St Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, UK; Genomics England, 1 Canada Square, London E14 5AB, UK.
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Cardoso PM, Rodrigues-Pinto E. Self-Expandable Metal Stents for Obstructing Colon Cancer and Extracolonic Cancer: A Review of Latest Evidence. Cancers (Basel) 2024; 17:87. [PMID: 39796716 PMCID: PMC11719978 DOI: 10.3390/cancers17010087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/16/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Colorectal cancer (CRC) is a leading cause of cancer mortality, with many patients presenting with malignant colorectal obstruction (MCO). Self-expandable metal stents (SEMSs) have emerged as a minimally invasive key intervention, both as a bridge to surgery (BTS) in curative setting sand for palliation in advanced disease. This review aims to provide an evidence-based analysis of SEMS indications, contraindications, and efficacy across curative and palliative contexts, with focus on long-term outcomes. Based on data from recent trials and guidelines, we examine SEMS placement outcomes, focusing on specific scenarios, including BTS for left-sided MCO, chemotherapy (with angiogenic agents) safety during stent therapy, the optimal timing between SEMS placement and surgery, and oncological outcomes. We also discuss the use of SEMSs in challenging contexts such as proximal colon obstruction and extracolonic obstruction, and the relevant technical considerations. Findings indicate that using a SEMS in the BTS setting reduces emergency surgery needs, minimizes complications, and decreases stoma formation. Long-term oncologic outcomes, particularly recurrence, are still debated, but recent evidence shows that SEMS placement is safe, without worsening long term outcomes. Palliative SEMS placement shows high efficacy in symptom relief with manageable adverse events. Success depends on patient selection and technical expertise, with multidisciplinary approaches essential for optimal outcomes.
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Affiliation(s)
- Pedro Marílio Cardoso
- Gastroenterology Department, Centro Hospitalar Universitário de São João, 4200-319 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Eduardo Rodrigues-Pinto
- Gastroenterology Department, Centro Hospitalar Universitário de São João, 4200-319 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
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Morera-Ocon FJ, Navarro-Campoy C, Cardona-Henao JD, Landete-Molina F. Colorectal cancer lymph node dissection and disease survival. World J Gastrointest Surg 2024; 16:3890-3894. [PMID: 39734457 PMCID: PMC11650237 DOI: 10.4240/wjgs.v16.i12.3890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/15/2024] [Accepted: 10/18/2024] [Indexed: 11/27/2024] Open
Abstract
The debate regarding the two possible roles of lymphadenectomy in surgical oncology, prognostic or therapeutic, is still ongoing. Furthermore, the use of lymphadenectomy as a proxy for the quality of the surgical procedure is another feature of discussion. Nevertheless, this reckoning depends on patient conditions, aggressiveness of the tumor, the surgeon, and the pathologist, and then it is not an absolute surrogate for the surgical quality. The international guidelines recommend a minimum of 12 lymph nodes harvested for pathological examination in colorectal cancer (CRC) surgery. There is a growing literature on reporting better survival when the lymph node yield is high, even when these nodes are negative for malignancy. On the other hand, there are studies reporting no survival benefit with high lymph node yield in stage I-II of CRC. Herein we review the roles of the lymphadenectomy in CRC, and discuss the results of studies on lymph node harvesting.
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Ceccon C, Borga C, Angerilli V, Bergamo F, Munari G, Sabbadin M, Gasparello J, Schiavi F, Zovato S, Scarpa M, Urso EDL, Dei Tos AP, Luchini C, Grillo F, Lonardi S, Parente P, Fassan M. MLH1 gene promoter methylation status partially overlaps with CpG methylator phenotype (CIMP) in colorectal adenocarcinoma. Pathol Res Pract 2024; 266:155786. [PMID: 39724851 DOI: 10.1016/j.prp.2024.155786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/18/2024] [Accepted: 12/18/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND RAS/BRAF mutations, mismatch DNA repair complex deficiency (MMRd)/microsatellite instability (MSI), and CpG methylator phenotype (CIMP) are key molecular actors in colorectal carcinogenesis. To date, conflicting evidence about the correlations between these molecular features has been reported. MATERIALS AND METHODS A retrospectively selected cohort of 123 CRCs was divided into 3 groups based on the molecular characteristics: MMR proficient (MMRp)/BRAF p.V600E mutated (BRAFmut), MMRd/BRAFmut, and MMRd/BRAF wild type (BRAFwt). MLH1 promoter (pMLH1) methylation status was assessed by pyrosequencing. For 82 samples the CIMP phenotype was evaluated using the EpiTect® MethyLight kit. RESULTS The MMRd/BRAFmut group showed a higher pMLH1 methylation rate compared to both the MMRd/BRAFwt and the MMRp/BRAFmut groups. Overall, the two MMRd groups had a higher methylation rate compared to the MMRp cases independently from the mutational status of BRAF (p-value <0.0001). The MMRd/BRAFmut group was characterized by a 90.0 % of CIMP high (CIMP-H) tumors of which 97.2 % were pMLH1 methylated. Instead, the MMRd/BRAFwt group presented 50.0 % of CIMP-H adenocarcinomas. CONCLUSIONS Our study demonstrates that pMLH1 hypermethylation, MMRd, BRAFmut and CIMP phenotype do not completely overlap in CRC. These findings further refine the knowledge on the molecular landscape of CRC and may have critical implications also for the clinical management of the disease.
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Affiliation(s)
- Carlotta Ceccon
- Department of Medicine - DIMED, University of Padova, Padova, Italy; Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Chiara Borga
- Department of Pathology, Azienda Ospedale-Università Padova, Padua, Italy
| | - Valentina Angerilli
- Department of Medicine - DIMED, University of Padova, Padova, Italy; Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | | | - Giada Munari
- Department of Pathology, Azienda Ospedale-Università Padova, Padua, Italy
| | - Marianna Sabbadin
- Department of Medicine - DIMED, University of Padova, Padova, Italy; Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | | | | | | | - Marco Scarpa
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), Azienda Ospedale-Università Padova, Padua, Italy
| | - Emanuele Damiano Luca Urso
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), Azienda Ospedale-Università Padova, Padua, Italy
| | - Angelo Paolo Dei Tos
- Department of Medicine - DIMED, University of Padova, Padova, Italy; Department of Pathology, Azienda Ospedale-Università Padova, Padua, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Federica Grillo
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Italy
| | - Sara Lonardi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Matteo Fassan
- Department of Medicine - DIMED, University of Padova, Padova, Italy; Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy.
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van den Berg K, van Hellemond IEG, Willems JMWE, Burger JWA, Rutten HJT, Creemers GJ. Neoadjuvant chemotherapy in locally advanced colon cancer: A systematic review with proportional meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 51:109560. [PMID: 39869958 DOI: 10.1016/j.ejso.2024.109560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/08/2024] [Accepted: 12/18/2024] [Indexed: 01/29/2025]
Abstract
Neoadjuvant chemotherapy is suggested in locally advanced colon cancer. Data on improved long-term oncological outcomes are lacking, which hampers the implementation in clinical practice. This systematic review provides an overview of the benefits and drawbacks of neoadjuvant chemotherapy in patients with locally advanced colon cancer. A systematic literature search was performed using Embase (OVID), MEDLINE (OvidSP), and the Cochrane Library. Studies reporting on the efficacy of neoadjuvant chemotherapy in patients with operable, locally advanced colon cancer without metastases at the time of diagnosis were considered eligible for inclusion. An overview of short- and long-term outcomes of neoadjuvant chemotherapy is provided based on available literature. Additionally, proportional meta-analyses were performed using MedCalc Statistical Software version 19.2.6. A total of 17 unique studies were included in this review, 3 randomised controlled trials and 14 prospective single-arm or retrospective studies. The maximum reported dropout before surgery was 7.8 % in the neoadjuvant chemotherapy group. A histopathological complete response after neoadjuvant chemotherapy was observed in 0-4.8 % of the patients. The occurrence of anastomotic leaks was less than 8 % for both patients treated with neoadjuvant chemotherapy and patients treated with upfront surgery. Neoadjuvant chemotherapy is a safe alternative for adjuvant chemotherapy based on the dropout rate before surgery and the peri-operative morbidity and peri-operative mortality. Robust long-term survival outcomes are lacking and serious concerns regarding the risk of overtreatment have been expressed. Hence, neoadjuvant chemotherapy might be considered in a select group of patients with locally advanced colon cancer.
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Affiliation(s)
- K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, Netherlands; Department of Surgery, Catharina Hospital, Eindhoven, Netherlands.
| | | | - J M W E Willems
- Department of Medical Oncology, Anna Hospital, Geldrop, Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, Netherlands
| | - G J Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, Netherlands
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Fu C, Liu X, Wang L, Hang D. The Potential of Metabolomics in Colorectal Cancer Prognosis. Metabolites 2024; 14:708. [PMID: 39728489 DOI: 10.3390/metabo14120708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/27/2024] [Accepted: 12/13/2024] [Indexed: 12/28/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, posing a serious threat to human health. Metabolic reprogramming represents a critical feature in the process of tumor development and progression, encompassing alterations in sugar metabolism, lipid metabolism, amino acid metabolism, and other pathways. Metabolites hold promise as innovative prognostic biomarkers for cancer patients, which is crucial for targeted follow-up care and interventions. This review aims to provide an overview of the progress in research on metabolic biomarkers for predicting the prognosis of CRC. We also discuss the future trends and challenges in this area.
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Affiliation(s)
- Chengqu Fu
- Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative, Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Xinyi Liu
- Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative, Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Le Wang
- Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
| | - Dong Hang
- Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative, Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
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Chibaudel B, Raeisi M, Cohen R, Yothers G, Goldberg RM, Bachet JB, Wolmark N, Yoshino T, Schmoll HJ, Kerr R, Lonardi S, George TJ, Shacham-Shmueli E, Shi Q, André T, de Gramont A. Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis. J Clin Oncol 2024; 42:4187-4195. [PMID: 39231393 PMCID: PMC11624096 DOI: 10.1200/jco.24.00394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/30/2024] [Accepted: 06/17/2024] [Indexed: 09/06/2024] Open
Abstract
PURPOSE The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined. PATIENTS AND METHODS One thousand five hundred and ninety-five patients with stage II CC receiving FP or FPOX were pooled. The overall survival (OS) benefit of OX was analyzed using Kaplan-Meier curves and unadjusted Cox models stratified by study. Three thousand and fifty-nine patients with stage III CC were used only for interaction tests between the allocated chemotherapy and stage. RESULTS In the pooled analysis of stage II patients, independent prognostic factors in multivariable analysis were sex, age, perforation/obstruction, and tumor sidedness. There was a significant interaction in OS between stage and allocated chemotherapy with hazard ratios (HRs) of 1.03 for stage II (95% CI, 0.82 to 1.29; P = .813) and 0.82 for stage III (95% CI, 0.73 to 0.92; P = .001; Pint = .073). There was no benefit from the addition of OX to FP for any of the prognostic factors. The number of high-risk factors tested was not predictive of OX benefit. According to the currently agreed clinicopathologic risk classification, no OS benefit of OX was observed, as HR was 0.86 (95% CI, 0.63 to 1.18; P = .349). CONCLUSION No OS benefit of adjuvant OX was found in high-risk stage II CC, regardless of the definition used to characterize tumors as having a high risk for recurrence. Hence, our analysis suggests that OX should not be the standard of care for adjuvant chemotherapy for stage II CC, even in high-risk patients.
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Affiliation(s)
- Benoist Chibaudel
- Department of Medical Oncology, Franco-British Hospital, Fondation Cognacq-Jay, Cancérologie Paris Ouest, Levallois-Perret, France
| | | | - Romain Cohen
- Sorbonne Université and Department of Medical Oncology, Saint-Antoine Hospital, Paris, France
| | - Greg Yothers
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, USA
| | - Richard M. Goldberg
- Department of Medicine, West Virginia University Cancer Institute, Morgantown, USA
| | - Jean-Baptiste Bachet
- Hepato-gastroenterology and Digestive Oncology Department, Sorbonne University, Pitié Salpêtrière Hospital, APHP, Paris, France
| | | | - Takayuki Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hans-Joachim Schmoll
- Division of Clinical Research in Oncology, Martin-Luther University Halle-Wittenberg, Halle/Saale, Germany
| | - Rachel Kerr
- Department of Oncology, University of Oxford, Oxford, United Kingdom
| | - Sara Lonardi
- Medical Oncology, Veneto Institute of Oncology IOV— IRCCS, Padua, Italy
| | - Thomas J. George
- Division of Hematology and Oncology, University of Florida, Gainesville, USA
| | | | - Qian Shi
- Department of Quantitative Health Science, Mayo Clinic, Rochester, USA
| | - Thierry André
- Sorbonne Université and Department of Medical Oncology, Saint-Antoine Hospital, Paris, France
- ARCAD Foundation, Paris, France
| | - Aimery de Gramont
- ARCAD Foundation, Paris, France
- Department of Medical Oncology, Franco-British Hospital, Levallois-Perret, France
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Sun L, Wei X, Feng T, Gu Q, Li J, Wang K, Zhou J. Electroacupuncture promotes gastrointestinal functional recovery after radical colorectal cancer surgery: a protocol of multicenter randomized controlled trial (CORRECT trial). Int J Colorectal Dis 2024; 39:198. [PMID: 39652211 PMCID: PMC11628438 DOI: 10.1007/s00384-024-04768-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/19/2024] [Indexed: 12/12/2024]
Abstract
INTRODUCTION The incidence of postoperative gastrointestinal dysfunction (POGD) is notably high among patients following colorectal cancer surgery, highlighting the urgency for the prompt development of efficacious preventive and therapeutic approaches. Electroacupuncture (EA) represents an intervention modality that holds promise for the management of POGD. However, the existing empirical evidence substantiating its efficacy remains scarce. The aim of this study is to evaluate the efficacy and safety of EA as a treatment for POGD in patients undergoing colorectal cancer surgery. METHODS This study is a multicenter, parallel-group, randomized controlled trial, named as CORRECT. CORRECT trial will recruit 300 participants diagnosed with colorectal cancer and about to undergo radical surgery across four sub-centers. The participants will be randomly assigned to one of three groups: the EA group, sham-electroacupuncture group, or control group, with a randomization ratio of 2:2:1. All groups will follow a standardized Enhanced Recovery After Surgery (ERAS) protocol. The EA group will receive EA at acupoints LI4, SJ6, ST36, and ST37, while the SA group will undergo sham-electroacupuncture. The treatments will be administered twice daily from the day of surgery until the fourth day after the operation. The primary endpoint is the time to first flatus, while secondary endpoints encompass time to first defecation, bowel sound emergence, initial water intake, duration of postoperative hospitalization, nausea and vomiting, pain levels, and blinded evaluations. Additional outcomes include medication usage and complication rates, et al. DISCUSSION: The CORRECT trial aims to provide high-quality evidence for the role of EA in the treatment of POGD following colorectal cancer surgery. It will contribute data towards the integration of acupuncture into ERAS protocols. Insights from the trial could help in tailoring treatment plans based on individual patient responses to EA, optimizing care on a case-by-case basis. TRIAL REGISTRATION Clinical Trial Registry registration was approved by the ClinicalTrials.gov committee on November 2023 with the ClinicalTrials.gov Identifier: NCT06128785. URL: https://clinicaltrials.gov/study/NCT06128785?tab=history&a=1#study-details-card .
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Affiliation(s)
- Linxi Sun
- Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Xuqiang Wei
- Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Tienan Feng
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, 227# South Chongqing Road, Xuhui, Shanghai, 200025, China
| | - Qunhao Gu
- Gastrointestinal Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Jing Li
- Department of Acupuncture and Moxibustion II, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Ke Wang
- Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
- Office of National Clinical Research Base of TCM, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
| | - Jia Zhou
- Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
- Office of National Clinical Research Base of TCM, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
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Aldriwesh MG, Aljaian AR, Alorf KM, Bayounis MA, Alrayani YH, Philip W, Algarni M, Alselaim NA, Alotibi RS. Comparative analysis of the clinical aspects of colorectal cancer in young adult and older adult patients in Saudi Arabia. Front Oncol 2024; 14:1460636. [PMID: 39703840 PMCID: PMC11655320 DOI: 10.3389/fonc.2024.1460636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 11/18/2024] [Indexed: 12/21/2024] Open
Abstract
Introduction Recent studies have shown an increase in the prevalence of early-onset colorectal cancer (CRC) in people aged 20-49 compared to those aged 50-74, with a more rapid increase in the younger age groups. Poorly differentiated, left-sided, and rectal tumors were more common in young adults than in older adult CRC patients. We aimed to improve the understanding of early-onset CRC and to guide primary care physicians on strategies to mitigate its impact. Methods Adult patients with CRC identified within 2015-2022 were recruited and divided into young adult-onset (CRC identified at age ≤49 years) and older adult-onset (CRC identified at age ≥50 years). Clinical data were retrieved from electronic medical records, then analyzed. Multivariable analyses were performed to predict the CRC prognosis in both age groups. Results The study cohort had 530 patients categorized into young adult (n=98; 18.5%) and older adult (n=432; 81.5%). Higher proportions of family histories of CRC, other malignancies, and inflammatory bowel disease in the young adult group were observed (P<0.05). Gastrointestinal symptoms mainly abdominal pain and nausea were more often identified in the young adults. Mucinous adenocarcinoma, signet ring cells, and poorly differentiated tumors were higher in the young adults (P<0.05). Lymphovascular invasion was an independent predictor for advanced stage CRC (AOR 8.638, 95%CI 2.152-34.673, P=0.002 for young adults and AOR 21.757, 95%CI 10.025-47.219, P=0.001 for older adults). Further, the mucinous (AOR 3.727, 95%CI 1.937-7.173, P=0.001 for young adults and AOR 3.534, 95%CI 1.698-7.354, P=0.001 for older adults) and lymphovascular invasion (AOR 3.371, 95%CI 2.107-5.393, P=0.001 for young adults and AOR 3.246, 95%CI 1.910-5.517, P=0.001 for older adults) were independent predictors for recurrence/late metastasis in both age groups. Conclusion We recommended to raise awareness among healthcare providers of the importance of lowering the threshold of suspicion in young people presenting with worrisome gastrointestinal symptoms. Our findings suggested the importance of reconsidering the current CRC screening guidelines to lower the threshold of the recommended starting age.
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Affiliation(s)
- Marwh G. Aldriwesh
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Amer R. Aljaian
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Khalid M. Alorf
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammed A. Bayounis
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Yazeed H. Alrayani
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Winnie Philip
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Research and Innovation Unit, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammed Algarni
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Oncology, Ministry of the National Guard–Health Affairs, Riyadh, Saudi Arabia
- Department of Medicine, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Nahar A. Alselaim
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Department of Medicine, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Department of General Surgery, Ministry of the National Guard–Health Affairs, Riyadh, Saudi Arabia
| | - Raniah S. Alotibi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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Boussios S, Sheriff M, Ovsepian SV. Molecular Biology of Cancer-Interplay of Malignant Cells with Emerging Therapies. Int J Mol Sci 2024; 25:13090. [PMID: 39684799 DOI: 10.3390/ijms252313090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Cancer is currently one of the leading causes of death worldwide, and according to data from the World Health Organization reported in 2020, it ranks as the second leading cause of death globally, accounting for 10 million fatalities [...].
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Affiliation(s)
- Stergios Boussios
- Faculty of Medicine, Health and Social Care, Canterbury Christ Church University, Canterbury CT1 1QU, UK
- Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King's College London, Strand, London WC2R 2LS, UK
- Kent Medway Medical School, University of Kent, Canterbury CT2 7LX, UK
- AELIA Organization, 9th Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Matin Sheriff
- Department of Urology, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK
| | - Saak V Ovsepian
- Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Gillingham ME4 4AG, UK
- Faculty of Medicine, Tbilisi State University, Tbilisi 0179, Georgia
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50
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Zhang Y, Meng R, Sha D, Gao H, Wang S, Zhou J, Wang X, Li F, Li X, Song W. Advances in the application of colorectal cancer organoids in precision medicine. Front Oncol 2024; 14:1506606. [PMID: 39697234 PMCID: PMC11653019 DOI: 10.3389/fonc.2024.1506606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 11/18/2024] [Indexed: 12/20/2024] Open
Abstract
Colorectal cancer (CRC) ranks among the most prevalent gastrointestinal tumors globally and poses a significant threat to human health. In recent years, tumor organoids have emerged as ideal models for clinical disease research owing to their ability to closely mimic the original tumor tissue and maintain a stable phenotypic structure. Organoid technology has found widespread application in basic tumor research, precision therapy, and new drug development, establishing itself as a reliable preclinical model in CRC research. This has significantly advanced individualized and precise tumor therapies. Additionally, the integration of single-cell technology has enhanced the precision of organoid studies, offering deeper insights into tumor heterogeneity and treatment response, thereby contributing to the development of personalized treatment approaches. This review outlines the evolution of colorectal cancer organoid technology and highlights its strengths in modeling colorectal malignancies. This review also summarizes the progress made in precision tumor medicine and addresses the challenges in organoid research, particularly when organoid research is combined with single-cell technology. Furthermore, this review explores the future potential of organoid technology in the standardization of culture techniques, high-throughput screening applications, and single-cell multi-omics integration, offering novel directions for future colorectal cancer research.
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Affiliation(s)
- Yanan Zhang
- The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
- Department of Oncology, Zibo Hospital of Traditional Chinese Medicine, Zibo, China
| | - Ruoyu Meng
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Dan Sha
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Huiquan Gao
- Department of Radiotherapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Shengxi Wang
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jun Zhou
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xiaoshan Wang
- The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Fuxia Li
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xinyu Li
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Wei Song
- Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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