|
1
|
Fan R, Mao C, Zhang J, Dai M, Zhang R, Wang X, Dai J, Li S, Zhuang Z. Predicting extensive metastasis in postoperative oligometastatic colorectal cancer. Int J Colorectal Dis 2025; 40:53. [PMID: 40000449 PMCID: PMC11861249 DOI: 10.1007/s00384-025-04841-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/16/2025] [Indexed: 02/27/2025]
Abstract
PURPOSE Oligometastatic colorectal cancer (OMCRC) patients can achieve long-term disease control with multidisciplinary treatment. However, the development of extensive metastasis worsens prognosis and restricts treatment options. This study aims to develop a predictive model for extensive metastasis in OMCRC to assist in clinical decision-making. METHODS Clinical and pathological data for OMCRC patients were collected from the Second Affiliated Hospital of Soochow University. Patients were randomly divided into training and testing cohorts. Risk factors for extensive metastasis were identified through LASSO regression analysis and COX regression analysis. Three predictive models were developed in the training cohort and validated in the testing cohort: COX regression analysis, Extreme Gradient Boosting (XGBoost), and Survival Support Vector Machine (SurvSVM). Finally, the optimal model was visualized with the nomogram. RESULTS A total of 214 patients with OMCRC were enrolled in the study. Four independent risk factors were identified: whether surgery has been undertaken following oligometastasis (WST), histological type (HT), carcinoembryonic antigen at the last follow-up (CAE at last-FU), and preoperative albumin to globulin ratio (Preop-AGR). In the testing cohort, the COX model (1-year AUC = 0.82, 3-year AUC = 0.72, 5-year AUC = 0.85, mean AUC = 0.80) performed best. Decision curve analysis (DCA) confirmed the net benefit of the Cox model, and the nomogram provided accurate predictions of metastasis risk. CONCLUSION CAE at last-FU, Preop-AGR, HT, and WST are independent risk factors for extensive metastasis in OMCRC. The nomogram model incorporating risk factors can assist clinicians in developing optimal treatment for OMCRC patients.
Collapse
Affiliation(s)
- Rencai Fan
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China
| | - Chenkai Mao
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China
| | - Jiaqi Zhang
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China
| | - Min Dai
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China
| | - Rong Zhang
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China
| | - Xinran Wang
- Department of Respiratory Medicine, Wu Zhong People's Hospital, No. 61 Dongwu North Road, Wu Zhong District, Soochow, 215100, Jiangsu Province, P.R. China
| | - Jiaxin Dai
- Department of Oncology, The Nuclear Industry 417 Hospital, No. 5 Kangfu Road, Lintong District, Xi'an, Shaanxi Province, 710600, P.R. China
| | - Shicheng Li
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China.
| | - Zhixiang Zhuang
- Center for Cancer Diagnosis and Treatment, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District, Soochow, 215004, Jiangsu Province, P.R. China.
| |
Collapse
|
|
2
|
Cazelles A, Tarhini A, Sabbagh C, Mege D, Bridoux V, Lakkis Z, Voron T, Abdalla S, Lecot F, Karoui M, Manceau G. Risk of metachronous peritoneal metastases after surgery for obstructive colon cancer: Multivariate analysis from a series of 1,085 patients. Surgery 2025; 178:108923. [PMID: 39592328 DOI: 10.1016/j.surg.2024.10.014] [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: 06/11/2024] [Revised: 10/01/2024] [Accepted: 10/08/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Data in the literature suggest that obstruction is an independent predictor of poor prognosis in colon cancer. Of all possible sites of recurrence, peritoneal metastases are associated with worse survival. Our aim was to report the incidence of metachronous peritoneal metastases from a cohort of patients undergoing resection of obstructive colon cancer with curative intent and to identify predictive factors for metachronous peritoneal metastases. METHODS From 2000 to 2015, a total of 2,325 patients were treated for obstructive colon cancer in French surgical centers, members of the French National Surgical Association (AFC). Patients with palliative management, synchronous metastatic disease, and with postoperative mortality were excluded. A multivariate analysis was performed to determine independent predictive factors of metachronous peritoneal metastases. RESULTS The cohort included 1,085 patients. The median follow-up was 21.5 months. Metachronous peritoneal metastases occurred in 12% of patients and were diagnosed after a median interval of 13.5 months. The cumulative 3-year metachronous peritoneal metastasis rate was 10.9%. Three-year overall survival was 85% for patients who did not develop recurrence, 71% for those who develop recurrence without peritoneal metastases, and 56% for those with metachronous peritoneal metastases (P < .0001). In multivariate analysis, 3 variables were identified as independent risk factors for metachronous peritoneal metastases: pT4 stage (odds ratio: 1.98; 95% confidence interval: 1.17-3.36; P = .011), pN2 stage (odds ratio: 2.57; 95% confidence interval: 1.89-4.45; P = .0007), and fewer than 12 lymph nodes examined (odds ratio: 2.01; 95% confidence interval: 1.08-3.74; P = .028). CONCLUSION This study showed a significant risk of metachronous peritoneal metastases after curative-intent resection of obstructive colon cancer. The awareness of factors predisposing to metachronous peritoneal metastases could improve the treatment strategy of these patients.
Collapse
Affiliation(s)
- Antoine Cazelles
- Department of Digestive Surgery, Paris Cité University, Georges Pompidou University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. https://twitter.com/AntoineCazelles
| | - Ahmad Tarhini
- Department of Digestive Surgery, Paris Cité University, Georges Pompidou University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Charles Sabbagh
- Department of Digestive Surgery, Amiens University Hospital, Amiens, France
| | - Diane Mege
- Department of Digestive Surgery, Timone University Hospital, Marseille, France. https://twitter.com/DianeMege
| | - Valérie Bridoux
- Department of Digestive Surgery, Charles Nicolle University Hospital, Rouen, France. https://twitter.com/ValBridoux
| | - Zaher Lakkis
- Department of Digestive Surgery, Besançon University Hospital, Besançon, France. https://twitter.com/ZaherLakkis
| | - Thibault Voron
- Department of Digestive Surgery, Sorbonne University, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. https://twitter.com/ThibaultVORON
| | - Solafah Abdalla
- Department of Digestive Surgery, Université Paris-Sud, Bicêtre University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. https://twitter.com/SolafahAbdalla
| | - Frederik Lecot
- Department of Digestive Surgery, Paris Cité University, Georges Pompidou University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. https://twitter.com/LecotFrederik
| | - Mehdi Karoui
- Department of Digestive Surgery, Paris Cité University, Georges Pompidou University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Gilles Manceau
- Department of Digestive Surgery, Paris Cité University, Georges Pompidou University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
| |
Collapse
|
|
3
|
Xia Y, Zhang B, Zhang Y. Deep survival analysis using pseudo values and its application to predict the recurrence of stage IV colorectal cancer after tumor resection. Comput Methods Biomech Biomed Engin 2024; 27:2189-2198. [PMID: 37916498 DOI: 10.1080/10255842.2023.2275246] [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: 05/09/2023] [Revised: 09/07/2023] [Accepted: 10/18/2023] [Indexed: 11/03/2023]
Abstract
An improved DeepSurv model is proposed for predicting the prognosis of colorectal cancer patients at stage IV. Our model, called as PseudoDeepSurv, is optimized by a novel loss function, which is the combination of the average negative log partial likelihood and the mean-squared error derived from the pseudo-observations approach. The public BioStudies dataset including 999 patients was utilized for performance evaluation. Our PseudoDeepSurv model produced a C-index of 0.684 and 0.633 on the training and testing dataset, respectively. While for the original DeepSurv model, the corresponding values are 0.671 and 0.618, respectively.
Collapse
Affiliation(s)
- Yi Xia
- School of Electrical Engineering and Automation, Anhui University, Hefei, China
| | - Baifu Zhang
- School of Electrical Engineering and Automation, Anhui University, Hefei, China
| | - Yongliang Zhang
- Health Management Center, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| |
Collapse
|
|
4
|
Ota E, Fukunaga Y, Mukai T, Hiyoshi Y, Yamaguchi T, Nagasaki T, Akiyoshi T. Cytoreductive surgery without intra-peritoneal chemotherapy for metachronous colorectal peritoneal metastases. World J Surg Oncol 2024; 22:205. [PMID: 39085860 PMCID: PMC11290162 DOI: 10.1186/s12957-024-03471-w] [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: 01/03/2024] [Accepted: 07/16/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Cytoreductive surgery and chemotherapy reportedly improve the prognosis of patients with metachronous peritoneal metastases. However, the types of peritoneal metastases indicated for cytoreductive surgery remains unclear. Therefore, we aimed to clarify the category of cases for which cytoreductive surgery would be effective and report the prognosis associated with cytoreductive surgery for metachronous peritoneal metastases. METHODS This study included 52 consecutive patients who underwent cytoreductive surgery for metachronous peritoneal metastases caused by colorectal cancer between January 2005 and December 2018 and fulfilled the selection criteria. The median follow-up period was 54.9 months. Relapse-free survival was calculated as the time from cytoreductive surgery of metachronous peritoneal metastases to recurrence. Overall survival was defined as the time from cytoreductive surgery of metachronous peritoneal metastases to death or the end of the follow-up period. RESULTS The 5-year relapse-free survival rate was 30.0% and the 5-year overall survival rate was 72.3%. None of the patients underwent hyperthermic intraperitoneal chemotherapy. The analysis indicated no potential risk factors for 5-year relapse-free survival. However, for 5-year overall survival, the multivariate analysis revealed that time to diagnosis of metachronous peritoneal metastases of < 2 years after primary surgery (hazard ratio = 4.1, 95% confidence interval = 2.0-8.6, p = 0.0002) and number of metachronous peritoneal metastases ≥ 3 (hazard ratio = 9.8, 95% confidence interval = 2.3-42.3, p = 0.002) as independent factors associated with a poor prognosis. CONCLUSIONS Long intervals of more than 2 years after primary surgery and 2 or less metachronous peritoneal metastases were good selection criteria for cytoreductive surgery for metachronous peritoneal metastases from colorectal cancer.
Collapse
Affiliation(s)
- Emi Ota
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Toshiki Mukai
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Yamaguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiya Nagasaki
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Akiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| |
Collapse
|
|
5
|
Cerdán-Santacruz C, Cano-Valderrama Ó, Peña Ros E, Serrano Del Moral Á, Pereira Pérez F, Flor Lorente B, Biondo S. Epidemiology, oncologic results and risk stratification model for metachronous peritoneal metastases after surgery for pT4 colon cancers: results from an observational retrospective multicentre long-term follow-up study. Tech Coloproctol 2023; 27:1025-1036. [PMID: 37248370 DOI: 10.1007/s10151-023-02816-z] [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: 01/04/2023] [Accepted: 04/25/2023] [Indexed: 05/31/2023]
Abstract
PURPOSE Metachronous peritoneal metastases (MPM) following a curative surgery procedure for pT4 colon cancer is a challenging condition. Current epidemiological studies on this topic are scarce. METHODS A retrospective multicentre trial was designed. All consecutive patients who underwent operations to treat pT4 cancers between 2015 and 2017 were reviewed. Demographic, clinical, operative, pathological and oncological follow-up variables were included. MPM were described as any oncological disease at the peritoneum, clearly different from a local recurrence. Univariate and multivariate Cox regression models were constructed. A risk stratification model was created on a cumulative factor basis. According to the calculated hazard ratio (HR), a scoring system was designed (HR < 3, 1 point; HR > 3, 2 points) and a scale from 0 to 6 was calculated for peritoneal disease-free rate (PDF-R). A risk stratification model was also created on the basis of these calculations. RESULTS Fifty different hospitals were involved, which included a total of 1356 patients. Incidence of MPM was 13.6% at 50 months median follow-up. The strongest independent risk factors for MPM were positive pN stage [HR 3.72 (95% CI 2.56-5.41; p < 0.01) for stage III disease], tumour perforation [HR 1.91 (95% CI 1.26-2.87; p < 0.01)], mucinous or signet ring cell histology [HR 1.68 (95% CI 1.1-2.58; p = 0.02)], poorly differentiated tumours [HR 1.54 (95% CI 1.1-2.2; p = 0.02)] and emergency surgery [HR 1.42 (95% CI 1.01-2.01; p = 0.049)]. In the absence of additional risk factors, pT4 tumours showed 98% and 96% PDF-R in 1-year and 5-year periods based on Kaplan-Meier curves. CONCLUSIONS Cumulative MPM incidence was 13.6% at 5-year follow-up. The sole presence of a pT4 tumour resulted in high rates of PDF-R at 1-year and 5-year follow-up (98% and 96% respectively). Five additional risk factors different from pT4 status itself were identified as possible MPM indicators during follow-up.
Collapse
Affiliation(s)
- C Cerdán-Santacruz
- Colorectal Surgery Department, Hospital Universitario de la Princesa, Diego de León, 62, 28006, Madrid, Spain.
| | - Ó Cano-Valderrama
- Colorectal Surgery Department, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
| | - E Peña Ros
- Colorectal Surgery Department, Hospital Reina Sofía, Murcia, Spain
| | | | - F Pereira Pérez
- General Surgery Department, Hospital de Fuenlabrada, Madrid, Spain
| | - B Flor Lorente
- Colorectal Surgery Department, Hospital Universitario y Politécnico la Fe, Valencia, Spain
| | - S Biondo
- Department of General and Digestive Surgery, Bellvitge University Hospital, University of Barcelona and IDIBELL, Barcelona, Spain
| |
Collapse
|
|
6
|
Dai J, Wang KX, Wu LY, Bai XH, Shi HY, Xu Q, Yu J. Development of a Nomogram to Predict Postoperative Peritoneal Metastasis of Colon Cancer. J Comput Assist Tomogr 2023; 47:864-872. [PMID: 37948360 DOI: 10.1097/rct.0000000000001500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2023]
Abstract
OBJECTIVE The aim of this study was to determine the clinicopathological and radiological risk factors for postoperative peritoneal metastasis and develop a prediction model for the early detection of peritoneal metastasis in patients with colon cancer. METHODS We included 174 patients with colon cancer. The clinicopathological and radiological data were retrospectively analyzed. A Cox proportional hazards regression model was used to identify risk factors for postoperative peritoneal metastasis. Based on these risk factors, a nomogram was developed. RESULTS At a median follow-up of 63 months, 43 (24.7%) patients developed peritoneal metastasis. Six independent risk factors (hazards ratio [95% confidence interval]) were identified for postoperative peritoneal metastasis: abdominopelvic fluid (2.12 [1.02-4.40]; P = 0.04), longer maximum tumor length (1.02 [1.00-1.03]; P = 0.02), pN1 (2.50 [1.13-5.56]; P = 0.02), pN2 (4.45 [1.77-11.17]; P = 0.02), nonadenocarcinoma (2.75 [1.18-6.38]; P = 0.02), and preoperative carcinoembryonic antigen levels ≥5 ng/mL (3.08 [1.50-6.30]; P < 0.01). A clinicopathological-radiological model was developed based on these factors. The model showed good discrimination (concordance index, 0.798 [0.723-0.876]; P < 0.001) and was well-calibrated. CONCLUSIONS The developed clinicopathological-radiological nomogram may assist clinicians in identifying patients at high risk of postoperative peritoneal metastasis.
Collapse
Affiliation(s)
- Jie Dai
- From the Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | | | | | | | | | | | | |
Collapse
|
|
7
|
Ban B, Shang A, Shi J. Development and validation of a nomogram for predicting metachronous peritoneal metastasis in colorectal cancer: A retrospective study. World J Gastrointest Oncol 2023; 15:112-127. [PMID: 36684053 PMCID: PMC9850763 DOI: 10.4251/wjgo.v15.i1.112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/23/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) after primary surgery for colorectal cancer (CRC) has the worst prognosis. Prediction and early detection of metachronous PM (m-PM) have an important role in improving postoperative prognosis of CRC. However, commonly used imaging methods have limited sensitivity to detect PM early. We aimed to establish a nomogram model to evaluate the individual probability of m-PM to facilitate early interventions for high-risk patients.
AIM To establish and validate a nomogram model for predicting the occurrence of m-PM in CRC within 3 years after surgery.
METHODS We used the clinical data of 878 patients at the Second Hospital of Jilin University, between January 1, 2014 and January 31, 2019. The patients were randomly divided into training and validation cohorts at a ratio of 2:1. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the variables with nonzero coefficients to predict the risk of m-PM. Multivariate logistic regression was used to verify the selected variables and to develop the predictive nomogram model. Harrell’s concordance index, receiver operating characteristic curve, Brier score, and decision curve analysis (DCA) were used to evaluate discrimination, distinctiveness, validity, and clinical utility of this nomogram model. The model was verified internally using bootstrapping method and verified externally using validation cohort.
RESULTS LASSO regression analysis identified six potential risk factors with nonzero coefficients. Multivariate logistic regression confirmed the risk factors to be independent. Based on the results of two regression analyses, a nomogram model was established. The nomogram included six predictors: Tumor site, histological type, pathological T stage, carbohydrate antigen 125, v-raf murine sarcoma viral oncogene homolog B mutation and microsatellite instability status. The model achieved good predictive accuracy on both the training and validation datasets. The C-index, area under the curve, and Brier scores were 0.796, 0.796 [95% confidence interval (CI) 0.735-0.856], and 0.081 for the training cohort and 0.782, 0.782 (95%CI 0.690-0.874), and 0.089 for the validation cohort, respectively. DCA showed that when the threshold probability was between 0.01 and 0.90, using this model to predict m-PM achieved a net clinical benefit.
CONCLUSION We have established and validated a nomogram model to predict m-PM in patients undergoing curative surgery, which shows good discrimination and high accuracy.
Collapse
Affiliation(s)
- Bo Ban
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - An Shang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jian Shi
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| |
Collapse
|
|
8
|
Mendoza-Moreno F, Diez-Alonso M, Matías-García B, Ovejero-Merino E, Gómez-Sanz R, Blázquez-Martín A, Quiroga-Valcárcel A, Vera-Mansilla C, Molina R, San-Juan A, Barrena-Blázquez S, Ortega MA, Alvarez-Mon M, Gutiérrez-Calvo A. Prognostic Factors of Survival in Patients with Peritoneal Metastasis from Colorectal Cancer. J Clin Med 2022; 11:jcm11164922. [PMID: 36013160 PMCID: PMC9410473 DOI: 10.3390/jcm11164922] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 11/16/2022] Open
Abstract
Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32−92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan−Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1−10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11−20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294−3.077), KRAS mutation (HR 1.751; 95% CI: 1.188−2.581), PCI 11−20 (HR: 9.935; 95% CI: 5.204−18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291−7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis.
Collapse
Affiliation(s)
- Fernando Mendoza-Moreno
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
- Correspondence:
| | - Manuel Diez-Alonso
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Belén Matías-García
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Enrique Ovejero-Merino
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Remedios Gómez-Sanz
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Alma Blázquez-Martín
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Ana Quiroga-Valcárcel
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Cristina Vera-Mansilla
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Raquel Molina
- Oncology, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Alberto San-Juan
- Oncology, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Silvestra Barrena-Blázquez
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Miguel A. Ortega
- Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Melchor Alvarez-Mon
- Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias (CIBEREHD), 28806 Alcalá de Henares, Spain
| | - Alberto Gutiérrez-Calvo
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| |
Collapse
|
|
9
|
Pedrazzani C, Turri G, Marrelli D, Kim HJ, Park EJ, Spolverato G, Foppa C, Spinelli A, Pucciarelli S, Baik SH, Choi GS. Prediction of Metachronous Peritoneal Metastases After Radical Surgery for Colon Cancer: A Scoring System Obtained from an International Multicenter Cohort. Ann Surg Oncol 2022; 29:7896-7906. [PMID: 35789302 PMCID: PMC9550705 DOI: 10.1245/s10434-022-12097-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/12/2022] [Indexed: 01/01/2023]
Abstract
Background Since novel strategies for prevention and treatment of metachronous peritoneal metastases (mPM) are under study, it appears crucial to identify their risk factors. Our aim is to establish the incidence of mPM after surgery for colon cancer (CC) and to build a statistical model to predict the risk of recurrence. Patients and Methods Retrospective analysis of consecutive pT3–4 CC operated at five referral centers (2014–2018). Patients who developed mPM were compared with patients who were PM-free at follow-up. A scoring system was built on the basis of a logistic regression model. Results Of the 1423 included patients, 74 (5.2%) developed mPM. Patients in the PM group presented higher preoperative carcinoembryonic antigen (CEA) [median (IQR): 4.5 (2.5–13.0) vs. 2.7 (1.5–5.9), P = 0.001] and CA 19-9 [median (IQR): 17.7 (12.0–37.0) vs. 10.8 (5.0–21.0), P = 0.001], advanced disease (pT4a 42.6% vs. 13.5%; pT4b 16.2% vs. 3.2%; P < 0.001), and negative pathological characteristics. Multivariate logistic regression identified CA 19-9, pT stage, pN stage, extent of lymphadenectomy, and lymphovascular invasion as significant predictors, and individual risk scores were calculated for each patient. The risk of recurrence increased remarkably with score values, and the model demonstrated a high negative predictive value (98.8%) and accuracy (83.9%) for scores below five. Conclusions Besides confirming incidence and risk factors for mPM, our study developed a useful clinical tool for prediction of mPM risk. After external validation, this scoring system may guide personalized decision-making for patients with locally advanced CC. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-022-12097-9.
Collapse
Affiliation(s)
- Corrado Pedrazzani
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Verona University Hospital, University of Verona, Verona, Italy.
| | - Giulia Turri
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Verona University Hospital, University of Verona, Verona, Italy
| | - Daniele Marrelli
- Department of Surgery, Policlinico le Scotte, University of Siena, Siena, Italy
| | - Hye Jin Kim
- Colorectal Cancer Centre, Kyungpook National University Medical Centre, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gaya Spolverato
- General Surgery 3, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Salvatore Pucciarelli
- General Surgery 3, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gyu Seog Choi
- Colorectal Cancer Centre, Kyungpook National University Medical Centre, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| |
Collapse
|
|
10
|
Uppal A, Helmink B, Grotz TE, Konishi T, Fournier KF, Nguyen S, Taggart MW, Shen JP, Bednarski BK, You YQN, Chang GJ. What is the Risk for Peritoneal Metastases and Survival Afterwards in T4 Colon Cancers? Ann Surg Oncol 2022; 29:4224-4233. [PMID: 35298760 DOI: 10.1245/s10434-022-11472-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 02/01/2022] [Indexed: 02/21/2024]
|
|
11
|
Abstract
Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes.
Collapse
|
|
12
|
Díez-Alonso M, Mendoza-Moreno F, Gómez-Sanz R, Matías-García B, Ovejero-Merino E, Molina R, Soto-Schütte S, San Juan A, Gutierrez-Calvo A. Prognostic Value of KRAS Gene Mutation on Survival of Patients with Peritoneal Metastases of Colorectal Adenocarcinoma. Int J Surg Oncol 2021; 2021:3946875. [PMID: 34557315 PMCID: PMC8455216 DOI: 10.1155/2021/3946875] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 08/31/2021] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE The main objective of the study was to determine the effect of the presence of mutation in the KRAS gene on the survival in patients with colorectal cancer (CRC) and peritoneal metastases (PM). MATERIALS AND METHODS A retrospective cohort study was performed. Patients diagnosed with CRC with synchronous or metachronous PM between January 2006 and December 2019 were included. Data on the histopathological, clinical, and treatment factors were collected. The effect of each variable on survival was evaluated by Cox regression. RESULTS A total of 149 patients were included (64 women (43%) and 85 men (57%); mean age, 63 years). The long-term survival rate at 36 months was 24% (median, 21 months). KRAS mutation was detected in 75 patients (50.3%). Kaplan-Meier analysis estimated that likelihood of survival was higher in patients with wild-type KRAS tumours (35%) than in mutated-type KRAS (14%) (median: 28 vs. 15, respectively) (P=0.001). Within the categories into which the peritoneal cancer index (PCI) was classified, survival at 36 months depended on the KRAS status. Survival in wild-type KRAS tumours with PCI 1-10 was 71% and with PCI 11-20 was 26%, while in mutant-type KRAS tumours, survival was 41% and 4%, respectively (P=0.025). In the multiple regression analysis, the KRAS mutation was revealed to have an independent prognostic value (HR: 2.144; 95% CI: 1.342-3.424). CONCLUSION The mutational status of the KRAS gene has demonstrated a strong association with survival and prognostic utility in patients with CRC with PM.
Collapse
Affiliation(s)
- Manuel Díez-Alonso
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Fernando Mendoza-Moreno
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Remedios Gómez-Sanz
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Belén Matías-García
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Enrique Ovejero-Merino
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Raquel Molina
- Department of Oncology, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Sonia Soto-Schütte
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Alberto San Juan
- Department of Oncology, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| | - Alberto Gutierrez-Calvo
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid, Spain
| |
Collapse
|
|
13
|
Bastiaenen VP, Aalbers AGJ, Arjona-Sánchez A, Bellato V, van der Bilt JDW, D'Hoore AD, Espinosa-Redondo E, Klaver CEL, Nagtegaal ID, van Ramshorst B, van Santvoort HC, Sica GS, Snaebjornsson P, Wasmann KATGM, de Wilt JHW, Wolthuis AM, Tanis PJ. Risk of metachronous peritoneal metastases in patients with pT4a versus pT4b colon cancer: An international multicentre cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:2405-2413. [PMID: 34030920 DOI: 10.1016/j.ejso.2021.05.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/25/2021] [Accepted: 05/06/2021] [Indexed: 01/01/2023]
Abstract
INTRODUCTION With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. MATERIALS AND METHODS From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). RESULTS In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23-60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. CONCLUSION Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies.
Collapse
Affiliation(s)
- Vivian P Bastiaenen
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| | - Arend G J Aalbers
- Department of Surgery, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - Alvaro Arjona-Sánchez
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital and GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, (IMIBIC), Cordoba, Spain.
| | - Vittoria Bellato
- Department of Surgical Science, University Hospital Tor Vergata, Rome, Italy.
| | - Jarmila D W van der Bilt
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands; Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium.
| | - André D D'Hoore
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium.
| | - Esther Espinosa-Redondo
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital and GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, (IMIBIC), Cordoba, Spain.
| | - Charlotte E L Klaver
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
| | - Bert van Ramshorst
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands.
| | - Hjalmar C van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands; Cancer Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
| | - Giuseppe S Sica
- Department of Surgical Science, University Hospital Tor Vergata, Rome, Italy.
| | - Petur Snaebjornsson
- Department of Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - Karin A T G M Wasmann
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands.
| | - Albert M Wolthuis
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium.
| | - Pieter J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| |
Collapse
|
|
14
|
Lepsenyi M, Algethami N, Al-Haidari AA, Algaber A, Syk I, Rahman M, Thorlacius H. CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells. Clin Exp Metastasis 2021; 38:401-410. [PMID: 34115261 PMCID: PMC8318971 DOI: 10.1007/s10585-021-10103-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 05/14/2021] [Indexed: 01/10/2023]
Abstract
Peritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.
Collapse
Affiliation(s)
- Mattias Lepsenyi
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Nader Algethami
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Amr A Al-Haidari
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Anwar Algaber
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Ingvar Syk
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Milladur Rahman
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden
| | - Henrik Thorlacius
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, 20502, Malmö, Sweden.
| |
Collapse
|
|
15
|
Borumandnia N, Doosti H, Jalali A, Khodakarim S, Charati JY, Pourhoseingholi MA, Talebi A, Agah S. Nomogram to Predict the Overall Survival of Colorectal Cancer Patients: A Multicenter National Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:7734. [PMID: 34360026 PMCID: PMC8345484 DOI: 10.3390/ijerph18157734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 07/18/2021] [Accepted: 07/20/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third foremost cause of cancer-related death and the fourth most commonly diagnosed cancer globally. The study aimed to evaluate the survival predictors using the Cox Proportional Hazards (CPH) and established a novel nomogram to predict the Overall Survival (OS) of the CRC patients. MATERIALS AND METHODS A historical cohort study, included 1868 patients with CRC, was performed using medical records gathered from Iran's three tertiary colorectal referral centers from 2006 to 2019. Two datasets were considered as train set and one set as the test set. First, the most significant prognostic risk factors on survival were selected using univariable CPH. Then, independent prognostic factors were identified to construct a nomogram using the multivariable CPH regression model. The nomogram performance was assessed by the concordance index (C-index) and the time-dependent area under the ROC curve. RESULTS The age of patients, body mass index (BMI), family history, tumor grading, tumor stage, primary site, diabetes history, T stage, N stage, and type of treatment were considered as significant predictors of CRC patients in univariable CPH model (p < 0.2). The multivariable CPH model revealed that BMI, family history, grade and tumor stage were significant (p < 0.05). The C-index in the train data was 0.692 (95% CI, 0.650-0.734), as well as 0.627 (0.670, 0.686) in the test data. CONCLUSION We improved a novel nomogram diagram according to factors for predicting OS in CRC patients, which could assist clinical decision-making and prognosis predictions in patients with CRC.
Collapse
Affiliation(s)
- Nasrin Borumandnia
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1666663111, Iran;
| | - Hassan Doosti
- Department of Mathematics and Statistics, Macquarie University, Sydney, NSW 2109, Australia;
| | - Amirhossein Jalali
- School of Mathematical Sciences, University College Cork, T12 XF62 Cork, Ireland;
| | - Soheila Khodakarim
- Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7188614228, Iran;
| | - Jamshid Yazdani Charati
- Health Sciences Research Center, Biostatistics Department, Addiction Institute, School of Public Health, Mazandaran University of Medical Sciences, Sari 1353447416, Iran;
| | - Mohamad Amin Pourhoseingholi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran;
| | - Atefeh Talebi
- Colorectal Research Center, Iran University of Medical Center, Tehran 1445613131, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Center, Tehran 1445613131, Iran
| |
Collapse
|
|
16
|
Simkens GA, Wintjens AGWE, Rovers KP, Nienhuijs SW, de Hingh IH. Effective Strategies to Predict Survival of Colorectal Peritoneal Metastases Patients Eligible for Cytoreductive Surgery and HIPEC. Cancer Manag Res 2021; 13:5239-5249. [PMID: 34234566 PMCID: PMC8257566 DOI: 10.2147/cmar.s277912] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), often combined with systemic therapy, can be offered to selected colorectal peritoneal metastases (PM) patients. However, clinical heterogeneity and the lack of high-level evidence challenges determination of the correct treatment strategy. This review aims to provide an overview of current strategies to predict survival of colorectal PM patients treated with CRS and HIPEC, guiding clinicians to select a suitable treatment-strategy and to inform patients about their prognosis. First, the prognostic relevance of several clinicopathological prognostic factors, such as extent of PM, location of primary tumor, histology type, and the presence of lymph node or liver metastases will be discussed. Subsequently, special attention will be given to recent developments in several aspects of tumor biology such as RAF/RAS mutations, circulating tumor DNA, immunoprofiling, and consensus molecular subtypes. Finally, currently available prognostic models to predict survival will be evaluated, concluding these models perform moderate to good, but most of them partly rely on intra-operative data. New insights in tumor biology, as well as the reliable assessment of extent of peritoneal disease by diffusion weighted MRI pose promising opportunities to establish an adequate and clinically meaningful preoperative prognostic model in the near future.
Collapse
Affiliation(s)
- Geert A Simkens
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands.,Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Anne G W E Wintjens
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Simon W Nienhuijs
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Ignace H de Hingh
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands.,GROW - School for Oncology and Development Biology, Maastricht University, Maastricht, The Netherlands
| |
Collapse
|
|
17
|
Tsai TY, You JF, Hsu YJ, Jhuang JR, Chern YJ, Hung HY, Yeh CY, Hsieh PS, Chiang SF, Lai CC, Chiang JM, Tang R, Tsai WS. A Prediction Model for Metachronous Peritoneal Carcinomatosis in Patients with Stage T4 Colon Cancer after Curative Resection. Cancers (Basel) 2021; 13:2808. [PMID: 34200032 PMCID: PMC8200190 DOI: 10.3390/cancers13112808] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/30/2021] [Accepted: 06/02/2021] [Indexed: 01/21/2023] Open
Abstract
(1) Background: The aim of this study was to develop a prediction model for assessing individual mPC risk in patients with pT4 colon cancer. Methods: A total of 2003 patients with pT4 colon cancer undergoing R0 resection were categorized into the training or testing set. Based on the training set, 2044 Cox prediction models were developed. Next, models with the maximal C-index and minimal prediction error were selected. The final model was then validated based on the testing set using a time-dependent area under the curve and Brier score, and a scoring system was developed. Patients were stratified into the high- or low-risk group by their risk score, with the cut-off points determined by a classification and regression tree (CART). (2) Results: The five candidate predictors were tumor location, preoperative carcinoembryonic antigen value, histologic type, T stage and nodal stage. Based on the CART, patients were categorized into the low-risk or high-risk groups. The model has high predictive accuracy (prediction error ≤5%) and good discrimination ability (area under the curve >0.7). (3) Conclusions: The prediction model quantifies individual risk and is feasible for selecting patients with pT4 colon cancer who are at high risk of developing mPC.
Collapse
Affiliation(s)
- Tzong-Yun Tsai
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Jeng-Fu You
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Yu-Jen Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Jing-Rong Jhuang
- Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei City 10055, Taiwan;
| | - Yih-Jong Chern
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Hsin-Yuan Hung
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Chien-Yuh Yeh
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Pao-Shiu Hsieh
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Sum-Fu Chiang
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Cheng-Chou Lai
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Jy-Ming Chiang
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Reiping Tang
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Wen-Sy Tsai
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| |
Collapse
|
|
18
|
Bijelic L, Ramos I, Goeré D. The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases. Ann Surg Oncol 2021; 28:4140-4150. [PMID: 33969466 DOI: 10.1245/s10434-021-10049-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 04/06/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases. METHODS This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection. RESULTS These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes. CONCLUSIONS Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.
Collapse
Affiliation(s)
- Lana Bijelic
- Peritoneal Malignancies Unit, Department of Surgery, Hospital Moises Broggi, Consorci Sanitari Integral, Barcelona, Spain.
| | - Isabel Ramos
- Peritoneal Malignancies Unit, Department of Surgery, Hospital Moises Broggi, Consorci Sanitari Integral, Barcelona, Spain
| | - Diane Goeré
- Department of Digestive and Oncological Surgery, Hôpital Saint-Louis - APHP, Université de Paris, Paris, France
| |
Collapse
|
|
19
|
Bakkers C, Simkens GAAM, De Hingh IHJT. Systemic therapy in addition to cytoreduction and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: recent insights from clinical studies and translational research. J Gastrointest Oncol 2021; 12:S206-S213. [PMID: 33968438 PMCID: PMC8100702 DOI: 10.21037/jgo-20-133] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 06/04/2020] [Indexed: 12/16/2022] Open
Abstract
There is a lack of randomized or high-quality intention-to-treat cohort studies addressing the role of systemic therapy in addition to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as part of the treatment of colorectal peritoneal metastases (PM). Therefore, the choice whether or not to treat patients with systemic therapy is currently mainly based on expert opinion. As a result, treatment with neoadjuvant and/or adjuvant systemic therapy is implemented in various ways around the world. The aim of this review was to provide an overview of recent insights with regard to the systemic treatment of PM of colorectal origin obtained from clinical studies and translational research.
Collapse
Affiliation(s)
- Checca Bakkers
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | | | - Ignace H. J. T. De Hingh
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
- GROW - School for Oncology and Development Biology, Maastricht University, Maastricht, The Netherlands
| |
Collapse
|
|
20
|
Kranenburg O, van der Speeten K, de Hingh I. Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges. Front Oncol 2021; 11:650098. [PMID: 33816304 PMCID: PMC8010649 DOI: 10.3389/fonc.2021.650098] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/15/2021] [Indexed: 12/19/2022] Open
Abstract
The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.
Collapse
Affiliation(s)
- Onno Kranenburg
- Department of Surgical Oncology, University Medical Center Utrecht, Utrecht, Netherlands
- Utrecht platform for Organoid Technology, Utrecht University, Utrecht, Netherlands
- *Correspondence: Onno Kranenburg
| | - Kurt van der Speeten
- Department of Surgical Oncology, Faculty of Medicine, Biomedical Research Institute (BIOMED) Research Institute, Hospital Oost-Limburg, Belgium and University Hasselt, Diepenbeek, Belgium
| | - Ignace de Hingh
- Department of Surgery, Research School for Oncology and Developmental Biology, Catharina Hospital Eindhoven, The Netherlands and Maastricht University, Maastricht, Netherlands
| |
Collapse
|
|
21
|
Narasimhan V, Tan S, Kong J, Pham T, Michael M, Ramsay R, Warrier S, Heriot A. Prognostic factors influencing survival in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for isolated colorectal peritoneal metastases: a systematic review and meta-analysis. Colorectal Dis 2020; 22:1482-1495. [PMID: 32027455 DOI: 10.1111/codi.15003] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/15/2019] [Indexed: 12/13/2022]
Abstract
AIM Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM. METHOD A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM. RESULTS Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis. CONCLUSION This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.
Collapse
Affiliation(s)
- V Narasimhan
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - S Tan
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - J Kong
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - T Pham
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - M Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - R Ramsay
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| | - S Warrier
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - A Heriot
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
|
22
|
Shelygin YA, Sushkov OI, Sukhina MA, Saifutdinova KR, Muratov II, Shakhmatov DG, Achkasov SI. [Effectiveness of intraperitoneal chemotherapy for t4 colon cancer]. Khirurgiia (Mosk) 2020:36-43. [PMID: 33047584 DOI: 10.17116/hirurgia202010136] [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: 12/24/2022]
Abstract
OBJECTIVE To determine the effect of intraperitoneal chemotherapy (IPC) with mitomycin C on expression of intraperitoneal cancer cells markers in patients with T4 colon cancer. MATERIAL AND METHODS For the period from January 2019 to April 2020, 65 patients with T4 colon cancer were included in prospective comparative study. There were 46 patients in the main group and 19 patients in the control group. In the main group, surgical procedure was followed by IPC with mitomycin C. No IPC was performed in the control group. An effectiveness of IPC was evaluated using CD133, CD24, CD26, CD44, CD184 markers expression in peritoneal lavages. RESULTS Significant between-group differences were observed for CD133 (p=0.0168), CD24 (p=0.0455) and CD44 (p=0.0012). There was a tendency to decrease in the level of CD184 expression in both groups in the second lavage (p=0.0605). CONCLUSION IPC in patients with T4 colon cancer can reduce the expression and proliferative potential of free cancer cells.
Collapse
Affiliation(s)
- Yu A Shelygin
- Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| | - O I Sushkov
- Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia
| | - M A Sukhina
- Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| | - K R Saifutdinova
- Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| | - I I Muratov
- Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia
| | - D G Shakhmatov
- Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| | - S I Achkasov
- Ryzhikh National Medical Research Centre for Coloproctology, Moscow, Russia.,Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| |
Collapse
|
|
23
|
Cho H, Kim JE, Kim SY, Kim KP, Kim TW, Park JH, Kim JH, Lim SB, Yu CS, Kim JC, Hong YS. Patterns of recurrence in patients with curative resected rectal cancer according to different chemoradiotherapy strategies: Does preoperative chemoradiotherapy lower the risk of peritoneal recurrence? Oncol Lett 2020; 20:242. [PMID: 32973956 DOI: 10.3892/ol.2020.12105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/10/2020] [Indexed: 01/04/2023] Open
Abstract
The present study aimed to compare the pattern of distant recurrence between patients with non-metastatic rectal cancer treated with pre-operative (OP) and those treated with post-operative (post-OP) chemoradiotherapy (CRT). A total of 631 patients with newly diagnosed non-metastatic rectal cancer who had received pre-OP or post-OP CRT with curative intent surgery between August 2008 and April 2015 were identified. Inverse probability of treatment weighting (IPTW) was performed to account for baseline differences between the two arms. Overall, 449 and 182 patients were treated with pre-OP and post-OP CRT, respectively. Sex, tumor location, clinical tumor stage, CRT regimen and adjuvant chemotherapy regimen were significantly different between the two arms. The median follow-up duration was 55.4 months (range, 53.7-57.1). The 5-year distant recurrence-free survival (RFS) rates and 5-year overall survival (OS) rates were not significantly different between the pre-OP and post-OP CRT arms (RFS, 67.5 vs. 71.6%, P=0.595 and OS, 81.9 vs. 77.0%, P=0.449), and no difference was observed in the distant recurrence patterns. Following IPTW, there was still no difference in distant RFS (pre-OP vs. post-OP CRT; hazard ratio (HR)=0.62; P=0.911), but pre-OP CRT was significantly associated with lower peritoneal recurrence (pre-OP vs. post-OP CRT; HR, 0.13; P=0.032). In addition, there was no significant difference in OS between the two arms (pre-OP vs. post-OP CRT; HR, 0.85; P=0.665). In conclusion, although distant RFS was not significantly different between the two arms, pre-OP CRT was significantly associated with a lower risk of peritoneal recurrence than post-OP CRT in patients non-metastatic rectal cancer.
Collapse
Affiliation(s)
- Hyungwoo Cho
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Jeong Eun Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Sun Young Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Tae Won Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Jin-Hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Seok-Byung Lim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Chang Sik Yu
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Jin Cheon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Yong Sang Hong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| |
Collapse
|
|
24
|
Cortes-Guiral D, Glehen O. Expanding Uses of HIPEC for Locally Advanced Colorectal Cancer: A European Perspective. Clin Colon Rectal Surg 2020; 33:253-257. [PMID: 32968360 DOI: 10.1055/s-0040-1713742] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Locally advanced colorectal cancer is a challenge for surgeons and medical oncologist; 10 to 20% colorectal cancer debut as locally advanced disease, with tumors extending through the colon wall with perforation and/or invasion of adjacent organs or structures. Those locally advanced tumors have a worse prognostic at any stage due not only to systemic dissemination but also in a high percentage of patients, to locoregional recurrence, in fact, peritoneal carcinomatosis of colorectal origin is so predictable that we can assess the risk for each patient according to some histopathological and clinical features: small peritoneal nodules resected in the first surgery (70% probability), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%), positive cytology (40%), and pT4/mucinous pT3 up to 40%. Prophylactic or adjuvant hyperthermic intraperitoneal chemotherapy seems to be a promising strategy for patients with advanced colorectal cancer to prevent the development of peritoneal recurrence and improve prognosis of this group of patients.
Collapse
Affiliation(s)
- Delia Cortes-Guiral
- General Surgery Department, Principe de Asturias University Hospital, Carretera de Alcala s/n, Alcalá de Henares, Madrid, Spain
| | - Olivier Glehen
- General Surgery Department (Surgical Oncology), Centre Hospitalier Lyon Sud (Hospices Civils de Lyon), Lyon, France
| |
Collapse
|
|
25
|
Spiegelberg J, Neeff H, Holzner P, Runkel M, Fichtner-Feigl S, Glatz T. Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer. World J Gastrointest Oncol 2020; 12:903-917. [PMID: 32879667 PMCID: PMC7443840 DOI: 10.4251/wjgo.v12.i8.903] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 05/29/2020] [Accepted: 06/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited.
AIM To evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors.
METHODS One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient’s demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival.
RESULTS The two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis.
CONCLUSION In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.
Collapse
Affiliation(s)
- Julia Spiegelberg
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Hannes Neeff
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Philipp Holzner
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Mira Runkel
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Torben Glatz
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
- Department of Surgery, Marien Hospital Herne, Ruhr-University Bochum, Herne 44625, Germany
| |
Collapse
|
|
26
|
Xu W, He Y, Wang Y, Li X, Young J, Ioannidis JPA, Dunlop MG, Theodoratou E. Risk factors and risk prediction models for colorectal cancer metastasis and recurrence: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med 2020; 18:172. [PMID: 32586325 PMCID: PMC7318747 DOI: 10.1186/s12916-020-01618-6] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 05/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There is a clear need for systematic appraisal of models/factors predicting colorectal cancer (CRC) metastasis and recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables. METHODS We conducted an umbrella review of all systematic reviews of observational studies (with/without meta-analysis) that evaluated risk factors of CRC metastasis and recurrence. We also generated an updated synthesis of risk prediction models for CRC metastasis and recurrence. We cross-assessed individual risk factors and risk prediction models. RESULTS Thirty-four risk factors for CRC metastasis and 17 for recurrence were investigated. Twelve of 34 and 4/17 risk factors with p < 0.05 were estimated to change the odds of the outcome at least 3-fold. Only one risk factor (vascular invasion for lymph node metastasis [LNM] in pT1 CRC) presented convincing evidence. We identified 24 CRC risk prediction models. Across 12 metastasis models, six out of 27 unique predictors were assessed in the umbrella review and four of them changed the odds of the outcome at least 3-fold. Across 12 recurrence models, five out of 25 unique predictors were assessed in the umbrella review and only one changed the odds of the outcome at least 3-fold. CONCLUSIONS This study provides an in-depth evaluation and cross-assessment of 51 risk factors and 24 prediction models. Our findings suggest that a minority of influential risk factors are employed in prediction models, which indicates the need for a more rigorous and systematic model construction process following evidence-based methods.
Collapse
Affiliation(s)
- Wei Xu
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, UK
| | - Yazhou He
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, UK
| | - Yuming Wang
- Henan Provincial People's Hospital, Henan, 450003, People's Republic of China
| | - Xue Li
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, UK
| | - Jane Young
- Sydney School of Public Health, University of Sydney, Sydney, NSW, 2006, Australia
| | - John P A Ioannidis
- Department of Medicine, School of Medicine, Stanford University, Stanford, CA, 94305, USA
- Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, 94305, USA
- Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, 94305, USA
- Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, 94305, USA
- Department of Statistics, School of Humanities and Sciences, Stanford University, Stanford, CA, 94305, USA
| | - Malcolm G Dunlop
- Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
- Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, UK.
- Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
| |
Collapse
|
|
27
|
Pei JP, Zhang CD, Liang Y, Zhang C, Wu KZ, Zhao ZM, Dai DQ. Novel Nomograms Individually Predicting Overall Survival of Non-metastatic Colon Cancer Patients. Front Oncol 2020; 10:733. [PMID: 32435623 PMCID: PMC7218119 DOI: 10.3389/fonc.2020.00733] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 04/17/2020] [Indexed: 12/14/2022] Open
Abstract
Background: This study aimed to develop an effective prognostic nomogram for predicting non-metastatic colon cancer. Methods: The Surveillance, Epidemiology, and End Results program was utilized to analyze patients who underwent surgical therapy (25,350 for training, 10,860 for validation). Nomograms were created depending upon multivariate analysis in the training cohort and were compared to current American Joint Committee on Cancer (AJCC) classifications. Areas under the receiver-operating characteristic curves (AUCs), Akaike's information criterions (AICs), and calibration curves were used. The clinical benefit was measured using decision curve analyses (DCAs). The validation cohort was used to validate the results. Results: Nomogram 1 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and N stage. Nomogram 2 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and number of positive lymph nodes. The prognostic discrimination of nomogram 1 (AUC, 0.729, 95% CI, 0.723-0.736) was better than that of nomogram 2 (AUC, 0.704, 95% CI, 0.698-0.710, p < 0.001) in five-year overall survival in the training cohort. Nomogram 1 (AIC, 137,319) also showed superior model-fitting compared to nomogram 2 (AIC, 137,453). Similarity, nomogram 1 was better than the AJCC 6th and 8th TNM classifications. DCA revealed that nomogram 1 had a superior net benefit than other models. These findings were validated using the validation cohort. Conclusions: The proposed nomogram 1 was a better prognostic prediction model with better discrimination and superior model-fitting for patients with non-metastatic colon cancer, which might prove to be clinically helpful.
Collapse
Affiliation(s)
- Jun-Peng Pei
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Chun-Dong Zhang
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.,Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yu Liang
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Cheng Zhang
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Kun-Zhe Wu
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhe-Ming Zhao
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Dong-Qiu Dai
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.,Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| |
Collapse
|
|
28
|
Zhang J, Yang Y, Fu X, Guo W. Development and validation of nomograms for prediction of overall survival and cancer-specific survival of patients of colorectal cancer. Jpn J Clin Oncol 2020; 50:261-269. [PMID: 31868876 DOI: 10.1093/jjco/hyz182] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 10/29/2019] [Accepted: 10/31/2019] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Nomograms are intuitive tools for individualized cancer prognosis. We sought to develop a clinical nomogram for prediction of overall survival and cancer-specific survival for patients with colorectal cancer. METHODS Patients with colorectal cancer diagnosed between 1988 and 2006 and those who underwent surgery were retrieved from the Surveillance, Epidemiology, and End Results database and randomly divided into the training (n = 119 797) and validation (n = 119 797) cohorts. Log-rank and multivariate Cox regression analyses were used in our analysis. To find out death from other cancer causes and non-cancer causes, a competing-risks model was used, based on which we integrated these significant prognostic factors into nomograms and subjected the nomograms to bootstrap internal validation and to external validation. RESULTS The 1-, 3-, 5- and 10-year probabilities of overall survival in patients of colorectal cancer after surgery intervention were 83.04, 65.54, 54.79 and 38.62%, respectively. The 1-, 3-, 5- and 10-year cancer-specific survival was 87.36, 73.44, 66.22 and 59.11%, respectively. Nine independent prognostic factors for overall survival and nine independent prognostic factors for cancer specific survival were included to build the nomograms. Internal and external validation CI indexes of overall survival were 0.722 and 0.721, and those of cancer-specific survival were 0.765 and 0.766, which was satisfactory. CONCLUSIONS Nomograms for prediction of overall survival and cancer-specific survival of patients with colorectal cancer. Performance of the model was excellent. This practical prognostic model may help clinicians in decision-making and design of clinical studies.
Collapse
Affiliation(s)
- Jieyun Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| | - Yue Yang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| | - Xiaojian Fu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Weijian Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| |
Collapse
|
|
29
|
Laparoscopic surgery for T4 colon cancer: a risk factor for peritoneal recurrences? Surgery 2020; 168:119-124. [PMID: 32305228 DOI: 10.1016/j.surg.2020.02.026] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 02/17/2020] [Accepted: 02/29/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Although some preclinical studies have inferred that laparoscopic surgery for advanced cancer may increase the risk of peritoneal metastasis, this potential hazard has not been fully evaluated in the clinical setting. This study aimed to clarify whether laparoscopic surgery is associated with an increased risk of postoperative peritoneal recurrence after resection of T4 colon cancer. METHODS This study included 272 patients who underwent curative resection for pathological T4a colon cancer without distant metastases at the University of Tokyo Hospital between 1997 and 2017. Multivariable Fine-Gray analysis was performed to evaluate whether the use of laparoscopy was an independent risk factor for postoperative peritoneal recurrence. Thereafter, oncological outcomes (overall and relapse-free survival, and organ-specific recurrence) were compared between laparoscopic colectomy and open colectomy using propensity score matching. RESULTS Multivariable analysis found that laparoscopic surgery was a significant risk factor for postoperative peritoneal recurrence (hazard ratio: 1.89; 95% confidence interval: 1.01-3.65; P = .046). Comparison after propensity score matching revealed that the incidence of peritoneal recurrence was significantly higher after laparoscopic colectomy than after open colectomy (5-year cumulative incidence: 28.1% vs 12.1%; P = .003). CONCLUSION This study suggested that laparoscopic surgery may be related to an increased risk of peritoneal recurrence in patients with pathological T4a colon cancer. Clinicians should be fully aware of this potential risk and seek an optimal treatment plan for the prevention and early detection of peritoneal metastasis.
Collapse
|
|
30
|
Baaten ICPA, West NP, Quyn AJ, Seymour MT, Seligmann JF. Colorectal cancer peritoneal metastases: Biology, treatment and next steps. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:675-683. [PMID: 31806517 DOI: 10.1016/j.ejso.2019.10.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/18/2019] [Accepted: 10/28/2019] [Indexed: 01/22/2023]
Abstract
The presence of peritoneal metastases in patients with advanced colorectal cancer is associated with poor prognosis but the mechanisms for this are unclear. This review summarises the current knowledge of the pathophysiology, clinical features, prevalence, prognosis, and molecular biology of peritoneal metastases and the risk factors for the development of peritoneal metastases following resection of a primary colorectal tumour. Furthermore, the evidence for treatment strategies are described including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, early post-operative intraperitoneal chemotherapy, sequential post-operative intraperitoneal chemotherapy and emerging novel strategies. Active areas of research should include the identification of individuals at high risk of peritoneal metastases after curative resection of primary tumour, development of a surveillance program for high-risk patients, optimisation of systematic therapies and further investigation of the use of intraperitoneal chemotherapy.
Collapse
Affiliation(s)
- Ilona C P A Baaten
- Leeds Institute of Clinical Trial Research, University of Leeds, Leeds, United Kingdom.
| | - Nicholas P West
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Aaron J Quyn
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Matthew T Seymour
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Jenny F Seligmann
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| |
Collapse
|
|
31
|
Veld JV, Wisselink DD, Amelung FJ, Consten ECJ, de Wilt JHW, de Hingh I, Bemelman WA, van Hooft JE, Tanis PJ. Synchronous and Metachronous Peritoneal Metastases in Patients with Left-Sided Obstructive Colon Cancer. Ann Surg Oncol 2020; 27:2762-2773. [PMID: 32170481 PMCID: PMC7334250 DOI: 10.1245/s10434-020-08327-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Indexed: 12/17/2022]
Abstract
Background Controversy exists on emergency setting as a risk factor for peritoneal metastases (PM) in colon cancer patients. Data in patients with obstruction are scarce. The aim of this study was to determine the incidence of synchronous and metachronous PM, risk factors for the development of metachronous PM, and prognostic implications within a large nationwide cohort of left-sided obstructive colon cancer (LSOCC). Methods Patients with LSOCC treated between 2009 and 2016 were selected from the Dutch ColoRectal Audit. Additional treatment and long-term outcome data were retrospectively collected from original patient files in 75 hospitals in 2017. Results In total, 3038 patients with confirmed obstruction and without perforation were included. Synchronous PM (at diagnosis or < 30 days postoperatively) were diagnosed in 148/2976 evaluable patients (5.0%), and 3-year cumulative metachronous PM rate was 9.9%. Multivariable Cox regression analyses revealed pT4 stage (HR 1.782, 95% CI 1.191–2.668) and pN2 stage (HR 2.101, 95% CI 1.208–3.653) of the primary tumor to be independent risk factors for the development of metachronous PM. Median overall survival in patients with or without synchronous PM was 20 and 63 months (p < 0.001) and 3-year overall survival of patients that did or did not develop metachronous PM was 48.1% and 77.0%, respectively (p < 0.001). Conclusion This population based study revealed a 5.0% incidence of synchronous peritoneal metastases in patients who underwent resection of left-sided obstructive colon cancer. The subsequent 3-year cumulative metachronous PM rate was 9.9%, with advanced tumor and nodal stage as independent risk factors for the development of PM. Electronic supplementary material The online version of this article (10.1245/s10434-020-08327-7) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Joyce Valerie Veld
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Daniel Derk Wisselink
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Femke Julie Amelung
- Department of Surgery, Meander Medical Center, Amersfoort, The Netherlands.,Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Esther Catharina Josephina Consten
- Department of Surgery, Meander Medical Center, Amersfoort, The Netherlands.,Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Ignace de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Wilhelmus Adrianus Bemelman
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Jeanin Elise van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Pieter Job Tanis
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands.
| | | |
Collapse
|
|
32
|
Ravn S, Heide-Jørgensen U, Christiansen CF, Verwaal VJ, Hagemann-Madsen RH, Iversen LH. Overall risk and risk factors for metachronous peritoneal metastasis after colorectal cancer surgery: a nationwide cohort study. BJS Open 2020; 4:284-292. [PMID: 32207578 PMCID: PMC7093782 DOI: 10.1002/bjs5.50247] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 11/12/2019] [Indexed: 01/16/2023] Open
Abstract
Background This study aimed to identify the cumulative incidence and risk factors of metachronous peritoneal metastasis (M‐PM) from colorectal cancer in patients who had intended curative treatment. Methods Patients with colorectal cancer were identified using the Danish Colorectal Cancer Group database for 2006–2015. The Danish Pathology Registry and the Danish National Patient Registry were used to identify M‐PM to 2017. Risk factors were estimated by multivariable absolute risk regression, treating death and other cancers as competing risks. Overall risk and risk differences (RDs) were estimated at 1, 3 and 5 years. Results In 22 586 patients with colorectal cancer, the overall risk of M‐PM was reported to be 0·9 (95 per cent c.i. 0·8 to 1·0) per cent at 1 year, 1·9 (1·8 to 2·1) per cent at 3 years and 2·2 (2·0 to 2·4) per cent at 5 years. Advanced tumour category ((y)pT4 versus (y)pT1) increased the RD of both M‐PM (2·9 (95 per cent c.i. 2·1 to 3·7) at 1 year and 6·0 (4·9 to 7·2) at 3 years) and lymph node involvement ((y)pN2 versus (y)pN0) (2·5 (1·8 to 3·2) at year and 4·3 (3·2 to 5·3) at 3 years). No further increase in risk was observed at 5 years. In a subanalysis, tumour‐involved resection margin (R1 versus R0) was associated with M‐PM with a RD of 3·9 (1·6 to 6·2) at 1 year and 5·9 (2·6 to 9·3) at 3 years. Conclusion The overall risk of M‐PM in patients with colorectal cancer is low, but is increased in advanced T and N status. Follow‐up of at least 3 years after colorectal cancer surgery may be necessary, given the potential curative treatment of early diagnosed M‐PM.
Collapse
Affiliation(s)
- S Ravn
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - U Heide-Jørgensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - C F Christiansen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - V J Verwaal
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | | | - L H Iversen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.,Danish Colorectal Cancer Group, Copenhagen, Denmark
| |
Collapse
|
|
33
|
Saifutdinova KR, Sushkov OI, Achkasov SI. [Prevention of carcinomatosis in colon cancer]. Khirurgiia (Mosk) 2019:88-92. [PMID: 31714536 DOI: 10.17116/hirurgia201911188] [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: 11/17/2022]
Abstract
Colorectal cancer (CRC) is one of the leading forms of cancer. In 2017, over 72,000 of Russian citizens have been diagnosed with CRC. Cancer stage IV was diagnosed in 18 149 of them. Peritoneal carcinomatosis (PC) is one of the forms of metastatic dissemination throughout the peritoneum. There no any unified and standardized approaches to the treatment or prevention of PC associated with CRC. Therefore, it is advisable to identify PC predictors in patients with colon cancer and prevention measures.
Collapse
Affiliation(s)
- K R Saifutdinova
- Russian Medical Academy of Continuing Professional Education, Moscow, Russia
| | - O I Sushkov
- State Scientific Centre of Coloproctology, Moscow, Russia
| | - S I Achkasov
- State Scientific Centre of Coloproctology, Moscow, Russia
| |
Collapse
|
|
34
|
Zhang GL, Zhou W. A Model for the Prediction of Survival in Patients With Upper Tract Urothelial Carcinoma After Surgery. Dose Response 2019; 17:1559325819882872. [PMID: 31662711 PMCID: PMC6794662 DOI: 10.1177/1559325819882872] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 09/18/2019] [Accepted: 09/24/2019] [Indexed: 12/29/2022] Open
Abstract
Objective: We aimed to formulate and validate prognostic nomograms that can be used to
predict the prognosis of patients with upper tract urothelial carcinoma
(UTUC). Methods: By consulting the Surveillance, Epidemiology, and End Results (SEER)
database, we identified patients who were surgically treated for UTUC
between 2004 and 2013. Variables were analyzed in both univariate and
multivariate analyses. Nomograms were constructed based on independent
prognostic factors. The prognostic nomogram models were established and
validated internally and externally to determine their ability to predict
the survival of patients with UTUC. Results: A total of 4990 patients were collected and enrolled in our analyses. Of
these, 3327 patients were assigned to the training set and 1663 to the
validation set. Nomograms were effectively applied to predict the 3- and
5-year survivals of patients with UTUC after surgery. The nomograms
exhibited better accuracy for predicting overall survival (OS) and
cancer-specific survival (CSS) than the tumor-node-metastasis (TNM) staging
system and the SEER stage in both the training and validation sets.
Calibration curves indicated that the nomograms exhibited high correlation
to actual observed results for both OS and CSS. Conclusions: The nomogram models showed stronger predictive ability than the TNM staging
system and the SEER stage. Precise estimates of the prognosis of UTUC might
help doctors to make better treatment decisions.
Collapse
Affiliation(s)
- Guang-Lin Zhang
- Department of Abdominal and Pelvic Medical Oncology II ward, Huangshi Central Hospital (Pu Ai Hospital), Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, People's Republic of China
| | - Wei Zhou
- Department of Urology, Huangshi Central Hospital (Pu Ai Hospital), Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, People's Republic of China
| |
Collapse
|
|
35
|
Bastiaenen VP, Klaver CEL, Kok NFM, de Wilt JHW, de Hingh IHJT, Aalbers AGJ, Boerma D, Bremers AJA, Burger JWA, van Duyn EB, Evers P, van Grevenstein WMU, Hemmer PHJ, Madsen EVE, Snaebjornsson P, Tuynman JB, Wiezer MJ, Dijkgraaf MGW, van der Bilt JDW, Tanis PJ. Second and third look laparoscopy in pT4 colon cancer patients for early detection of peritoneal metastases; the COLOPEC 2 randomized multicentre trial. BMC Cancer 2019; 19:254. [PMID: 30898098 PMCID: PMC6429794 DOI: 10.1186/s12885-019-5408-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 02/25/2019] [Indexed: 12/24/2022] Open
Abstract
Background Approximately 20–30% of patients with pT4 colon cancer develop metachronous peritoneal metastases (PM). Due to restricted accuracy of imaging modalities and absence of early symptoms, PM are often detected at a stage in which only a quarter of patients are eligible for curative intent treatment. Preliminary findings of the COLOPEC trial (NCT02231086) revealed that PM were already detected during surgical re-exploration within two months after primary resection in 9% of patients with pT4 colon cancer. Therefore, second look diagnostic laparoscopy (DLS) to detect PM at a subclinical stage may be considered an essential component of early follow-up in these patients, although this needs confirmation in a larger patient cohort. Furthermore, a third look DLS after a negative second look DLS might be beneficial for detection of PM occurring at a later stage. Methods The aim of this study is to determine the yield of second look DLS and added value of third look DLS after negative second look DLS in detecting occult PM in pT4N0-2 M0 colon cancer patients after completion of primary treatment. Patients will undergo an abdominal CT at 6 months postoperative, followed by a second look DLS within 1 month if no PM or other metastases not amenable for local treatment are detected. Patients without PM will subsequently be randomized between routine follow-up including 18 months abdominal CT, or an experimental arm with a third look DLS provided that PM or incurable metastases are absent at the 18 months abdominal CT. Primary endpoint is the proportion of PM detected after a negative second look DLS and will be determined at 20 months postoperative. Discussion Second look DLS is supposed to result in 10% occult PM, and third look DLS after negative second look DLS is expected to detect an additional 10% of PM compared to routine follow-up alone in patients with pT4 colon cancer. Detection of PM at an early stage will likely increase the proportion of patients eligible for curative intent treatment and subsequently improve survival, given the uniformly reported direct association between the extent of peritoneal disease and survival. Trial registration ClinicalTrials.gov: NCT03413254, January 2018. Electronic supplementary material The online version of this article (10.1186/s12885-019-5408-8) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Vivian P Bastiaenen
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, PO Box 22660, 1105 AZ, Amsterdam, the Netherlands.
| | - Charlotte E L Klaver
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, PO Box 22660, 1105 AZ, Amsterdam, the Netherlands
| | - Niels F M Kok
- Department of Surgery, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | | | - Arend G J Aalbers
- Department of Surgery, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Djamila Boerma
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Andre J A Bremers
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | | | - Eino B van Duyn
- Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands
| | - Pauline Evers
- Dutch Federation of Cancer Patient Organizations (NFK), Utrecht, the Netherlands
| | | | - Patrick H J Hemmer
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Eva V E Madsen
- Department of Surgery, Erasmus MC, Rotterdam, the Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Jurriaan B Tuynman
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Marinus J Wiezer
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Marcel G W Dijkgraaf
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Jarmila D W van der Bilt
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, PO Box 22660, 1105 AZ, Amsterdam, the Netherlands.,Department of Surgery, Flevo hospital, Almere, the Netherlands
| | - Pieter J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, PO Box 22660, 1105 AZ, Amsterdam, the Netherlands.
| |
Collapse
|
|
36
|
Metastatic Colorectal Cancer to the Peritoneum: Current Treatment Options. Curr Treat Options Oncol 2018; 19:49. [DOI: 10.1007/s11864-018-0563-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
|
37
|
The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI). Eur J Surg Oncol 2018; 44:1942-1948. [PMID: 30075978 DOI: 10.1016/j.ejso.2018.07.003] [Citation(s) in RCA: 107] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 06/28/2018] [Accepted: 07/08/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. METHODS HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. RESULTS It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. CONCLUSION This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.
Collapse
|
|
38
|
Goéré D, Sourrouille I, Gelli M, Benhaim L, Faron M, Honoré C. Peritoneal Metastases from Colorectal Cancer. Surg Oncol Clin N Am 2018; 27:563-583. [DOI: 10.1016/j.soc.2018.02.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
|
39
|
Honoré C, Gelli M, Francoual J, Benhaim L, Elias D, Goéré D. Ninety percent of the adverse outcomes occur in 10% of patients: can we identify the populations at high risk of developing peritoneal metastases after curative surgery for colorectal cancer? Int J Hyperthermia 2018; 33:505-510. [PMID: 28540831 DOI: 10.1080/02656736.2017.1306119] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Peritoneal metastases (PM) occur in 3.4-6.3% after curative surgery for non-metastatic colorectal cancer. Systematic "2nd look" surgery helps overcoming the diagnostic problem but can be only proposed to selected patients. The aim of this study was to update the knowledge on risk factors of developing PM after curative surgery for colorectal cancer. METHODS A systematic review of the literature published between 2011 and 2016 was made, searching for all clinical studies reporting the incidence of recurrent PM after curative surgery for colorectal cancer and factors associated with the primary tumour that were likely to influence this recurrence rate. RESULTS Seven new clinical studies were considered informative for risk factors and added to the 16 reviewed in 2013. Even if the level of evidence was low, data suggested rates of recurrent PM at 1 year between 54% and 71% after completely resected synchronous PM, between 62% and 71% after resection of isolated synchronous ovarian metastases, of 27% after surgery for a perforated primary tumour, of 16% after surgery for a pT4 tumour, and between 11% and 36% after surgery for a mucinous histological subtype. No new risk factor was identified. CONCLUSIONS Evidence regarding the incidence of recurrent PM after curative surgery for colorectal cancer is poor. Situations at higher risk of recurrent PM are synchronous PM, synchronous isolated ovarian metastases, perforated primary tumour with serosa invasion and mucinous histological subtype.
Collapse
Affiliation(s)
- Charles Honoré
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Maximiliano Gelli
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Julie Francoual
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Léonor Benhaim
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Dominique Elias
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Diane Goéré
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| |
Collapse
|
|
40
|
Kyang LS, Valle SJ, Alzahrani NA, Morris DL. Prevention of peritoneal recurrence in high-risk colorectal cancer and evidence of T4 status as a potential risk factor. ANZ J Surg 2018; 88:975-981. [PMID: 29510456 DOI: 10.1111/ans.14428] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 01/03/2018] [Accepted: 01/13/2018] [Indexed: 01/13/2023]
Affiliation(s)
- Lee Shyang Kyang
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
| | - Sarah J. Valle
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
| | - Nayef A. Alzahrani
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
- College of Medicine; Al Imam Muhammad Ibn Saud Islamic University (IMSIU); Riyadh Saudi Arabia
| | - David L. Morris
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
| |
Collapse
|
|
41
|
Nagata H, Ishihara S, Oba K, Tanaka T, Hata K, Kawai K, Nozawa H. Development and Validation of a Prediction Model for Postoperative Peritoneal Metastasis After Curative Resection of Colon Cancer. Ann Surg Oncol 2018; 25:1366-1373. [PMID: 29508182 DOI: 10.1245/s10434-018-6403-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Indexed: 01/02/2023]
Abstract
BACKGROUND Detection of peritoneal metastasis remains challenging due to the limited sensitivity of current examination methods. This study aimed to establish a prediction model for estimating the individual risk of postoperative peritoneal metastasis from colon cancer to facilitate early interventions for high-risk patients. METHODS This study investigated 1720 patients with stages 1-3 colon cancer who underwent curative resection at the University of Tokyo Hospital between 1997 and 2015. The data for the patients were retrospectively retrieved from their medical records. The risk score was developed using the elastic net techniques in a derivation cohort (973 patients treated in 1997-2009) and validated in a validation cohort (747 patients treated in 2010-2015). RESULTS The factors selected using the elastic net approaches included the T stage, N stage, number of examined lymph nodes, preoperative carcinoembryonic antigen level, large bowel obstruction, and anastomotic leakage. The model had good discrimination (c-index, 0.85) and was well-calibrated after application of the bootstrap resampling method. Discrimination and calibration were favorable in external validation (c-index, 0.83). The model presented a clear stratification of patients' risk for postoperative peritoneal recurrence, and decision curve analysis showed its net benefit across a wide range of threshold probabilities. CONCLUSIONS This study established and validated a prediction model that can aid clinicians in optimizing postoperative surveillance and therapeutic strategies according to the individual patient risk of peritoneal recurrence.
Collapse
Affiliation(s)
- Hiroshi Nagata
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Surgery Department, Sanno Hospital, International University of Health and Welfare, Tokyo, Japan
| | - Koji Oba
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
42
|
Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials. Oncotarget 2017; 8:99150-99160. [PMID: 29228760 PMCID: PMC5716800 DOI: 10.18632/oncotarget.21845] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 09/21/2017] [Indexed: 12/11/2022] Open
Abstract
Background Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan–Meier curves for OS and DFS in the external validation dataset. Conclusions We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset.
Collapse
|
|
43
|
Simkens GA, Rovers KP, Nienhuijs SW, de Hingh IH. Patient selection for cytoreductive surgery and HIPEC for the treatment of peritoneal metastases from colorectal cancer. Cancer Manag Res 2017; 9:259-266. [PMID: 28721098 PMCID: PMC5501638 DOI: 10.2147/cmar.s119569] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a viable option for selected patients with peritoneal metastases (PM) from colorectal origin, resulting in long-term survival and even cure in some cases. However, adequate patient selection for this treatment is currently one of the major challenges. The aim of this review is to provide a comprehensive overview of clinically relevant factors associated with overall survival. This may help to guide clinicians through the complex interplay of patient, tumor, and treatment characteristics to adequately select patients who benefit the most from this extensive surgical treatment. First, basic principles of colorectal PM and the CRS and HIPEC treatment will be discussed. According to available literature, especially extent of peritoneal disease, completeness of cytoreduction, and signet ring cell histology have great influence on the outcome after CRS and HIPEC. Other factors that seem to have a negative prognostic value are the presence of liver metastases and the absence of treatment with neo-adjuvant systemic therapy. Prognostic models combining the above-mentioned factors, such as the Colorectal Peritoneal Metastases Prognostic Surgical Score nomogram, may provide clinically relevant tools to use in everyday practice.
Collapse
Affiliation(s)
- Geert A Simkens
- Department of Surgical Oncology, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Koen P Rovers
- Department of Surgical Oncology, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Simon W Nienhuijs
- Department of Surgical Oncology, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Ignace H de Hingh
- Department of Surgical Oncology, Catharina Cancer Institute, Eindhoven, The Netherlands
| |
Collapse
|
|
44
|
Cortes-Guiral D, Elias D, Cascales-Campos PA, Badía Yébenes A, Guijo Castellano I, León Carbonero AI, Martín Valadés JI, Garcia-Foncillas J, Garcia-Olmo D. Second-look surgery plus hyperthermic intraperitoneal chemotherapy for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Does it really save lives? World J Gastroenterol 2017; 23:377-381. [PMID: 28210074 PMCID: PMC5291843 DOI: 10.3748/wjg.v23.i3.377] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Revised: 11/02/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
The treatment of peritoneal carcinomatosis (PC) of colorectal origin with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%, so it is no longer labeled as a fatal disease, and offers prolonged survival for patients with a low peritoneal carcinomatosis index. Metachronous PC of colorectal origin is so predictable that there is a model which has been used to successfully determine the individual risk of each patient. Patients at risk are clearly identified; those with the highest risk have small peritoneal nodules present in the first surgery (70% probability of developing PC), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%). Current clinical, biological and imaging techniques still lack sufficient sensitivity to diagnose PC in its initial stages, when CRS plus HIPEC has a greater impact and a higher cure rate. Second-look surgery with HIPEC or prophylactic HIPEC at the time of the first intervention have been proposed as means of preventing and/or anticipating clinical or radiological relapse in at-risk patients. Both techniques have shown a significant decrease in peritoneal relapses and should be considered essential weapons in the management of colorectal cancer.
Collapse
|
|
45
|
Gelli M, Huguenin JF, Cerebelli C, Benhaim L, Honoré C, Elias D, Goéré D. Strategies to prevent peritoneal carcinomatosis arising from colorectal cancer. Future Oncol 2017; 13:907-918. [PMID: 28052691 DOI: 10.2217/fon-2016-0389] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
In the last decades, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy became a curative option for peritoneal metastases in selected patients, otherwise considered for palliative therapy alone. Better knowledge of physiopathology of peritoneal spread and identification of predictive factors for peritoneal relapse prompted specialized centers to investigate the role of a 'proactive approach' in order to early detect peritoneal metastasis. These encouraging data could justify an active attitude in selected patients at high risk of peritoneal recurrence after curative resection of primary tumor. Selection criteria and the timing of complementary hyperthermic intraperitoneal chemotherapy remain important points of discussion. In this article, we will discuss treatment principles and future perspectives to early treat and, if possible, to prevent peritoneal dissemination after curative treatment of colorectal cancer.
Collapse
Affiliation(s)
- Maximiliano Gelli
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Janina Fl Huguenin
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Cecilia Cerebelli
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Léonor Benhaim
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Charles Honoré
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Dominique Elias
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Diane Goéré
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| |
Collapse
|
|
46
|
Nagata H, Ishihara S, Hata K, Murono K, Kaneko M, Yasuda K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Nozawa H, Watanabe T. Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer. Ann Surg Oncol 2016; 24:1269-1280. [PMID: 27995451 DOI: 10.1245/s10434-016-5732-z] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. METHODS Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. RESULTS Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of <1 year (HR 2.02, 95% CI 1.04-3.87; p = 0.040), Peritoneal Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p < 0.001), and peritoneal nodule resection (HR 0.31, 95% CI 0.13-0.65; p = 0.002). CONCLUSIONS A proportion of colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.
Collapse
Affiliation(s)
- Hiroshi Nagata
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Manabu Kaneko
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Koji Yasuda
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Kensuke Otani
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Takeshi Nishikawa
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| |
Collapse
|
|
47
|
Segelman J, Akre O, Gustafsson UO, Bottai M, Martling A. External validation of models predicting the individual risk of metachronous peritoneal carcinomatosis from colon and rectal cancer. Colorectal Dis 2016; 18:378-85. [PMID: 26588669 DOI: 10.1111/codi.13219] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 10/08/2015] [Indexed: 12/16/2022]
Abstract
AIM To externally validate previously published predictive models of the risk of developing metachronous peritoneal carcinomatosis (PC) after resection of nonmetastatic colon or rectal cancer and to update the predictive model for colon cancer by adding new prognostic predictors. METHOD Data from all patients with Stage I-III colorectal cancer identified from a population-based database in Stockholm between 2008 and 2010 were used. We assessed the concordance between the predicted and observed probabilities of PC and utilized proportional-hazard regression to update the predictive model for colon cancer. RESULTS When applied to the new validation dataset (n = 2011), the colon and rectal cancer risk-score models predicted metachronous PC with a concordance index of 79% and 67%, respectively. After adding the subclasses of pT3 and pT4 stage and mucinous tumour to the colon cancer model, the concordance index increased to 82%. CONCLUSION In validation of external and recent cohorts, the predictive accuracy was strong in colon cancer and moderate in rectal cancer patients. The model can be used to identify high-risk patients for planned second-look laparoscopy/laparotomy for possible subsequent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Collapse
Affiliation(s)
- J Segelman
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - O Akre
- Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - U O Gustafsson
- Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
| | - M Bottai
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - A Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
48
|
Kawai K, Sunami E, Yamaguchi H, Ishihara S, Kazama S, Nozawa H, Hata K, Kiyomatsu T, Tanaka J, Tanaka T, Nishikawa T, Kitayama J, Watanabe T. Nomograms for colorectal cancer: A systematic review. World J Gastroenterol 2015; 21:11877-86. [PMID: 26557011 PMCID: PMC4631985 DOI: 10.3748/wjg.v21.i41.11877] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Revised: 05/28/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To assist in the selection of suitable nomograms for obtaining desired predictions in daily clinical practice. METHODS We conducted electronic searches for journal articles on colorectal cancer (CRC)-associated nomograms using the search terms colon/rectal/colorectal/nomogram. Of 174 articles initially found, we retrieved 28 studies in which a nomogram for CRC was developed. RESULTS We discuss the currently available CRC-associated nomograms, including those that predict the oncological prognosis, the short-term outcome of treatments, such as surgery or neoadjuvant chemoradiotherapy, and the future development of CRC. Developing nomograms always presents a dilemma. On the one hand, the desire to cover as wide a patient range as possible tends to produce nomograms that are too complex and yet have C-indexes that are not sufficiently high. Conversely, confining the target patients might impair the clinical applicability of constructed nomograms. CONCLUSION The information provided in this review should be of use in selecting a nomogram suitable for obtaining desired predictions in daily clinical practice.
Collapse
|
|
49
|
Mulsow J, Shields C. Improving timely detection and recording of colorectal peritoneal metastases. Colorectal Dis 2014; 16:1019-20. [PMID: 25283313 DOI: 10.1111/codi.12794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Accepted: 08/18/2014] [Indexed: 02/08/2023]
Affiliation(s)
- J Mulsow
- Peritoneal Malignancy Institute, Mater Misericordiae University Hospital, Dublin 7, Ireland.
| | | |
Collapse
|
|
50
|
Aoyagi T, Terracina KP, Raza A, Takabe K. Current treatment options for colon cancer peritoneal carcinomatosis. World J Gastroenterol 2014; 20:12493-12500. [PMID: 25253949 PMCID: PMC4168082 DOI: 10.3748/wjg.v20.i35.12493] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/10/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) prolongs the life of colon cancer PC patients. Here, we will review the clinical presentation, the mechanisms of disease progression, and current treatment options for colon cancer PC, with a focus on the benefits and limitations of CRS-HIPEC.
Collapse
|