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Liang GZ, Li XS, Hu ZH, Xu QJ, Wu F, Wu XL, Lei HK. Development and validation of a nomogram model for predicting overall survival in patients with gastric carcinoma. World J Gastrointest Oncol 2025; 17:95423. [PMID: 39958550 PMCID: PMC11755997 DOI: 10.4251/wjgo.v17.i2.95423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/01/2024] [Accepted: 11/06/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China, with the disease's intricate and varied characteristics further amplifying its health impact. Precise forecasting of overall survival (OS) is of paramount importance for the clinical management of individuals afflicted with this malignancy. AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma. METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020. Least absolute shrinkage and selection operator, univariate, and multivariate Cox regression analyses were employed to identify independent prognostic factors. A nomogram model was developed to predict gastric cancer patient outcomes. The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves. To evaluate the clinical utility of the model, Kaplan-Meier and decision curve analyses were performed. RESULTS A total of ten independent prognostic factors were identified, including body mass index, tumor-node-metastasis (TNM) stage, radiation, chemotherapy, surgery, albumin, globulin, neutrophil count, lactate dehydrogenase, and platelet-to-lymphocyte ratio. The area under the curve (AUC) values for the 1-, 3-, and 5-year survival prediction in the training set were 0.843, 0.850, and 0.821, respectively. The AUC values were 0.864, 0.820, and 0.786 for the 1-, 3-, and 5-year survival prediction in the validation set, respectively. The model exhibited strong discriminative ability, with both the time AUC and time C-index exceeding 0.75. Compared with TNM staging, the model demonstrated superior clinical utility. Ultimately, a nomogram was developed via a web-based interface. CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients, which demonstrated strong predictive ability. Based on these findings, this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.
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Affiliation(s)
- Guan-Zhong Liang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Xiao-Sheng Li
- Chongqing Cancer Multi-omics Big Data Application Engineering Research Center, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Zu-Hai Hu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Qian-Jie Xu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Fang Wu
- Research Center for Medicine and Social Development, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Xiang-Lin Wu
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Hai-Ke Lei
- The Research Center of Big Data, Chongqing University Cancer Hospital, Chongqing 400030, China
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Wang M, Huang K, Fan X, Wang J, Jin Y, Zheng ZJ. Access to radiotherapy in improving gastric cancer care quality and equality. COMMUNICATIONS MEDICINE 2024; 4:225. [PMID: 39488624 PMCID: PMC11531536 DOI: 10.1038/s43856-024-00655-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 10/23/2024] [Indexed: 11/04/2024] Open
Abstract
BACKGROUND Quality health services could improve patient outcomes and prognosis. Gastric cancer care was of great disparity across genders. Disparities within radiotherapy units could impact gastric cancer care, potentially exacerbating gender-based inequalities. METHODS We retrieved the disease burden data from Global Burden of Disease 2019. A quality of care index was constructed by applying principal component analysis techniques. The disparity of gastric cancer care across genders was described, and the association of access to radiotherapy with gastric cancer care as well as gender disparity was explored. RESULTS Males receive better quality of gastric cancer care than females, and this gender disparity is widening in middle-low socio-development regions. A positive correlation emerges between the density of radiotherapy facilities and an elevated quality of care, and reduced gender-based disparities. CONCLUSIONS The association between robust radiotherapy access, improved gastric cancer QCI, and reduced gender-based disparities spotlights the imperative of fortifying radiotherapy infrastructure within areas and populations in greatest need.
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Affiliation(s)
- Minmin Wang
- Department of Global Health, School of Public Health, Peking University, Beijing, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Kepei Huang
- Department of Global Health, School of Public Health, Peking University, Beijing, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Xiaohan Fan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jia Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yinzi Jin
- Department of Global Health, School of Public Health, Peking University, Beijing, China.
- Institute for Global Health and Development, Peking University, Beijing, China.
| | - Zhi-Jie Zheng
- Department of Global Health, School of Public Health, Peking University, Beijing, China
- Institute for Global Health and Development, Peking University, Beijing, China
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Hao JL, Li XY, Liu YT, Lang JX, Liu DJ, Zhang CD. Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies. Gastric Cancer 2024; 27:887-906. [PMID: 38963593 DOI: 10.1007/s10120-024-01529-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 06/25/2024] [Indexed: 07/05/2024]
Abstract
Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.
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Affiliation(s)
- Jia-Lin Hao
- Central Laboratory, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Xin-Yun Li
- Clinical Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Yu-Tong Liu
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110022, China
| | - Ji-Xuan Lang
- Department of Surgical Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Di-Jie Liu
- Central Laboratory, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Chun-Dong Zhang
- Central Laboratory, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.
- Department of Surgical Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China.
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Tian Z, Xia M, Cheng Y, Zhou J, Li R, Zhao S, Sun Q, Wang D. Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis. Surg Endosc 2024; 38:2756-2769. [PMID: 38575830 DOI: 10.1007/s00464-024-10798-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/10/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78 years). METHODS This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. RESULTS Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. CONCLUSIONS LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.
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Affiliation(s)
- Zhen Tian
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Mingyu Xia
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, China
| | - Yifan Cheng
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Jiajie Zhou
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Ruiqi Li
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Shuai Zhao
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Qiannan Sun
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, China
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, China
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, China
| | - Daorong Wang
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
- Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, China.
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, China.
- General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, China.
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, China.
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Cheung KS, Chan AOO, Yu Wong BC. Intestinal‐type Gastric Cancer. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:120-138. [DOI: 10.1002/9781119756422.ch7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Shirasaka Y, Yamada K, Etoh T, Noguchi K, Hasegawa T, Ogawa K, Kobayashi T, Nishizono A, Inomata M. Cytocidal Effect of Irradiation on Gastric Cancer Cells Infected with a Recombinant Mammalian Orthoreovirus Expressing a Membrane-Targeted KillerRed. Pharmaceuticals (Basel) 2024; 17:79. [PMID: 38256912 PMCID: PMC10818543 DOI: 10.3390/ph17010079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/23/2023] [Accepted: 01/06/2024] [Indexed: 01/24/2024] Open
Abstract
The outcomes of unresectable gastric cancer (GC) are unfavorable even with chemotherapy; therefore, a new treatment modality is required. The combination of an oncolytic virus and photodynamic therapy can be one of the promising modalities to overcome this. Mammalian orthoreovirus (MRV) is an oncolytic virus that has been used in clinical trials for several cancers. In this study, we developed and evaluated a recombinant MRV strain type 3 Dearing (T3D) that expresses membrane-targeting KillerRed (KRmem), a phototoxic fluorescent protein that produces cytotoxic reactive oxygen species upon light irradiation. KRmem was fused in-frame to the 3' end of the σ2 viral gene in the S2 segment using a 2A peptide linker, enabling the expression of multiple proteins from a single transcript. RNA electrophoresis, Western blotting, and immunofluorescence analyses confirmed functional insertion of KRmem into the recombinant virus. The growth activity of the recombinant virus was comparable to that of the wild-type MRV in a cultured cell line. The recombinant virus infected two GC cell lines (MKN45P and MKN7), and a significant cytocidal effect was observed in MKN45P cells infected with the recombinant virus after light irradiation. Thus, recombinant MRV-expressing KRmem has the potential to serve as a novel treatment tool for GC.
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Affiliation(s)
- Yoshinori Shirasaka
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan; (Y.S.); (T.H.); (K.O.); (M.I.)
| | - Kentaro Yamada
- Laboratory of Veterinary Public Health, Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-Nishi, Miyazaki City 889-2192, Miyazaki, Japan;
- Department of Microbiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan;
| | - Tsuyoshi Etoh
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan; (Y.S.); (T.H.); (K.O.); (M.I.)
- Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan
| | - Kazuko Noguchi
- Laboratory of Veterinary Public Health, Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-Nishi, Miyazaki City 889-2192, Miyazaki, Japan;
- Department of Microbiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan;
| | - Takumi Hasegawa
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan; (Y.S.); (T.H.); (K.O.); (M.I.)
| | - Katsuhiro Ogawa
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan; (Y.S.); (T.H.); (K.O.); (M.I.)
| | - Takeshi Kobayashi
- Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City 565-0871, Osaka, Japan;
| | - Akira Nishizono
- Department of Microbiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan;
- Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasamamachi, Yufu City 879-5593, Oita, Japan; (Y.S.); (T.H.); (K.O.); (M.I.)
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Kumar R, Tchelebi L, Anker CJ, Sharma N, Bianchi NA, Dragovic J, Goodman KA, Herman JM, Jiang Y, Jones WE, Kennedy TJ, Lee P, Kundranda M, Russo S, Small W, Suh WW, Yee N, Jabbour SK. American Radium Society (ARS) Appropriate Use Criteria (AUC) for Locoregional Gastric Adenocarcinoma: Systematic Review and Guidelines. Am J Clin Oncol 2022; 45:391-402. [PMID: 35947781 PMCID: PMC10865426 DOI: 10.1097/coc.0000000000000930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The objective of this study was to systematically evaluate the data regarding the use of neoadjuvant, perioperative, surgical, and adjuvant treatment options in localized gastric cancer patients and to develop Appropriate Use Criteria recommended by a panel of experts convened by the American Radium Society. METHODS Preferred reporting items for systematic reviews and meta-analyses methodology was used to develop an extensive analysis of peer-reviewed phase 2/2R/3 trials, as well as meta-analyses found within the Ovid Medline database between 2010 and 2020. The expert panel then rated the appropriateness of various treatments in 5 representative clinical scenarios through a well-established consensus methodology (modified Delphi). RESULTS For patients with medically operable locally advanced gastric cancer, the strongest recommendation was for perioperative chemotherapy based on high-quality data. Acceptable alternatives included surgery followed by either chemotherapy or concurrent chemoradiotherapy (CRT). For patients with upfront resection of stages I to III gastric cancer (no neoadjuvant therapy), the group strongly recommended adjuvant therapy with either chemotherapy alone or CRT, based on high-quality data. For patients with locally advanced disease who received preoperative chemotherapy without tumor regression, the group strongly recommended postoperative chemotherapy or postoperative CRT. Finally, for medically inoperable gastric cancer patients, there was moderate consensus recommending definitive concurrent CRT. CONCLUSIONS The addition of chemotherapy and/or radiation, either in the neoadjuvant, adjuvant, or perioperative setting, results in improved survival rates for patients compared with surgery alone. For inoperable patients, definitive CRT is a reasonable treatment option, though largely palliative.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Yixing Jiang
- UT Health Cancer Center, University of Texas Health Science Center, San Antonio
| | | | | | - Percy Lee
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Suzanne Russo
- School of Medicine, University Hospitals, Case Western Reserve University, Cleveland, OH
| | - William Small
- Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL
| | - Wonsuk W. Suh
- Ridley-Tree Cancer Center Santa Barbara at Sansum Clinic, Santa Barbara, CA
| | - Nelson Yee
- Northwell Health Cancer Institute, Mount Kisco
| | - Salma K. Jabbour
- Panel Chair, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
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Hu Y, Luo M. NORAD-sponged miR-378c alleviates malignant behaviors of stomach adenocarcinoma via targeting NRP1. Cancer Cell Int 2022; 22:79. [PMID: 35164743 PMCID: PMC8842946 DOI: 10.1186/s12935-022-02474-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 01/19/2022] [Indexed: 01/25/2023] Open
Abstract
Background Stomach adenocarcinoma (STAD) is the most common type of gastric cancer (GC), with a high recurrence rate and poor prognosis, but the potential indicators for STAD are insufficient. Methods Herein, we found that MicroRNA-378c (miR-378c) was lowly expressed in STAD, and the low expression of miR-378c was highly correlated with poor overall survival (OS), T stage, Reflux history, DSS events and PFI events of STAD patients. Results In addition, univariate analysis displayed that miR-378c was significantly associated with OS (Hazard ratio 0.735; 95% CI, 0.542–0.995; P = 0.046). Furthermore, it was validated that miR-378c inhibition accelerated STAD cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), while they were suppressed by miR-378c overexpression. Mechanistically, Neuropilin 1 (NRP1) was confirmed as the target of miR-378c, and Lnc-NORAD was identified as its sponger. More importantly, NORAD-mediated miR-378c inhibited malignant behaviors of STAD both in vitro and in vivo. Conclusions Collectively, these results suggest miR-378c as a promising indicator for the treatment of STAD. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-022-02474-5.
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Affiliation(s)
- Yongjun Hu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, No.139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ming Luo
- Department of General Surgery, The Second Xiangya Hospital, Central South University, No.139 Renmin Middle Road, Changsha, 410011, Hunan, China.
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Zhang F, Feng X, Li Y, Yan J, Zhang Z, Song X. Survival outcomes of neoadjuvant and adjuvant chemoradiotherapy for locally advanced adenocarcinoma of the oesophagogastric junction: a retrospective cohort study using the SEER database. J Gastrointest Oncol 2022; 13:26-39. [PMID: 35284136 PMCID: PMC8899751 DOI: 10.21037/jgo-21-815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/30/2021] [Indexed: 10/30/2023] Open
Abstract
BACKGROUND Both neoadjuvant chemoradiotherapy (nCRT) and adjuvant chemoradiotherapy (aCRT) have survival advantages over surgery alone in patients with adenocarcinoma of the oesophagogastric junction (AEG). However, whether there is a difference in the survival benefit between these two treatments and who can benefit from them remains controversial, and there are currently no randomised controlled trials to address these issues. This study compared the survival outcomes of patients with locally advanced AEG receiving nCRT and aCRT. METHODS The data of patients with locally advanced AEG were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Patients in the nCRT and aCRT groups were propensity-score matched 1:1, and the Kaplan-Meier method and log-rank test were used for survival analysis between the two groups. Univariable and multivariable Cox regression models were performed to identify the prognostic factors. RESULTS Of the 1,436 cases diagnosed as locally advanced AEG, we included 442 in the final analysis. The median overall survival (OS) of the nCRT and aCRT cohorts were 30.0 and 25.0 months, respectively (P=0.042), and the median tumour specific survival times were 37.0 and 31.0 months, respectively (P=0.249). Multivariable Cox regression analysis showed that OS was independently related to age [<60 years vs. ≥70 years, hazard ratio (HR) =0.619, 95% CI: 0.510-0.751, P<0.001; 60-69 years vs. ≥70 years, HR =0.661, 95% CI: 0.536-0.814, P<0.001] and N stage (N2 vs. N1, HR =1.213, 95% CI: 1.002-1.468, P=0.048; N3 vs. N1, HR =1.606, 95% CI: 1.190-2.167, P=0.002). Through stratifying patients by TNM stage, stage IIIB, and N1 stage, we observed that patients receiving nCRT had a better prognosis. CONCLUSIONS Patients receiving nCRT had significantly better survival than those receiving aCRT. nCRT may offer some therapeutic benefits in patients with IIIB stage AEG.
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Affiliation(s)
- Fan Zhang
- School of Graduate Studies, Hebei North University, Zhangjiakou, China
| | - Xingyu Feng
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangzhou, China
| | - Yong Li
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangzhou, China
| | - Juan Yan
- Department of Pharmacy, the First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Zhilin Zhang
- Department of Radiotherapy, the First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Xiao Song
- Department of Radiotherapy, the First Affiliated Hospital of Hebei North University, Zhangjiakou, China
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LncRNA OGFRP1 promotes cell proliferation and suppresses cell radiosensitivity in gastric cancer by targeting the miR-149-5p/MAP3K3 axis. J Mol Histol 2022; 53:257-271. [DOI: 10.1007/s10735-022-10058-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 01/06/2022] [Indexed: 12/11/2022]
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Capelli G, Tonello AS, Chiminazzo V, Lorenzoni G, Bao QR, Marchet A, Gregori D, Pawlik TM, Pucciarelli S, Spolverato G. Validation of a Nomogram to Predict Long Term Outcomes After Curative Surgery for Gastric Cancer in an Italian Cohort of Patients. J Visc Surg 2021; 159:471-479. [PMID: 34794901 DOI: 10.1016/j.jviscsurg.2021.09.001] [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: 10/19/2022]
Abstract
AIM OF THE STUDY Nomograms have been proposed to assess prognosis following curative surgery for gastric cancer. The objective of the current study was to evaluate the performance of the Gastric Cancer Collaborative Group nomograms developed in 2014 by Kim et al., using a cohort of patients from a 10-year single institution experience in gastric cancer management. PATIENTS AND METHODS We retrospectively reviewed patients who underwent curative-intent surgery for histologically confirmed gastric cancer at First Surgical Clinic of Padua University Hospital (Italy) from January 2010 to May 2020. Univariable and multivariable Cox proportional hazard models were employed to assess the effect of the variables of interest on mortality and recurrence. Multivariable analysis was performed by considering the variables included in the Gastric Cancer Collaborative Group nomograms in order to validate them. The performance of the nomograms was evaluated using Harrell's C-index and calibration plots. RESULTS Overall, 168 patients were included, with a median follow-up of 20.1 months. On multivariable analysis, tumor location, lymph node ratio, and pathological T stage were associated with recurrence; age, tumor location, lymph node ratio, and pT stage were associated with OS (overall survival). The nomograms had good discriminatory capability to classify both OS (C-index: 0.75) and DFS (disease-free survival) (C-index 0.72). The corrected C-Index for DFS based on the AJCC staging system revealed better prediction (C-Index 0.75), while the corrected C-Index for OS had worse discrimination ability compared with the current nomogram (C-Index 0.72). CONCLUSIONS The Gastric Cancer Collaborative Group nomograms demonstrated good performances in terms of prediction of both OS and DFS on external validation. The two nomograms are easy to apply, and variables included are widely available to most facilities.
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Affiliation(s)
- G Capelli
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), First Surgical Clinic, University of Padua, Padua, Italy
| | - A S Tonello
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), First Surgical Clinic, University of Padua, Padua, Italy
| | - V Chiminazzo
- Unit of Biostatistics, Epidemiology, and Public Health, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy
| | - G Lorenzoni
- Unit of Biostatistics, Epidemiology, and Public Health, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy
| | - Q R Bao
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), First Surgical Clinic, University of Padua, Padua, Italy
| | - A Marchet
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), First Surgical Clinic, University of Padua, Padua, Italy
| | - D Gregori
- Unit of Biostatistics, Epidemiology, and Public Health, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy
| | - T M Pawlik
- Department of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - S Pucciarelli
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), First Surgical Clinic, University of Padua, Padua, Italy
| | - G Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), First Surgical Clinic, University of Padua, Padua, Italy.
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12
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Post-surgery Survival in Patients with Adenocarcinoma of Stomach Using Multistate Model. J Gastrointest Cancer 2021; 53:311-317. [PMID: 33591561 DOI: 10.1007/s12029-021-00599-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE Stomach neoplasms are the fifth common cancer worldwide. The related factors for survival following stomach neoplasms are well-studied; however, information on recurrent events is limited. This study aimed to identify the related factors on recurrent and deaths following stomach neoplasms. METHODS In this cohort study, information on 672 patients with adenocarcinoma who were hospitalized during 1995-2012 was used. Multistate models were applied to determine the effective factors on recurrent and death events. RESULTS Median of survival time (months) and 5-year survival was estimated as 24.5 and 25%, respectively. The probability of death was 57% for non-recurrent patients, which increased to 88% among recurrent patients. Hazard of death was 49% lower for females (Hazard Ratio (HR):0.51, P = 0.009) while females had higher hazard of death following recurrent (HR:3.55, P < 0.001). Male patients and those with cardia involvement had higher risk of recurrence. A significant effect of age on the risk of death among patients with and without recurrence was estimated (HR:1.02, 1.03; P = 0.001 for both). Age, cardia involvement, and disease stage are amongst the effective factors on non-recurrent death while complement treatments increased the non-recurrent and recurrent survival. CONCLUSION In patients, effects of some factors for survival may vary throughout the course of disease and depend on recurrence status. We found that while female patients experienced lower recurrence, they had higher risk of death following recurrence. Age, tumor location, and type of therapy were risk factors for non-recurrent death. Finally, tumor location and type of surgery had significant effects on recurrence.
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13
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Pan S, Yin S, Zhu Z, Liu F, Xu H. Decision-making of adjuvant therapy in pT1N1M0 gastric cancer: Should radiotherapy be added to chemotherapy? A propensity score-matched analysis. J Cancer 2021; 12:1179-1189. [PMID: 33442416 PMCID: PMC7797651 DOI: 10.7150/jca.52123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 12/01/2020] [Indexed: 11/21/2022] Open
Abstract
Background: Early gastric cancer (EGC) with metastatic lymph nodes (mLNs) has a relatively higher recurrence rate and poorer prognosis than EGC without mLNs. However, the postoperative treatment directions of pT1N1M0 vary from different guidelines. This study attempted to confirm the value of postoperative treatments in pT1N1M0 GC patients. Methods: Overall, 379 patients with pT1N1M0 GC following gastrectomy from 2000 to 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score-matched (PSM) analysis was used to reduce bias. Overall survival was analyzed by Kaplan-Meier method and the log-rank test. Cox proportional hazards regression analyses were used to confirm the independent prognostic factors. Results: Before matching, the results of survival analyses indicated that adjuvant chemotherapy (ACT) and chemoradiotherapy (ACRT) could significantly prolong the survival time of the cohort (P < 0.05). After PSM analysis, 136 patients remained and ACRT maintained significance in the survival analysis (P = 0.018). Furthermore, patients with well or moderately differentiated GC (HR = 0.226, P =0.018) or intestinal type GC (HR = 0.380, P = 0.040) achieved a significantly superior prognosis with ACRT, compared to patients receiving ACT. Conclusion: The survival benefit of ACRT and ACT for pT1N1M0 GC patients following gastrectomy was confirmed in the SEER cohort. RT added to ACT might be recommended according to Lauren's classification and tumor grade in clinical decision making.
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Affiliation(s)
- Siwei Pan
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Songcheng Yin
- Center for Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhi Zhu
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Funan Liu
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Huimian Xu
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang, China.,Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China
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14
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Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, Sun L, Chen H. Comparison of 68Ga-FAPI and 18F-FDG Uptake in Gastric, Duodenal, and Colorectal Cancers. Radiology 2020; 298:393-402. [PMID: 33258746 DOI: 10.1148/radiol.2020203275] [Citation(s) in RCA: 183] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Accurate clinical staging is crucial to managing gastrointestinal cancer, but fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has limitations. Targeting fibroblast-activation protein is a newer diagnostic approach for the visualization of tumor stroma, and gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitors (FAPIs), hereafter 68Ga-FAPIs, present a promising alternative to 18F-FDG. Purpose To compare the diagnostic efficacy of 68Ga-FAPI PET/CT in primary and metastatic lesions of gastrointestinal malignancies with that of 18F-FDG PET/CT. Materials and Methods Images from patients with gastric, duodenal, and colorectal cancers who underwent contemporaneous 18F-FDG and 68Ga-FAPI PET/CT between October 2019 through June 2020 were retrospectively analyzed. 18F-FDG and 68Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic performance between the two techniques. Results Thirty-five patients (median age, 64 years [interquartile range, 53-68 years]; 18 men) were evaluated. In treatment-naive patients (n = 19), 68Ga-FAPI PET/CT led to upstaging of the clinical TNM stage in four (21%) patients compared with 18F-FDG PET/CT. Tracer uptake was higher with 68Ga-FAPI PET/CT than with 18F-FDG PET/CT in primary lesions (gastric cancer: 12.7 vs 3.7, respectively, P = .003; colorectal cancer: 15.9 vs 7.9, P = .03), involved lymph nodes (6.7 vs 2.4, P < .001), and bone and visceral metastases (liver metastases: 9.7 vs 5.2, P < .001; peritoneal metastases: 8.4 vs 3.6, P < .001; bone metastases: 4.3 vs 2.2, P < .001; lung metastases: 4.4 vs 1.9, P = .01). In addition, the sensitivity of 68Ga-FAPI PET/CT was higher than that of 18F-FDG PET/CT in the detection of primary tumors (100% [19 of 19] vs 53% [10 of 19], respectively; P = .004), lymph nodes (79% [22 of 28] vs 54% [15 of 28], P < .001), and bone and visceral metastases (89% [31 of 35] vs 57% [20 of 35], P < .001). Conclusion Gallium 68 fibroblast-activation protein inhibitor PET/CT was superior to fluorine 18 fluorodeoxyglucose PET/CT in the detection of primary and metastatic lesions in gastric, duodenal, and colorectal cancers, with higher tracer uptake in most primary and metastatic lesions. Published under a CC BY 4.0 license.
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Affiliation(s)
- Yizhen Pang
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Liang Zhao
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Zuoming Luo
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Bing Hao
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Hua Wu
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Qin Lin
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Long Sun
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
| | - Haojun Chen
- From the Department of Nuclear Medicine & Minnan PET Center (Y.P., Z.L., B.H., H.W., L.S., H.C.) and Department of Radiation Oncology (L.Z., Q.L.), Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd, Xiamen 361003, China
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15
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Yang W, Zhou M, Li G, Shen L, Wang Y, Zhang H, Wang Y, Zhang J, Sun X, Zhang Z, Zou W, Zhang Z. Preoperative Chemoradiotherapy Versus Postoperative Chemoradiotherapy for Patients With Locally Advanced Gastric Cancer: A Retrospective Study Based on Propensity Score Analyses. Front Oncol 2020; 10:560115. [PMID: 33178589 PMCID: PMC7596744 DOI: 10.3389/fonc.2020.560115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 09/28/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose Although adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT versus that of postoperative CRT for resectable or potentially resectable gastric cancer. Methods From January 2005 to December 2017, patients with clinical stage III/IVa (i.e., T3-4aN+M0 or T4bNxM0) locally advanced gastric cancer were retrospectively identified. Survival after preoperative CRT and postoperative CRT was assessed by unadjusted, propensity score matching (PSM) and inverse probability of treatment weight (IPTW) analyses. Moreover, exploratory subgroup analyses were performed, and toxicity and patterns of failure were also investigated. Results The median follow-up time was 32.5 months. A total of 82 and 463 patients were enrolled in the preoperative and postoperative CRT groups, respectively. After propensity score matching, preoperative CRT was associated with improved overall survival (OS) and disease-free survival (DFS) compared with postoperative CRT (3-year OS: 72.6 vs. 54.4%, log-rank p = 0.0021; 3-year DFS: 61.7 vs. 44.7%, log-rank p = 0.002). The unadjusted and IPTW analyses yielded consistent results. A complete pathologic response was achieved in 13.4% of the preoperative CRT group. Although the incidence of grade 3 or 4 adverse effects and surgical complications were similar between the two groups, significantly fewer patients experienced treatment interruptions or dose reductions due to toxic effects in the preoperative CRT setting than in the postoperative CRT setting (3.7 vs. 10.6%, p = 0.049). Conclusions Compared with postoperative CRT, preoperative CRT was associated with improved OS and DFS, superior treatment compliance and comparable surgical complications for patients with locally advanced gastric cancer. Our findings provide important evidence for the optimal combination modalities of surgery and CRT in the absence of randomized clinical data.
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Affiliation(s)
- Wang Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Menglong Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Guichao Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Lijun Shen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yan Wang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Hui Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yaqi Wang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jing Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaoyang Sun
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiyuan Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Wei Zou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhen Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
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Gong H, Chu Y, Hu Q, Song Q. Preoperative Radiotherapy Is Associated With Significant Survival Benefits for Patients With Gastric Signet Ring Cell Carcinoma: A SEER-Based Approach. Technol Cancer Res Treat 2020; 19:1533033820960746. [PMID: 32945232 PMCID: PMC7506782 DOI: 10.1177/1533033820960746] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Objective: To explore the clinical and pathological features of gastric signet ring cell
carcinoma, and evaluate the survival impact of preoperative radiotherapy on
these patients. Methods: The Surveillance, Epidemiology, and End Results database was used to extract
eligible patients from 2004 to 2015. The patients were divided into those
with and without preoperative radiotherapy. The categorical variables were
described by chi-square tests. The patients’ survival was compared between
the 2 groups by Kaplan-Meier method with log-rank tests. Cox proportional
hazard model was adopted to identify prognostic factors of cancer-specific
survival. Results: Totally 4771 patients were recruited, of whom 218(4.6%) patients received
preoperative radiotherapy, while 4553(95.4%) patients didn’t receive this
treatment. Survival analysis of the entire cohort demonstrated that
preoperative radiotherapy improved both cancer-specific survival and overall
survival (p < 0.001) of the patients. Cox proportional hazard models
identified age >60, tumor size >50 mm, TNM stage II-IV as independent
risk factors for poor prognosis (HR > 1, p < 0.05). Notably,
preoperative radiotherapy was identified as an independent protective factor
for favorable prognosis (HR < 1, p < 0.05). Subgroup survival analysis
showed that preoperative radiotherapy exerted significant survival benefits
for the stages III and IV patients. Conclusions: In this population-based study, preoperative radiotherapy is associated with
significant survival benefits for the patients with advanced gastric signet
ring cell carcinoma. Hence preoperative radiotherapy is feasible for these
patients.
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Affiliation(s)
- Hongyun Gong
- Department of Oncology I, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuxin Chu
- Department of Oncology I, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qinyong Hu
- Department of Oncology I, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qibin Song
- Department of Oncology I, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
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Badiyan S, Kaiser A, Eastman B, Forsthoefel M, Zeng J, Unger K, Chuong M. Immunotherapy and radiation therapy for gastrointestinal malignancies: hope or hype? Transl Gastroenterol Hepatol 2020; 5:21. [PMID: 32258525 PMCID: PMC7063525 DOI: 10.21037/tgh.2019.10.07] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 10/04/2019] [Indexed: 12/24/2022] Open
Abstract
Immunotherapy represents the newest pillar in cancer care. Although there are increasing data showing the efficacy of immunotherapy there is a spectrum of response across unselected populations of cancer patients. In fact, response rates can be poor even among patients with immunogenic tumors for reasons that remain poorly understood. A promising clinical strategy to improve outcomes, which is supported by an abundance of preclinical data, is combining immunotherapy with radiation therapy. Here we review the existing evidence and future directions for combining immunotherapy and radiation therapy for patients with gastrointestinal cancers.
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Affiliation(s)
- Shahed Badiyan
- Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Adeel Kaiser
- University of Maryland Medical Center, Baltimore, MD, USA
| | - Bory Eastman
- University of Washington Medical Center, Seattle, WA, USA
| | - Matthew Forsthoefel
- Department of Radiation Oncology, Georgetown University Hospital, Washington, DC, USA
| | - Jing Zeng
- University of Washington Medical Center, Seattle, WA, USA
| | - Keith Unger
- Department of Radiation Oncology, Georgetown University Hospital, Washington, DC, USA
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Study of Survival in Gastric Cancer with Emphasis on Lymph Node Status as an Independent Prognostic Factor. JOURNAL OF INTERDISCIPLINARY MEDICINE 2019. [DOI: 10.2478/jim-2019-0031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Background: Lymph node status in gastric cancer is known as an independent prognostic factor that guides the surgical and oncological treatment and independently influences long-term survival. Several studies suggest that the lymph node ratio has a greater importance in survival than the number of metastatic lymph nodes.
Aim: The aim of this study was to evaluate the clinical and morphological factors that can influence the survival of gastric cancer patients, with an emphasis on nodal status and the lymph node ratio.
Material and methods: We conducted a retrospective study in which 303 patients with gastric cancer admitted to the Department of Surgery of the Mureș County Hospital between 2008 and 2018 were screened for study enrolment. Data were obtained from the records of the department and from the histopathological reports. The examined variables included: age, gender, tumor localization, T stage, histological type, grade of differentiation, surgical procedure, lympho-vascular invasion, excised lymph nodes, metastatic lymph nodes, lymph node ratio. After screening, the study included a total number of 100 patients, for which follow-up data was available.
Results: The mean age of the study population was 66.43 ± 10 years, and 71% were males. The average survival period was 21.42 months. Statistical analysis showed that the localization of the tumor (p = 0.021), vascular invasion (p ---lt---0.001), T (p = 0.004) and N (p ---lt---0.001) stages, type of surgery (partial gastrectomy 59% vs. total gastrectomy 41%, p = 0.005), as well as the lymph node ratio (p ---lt---0.001) were prognostic factors for survival in patients with gastric cancer undergoing surgical therapy.
Conclusions: The survival of gastric cancer patients is significantly influenced by tumor localization, T stage, vascular invasion, type of surgery, N stage and the lymph node ratio based on univariate analysis. Also, the lymph node ratio proved to be an independent prognostic factor for survival.
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Ren F, Li S, Zhang Y, Zhao Z, Wang H, Cui Y, Wang M. Efficacy and safety of intensity-modulated radiation therapy versus three-dimensional conformal radiation treatment for patients with gastric cancer: a systematic review and meta-analysis. Radiat Oncol 2019; 14:84. [PMID: 31118042 PMCID: PMC6532249 DOI: 10.1186/s13014-019-1294-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 05/08/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Radiation or radiochemotherapy is a common adjuvant therapy for gastric cancer. Intensity-modulated radiation therapy (IMRT) has been demonstrated to provide better dose conformity, allowing dose escalation and/or reduction of normal tissue exposure compared with three-dimensional conformal radiation treatment (3D-CRT). However, the efficacy of IMRT and 3D-CRT in gastric cancer remains controversial. This study aimed to compare the efficacy and safety of IMRT with those of 3D-CRT in treating patients with gastric cancer through conducting a meta-analysis of 3-year survival rates [overall survival (OS) and disease-free survival (DFS)], local control rates, and toxic event rates. METHODS Embase, PubMed, the Cochrane Library, and clinical trial databases were searched to identify the clinical trials of IMRT versus 3D-CRT for treating patients with gastric cancer. The obtained data of survival and safety were analyzed using the Stata 14.0 software. RESULTS A total of 9 controlled clinical studies, including 516 patients with gastric cancer, met the inclusion criteria and were included in this meta-analysis. The results of the meta-analysis showed that the 3-year OS rate was slightly higher in the IMRT group than in the 3D-CRT group, without any statistical significance. The 3-year local control rate was significantly higher in the IMRT group than in the 3D-CRT group. No significant difference in the 3-year DFS rate was found between the IMRT and 3D-CRT groups. Grade 2-4 toxicities were similar between the IMRT and 3D-CRT groups. CONCLUSION The findings suggested that IMRT might be superior to 3D-CRT in treating patients with gastric cancer in terms of local control rates without increasing toxicity.
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Affiliation(s)
- Fang Ren
- Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853 China
| | - Shaodan Li
- Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853 China
| | - Yin Zhang
- Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853 China
| | - Zhifei Zhao
- Department of Radiotherapy, Chinese PLA General Hospital, Beijing, 100853 China
| | - Haiming Wang
- Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853 China
| | - Yixin Cui
- Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853 China
| | - Maoyun Wang
- Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853 China
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Korean Practice Guideline for Gastric Cancer 2018: an Evidence-based, Multi-disciplinary Approach. J Gastric Cancer 2019; 19:1-48. [PMID: 30944757 PMCID: PMC6441770 DOI: 10.5230/jgc.2019.19.e8] [Citation(s) in RCA: 294] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 02/12/2019] [Accepted: 02/14/2019] [Indexed: 12/13/2022] Open
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Skrobala A, Adamczyk M, Karczewska-Dzionk A. Feasibility of intensity-modulated radiotherapy to treat gastric cancer. Rep Pract Oncol Radiother 2019; 24:68-73. [DOI: 10.1016/j.rpor.2018.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 07/13/2018] [Accepted: 10/25/2018] [Indexed: 11/27/2022] Open
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Zaanan A, Bouché O, Benhaim L, Buecher B, Chapelle N, Dubreuil O, Fares N, Granger V, Lefort C, Gagniere J, Meilleroux J, Baumann AS, Vendrely V, Ducreux M, Michel P. Gastric cancer: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis 2018; 50:768-779. [PMID: 29886081 DOI: 10.1016/j.dld.2018.04.025] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Revised: 04/25/2018] [Accepted: 04/26/2018] [Indexed: 02/06/2023]
Abstract
INTRODUCTION This document is a summary of the French Intergroup guidelines regarding the management of gastric cancer published in October 2016, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org), updated in October 2017. METHODS This collaborative work was realized under the auspices of several French medical societies involved in management of gastric cancer. Recommendations are graded in three categories (A-C), according to the amount of evidence found in the literature until July 2017. RESULTS There are several known risk factors for gastric cancer, including Helicobacter pylori and genetic predispositions, both requiring a specific screening for patients and their relatives. The diagnosis and staging evaluation are essentially based on gastroscopy plus biopsies and computed tomography scan. The endoscopic ultrasonography can be used for superficial tumors in case of discussion for endoscopic resection (T1N0). For local disease (N+ and/or T > T1), the strategic therapy is based on surgery associated with perioperative chemotherapy. In the absence of preoperative treatment (for any raison), the postoperative chemoradiotherapy (or chemotherapy) should be discussed for patients with stage II or III tumor. For metastatic disease, the treatment is based on "palliative" chemotherapy consisting in a doublet or triplet regimens depending of age, performance status and HER2 tumor status. For patients with limited metastatic disease, surgical resection could be discussed in multidisciplinary meeting in case of stable disease after chemotherapy. CONCLUSION These guidelines in gastric cancer are done to help decision for daily clinical practice. These recommendations are permanently being reviewed. Each individual case must be discussed within a multidisciplinary team.
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Affiliation(s)
- Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, APHP, Paris, France.
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, CHU Reims, Reims, France
| | - Leonor Benhaim
- Department of Surgical Oncology, Gustave Roussy Cancer Center, UNICANCER, Villejuif, France
| | - Bruno Buecher
- Departments of Genetics and Medical Oncology, Curie Institute, UNICANCER, Paris, France
| | - Nicolas Chapelle
- Department of Hepato-Gastroenterology and Digestive Oncology, Institute for Diseases of the Digestive System, CHU Nantes, France
| | - Olivier Dubreuil
- Department of Gastroenterology and Digestive Oncology, Pitié-Salpêtrière Hospital, APHP, Paris, France
| | - Nadim Fares
- Department of Digestive Oncology, CHU Toulouse, Toulouse, France
| | - Victoire Granger
- Department of Hepato-Gastroenterology and Digestive Oncology, CHU Grenoble, Grenoble, France
| | - Christine Lefort
- Department of Gastroenterology and Endoscopy, Private Hospital Jean Mermoz, Lyon, France
| | - Johan Gagniere
- Department of Digestive and Hepatobiliary Surgery, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | | | - Anne-Sophie Baumann
- Department of Radiotherapy, Lorraine Institute of Oncology, UNICANCER, Vandœuvre-lès-Nancy, France
| | | | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy Cancer Center, UNICANCER, Villejuif, France
| | - Pierre Michel
- Department of Hepato-gastroenterology and Digestive Oncology, CHU Rouen, Rouen, France
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Giampieri R, Del Prete M, Cantini L, Baleani MG, Bittoni A, Maccaroni E, Berardi R. Optimal management of resected gastric cancer. Cancer Manag Res 2018; 10:1605-1618. [PMID: 29950898 PMCID: PMC6016582 DOI: 10.2147/cmar.s151552] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Although advances in medical treatment for gastric cancer (GC) have been made, surgery remains the mainstay of cure for patients with localized disease. Improvement in surgical modalities leads to increased chance of cure for resected patients, but a non-negligible number of patients eventually relapse. On this basis, it has been hypothesized that the addition of complementary systemic or local treatments (such as chemotherapy and radiotherapy) could help in improving patients' survival by reducing the risk of recurrence. Several studies have tried to identify the best approach in localized GC: some of them have assessed the role of perioperative chemotherapy [CT] with different drug combinations, while others have focused on the benefit obtained by addition of radiotherapy, whose role is still under investigation. In particular, the role of chemoradiotherapy, both in adjuvant and neoadjuvant settings, is still uncertain. In the last few years, several clinicopathological and molecular factors have been investigated and identified as potential prognostic markers in GC. Many of these factors could have influenced the outcome of patients receiving combined treatments in the abovementioned studies. Patients have not been generally distinguished by the site of disease (esophageal, gastric and junctional cancers) and surgical approach, making data difficult to be interpreted. The purpose of this review was to shed light on these highly controversial topics.
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Affiliation(s)
- Riccardo Giampieri
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Michela Del Prete
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Luca Cantini
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Maria Giuditta Baleani
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Alessandro Bittoni
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Elena Maccaroni
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Rossana Berardi
- Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
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Szász AM, Lánczky A, Nagy Á, Förster S, Hark K, Green JE, Boussioutas A, Busuttil R, Szabó A, Győrffy B. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget 2018; 7:49322-49333. [PMID: 27384994 PMCID: PMC5226511 DOI: 10.18632/oncotarget.10337] [Citation(s) in RCA: 752] [Impact Index Per Article: 107.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 06/13/2016] [Indexed: 02/07/2023] Open
Abstract
Introduction Multiple gene expression based prognostic biomarkers have been repeatedly identified in gastric carcinoma. However, without confirmation in an independent validation study, their clinical utility is limited. Our goal was to establish a robust database enabling the swift validation of previous and future gastric cancer survival biomarker candidates. Results The entire database incorporates 1,065 gastric carcinoma samples, gene expression data. Out of 29 established markers, higher expression of BECN1 (HR = 0.68, p = 1.5E-05), CASP3 (HR = 0.5, p = 6E-14), COX2 (HR = 0.72, p = 0.0013), CTGF (HR = 0.72, p = 0.00051), CTNNB1 (HR = 0.47, p = 4.3E-15), MET (HR = 0.63, p = 1.3E-05), and SIRT1 (HR = 0.64, p = 2.2E-07) correlated to longer OS. Higher expression of BIRC5 (HR = 1.45, p = 1E-04), CNTN1 (HR = 1.44, p = 3.5E- 05), EGFR (HR = 1.86, p = 8.5E-11), ERCC1 (HR = 1.36, p = 0.0012), HER2 (HR = 1.41, p = 0.00011), MMP2 (HR = 1.78, p = 2.6E-09), PFKB4 (HR = 1.56, p = 3.2E-07), SPHK1 (HR = 1.61, p = 3.1E-06), SP1 (HR = 1.45, p = 1.6E-05), TIMP1 (HR = 1.92, p = 2.2E- 10) and VEGF (HR = 1.53, p = 5.7E-06) were predictive for poor OS. MATERIALS AND METHODS We integrated samples of three major cancer research centers (Berlin, Bethesda and Melbourne datasets) and publicly available datasets with available follow-up data to form a single integrated database. Subsequently, we performed a literature search for prognostic markers in gastric carcinomas (PubMed, 2012–2015) and re-validated their findings predicting first progression (FP) and overall survival (OS) using uni- and multivariate Cox proportional hazards regression analysis. Conclusions The major advantage of our analysis is that we evaluated all genes in the same set of patients thereby making direct comparison of the markers feasible. The best performing genes include BIRC5, CASP3, CTNNB1, TIMP-1, MMP-2, SIRT, and VEGF.
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Affiliation(s)
- A Marcell Szász
- MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.,2nd Department of Pathology, Semmelweis University, Budapest, Hungary
| | - András Lánczky
- MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary
| | - Ádám Nagy
- MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary
| | - Susann Förster
- Max Delbrück Center for Molecular Medicine, Berlin, Germany
| | - Kim Hark
- Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Jeffrey E Green
- Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Alex Boussioutas
- Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.,Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.,Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia
| | - Rita Busuttil
- Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.,Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.,Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia
| | - András Szabó
- 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Balázs Győrffy
- MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.,2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
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Gong W, Zhao H, Liu S, Guan J, Liu X, Hou Q, Zhu Z, Guo H. Outcomes of radiation therapy for resectable M0 gastric cancer. Oncotarget 2018; 9:1726-1734. [PMID: 29416726 PMCID: PMC5788594 DOI: 10.18632/oncotarget.22574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 08/28/2017] [Indexed: 11/25/2022] Open
Abstract
Background The role of radiaotion therapy in resectable gastric cancer patients without distant metastases remains controversial. This retrospective analysis was performed to identify whether resectable gastric cancer patients without distant metastases might benefit from radiation. Results The results of the Kaplan-Meier analysis and log-rank test showed that a total of 3309 patients had a MST of 29.0 months, a 1-year survival rate of 74.7%, and a 3-year survival rate of 45.5%. Among them, the MST of the "RPS" group and the "RAS" group were significantly longer compared with that of the "No Radiation" group (32.7vs 32.9 vs 25.3 months, P < 0.05). The 1-year survival rates were 83.7%, 83.5% and 65.6% for the "RPS", "RAS" and "No radiation" groups, respectively (P < 0.05) and the 3-year survival rates were 52.6%, 63.6% and 44.9%, respectively (P < 0.05). The multivariate Cox proportional hazard regression analysis showed that radiation was an independent prognostic factor. Materials and Methods A total of 5744 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer without distant metastases from 2010 to 2013 were included. Patients were divided into three groups as follows: patients who underwent radiation after surgery ("RAS" group), patients who underwent radiation prior to surgery ("RPS" group) and patients who did not undergo radiation ,only surgery performed ("No radiation'"group). Conclusions This retrospective analysis demonstrated that "RPS" or "RAS"alone were independent prognostic factors for survival improvement in selected gastric cancer patients without distant metastases.
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Affiliation(s)
- Weipeng Gong
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Hongwei Zhao
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Shanshan Liu
- Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Jie Guan
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Xin Liu
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Qingsheng Hou
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Zhenyu Zhu
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
| | - Hongliang Guo
- Department of Surgical Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250117, China
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Serum miR-125b is a non-invasive predictive biomarker of the pre-operative chemoradiotherapy responsiveness in patients with rectal adenocarcinoma. Oncotarget 2017; 7:28647-57. [PMID: 27081702 PMCID: PMC5053752 DOI: 10.18632/oncotarget.8725] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 03/28/2016] [Indexed: 02/07/2023] Open
Abstract
Background Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradiotherapy (pCRT) followed by surgery. However, after pCRT the complete pathological response is approximately 20%, whereas in 20 to 40% of patients the response is poor or absent. Methods Cancer biopsy specimens (n= 38) and serum samples (n= 34) obtained before pCRT from 38 LARC patients were included in the study. Patients were classified in responders (R, tumor regression grade [TRG] 1-2; n= 16) and non-responders (NR, TRG 3-5; n= 22) according to the pathological response observed upon surgery. We performed miRNA microarrays analysis on biopsy specimens, and validated the selected candidates both by qRT-PCR (tissue and serum) and by in situ hybridization (tissue, miR-125b) analyses. Results Eleven miRNAs were significantly different between R and NR (miR-154, miR-409-3p, miR-127-3p, miR-214*, miR-299-5p and miR-125b overexpressed in NR; miR-33a, miR-30e, miR-338-3p, miR-200a and miR-378 decreased). In particular, miR-125b resulted to be the best candidate to discriminate the two groups (AUC of 0.9026; 95% CI, 0.7618-1.043). Additionally, miR-125b serum levels were significantly overexpressed in NR patients compared to R (p-value=0.0087), with an excellent discriminating power (AUC of 0.782; 95% CI, 0.6123-0.9518). Conclusions The obtained results further support the clinical impact of miRNA analysis. High miR-125b expression in tissue and serum were associated with a poor treatment response in LARC patients, therefore miR-125b could be considered as a possible novel non-invasive biomarker of response in LARC treatment.
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Onal C, Dölek Y, Akkuş Yıldırım B. Dosimetric comparison of 3-dimensional conformal radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for postoperative gastric cancer patients. Jpn J Radiol 2017; 36:30-39. [PMID: 29101643 DOI: 10.1007/s11604-017-0696-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Accepted: 10/16/2017] [Indexed: 12/12/2022]
Abstract
PURPOSE To compare dosimetric data for the planning target volume (PTV) and organs at risk (OARs) between 3-dimensional conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy [1]. MATERIALS AND METHODS The dosimetric data for 15 gastric cancer patients treated with 3DCRT, VMAT, or HT techniques were used. Cumulative dosimetric parameters, homogeneity index (HI), and conformal index (CI) were compared for the PTV and OARs. RESULTS The average maximum doses of PTV were significantly higher in VMAT plans than in 3DCRT (p = 0.04) and HT (p = 0.02) plans, whereas minimum dose values were significantly lower in 3DCRT plans compared with VMAT (p < 0.001) and HT (p = 0.02) plans. Liver mean dose (D mean) and D mean values for both kidneys were significantly lower in HT plans than in 3DCRT and VMAT plans. The doses in high dose regions (V30-V45) using 3DCRT plans were significantly higher compared to both VMAT and HT plans. The bowel V5-V30 and V45 was significantly less in HT plans compared to VMAT plans. There were no significant differences in dose sparing of the spinal cord. CONCLUSIONS The HT plans reduced the maximum dose applied to the target and improved the conformality and homogeneity of radiation, while providing sufficient PTV coverage.
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Affiliation(s)
- Cem Onal
- Department of Radiation Oncology, Adana Dr Turgut Noyan Research and Treatment Centre, Baskent University Faculty of Medicine, 01120, Adana, Turkey.
| | - Yemliha Dölek
- Department of Radiation Oncology, Adana Dr Turgut Noyan Research and Treatment Centre, Baskent University Faculty of Medicine, 01120, Adana, Turkey
| | - Berna Akkuş Yıldırım
- Department of Radiation Oncology, Adana Dr Turgut Noyan Research and Treatment Centre, Baskent University Faculty of Medicine, 01120, Adana, Turkey
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Ng J, Lee P. The Role of Radiotherapy in Localized Esophageal and Gastric Cancer. Hematol Oncol Clin North Am 2017; 31:453-468. [DOI: 10.1016/j.hoc.2017.01.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Stumpf PK, Amini A, Jones BL, Koshy M, Sher DJ, Lieu CH, Schefter TE, Goodman KA, Rusthoven CG. Adjuvant radiotherapy improves overall survival in patients with resected gastric adenocarcinoma: A National Cancer Data Base analysis. Cancer 2017; 123:3402-3409. [PMID: 28513823 DOI: 10.1002/cncr.30748] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 03/08/2017] [Accepted: 03/28/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens. METHODS Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed. RESULTS A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001). CONCLUSIONS In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017;123:3402-9. © 2017 American Cancer Society.
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Affiliation(s)
- Priscilla K Stumpf
- Department of Radiation Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
| | - Arya Amini
- Department of Radiation Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
| | - Bernard L Jones
- Department of Radiation Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
| | - Matthew Koshy
- Department of Radiation Oncology, University of Illinois at Chicago School of Medicine, Chicago, Illinois
| | - David J Sher
- Radiation Oncology, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Christopher H Lieu
- Department of Medical Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
| | - Tracey E Schefter
- Department of Radiation Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
| | - Karyn A Goodman
- Department of Radiation Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
| | - Chad G Rusthoven
- Department of Radiation Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado
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Onal C, Cengiz M, Guler OC, Dolek Y, Ozkok S. The role of delineation education programs for improving interobserver variability in target volume delineation in gastric cancer. Br J Radiol 2017; 90:20160826. [PMID: 28339289 DOI: 10.1259/bjr.20160826] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To assess whether delineation courses for radiation oncologists improve interobserver variability in target volume delineation for post-operative gastric cancer radiotherapy planning. METHODS 29 radiation oncologists delineated target volumes in a gastric cancer patient. An experienced radiation oncologist lectured about delineation based on contouring atlas and delineation recommendations. After the course, the radiation oncologists, blinded to the previous delineation, provided delineation for the same patient. RESULTS The difference between delineated volumes and reference volumes for pre- and post-course clinical target volume (CTV) were 19.8% (-42.4 to 70.6%) and 12.3% (-12.0 to 27.3%) (p = 0.26), respectively. The planning target volume (PTV) differences pre- and post-course according to the reference volume were 20.5% (-40.7 to 93.7%) and 13.1% (-10.6 to 29.5%) (p = 0.30), respectively. The concordance volumes between the pre- and post-course CTVs and PTVs were 467.1 ± 89.2 vs 597.7 ± 54.6 cm3 (p < 0.001) and 738.6 ± 135.1 vs 893.2 ± 144.6 cm3 (p < 0.001), respectively. Minimum and maximum observer variations were seen at the cranial part and splenic hilus and at the caudal part of the CTV. The kappa indices compared with the reference contouring at pre- and post-course delineations were 0.68 and 0.82, respectively. CONCLUSION The delineation course improved interobserver variability for gastric cancer. However, impact of target volume changes on toxicity and local control should be evaluated for further studies. Advances in knowledge: This study demonstrated that a delineation course based on current recommendations helped physicians delineate smaller and more homogeneous target volumes. Better target volume delineation allows proper target volume irradiation and preventing unnecessary normal tissue irradiation.
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Affiliation(s)
- Cem Onal
- 1 Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey
| | - Mustafa Cengiz
- 2 Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ozan C Guler
- 1 Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey
| | - Yemliha Dolek
- 1 Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey
| | - Serdar Ozkok
- 3 Department of Radiation Oncology, Faculty of Medicine, Ege University, Izmir, Turkey
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Chen K, Huang L, Cai Z, Shi J, You K, Shen H. Micro-invasive surgery combined with intraoperative radiotherapy for the treatment of spinal metastasis. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2016; 26:1893-1901. [PMID: 27807777 DOI: 10.1007/s00586-016-4826-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/23/2016] [Accepted: 09/22/2016] [Indexed: 12/25/2022]
Abstract
PURPOSE This is a retrospective analysis of the strategy and clinical results of surgery combined with intraoperative radiotherapy (IORT) to treat spinal metastases. METHODS We delivered tumour-conformal IORT in 40 patients with 52 metastatic vertebrae based on our surgical classification system. The strategies were evaluated with respect to neurologic function and spinal stability. The EORTC QLQ-BM22, visual analogue scale (VAS) and the Frankel Scale were used to assess quality of life, pain and neurologic function. Local control was evaluated every 3 months using X-rays and MRI. RESULTS Micro-invasive IORT was performed in 42 vertebrae (80.8%), and open surgery with IORT was performed in 10 vertebrae (19.2%). Single-level, 2-level and 3-level IORT was performed in 30, 8 and 2 cases, respectively. The delivered dose was 9.2 ± 3.6 Gy (8-15 Gy) with a depth of 10.1 ± 2.1 mm. The actual IORT treatment time was 5 min and 16 s. The follow-up period was 6-23 months (mean: 12.5 months). The local control rate was 92.3%. The EORTC QLQ-BM22 scores showed that patients had significant improvements in pain location, degree and function after treatment (P < 0.01). Thirty-five patients (89.7%) achieved pain relief throughout the follow-up period. VAS scores were significantly reduced by 3.4 points 3 months after treatment. Neurological function was improved in 7 patients (87.5%). No radiation-related complications were observed. CONCLUSIONS Surgery combined with tumour-conformal IORT can effectively relieve pain, achieve good local control and improve QOL.
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Affiliation(s)
- Keng Chen
- Department of Orthopaedics, Research Center of Spinal and Pelvic Tumour, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.,Research Institute for Spinal Cord Injury of Sun Yat-sen University, Guangzhou, 510120, China.,Research Center of Spinal and Spinal Cord Disease, Guangzhou, 510120, China
| | - Lin Huang
- Department of Orthopaedics, Research Center of Spinal and Pelvic Tumour, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.,Research Institute for Spinal Cord Injury of Sun Yat-sen University, Guangzhou, 510120, China.,Research Center of Spinal and Spinal Cord Disease, Guangzhou, 510120, China
| | - Zhaopeng Cai
- Department of Orthopaedics, Research Center of Spinal and Pelvic Tumour, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.,Research Institute for Spinal Cord Injury of Sun Yat-sen University, Guangzhou, 510120, China.,Research Center of Spinal and Spinal Cord Disease, Guangzhou, 510120, China
| | - Juntian Shi
- Radiotherapy Department of Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Kaiyun You
- Radiotherapy Department of Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Huiyong Shen
- Department of Orthopaedics, Research Center of Spinal and Pelvic Tumour, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China. .,Research Institute for Spinal Cord Injury of Sun Yat-sen University, Guangzhou, 510120, China. .,Research Center of Spinal and Spinal Cord Disease, Guangzhou, 510120, China.
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Wang J, Zhang YJ. Combination of concept and clinical practice - putting a high premium on neoadjuvant therapy for adenocarcinoma of the esophagogastric junction. Shijie Huaren Xiaohua Zazhi 2016; 24:3223-3231. [DOI: 10.11569/wcjd.v24.i21.3223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rising rapidly in recent years. The opinion that AEG is an independent disease different from squamous cell carcinoma of the esophagus and gastric adenocarcinoma has been accepted by more and more scholars. R0 resection with D2 lymph node dissection is the cornerstone of treatment, but surgical techniques remain controversial with particular uncertainty about the operation ways, appropriate resection extent about the esophagus and stomach, and lymphadenectomy sites. Neoadjuvant therapy has attracted increasing attention due to a high rate of relapse after resection and poor survival rate for most patients with advanced disease at diagnosis. Although clinical literature and meta-analyses show that neoadjuvant chemotherapy results in a significant survival benefit at 5 years for resectable locally advanced AEG, and preoperative chemoradiotherapy also should be as a standard treatment for AEG versus surgery alone, the optimal regimens of neoadjuvant therapy and comparisons between preoperative chemotherapy and chemoradiotherapy still need to be studied further.
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Agolli L, Maurizi Enrici R, Osti MF. Adjuvant radiochemotherapy for gastric cancer: Should we use prognostic factors to select patients? World J Gastroenterol 2016; 22:1131-1138. [PMID: 26811652 PMCID: PMC4716025 DOI: 10.3748/wjg.v22.i3.1131] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/24/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
Radiotherapy has a not well-established role in the pre-operative and in the post-operative setting in gastric cancer (GC) patients. Randomized trials report controversial outcomes and impact on survival. In the D2 loco-regional node resection era, after a well-performed radical surgery, local treatment using radiotherapy combined to chemotherapy should be considered for locally advanced GC. Prognostic factors could help the better selection of subgroups that present high risk of loco-regional recurrence. Then, the addition of radiotherapy could improve the disease-free survival and also quality of life. There are no large prospective studies that have assessed specific factors predicting for recurrence or survival, but only retrospective series, some of them including high number of patients with homogeneous characteristics. In locally advanced GC adding radiotherapy to the post-operative chemotherapy seems to improve outcomes and quality of life. Prognostic factors such as T-stage, N-status, nodal ratio, and other histological factors should be considered to submit patients to post-operative combined treatment. Larger prospective series are necessary to investigate the role of combined chemoradiation after radical D2-resection, especially in locally advanced GC. Further prospective investigations are needed to suggest prognostic factors that have significant impact on survival and recurrence, improving the management and outcomes, particularly in locally advanced GC patients.
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Yu JI, Lim DH, Ahn YC, Lee J, Kang WK, Park SH, Park JO, Park YS, Lim HY, Kim ST, Kim S, Sohn TS, Choi MG, Bae JM, Nam H. Effects of adjuvant radiotherapy on completely resected gastric cancer: A radiation oncologist's view of the ARTIST randomized phase III trial. Radiother Oncol 2015; 117:171-7. [PMID: 26299196 DOI: 10.1016/j.radonc.2015.08.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Revised: 07/13/2015] [Accepted: 08/08/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE We investigated which subgroups might benefit from adjuvant radiotherapy (RT) and suggested optimal RT targets by analyzing the results of the Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial. METHODS We conducted randomized controlled trial in 458 gastric cancer patients. Patients were randomly assigned to XP (6 cycles of capecitabine and) or XPRT (2 cycles of XP+RT 45Gy/25 fraction with capecitabine+2 cycles of XP) groups after D2 resection. Minimum follow-up was 5years. RESULTS During follow-up, 77 patients (33.8%) in the XP arm and 60 (26.1%) in the XPRT arm experienced recurrence. Among these patients, locoregional recurrence (LRR) developed in 44 (9.6%; 29 in XP, 15 in XPRT; P=0.03). The local recurrence rate (4.8%) did not vary between arms. Regional recurrence was the most important difference between the two groups (23 in the XP arm, 5 in the XPRT arm, P<0.001). LRR-free survival (LRRFS) was significantly different between study arms (P=0.03), especially in patients with LN metastasis (P=0.009). CONCLUSIONS Adjuvant RT after D2 resection in gastric cancer reduced LRR, especially in group 3 LNs, and improved LRRFS. Patients with LN metastasis benefited more from the adjuvant RT treatment than the other subgroups.
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Affiliation(s)
- Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Do Hoon Lim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Yong Chan Ahn
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeeyun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Ki Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Se Hoon Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joon Oh Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Suk Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ho Yeong Lim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seung Tae Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae Sung Sohn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Min Gew Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Moon Bae
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Heerim Nam
- Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Leong T, Smithers BM, Michael M, Gebski V, Boussioutas A, Miller D, Simes J, Zalcberg J, Haustermans K, Lordick F, Schuhmacher C, Swallow C, Darling G, Wong R. TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG). BMC Cancer 2015; 15:532. [PMID: 26194186 PMCID: PMC4507314 DOI: 10.1186/s12885-015-1529-x] [Citation(s) in RCA: 122] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Accepted: 06/30/2015] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy. METHODS/DESIGN Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given. The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. DISCUSSION TOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry: ACTRN12609000035224 . Registered 30 May 2009.
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Affiliation(s)
- Trevor Leong
- Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia.
| | - B Mark Smithers
- Upper Gastro-intestinal and Soft Tissue Unit, School of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD, 4102, Australia.
| | - Michael Michael
- Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia.
| | - Val Gebski
- NHMRC Clinical Trials Centre, University of Sydney, Locked bag 77, Camperdown, NSW, 1450, Australia.
| | - Alex Boussioutas
- Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria, 8006, Australia.
| | - Danielle Miller
- NHMRC Clinical Trials Centre, University of Sydney, Locked bag 77, Camperdown, NSW, 1450, Australia.
| | - John Simes
- NHMRC Clinical Trials Centre, University of Sydney, Locked bag 77, Camperdown, NSW, 1450, Australia.
| | - John Zalcberg
- School of Public Health and Preventive Medicine, Monash University, Level 5 The Alfred Centre, 99 Commercial Road, Melbourne, VIC, 3004, Australia.
| | - Karin Haustermans
- Radiation Oncology, University Hospitals Leuven, Department of Oncology, KU, Leuven, Belgium.
| | - Florian Lordick
- University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Leipzig, Germany.
| | - Christoph Schuhmacher
- European Clinical Research Infrastructure Network, ECRIN-ERIC, Paris Biopark, 5 rue Watt, 75013, Paris, France.
| | - Carol Swallow
- Mount Sinai Hospital, Rm 1225, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
| | - Gail Darling
- Toronto General Hospital, 9N-955, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada.
| | - Rebecca Wong
- Princess Margaret Hospital, Rm 5-807, 610 University Avenue, Toronto, M5G 2M9, Canada.
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Yang Y, Jiang M, Hu J, Lv X, Yu L, Qian X, Liu B. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line. PLoS One 2015; 10:e0133169. [PMID: 26177078 PMCID: PMC4503735 DOI: 10.1371/journal.pone.0133169] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 06/24/2015] [Indexed: 01/08/2023] Open
Abstract
Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA), which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS), down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.
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Affiliation(s)
- Yang Yang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
| | - Man Jiang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
| | - Jing Hu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
| | - Xin Lv
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
| | - Lixia Yu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
| | - Xiaoping Qian
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, China
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Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward. Gastroenterol Res Pract 2015; 2015:650846. [PMID: 26101524 PMCID: PMC4460248 DOI: 10.1155/2015/650846] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 05/10/2015] [Accepted: 05/12/2015] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches.
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Adjuvant chemoradiotherapy in gastric cancer: a pooled analysis of the AIRO gastrointestinal group experience. TUMORI JOURNAL 2015; 101:91-7. [PMID: 25712602 DOI: 10.5301/tj.5000265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND Given the poor compliance with adjuvant chemoradiotherapy (CRT) in gastric cancer reported in previous studies, a survey was conducted among 18 Italian institutions within the AIRO Gastrointestinal Group to investigate current treatment modalities, toxicities, and compliance with adjuvant CRT. PATIENTS AND METHODS Data from 348 patients operated on for gastric cancer were collected retrospectively from September 2000 to June 2008 and analyzed. The adjuvant treatments included CRT according to center guidelines. In multivariate analysis, acute hematological, gastrointestinal, and renal toxicity (according to the RTOG Acute Radiation Morbidity Scoring Criteria) and compliance with treatment were studied, as well as risk factors for local control, metastasis-free survival, disease-free survival, and overall survival. RESULTS Compliance with treatment was excellent: 95.7% of patients completed CRT. During CRT, acute G3-G4 hematological toxicity was 3.7% and acute G3-G4 gastrointestinal toxicity 4%. 78.4% of patients completed chemotherapy (CT), either before or after CRT. During CT acute G3-G4 hematological toxicity was 5.4% and acute G3-G4 gastrointestinal toxicity 6%. Overall, 74.1% of patients completed the prescribed treatment (CRT and CT). Doses greater than 4500 cGy did not compensate for more aggressive disease. The 5-year overall survival was 51%. CONCLUSIONS The adjuvant treatment of gastric cancer within the AIRO group was diverse, but radiotherapy treatment was homogeneous (in terms of technique) and well tolerated. Toxicity was low and compliance with treatment was good during CRT; these results may be due to the radiotherapy technique applied. This survey could be used as a benchmark for further studies.
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Survival benefit of neoadjuvant chemotherapy for resectable cancer of the gastric and gastroesophageal junction: a meta-analysis. J Clin Gastroenterol 2015; 49:387-94. [PMID: 25144898 DOI: 10.1097/mcg.0000000000000212] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The objective of the present meta-analysis was to estimate the magnitude of survival benefits of neoadjuvant chemotherapy (NAT) in resectable cancer of the gastric and gastroesophageal junction. MATERIALS AND METHODS We searched PubMed, Embase, the Cochrane Library, ISI Web of Knowledge, Chinese biomedical literature database, Chinese Scientific Journals full-text database of retrieved articles from their inception to 2013. Two reviewers independently retrieved study and data extraction of included studies. Results regarding the overall survival and progression-free survival in the meta-analysis were expressed as hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS Twelve randomized control trials (n=1755) were eligible for final meta-analysis. NAT was associated with a statistically significant benefit in terms of overall survival (HR=0.72; 95% CI, 0.56-0.93, P=0.01), progression-free survival (HR=0.73; 95% CI, 0.62-0.87, P=0.0003), 5-year survival rate [relative risk (RR)=1.36; 95% CI, 1.10-1.67, P=0.0004], and curative resection rate (RR=1.11; 95% CI, 1.03-1.20, P=0.009). Five-year survival rate increased from 30% to 42% with NAT. No significant difference with regards to overall postoperative complications rate (RR=1.08; 95% CI, 0.92-1.27, P=0.28) was found between 2 groups. CONCLUSION There is convincing evidence for a survival benefit of NAT over surgery alone in patient with cancer of the gastric and gastroesophageal junction.
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Fan M, Hu W, Zhang Z. Chemoradiation for gastric cancer: controversies, updates and novel techniques. Br J Radiol 2015; 88:20150027. [PMID: 25827208 DOI: 10.1259/bjr.20150027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The INT0116 trial established the role of adjuvant chemoradiation (CRT) in the multidisciplinary approach to the management of locally advanced gastric cancer. However, whether adjuvant CRT is indispensable for patients undergoing D2 dissection remains undefined. The adjuvant chemoradiation therapy in stomach cancer (ARTIST) trial, which was designed to compare adjuvant chemotherapy to CRT, failed to demonstrate differences in disease-free and overall survival in the whole study group; however, subgroup analysis indicated that patients with lymph node metastasis may benefit from additional radiation. A follow-up ARTIST II trial is currently under way. The efficacy of adjuvant CRT remains controversial because of variation among studies in the inclusion criteria and treatment delivery methods; however, the identification of patients who would benefit from CRT is critical. Advanced radiotherapy techniques such as intensity-modulated radiotherapy protect normal tissues via motion management and decreased radiation-induced toxicity and contribute to plan optimization. Further studies integrating clinical and molecular factors as well as neoadjuvant CRT are warranted.
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Affiliation(s)
- M Fan
- 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - W Hu
- 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Z Zhang
- 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Bauer K, Schroeder M, Porzsolt F, Henne-Bruns D. Comparison of international guidelines on the accompanying therapy for advanced gastric cancer: reasons for the differences. J Gastric Cancer 2015; 15:10-8. [PMID: 25861518 PMCID: PMC4389092 DOI: 10.5230/jgc.2015.15.1.10] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Revised: 03/17/2015] [Accepted: 03/17/2015] [Indexed: 12/19/2022] Open
Abstract
The purpose of this study was to determine if international guidelines differ in their recommendations concerning additive therapy for advanced, but potentially curable, gastric cancer. A systematic search of the English and German literature was conducted in the databases Medline, Cochrane Database, Embase, and PubMed. The search terms used were 'guidelines gastric cancer,' 'guidelines stomach cancer,' and 'Leitlinien Magenkarzinom.' Six different guidelines published after January 1, 2010, in which the tumors were classified according to the seventh edition of the TNM system (2010), were identified. Although the examined guidelines were based on the same study results, their recommendations concerning accompanying therapy for gastric cancer differ considerably. While perioperative chemotherapy is recommended in Germany, Great Britain, and large parts of Europe, postoperative adjuvant radiochemotherapy or perioperative chemotherapy is recommended in the USA and Canada. In Japan, postoperative adjuvant chemotherapy is recommended.The results of identical studies were interpreted differently in different countries. Since considerable effort is required for each country to separately test relevant studies for their validity and suitability, an international cooperation could simplify the creation of a common basis for guidelines and contribute to improved comparability of international guidelines.
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Affiliation(s)
- Katrin Bauer
- Department for General, Visceral, Vascular, Thoracic and Pediatric Surgery of the Kempten Clinic, Kempten, Germany
| | - Marcel Schroeder
- Department for General and Visceral Surgery of the Ulm University Clinic, Ulm, Germany
| | - Franz Porzsolt
- Working Group "Healthcare Research" at the Department for General and Visceral Surgery of the Ulm University Clinic, Ulm, Germany
| | - Doris Henne-Bruns
- Department for General and Visceral Surgery of the Ulm University Clinic, Ulm, Germany
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Ozden S, Ozgen Z, Ozyurt H, Gemici C, Yaprak G, Tepetam H, Mayadagli A. Survival in gastric cancer in relation to postoperative adjuvant therapy and determinants. World J Gastroenterol 2015; 21:1222-1233. [PMID: 25632196 PMCID: PMC4306167 DOI: 10.3748/wjg.v21.i4.1222] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 08/16/2014] [Accepted: 10/15/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To evaluate survival data in patients with gastric cancer in relation to postoperative adjuvant therapy and survival determinants
METHODS: A total of 201 patients (mean ± SD age: 56.0 ± 11.9 years, 69.7% were males) with gastric carcinoma who were operated and followed up at Lutfi Kirdar Kartal Training and Research Hospital between 1998 and 2010 were included in this retrospective study. Follow up was evaluated divided into two consecutive periods (before 2008 and 2008-2010, respectively) based on introduction of 3-D conformal technique in radiotherapy at our clinic in 2008. Data on patient demographics, clinical and histopathological characteristics of gastric carcinoma and the type of treatment applied after surgery [postoperative adjuvant treatment protocols including chemoradiotherapy (CRT) and chemotherapy (CT), supportive therapy or follow up without any treatment] were recorded. The median duration and determinants of local recurrence free (LRF) survival, distant metastasis free (DMF) survival and overall survival were evaluated in the overall population as well as with respect to follow up years [1998-2008 (n = 127) vs 2008-2010 (n = 74)].
RESULTS: Median duration for LRF survival, DMF survival and overall survival were 31.9, 24.1 and 31.9 mo, respectively in patients with postoperative adjuvant CRT. No significant difference was noted in median duration for LRF survival, DMF survival and overall survival with respect to treatment protocols in the overall population and also with respect to followed up periods. In the overall population, CT protocols FUFA [5-fluorouracil (400 mg/m2) and leucovorin-folinic acid (FA, 20 mg/m2)] (29.9 mo) and UFT® + Antrex® [a fixed combination of the oral FU prodrug tegafur (flouroprymidine, FT, 300 mg/m2 per day) with FA (Antrex®), 15 mg tablet, two times a day] (42.5 mo) was significantly associated with longer LRF survival times than other CT protocols (P = 0.036), while no difference was noted between CT protocols in terms of DMF survival and overall survival. Among patients received CRT, overall survival was significantly longer in patients with negative than positive surgical margin (27.7 mo vs 22.4 mo, P = 0.016) in the overall study population, while time of radiotherapy initiation had no significant impact on survival times. Nodal stage was determined to be independent predictor of LRF survival in the overall study population with 4.959 fold (P = 0.042) increase in mortality in patients with nodal stage N2 compared to patients with nodal stage N0, and independent predictor of overall survival with 5.132 fold (P = 0.006), 5.263 fold (P = 0.027) and 4.056 fold (P = 0.009) increase in the mortality in patients with nodal stage N3a (before 2008), N3b (before 2008) and N2 (overall study population) when compared to patients with N0 stage, respectively.
CONCLUSION: Our findings emphasize the likelihood of postoperative adjuvant CRT to have a survival benefit in patients with resectable gastric carcinoma.
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Yoney A, Isikli L. Can capecitabine be used instead of concurrent bolus 5-FU in postoperative chemoradiotherapy for gastric adenocarcinoma? Asian Pac J Cancer Prev 2014; 14:5127-31. [PMID: 24175788 DOI: 10.7314/apjcp.2013.14.9.5127] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND 5-fluoro-uracil (FU) is a common agent in postoperative chemoradiation in gastric adenocarcinoma. However, FU is not well tolerated in a significant proportion of patients. Capecitabine (CA) is an orally administered fluoropyrimidine carbamate which is preferentially converted to active 5-FU and is one of the agents used instead of FU in such cases. We compared the toxicity, local and distant control and survival rates with FU or oral CA during the course of concurrent radiotherapy to assess the role of CA used instead of FU. MATERIALS AND METHODS We conducted an analysis of survival, disease control and toxicity data in 46 patients treated with postoperative chemoradiation following total or subtotal gastrectomy for gastric adenocarcinoma with either FU or CA between January 2008 and December 2012. RESULTS Median follow-up was 19 months (range: 3-59), median survival time was 23 (± 6.08) months and 1-3 years overall survival (OS) rates were 64.9- 39% for all patients. Compared with the CA regimen, the incidence of treatment interruption was higher with FU (p=0.023), but no significant differences were seen in local control (p=0.510), distant recurrences (p=0.721) and survival rates (p=0.866) among patients. CONCLUSIONS Concurrent CA with radiotherapy seems to be a more tolerable and an equally effective regimen for the postoperative treatment of gastric adenocarcinoma when compared to FU.
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Affiliation(s)
- Adnan Yoney
- Karadeniz Technical University, Faculty of Medicine, Department of Radiation Oncology, Trabzon, Turkey E-mail :
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Foo M, Leong T. Adjuvant therapy for gastric cancer: Current and future directions. World J Gastroenterol 2014; 20:13718-13727. [PMID: 25320509 PMCID: PMC4194555 DOI: 10.3748/wjg.v20.i38.13718] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 07/06/2014] [Accepted: 07/30/2014] [Indexed: 02/06/2023] Open
Abstract
The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies.
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Dionisi F, Avery S, Lukens JN, Ding X, Kralik J, Kirk M, Roses RE, Amichetti M, Metz JM, Plastaras JP. Proton therapy in adjuvant treatment of gastric cancer: planning comparison with advanced x-ray therapy and feasibility report. Acta Oncol 2014; 53:1312-20. [PMID: 24797885 DOI: 10.3109/0284186x.2014.912351] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Adjuvant chemoradiotherapy improves both overall- and relapse-free survival in patients with resected gastric cancer. However, this comes at the cost of increased treatment-related toxicity. Proton therapy (PT) has distinct dosimetric characteristics that may reduce dose to normal tissues, improving the therapeutic ratio. The purpose of this treatment planning study is to compare PT and intensity-modulated x-ray therapy (IMXT) in gastric cancer with regards to normal tissue sparing. MATERIAL AND METHODS The patient population consisted of resected gastric cancer patients treated at a single institution between 2008 and 2013. Patients who had undergone 4D CT simulation were replanned to the originally delivered doses (45-54 Gy in 25-30 daily fractions) using six-field photon IMXT and 2-3-field PT (double scattering-uniform scanning techniques). RESULTS Thirteen patients were eligible for the planning comparison. IMXT provided slightly higher homogeneity indices (median values 0.04 ± 0.01 vs. 0.07 ± 0.01, p = 0.03). PT resulted in significantly (p < 0.05) lower intermediate-low doses for all the normal tissues examined (small bowel V15 82 ml vs. 133 ml, liver mean doses Gy 11.9 vs. 14.4 Gy, left/right kidney mean doses 5/0.9 Gy vs. 7.8/3.1 Gy, heart mean doses 7.4 Gy vs. 9.5 Gy). The total energy deposited outside the target volume was significantly lower with PT (median integral dose 90.1 J vs. 129 J). Four patients were treated with PT: treatment was feasible and verifications scans showed that target coverage was robust. CONCLUSION PT can contribute to normal tissue sparing in the adjuvant treatment of gastric cancer, with a potential benefit in terms of compliance to treatment, acute and late toxicities.
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Affiliation(s)
- Francesco Dionisi
- Proton Therapy Unit, Department of Oncology, Azienda Provinciale per i Servizi Sanitari (APSS) , Trento , Italy
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Dai Q, Jiang L, Lin RJ, Wei KK, Gan LL, Deng CH, Guan QL. Adjuvant chemoradiotherapy versus chemotherapy for gastric cancer: a meta-analysis of randomized controlled trials. J Surg Oncol 2014; 111:277-84. [PMID: 25273525 DOI: 10.1002/jso.23795] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 08/29/2014] [Indexed: 01/05/2023]
Abstract
OBJECTIVE The aim of this study was to evaluate the efficacy and safety of adjuvant chemoradiotherapy (CRT) versus chemotherapy (CT) for patients with gastric cancer. METHODS Electronic databases including PUBMED, EMBASE, and Cochrane Library were retrieved for original studies from their inception to April 2014. Two reviewers independently evaluated the quality of the included studies and extracted the data. All Statistical analyses were performed using RevMan Version 5.2 software. RESULTS Six randomized controlled trials involving 1,171 patients were included. The meta-analysis showed that there were statistical significances between chemoradiotherapy group and chemotherapy group in 5-year disease free survival rate (OR = 1.56, 95% CI: 1.09-2.24), local-regional recurrence rate (OR = 0.46, 95% CI: 0.32-0.67) and neutropenia (OR = 1.47, 95% CI: 1.11-1.96). While treatment efficacy did not differ significantly by the 5-year overall survival rate (OR = 1.32, 95% CI: 0.92-1.88), 3-year disease free survival rate (OR = 1.28, 95% CI: 0.92-1.80), and new metastases (OR = 0.76, 95% CI: 0.57-1.03). Toxicities were not significantly different between two groups for nausea/vomiting, diarrhea, anemia, and thrombocytopenia. CONCLUSIONS For patients with gastric cancer, adjuvant chemoradiotherapy could significantly improve 5-year disease free survival rate and reduce local-regional recurrence rate compared with chemotherapy and, can be well accepted and tolerated.
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Affiliation(s)
- Qiang Dai
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
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Soon YY, Leong CN, Tey JCS, Tham IWK, Lu JJ. Postoperative chemo-radiotherapy versus chemotherapy for resected gastric cancer: a systematic review and meta-analysis. J Med Imaging Radiat Oncol 2014; 58:483-96. [PMID: 24995607 DOI: 10.1111/1754-9485.12190] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Accepted: 04/17/2014] [Indexed: 12/16/2022]
Abstract
INTRODUCTION This study conducted a systematic review and meta-analysis (direct and indirect) of published randomised controlled trials (RCTs) to compare the effects of postoperative chemo-radiotherapy (ChRT) with chemotherapy (Ch) on overall and disease-free survival (DFS) for patients with resectable gastric cancer. METHODS We searched MEDLINE and CENTRAL from the date of inception and annual meeting proceedings of American Society of Clinical Oncology and American Society for Radiation Oncology from 1999 to November 2012 for RCTs comparing postoperative ChRT with Ch, postoperative ChRT with surgery alone and postoperative Ch with surgery alone. The primary outcome was overall survival (OS); secondary outcomes included DFS and toxicity. Hazard ratios (HRs), confidence intervals (CIs) and P values (P) were estimated with fixed effects models using Revman 5.1. RESULTS We found six trials comparing postoperative ChRT with Ch (n = 1171). Meta-analysis of direct comparison trials showed that postoperative ChRT significantly improved both OS (HR 0.80, 95% CI 0.65-0.98, P = 0.03) and DFS (HR 0.76, 95% CI 0.63-0.91, P = 0.003) when compared with Ch. There were no significant differences in toxicity between the two groups. CONCLUSIONS This study suggests a survival benefit of postoperative ChRT over Ch in patients with resected gastric cancer.
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Affiliation(s)
- Yu Yang Soon
- Department of Radiation Oncology, National University Cancer Institute, Singapore, National University Health System, National University of Singapore, Singapore
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Foo M, Crosby T, Rackley T, Leong T. Role of (chemo)-radiotherapy in resectable gastric cancer. Clin Oncol (R Coll Radiol) 2014; 26:541-50. [PMID: 24996375 DOI: 10.1016/j.clon.2014.06.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Revised: 03/17/2014] [Accepted: 06/10/2014] [Indexed: 12/17/2022]
Abstract
The prognosis of patients with locally advanced gastric cancer remains poor, despite radical surgical resection. Adjuvant therapy has been shown to improve survival and, in Western countries, is delivered either postoperatively (chemoradiotherapy) or perioperatively (chemotherapy). Debate continues as to which of these represents the optimal strategy. High-dose gastric irradiation comes at the expense of significant toxicity, and increasing efforts have focused on attempts to reduce toxicity and normal tissue doses. The development of advancing radiotherapy technologies now allows improved target delineation and coverage. However, gastric irradiation remains technically challenging and requires an understanding of postoperative surgical anatomy, patterns of failure and lymph node drainage, as well as an appreciation of the uncertainties around organ motion and filling. Ongoing trials are examining the optimal strategy in which to incorporate (chemo)-radiotherapy, as well as the addition of targeted therapies, in gastric cancer. This overview discusses the current role and evidence for (chemo)-radiotherapy, as well as the technical challenges encountered in the radiotherapeutic management of resectable gastric cancer.
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Affiliation(s)
- M Foo
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
| | - T Crosby
- Velindre Cancer Centre, Cardiff, UK
| | | | - T Leong
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; University of Melbourne, Australia
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Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F. Treatment of gastric cancer. World J Gastroenterol 2014; 20:1635-1649. [PMID: 24587643 PMCID: PMC3930964 DOI: 10.3748/wjg.v20.i7.1635] [Citation(s) in RCA: 472] [Impact Index Per Article: 42.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/29/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status
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Benefit of radiotherapy on survival in resectable gastric carcinoma: a meta-analysis. Tumour Biol 2014; 35:4957-66. [DOI: 10.1007/s13277-014-1653-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 01/13/2014] [Indexed: 01/09/2023] Open
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