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Wilkie BD, Chan JM, Paratz E, Proud D, Smart P, An V. Lymph Node Yield and Colorectal Cancer Survival: A Bowel Cancer Outcomes Registry Cohort Study. ANZ J Surg 2025. [PMID: 40265735 DOI: 10.1111/ans.70150] [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: 03/06/2024] [Revised: 03/23/2025] [Accepted: 04/07/2025] [Indexed: 04/24/2025]
Abstract
BACKGROUND The current standard for lymph node (LN) sampling in colorectal cancer (CRC) surgery is a minimum of 12 LNs. Emerging evidence suggests higher LN yields may improve disease-free survival (DFS); however, an "optimal" number of LNs has yet to be definitively established. The aim of this study was to correlate LN yield with survival outcomes in patients undergoing surgery for nonmetastatic CRC. METHODS The Bowel Cancer Outcomes Registry (BCOR) is a clinical quality registry in Australia and New Zealand. Post-operative patients aged ≥ 18 years with histologically confirmed CRC, nonmetastatic disease at diagnosis and with follow-up status documented were included. Post-operative outcomes and survival were assessed with logistic regression. The primary endpoint was CRC-specific mortality. Secondary endpoints were CRC recurrence and all-cause mortality. RESULTS Of 91 271 patient episodes, 10 616 individual eligible patients were identified (45.4% male, n = 4828). The median number of LNs resected was 18 [quartiles 0-12, 13-17, 18-23 and > 23]. A significant difference in CRC-specific mortality was seen between quartiles (p = 0.023), with the primary significant difference demonstrated between the lowest quartile (≤ 12 LNs) and other groups. On long-term follow-up, CRC recurrence and CRC-specific mortality were higher in the group with ≤ 12 LNs resected (16.0% vs. 14.0%, adjusted p = 0.049 and 4.5% vs. 3.3%, adjusted p = 0.037 respectively). CONCLUSION This study supports the current consensus that > 12 LNs are required for adequate staging and oncological clearance in CRC surgery, and demonstrates yields ≤ 12 LNs are associated with higher CRC recurrence and mortality.
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Affiliation(s)
- Bruce D Wilkie
- Department of Surgery, Eastern Health, Box Hill, Victoria, Australia
- Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, Victoria, Australia
- Department of General Surgery, Austin Health, Heidelberg, Victoria, Australia
| | - James M Chan
- Department of Surgery, Eastern Health, Box Hill, Victoria, Australia
| | - Elizabeth Paratz
- Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, Victoria, Australia
- Department of Cardiology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - David Proud
- Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Parkville, Victoria, Australia
- Department of General Surgery, Austin Health, Heidelberg, Victoria, Australia
| | - Philip Smart
- Department of Surgery, Eastern Health, Box Hill, Victoria, Australia
- Department of General Surgery, Austin Health, Heidelberg, Victoria, Australia
| | - Vinna An
- Department of Surgery, Eastern Health, Box Hill, Victoria, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
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Ogata Y, Sadahiro S, Sakamoto K, Tsuchiya T, Takahashi T, Ohge H, Sato T, Kondo K, Baba H, Itabashi M, Ikeda M, Hamada M, Maeda K, Masuko H, Takahashi K, Kusano M, Hyodo I, Sakamoto J, Taguri M, Morita S. Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201). Int J Clin Oncol 2024; 29:1284-1292. [PMID: 38833114 PMCID: PMC11347494 DOI: 10.1007/s10147-024-02565-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/28/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).
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Affiliation(s)
- Yutaka Ogata
- Department of Surgery, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan.
| | - Sotaro Sadahiro
- Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Takashi Tsuchiya
- Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, Miyagi, 983-0824, Japan
| | - Takao Takahashi
- Department of Digestive Surgery, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan
- Department of Surgery, Seino Kosei Hospital, 293-1 Shimoiso Ono-Cho, Ibi-Gun, Gifu, 501-0532, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Toshihiko Sato
- Department of Surgery, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata, 990-2292, Japan
| | - Ken Kondo
- Department of Surgery, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan
| | - Hideo Baba
- Department of Gastroen- Terological Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Michio Itabashi
- Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
| | - Masataka Ikeda
- Department of Gastroenterological Surgery, Division of Lower GI, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Madoka Hamada
- Department of Gastrointestinal Surgery, Kansai Medical University Hospital, 2-3-1 Shinmachi Hirakata, Osaka, 573-1191, Japan
| | - Kiyoshi Maeda
- Department of Gastroenterological Surgery, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Hiroyuki Masuko
- Department of Surgery, Nikko Memorial Hospital, 1-5-13 Shintomi-Cho, Muroran, Hokkaido, 051-8501, Japan
| | - Keiichi Takahashi
- Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, 2-44-1 Kabuki-Cho, Shinjuku-Ku, Tokyo, 160-8488, Japan
| | - Mitsuo Kusano
- Department of Physical Medicine, Yoichi Hospital, 19-1-1 Kurokawa-Cho Yoichi, Hokkaido, 046-0003, Japan
| | - Ichinosuke Hyodo
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto, Matsuyama, Ehime, 791-0280, Japan
| | - Junichi Sakamoto
- Tokai Central Hospital, 4-6-2 Sohara Higashijima-Cho, Kakamigahara, Gifu, 504-8601, Japan
| | - Masataka Taguri
- Department of Health Data Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-Ku, Tokyo, 160-8402, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
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Gottschalk Z, Cohen SA. Use of Circulating Tumor DNA to Guide Decision-making in Adjuvant Colon Cancer. Curr Oncol Rep 2024; 26:959-966. [PMID: 38842605 DOI: 10.1007/s11912-024-01565-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2024] [Indexed: 06/07/2024]
Abstract
PURPOSE OF REVIEW The use of circulating tumor DNA (ctDNA) assays to guide clinical decision-making in early-stage colon cancer is an area of rapidly advancing active research. With assays clinically available, clinicians must be informed how to best use this novel tool to treat patients. RECENT FINDINGS Recent observational and prospective studies have suggested that ctDNA has potential to guide clinical decision-making in early-stage colon cancer by detecting minimal residual disease (MRD) and predicting recurrence risks. MRD-negative patients may be able to de-escalate or forgo adjuvant chemotherapy (ACT) without compromising disease-free survival or overall survival, while MRD-positive patients may benefit significantly from ACT. Recent and ongoing studies have given reason for optimism about the future of ctDNA as a useful biomarker for clinicians treating early-stage colon cancer. Data thus far are mostly limited to observational studies; inconsistent results highlight the need for caution. As more evidence emerges, ctDNA may become standard of care for colon cancer patients.
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Affiliation(s)
- Zachary Gottschalk
- Fred Hutchinson Cancer Center, 825 Eastlake Ave E, LG-465, Seattle, WA, 98177, USA
| | - Stacey A Cohen
- Fred Hutchinson Cancer Center, 825 Eastlake Ave E, LG-465, Seattle, WA, 98177, USA.
- University of Washington, Seattle, WA, USA.
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Wilson JJ, Bennie L, Eguaogie O, Elkashif A, Conlon PF, Jena L, McErlean E, Buckley N, Englert K, Dunne NJ, Tucker JHR, Vyle JS, McCarthy HO. Synthesis and characterisation of a nucleotide based pro-drug formulated with a peptide into a nano-chemotherapy for colorectal cancer. J Control Release 2024; 369:63-74. [PMID: 38513729 DOI: 10.1016/j.jconrel.2024.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/01/2024] [Accepted: 03/18/2024] [Indexed: 03/23/2024]
Abstract
Recent studies in colorectal cancer patients (CRC) have shown that increased resistance to thymidylate synthase (TS) inhibitors such as 5-fluorouracil (5-FU), reduce the efficacy of standard of care (SoC) treatment regimens. The nucleotide pool cleanser dUTPase is highly expressed in CRC and is an attractive target for potentiating anticancer activity of chemotherapy. The purpose of the current work was to investigate the activity of P1, P4-di(2',5'-dideoxy-5'-selenouridinyl)-tetraphosphate (P4-SedU2), a selenium-modified symmetrically capped dinucleoside with prodrug capabilities that is specifically activated by dUTPase. Using mechanochemistry, P4-SedU2 and the corresponding selenothymidine analogue P4-SeT2 were prepared with a yield of 19% and 30% respectively. The phosphate functionality facilitated complexation with the amphipathic cell-penetrating peptide RALA to produce nanoparticles (NPs). These NPs were designed to deliver P4-SedU2 intracellularly and thereby maximise in vivo activity. The NPs demonstrated effective anti-cancer activity and selectivity in the HCT116 CRC cell line, a cell line that overexpresses dUTPase; compared to HT29 CRC cells and NCTC-929 fibroblast cells which have reduced levels of dUTPase expression. In vivo studies in BALB/c SCID mice revealed no significant toxicity with respect to weight or organ histology. Pharmacokinetic analysis of blood serum showed that RALA facilitates effective delivery and rapid internalisation into surrounding tissues with NPs eliciting lower plasma Cmax than the equivalent injection of free P4-SedU2, translating the in vitro findings. Tumour growth delay studies have demonstrated significant inhibition of growth dynamics with the tumour doubling time extended by >2weeks. These studies demonstrate the functionality and action of a new pro-drug nucleotide for CRC.
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Affiliation(s)
- Jordan J Wilson
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK; School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK
| | - Lindsey Bennie
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK
| | - Olga Eguaogie
- School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK
| | - Ahmed Elkashif
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK
| | - Patrick F Conlon
- School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK
| | - Lynn Jena
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK
| | - Emma McErlean
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK
| | - Niamh Buckley
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK
| | - Klaudia Englert
- School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Nicholas J Dunne
- School of Mechanical and Manufacturing Engineering, Dublin City University, Centre for Medical Engineering Research, Dublin City University, Ireland
| | - James H R Tucker
- School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Joseph S Vyle
- School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK
| | - Helen O McCarthy
- School of Pharmacy, Queen's University Belfast, Medical Biological Centre, 97 Lisburn Road, Belfast BT9 7LB, UK; School of Chemical Sciences, Dublin City University, Collins Avenue, Dublin 9, Ireland.
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Emile SH, Horesh N, Garoufalia Z, Gefen R, Strassmann V, Wexner SD. Propensity-Score Matched Analysis of Survival Outcomes of Adjuvant Therapy in Stage II-III Signet-Ring Cell Carcinoma of the Colon. Clin Colorectal Cancer 2024; 23:35-45. [PMID: 37980215 DOI: 10.1016/j.clcc.2023.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 10/16/2023] [Accepted: 10/23/2023] [Indexed: 11/20/2023]
Abstract
BACKGROUND Colonic signet ring cell carcinoma (SRCC) is a mucinous adenocarcinoma subtype often associated with poor prognosis. This study assessed the survival benefits of adjuvant therapy after curative resection of stage II-III colonic SRCC. METHODS This was a retrospective analysis of outcomes of adjuvant therapy in colonic SRCC using National Cancer Database (2010-2019) data. Patients who received adjuvant therapy were matched to those who did not use the nearest neighbor propensity-score matching. The primary outcome was 5-year overall survival (OS). RESULTS The unmatched cohort included 3530 patients. Patients who received adjuvant therapy were significantly younger, more often male, and more often had Charlson scores 0-1, left-sided cancers, stage III disease, lymphovascular invasion, and perineural invasion. The matched cohort included 958 patients (53.6% female); 479 received adjuvant therapy and 479 did not. Adjuvant therapy was associated with longer mean OS (39.9 vs. 29.2 months; P < .001). Survival benefit of adjuvant therapy was evident in stage III disease (37.5 vs. 24.7 months; P < .001), right-sided colon cancer (40.2 vs. 27.7 months; P < .001), and transverse colon cancer (40.6 vs. 31.1 months; P = .002), but not stage II disease (52.1 vs. 53.1 months; P = .694) or left-sided colon cancer (35.8 vs. 32.6 months; P = .417). Independent predictors of improved OS were adjuvant therapy (HR: 0.539; P < .001), laparoscopic surgery (HR: 0.829; P = .001), robotic-assisted surgery (HR: 0.63; P = .007), and number of harvested lymph nodes (HR: 0.976; P < .001). CONCLUSIONS Adjuvant therapy was associated with improved OS in stage III, right-sided, and transverse colon SRCC. The survival benefit of adjuvant therapy in stage II and left-sided colon SRCC was limited.
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Affiliation(s)
- Sameh Hany Emile
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL; General Surgery Department, Colorectal Surgery Unit, Mansoura University Hospitals, Mansoura, Egypt
| | - Nir Horesh
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL; Department of Surgery and transplantation, Sheba Medical Center, Ramat-Gan, Israel
| | - Zoe Garoufalia
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL
| | - Rachel Gefen
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL; Department of General Surgery, Faculty of Medicine, Hadassah Medical Organization, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Victor Strassmann
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL
| | - Steven D Wexner
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL.
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Deng X, Yang J, Zhang Y, Chen X, Wang C, Suo H, Song J. An Update on the Pivotal Roles of Probiotics, Their Components, and Metabolites in Preventing Colon Cancer. Foods 2023; 12:3706. [PMID: 37835359 PMCID: PMC10572180 DOI: 10.3390/foods12193706] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/01/2023] [Accepted: 10/08/2023] [Indexed: 10/15/2023] Open
Abstract
Diet, lifestyle, and gut microbiota composition are key risk factors for the progression of colon cancer. Probiotics are living microorganisms that can offer health benefits to the parasitifer when ingested in competent quantities. Several in vivo, in vitro, and clinical studies have demonstrated that probiotics can prevent and mitigate the development of colon cancer. The anti-colon cancer mechanisms of probiotics include the suppression of cell proliferation and the promotion of cancer cell apoptosis, immunomodulation, the modulation of intestinal microorganisms and their metabolism, strengthening the intestinal barrier, and antioxidant effects. This article describes the pathogenesis of colon cancer and the available therapeutic options. In addition, this paper reviews the mechanisms by which probiotics mitigate colon cancer as well as the mitigating effects of probiotic components and metabolites on colon cancer.
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Affiliation(s)
- Xue Deng
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Jing Yang
- Chongqing Engineering Research Center for Processing & Storage of Distinct Agricultural Products, Chongqing Technology and Business University, Chongqing 400067, China;
| | - Yu Zhang
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Xiaoyong Chen
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Chen Wang
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Huayi Suo
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
- National Citrus Engineering Research Center, Southwest University, Chongqing 400712, China
| | - Jiajia Song
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
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Zhang L, Li Q, Hu C, Zhang Z, She J, Shi F. Real-world analysis of survival benefit of surgery and adjuvant therapy in elderly patients with colorectal cancer. Sci Rep 2023; 13:14866. [PMID: 37684265 PMCID: PMC10491681 DOI: 10.1038/s41598-023-41713-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 08/30/2023] [Indexed: 09/10/2023] Open
Abstract
Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70-74; 75-79; 80-84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.
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Affiliation(s)
- Lei Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Qixin Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chenhao Hu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhe Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China.
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Feiyu Shi
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, China.
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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8
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Xiong ZZ, Xie MH, Li XZ, Jin LY, Zhang FX, Yin S, Chen HX, Lian L. Risk factors for postoperative recurrence in patients with stage II colorectal cancer. BMC Cancer 2023; 23:658. [PMID: 37452325 PMCID: PMC10347847 DOI: 10.1186/s12885-023-11093-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 06/20/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND Recurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC. METHODS Eligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan-Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence. RESULTS There were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) [95% confidence interval (CI)] = 1.79[1.38, 2.33]), preoperative carbohydrate antigen (CA) 125 level (HR [95% CI] = 1.78[1.17, 2.70]), preoperative CA 199 level (HR [95% CI] = 1.56[1.09, 2.22]), and ulcerating tumor (HR [95% CI] = 1.61[1.19, 2.17]) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096). CONCLUSION The tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.
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Affiliation(s)
- Zhi-Zhong Xiong
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ming-Hao Xie
- Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xian-Zhe Li
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Long-Yang Jin
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Feng-Xiang Zhang
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shi Yin
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Hua-Xian Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Lei Lian
- Department of Gastrointestinal Surgery, Department of General Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China.
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
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9
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Xin C, Lai Y, Ji L, Wang Y, Li S, Hao L, Zhang W, Meng R, Xu J, Hong Y, Lou Z. A novel 9-gene signature for the prediction of postoperative recurrence in stage II/III colorectal cancer. Front Genet 2023; 13:1097234. [PMID: 36704343 PMCID: PMC9871489 DOI: 10.3389/fgene.2022.1097234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 12/19/2022] [Indexed: 01/11/2023] Open
Abstract
Background: Individualized recurrence risk prediction in patients with stage II/III colorectal cancer (CRC) is crucial for making postoperative treatment decisions. However, there is still a lack of effective approaches for identifying patients with stage II and III CRC at a high risk of recurrence. In this study, we aimed to establish a credible gene model for improving the risk assessment of patients with stage II/III CRC. Methods: Recurrence-free survival (RFS)-related genes were screened using Univariate Cox regression analysis in GSE17538, GSE39582, and GSE161158 cohorts. Common prognostic genes were identified by Venn diagram and subsequently subjected to least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis for signature construction. Kaplan-Meier (K-M), calibration, and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy and superiority of our risk model. Single-sample gene set enrichment analysis (ssGSEA) was employed to investigate the relationship between the infiltrative abundances of immune cells and risk scores. Genes significantly associated with the risk scores were identified to explore the biological implications of the 9-gene signature. Results: Survival analysis identified 347 RFS-related genes. Using these genes, a 9-gene signature was constructed, which was composed of MRPL41, FGD3, RBM38, SPINK1, DKK1, GAL3ST4, INHBB, CTB-113P19.1, and FAM214B. K-M curves verified the survival differences between the low- and high-risk groups classified by the 9-gene signature. The area under the curve (AUC) values of this signature were close to or no less than the previously reported prognostic signatures and clinical factors, suggesting that this model could provide improved RFS prediction. The ssGSEA algorithm estimated that eight immune cells, including regulatory T cells, were aberrantly infiltrated in the high-risk group. Furthermore, the signature was associated with multiple oncogenic pathways, including cell adhesion and angiogenesis. Conclusion: A novel RFS prediction model for patients with stage II/III CRC was constructed using multicohort validation. The proposed signature may help clinicians better manage patients with stage II/III CRC.
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Affiliation(s)
- Cheng Xin
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Yi Lai
- Department of Head and Neck Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | | | - Ye Wang
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Shihao Li
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Liqiang Hao
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Wei Zhang
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Ronggui Meng
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Jun Xu
- Department of Gastrointestinal Surgery, Changhai Hospital, Shanghai, China,*Correspondence: Jun Xu, ; Yonggang Hong, ; Zheng Lou,
| | - Yonggang Hong
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China,*Correspondence: Jun Xu, ; Yonggang Hong, ; Zheng Lou,
| | - Zheng Lou
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China,*Correspondence: Jun Xu, ; Yonggang Hong, ; Zheng Lou,
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10
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Cockrell C, Axelrod DE. Combination Chemotherapy of Multidrug-resistant Early-stage Colon Cancer: Determining Optimal Dose Schedules by High-performance Computer Simulation. CANCER RESEARCH COMMUNICATIONS 2023; 3:21-30. [PMID: 36685168 PMCID: PMC9851383 DOI: 10.1158/2767-9764.crc-22-0271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The goal of this project was to utilize mechanistic simulation to demonstrate a methodology that could determine drug combination dose schedules and dose intensities that would be most effective in eliminating multidrug resistant cancer cells in early-stage colon cancer. An agent-based model of cell dynamics in human colon crypts was calibrated using measurements of human biopsy specimens. Mutant cancer cells were simulated as cells that were resistant to each of two drugs when the drugs were used separately. The drugs, 5-flurouracil and sulindac, have different mechanisms of action. An artificial neural network was used to generate nearly two hundred thousand two-drug dose schedules. A high-performance computer simulated each dose schedule as a in silico clinical trial and evaluated each dose schedule for its efficiency to cure (eliminate) multidrug resistant cancer cells and its toxicity to the host, as indicated by continued crypt function. Among the dose schedules that were generated, 2430 dose schedules were found to cure all multidrug resistant mutants in each of the 50 simulated trials and retained colon crypt function. One dose schedule was optimal; it eliminated multidrug resistant cancer cells with the minimum toxicity and had a time schedule that would be practical for implementation in the clinic. These results demonstrate a procedure to identify which combination drug dose schedules could be most effective in eliminating drug resistant cancer cells. This was accomplished using a calibrated agent-based model of a human tissue, and a high-performance computer simulation of clinical trials.
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Affiliation(s)
- Chase Cockrell
- Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont
| | - David E. Axelrod
- Department of Genetics, and Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey
- Corresponding Author: David E. Axelrod, Rutgers University, Nelson Biolabs, 604 Allison Rd, Piscataway, NJ 08854-8082. Phone: 848-445-2011; E-mail:
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11
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Hagerty BL, Aversa JG, Dominguez DA, Davis JL, Hernandez JM, McCormick JT, Blakely AM. Age Determines Adjuvant Chemotherapy Use in Resected Stage II Colon Cancer. Dis Colon Rectum 2022; 65:1206-1214. [PMID: 34897212 PMCID: PMC9177898 DOI: 10.1097/dcr.0000000000002074] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The role of adjuvant chemotherapy in resected stage II colon cancer remains controversial. Treatment recommendations rely largely on the presence of certain high-risk features for recurrence. OBJECTIVE We sought to define patient and clinicopathologic differences between early-onset and late-onset colorectal cancer and determine whether these differences impact treatment. We hypothesized that high-risk features in stage II colorectal cancer differed between age groups and would most strongly influence administration of adjuvant chemotherapy. DESIGN This was a retrospective cohort study. SETTING The study was conducted at a Commission on Cancer designated hospital as well as the National Cancer Institute Intramural Research Program. PATIENTS Patients with resected stage II colon cancer were identified in the National Cancer Database, and clinicopathologic characteristics were recorded. Patients were stratified into young (≤45), middle-aged (50-75), and older (>75) age groups. MAIN OUTCOME MEASURES Incidence of high-risk clinicopathologic features and receipt of adjuvant chemotherapy were measured. RESULTS A total of 14,966 patients met inclusion criteria. Young patients were found to have had at least one high-risk feature ( n = 489, 44%) slightly more often than both middle-aged ( n = 3734, 40%) and older patients ( n = 1890, 42%). A total of 332 (7%) older patients received adjuvant chemotherapy compared to 627 (56%) young patients and 2854 (30%) middle-aged patients. Age group was independently associated with receipt of adjuvant chemotherapy when controlling for relevant clinicopathologic factors. LIMITATIONS This was a retrospective study without granular detail on treatment decisions. CONCLUSIONS Young patients are frequently prescribed adjuvant chemotherapy for both high- and low-risk tumors despite questionable benefit in the latter. Older patients rarely receive adjuvant therapy. Both medical and surgical oncologists should be aware of disparities in cancer treatment and remain conscientious about making treatment decisions solely based on age. See Video Abstract at http://links.lww.com/DCR/B846 . LA EDAD DETERMINA EL USO DE QUIMIOTERAPIA ADYUVANTE EN EL CNCER DE COLON RESECADO EN ESTADIO II ANTECEDENTES:El papel de la quimioterapia adyuvante en el cáncer de colon resecado en estadio II sigue siendo controversial . Las recobmendaciones para el tratamiento dependen en gran medida de la presencia de ciertas características de alto riesgo de recurrencia.OBJETIVO:Buscamos definir las diferencias clínico-patológicas del paciente entre el CCR de inicio temprano y tardío; y determinar si estas diferencias afectan el tratamiento. Hipotetizamos que las características de alto riesgo del cáncer colorrectal en estadio II difieren entre los grupos de edad y que influyen fuertemente en la administración de quimioterapia adyuvante.DISEÑO:Este fue un estudio de cohorte retrospectivo.ENTORNO CLINICO:El estudio se llevó a cabo en un hospital designado por la Comisión sobre el Cáncer, así como el Programa de Investigación Intramural del Instituto Nacional del Cáncer.PACIENTES:Se identificaron los pacientes con cáncer de colon resecado en estadio II en la Base de datos nacional del cáncer y se registraron las características clínico-patológicas. Los pacientes se estratificaron en grupos de edad jóvenes (≤45), de mediana edad (50-75) y mayores (> 75).PRINCIPALES MEDIDAS DE RESULTADO:Se estudiaron la incidencia de las características clínico-patológicas de alto riesgo y la recepción de quimioterapia adyuvante.RESULTADOS:Un total de 14.966 pacientes cumplieron con los criterios de inclusión. Se encontró que los pacientes jóvenes tenían al menos una característica de alto riesgo (n = 489, 44%) un poco más frecuente que los pacientes de mediana edad (n = 3734, 40%) y los pacientes mayores (n = 1890, 42%). Un total de 332 (7%) de los pacientes mayores recibieron quimioterapia adyuvante en comparación con 627 (56%) de los pacientes jóvenes y 2854 (30%) de los pacientes de mediana edad. El grupo de edad se asoció de forma independiente con la recepción de quimioterapia adyuvante al controlar los factores clínico-patológicos relevantes.LIMITACIONES:Este fue un estudio retrospectivo sin detalles granulares sobre las decisiones de tratamiento.CONCLUSIONES:A los pacientes jóvenes se les prescribe con frecuencia quimioterapia adyuvante para tumores de alto y bajo riesgo, a pesar de los cuestionables beneficios en estos últimos. Los pacientes de edad avanzada rara vez reciben terapia adyuvante. Tanto los oncólogos clínicos como los quirúrgicos deben ser conscientes de las disparidades en el tratamiento del cáncer y ser conscientes de tomar decisiones de tratamiento basadas únicamente en la edad. Consulte Video Resumen en http://links.lww.com/DCR/B846 . (Traducción- Dr. Francisco M. Abarca-Rendon ).
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Affiliation(s)
- Brendan L Hagerty
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
- Division of Colon and Rectal Surgery, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - John G Aversa
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Dana A Dominguez
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Jeremy L Davis
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Jonathan M Hernandez
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - James T McCormick
- Division of Colon and Rectal Surgery, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Andrew M Blakely
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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12
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Chang J, Lin S, Mao Y, Xu Y, Zhang Z, Wu Q, Chen Y, Wei Y, Feng Q, Xu J. CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy. Cancers (Basel) 2022; 14:cancers14194646. [PMID: 36230570 PMCID: PMC9562861 DOI: 10.3390/cancers14194646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
We explored the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer (CC) patients and assessed predictive ability as a biomarker for different ACT regimens among high-risk stage II and stage III patients in both primary and validation cohorts. Two independent cohorts of 360 and 126 consecutive colon cancer patients were enrolled from two medical centers of Zhongshan Hospital. Immunofluorescence and immunohistochemistry were performed to detect the density of CXCR6+TAMs and activated CD8+ T cells. The infiltration of CXCR6+TAMs was higher in tumor tissues and increased with advanced tumor stage. A high density of CXCR6+TAMs predicted worse overall survival (OS) in all CC patients (HR = 2.49, 95% CI = (1.68, 3.70), p < 0.001), and was an independent risk factor verified by Cox regression analysis (HR = 1.68, 95% CI = (1.09, 2.59), p = 0.019). For high-risk stage II and stage III patients with a high density of CXCR6+TAMs, better disease-free survival (DFS) (HR = 0.32, 95% CI = (0.11, 0.89), p = 0.003), and OS (HR = 0.28, 95% CI = (0.07, 1.11), p = 0.014) were observed in the 6-month treatment group. There was a negative relationship between the density of CXCR6+TAMs and CD8+ T cells (R = −0.51, p < 0.001) as well as activated CD8+ T cells (R = −0.54, p < 0.001). Higher levels of IL-6 and lower levels of IL-2R and TNF-α were expressed in high-CXCR6+ TAM-density patients, which indicates that CXCR6+TAMs contribute to an immunosuppressive microenvironment. CXCR6+TAMs predicted prognosis and response to different durations of ACT in CC patients. CXCR6+TAMs were associated with an immunosuppressive microenvironment and suppressed the activation of CD8+ T cells.
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Affiliation(s)
- Jiang Chang
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
| | - Songbin Lin
- General Surgery Department, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen 361000, China
| | - Yihao Mao
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
| | - Yuqiu Xu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
| | - Zhiyuan Zhang
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
| | - Qi Wu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
| | - Yijiao Chen
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
| | - Ye Wei
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai 200000, China
- Correspondence: (Y.W.); (Q.F.); Tel.: +86-021-6564-2660 (Y.W. & Q.F.)
| | - Qingyang Feng
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai 200000, China
- Correspondence: (Y.W.); (Q.F.); Tel.: +86-021-6564-2660 (Y.W. & Q.F.)
| | - Jianmin Xu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai 200000, China
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13
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New Insights into Adjuvant Therapy for Localized Colon Cancer. Hematol Oncol Clin North Am 2022; 36:507-520. [DOI: 10.1016/j.hoc.2022.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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14
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Chen J, Zhang C, Wu Y. Does adjuvant chemotherapy improve outcomes in elderly patients with colorectal cancer? A systematic review and meta-analysis of real-world studies. Expert Rev Gastroenterol Hepatol 2022; 16:383-391. [PMID: 35303773 DOI: 10.1080/17474124.2022.2056014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Elderly patients are frequently excluded from randomized trials. It is unclear if adjuvant chemotherapy improves outcomes of colorectal cancer in such patients. The current study aimed to review evidence on the impact of adjuvant chemotherapy on overall survival (OS) and disease-free survival (DFS) in elderly patients with stage II/III colorectal cancer by pooling data from real-world studies. METHODS PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched for observational studies reporting adjusted data on OS and DFS in elderly (≥70 years) colorectal cancer patients based on receipt of adjuvant chemotherapy. RESULTS Thirteen studies included. The meta-analysis demonstrated statistically significant improved OS in elderly patients receiving adjuvant chemotherapy (p < 0.00001). Results were similar for sub-group analysis based on cancer stage and definition of elderly. Improvement in OS was noted in only Western population studies with no difference in Asian patients. The meta-analysis also revealed no statistically significant difference in DFS in elderly patients receiving adjuvant chemotherapy vs surgery alone (p = 0.14). CONCLUSION Real-world evidence indicates that adjuvant chemotherapy significantly improved OS but not DFS in elderly colorectal cancer patients. Scarce evidence suggests a limited role of adjuvant chemotherapy in Asian patients which needs confirmation by further studies.
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Affiliation(s)
- Jianbing Chen
- Department of Radiotherapy, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, P.R China
| | - Chengda Zhang
- Department of Gastroenterology, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, P.R China
| | - Yajuan Wu
- The Second Chest Radiotheropy Department, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, P.R China
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15
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Sadahiro S, Sakamoto K, Tsuchiya T, Takahashi T, Ohge H, Sato T, Kondo K, Ogata Y, Baba H, Itabashi M, Ikeda M, Hamada M, Maeda K, Masuko H, Takahashi K, Sakamoto J, Kusano M, Hyodo I, Taguri M, Morita S. Prospective observational study of the efficacy of oral uracil and tegafur plus leucovorin for stage II colon cancer with risk factors for recurrence using propensity score matching (JFMC46-1201). BMC Cancer 2022; 22:170. [PMID: 35168560 PMCID: PMC8845390 DOI: 10.1186/s12885-022-09267-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 01/31/2022] [Indexed: 11/24/2022] Open
Abstract
Background The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors. Methods We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm. Results Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%–83.4%]) than in NR-Group S (74.0% [69.3%–78.0%]) (hazard ratio, 0.64 [0.50–0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW. Conclusions Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Trial registration Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783, date of registration: 18/04/2012). Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09267-z.
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Affiliation(s)
- Sotaro Sadahiro
- Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takashi Tsuchiya
- Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-ku, Sendai, Miyagi, 983-0824, Japan
| | - Takao Takahashi
- Department of Digestive Surgery, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Toshihiko Sato
- Department of Surgery, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata, 990-2292, Japan
| | - Ken Kondo
- Department of Surgery, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, 460-0001, Japan
| | - Yutaka Ogata
- Department of Surgery, Kurume University Hospital Cancer Center, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Michio Itabashi
- Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Masataka Ikeda
- Department of Gastroenterological Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Madoka Hamada
- Division of Gastrointestinal Surgery, Kansai Medical University Hospital, 2-3-1 Shinmachi Hirakata, Osaka, 573-1191, Japan
| | - Kiyoshi Maeda
- Department of Gastroenterological Surgery, Osaka City General Hospital, 2-13-22 Miyakojimahondori, Miyakojima-ku, Osaka, 534-0021, Japan
| | - Hiroyuki Masuko
- Department of Surgery, Nikko Memorial Hospital, 1-5-13 Shintomi-cho, Muroran, Hokkaido, 051-8501, Japan
| | - Keiichi Takahashi
- Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, 2-44-1 Kabuki-cho, Shinjuku-ku, Tokyo, 160-8488, Japan
| | - Junichi Sakamoto
- Tokai Central Hospital, 4-6-2 Sohara Higashijima-cho, Kakamigahara, Gifu, 504-8601, Japan
| | - Mitsuo Kusano
- Department of Physical Medicine, Yoichi Hospital, 19-1-1 Kurokawa-cho Yoichi, Hokkaido, 046-0003, Japan
| | - Ichinosuke Hyodo
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto, Matsuyama, Ehime, 791-0280, Japan
| | - Masataka Taguri
- Department of Data Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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Allar BG, Messaris E, Poylin VY, Schlechter BL, Cataldo TE. Oncotype DX testing does not affect clinical practice in stage IIa colon cancer. Med Oncol 2022; 39:59. [PMID: 35150339 DOI: 10.1007/s12032-022-01660-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 01/18/2022] [Indexed: 11/24/2022]
Abstract
Although studies have demonstrated the 12-gene Oncotype DX Colon Recurrence Score's (RS) validity in predicting recurrence and influence on physician-patient decision-making, its discriminatory power and inability to predict response to treatment make its clinical impact uncertain. We sought to evaluate the influence of RS in the decision to offer adjuvant chemotherapy after resection of stage IIa colon cancer. A review of patients with stage IIa colon cancer who obtained the RS at a tertiary academic medical center was conducted. The main study outcome was decision to start adjuvant chemotherapy. The association between RS and the decision to obtain adjuvant chemotherapy was evaluated utilizing the Wilcoxon rank-sum test and area under the receiver operating characteristic curve. 52 of 105 patients with stage IIa colon cancer underwent RS testing. Overall, seven of 52 patients (13%) received adjuvant chemotherapy. 34 (65%) patients obtained the RS test despite having multiple other recurrence risk factors. There were no significant associations between any patient/tumor characteristic and RS score (all p > 0.08) or starting adjuvant chemotherapy (all p > 0.15). On multivariable analysis, there was no significant effect of RS on the odds of undergoing chemotherapy (OR 1.07, 95% CI 0.98-1.19; p = 0.14). There was no clear association between RS and starting adjuvant chemotherapy (AUC 0.64, 95% CI 0.36-0.91; p = 0.25). RS was not associated with the decision to start adjuvant chemotherapy. Given its lack of association with clinical decision-making and inability to predict clinical outcome, our data suggest the RS should not be obtained in patients with stage IIa colon cancer.
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Affiliation(s)
- Benjamin G Allar
- Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA
| | - Evangelos Messaris
- Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA
| | - Vitaliy Y Poylin
- Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.,Division of Gastrointestinal Surgery, Northwestern Medicine, Feinberg School of Medicine, Chicago, IL, USA
| | - Benjamin L Schlechter
- Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Thomas E Cataldo
- Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
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Axelrod DE. Chronotherapy of Early Colon Cancer: Advantage of Morning Dose Schedules. Cancer Inform 2022; 21:11769351211067697. [PMID: 35110963 PMCID: PMC8801641 DOI: 10.1177/11769351211067697] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 11/29/2021] [Indexed: 12/01/2022] Open
Abstract
Colon adenomas with proliferating mutant cells may progress to invasive carcinomas. Proliferation of cells in human colorectal tissue is circadian, greater in the interval 4 to 12 hours after midnight than 16 to 24 hours after midnight. We have tested the hypothesis that chemotherapy administered during the time of greater cell proliferation will be more effective than chemotherapy administered during the time of lesser proliferation. An agent-based computer model of cell proliferation in colon crypts was calibrated with measurements of cell numbers in human biopsy specimens. It was used to simulate cytotoxic chemotherapy of an early stage of colon cancer, adenomas with about 20% of mutant cells. Chemotherapy doses were scheduled at different 4-hour intervals during the 24-hour day, and repeated at weekly intervals. Chemotherapy administered at 4 to 8 hours after midnight cured mutant cells in 100% of 50 trials with an average time to cure of 7.82 days (s.e.m. = 0.99). In contrast, chemotherapy administered at 20 to 24 hours after midnight cured only 18% of 50 trials, with the average time to cure of 23.51 days (s.e.m. = 2.42). These simulation results suggest that clinical chemotherapy of early colon cancer may be more effective when given in the morning than later in the day.
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Affiliation(s)
- David E Axelrod
- Department of Genetics and Rutgers Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ, USA
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18
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Hamed RA, Marks S, Mcelligott H, Kalachand R, Ibrahim H, Atyani S, Korpanty G, Osman N. Inoperable de novo metastatic colorectal cancer with primary tumour in situ: Evaluating discordant responses to upfront systemic therapy of the primary tumours and metastatic sites and complications arising from primary tumours (experiences from an Irish Cancer Centre). Mol Clin Oncol 2022; 16:40. [PMID: 35003738 PMCID: PMC8739439 DOI: 10.3892/mco.2021.2472] [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: 03/25/2021] [Accepted: 11/22/2021] [Indexed: 12/24/2022] Open
Abstract
Systemic therapy is the mainstay of treatment for de novo metastatic colorectal cancer (mCRC). Heterogeneity between primary tumours and metastases may lead to discordant responses to systemic therapy at these sites. The aim of the present study was to examine these discrepancies and to evaluate the rates of complications arising from the primary tumour and the strategies employed to manage these complications. Electronic medical records were screened for patients eligible for data analysis between January 1st, 2014 and December 31st, 2019. All patients diagnosed with de novo mCRC with primary tumour in situ at the time of initial systemic therapy were included in data analysis. Responses in primary tumour and metastatic sites (according to the Response Evaluation Criteria In Solid Tumours v1.1), discrepancies in these responses and rates of complications arising from primary tumours were assessed along with patient, pathological or molecular factors that may be associated with these discrepant responses or primary tumour complications. A total of 50 patients were identified (median age, 62 years). Right-colon, left-colon and rectal primary tumours comprised 34, 44 and 22% of CRC cases, respectively. All patients received 5-fluorouracil-based chemotherapy (either alone or in combination with oxaliplatin or irinotecan). Disease response (DR), stable disease (SD) and progressive disease (PD) were observed as the first response to systemic therapy in 24, 62 and 12% of primary tumours and in 36, 18 and 44% of metastatic sites, respectively. Only 36% of patients demonstrated concordant responses between the primary tumours and metastases, while the remaining 62% demonstrated discordant responses between the primary tumour and distant metastases (22% had DR with SD; 36% had DR or SD with PD; and 4% had PD with SD in the primary tumour and metastases, respectively). Restaging images were not available for 2% of the patients. Approximately 30% of patients developed complications from primary tumours, including bowel obstruction (6.12%), perforation (6%), rectal pain (6%) and rectal bleeding (10%). Approximately 10% of patients underwent palliative stoma creation. Additionally, 12% required palliative radiotherapy to the primary tumour (due to localized complications arising from the tumour). Discordant responses to systemic therapy between primary tumours and metastases occurred in 60% of patients with de novo mCRC (with primary tumour in situ at the time of first systemic therapy). The observations of the present study have potential implications for molecular tissue analysis to help guide systemic therapy. Tissue from metastatic sites may be preferable to confirm biomarker status in mCRC based on this study.
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Affiliation(s)
- Ruba A Hamed
- Department of Oncology, Mid-Western Cancer Centre, University Hospital Limerick, Limerick V94 F858, Ireland
| | - Sam Marks
- Department of Oncology, Mid-Western Cancer Centre, University Hospital Limerick, Limerick V94 F858, Ireland
| | - Helen Mcelligott
- Department of Oncology, Mid-Western Cancer Centre, University Hospital Limerick, Limerick V94 F858, Ireland
| | - Roshni Kalachand
- Department of Oncology, Mid-Western Cancer Centre, University Hospital Limerick, Limerick V94 F858, Ireland
| | - Hawa Ibrahim
- Palliative Department, St. Francis Hospice, Dublin 5 D05 T9K8, Ireland
| | - Said Atyani
- Radiology Department, University Hospital Limerick, Limerick V94 F858, Ireland
| | - Greg Korpanty
- Department of Oncology, Mid-Western Cancer Centre, University Hospital Limerick, Limerick V94 F858, Ireland
| | - Nemer Osman
- Department of Oncology, Mid-Western Cancer Centre, University Hospital Limerick, Limerick V94 F858, Ireland
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19
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Li X, Xiong Z, Xie M, Huang Q, Jin L, Yin S, Chen S, Lan P, Lian L. Prognostic value of the ratio of carcinoembryonic antigen concentration to maximum tumor diameter in patients with stage II colorectal cancer. J Gastrointest Oncol 2021; 12:1470-1481. [PMID: 34532103 DOI: 10.21037/jgo-21-61] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/08/2021] [Indexed: 12/16/2022] Open
Abstract
Background Recently, a study from our center indicated that the ratio of preoperative carcinoembryonic antigen (CEA) concentration to maximum tumor diameter (DMAX) may be a prognostic marker for patients with rectal cancer. Therefore, the study aimed to evaluate whether this ratio (CEA/DMAX) has prognostic value for patients with stage II colorectal cancer (CRC). Methods A prospectively maintained database was searched for patients with pathologically confirmed stage II CRC who underwent surgery between January 2010 and March 2019. Patients were stratified according to the mean CEA/DMAX value into low and high CEA/DMAX groups. Kaplan-Meier, univariable, and multivariable Cox regression analyses were used to evaluate whether the CEA/DMAX could predict overall survival (OS) and disease-free survival (DFS). Nomograms were constructed in terms of the results of multivariable Cox regression analyses. Results The study included 2,499 patients with stage II CRC. The mean CEA/DMAX value was 2.33 (ng/mL per cm). Kaplan-Meier analyses revealed that, relative to the low CEA/DMAX group, the high CEA/DMAX group had significantly poorer OS (67.31% vs. 85.02%, P<0.001) and DFS (61.41% vs. 77.10%, P<0.001). The multivariable Cox regression analysis revealed that CEA/DMAX independently predicted OS (hazard ratio: 2.58, 95% confidence interval: 1.51-4.38, P<0.001) and DFS (hazard ratio: 1.97, 95% confidence interval: 1.38-2.83, P<0.001). Two simple-to-use nomograms comprising CEA/DMAX, age, T stage, and lymphovascular invasion were developed to predict 1-, 3-, and 5-year rates of OS and DFS among patients with stage II CRC. The nomograms had good performance based on the concordance index, receiver operating characteristic (ROC) curve analysis, and calibration curves. Subgroup analyses further confirmed that a high CEA/DMAX was associated with poor OS and DFS among patients with stage II colon cancer and among patients with stage II rectal cancer (both P<0.05). Conclusions Among patients with stage II CRC, a high CEA/DMAX independently predicted poor OS and DFS, and the predictive abilities were also observed in subgroup analyses of patients with stage II colon cancer or rectal cancer. Furthermore, we developed two nomograms that had good accuracy for predicting the prognosis of stage II CRC.
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Affiliation(s)
- Xianzhe Li
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhizhong Xiong
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minghao Xie
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qunsheng Huang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Longyang Jin
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shi Yin
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuanggang Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ping Lan
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lei Lian
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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20
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Li W, Guo L, Tang W, Ma Y, Wang X, Shao Y, Zhao H, Ying J. Identification of DNA methylation biomarkers for risk of liver metastasis in early-stage colorectal cancer. Clin Epigenetics 2021; 13:126. [PMID: 34108011 PMCID: PMC8190869 DOI: 10.1186/s13148-021-01108-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/31/2021] [Indexed: 12/23/2022] Open
Abstract
Background Liver metastases can occur even in CRC patients who underwent curative surgery. While evidence suggested that adjuvant chemotherapy can help to reduce the occurrence of liver metastases for certain patients, it is not a recommended routine as the side effects outweigh the potential benefits, especially in Stage II CRC patients. This study aims to construct a model for predicting liver metastasis risk using differential methylation signals in primary CRC tumors, which can facilitate the decision for adjuvant chemotherapy. Methods Fifty-nine stage I/II and IV CRC patients were enrolled. Primary tumor, adjacent normal tissue, and metastatic tumor tissues were subject to targeted bisulfite sequencing for DNA methylation. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to identify potential DMRs for predicting liver metastasis of CRC. Results We identified a total of 241,573 DMRs by comparing the DNA methylation profile of primary tumors of stage II patients who developed metastasis to those who were metastasis-free during the follow up period. 213 DMRs were associated with poor prognosis, among which 182 DMRS were found to be hypermethylated in the primary tumor of patients with metastases. Furthermore, by using the LASSO regression model, we identified 23 DMRs that contributed to a high probability of liver metastasis of CRC. The leave-one-out cross validation (LOOCV) was used to evaluate model predictive performance at an AUC of 0.701. In particular, 7 out of those 23 DMRs were found to be in the promoter region of genes that were previously reported prognostic biomarkers in diverse tumor types, including TNNI2, PAX8, GUF1, KLF4, EVI2B, CEP112, and long non-coding RNA AC011298. In addition, the model was also able to distinguish metastases of different sites (liver or lung) at an AUC of 0.933. Conclusion We have identified DNA methylation biomarkers associated with the risk of cancer liver metastasis in early-stage CRC patients. A risk prediction model based on those epigenetic markers was proposed for outcome assessment. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-021-01108-3.
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Affiliation(s)
- Weihua Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Lei Guo
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | | | - Yutong Ma
- Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China
| | - Xiaonan Wang
- Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China
| | - Yang Shao
- Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China.
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21
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Li X, Xie M, Yin S, Xiong Z, Mao C, Zhang F, Chen H, Jin L, Lan P, Lian L. Identification and Validation of a Six Immune-Related Genes Signature for Predicting Prognosis in Patients With Stage II Colorectal Cancer. Front Genet 2021; 12:666003. [PMID: 34017356 PMCID: PMC8129521 DOI: 10.3389/fgene.2021.666003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 04/14/2021] [Indexed: 01/20/2023] Open
Abstract
Background Immune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC). Methods Gene expression profiles and clinical data for stage II CRC patients were collected from the Cancer Genome Atlas and Gene Expression Omnibus database. Univariate, multivariate Cox regression, and least absolute shrinkage and selection operator regression were used to develop the IRG signature, namely IRGCRCII. A nomogram was constructed, and the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method was used to estimate immune cell infiltration. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in 30 pairs of primary stage II CRC and matched normal tissues. Results A total of 466 patients with stage II CRC were included, and 274 differentially expressed IRGs were identified. Six differentially expressed IRGs were detected and used to construct the IRGCRCII signature, which could significantly stratify patients into high-risk and low-risk groups in terms of disease-free survival in three cohorts: training, test, and external validation (GSE39582). Receiver operating characteristics analysis revealed that the area under the curves of the IRGCRCII signature were significantly greater than those of the OncotypeDX colon signature at 1 (0.759 vs. 0.623), 3 (0.875 vs. 0.629), and 5 years (0.906 vs. 0.698) disease-free survival, respectively. The nomogram performed well in the concordance index (0.779) and calibration curves. The high-risk group had a significantly higher percentage of infiltrated immune cells (e.g., M2 macrophages, plasma cells, resting mast cells) than the low-risk group. Finally, the results of qRT-PCR and immunohistochemistry experiments performed on 30 pairs of clinical specimens were consistent with bioinformatics analysis. Conclusion This study developed and validated a novel immune prognostic signature based on six differentially expressed IRGs for predicting disease-free survival and immune status in patients with stage II CRC, which may reflect immune dysregulation in the tumor immune microenvironment.
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Affiliation(s)
- Xianzhe Li
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minghao Xie
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shi Yin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhizhong Xiong
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chaobin Mao
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fengxiang Zhang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Huaxian Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Longyang Jin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lei Lian
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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22
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Tu J, Yao Z, Wu W, Ju J, Xu Y, Liu Y. Perineural Invasion Is a Strong Prognostic Factor but Not a Predictive Factor of Response to Adjuvant Chemotherapy in Node-Negative Colon Cancer. Front Oncol 2021; 11:663154. [PMID: 33859950 PMCID: PMC8042311 DOI: 10.3389/fonc.2021.663154] [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: 02/02/2021] [Accepted: 03/04/2021] [Indexed: 12/19/2022] Open
Abstract
Purpose To validate the prognostic value and evaluate the predictive value of response to adjuvant chemotherapy of perineural invasion (PNI) in node-negative colon cancer using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 tumor registry database. Methods Patients diagnosed with colon cancer from the SEER database between January 1, 2010 and December 31, 2015 were identified. Chi-square analysis was performed to evaluate different demographic and clinical features of patients between PNI-negative (PNI (-)) and PNI-positive (PNI (+)) groups. Univariate and multivariate Cox proportional hazard regression models were built to examine the relationship of demographic and clinical features and survival outcomes with the hazard ratios (HRs) and 95% confidence intervals (CIs). Results In total, 57,255 node-negative colon cancer patients were extracted from the SEER database. The receipt of chemotherapy was not an independent prognostic factor for CSS in T3 colon cancer with or without the presence of PNI (P >0.05). The receipt of chemotherapy was independently associated with 34.0% decreased risk of cancer-specific mortality compared with those without the receipt of chemotherapy in T4 colon cancer without the presence of PNI (HR = 0.660, 95%CI = 0.559-0.779, P <0.001); the receipt of chemotherapy was independently associated with 36.0% decreased risk of cancer-specific mortality compared with those without the receipt of chemotherapy in T4 colon cancer with the presence of PNI (HR = 0.640, 95%CI = 0.438-0.935, P = 0.021). Conclusions The present study demonstrated the poor prognosis of PNI (+) in both stage I and II colon cancer. However, the presence of PNI was not a predictive factor of response to adjuvant chemotherapy in node-negative colon cancer.
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Affiliation(s)
- Junhao Tu
- Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou, China
| | - Zongxi Yao
- Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou, China
| | - Wenqing Wu
- Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou, China
| | - Jianxiang Ju
- Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou, China
| | - Yinkai Xu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yulin Liu
- Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou, China
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Chan HC, Chattopadhyay A, Chuang EY, Lu TP. Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm. Front Oncol 2021; 11:631056. [PMID: 33692961 PMCID: PMC7938710 DOI: 10.3389/fonc.2021.631056] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/05/2021] [Indexed: 01/21/2023] Open
Abstract
It is difficult to determine which patients with stage I and II colorectal cancer are at high risk of recurrence, qualifying them to undergo adjuvant chemotherapy. In this study, we aimed to determine a gene signature using gene expression data that could successfully identify high risk of recurrence among stage I and II colorectal cancer patients. First, a synthetic minority oversampling technique was used to address the problem of imbalanced data due to rare recurrence events. We then applied a sequential workflow of three methods (significance analysis of microarrays, logistic regression, and recursive feature elimination) to identify genes differentially expressed between patients with and without recurrence. To stabilize the prediction algorithm, we repeated the above processes on 10 subsets by bagging the training data set and then used support vector machine methods to construct the prediction models. The final predictions were determined by majority voting. The 10 models, using 51 differentially expressed genes, successfully predicted a high risk of recurrence within 3 years in the training data set, with a sensitivity of 91.18%. For the validation data sets, the sensitivity of the prediction with samples from two other countries was 80.00% and 91.67%. These prediction models can potentially function as a tool to decide if adjuvant chemotherapy should be administered after surgery for patients with stage I and II colorectal cancer.
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Affiliation(s)
- Han-Ching Chan
- Department of Public Health, College of Public Health, National Taiwan University, Institute of Epidemiology and Preventive Medicine, Taipei, Taiwan
| | - Amrita Chattopadhyay
- Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan
| | - Eric Y Chuang
- Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.,Department of Electrical Engineering, Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
| | - Tzu-Pin Lu
- Department of Public Health, College of Public Health, National Taiwan University, Institute of Epidemiology and Preventive Medicine, Taipei, Taiwan.,Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan
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24
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Novel Genetic and Epigenetic Biomarkers of Prognostic and Predictive Significance in Stage II/III Colorectal Cancer. Mol Ther 2020; 29:587-596. [PMID: 33333293 DOI: 10.1016/j.ymthe.2020.12.017] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/15/2020] [Accepted: 12/09/2020] [Indexed: 12/18/2022] Open
Abstract
The therapeutic strategies of stage II/III colorectal cancer (CRC) patients after curative surgery remain controversial. In the clinical decision-making process, oncologists need to answer questions such as whether adjuvant chemotherapy is necessary or which therapeutic regimen should be given to each patient. At present, whether adjuvant chemotherapy should be applied is primarily based on histopathological features and clinical risk factors. However, only a fraction of patients can benefit from it. More rigorous stratifying biomarkers are urgently needed to help further distinguishing these populations of patients. Recent progress in next-generation sequencing and high-throughput technologies has greatly promoted biomarker discovery as well as our understanding of the underlying mechanisms in CRC. Novel genetic and epigenetic biomarkers that are associated with prognosis or therapeutic responses have emerged. In this review, we discuss the strategies of biomarker discovery and summarize the status and assess the utility of previously published biomarkers in CRC.
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25
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Knapen DG, Cherny NI, Zygoura P, Latino NJ, Douillard JY, Dafni U, de Vries EGE, de Groot DJ. Lessons learnt from scoring adjuvant colon cancer trials and meta-analyses using the ESMO-Magnitude of Clinical Benefit Scale V.1.1. ESMO Open 2020; 5:e000681. [PMID: 32893188 PMCID: PMC7476457 DOI: 10.1136/esmoopen-2020-000681] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/12/2020] [Accepted: 03/13/2020] [Indexed: 12/13/2022] Open
Abstract
Click here to listen to the Podcast BACKGROUND: Form 1 of the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) serves to grade therapies with curative intent. Hitherto only few trials with curative intent have been field tested using form 1. We aimed to evaluate the applicability of the scale and to assess the reasonableness of the generated scores in early colon cancer, in order to identify shortcomings that may be rectified in future amendments. METHODS Adjuvant studies were identified in PubMed, Food and Drug Administration and European Medicines Agency registration sites, as well as ESMO and National Comprehensive Cancer Network guidelines. Studies meeting inclusion criteria were graded using form 1 of the ESMO-MCBS V.1.1 and field tested by ESMO Colorectal Cancer Faculty. Shortcomings of the scale were identified and evaluated. RESULTS Eighteen of 57 trials and 7 out of 14 meta-analyses identified met criteria for ESMO-MCBS V.1.1 grading. In stage III colon cancer, randomised clinical trials and meta-analyses of modulated 5-fluorouracil (5-FU) based chemotherapy versus surgery scored ESMO-MCBS grade A and randomised controlled trials (RCTs) and meta-analyses comprising oxaliplatin added to this 5-FU backbone showed a more modest additional overall survival benefit (grade A and B). For stage II colon cancer, the findings are less consistent. The fluoropyrimidine trials in stage II were graded 'no evaluable benefit' but the most recent meta-analysis demonstrated a 5.4% survival advantage after 8 years follow-up (grade A). RCTs and a meta-analysis adding oxaliplatin demonstrated no added benefit. Exploratory toxicity evaluation and annotation was problematic given inconsistent toxicity reporting and limited results of late toxicity. Field testers (n=37) reviewed the scores, 25 confirmed their reasonableness, 12 found them mostly reasonable. Moreover, they identified the inability of crediting improved convenience in non-inferiority trials as a shortcoming. CONCLUSION Form 1 of the ESMO-MCBS V.1.1 provided very reasonable grading for adjuvant colon cancer studies.
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Affiliation(s)
- Daan Geert Knapen
- Medical Oncology, University Medical Centre Groningen, Groningen, Groningen, Netherlands
| | - Nathan I Cherny
- Medical Oncology, Shaare Zedek Medical Center, Jerusalem, Jerusalem, Israel
| | - Panagiota Zygoura
- Statistics, Frontier Science Foundation-Hellas, Statistics, Athens, Zografou, Greece
| | - Nicola Jane Latino
- ESMO-MCBS Working Group, European Society for Medical Oncology, Viganello, Switzerland
| | - Jean-Yves Douillard
- ESMO-MCBS Working Group, European Society for Medical Oncology, Viganello, Switzerland
| | - Urania Dafni
- Nursing, National and Kapodistrian University of Athens, Goudi-Athens, Greece; University of Athens, Athens, Greece
| | - Elisabeth G E de Vries
- Medical Oncology, University Medical Centre Groningen, Groningen, Groningen, Netherlands
| | - Derk Jan de Groot
- Medical Oncology, University Medical Centre Groningen, Groningen, Groningen, Netherlands.
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26
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Komorowski AS, MacKay HJ, Pezo RC. Quality of adverse event reporting in phase III randomized controlled trials of breast and colorectal cancer: A systematic review. Cancer Med 2020; 9:5035-5050. [PMID: 32452660 PMCID: PMC7367648 DOI: 10.1002/cam4.3095] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 04/11/2020] [Accepted: 04/13/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Clinical trial reports often emphasize efficacy over harms, leading to misinterpretation of the risk-to-benefit ratio of new therapies. Clear and sufficiently detailed reporting of methods and results is especially important in the abstracts of trial reports, as readers often base their assessment of a trial on such information. In this study, we evaluated the quality of adverse event (AE) reporting and abstract quality in phase III randomized controlled trials (RCTs) of systemic therapies in breast and colorectal cancer. METHODS Medline, EMBASE, Cochrane Database of RCTs, and Cochrane Database of Systematic Reviews were searched from November 2005 to September 2018. Phase III RCTs evaluating systemic therapies in breast or colorectal cancer were included. Each article was independently reviewed by two investigators using a standardized data extraction form based on guidelines developed by the Consolidated Standards of Reporting Trials (CONSORT) group. Descriptive statistics, bivariate analysis, and multivariable linear regression were used to analyze data. All statistical tests were two-sided. RESULTS Of 166 RCTs identified, 99.4% reported harms in the manuscript body, and 59.6% reported harms in the abstract. Reporting was restricted to severe harms in 15.6% of RCTs. Statistical comparison of AE rates went unreported in 59.0% of studies. Information regarding AEs leading to dose reductions, treatment discontinuations, or study withdrawals went unreported in 59.3%, 18.7%, and 86.8% of studies, respectively. Recently published RCTs (P = .009) and those sponsored at least partially by for-profit companies (P = .003) had higher abstract quality scores. CONCLUSIONS Breast and colorectal cancer phase III RCTs inadequately report CONSORT-compliant AE data. Improved guideline adherence and abstract reporting is required to properly weigh benefits and harms of new oncologic therapies. SYSTEMATIC REVIEW REGISTRATION NUMBER CRD42019140673.
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Affiliation(s)
- Adam S. Komorowski
- Division of Medical MicrobiologyMcMaster UniversityHamiltonONCanada
- Sunnybrook Research InstituteSunnybrook Health Sciences CentreTorontoONCanada
| | - Helen J. MacKay
- Division of Medical OncologySunnybrook Health Sciences CentreTorontoONCanada
- Department of MedicineUniversity of TorontoTorontoONCanada
| | - Rossanna C. Pezo
- Division of Medical OncologySunnybrook Health Sciences CentreTorontoONCanada
- Department of MedicineUniversity of TorontoTorontoONCanada
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27
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Taghizadeh H, Prager GW. Personalized Adjuvant Treatment of Colon Cancer. Visc Med 2020; 36:397-406. [PMID: 33178737 DOI: 10.1159/000508175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 04/23/2020] [Indexed: 12/15/2022] Open
Abstract
Introduction Colon cancer (CC) is one of the most frequent malignant diseases. Adjuvant chemotherapy is of utmost importance in the management of localized disease. With the emergence of precision medicine, treatment approaches are becoming increasingly personalized and complex. This review contributes to a broader understanding of the role and relevance of personalized adjuvant treatment strategies in colon carcinoma, and summarizes the current status in this disease entity. Methods We searched the websites ClinicalTrials.gov, PubMed, and ASCO (American Society of Medical Oncology) Meeting Library for clinical trials and retrospective analyses in the field of adjuvant treatment of CC with special attention to personalized approaches. Results Various factors, including gender, age, sidedness, stage, dMMR/MSI-H, mutations, molecular profile, CMS, immunoscore, minimal residual disease, type of adjuvant therapy, therapy duration, and the patient's wish play an important role in the adjuvant setting of CC and should be considered in treatment decision making. Conclusion Future molecular profiling ideally assessed and monitored by liquid biopsy might personalize decision making even more in the adjuvant setting of CC patients. Further research and clinical trials are needed to clarify relevant questions and to highlight important clinical aspects.
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Affiliation(s)
- Hossein Taghizadeh
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.,Comprehensive Cancer Center Vienna, Vienna, Austria
| | - Gerald W Prager
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.,Comprehensive Cancer Center Vienna, Vienna, Austria
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28
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Ouchi A, Shida D, Hamaguchi T, Takashima A, Ito Y, Ueno H, Ishiguro M, Takii Y, Ikeda S, Ohue M, Fujita S, Shiozawa M, Kataoka K, Ito M, Tsukada Y, Akagi T, Inomata M, Shimada Y, Kanemitsu Y. Challenges of improving treatment outcomes for colorectal and anal cancers in Japan: the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG). Jpn J Clin Oncol 2020; 50:368-378. [PMID: 32115643 DOI: 10.1093/jjco/hyaa014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 01/15/2020] [Accepted: 01/23/2020] [Indexed: 12/20/2022] Open
Abstract
Colorectal cancer is a major public health concern in Japan. While early-stage colorectal adenocarcinoma treatment entails radical resection of the primary tumor, the importance of perioperative treatment is growing as physicians seek to further improve treatment outcomes. For anal squamous cell carcinoma, definitive chemoradiotherapy is superior to radical surgery in terms of improved patient quality of life. The Colorectal Cancer Study Group of the Japanese Clinical Oncology Group was established in 2001 and has worked to provide answers to common clinical questions and improve treatment outcomes for colorectal and anal cancers through 15 large-scale prospective clinical trials. Here, we discuss the current state of perioperative treatment for early-stage colon, rectal and anal cancers in Japan and approaches taken by the Colorectal Cancer Study Group/the Japanese Clinical Oncology Group to improve treatment outcomes for these cancers.
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Affiliation(s)
- Akira Ouchi
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Aichi
| | - Dai Shida
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo
| | - Tetsuya Hamaguchi
- Department of Gastroenterological Oncology, Saitama Medical University International Medical Center, Saitama
| | - Atsuo Takashima
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University Graduate School of Medicine, Tokyo
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama
| | - Megumi Ishiguro
- Department of Chemotherapy and Oncosurgery, Tokyo Medical and Dental University Medical Hospital, Tokyo
| | - Yasumasa Takii
- Department of Surgery, Niigata Cancer Center Hospital, Niigata
| | - Satoshi Ikeda
- Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Osaka
| | - Shin Fujita
- Department of Surgery, Tochigi Cancer Center, Tochigi
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama
| | - Kozo Kataoka
- Division of Lower GI, Department of Surgery, Hyogo College of Medicine, Hyogo
| | - Masaaki Ito
- Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba
| | - Yuichiro Tsukada
- Department of Colorectal Surgery, National Cancer Center Hospital East, Chiba
| | - Tomonori Akagi
- Department of Gastroenterological and Pediatric Surgery, Oita University Hospital, Oita
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Oita University Hospital, Oita
| | - Yasuhiro Shimada
- Division of Clinical Oncology, Kochi Health Sciences Center, Kochi, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo
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29
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Batra A, Rigo R, Sheka D, Cheung WY. Real-world evidence on adjuvant chemotherapy in older adults with stage II/III colon cancer. World J Gastrointest Oncol 2020; 12:604-618. [PMID: 32699576 PMCID: PMC7340998 DOI: 10.4251/wjgo.v12.i6.604] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/08/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Colon cancer represents one of the most common cancers diagnosed in older adults worldwide. The standard of care in resected stage II and stage III colon cancer continues to evolve. While there is unequivocal evidence to suggest both disease free and overall survival benefits with the use of combination chemotherapy in patients with stage III colon cancer, data regarding its use in patients with stage II colon cancer are less clear. Further, although colon cancer is a disease that affects older adults, there is considerable debate on the value of adjuvant chemotherapy in the aging population. In particular, many older patients are undertreated when compared to their younger counterparts. In this review, we will describe the clinical trials that contributed to the current adjuvant chemotherapy approach in colon cancer, discuss representation of older adults in trials and the specific challenges associated with the management of this sub-population, and highlight the role of comprehensive geriatric assessments. We will also review how real-world evidence complements the data gaps from clinical trials of early stage colon cancer.
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Affiliation(s)
- Atul Batra
- Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta T2N 1N4, Canada
| | - Rodrigo Rigo
- Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta T2N 1N4, Canada
| | - Dropen Sheka
- Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta T2N 1N4, Canada
| | - Winson Y Cheung
- Department of Oncology, University of Calgary, Calgary, Alberta T2N 4N2, Canada
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30
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Cockrell C, Teague J, Axelrod DE. Prevention of Colon Cancer Recurrence From Minimal Residual Disease: Computer Optimized Dose Schedules of Intermittent Apoptotic Adjuvant Therapy. JCO Clin Cancer Inform 2020; 4:514-520. [PMID: 32510974 DOI: 10.1200/cci.20.00016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
PURPOSE Adjuvant chemotherapy is used after surgery for stages II and III colorectal cancer to reduce recurrence. Nevertheless, recurrence may occur years later with the emergence of initially undetected minimal residual disease (MRD). Attempts to reduce recurrence by increasing the dose intensity and increasing the time of adjuvant therapy have been limited by the adverse effects of the recommended cytotoxic agents. The goals of this study were to suggest an alternative to the recommended cytotoxic agents and to determine optimal adjuvant therapy dose schedules that would reduce the percentage of recurrence at 5 years while retaining colon crypt function. METHODS A total of 84,400 dose schedules with different duration, interval between doses, and intensity of treatment were simulated with a high-performance computer. Simulated treatments used the drug sulindac, which had previously been used in primary prevention. With appropriate dose schedules, it can induce apoptosis at the crypt lumen surface while retaining crypt function. We used a computer model of cell dynamics in colon crypts that had been calibrated with measurements of human biopsy specimens. Proliferating mutant cells were assumed to emerge from MRD within crypts. Simulated outcomes included the recurrence percentage at 5 years and the retention of crypt function. RESULTS Optimal dose schedules were determined for adjuvant treatment of MRD that reduced the percentage of recurrence at 5 years of stages I, II, and III colon cancer to zero. CONCLUSION A new adjuvant therapy for colon cancer based upon optimum dose schedules of intermittent apoptotic treatment may prevent the recurrence of colon cancer from MRD and avoid the adverse effects of cytotoxic treatments.
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Affiliation(s)
- Chase Cockrell
- Department of Surgery, University of Vermont College of Medicine, Burlington, VT
| | - Joseph Teague
- Department of Surgery, University of Vermont College of Medicine, Burlington, VT
| | - David E Axelrod
- Department of Genetics and Rutgers Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ
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31
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Pflügler S, Svinka J, Scharf I, Crncec I, Filipits M, Charoentong P, Tschurtschenthaler M, Kenner L, Awad M, Stift J, Schernthanner M, Bischl R, Herndler-Brandstetter D, Glitzner E, Moll HP, Casanova E, Timelthaler G, Sibilia M, Gnant M, Lax S, Thaler J, Müller M, Strobl B, Mohr T, Kaser A, Trajanoski Z, Heller G, Eferl R. IDO1 + Paneth cells promote immune escape of colorectal cancer. Commun Biol 2020; 3:252. [PMID: 32444775 PMCID: PMC7244549 DOI: 10.1038/s42003-020-0989-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 04/10/2020] [Indexed: 02/07/2023] Open
Abstract
Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy.
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Affiliation(s)
- Sandra Pflügler
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Jasmin Svinka
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Irene Scharf
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Ilija Crncec
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Martin Filipits
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Pornpimol Charoentong
- Institute of Bioinformatics, Medical University Innsbruck, Biocenter, 6020, Innsbruck, Austria
- Department of Medical Oncology, National Center for Tumor diseases, University Hospital Heidelberg, 69120, Heidelberg, Germany
- German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
| | - Markus Tschurtschenthaler
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, 81675, Munich, Germany
| | - Lukas Kenner
- Ludwig Boltzmann Institute for Cancer Research LBICR, 1090, Vienna, Austria
- Institute of Clinical Pathology, Medical University of Vienna, 1090, Vienna, Austria
- Department of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, 1210, Vienna, Austria
| | - Monira Awad
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Judith Stift
- Institute of Clinical Pathology, Medical University of Vienna, 1090, Vienna, Austria
| | - Marina Schernthanner
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Romana Bischl
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | | | - Elisabeth Glitzner
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Herwig P Moll
- Department of Physiology, Center of Physiology and Pharmacology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090, Vienna, Austria
| | - Emilio Casanova
- Ludwig Boltzmann Institute for Cancer Research LBICR, 1090, Vienna, Austria
- Department of Physiology, Center of Physiology and Pharmacology, Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090, Vienna, Austria
| | - Gerald Timelthaler
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Maria Sibilia
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Michael Gnant
- Department of Surgery, Breast Health Center, Comprehensive Cancer Center, Medical University of Vienna, 1090, Vienna, Austria
| | - Sigurd Lax
- Department of Pathology, Hospital Graz II, 8020, Graz, Austria
- Institute of Pathology and Molecular Pathology, Johannes Kepler University, 4040, Linz, Austria
| | - Josef Thaler
- Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, 4600, Wels, Austria
| | - Mathias Müller
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210, Vienna, Austria
| | - Birgit Strobl
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210, Vienna, Austria
| | - Thomas Mohr
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Arthur Kaser
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Zlatko Trajanoski
- Institute of Bioinformatics, Medical University Innsbruck, Biocenter, 6020, Innsbruck, Austria
| | - Gerwin Heller
- Division of Oncology, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria
| | - Robert Eferl
- Institute of Cancer Research, Medical University of Vienna and Comprehensive Cancer Center, 1090, Vienna, Austria.
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32
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Salimzadeh H, Lindskog EB, Gustavsson B, Wettergren Y, Ljungman D. Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival. BMC Cancer 2020; 20:409. [PMID: 32397974 PMCID: PMC7216326 DOI: 10.1186/s12885-020-06924-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 05/03/2020] [Indexed: 02/08/2023] Open
Abstract
Background Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy. Methods SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan–Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS. Results The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p = 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p = 0.006 and p = 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p = 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p = 0.02). However, there was no significant association between the SNPs and 5-year RFS. Conclusions Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.
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Affiliation(s)
- Hamideh Salimzadeh
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Östra, 416 85, Gothenburg, Sweden.,Digestive Oncology Research Centre, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Elinor Bexe Lindskog
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Östra, 416 85, Gothenburg, Sweden.,Region Västra Götaland, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Bengt Gustavsson
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Östra, 416 85, Gothenburg, Sweden
| | - Yvonne Wettergren
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Östra, 416 85, Gothenburg, Sweden
| | - David Ljungman
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Östra, 416 85, Gothenburg, Sweden. .,Region Västra Götaland, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
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33
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Cohen R, Vernerey D, Bellera C, Meurisse A, Henriques J, Paoletti X, Rousseau B, Alberts S, Aparicio T, Boukovinas I, Gill S, Goldberg RM, Grothey A, Hamaguchi T, Iveson T, Kerr R, Labianca R, Lonardi S, Meyerhardt J, Paul J, Punt CJA, Saltz L, Saunders MP, Schmoll HJ, Shah M, Sobrero A, Souglakos I, Taieb J, Takashima A, Wagner AD, Ychou M, Bonnetain F, Gourgou S, Yoshino T, Yothers G, de Gramont A, Shi Q, André T. Guidelines for time-to-event end-point definitions in adjuvant randomised trials for patients with localised colon cancer: Results of the DATECAN initiative. Eur J Cancer 2020; 130:63-71. [PMID: 32172199 PMCID: PMC7409551 DOI: 10.1016/j.ejca.2020.02.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 02/05/2020] [Accepted: 02/08/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND The variability of definitions for time-to-event (TTE) end-points impacts the conclusions of randomised clinical trials (RCTs). The Definition for the Assessment of Time-to-event Endpoints in CANcer (DATECAN) initiative aims to provide consensus definitions for TTE end-points used in RCTs. Here, we formulate guidelines for adjuvant colon cancer RCTs. METHODS We performed a literature review to identify TTE end-points and events included in their definition in RCT publications. Then, a consensus was reached among a panel of international experts, using a formal modified Delphi method, with 2 rounds of questionnaires and an in-person meeting. RESULTS Twenty-four experts scored 72 events involved in 6 TTE end-points. Consensus was reached for 24%, 57% and 100% events after the first round, second round and in-person meeting. For RCTs not using overall survival as their primary end-point, the experts recommend using disease-free survival (DFS) rather than recurrence-free survival (RFS) or time to recurrence (TTR) as the primary end-point. The consensus definition of DFS includes all causes of death, second primary colorectal cancers (CRCs), anastomotic relapse and metastatic relapse as an event, but not second primary non-CRCs. Events included in the RFS definition are the same as for DFS with the exception of second primary CRCs. The consensus definition of TTR includes anastomotic or metastatic relapse, death with evidence of recurrence and death from CC cause. CONCLUSION Standardised definitions of TTE end-points ensure the reproducibility of the end-points between RCTs and facilitate cross-trial comparisons. These definitions should be integrated in standard practice for the design, reporting and interpretation of adjuvant CC RCTs.
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Affiliation(s)
- Romain Cohen
- Sorbonne Université, Department of Medical Oncology, AP-HP, Hôpital Saint-Antoine, F-7512, Paris, France; Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA.
| | - Dewi Vernerey
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, F-25000, Besançon, France; University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France
| | - Carine Bellera
- Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Epicene Team, UMR 1219, F-33000 Bordeaux, France; Inserm CIC1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, F-33000, Bordeaux, France
| | - Aurélia Meurisse
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, F-25000, Besançon, France; University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France
| | - Julie Henriques
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, F-25000, Besançon, France; University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France
| | - Xavier Paoletti
- Université de Versailles-St Quentin & Institut Curie, INSERM U900, équipe Biostatistique, France
| | | | | | - Thomas Aparicio
- Service de Gastroentérologie et Cancérologie Digestive, Hôpital Saint Louis, APHP, Université de Paris, Paris, France
| | | | | | | | - Axel Grothey
- West Cancer Center and Research Institute, Germantown, TN, USA
| | - Tetsuya Hamaguchi
- Department of Gastroenterological Oncology, Saitama Medical University International Medical Center, Saitama, Japan
| | - Timothy Iveson
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Rachel Kerr
- Adjuvant Colorectal Cancer Group, University of Oxford, UK
| | | | | | - Jeffrey Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
| | - James Paul
- Cancer Research UK Clinical Trials Unit (CTU), Institute of Cancer Sciences, University of Glasgow, UK
| | - Cornelis J A Punt
- Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Netherlands
| | - Leonard Saltz
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marck P Saunders
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Hans-Joachim Schmoll
- EORTC GI Study Group, AIO Colorectal Cancer Group, Martin Luther University, Halle, Germany
| | - Manish Shah
- Department of Medicine, Division of Hematology and Medical Oncology, Center for Advanced Digestive Care, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA
| | - Alberto Sobrero
- Medical Oncology Unit at Ospedale San Martino, Genova, Italy
| | | | - Julien Taieb
- Sorbonne Paris Cité, Paris Descartes University, Department of Digestive Oncology, Georges Pompidou European Hospital, Paris, France
| | | | - Anna Dorothea Wagner
- Department of Oncology, Lausanne University Hospital and University of Lausanne, Switzerland
| | - Marc Ychou
- Department of Medical Oncology, Institut Régional Du Cancer de Montpellier (ICM), France
| | - Franck Bonnetain
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, F-25000, Besançon, France; University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France
| | - Sophie Gourgou
- Biometrics Unit, Montpellier Cancer Institute, Univ Montpellier, Montpellier, France
| | | | | | - Aimery de Gramont
- Department of Medical Oncology, Institut Hospitalier Franco Britannique, Levallois-Perret, France
| | - Qian Shi
- Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
| | - Thierry André
- Sorbonne Université, Department of Medical Oncology, AP-HP, Hôpital Saint-Antoine, F-7512, Paris, France
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Sanford NN, Aguilera TA, Beg MS, Sanjeevaiah A, Hong TS, Wo JY, Folkert MR. Patterns of Care for Stage II-III Rectosigmoid Cancers in the United States, 2004-2015. Am J Clin Oncol 2020; 43:311-318. [DOI: 10.1097/coc.0000000000000674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Adjuvant Therapy for High-Risk Stage II or III Colon Adenocarcinoma: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study. Cancers (Basel) 2019; 11:cancers11122003. [PMID: 31842371 PMCID: PMC6966630 DOI: 10.3390/cancers11122003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 12/07/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose: To determine the optimal adjuvant chemotherapy regimen for patients with high-risk stage II or III colon adenocarcinoma, we conducted this propensity score-matched, nationwide, population-based cohort study to estimate the effects of adjuvant treatments in high-risk stage II or III colon adenocarcinoma. Patients and Methods: Using propensity score matching, we minimized the confounding effects of sex, age, pathologic stage, tumor location, total chemotherapy cycles, and Charlson comorbidity index scores on adjuvant treatment outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. We selected the patients from the Taiwan Cancer Registry database and divided them into four groups: Group 1, comprising patients who received surgery alone; group 2, comprising those who received adjuvant fluoropyrimidine alone; group 3, comprising those who received adjuvant oxaliplatin-fluoropyrimidine-leucovorin (FOLFOX); and group 4, comprising those who received adjuvant folinic acid-fluorouracil-irinotecan (FOLFIRI). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs, as well as the 95% confidence intervals (Cis)) for mortality observed for groups 1, 2, and 4 relative to group 3 were 1.55 (1.32 to 1.82), 1.22 (1.05 to 1.43), and 2.97 (2.43 to 3.63), respectively. After a stratified subgroup analysis for high-risk stage II colon adenocarcinoma, we noted that the aHR (95% CI) for mortality for group 2 relative to group 3 was 0.52 (0.30 to 0.89). Conclusions: Adjuvant fluoropyrimidine alone is the most optimal regimen for patients with high-risk stage II colon adenocarcinoma compared with the other adjuvant chemotherapy regimens. Adjuvant FOLFOX can serve as an optimal regimen for patients with pathologic stage III colon adenocarcinoma, regardless of age, sex, or tumor location.
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Jongeneel G, Klausch T, van Erning FN, Vink GR, Koopman M, Punt CJA, Greuter MJE, Coupé VMH. Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data. Int J Cancer 2019; 146:2968-2978. [PMID: 31424568 PMCID: PMC7187209 DOI: 10.1002/ijc.32629] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 07/22/2019] [Accepted: 07/24/2019] [Indexed: 11/29/2022]
Abstract
There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease‐free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real‐world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient‐level data from reported DFS data and (iii) estimating treatment effect in the patient‐level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient‐level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups. What's new? There is an ongoing discussion regarding the impact of adjuvant chemotherapy in stage II colon cancer. This study presents the most recent pooled estimate based on available RCT data since 1999, resulting in a pooled hazard ratio of 0.77 (95% CI 0.43;1.10) for fluoropyrimidine compared to no treatment. Even though no significant treatment effect was found, neither in the RCT approach nor in the real‐world data approach, the RCT data suggest a clinically‐relevant benefit of adjuvant chemotherapy. To improve guidance in treatment decisions, larger sample sizes, pooling of true patient‐level data with covariate information, and subgroup specific analyses are required.
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Affiliation(s)
- Gabrielle Jongeneel
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Thomas Klausch
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Felice N van Erning
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Geraldine R Vink
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands.,University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Miriam Koopman
- University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Cornelis J A Punt
- Department of medical oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marjolein J E Greuter
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University, Amsterdam, The Netherlands
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Gelibter AJ, Caponnetto S, Urbano F, Emiliani A, Scagnoli S, Sirgiovanni G, Napoli VM, Cortesi E. Adjuvant chemotherapy in resected colon cancer: When, how and how long? Surg Oncol 2019; 30:100-107. [PMID: 31500770 DOI: 10.1016/j.suronc.2019.06.003] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 02/11/2019] [Accepted: 06/21/2019] [Indexed: 12/13/2022]
Abstract
The benefit of adjuvant chemotherapy has been clearly established in the adjuvant setting for node-positive colon cancer. A number of trials in the adjuvant setting have analyzed the efficacy of multiple-agent combinations, including irinotecan, oxaliplatin, bevacizumab and cetuximab. Only oxaliplatin added to fluorouracil/capecitabine has been shown to be superior beyond a fluropyrimidine alone in the adjuvant setting. As such, standard treatment options include fluorouracil (FU) or capecitabine with or without oxaliplatin. However, oxaliplatin is associated with cumulative dose-dependent neurotoxicity, characterized by distal or perioral paresthesias or dysesthesias; for this reason, in this review we discuss the results of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) trial. The IDEA trail is the largest prospective clinical trial ever conducted in colorectal cancer, wherein patients were treated with either 3 months or 6 months of adjuvant chemotherapy. In the era of cancer gene expression-based subtyping, the Colorectal Cancer Subtyping Consortium has proposed a four-subgroup molecular classification system for colorectal cancer, consisting of CMS1 (immune), CMS2 (canonical), CMS3 (metabolic) and CMS4 (mesenchymal). In this review, we present and analyze the available data on efficacy and toxicity of the combination regimen approved for treatment of resected colon cancer, and discuss the questions of when, how and how long we need to treat such patients.
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Affiliation(s)
- Alain J Gelibter
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy.
| | - Salvatore Caponnetto
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
| | - Federica Urbano
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
| | - Alessandra Emiliani
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
| | - Simone Scagnoli
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
| | - Grazia Sirgiovanni
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
| | - Valerio M Napoli
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
| | - Enrico Cortesi
- Department of Radiology, Oncology and Pathology, Policlinico Umberto, I Sapienza University of Rome, Italy
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Karim S, Booth CM. Effectiveness in the Absence of Efficacy: Cautionary Tales From Real-World Evidence. J Clin Oncol 2019; 37:1047-1050. [DOI: 10.1200/jco.18.02105] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Lymphovascular Invasion and Perineural Invasion Negatively Impact Overall Survival for Stage II Adenocarcinoma of the Colon. Dis Colon Rectum 2019; 62:181-188. [PMID: 30640833 DOI: 10.1097/dcr.0000000000001258] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Lymphovascular invasion and perineural invasion are histopathological features associated with higher-risk colon cancer. OBJECTIVE The purpose of this study was to quantify the impact of lymphovascular and perineural invasion on overall survival after diagnosis and to determine the protective effect of adjuvant chemotherapy for early adenocarcinoma with high-risk factors. DESIGN This was a retrospective database review of the 2010-2014 National Cancer Database for colon cancer. SETTINGS Individuals diagnosed with invasive adenocarcinoma of the colon (histology code 8140) with primary surgical resection with >12 nodes harvested and no positive nodes on pathological examination were included. PATIENTS A total of 32,493 patients underwent surgical resection for stage II adenocarcinoma of the colon. INTERVENTIONS The study involved multivariate Cox regression analysis of the impact of lymphovascular and perineural invasion and adjuvant chemotherapy on overall survival after a diagnosis of stage II adenocarcinoma of the colon. MAIN OUTCOME MEASURES Survival after a diagnosis of stage II adenocarcinoma of the colon was measured. RESULTS Five-year survival after diagnosis and surgical resection without adjuvant chemotherapy was lower for patients with lymphovascular (60.0%), perineural (56.9%), and lymphovascular and perineural invasion (55.8%) compared with double-negative disease (66.1%). Log-rank testing confirmed that adjuvant chemotherapy improved 5-year survival after diagnosis for lymphovascular (85.5%), perineural (83.6%), and lymphovascular and perineural invasion (74.3%). After controlling for differences in cohorts, Cox regression analysis showed an increased HR for mortality of 14.0% for lymphovascular (HR = 1.141 (95% CI, 1.060-1.228)), 32.1% for perineural (HR = 1.321 (95% CI, 1.176-1.483)), and 41.0% for lymphovascular and perineural invasion (HR = 1.409 (95% CI, 1.231-1.612)) compared with having neither. Chemotherapy showed a 43% reduction in hazard for mortality (HR = 0.570 (95% CI, 0.513-0.633)). LIMITATIONS The study was limited by its retrospective review and observational bias. CONCLUSIONS Lymphovascular and perineural invasion have a detrimental effect on survival after diagnosis of stage II adenocarcinoma of the colon. Chemotherapy may be protective specifically when lymphovascular and perineural invasion are present. See Video Abstract at http://links.lww.com/DCR/A786.
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Sirinukunwattana K, Snead D, Epstein D, Aftab Z, Mujeeb I, Tsang YW, Cree I, Rajpoot N. Novel digital signatures of tissue phenotypes for predicting distant metastasis in colorectal cancer. Sci Rep 2018; 8:13692. [PMID: 30209315 PMCID: PMC6135776 DOI: 10.1038/s41598-018-31799-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 08/07/2018] [Indexed: 12/18/2022] Open
Abstract
Distant metastasis is the major cause of death in colorectal cancer (CRC). Patients at high risk of developing distant metastasis could benefit from appropriate adjuvant and follow-up treatments if stratified accurately at an early stage of the disease. Studies have increasingly recognized the role of diverse cellular components within the tumor microenvironment in the development and progression of CRC tumors. In this paper, we show that automated analysis of digitized images from locally advanced colorectal cancer tissue slides can provide estimate of risk of distant metastasis on the basis of novel tissue phenotypic signatures of the tumor microenvironment. Specifically, we determine what cell types are found in the vicinity of other cell types, and in what numbers, rather than concentrating exclusively on the cancerous cells. We then extract novel tissue phenotypic signatures using statistical measurements about tissue composition. Such signatures can underpin clinical decisions about the advisability of various types of adjuvant therapy.
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Affiliation(s)
| | - David Snead
- Department of Pathology, University Hospitals Coventry and Warwickshire, Coventry, UK
| | - David Epstein
- Mathematics Institute, University of Warwick, Coventry, UK
| | - Zia Aftab
- Hamad Medical Corporation, Doha, Qatar
| | | | - Yee Wah Tsang
- Department of Pathology, University Hospitals Coventry and Warwickshire, Coventry, UK
| | - Ian Cree
- International Agency for Research on Cancer, Lyon, France
| | - Nasir Rajpoot
- Department of Pathology, University Hospitals Coventry and Warwickshire, Coventry, UK.
- Department of Computer Science, University of Warwick, Coventry, UK.
- The Alan Turing Institute, London, UK.
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Yang Y, Yang Y, Yang H, Wang F, Wang H, Chen Q, Liu Y, Li A, Zhang Q. Adjuvant chemotherapy for stage II colon cancer: who really needs it. Cancer Manag Res 2018; 10:2509-2520. [PMID: 30123000 PMCID: PMC6087016 DOI: 10.2147/cmar.s160886] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background Although there is evidence that failure to reach the baseline of 12–13 lymph nodes in resected specimens is related to poor prognosis of patients with stage II colon cancer, and may be a marker of adjuvant therapy, the use of these markers remains controversial. The objective of this study was to determine the advantage of chemotherapy treatment in patients with stage II colon cancer on the basis of the number of lymph nodes examined in radical surgery. Patients and methods Using monitoring, epidemiology, and final outcome Medicare database, we authenticated 9,651 patients aged ≥66 years diagnosed with resected stage II colon cancer from 1999 to 2004. Medical insurance claims determined the adoption of chemotherapy within 3 months after radical operation. The relation between patient/tumor characteristics (including the number of lymph nodes examined) and the use of adjuvant chemotherapy was tested using chi-squared test and multiple logistic regression. Multivariate Cox model was used to compare survival rates between the treatment and untreated groups. Results Most patients (54.8%) had only 1–12 lymph nodes examined, while only 41.6% of the patients had >12 lymph nodes examined. Overall, 20.9% of patients received adjuvant chemotherapy; there was no relationship between chemotherapy and the number of lymph nodes examined (P=0.984). The presence of 12 or fewer lymph nodes in surgical specimens was related to poor overall survival (OS; adjusted hazard ratio [HR] 1.31, 95% CI 1.21–1.41). Although adjuvant chemotherapy was related to our cohort improvement, its beneficial effects on OS (HR: 0.73; 95% CI: 0.64–0.83) and disease-free survival (HR: 0.71; 95% CI: 0.60–0.85) only existed in patients with 0–12 lymph nodes examined. Conclusion The presence of 12 or fewer lymph nodes in surgical specimens is related to poor prognosis and survival benefit in adjuvant chemotherapy for stage II colon cancer patients. More attention should be paid to the implementation of recommendations for lymph node dissection to help identify patients who really benefit from adjuvant chemotherapy after colectomy.
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Affiliation(s)
- Yan Yang
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Yang Yang
- Department of Medicine, Medical University of South Carolina (MUSC), Charleston, SC, USA
| | - Hui Yang
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Fen Wang
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Huihui Wang
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Qi Chen
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Ying Liu
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Aiying Li
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
| | - Quanan Zhang
- Department of Oncology, the Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People's Republic of China,
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Babcock BD, Aljehani MA, Jabo B, Choi AH, Morgan JW, Selleck MJ, Luca F, Raskin E, Reeves ME, Garberoglio CA, Lum SS, Senthil M. High-Risk Stage II Colon Cancer: Not All Risks Are Created Equal. Ann Surg Oncol 2018; 25:1980-1985. [PMID: 29675762 DOI: 10.1245/s10434-018-6484-8] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Adjuvant chemotherapy is recommended in patients with stage II colon cancer with high-risk features (HRF). However, there is no quantification of the amount of risk conferred by each HRF or the overall survival (OS) benefit gained by chemotherapy based on the risk factor. OBJECTIVE To assess survival benefits associated with adjuvant chemotherapy among stage II colon cancer patients having one or more HRF [T4 tumors, less than 12 lymph nodes examined (< 12LN), positive margins, high-grade tumor, perineural invasion (PNI), and lymphovascular invasion (LVI)]. METHODS Patients diagnosed with stage II colon cancer between 2010 and 2013 were identified from California Cancer Registry. Propensity score weighted all-cause mortality hazard ratios (HR) were calculated for combinations of HRF. RESULTS A total of 5160 stage II colon cancer patients were identified, of which 2398 had at least one HRF and 510 of 2398 (21%) received adjuvant chemotherapy. Compared with patients with a single HRF, presence of any 2 or ≥ 3 HRF showed increasingly poorer survival [HR 1.42, 95% confidence interval (CI) 1.16-1.73 and HR 2.50, 95% CI 1.96-3.20, respectively]. Chemotherapy was associated with improved overall survival only among patients with T4 as the single HRF (HR 0.51, 95% CI 0.34-0.78) or combinations involving T4 as T4/< 12 LN (HR 0.31, 95% CI 0.11-0.90), T4/high grade (HR 0.26, 95% CI 0.11-0.61), and T4/LVI (HR 0.16, 95% CI 0.04-0.61). CONCLUSIONS Not all high-risk features have similar adverse effects on OS. T4 tumors and their combination with other HRF achieve the most survival benefit with adjuvant therapy. Type and number of high-risk features should be taken into consideration when recommending adjuvant chemotherapy in stage II colon cancer.
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Affiliation(s)
| | | | - Brice Jabo
- Loma Linda University Cancer Center, Loma Linda, CA, USA
| | - Audrey H Choi
- Loma Linda University Cancer Center, Loma Linda, CA, USA
| | - John W Morgan
- Loma Linda University Cancer Center, Loma Linda, CA, USA
| | | | - Fabrizio Luca
- Loma Linda University Cancer Center, Loma Linda, CA, USA
| | | | - Mark E Reeves
- Loma Linda University Cancer Center, Loma Linda, CA, USA
| | | | - Sharon S Lum
- Loma Linda University Cancer Center, Loma Linda, CA, USA
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Extramural Venous Invasion as Prognostic Factor of Recurrence in Stage 1 and 2 Colon Cancer. Gastroenterol Res Pract 2017; 2017:1598670. [PMID: 29317863 PMCID: PMC5727620 DOI: 10.1155/2017/1598670] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 09/26/2017] [Accepted: 10/22/2017] [Indexed: 12/18/2022] Open
Abstract
Aim Extramural venous invasion (EMVI) is a prognostic indicator in patients with colorectal cancer. However, its additional value in patients with stage 1 and 2 colorectal cancer is uncertain. In the present study, the incidence of EMVI and the hazard ratio for recurrence in patients with stage 1 and 2 colon cancer were studied. Methods 184 patients treated for stage 1 and 2 colon cancer were included with a follow-up of at least 5 years. Chart review was performed and EMVI was assessed by two separate pathologists. EMVI was scored with additional caldesmon staining on the resection specimen. Primary outcomes were recurrence-free survival (RFS) measured through the Cox regression analysis and prevalence of EMVI. Results There were 10 cases of EMVI and 3 cases of intramural venous invasion (IMVI) all occurring in patients with stage 2 disease corresponding to a prevalence of 9%. Thirty-one percent of the patients with venous invasion experienced recurrence versus 14% in patients without, corresponding with a hazard ratio of 2.39 (p = 0.11). Conclusion The present study demonstrates a trend towards an increased risk of recurrence in patients with stage 2 colon cancer with venous invasion. This warrants consideration of adjuvant chemotherapy despite the lack of lymph node metastases.
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Kim CG, Ahn JB, Shin SJ, Beom SH, Heo SJ, Park HS, Kim JH, Choe EA, Koom WS, Hur H, Min BS, Kim NK, Kim H, Kim C, Jung I, Jung M. Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery. BMC Cancer 2017; 17:615. [PMID: 28865435 PMCID: PMC5581409 DOI: 10.1186/s12885-017-3624-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 08/28/2017] [Indexed: 12/19/2022] Open
Abstract
Background We aimed to explore the clinical benefit of adjuvant chemotherapy (AC) with fluoropyrimidine in patients with ypT0-3N0 rectal cancer after preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME). Methods Patients with ypT0-3N0 rectal cancer after preoperative CRT and TME were included using prospectively collected tumor registry cohort between January 2001 and December 2013. Patients were categorized into two groups according to the receipt of AC. Disease-free survival (DFS) and overall survival (OS) were compared between the adjuvant and observation groups. To control for potential confounding factors, we also calculated propensity scores and performed propensity score-matched analysis for DFS and OS. Results Of the 339 evaluated patients, 87 patients (25.7%) did not receive AC. There were no differences in DFS (hazard ratio [HR], 0.921; 95% confidence interval [CI], 0.562–1.507; P = 0.742) and OS (HR, 0.835; 95% CI, 0.423–1.648; P = 0.603) between the adjuvant and observation groups. After propensity score matching, DFS (HR, 1.129; 95% CI, 0.626–2.035; P = 0.688) and OS (HR, 1.200; 95% CI, 0.539–2.669; P = 0.655) did not differ between the adjuvant and observation groups. Advanced T stage and positive resection margin were independently associated with inferior DFS and OS on multivariate analysis. Conclusions AC did not improve DFS and OS for patients with ypT0-3N0 rectal cancer after preoperative CRT followed by TME in this cohort study. The confirmative role of AC in locally advanced rectal cancer should be evaluated in prospective randomized trials with a larger sample size. Electronic supplementary material The online version of this article (10.1186/s12885-017-3624-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chang Gon Kim
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.,Graduate School of Medical Science and Engineering, KAIST, Daejeon, South Korea
| | - Joong Bae Ahn
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Sang Joon Shin
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Seung Hoon Beom
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Su Jin Heo
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Hyung Soon Park
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Jee Hung Kim
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Eun Ah Choe
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Seoul, South Korea
| | - Hyuk Hur
- Department of Surgery, Yonsei Cancer Center, Seoul, South Korea
| | - Byung Soh Min
- Department of Surgery, Yonsei Cancer Center, Seoul, South Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei Cancer Center, Seoul, South Korea
| | - Hoguen Kim
- Department of Pathology, Yonsei Cancer Center, Seoul, South Korea
| | - Chan Kim
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, Seongnam, South Korea
| | - Inkyung Jung
- Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
| | - Minkyu Jung
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
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Santullo F, Biondi A, Cananzi FCM, Fico V, Tirelli F, Ricci R, Rizzo G, Coco C, Mattana C, D'Ugo D, Persiani R. Tumor size as a prognostic factor in patients with stage IIa colon cancer. Am J Surg 2017; 215:71-77. [PMID: 28410630 DOI: 10.1016/j.amjsurg.2017.03.038] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 03/01/2017] [Accepted: 03/21/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND The aim of this study was to identify stage II colon cancer patients with a high risk of recurrence. METHODS All patients who underwent surgery for stage II colon cancer (CC) were retrospectively enrolled and sub-grouped according to TNM staging (IIa-b-c) and stage IIa in high (IIaHR) and low risk (IIaLR) according to pathologic features. The primary outcomes measured were the 5-year overall survival (OS) and disease-free survival (DFS). RESULTS A total of 214 patients were reviewed. Only a maximum tumor diameter<4 cm in the IIaLR group was associated with a higher recurrence rate than a large tumor size (5-year DFS 71.7%vs.87.6%, p = 0.028). The DFS in the large IIaLR CC group was better than that in the IIaHR and IIb-c groups (5-year DFS: 92.7%vs.79.3%, p = 0.023). In contrast, the recurrence rate in the small IIaLR CC group was similar to that in the IIaHR, IIb-c stage CC group. CONCLUSIONS In stage IIa CC evaluation of the tumor size as a prognostic factor may help identify patients who could benefit from additional postoperative therapy.
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Affiliation(s)
- Francesco Santullo
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Alberto Biondi
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | | | - Valeria Fico
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Flavio Tirelli
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Riccardo Ricci
- Department of Pathology, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Gianluca Rizzo
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Claudio Coco
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Claudio Mattana
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Domenico D'Ugo
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
| | - Roberto Persiani
- General Surgery Unit, Department of Surgery, "A. Gemelli" University Hospital, Catholic University of Rome, Rome, Italy.
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Ejaz A, Casadaban L, Maker AV. Utilization and impact of adjuvant chemotherapy among patients with resected stage II colon cancer: a multi-institutional analysis. J Surg Res 2017; 215:12-20. [PMID: 28688636 DOI: 10.1016/j.jss.2017.03.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/05/2017] [Accepted: 03/23/2017] [Indexed: 01/23/2023]
Abstract
BACKGROUND The use of chemotherapy among patients with stage II colon cancer is controversial. We aimed to define the utilization and factors associated with the receipt of chemotherapy and the impact of chemotherapy on long-term prognosis among a large, multiinstitutional cohort of patients. MATERIALS AND METHODS We identified 876 patients who underwent resection for stage II colon cancer between 2004 and 2013 at one of seven participating institutions. Overall survival (OS) and recurrence-free survival (RFS) time was calculated from the date of the index procedure to the date of death. RESULTS A total of 163 patients (18.6%) received adjuvant chemotherapy and this utilization decreased over time (P = 0.003). Younger age (P < 0.001), margin positivity (odds ratio [OR], 12.16; 95% confidence interval [CI]: 2.57-57.52; P = 0.002), and the presence of perineural invasion (OR, 1.24; 95% CI: 1.07-1.44; P = 0.005) increased the likelihood of receiving chemotherapy. Receipt of chemotherapy was associated with improved median OS and RFS. After controlling for all factors, the addition of oxaliplatin to 5-fluorouracil did not affect survival, and there was no difference in OS (hazard ratio [HR], 0.74; 95% CI: 0.27-2.06; P = 0.57) or RFS (HR, 0.71; 95% CI: 0.32-1.58; P = 0.88) with adjuvant treatment, including for patients with high-risk features (OS-HR, 0.63; 95% CI: 0.33-1.19; P = 0.15; RFS-HR, 0.77; 95% CI: 0.32-1.86; P = 0.56). CONCLUSIONS The utilization of chemotherapy has declined over time after resection for stage II colon cancer. Chemotherapy was not independently associated with improved OS or RFS in this study group, including in patients with high-risk features. Future prospective studies should strive to identify the subset of stage II colon cancer patients that will benefit the most from the addition of adjuvant chemotherapy.
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Affiliation(s)
- Aslam Ejaz
- Division of Surgical Oncology, Department of Surgery, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Leigh Casadaban
- Division of Surgical Oncology, Department of Surgery, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Creticos Cancer Center at Advocate Illinois Masonic Medical Center, Chicago, Illinois
| | - Ajay V Maker
- Division of Surgical Oncology, Department of Surgery, University of Illinois Hospital and Health Sciences System, Chicago, Illinois; Creticos Cancer Center at Advocate Illinois Masonic Medical Center, Chicago, Illinois.
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47
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Meyers BM, Cosby R, Quereshy F, Jonker D. Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline. ACTA ACUST UNITED AC 2016; 23:418-424. [PMID: 28050138 DOI: 10.3747/co.23.3330] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario's Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. METHODS Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. RESULTS Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. CONCLUSIONS Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)-based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without "high-risk" features should not receive adjuvant chemotherapy. For patients with "high-risk" features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.
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Affiliation(s)
- B M Meyers
- Juravinski Cancer Centre, Department of Oncology, McMaster University, Hamilton, ON
| | - R Cosby
- Program in Evidence-Based Care, Department of Oncology, McMaster University, Juravinski Campus, Hamilton, ON
| | | | - D Jonker
- The Ottawa Hospital Cancer Centre, Ottawa, ON
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Lee LH, Sadot E, Ivelja S, Vakiani E, Hechtman JF, Sevinsky CJ, Klimstra DS, Ginty F, Shia J. ARID1A expression in early stage colorectal adenocarcinoma: an exploration of its prognostic significance. Hum Pathol 2016; 53:97-104. [PMID: 26980037 PMCID: PMC4994515 DOI: 10.1016/j.humpath.2016.02.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 01/23/2016] [Accepted: 02/04/2016] [Indexed: 02/07/2023]
Abstract
ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent. Major limitations of some outcome studies include small sample size and heterogeneous patient population. In this study, we evaluated the prognostic value of ARID1A in a homogeneous group of early stage CRC patients, a population where prognostic markers are particularly relevant. We collected a retrospective series of 578 stage I or II CRCs. All patients underwent surgery with curative intent and without neoadjuvant or adjuvant therapy. ARID1A expression was analyzed by immunohistochemistry using tissue microarray. We found ARID1A loss in 49 of 552 analyzable tumors (8.9%). Compared with the ARID1A-retained group, cases with ARID1A loss were associated with female sex (P<.001), mismatch-repair protein deficiency (P<.001), poor differentiation (P<.001), lymphovascular invasion (P=.001), and higher pT stage (P=.047). However, at a median follow-up of 49months, ARID1A loss did not correlate with overall, disease-specific, or recurrence-free survival. This is the first systematic analysis to evaluate the prognostic significance of ARID1A in stage I/II CRCs, and our data indicate that ARID1A loss lacks prognostic significance in this population despite its association with other adverse features. Such data are clinically relevant, as efforts are ongoing in identifying markers that can detect the small but significant subset of early stage CRCs that will have a poor outcome.
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Affiliation(s)
- Lik Hang Lee
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
| | - Eran Sadot
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
| | - Sinisa Ivelja
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
| | - Jaclyn F Hechtman
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
| | - Christopher J Sevinsky
- Life Sciences & Molecular Diagnostics, GE Global Research, General Electric Company, 1 Research Circle, Niskayuna, NY, 12309.
| | - David S Klimstra
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
| | - Fiona Ginty
- Life Sciences & Molecular Diagnostics, GE Global Research, General Electric Company, 1 Research Circle, Niskayuna, NY, 12309.
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065.
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Kwon HY, Kim IK, Kang J, Sohn SK, Lee KY. In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer. Cancer Res Treat 2016; 48:970-977. [PMID: 26511802 PMCID: PMC4946364 DOI: 10.4143/crt.2015.140] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 09/30/2015] [Indexed: 12/20/2022] Open
Abstract
PURPOSE We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. MATERIALS AND METHODS Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. RESULTS Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. CONCLUSION In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy.
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Affiliation(s)
- Hye Youn Kwon
- Department of Surgery, Sahmyook Medical Center, Seoul, Korea
| | - Im-kyung Kim
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jeonghyun Kang
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Kook Sohn
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kang Young Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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50
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Eheman CR, O’Neil ME, Styles TS, Thompson TD, Morris CR, Babcock FA, Chen VW. Use of Adjuvant Chemotherapy among Stage II Colon Cancer Patients in 10 Population-Based National Program of Cancer Registries. JOURNAL OF REGISTRY MANAGEMENT 2016; 43:179-186. [PMID: 29308117 PMCID: PMC5752107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
BACKGROUND Some guidelines advise adjuvant chemotherapy be considered after surgical resection for high-risk stage II colon cancer patients; however, high-risk criteria are poorly defined and the long-term benefits are still debated. This study documents patterns of care by selected patient and tumor characteristics using a US population-based cohort of stage II colon cancer patients diagnosed in 2011. METHODS Data were collected from 10 specialized cancer registries participating in the Centers for Disease Control and Prevention's National Program of Cancer Registries' Enhancing Cancer Registry Data for Comparative Effectiveness Research project. The data were used to describe characteristics of stage II colon cancer patients treated by surgery to evaluate factors associated with receiving adjuvant chemotherapy. RESULTS Of the 3,891 stage II colon cancer patients, 14.3% were treated with surgery and adjuvant chemotherapy compared to 82.9% by surgery alone. The patients treated with adjuvant chemotherapy were predominately non-Hispanic white (66.1%), of younger age, and had private insurance (39.9%). Compared to surgery alone, the 5 characteristics associated with adjuvant therapy were younger age (adjusted odds ratio [AOR] for 5-year decrease below 75 years, 1.25; P < .001); more advanced stage (IIB/IIC vs IIA) (AOR, 4.79; P < .001); lymphovascular invasion (AOR, 1.76, P < .001); higher grade (III/IV vs I/II) (AOR, 1.84; P < .001); and registry area. CONCLUSIONS In this population-based cohort, younger patients with more advanced stage II colon tumors, with lymphovascular invasion, and poor differentiation were more likely to receive adjuvant chemotherapy in addition to surgery. These characteristics align with high-risk profiles defined in guidelines. Ongoing data collection on outcomes, including recurrence and survival, will help clarify the benefits of adjuvant treatments for stage II colon patients.
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Affiliation(s)
- Christie R. Eheman
- Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Mary Elizabeth O’Neil
- Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Timothy S. Styles
- Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Trevor D. Thompson
- Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Cyllene R. Morris
- California Cancer Reporting and Epidemiologic Surveillance (CalCARES) Program, IPHI, UC Davis Health System, Sacramento, California
| | - Frances A. Babcock
- Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Vivien W. Chen
- Louisiana Tumor Registry and Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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