Journal of Yeungnam Medical Science

영남대 의대 학술지 편집위원회 (Yeungnam University College of Medicine, Yeungnam University Institute Medical Science)
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Clinical implication of adjuvant chemotherapy according to mismatch repair status in patients with intermediate-risk stage II colon cancer: a retrospective study

  • Kang, Byung Woog (Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University Cancer Research Institute, School of Medicine, Kyungpook National University) ;
  • Baek, Dong Won (Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University Cancer Research Institute, School of Medicine, Kyungpook National University) ;
  • Chang, Eunhye (Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Kim, Hye Jin (Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Park, Su Yeon (Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Park, Jun Seok (Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Choi, Gyu Seog (Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Baek, Jin Ho (Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University Cancer Research Institute, School of Medicine, Kyungpook National University) ;
  • Kim, Jong Gwang (Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University Cancer Research Institute, School of Medicine, Kyungpook National University)
  • 투고 : 2021.10.20
  • 심사 : 2021.11.20
  • 발행 : 2022.04.30
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초록

Background: The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC). Methods: This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria: (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study. Results: Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR. Conclusion: The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.

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참고문헌

  1. Des Guetz G, Uzzan B, Morere JF, Perret G, Nicolas P. Duration of adjuvant chemotherapy for patients with non-metastatic colorectal cancer. Cochrane Database Syst Rev 2010;(1):CD007046.
  2. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343-51. https://doi.org/10.1056/NEJMoa032709
  3. Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004;22:3408-19. https://doi.org/10.1200/JCO.2004.05.063
  4. Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, Hamilton SR, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000;124:979-94. https://doi.org/10.5858/2000-124-0979-PFICC
  5. Andre T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC Study. J Clin Oncol 2015;33:4176-87. https://doi.org/10.1200/JCO.2015.63.4238
  6. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, et al. Colon cancer, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021;19:329-59. https://doi.org/10.6004/jnccn.2021.0012
  7. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993;260:816-9. https://doi.org/10.1126/science.8484122
  8. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 2009;361:2449-60. https://doi.org/10.1056/NEJMra0804588
  9. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010;28:3219-26. https://doi.org/10.1200/JCO.2009.27.1825
  10. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247-57. https://doi.org/10.1056/NEJMoa022289
  11. Klingbiel D, Saridaki Z, Roth AD, Bosman FT, Delorenzi M, Tejpar S. Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Ann Oncol 2015;26:126-32. https://doi.org/10.1093/annonc/mdu499
  12. Argiles G, Tabernero J, Labianca R, Hochhauser D, Salazar R, Iveson T, et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020;31:1291-305. https://doi.org/10.1016/j.annonc.2020.06.022
  13. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-4. https://doi.org/10.1245/s10434-010-0985-4
  14. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696-704. https://doi.org/10.1056/NEJMoa043116
  15. Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011;29:1465-71. https://doi.org/10.1200/JCO.2010.33.6297
  16. Haller DG, Catalano PJ, Macdonald JS, O'Rourke MA, Frontiera MS, Jackson DV, et al. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol 2005;23:8671-8. https://doi.org/10.1200/JCO.2004.00.5686
  17. Andre T, Sargent D, Tabernero J, O'Connell M, Buyse M, Sobrero A, et al. Current issues in adjuvant treatment of stage II colon cancer. Ann Surg Oncol 2006;13:887-98. https://doi.org/10.1245/ASO.2006.07.003
  18. de Gramont A, de Gramont A, Chibaudel B, Larsen AK, Tournigand C, Andre T, et al. The evolution of adjuvant therapy in the treatment of early-stage colon cancer. Clin Colorectal Cancer 2011;10:218-26. https://doi.org/10.1016/j.clcc.2011.10.001
  19. Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002;20:1043-8. https://doi.org/10.1200/JCO.20.4.1043
  20. Chakrabarti S, Peterson CY, Sriram D, Mahipal A. Early stage colon cancer: current treatment standards, evolving paradigms, and future directions. World J Gastrointest Oncol 2020;12:808-32. https://doi.org/10.4251/wjgo.v12.i8.808
  21. Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol 2015;33:1787-96. https://doi.org/10.1200/JCO.2014.60.0213
  22. Varghese A. Chemotherapy for stage II colon cancer. Clin Colon Rectal Surg 2015;28:256-61. https://doi.org/10.1055/s-0035-1564430
  23. Rebuzzi SE, Pesola G, Martelli V, Sobrero AF. Adjuvant chemotherapy for stage II colon cancer. Cancers (Basel) 2020;12:2584. https://doi.org/10.3390/cancers12092584
  24. Tournigand C, Andre T, Bonnetain F, Chibaudel B, Lledo G, Hickish T, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol 2012;30:3353-60. https://doi.org/10.1200/JCO.2012.42.5645
  25. Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 2011;29:3768-74. https://doi.org/10.1200/JCO.2011.36.4539
  26. Bertagnolli MM, Redston M, Compton CC, Niedzwiecki D, Mayer RJ, Goldberg RM, et al. Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer: a study of CALGB 9581 and 89803. J Clin Oncol 2011;29:3153-62. https://doi.org/10.1200/JCO.2010.33.0092
  27. Hutchins G, Southward K, Handley K, Magill L, Beaumont C, Stahlschmidt J, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011;29:1261-70. https://doi.org/10.1200/JCO.2010.30.1366