BRAF V600E変異陽性進行再発大腸癌の治療成績から考える転移巣切除の至適適応
目的：BRAF V600E変異陽性進行再発大腸癌は薬物療法の効果が乏しく極めて予後不良で，転移巣が切除可能でも切除すべきか否かの判断が難しい．BRAF変異大腸癌の治療成績から切除可能転移巣の手術適応について後ろ向きに検討した．方法：2016年から2020年に治療を開始したBRAF変異大腸癌14例を対象とした．一次治療の初回画像効果判定で，腫瘍がベースラインより縮小または不変の症例をcontrolled disease（以下，CDと略記）群（n=8），増大した症例をuncontrolled disease（以下，UDと略記）群（n=6）に分類し比較検討した．結果：経過観察期間中央値は39.7か月...
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| Published in | 日本消化器外科学会雑誌 Vol. 55; no. 8; pp. 473 - 482 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本消化器外科学会
01.08.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0386-9768 1348-9372 |
| DOI | 10.5833/jjgs.2021.0129 |
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| Abstract | 目的：BRAF V600E変異陽性進行再発大腸癌は薬物療法の効果が乏しく極めて予後不良で，転移巣が切除可能でも切除すべきか否かの判断が難しい．BRAF変異大腸癌の治療成績から切除可能転移巣の手術適応について後ろ向きに検討した．方法：2016年から2020年に治療を開始したBRAF変異大腸癌14例を対象とした．一次治療の初回画像効果判定で，腫瘍がベースラインより縮小または不変の症例をcontrolled disease（以下，CDと略記）群（n=8），増大した症例をuncontrolled disease（以下，UDと略記）群（n=6）に分類し比較検討した．結果：経過観察期間中央値は39.7か月であった．全体の2年全生存率は35.7%で，CD群およびUD群ではそれぞれ50.0%および16.7%であった（P=0.051）．転移巣根治切除を6例（42.9%）に施行し，4例で再発を来したが，1例は再転移巣切除を施行した．CD群では転移巣切除を行った3例中2例が無担癌生存中であるが，UD群の3例は全例で術後再発を来し，2例が術後3か月以内の早期再発であった．結語：BRAF変異大腸癌の予後予測因子として一次治療での初回病勢コントロール評価が有用である可能性が示唆された．たとえ切除可能であっても，一次治療での病勢コントロール不良例に対する転移巣切除の適応は慎重に考慮すべきである． |
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| AbstractList | 目的：BRAF V600E変異陽性進行再発大腸癌は薬物療法の効果が乏しく極めて予後不良で，転移巣が切除可能でも切除すべきか否かの判断が難しい．BRAF変異大腸癌の治療成績から切除可能転移巣の手術適応について後ろ向きに検討した．方法：2016年から2020年に治療を開始したBRAF変異大腸癌14例を対象とした．一次治療の初回画像効果判定で，腫瘍がベースラインより縮小または不変の症例をcontrolled disease（以下，CDと略記）群（n=8），増大した症例をuncontrolled disease（以下，UDと略記）群（n=6）に分類し比較検討した．結果：経過観察期間中央値は39.7か月であった．全体の2年全生存率は35.7%で，CD群およびUD群ではそれぞれ50.0%および16.7%であった（P=0.051）．転移巣根治切除を6例（42.9%）に施行し，4例で再発を来したが，1例は再転移巣切除を施行した．CD群では転移巣切除を行った3例中2例が無担癌生存中であるが，UD群の3例は全例で術後再発を来し，2例が術後3か月以内の早期再発であった．結語：BRAF変異大腸癌の予後予測因子として一次治療での初回病勢コントロール評価が有用である可能性が示唆された．たとえ切除可能であっても，一次治療での病勢コントロール不良例に対する転移巣切除の適応は慎重に考慮すべきである． |
| Author | 横山, 幸浩 水野, 隆史 小倉, 淳司 村田, 悠記 伊神, 剛 山口, 淳平 神野, 孝徳 國料, 俊男 江畑, 智希 上原, 圭 |
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Clin Cancer Res. 2017 Jan;23(1):104–115. 20) Bachet JB, Moreno-Lopez N, Vigano L, Marchese U, Gelli M, Raoux L, et al. BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases. Br J Surg. 2019 Aug;106(9):1237–1247. 12) Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007 Jul;370(9582):143–152. 7) Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, et al. Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020 Jan;25(1):1–42. 22) Medina BD, Choi BH, Rodogiannis KG, Moran U, Shapiro RL, Pavlick A, et al. 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FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306–1315. 1) Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015 Jun;33(16):1809–1824. 5) Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009 Jul;361(1):98–99. 4) Tie J, Gibbs P, Lipton L, Christie M, Jorissen RN, Burgess AW, et al. Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer. 2011 May;128(9):2075–2084. 11) Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May;29(15):2011–2019. 8) Schirripa M, Bergamo F, Cremolini C, Casagrande M, Lonardi S, Aprile G, et al. BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection. Br J Cancer. 2015 Jun;112(12):1921–1928. 2) Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun;417(6892):949–954. 19) Margonis GA, Buettner S, Andreatos N, Kim Y, Wagner D, Sasaki K, et al. Association of BRAF mutations with survival and recurrence in surgically treated patients with metastatic colorectal liver cancer. JAMA Surg. 2018 Jul;153(7):e180996. 16) Seppälä TT, Böhm JP, Friman M, Lahtinen L, Väyrynen VM, Liipo TK, et al. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer. Br J Cancer. 2015 Jun;112(12):1966–1975. 9) Gagnière J, Dupré A, Gholami SS, Pezet D, Boerner T, Gönen M, et al. Is hepatectomy justified for BRAF mutant colorectal liver metastases?: a multi-institutional analysis of 1497 patients. Ann Surg. 2020 Jan;271(1):147–154. 13) Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011 Jun;377(9783):2103–2114. 21) Kobayashi S, Takahashi S, Takahashi N, Masuishi T, Shoji H, Shinozaki E, et al. Survival outcomes of resected BRAF V600E mutant colorectal liver metastases: a multicenter retrospective cohort study in Japan. Ann Surg Oncol. 2020 Sep;27(9):3307–3315. |
| References_xml | – reference: 14) Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011 Jul;12(7):642–653. – reference: 11) Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May;29(15):2011–2019. – reference: 13) Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011 Jun;377(9783):2103–2114. – reference: 20) Bachet JB, Moreno-Lopez N, Vigano L, Marchese U, Gelli M, Raoux L, et al. BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases. Br J Surg. 2019 Aug;106(9):1237–1247. – reference: 8) Schirripa M, Bergamo F, Cremolini C, Casagrande M, Lonardi S, Aprile G, et al. BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection. Br J Cancer. 2015 Jun;112(12):1921–1928. – reference: 24) Barras D, Missiaglia E, Wirapati P, Sieber OM, Jorissen RN, Love C, et al. BRAF V600E mutant colorectal cancer subtypes based on gene expression. Clin Cancer Res. 2017 Jan;23(1):104–115. – reference: 5) Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009 Jul;361(1):98–99. – reference: 1) Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015 Jun;33(16):1809–1824. – reference: 21) Kobayashi S, Takahashi S, Takahashi N, Masuishi T, Shoji H, Shinozaki E, et al. Survival outcomes of resected BRAF V600E mutant colorectal liver metastases: a multicenter retrospective cohort study in Japan. Ann Surg Oncol. 2020 Sep;27(9):3307–3315. – reference: 22) Medina BD, Choi BH, Rodogiannis KG, Moran U, Shapiro RL, Pavlick A, et al. Metastasectomy for melanoma is associated with improved overall survival in responders to targeted molecular or immunotherapy. J Surg Oncol. 2020 Sep;122(3):555–561. – reference: 10) Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306–1315. – reference: 16) Seppälä TT, Böhm JP, Friman M, Lahtinen L, Väyrynen VM, Liipo TK, et al. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer. Br J Cancer. 2015 Jun;112(12):1966–1975. – reference: 4) Tie J, Gibbs P, Lipton L, Christie M, Jorissen RN, Burgess AW, et al. Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer. 2011 May;128(9):2075–2084. – reference: 17) André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020 Dec;383(23):2207–2218. – reference: 7) Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, et al. Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020 Jan;25(1):1–42. – reference: 9) Gagnière J, Dupré A, Gholami SS, Pezet D, Boerner T, Gönen M, et al. Is hepatectomy justified for BRAF mutant colorectal liver metastases?: a multi-institutional analysis of 1497 patients. Ann Surg. 2020 Jan;271(1):147–154. – reference: 12) Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007 Jul;370(9582):143–152. – reference: 23) Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350–1356. – reference: 2) Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun;417(6892):949–954. – reference: 19) Margonis GA, Buettner S, Andreatos N, Kim Y, Wagner D, Sasaki K, et al. Association of BRAF mutations with survival and recurrence in surgically treated patients with metastatic colorectal liver cancer. JAMA Surg. 2018 Jul;153(7):e180996. – reference: 15) Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019 Oct;381(17):1632–1643. – reference: 3) Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, et al. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 2011 Mar;104(5):856–862. – reference: 18) Adam R, Wicherts DA, de Haas RJ, Ciacio O, Lévi F, Paule B, et al. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol. 2009 Apr;27(11):1829–1835. – reference: 6) Tran B, Kopetz S, Tie J, Gibbs P, Jiang ZQ, Lieu CH, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011 Oct;117(20):4623–4632. |
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| Snippet | 目的：BRAF V600E変異陽性進行再発大腸癌は薬物療法の効果が乏しく極めて予後不良で，転移巣が切除可能でも切除すべきか否かの判断が難しい．BRAF変異大腸癌の治療成... |
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| SubjectTerms | BRAF V600E変異 手術適応 転移巣切除 進行再発大腸癌 |
| Title | BRAF V600E変異陽性進行再発大腸癌の治療成績から考える転移巣切除の至適適応 |
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| ispartofPNX | 日本消化器外科学会雑誌, 2022/08/01, Vol.55(8), pp.473-482 |
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