So sánh các phác đồ hóa trị hệ thống neoadjuvant trong quản lý mục đích chữa trị di căn phúc mạc từ ung thư đại trực tràng, liên quan đến phản ứng hình thái, phản ứng bệnh lý và kết quả lâu dài: Một nghiên cứu hồi cứu

Annals of Surgical Oncology - Tập 30 - Trang 3304-3315 - 2023
Florian Fanget1,2, Amaniel Kefleyesus1,3, Julien Peron4, Isabelle Bonnefoy2, Laurent Villeneuve2, Guillaume Passot1,2, Pascal Rousset2,5, Benoit You2,4, Nazim Benzerdjeb2,6, Olivier Glehen1,2, Vahan Kepenekian1,2
1Surgical Oncology Department, Service de Chirurgie Digestive et Oncologique, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
2EA3738 CICLY, Université Claude Bernard Lyon 1 (UCBL1), Villeurbanne, France
3Department of Visceral Surgery, CHUV, Lausanne University Hospital, Lausanne, Switzerland
4Medical Oncology Department, Laboratoire de Biométrie et Biologie Evolutive, Université Claude Bernard Lyon I (UCBL1), Hôpital Lyon Sud, Hospices Civils de Lyon, Equipe Biostatistique-Santé, Lyon, France
5Department of Radiology, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre Bénite, France
6Department of Pathology, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre Bénite, France

Tóm tắt

Các bệnh nhân được lựa chọn có di căn phúc mạc do ung thư đại trực tràng (CRPM) có thể được cung cấp một chiến lược nhằm mục đích chữa trị dựa trên phẫu thuật cắt bỏ triệt để hoàn toàn (CRS), có thể kết hợp với hóa trị nhiệt trong ổ bụng (HIPEC) và hóa trị toàn thân trong quá trình phẫu thuật. Ảnh hưởng của các phác đồ hóa trị toàn thân neoadjuvant (NACT) khác nhau vẫn chưa rõ do thiếu dữ liệu so sánh. Bệnh nhân CRPM liên tục từ một cơ sở dữ liệu đơn trung tâm được điều trị bằng phẫu thuật CRS hoàn toàn sau NACT một dòng được đưa vào nghiên cứu này. Các phác đồ hóa trị được điều chỉnh thành phác đồ đôi (FOLFOX/FOLFIRI) với/không có liệu pháp nhắm mục tiêu (kháng thể chống thụ thể yếu tố tăng trưởng biểu bì/bevacizumab) và tổ hợp ba loại thuốc (FOLFIRINOX). Phản ứng hình thái (MR) được đánh giá theo tiêu chí Đánh giá Phản ứng trong Khối u rắn, và phản ứng bệnh lý (PR) được đánh giá theo Điểm phân loại thoái triển phúc mạc (PRGS). Kết quả ung thư lâu dài được so sánh. Nhóm nghiên cứu gồm 388 bệnh nhân, bao gồm 127, 202 và 59 bệnh nhân trong nhóm đôi, nhóm đôi + nhắm mục tiêu và nhóm ba, tương ứng. Tỷ lệ MR cao hơn ở nhóm ba (68,0%) và nhóm đôi + nhắm mục tiêu (64,2%) so với nhóm đôi (42,4%, p = 0,003). Phản ứng PR hoàn toàn và quan trọng được quan sát ở 13,6% và 32,0% bệnh nhân, tương ứng. Tỷ lệ MR cao hơn được quan sát sau các phác đồ đôi + nhắm mục tiêu hoặc ba, trong khi không có sự khác biệt nào được quan sát cho tỷ lệ PR. Trong phân tích đa biến, FOLFIRINOX có liên quan độc lập với tỷ lệ sống sót tổng thể tốt hơn (tỷ lệ nguy cơ 0,49, khoảng tin cậy 95% 0,25–0,96; p = 0,037). FOLFIRINOX cũng dẫn đến tỷ lệ biến chứng nghiêm trọng sau phẫu thuật cao hơn. Trong nghiên cứu hồi cứu này, phác đồ FOLFIRINOX như NACT dường như dẫn đến kết quả lâu dài tốt hơn cho bệnh nhân CRPM sau CRS/HIPEC hoàn toàn, mặc dù đi kèm với tỷ lệ bệnh tật cao hơn. Cần có các nghiên cứu tiềm năng, bao gồm nhóm không có NACT và những người có FOLFIRINOX + bevacizumab.

Từ khóa

#di căn phúc mạc #ung thư đại trực tràng #hóa trị neoadjuvant #phẫu thuật cắt bỏ triệt để #phản ứng hình thái #phản ứng bệnh lý #kết quả lâu dài

Tài liệu tham khảo

Franko J, Shi Q, Meyers JP, et al. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016;17(12):1709–19. https://doi.org/10.1016/s1470-2045(16)30500-9. Yan TD, Black D, Savady R, Sugarbaker PH. Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J Clin Oncol. 2006;24(24):4011–9. https://doi.org/10.1200/jco.2006.07.1142. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16. https://doi.org/10.1016/s0140-6736(08)60455-9. Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28(1):63–8. https://doi.org/10.1200/jco.2009.23.9285. Goere D, Malka D, Tzanis D, et al. Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg. 2013;257(6):1065–71. https://doi.org/10.1097/sla.0b013e31827e9289. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80. https://doi.org/10.1200/jco.2007.11.0833. Ceelen W, Nieuwenhove YV, Putte DV, Pattyn P. Neoadjuvant chemotherapy with bevacizumab may improve outcome after cytoreduction and hyperthermic intraperitoneal chemoperfusion (HIPEC) for colorectal carcinomatosis. Ann Surg Oncol. 2014;21(9):3023–8. https://doi.org/10.1245/s10434-014-3713-7. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42. https://doi.org/10.1056/nejmoa032691. Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18. https://doi.org/10.1056/nejmoa1403108. Cremolini C, Antoniotti C, Stein A, et al. Individual patient data meta-analysis of FOLFOXIRI plus bevacizumab versus doublets plus bevacizumab as initial therapy of unresectable metastatic colorectal cancer. J Clin Oncol. 2020;38(28):JCO2001225. https://doi.org/10.1200/jco.20.01225. Rossini D, Antoniotti C, Lonardi S, et al. Upfront modified fluorouracil, leucovorin, oxaliplatin, and irinotecan plus panitumumab versus fluorouracil, leucovorin, and oxaliplatin plus panitumumab for patients with RAS/BRAF wild-type metastatic colorectal cancer: the Phase III TRIPLETE study by GONO. J Clin Oncol. 2022;40(25):2878–88. https://doi.org/10.1200/jco.22.00839. Quenet F, Elias D, Roca L, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256–66. https://doi.org/10.1016/s1470-2045(20)30599-4. Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681–5. https://doi.org/10.1200/jco.2008.19.7160. Passot G, You B, Boschetti G, et al. Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis. Ann Surg Oncol. 2014;21(8):2608–14. https://doi.org/10.1245/s10434-014-3647-0. Glehen O, Gilly FN. Quantitative prognostic indicators of peritoneal surface malignancy: carcinomatosis, sarcomatosis, and peritoneal mesothelioma. Surg Oncol Clin N Am. 2003;12(3):649–71. https://doi.org/10.1016/s1055-3207(03)00037-1. Phelip JM, Tougeron D, Léonard D, et al. Metastatic colorectal cancer (mCRC): French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Updated July 2022. https://www.snfge.org/content/4-cancer-colorectal-metastatique. Accessed Dec 2022. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. https://doi.org/10.1016/j.ejca.2008.10.026. Dohan A, Hoeffel C, Soyer P, et al. Evaluation of the peritoneal carcinomatosis index with CT and MRI. Br J Surg. 2017;104(9):1244–9. https://doi.org/10.1002/bjs.10527. Solass W, Sempoux C, Detlefsen S, Carr NJ, Bibeau F. Peritoneal sampling and histological assessment of therapeutic response in peritoneal metastasis: proposal of the Peritoneal Regression Grading Score (PRGS). Pleura Peritoneum. 2016;1(2):99–107. https://doi.org/10.1515/pp-2016-0011. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. In: PH Sugarbaker, editor. Peritoneal carcinomatosis: principles of management, vol 82, Kluwer Academic Publishers; 1996. p. 359–74. https://doi.org/10.1007/978-1-4613-1247-5_23. Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221(1):29–42. https://doi.org/10.1097/00000658-199501000-00004. García-Fadrique A, Estevan RE, Ortí LS. Quality standards for surgery of colorectal peritoneal metastasis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2022;29(1):188–202. https://doi.org/10.1245/s10434-021-10642-6. Abboud K, André T, Brunel M, et al. Accord d’experts français pour la prise en charge des métastases péritonéales de cancers colo-rectaux. J Chir Visc. 2019;156(5):412–5. https://doi.org/10.1016/j.jchirv.2019.05.007. Glehen O, Osinsky D, Cotte E, et al. Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol. 2003;10(8):863–9. https://doi.org/10.1245/aso.2003.01.018. Passot G, Vaudoyer D, Villeneuve L, et al. What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: a 25-year experience with 1,125 procedures. J Surg Oncol. 2016;113(7):796–803. https://doi.org/10.1002/jso.24248. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. https://doi.org/10.1097/01.sla.0000133083.54934.ae. Schneider MA, Eden J, Pache B, et al. Mutations of RAS/RAF proto-oncogenes impair survival after cytoreductive surgery and HIPEC for peritoneal metastasis of colorectal origin. Ann Surg. 2018;268(5):845–53. https://doi.org/10.1097/sla.0000000000002899. Rovers KP, Bakkers C, van Erning FN, et al. Adjuvant systemic chemotherapy vs active surveillance following up-front resection of isolated synchronous colorectal peritoneal metastases. JAMA Oncol. 2020;6(8):e202701. https://doi.org/10.1001/jamaoncol.2020.2701. Rovers KP, Simkens GA, Punt CJ, van Dieren S, Tanis PJ, de Hingh IH. Perioperative systemic therapy for resectable colorectal peritoneal metastases: sufficient evidence for its widespread use? A critical systematic review. Crit Rev Oncol Hematol. 2017;114:53–62. https://doi.org/10.1016/j.critrevonc.2017.03.028. Eveno C, Passot G, Goere D, et al. Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2014;21(6):1792–800. https://doi.org/10.1245/s10434-013-3442-3. Rovers KP, Bakkers C, Nienhuijs SW, et al. Perioperative systemic therapy vs cytoreductive surgery and hyperthermic intraperitoneal chemotherapy alone for resectable colorectal peritoneal metastases. JAMA Surg. 2021. https://doi.org/10.1001/jamasurg.2021.1642. Fornaro L, Lonardi S, Masi G, et al. FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol. 2013;24(8):2062–7. https://doi.org/10.1093/annonc/mdt165. Cremolini C, Antoniotti C, Lonardi S, et al. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a randomized phase 2 clinical trial. JAMA Oncol. 2018;4(4):529. https://doi.org/10.1001/jamaoncol.2017.5314. Ychou M, Rivoire M, Thezenas S, et al. Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial. Br J Cancer. 2022;126(9):1264–70. https://doi.org/10.1038/s41416-021-01644-y. Rubbia-Brandt L, Giostra E, Brezault C, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007;18(2):299–304. https://doi.org/10.1093/annonc/mdl386. Blazer DG, Kishi Y, Maru DM, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(33):5344–51. https://doi.org/10.1200/jco.2008.17.5299. Köhne CH, Cunningham D, Costanzo FD, et al. Clinical determinants of survival in patients with 5-fluorouracil- based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol. 2002;13(2):308–17. https://doi.org/10.1093/annonc/mdf034. Assersohn L, Norman A, Cunningham D, Benepal T, Ross PJ, Oates J. Influence of metastatic site as an additional predictor for response and outcome in advanced colorectal carcinoma. Br J Cancer. 1999;79(11/12):1800–5. https://doi.org/10.1038/sj.bjc.6690287. Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6(8):583–92. https://doi.org/10.1038/nrc1893. Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF. Heterogeneity of the tumor vasculature. Semin Thromb Hemost. 2010;36(3):321–31. https://doi.org/10.1055/s-0030-1253454. Heldin CH, Rubin K, Pietras K, Östman A. High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806–13. https://doi.org/10.1038/nrc1456. Steuperaert M, Labate GFD, Debbaut C, et al. Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule. Drug Deliv. 2017;24(1):491–501. https://doi.org/10.1080/10717544.2016.1269848. Ceelen WP, Flessner MF. Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence. Nat Rev Clin Oncol. 2010;7(2):108–15. https://doi.org/10.1038/nrclinonc.2009.217. Löke DR, Helderman RFCPA, Franken NAP, et al. Simulating drug penetration during hyperthermic intraperitoneal chemotherapy. Drug Deliv. 2021;28(1):145–61. https://doi.org/10.1080/10717544.2020.1862364. Goere D, Glehen O, Quenet F, et al. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study. Lancet Oncol. 2020;21(9):1147–54. https://doi.org/10.1016/s1470-2045(20)30322-3. Klaver CEL, Wisselink DD, Punt CJA, et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol Hepatol. 2019;4(10):761–70. https://doi.org/10.1016/s2468-1253(19)30239-0. Ceelen W. HIPEC with oxaliplatin for colorectal peritoneal metastasis: the end of the road? Eur J Surg Oncol. 2019;45(3):400–2. https://doi.org/10.1016/j.ejso.2018.10.542. Nagourney RA, Evans S, Tran PH, Nagourney AJ, Sugarbaker PH. Colorectal cancer cells from patients treated with FOLFOX or CAPOX are resistant to oxaliplatin. Eur J Surg Oncol. 2021;47(4):738–42. https://doi.org/10.1016/j.ejso.2020.09.017. Prabhu A, Brandl A, Wakama S, et al. Effect of oxaliplatin-based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof-of-concept study. BJS Open. 2021. https://doi.org/10.1093/bjsopen/zraa075. Kepenekian V, Bhatt A, Péron J, et al. Advances in the management of peritoneal malignancies. Nat Rev Clin Oncol. 2022;19(11):698–718. https://doi.org/10.1038/s41571-022-00675-5. Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004;15(2):257–60. https://doi.org/10.1093/annonc/mdh059. Ljunggren M, Nordenvall C, Palmer G. Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases. Eur J Surg Oncol. 2021;47(11):2865–72. https://doi.org/10.1016/j.ejso.2021.05.046.