Node-Sparing Short-Course Radiation With CAPOX and Sintilimab for MSS Locally Advanced Colon Cancer: A Randomized, Prospective, Multicenter Study

Summary

This study aims to evaluate the use of node-sparing short-course radiotherapy combined with chemotherapy and Sintilimab, or chemotherapy alone, as neoadjuvant therapy for MSS-type locally advanced colon cancer. The goal is to explore the efficacy and safety of combining node-sparing short-course radiotherapy with chemotherapy and immunotherapy in the neoadjuvant setting for MSS-type locally advanced colon cancer, while also investigating the specific role of regional lymph nodes in tumor immunotherapy.

Timeline

Start

2024-10

Primary completion

2025-09-30

Completion

2026-09-30

Publications

• Results Wang Q, Zhong W, Shen X, Hao Z, Wan M, Yang X, An R, Zhu H, Cai H, Li T, Lv Y, Dong X, Chen G, Liu A, Du J. Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer. NPJ Precis Oncol. 2024 Mar 2;8(1):61. doi: 10.1038/s41698-024-00533-w.
• Results Vanhersecke L, Brunet M, Guegan JP, Rey C, Bougouin A, Cousin S, Moulec SL, Besse B, Loriot Y, Larroquette M, Soubeyran I, Toulmonde M, Roubaud G, Pernot S, Cabart M, Chomy F, Lefevre C, Bourcier K, Kind M, Giglioli I, Sautes-Fridman C, Velasco V, Courgeon F, Oflazoglu E, Savina A, Marabelle A, Soria JC, Bellera C, Sofeu C, Bessede A, Fridman WH, Loarer FL, Italiano A. Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression. Nat Cancer. 2021 Aug;2(8):794-802. doi: 10.1038/s43018-021-00232-6. Epub 2021 Aug 12.
• Results Rahim MK, Okholm TLH, Jones KB, McCarthy EE, Liu CC, Yee JL, Tamaki SJ, Marquez DM, Tenvooren I, Wai K, Cheung A, Davidson BR, Johri V, Samad B, O'Gorman WE, Krummel MF, van Zante A, Combes AJ, Angelo M, Fong L, Algazi AP, Ha P, Spitzer MH. Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell. 2023 Mar 16;186(6):1127-1143.e18. doi: 10.1016/j.cell.2023.02.021.
• Results Zhang C, Zhang L, Xu T, Xue R, Yu L, Zhu Y, Wu Y, Zhang Q, Li D, Shen S, Tan D, Bai F, Zhang H. Mapping the spreading routes of lymphatic metastases in human colorectal cancer. Nat Commun. 2020 Apr 24;11(1):1993. doi: 10.1038/s41467-020-15886-6.
• Results Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, Cai K, Nie X, Wang J, Liu J, Liu H, Zhang W, Gao J, Wu C, Wang L, Fan J, Zhang L, Wang Z, Hou Z, Ma C, Yang K, Wu G, Tao K, Zhang T. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021 Nov;9(11):e003554. doi: 10.1136/jitc-2021-003554.
• Results Seo I, Lee HW, Byun SJ, Park JY, Min H, Lee SH, Lee JS, Kim S, Bae SU. Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer. J Immunother Cancer. 2021 Mar;9(3):e001610. doi: 10.1136/jitc-2020-001610.
• Results Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, Monkhorst K, Baas P. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1276-1282. doi: 10.1001/jamaoncol.2019.1478.
• Results Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May;23(5):659-670. doi: 10.1016/S1470-2045(22)00197-8. Epub 2022 Apr 12.
• Results Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 23;386(25):2363-2376. doi: 10.1056/NEJMoa2201445. Epub 2022 Jun 5.
• Results Yuan Y, Xiao WW, Xie WH, Cai PQ, Wang QX, Chang H, Chen BQ, Zhou WH, Zeng ZF, Wu XJ, Liu Q, Li LR, Zhang R, Gao YH. Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection. BMC Cancer. 2021 Feb 19;21(1):179. doi: 10.1186/s12885-021-07894-6.
• Results Chang H, Yu X, Xiao WW, Wang QX, Zhou WH, Zeng ZF, Ding PR, Li LR, Gao YH. Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study. Onco Targets Ther. 2018 Jan 17;11:409-418. doi: 10.2147/OTT.S150367. eCollection 2018.
• Results Qiu B, Ding PR, Cai L, Xiao WW, Zeng ZF, Chen G, Lu ZH, Li LR, Wu XJ, Mirimanoff RO, Pan ZZ, Xu RH, Gao YH. Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer. Chin J Cancer. 2016 Jul 7;35(1):65. doi: 10.1186/s40880-016-0126-y.
• Results Ludmir EB, Arya R, Wu Y, Palta M, Willett CG, Czito BG. Role of Adjuvant Radiotherapy in Locally Advanced Colonic Carcinoma in the Modern Chemotherapy Era. Ann Surg Oncol. 2016 Mar;23(3):856-62. doi: 10.1245/s10434-015-4907-3. Epub 2015 Oct 19.
• Results Agas RAF, Co LBA, Sogono PG, Jacinto JCKM, Yu KKL, Jacomina LE, Bacorro WR, Sy Ortin TT. Assessing the Effect of Radiotherapy in Addition to Surgery in Colon Adenocarcinomas: a Systematic Review and Meta-analysis of Contemporary Evidence. J Gastrointest Cancer. 2020 Jun;51(2):445-460. doi: 10.1007/s12029-019-00300-2.
• Results Fernandez LM, Sao Juliao GP, Figueiredo NL, Beets GL, van der Valk MJM, Bahadoer RR, Hilling DE, Meershoek-Klein Kranenbarg E, Roodvoets AGH, Renehan AG, van de Velde CJH, Habr-Gama A, Perez RO; International Watch & Wait Database Consortium. Conditional recurrence-free survival of clinical complete responders managed by watch and wait after neoadjuvant chemoradiotherapy for rectal cancer in the International Watch & Wait Database: a retrospective, international, multicentre registry study. Lancet Oncol. 2021 Jan;22(1):43-50. doi: 10.1016/S1470-2045(20)30557-X. Epub 2020 Dec 11.
• Results Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
• Results Hu H, Zhang J, Li Y, Wang X, Wang Z, Wang H, Kang L, Liu P, Lan P, Wu X, Zhen Y, Pei H, Huang Z, Zhang H, Chen W, Zeng Y, Lai J, Wei H, Huang X, Chen J, Chen J, Tao K, Xu Q, Peng X, Liang J, Cai G, Ding K, Ding Z, Hu M, Zhang W, Tang B, Hong C, Cao J, Huang Z, Cao W, Li F, Wang X, Wang C, Huang Y, Zhao Y, Cai Y, Ling J, Xie X, Wu Z, Shi L, Ling L, Liu H, Wang J, Huang M, Deng Y; OPTICAL study group. Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial. J Clin Oncol. 2024 Sep 1;42(25):2978-2988. doi: 10.1200/JCO.23.01889. Epub 2024 Apr 2.
• Results Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R; FOxTROT Collaborative Group. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552. doi: 10.1200/JCO.22.00046. Epub 2023 Jan 19.
• Results Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, Suarez CJ, Berghoff AS, Cremolini C, Falcone A, Loupakis F, Birner P, Preusser M, Lenz HJ, Curtis C. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019 Jul;51(7):1113-1122. doi: 10.1038/s41588-019-0423-x. Epub 2019 Jun 17.
• Results van der Bij GJ, Oosterling SJ, Beelen RH, Meijer S, Coffey JC, van Egmond M. The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg. 2009 May;249(5):727-34. doi: 10.1097/SLA.0b013e3181a3ddbd.
• Results Lin G, Feng Z, Liu H, Li Y, Nie Y, Liang Y, Li K. Mass screening for colorectal cancer in a population of two million older adults in Guangzhou, China. Sci Rep. 2019 Jul 18;9(1):10424. doi: 10.1038/s41598-019-46670-2.
• Results Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar.
• Results Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.
• Results Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12.

Drugs

Indications