局部晚期直肠癌新辅助放化疗联合免疫治疗的研究进展

doi:10.3760/cma.j.cn113030-20210812-00300

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Abstract For locally advanced (T_3-4/N₊M₀) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment, which have been demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. Radiotherapy and immunotherapy can supplement each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. These trials have achieved promising short-term efficacy in both microsatellite instability-high (MSI-H) and microsatellite stable (MSS) rectal cancers, which could further improve the rate of tumor response and rate of pathological complete response, increase the possibility of organ preservation and "watch and wait" approach. Large-scale clinical trials need to be performed in the future to demonstrate these findings and to improve long-term prognosis.

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	Articles by authors
	Wang Yaqi
	Xia Fan
	Zhang Zhen

Key words： Rectal neoplasms, locally advanced Neoadjuvant chemoradiotherapy Immunotherapy Research progress

Received: 12 August 2021

Fund:Shanghai Anticancer Association Eyas Project (SACA-CY20A03)

Corresponding Authors: Zhang Zhen, Email: zhen_zhang@fudan.edu.cn

Cite this article:

Wang Yaqi,Xia Fan,Zhang Zhen. Research progress on neoadjuvant chemoradiotherapy combined with immunotherapy in locally advanced rectal cancer[J]. Chinese Journal of Radiation Oncology, 2023, 32(1): 70-74.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.cn113030-20210812-00300 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2023/V32/I1/70

[1] Martin ST, Heneghan HM, Winter DC.Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer[J]. Br J Surg, 2012,99(7):918-928. DOI: 10.1002/bjs.8702.
[2] van der Valk M, Hilling DE, Bastiaannet E, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study[J]. Lancet, 2018,391(10139):2537-2545. DOI: 10.1016/S0140-6736(18)31078-X.
[3] Zhu J, Liu A, Sun X, et al.Multicenter, randomized, phase III trial of neoadjuvant chemoradiation with capecitabine and irinotecan guided by UGT1A1 status in patients with locally advanced rectal cancer[J]. J Clin Oncol, 2020,38(36):4231-4239. DOI: 10.1200/JCO.20.01932.
[4] Garcia-Aguilar J, Chow OS, Smith DD, et al.Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial[J]. Lancet Oncol, 2015,16(8):957-966. DOI: 10.1016/S1470-2045(15)00004-2.
[5] Fernández-Martos C, Pericay C, Aparicio J, et al.Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: grupo cancer de recto 3 study[J]. J Clin Oncol, 2010,28(5):859-865. DOI: 10.1200/JCO.2009.25.8541.
[6] Cercek A, Roxburgh C, Strombom P, et al.Adoption of total neoadjuvant therapy for locally advanced rectal cancer[J]. JAMA Oncol, 2018,4(6):e180071. DOI: 10.1001/jamaoncol.2018.0071.
[7] Le DT, Durham JN, Smith KN, et al.Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade[J]. Science, 2017,357(6349):409-413. DOI: 10.1126/science.aan6733.
[8] Michael-Robinson JM, Biemer-Hüttmann A, Purdie DM, et al.Tumour infiltrating lymphocytes and apoptosis are independent features in colorectal cancer stratified according to microsatellite instability status[J]. Gut, 2001,48(3):360-366. DOI: 10.1136/gut.48.3.360.
[9] André T, Shiu KK, Kim TW, et al.Pembrolizumab in microsatellite-instability-high advanced colorectal cancer[J]. N Engl J Med, 2020,383(23):2207-2218. DOI: 10.1056/NEJMoa2017699.
[10] Lugade AA, Moran JP, Gerber SA, et al. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor[J]. Journal of immunology, 2005,174(12):7516-7523. DOI: 10.4049/jimmunol.174.12.7516.
[11] Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J]. Nature, 2015,520(7547):373-377. DOI: 10.1038/nature14292.
[12] Dovedi SJ, Illidge TM.The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade[J]. Oncoimmunology, 2015,4(7):e1016709. DOI: 10.1080/2162402X.2015.1016709.
[13] Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al.Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade[J]. Cancer Res, 2014,74(19):5458-5468. DOI: 10.1158/0008-5472.CAN-14-1258.
[14] Postow MA, Callahan MK, Barker CA, et al.Immunologic correlates of the abscopal effect in a patient with melanoma[J]. N Engl J Med, 2012,366(10):925-931. DOI: 10.1056/NEJMoa1112824.
[15] Brix N, Tiefenthaller A, Anders H, et al.Abscopal, immunological effects of radiotherapy: narrowing the gap between clinical and preclinical experiences[J]. Immunol Rev, 2017,280(1):249-279. DOI: 10.1111/imr.12573.
[16] Crocenzi T, Cottam B, Newell P, et al.A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma[J]. J Immunother Cancer, 2016,4:45. DOI: 10.1186/s40425-016-0149-6.
[17] Lan J, Li R, Yin LM, et al.Targeting myeloid-derived suppressor cells and programmed death ligand 1 confers therapeutic advantage of ablative hypofractionated radiation therapy compared with conventional fractionated radiation therapy[J]. Int J Radiat Oncol Biol Phys, 2018,101(1):74-87. DOI: 10.1016/j.ijrobp.2018.01.071.
[18] Dewan MZ, Galloway AE, Kawashima N, et al.Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody[J]. Clin Cancer Res, 2009,15(17):5379-5388. DOI: 10.1158/1078-0432.CCR-09-0265.
[19] Yuki S, Bando H, Tsukada Y, et al.Short-term results of VOLTAGE-A: nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer[C]. Chicago: ASCO, 2020.
[20] Tamberi S, Grassi E, Corbelli J, et al.A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (medi4736) as preoperative treatment in rectal cancer: pandora study first stage[C]. Chicago: ASCO, 2021.
[21] Salvatore L, Bensi M, Corallo S, et al.Phase II study of preoperative chemoradiotherapy plus avelumab in patients with locally advanced rectal cancer: the AVANA study[C]. San Francisco: ASCO GI, 2021.
[22] Rahma OE, Yothers G, Hong TS, et al.Use of total neoadjuvant therapy for locally advanced rectal cancer: initial results from the pembrolizumab arm of a phase 2 randomized clinical trial[J]. JAMA Oncol, 2021,7(8):1225-1230. DOI: 10.1001/jamaoncol.2021.1683.
[23] Lin Z, Cai M, Zhang P, et al.Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer[J]. J Immunother Cancer, 2021, 9(11): e003554. DOI: 10.1136/jitc-2021-003554.
[24] Shamseddine A, Zeidan YH, El Husseini Z, et al.Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma[J]. Radiat Oncol, 2020,15(1):233. DOI: 10.1186/s13014-020-01673-6.
[25] Conroy T, Bosset JF, Etienne PL, et al.Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021,22(5):702-715. DOI: 10.1016/S1470-2045(21)00079-6.
[26] Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021,22(1):29-42. DOI: 10.1016/S1470-2045(20)30555-6.