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      46 46 Gérard, J.‐P., Azria, D., Gourgou‐Bourgade, S. et al. (2012). Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J. Clin. Oncol. Off. 30: 4558–4565.

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      49 49 Hüttner, F.J., Probst, P., Kalkum, E. et al. (2019). Addition of platinum derivatives to fluoropyrimidine‐based neoadjuvant chemoradiotherapy for stage II/III rectal cancer: systematic review and meta‐analysis. J. Natl Cancer Inst. 111: 887–902.

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      54 54 Clifford, R., Govindarajah, N., Parsons, J.L. et al. (2018). Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer. Br. J. Surg. 105: 1553–1572.

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      57 57 Konishi, T., Shinozaki, E., Murofushi, K. et al. (2019). Phase II trial of neoadjuvant chemotherapy, chemoradiotherapy, and laparoscopic surgery with selective lateral node dissection for poor‐risk low rectal cancer. Ann. Surg. Oncol. 26: 2507–2513.

      58 58 Conroy, T., Hammel, P., Hebbar, M. et al. (2018). FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N. Engl. J. Med. 379: 2395–2406.

      59 59 Masi, G., Vivaldi, C., Fornaro, L. et al. (2019). Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial. Eur. J. Cancer Oxf. Engl. 110: 32–41.

      60 60 Fernández‐Martos, C., Pericay, C., Losa, F. et al. (2019). Effect of aflibercept plus modified FOLFOX6 induction chemotherapy before standard chemoradiotherapy and surgery in patients with high‐risk rectal adenocarcinoma: the GEMCAD 1402 randomized clinical trial. JAMA Oncol. 5 (11): 1566–1573.

      61 61 Dewdney, A., Cunningham, D., Tabernero, J. et al. (2012). Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high‐risk rectal cancer (EXPERT‐C). J. Clin. Oncol. 30: 1620–1627.

      62 62 Nogué, M., Salud, A., Vicente, P. et al. (2011). Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine‐based chemoradiotherapy in magnetic resonance imaging–defined poor‐prognosis locally advanced rectal cancer: the AVACROSS study. The Oncologist 16: 614–620.

      63 63 George, T.J., Yothers, G., Hong, T.S. et al. (2019). NRG‐GI002: a phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC)—first experimental arm (EA) initial results. J. Clin. Oncol. 15: 3505.

      64 64 Le, D.T., Uram, J.N., Wang, H. et al. (2015). PD‐1 blockade in tumors with mismatch‐repair deficiency. New Engl. J.Med. 372: 2509–2520.

      65 65 André, T., Shiu, K.‐K., Kim, T.W. et al. (2020). Pembrolizumab in microsatellite‐instability–high advanced colorectal cancer. N. Engl. J. Med. 383: 2207–2218.

      66 66 Zhang, J., Cai, J., Deng, Y., and Wang, H. (2019). Complete response in patients with locally advanced rectal cancer after neoadjuvant treatment with nivolumab. Oncoimmunology 8.

      67 67 Chiang, S.‐F., Huang, C.‐Y., Ke, T.‐W. et al. (2019). Upregulation of tumor PD‐L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers. Cancer Immunol. Immunother. 68: 283–296.

      68 68 Hecht, M., Büttner‐Herold, M., Erlenbach‐Wünsch, K. et al. (1990). PD‐L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis. Eur. J. Cancer Oxf. Engl. 65: 52–60.

      69 69 Salvatore, L., Bensi, M., Pietrantonio, F. et al. (2019). 662TiP—phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): the AVANA Study. Ann. Oncol. 30: v249.

      70 70 Cohen, R., Shi, Q., and André, T. (2020). Immunotherapy for early stage colorectal cancer: a glance into the future. Cancers 12.

      71 71 Arnold, C.R., Mangesius, J., Jäger, R., and Ganswindt, U. (2020). Neoadjuvant chemoradiotherapy in rectal cancer. Mag. Eur. Med. Oncol. 13: 329–333.

      72 72 Kössler, T., Buchs, N., Dutoit, V. et al. (2020). P‐115 PEMREC: a phase II study to evaluate safety and efficacy of neo‐adjuvant pembrolizumab and radiotherapy in localized microsatellite stable rectal cancer. Ann. Oncol. 31: S127.

      73 73 Antonia, S.J., Villegas, A., Daniel, D. et al. (2018). Overall survival with durvalumab after chemoradiotherapy in stage III. N. Engl. J. Med. 379: 2342–2350.

      74 74 van Zoggel, D.M.G.I., Bosman, S.J., Kusters, M. et al. (2018). Preliminary results of a cohort study of induction chemotherapy‐based treatment for locally recurrent rectal cancer. Br. J. Surg. 105: 447–452.

      75 75 Bossé, D., Mercer, J., Raissouni, S. et al. (2016). PROSPECT eligibility and clinical outcomes: results from the Pan‐Canadian Rectal Cancer Consortium. Clin. Colorectal Cancer 15: 243–249.

      76 76 Rullier, E., Rouanet, P., Tuech, J.‐J. et al. (2017). Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open‐label, multicentre, phase 3 trial. Lancet 390: 469–479.

      77 77 Rullier, E., Vendrely, V., Asselineau, J. et al. (2020). Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5‐year results of the GRECCAR 2 randomised trial. Lancet Gastroenterol. Hepatol. 5: 465–474.

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