A previous study has revealed that MSI-H/dMMR metastatic colorectal cancer (mCRC) with KRAS or NRAS mutations could not benefit from single PD-1 inhibitor compared with chemotherapy in overall survival ( 9). Meanwhile, chemoradiotherapy followed by surgery is the standard of care for patients with LARC irrespective of KRAS status. For mCRC patients with KRAS mutations, the standard treatment is chemotherapy with or without bevacizumab. KRAS mutation occurred in approximately 40% of all colorectal cancer ( 8). These findings indicated that neoadjuvant immunotherapy could achieve a remarkable clinical response in downstaging tumors in dMMR/MSI-H rectal cancer. The latter phase II trial investigated the efficacy of neoadjuvant programmed cell death protein 1 (PD-1) inhibitor with celecoxib and found that the pCR rate was 88% in dMMR/MSI-H colorectal cancer ( 7). The NICHE trial showed a pathological complete response (pCR) rate of 60% in dMMR/MSI-H patients after surgery, with neoadjuvant immunotherapy of ipilimumab and nivolumab ( 6). The mismatch repair-deficient (dMMR) or high microsatellite instability (MSI-H) phenotype, accounting for approximately <10% of all rectal cancer, was considered to be sensitive to immunotherapy ( 4, 5). However, distant metastatic rate remains high, which was 20% at 3 years in the RAPIDO trial ( 1– 3). CRT before surgery could downstage tumors and increase local control rate, with a pCR rate of 30% in the RAPIDO trial. Preoperative chemoradiation (CRT) is the standard of care for patients with locally advanced rectal cancer (LARC). This case indicates that this combined treatment strategy has remarkable clinical response both in locoregional and distant diseases, which potentially leads to reduction in the risk of distant metastases and better locoregional control for this subgroup of population. We report a case of dMMR and MSI-H LARC with KRAS mutation that achieved pathological complete response of primary lesion and liver metastases after neoadjuvant short-course radiotherapy followed by four cycles chemotherapy of XELOX plus PD-1 inhibitor tislelizumab and a subsequent total mesorectal excision. Additionally, very few studies reported on whether such combination could induce abscopal effect. The efficacy of CRT plus programmed death 1 (PD-1) inhibitor in these patients with complex gene mutation remains unclear. Immunotherapy showed promising results in the neoadjuvant treatment trials in patients with mismatch repair-deficient (dMMR) or high microsatellite instability (MSI-H) LARC. To date, preoperative chemoradiation (CRT) is the standard of care for patients with locally advanced rectal cancer (LARC) regardless of status of mismatch repair. 3Department of Gastrointestinal Surgery, The First Affiliated Hospital, Air Force Medical University, Xi an, China.2Department of Pathology, The First Affiliated Hospital, Air Force Medical University, Xi an, China.1Department of Radiation Oncology, The First Affiliated Hospital, Air Force Medical University, Xi an, China.Mai Zhang 1†, Hua Yang 1†, Ling Chen 2, Kunli Du 3, Lina Zhao 1* and Lichun Wei 1*
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