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Complete Pathologic Response After Concurrent Treatment with Pembrolizumab and Radiotherapy in Metastatic Colorectal Cancer: A Case Report.

ABSTRACT: Due to specific genetic characteristics, therapeutic options for colorectal cancer (CRC) with DNA mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) are limited. Although programmed death 1 (PD-1) blockade has been shown to be highly effective therapy for dMMR/MSI-H CRC, there is a need to develop new therapeutic paradigms to further improve survival rates of patients with dMMR/MSI-H CRC. So far, there is no case report on the use of immunotherapy combined with radiotherapy (RT) for the treatment of dMMR/MSI-H metastatic CRC (mCRC). Here, we report a 64-year-old patient diagnosed with mCRC who experienced a complete pathological response (pCR) after successfully conversion treatment with pembrolizumab and RT, and remains to be tumor-free during a follow-up of 11 months while off therapy. Immunohistochemical staining for MLH1, MSH2, MSH6, and PMS2 on the intestinal biopsy samples revealed loss of MLH1 and PMS2 protein expression. The present case report adds to the limited data on the safety and effectiveness of local RT combined with immunotherapy for patients with dMMR/MSI-H mCRC. This combination therapy appears to be a potential treatment for dMMR/MSI-H mCRC and deserves further exploration.

SUBMITTER: Yang J

PROVIDER: S-EPMC8053529 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Merkel cell carcinoma has historically had dismal prognosis with limited cytotoxic chemotherapy options that provide durable control of metastatic disease. The advent of anti-programmed death protein (anti-PD1)/anti-programmed death-ligand 1 (anti-PD-L1) directed immunotherapy has shown initial promise in Merkel cell carcinoma and radiation might augment immune responses. We present a case report of a 70-year-old male who underwent resection of Merkel cell carcinoma of the right thigh with a close margin and positive right inguinal involvement. Due to high-risk features, the patient was treated with adjuvant radiation to the right groin and with systemic carboplatin/etoposide, but developed local failure requiring salvage surgical resection. The patient then developed metastatic disease with biopsy proven retroperitoneal involvement refractory to doxorubicin/cyclophosphamide chemotherapy. The patient was then transitioned to single-agent pembrolizumab with a partial response for 10 months until developing progressive disease involving the left inguinal and left external iliac nodal regions. The progressive left inguinal/pelvic disease was treated with conventionally fractionated intensity modulated radiation therapy to a dose of 45 Gy delivered in 25 fractions. Following radiation therapy, the patient had complete response of all sites of disease throughout the body on imaging by RECIST criteria including retroperitoneal and mediastinal disease outside the radiation field. At 20 months post-radiation, the patient remains on pembrolizumab without evidence of disease on imaging. Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy. Ongoing prospective trials evaluating the utility of radiation in conjunction with immunotherapy for Merkel cell carcinoma are anticipated to provide clarity on the frequency and durability of abscopal responses when radiation is combined with immune checkpoint inhibitors.

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Complete Pathologic Response After Concurrent Treatment with Pembrolizumab and Radiotherapy in Metastatic Colorectal Cancer: A Case Report.

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