Mismatch Repair-Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Andrea CercekZsofia K Stadler

Abstract

Evaluate response of mismatch repair-deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. dMMR rectal tumors at Memorial Sloan Kettering Cancer Center (New York, NY) were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty patients with dMMR rectal cancer were identified by IHC and/or microsatellite instability analysis, with initial treatment response compared with a matched MMR-proficient (pMMR) rectal cancer cohort. Germline and somatic mutation analyses were evaluated. Patient-derived dMMR rectal tumoroids were assessed for chemotherapy sensitivity. Of 21 patients receiving neoadjuvant chemotherapy (fluorouracil/oxaliplatin), six (29%) had progression of disease. In comparison, no progression was noted in 63 pMMR rectal tumors (P = 0.0001). Rectal cancer dMMR tumoroids reflected this resistance to chemotherapy. No genomic predictors of chemotherapy response were identified. Of 16 patients receiving chemoradiation, 13 (93%) experienced tumor downstaging; one patient had stable disease, comparable with 48 pMMR rectal cancers. Of 13 patients undergoing surgery, 12 (92%) had early-stage disease. Forty-two (84%) of the 50 patients tested positive for Lynch syndrome with enrichment of germline MSH2...Continue Reading

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Citations

Jul 28, 2020·Cancers·Romain CohenThierry André
Sep 19, 2020·Cancer Communications·Feng WangRui-Hua Xu
Feb 18, 2021·Journal of Surgical Oncology·Melissa A Lumish, Andrea Cercek
Mar 24, 2021·Journal of Clinical Pathology·Kate WilkinsonCheok Soon Lee
Mar 26, 2021·Cancer Management and Research·Amy BodyEva Segelov
Dec 12, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Ebunoluwa E OtegbeyeMatthew A Ciorba
Jul 18, 2021·International Journal of Radiation Oncology, Biology, Physics·Christopher J AnkerJeffrey R Olsen
Oct 26, 2021·The British Journal of Surgery·A KananiK Søreide
Nov 7, 2021·Journal of Experimental & Clinical Cancer Research : CR·Qingguo LiZiliang Wang

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