Casper Reijnen1, Heidi V N Küsters-Vandevelde2, Clemens F Prinsen2, Leon F A G Massuger3, Marc P M L Snijders4, Stefan Kommoss5, Sara Y Brucker5, Janice S Kwon6, Jessica N McAlpine6, Johanna M A Pijnenborg3. 1. Department Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. Electronic address: casper.reijnen@radboudumc.nl. 2. Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 3. Department Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands. 4. Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 5. Department of Women's Health, Tübingen University Hospital, Tübingen, Germany. 6. Division of Gynecologic Oncology, University of British Columbia and British Columbia Cancer Agency, Vancouver, Canada.
Abstract
BACKGROUND: Mismatch repair (MMR) deficiency is found in 20 to 40% of endometrial cancers (ECs) and was recently identified as a discerning feature of one of the four prognostic subgroups identified by The Cancer Genome Atlas. There is accumulating evidence that MMR proteins are involved in the DNA repair processes following radiotherapy. We investigated the predictive value of MMR status for response to adjuvant radiotherapy in patients with stage IB/II, grade 3 endometrioid endometrial cancer (EEC). METHODS: A retrospective multicenter cohort study was performed to compare patients with histopathologically confirmed stage IB/II grade 3 EEC with and without adjuvant radiotherapy. Patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifying ECs as either MMR-deficient, POLE, p53abn or p53wt. Multivariable Cox regression analysis explored associations between adjuvant treatment and outcome. RESULTS: A total of 128 patients were analyzed, including 57 patients (43.0%) with MMR-deficient EECs. Baseline characteristics were comparable, except a higher proportion of MMR-deficient EECs were stage II (36.8% vs. 15.5%, p = 0.006). Eighty-two patients (64.1%) received adjuvant radiotherapy (external beam [n = 55], vaginal brachytherapy [n = 27]). In multivariable analysis, adjuvant radiotherapy was associated with improved disease-specific survival in patients with MMR-deficient EECs (hazard ratio 0.19, 95%-CI 0.05-0.77), but not in patients with MMR-proficient EECs (hazard ratio 0.92, 95%-CI 0.37-2.31). CONCLUSION: Adjuvant radiotherapy improved survival in patients with MMR-deficient EECs. MMR status could be used as a predictive biomarker to select patients that benefit most from adjuvant radiotherapy.
BACKGROUND: Mismatch repair (MMR) deficiency is found in 20 to 40% of endometrial cancers (ECs) and was recently identified as a discerning feature of one of the four prognostic subgroups identified by The Cancer Genome Atlas. There is accumulating evidence that MMR proteins are involved in the DNA repair processes following radiotherapy. We investigated the predictive value of MMR status for response to adjuvant radiotherapy in patients with stage IB/II, grade 3 endometrioid endometrial cancer (EEC). METHODS: A retrospective multicenter cohort study was performed to compare patients with histopathologically confirmed stage IB/II grade 3 EEC with and without adjuvant radiotherapy. Patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifying ECs as either MMR-deficient, POLE, p53abn or p53wt. Multivariable Cox regression analysis explored associations between adjuvant treatment and outcome. RESULTS: A total of 128 patients were analyzed, including 57 patients (43.0%) with MMR-deficient EECs. Baseline characteristics were comparable, except a higher proportion of MMR-deficient EECs were stage II (36.8% vs. 15.5%, p = 0.006). Eighty-two patients (64.1%) received adjuvant radiotherapy (external beam [n = 55], vaginal brachytherapy [n = 27]). In multivariable analysis, adjuvant radiotherapy was associated with improved disease-specific survival in patients with MMR-deficient EECs (hazard ratio 0.19, 95%-CI 0.05-0.77), but not in patients with MMR-proficient EECs (hazard ratio 0.92, 95%-CI 0.37-2.31). CONCLUSION: Adjuvant radiotherapy improved survival in patients with MMR-deficient EECs. MMR status could be used as a predictive biomarker to select patients that benefit most from adjuvant radiotherapy.
Authors: Ji Geun Yoo; Jin Hwi Kim; Chan Joo Kim; Hae Nam Lee; Min Jong Song; Dong Choon Park; Joo Hee Yoon; Sang Il Kim; Soo Young Hur; Sung Jong Lee Journal: Cancer Control Date: 2022 Jan-Dec Impact factor: 2.339
Authors: Alicia León-Castillo; Ester Gilvazquez; Remi Nout; Vincent Thbm Smit; Jessica N McAlpine; Melissa McConechy; Stefan Kommoss; Sara Y Brucker; Joseph W Carlson; Elisabeth Epstein; Tilman T Rau; Robert A Soslow; Raji Ganesan; Xavier Matias-Guiu; Esther Oliva; Beth T Harrison; David N Church; C Blake Gilks; Tjalling Bosse Journal: J Pathol Date: 2020-01-12 Impact factor: 7.996
Authors: Alicia León-Castillo; Stephanie M de Boer; Melanie E Powell; Linda R Mileshkin; Helen J Mackay; Alexandra Leary; Hans W Nijman; Naveena Singh; Pamela M Pollock; Paul Bessette; Anthony Fyles; Christine Haie-Meder; Vincent T H B M Smit; Richard J Edmondson; Hein Putter; Henry C Kitchener; Emma J Crosbie; Marco de Bruyn; Remi A Nout; Nanda Horeweg; Carien L Creutzberg; Tjalling Bosse Journal: J Clin Oncol Date: 2020-08-04 Impact factor: 44.544