Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer
Publication year
2019Source
Gynecologic Oncology, 154, 1, (2019), pp. 124-130ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Gynaecology
Journal title
Gynecologic Oncology
Volume
vol. 154
Issue
iss. 1
Page start
p. 124
Page end
p. 130
Subject
Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences; Radboudumc 17: Women's cancers RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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.
This item appears in the following Collection(s)
- Academic publications [227902]
- Faculty of Medical Sciences [86234]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.