Mismatch repair deficiency as a predictive marker for response to adjuvant radiotherapy in endometrial cancer
| Autor: | Janice S. Kwon, Sara Y. Brucker, Stefan Kommoss, Jessica N. McAlpine, Leon F.A.G. Massuger, Clemens F. M. Prinsen, Johanna M.A. Pijnenborg, Heidi V.N. Küsters-Vandevelde, Marc P.M.L. Snijders, Casper Reijnen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Adult medicine.medical_specialty medicine.medical_treatment DNA Mismatch Repair 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Aged Neoplasm Staging Retrospective Studies Aged 80 and over Predictive marker Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] business.industry Proportional hazards model Endometrial cancer Hazard ratio Obstetrics and Gynecology Middle Aged medicine.disease Endometrial Neoplasms Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] Radiation therapy Survival Rate 030104 developmental biology 030220 oncology & carcinogenesis DNA mismatch repair Female Radiotherapy Adjuvant business Adjuvant Carcinoma Endometrioid Cohort study |
| Zdroj: | Gynecologic Oncology, 154, 124-130 Gynecologic Oncology, 154, 1, pp. 124-130 |
| ISSN: | 0090-8258 |
| Popis: | Item does not contain fulltext 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. |
| Databáze: | OpenAIRE |
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