Anja Smits1,2, Malgorzata Lysiak3, Andreas Magnusson4, Johan Rosell5, Peter Söderkvist3,6, Annika Malmström3,7. 1. Department of Neuroscience and Physiology, Clinical Neuroscience, Sahlgrenska Academy, Gothenburg University, Blå Stråket 7, Plan 3, SE-413 45 Gothenburg, Sweden. 2. Department of Neuroscience, Neurology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. 3. Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85 Linköping, Sweden. 4. NU-Hospital, SE-451 53 Uddevalla, Sweden. 5. Regional Cancer Center South East Sweden, Region Östergötland, SE-581 85 Linköping, Sweden. 6. Clinical Genomics Linköping, Science for Life Laboratory, Linköping University, SE-581 85 Linköping, Sweden. 7. Department of Advanced Home Care, Linköping University, SE-581 85 Linköping, Sweden.
Abstract
INTRODUCTION: Recent studies suggest an overrepresentation of MGMT promoter methylated tumors in females with IDHwt glioblastoma (GBM) compared to males, with a subsequent better response to alkylating treatment. METHODS: To reveal sex-bound associations that may have gone unnoticed in the original analysis, we re-analyzed two previously published clinical cohorts. One was the multicenter Nordic trial of elderly patients with GBM, randomizing patients into three different treatment arms, including 203 cases with known MGMT promoter methylation status. The other was a population-based study of 179 patients with IDHwt GBM, receiving concomittant radiotherapy and chemotherapy with temozolomide. Cohorts were stratified by sex to test the hypothesis that female sex in combination with MGMT promoter methylation constitutes a subgroup with more favorable outcome. RESULTS: There was a significantly larger proportion of MGMT promoter methylation and better outcome for female patients with MGMT promoter methylated tumors. Results were confirmed in 257 TCGA-derived IDHwt GBM with known sex and MGMT status. CONCLUSIONS: These results confirm that patient sex in combination with MGMT promoter methylation is a key determinant in GBM to be considered prior to treatment decisions. Our study also illustrates the need for stratification to identify such sex-bound associations.
INTRODUCTION: Recent studies suggest an overrepresentation of MGMT promoter methylated tumors in females with IDHwt glioblastoma (GBM) compared to males, with a subsequent better response to alkylating treatment. METHODS: To reveal sex-bound associations that may have gone unnoticed in the original analysis, we re-analyzed two previously published clinical cohorts. One was the multicenter Nordic trial of elderly patients with GBM, randomizing patients into three different treatment arms, including 203 cases with known MGMT promoter methylation status. The other was a population-based study of 179 patients with IDHwt GBM, receiving concomittant radiotherapy and chemotherapy with temozolomide. Cohorts were stratified by sex to test the hypothesis that female sex in combination with MGMT promoter methylation constitutes a subgroup with more favorable outcome. RESULTS: There was a significantly larger proportion of MGMT promoter methylation and better outcome for female patients with MGMT promoter methylated tumors. Results were confirmed in 257 TCGA-derived IDHwt GBM with known sex and MGMT status. CONCLUSIONS: These results confirm that patient sex in combination with MGMT promoter methylation is a key determinant in GBM to be considered prior to treatment decisions. Our study also illustrates the need for stratification to identify such sex-bound associations.
Entities:
Keywords:
MGMT promoter methylation; glioblastoma; sex disparities; survival
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