Dataset Information

Germline polymorphisms in MGMT associated with temozolomide-related myelotoxicity risk in patients with glioblastoma treated on NRG Oncology/RTOG 0825.

ABSTRACT:

Background

We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma.

Methods

Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity.

Results

23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 stopped treatment due to toxicity. Among those who continued therapy (n = 26), 11 experienced myelotoxicity again. The final multivariable clinical factor model included treatment arm, gender, and anticonvulsant status and had low prediction accuracy (area under the curve [AUC] = 0.672). The final extended risk prediction model including four polymorphisms in MGMT had better prediction (AUC = 0.827). Receiving combination chemotherapy (OR, 1.82; 95% CI, 1.02-3.27) and being female (OR, 4.45; 95% CI, 2.45-8.08) significantly increased myelotoxicity risk. For each additional minor allele in the polymorphisms, the risk increased by 64% (OR, 1.64; 95% CI, 1.43-1.89).

Conclusions

Myelotoxicity during concurrent chemoradiation with temozolomide is an uncommon but serious event, often leading to treatment cessation. Successful prediction of toxicity may lead to more cost-effective individualized monitoring of at-risk subjects. The addition of genetic factors greatly enhanced our ability to predict toxicity among a group of similarly treated glioblastoma patients.

SUBMITTER: Scheurer ME

PROVIDER: S-EPMC9587696 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature

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Germline polymorphisms in <i>MGMT</i> associated with temozolomide-related myelotoxicity risk in patients with glioblastoma treated on NRG Oncology/RTOG 0825.

Scheurer Michael E ME Zhou Renke R Gilbert Mark R MR Bondy Melissa L ML Sulman Erik P EP Yuan Ying Y Liu Yanhong Y Vera Elizabeth E Wendland Merideth M MM Youssef Emad F EF Stieber Volker W VW Komaki Ritsuko R RR Flickinger John C JC Kenyon Lawrence C LC Robins H Ian HI Hunter Grant K GK Crocker Ian R IR Chao Samuel T ST Pugh Stephanie L SL Armstrong Terri S TS

Neuro-oncology advances 20220101 1

<h4>Background</h4>We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma.<h4>Methods</h4>Patients (<i>n</i> = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by lo ...[more]

PMID: 36299794

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