{"doi":"10.1093/noajnl/vdac152","title":"Germline polymorphisms in <i>MGMT</i> associated with temozolomide-related myelotoxicity risk in patients with glioblastoma treated on NRG Oncology/RTOG 0825","abstract":"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.","journal":"Neuro-Oncology Advances","year":2022,"id":288347,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":801286,"name":"Renke Zhou","orcid":null,"position":1,"is_corresponding":false},{"id":109755,"name":"Mark R. Gilbert","orcid":"0000-0003-2556-9722","position":2,"is_corresponding":false},{"id":249443,"name":"Melissa L. Bondy","orcid":"0000-0002-0278-414X","position":3,"is_corresponding":false},{"id":275936,"name":"Erik P. Sulman","orcid":"0000-0003-4933-9120","position":4,"is_corresponding":false},{"id":268557,"name":"Ying Yuan","orcid":"0000-0003-3163-480X","position":5,"is_corresponding":false},{"id":684676,"name":"Yanhong Liu","orcid":"0000-0003-0749-2602","position":6,"is_corresponding":false},{"id":292544,"name":"Elizabeth Vera","orcid":"0000-0001-7604-2555","position":7,"is_corresponding":false},{"id":969576,"name":"Merideth M Wendland","orcid":null,"position":8,"is_corresponding":false},{"id":969577,"name":"Emad Youssef","orcid":null,"position":9,"is_corresponding":false},{"id":969159,"name":"Volker W. Stieber","orcid":"0000-0001-9785-8588","position":10,"is_corresponding":false},{"id":542344,"name":"Ritsuko Komaki","orcid":"0000-0002-8238-7055","position":11,"is_corresponding":false},{"id":969160,"name":"John C. Flíckinger","orcid":"0000-0001-6900-1384","position":12,"is_corresponding":false},{"id":486077,"name":"Lawrence C. Kenyon","orcid":"0000-0002-3719-9565","position":13,"is_corresponding":false},{"id":133424,"name":"H. Ian Robins","orcid":null,"position":14,"is_corresponding":false},{"id":969578,"name":"G.K. Hunter","orcid":null,"position":15,"is_corresponding":false},{"id":426291,"name":"Ian Crocker","orcid":"0000-0002-8207-215X","position":16,"is_corresponding":false},{"id":969161,"name":"Samuel T. Chao","orcid":"0000-0002-1087-2764","position":17,"is_corresponding":false},{"id":5104,"name":"Stephanie L. Pugh","orcid":"0000-0002-5977-8912","position":18,"is_corresponding":false},{"id":292546,"name":"Terri S. Armstrong","orcid":"0000-0002-2414-0492","position":19,"is_corresponding":false},{"id":247449,"name":"Michael E. Scheurer","orcid":"0000-0002-8379-6088","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T00:30:14.968626Z","pmid":"36299794","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}