Association between temozolomide-related hematologic toxicity and health-related quality of life in patients with newly diagnosed glioblastoma

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Abstract
Background: Hematologic toxicity is a major adverse event of temozolomide chemoradiotherapy for newly diagnosed glioblastoma. Although severe hematologic toxicity occurs in approximately 10% of patients, its impact on health-related quality of life (HRQoL) is unknown. This study evaluated the association between temozolomide-related hematologic toxicity and HRQoL in patients with newly diagnosed glioblastoma. Methods: Patients with newly diagnosed glioblastoma treated with temozolomide chemoradiotherapy and available HRQoL data from 3 clinical trials were included. Primary HRQoL outcomes were physical, social, and role functioning, pain, fatigue, nausea/vomiting, and global health status. Severe hematologic toxicity was defined as grade 3-4 neutropenia, lymphopenia, thrombocytopenia, or anemia; febrile neutropenia; or prolonged (>30 days) grade 2 toxicity. Associations between severe hematologic toxicity and HRQoL were evaluated using linear mixed models. Clinical relevance was interpreted as glioma-specific minimally important difference thresholds. Results: Among 1288 patients, 8% experienced severe hematologic toxicity during the concomitant phase, 6% during the maintenance and 1% during both. During the concomitant phase, severe hematologic toxicity was more frequent in females and in patients with MGMT promoter methylation. From baseline to week 6, global health mean scores declined by −8.52 points in patients with severe toxicity and −4.78 points in those without, with a non-significant difference (P = .24). Similar patterns were observed for physical, social, and role functioning. Symptom scales were numerically worse in severe toxicity but not significantly different. During the maintenance phase, differences were minor. Conclusion: Severe temozolomide-related hematologic toxicity showed no statistically significant association with impaired HRQoL, suggesting limited impact on patient-reported functioning and symptoms. Possible effects on psychological functioning should be examined further.

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