Factors Associated With Neurocognitive Impairment Following Chemoradiotherapy in Patients With High-Grade Glioma: Results of a Prospective Trial.

Background: High-grade gliomas (HGG) are highly fatal tumors despite advanced multimodality management. They are also associated with neurocognitive impairment, both due to disease pathology and treatment. We aimed to assess various risk factors responsible for neurocognitive decline in HGG patients undergoing adjuvant chemoradiation.

Methods: Newly diagnosed HGG patients who underwent maximal safe resection were included. Patients received volumetric modulated arc therapy to a dose of 60 Gy in 30 fractions, along with concurrent temozolomide (TMZ) at a dose of 75 mg/m²/day orally; thereafter adjuvant TMZ (150-200 mg/m² for 5 days), given every 28 days for 6 to 8 cycles. The Mini-Mental State Examination questionnaire was used to measure cognitive impairment of each study patient at various time points. Cox regression model was used for univariate and multivariable analysis of data to establish possible risk factors.

Results: Fifty-three patients were enrolled and analyzed. At a median follow-up of 15 months, 30 patients (56.6%) developed cognitive impairment, and 23 patients (43.4%) did not. On univariate analysis, HGG with WHO grade 4, glioblastoma and diffuse midline glioma histology, IDH-wild type, recursive partitioning analysis class IV/V, and only biopsy of primary tumor were significantly associated with neurocognitive impairment, but none of them were independent risk factors on multivariable analysis. Planning target volume and dose received by ipsilateral hippocampus were also significantly correlated with cognitive decline in HGG patients.

Conclusion: Decline in neurocognitive functions in HGG patients is multifactorial and can be attributed to an amalgam of various tumor, patient, and treatment-related factors.