Early Neurocognitive Outcomes Following Hypofractionated Radiotherapy (60 Gy in 20 Fractions) with Concurrent And Adjuvant Temozolomide in Post-Operative Glioblastoma: A Prospective Serial MMSE Analysis

Background Hypofractionated radiotherapy with concurrent temozolomide (TMZ) shortens overall treatment time in glioblastoma (GBM), but concerns remain regarding potential neurocognitive toxicity due to larger fraction size. Prospective serial cognitive data with this approach are limited. Objective To evaluate early neurocognitive outcomes using serial Mini-Mental State Examination (MMSE) scores in postoperative GBM patients treated with hypofractionated radiotherapy (60 Gy in 20 fractions) with concurrent and adjuvant TMZ. Methods In this prospective observational cohort, 23 postoperative GBM patients (Karnofsky Performance Status ≥ 70) received 60 Gy in 20 fractions over 4 weeks with concurrent daily TMZ (75 mg/m²), followed by adjuvant TMZ. MMSE was recorded at baseline, weekly during radiotherapy, at completion of radiotherapy, and at 3- and 6-month follow-up. The primary endpoint was change in MMSE from baseline across time points. A decline of ≥ 3 points was predefined as clinically significant. Results The mean baseline MMSE was 21.04. Mean MMSE remained largely stable during radiotherapy, with a minimal decline at end of radiotherapy (20.22), partial recovery at 3 months (20.78), and a mean MMSE of 20.22 at 6 months. Clinically significant MMSE decline (≥ 3 points) was observed in 3/23 patients (13%) at end of radiotherapy and in 3/23 patients (13%) at 3 months. Overall, 83% of patients demonstrated preservation of cognitive function through 6 months of follow-up. Conclusions Hypofractionated radiotherapy (60 Gy in 20 fractions) with concurrent and adjuvant TMZ was associated with low rates of early neurocognitive deterioration on serial MMSE assessment in postoperative GBM patients with good performance status. These findings support the neurocognitive feasibility of this hypofractionated regimen and warrant further evaluation using comprehensive neurocognitive batteries and longer follow-up.