Prospective Evaluation of Acute Toxicities in Postoperative Patients of Glioblastoma Treated With Adjuvant Hypofractionated Radiotherapy (60 Gray in 20 Fractions)

Abstract

<h3>Purpose/Objective(s)</h3> The current standard of care for post operated patients of glioblastoma (PO-GBM) is adjuvant radiotherapy with concurrent and adjuvant temozolomide (RT-TMZ). Accelerated tumor repopulation due to increased overall treatment time could be responsible for radio resistance and poorer outcomes. The role of hypofractionated adjuvant radiotherapy (HYPO-RT) has been evaluated in elderly patients but is unknown in other subsets of age group. We aim to evaluate prospectively the safety and tolerability of HYPO-RT with concurrent and adjuvant temozolomide in PO-GBM patients. <h3>Materials/Methods</h3> Between December 2019 to December 2020, we enrolled 15 PO-GBM patients in a prospective ethic approved institutional study (IEC No. 53/19). Computed- tomography based planning with aid of contrast enhanced pre-operative MRI fusion was done. All patient received HYPO-RT 60 Gray in 20 fractions at 3 Gy per fraction over 4 weeks with concurrent Temozolomide 75 mg/m² with 3D-conformal radiotherapy technique. 45 Gray in 15 fractions were delivered in phase 1 followed by a phase 2 boost of 15 Gray in 5 fractions. Toxicity assessment was done according to common terminology criteria for adverse events 5.0. Memory impairment and cognitive dysfunction were assessed with mini mental status examination (MMSE). <h3>Results</h3> All patients completed the full course of radiotherapy without any interruption with median radiotherapy treatment time of 4 weeks (4-5 weeks). Median age was 52 years (20-65), median Karnofsky performance score was 70 (range 70-90) with M: F ratio of 10:5. 4 (27%) and 11 (73%) patients were RTOG-RPA class IV and class V respectively. 5 (33%) patients underwent gross total resection, 9 (60%) underwent subtotal resection and 1 (7%) patient had biopsy only. IDH-wild type was reported in 4 patients. Median follow was 5 months (range 3-10 months). No patient reported grade 2 or higher hematological toxicity during RT. None of the patient showed grade 3 or 4 non-hematological toxicity. 11 (73%) patients have grade 1 and 4 (26%) patients had grade 2 cognitive dysfunction. Six (40%) patients had grade 1 and 2 (13%) had grade 2 headache. Only 1 (6.6%) patient showed depressed level of consciousness and there was no reported episode of seizure. 11 (73%) patients had grade 1 and 1 (6.6%) patient showed grade 2 memory impairment. At the time of last follow up; 8 patients have completed adjuvant TMZ, 4 patients are on adjuvant TMZ and 3 patients have died. <h3>Conclusion</h3> Adjuvant HYPO-RT with RT-TMZ is well tolerated in terms of acute toxicity and may be a good alternative to reduce overall treatment time and counteract tumor repopulation in PO- GBM. Further follow up of our study cohort will elucidate the clinical outcome of patients treated with this HYPO-RT approach.