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

2021 
Purpose/objective(s) 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. Materials/methods 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). Results 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. Conclusion 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.
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