Abstract
BACKGROUND: IDH wildtype Glioblastoma Multiforme (GBM) is the most common and aggressive form of primary brain malignancy. Hypofractionated cranial irradiation with 40Gy in 15 fractions is commonly used for those over the age of 65 or with a worse performance status. The Perry regimen (2017) provided evidence for the combination of chemotherapy (concurrent + adjuvant) with short course radiotherapy. This study provides a real world experience of short course radiotherapy in a UK tertiary centre. MATERIAL AND METHODS: A retrospective observational study based on electronic patient records March 2016-May 2022 in a large UK tertiary centre (N=77). All patients received 40Gy in 15 fractions ± concurrent/adjuvant temozolomide chemotherapy. Overall Survival (OS) and Progression Free Survival (PFS) were assessed using Kaplan Meier methodology and Cox proportional hazards modeling with the R language for statistical programming. Subgroup analysis of those >600 days survival was performed using chi squared. RESULTS: The median age 72 (33-84). Patients were selected due to age >70 years or due to performance status of 2. All completed radiotherapy, 44 (57.1%) were MGMT promoter methylated, 57 (74%) received concurrent chemotherapy, 42 (54.5%) received adjuvant chemotherapy, 33 (42.9%) followed a Perry regimen. Median OS (mOS) for the whole cohort is 11.3 months (95%CI:9-13.7 months) and PFS 8.17 months (95%CI:5.43-12.7). On univariate analysis adjuvant chemotherapy (p=0.0068) predicts survival and MGMT promoter methylation status trends towards this (0.063). Concurrent chemotherapy and extent of resection do not. On Cox proportional hazard modeling, adjuvant chemotherapy independently predicts survival (Hazard ratio 0.55, p=0.019), age, concurrent chemotherapy, performance status, extent of resection and MGMT methylation status do not. In those aged over 65 (N=62), mOS 9.67months (95%CI:8.47-13.37). Only adjuvant chemotherapy predicts survival (p=0.0067) in this cohort. In those with MGMT promoter methylation, mOS 13.4 months (95%CI:9.3-18.47). Use of concurrent and adjuvant chemotherapy has a significant impact on survival: 19.67 months vs 8.5 months (p=0.00078). Over a quarter of patients (25.9%) survive >600 days. The chi-squared test was used to compare differences in groups with OS>600 days (n=20) and OS<600 days (n=57). No significant differences could be identified. CONCLUSION: This data shows comparable survival outcomes with reference to the Perry regimen (2017). In this cohort, the most important factor in predicting survival was adjuvant chemotherapy rather than: extent of resection, age, performance status, MGMT methylation status and concurrent chemotherapy. Over a quarter of patients survived >600days. In this cohort it has not been possible to delineate factors which may explain this. Further work is needed to investigate this.