Radiotherapy in glioblastoma: the past, the present and the future

The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered. In addition, current controversies including decreasing margin size, re-irradiation, treatment of elderly patients, and novel imaging tracers will be discussed. Future directions including immunotherapy and tumour treating fields are examined. Radiotherapy-based treatments cannot rely solely on advances in chemotherapy or immunotherapy to improve the overall survival of patients with glioblastoma. Radiation oncology needs to continue to develop and improve the delivery, target definition, and dose of radiotherapy to these patients to improve their survival and the toxicity associated with treatment

QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

Abstract INTRODUCTION Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma. AIM To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG. METHODS Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance). RESULTS Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dose reduction from baseline by 28 days maintained for 7 days, and no deterioration in performance status). Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: 5 participants (33%), 6 events, 2 related). DISCUSSION The addition of acetazolamide did not facilitate dexamethasone reduction. The study closed early due to poor accrual and increasing availability of bevacizumab. </jats:sec

Factors Associated with Increased Survival after Surgical Resection of Glioblastoma in Octogenarians

Elderly patients with glioblastoma represent a clinical challenge for neurosurgeons and oncologists. The data available on outcomes of patients greater than 80 undergoing resection is limited. In this study, factors linked to increased survival in patients over the age of 80 were analyzed. A retrospective chart review of all patients over the age of 80 with a new diagnosis of glioblastoma and who underwent surgical resection with intent for maximal resection were examined. Patients who had only stereotactic biopsies were excluded. Immunohistochemical expression of oncogenic drivers (p53, EGFR, IDH-1) and a marker of cell proliferation (Ki-67 index) performed upon routine neuropathological examination were recorded. Stepwise logistic regression and Kaplan Meier survival curves were plotted to determine correlations to overall survival. Fifty-eight patients fit inclusion criteria with a mean age of 83 (range 80-93 years). The overall median survival was 4.2 months. There was a statistically significant correlation between Karnofsky Performance Status (KPS) and overall survival (P < 0.05). There was a significantly longer survival among patients undergoing either radiation alone or radiation and chemotherapy compared to those who underwent no postoperative adjuvant therapy (p < 0.05). There was also an association between overall survival and lack of p53 expression (p < 0.001) and lack of EGFR expression (p <0.05). In this very elderly population, overall survival advantage was conferred to those with higher preoperative KPS, postoperative adjuvant therapy, and lack of protein expression of EGFR and p53. These findings may be useful in clinical decision analysis for management of patients with glioblastoma who are octogenarians, and also validate the critical role of EGFR and p53 expression in oncogenesis, particularly with advancing age