Multicentric Assessment of Safety and Efficacy of Combinatorial Adjuvant Brain Metastasis Treatment by Intraoperative Radiation Therapy and Immunotherapy.

PURPOSE: After surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy by enabling superior organ-at-risk preservation, reduction of in-hospital times, and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess the safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs). METHODS AND MATERIALS: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival. RESULTS: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival. CONCLUSIONS: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.

Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail patients with glioblastoma.

BACKGROUND AND PURPOSE: Short-course radiotherapy (25 Gy in five fractions) was recently shown in a randomized phase III trial to be non-inferior to 40 Gy in 15 fractions in elderly and/or frail patients with glioblastoma multiforme. This study compared the cost-effectiveness of the two regimens. MATERIAL AND METHODS: The direct unit costs of imaging, radiotherapy (RT), and dexamethasone were collected from the five primary contributing countries to the trial, constituting the data of 88% of all patients. Effectiveness was measured by the restricted mean overall survival (RMOS) and progression free survival (RMPFS). The incremental cost-effectiveness ratio (ICER) was calculated. Indirect costs were also estimated for comparison. RESULTS: The median OSs for the short-course and commonly used RTs were 8.2 (95% confidence interval [CI] 6.1-10.3) and 7.7 (95% CI 5.5-9.9) months, respectively (log rank p = 0.340). Median PFSs were also not different (p = 0.686). The differences in the RMOS and the ICER, however, were +0.11 life-years and -$3062 United States dollars (USD) per life-year gained, respectively. The differences in the RMPFS and the ICER were +0.02 PFS and -$17,693 USD, respectively. CONCLUSION: The ICER of -$3062 per life-year gained and -$17,693 per PFS gained indicates that the short-course RT is less costly compared to the longer RT regimen.