Palliative Whole Brain Radiotherapy: International State of Practice 2022

Abstract

Increasing technology of radiation treatment planning and delivery, better systemic therapies, and randomized trials in the population of patients (pts) with brain metastases have provided robust targeted options. This has resulted in palliative whole brain radiation therapy (WBRT) being used far less frequently than previously. Most centers preferentially use stereotactic radiation surgery (SRS) for pts with several lesions and may reserve WBRT for those with poor performance, with rapidly progressive disease, or with leptomeningeal presentation. We hypothesize that different trends in current WBRT regimens exist across different continents with varying rates of use of hippocampal avoidance (HA) and memantine. Despite differences in dose, fractionation, and treatment technique, we predict that survival post-WBRT will remain poor-indicating appropriate application of whole brain treatment in this era of SRS and improved systemic therapies. A multi-center international analysis of pts receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. Participating centers were located in Belgium, the United Kingdom, Hong Kong, Cyprus, Italy, Germany, Ghana, and the United States. De-identified data were collected and analyzed centrally. Pts receiving WBRT as part of a curative regimen (e.g., medulloblastoma, primary CNS lymphomas), prophylactically in small cell lung cancer, or as bridging prior to CAR-T were excluded. The collected data consisted of pt parameters including prior stereotactic radiosurgery (SRS), prescription dose and fractionation, use of HA technique with or without memantine, and survival after WBRT. Survival was calculated via the Kaplan-Meier method. Of 23,332 RT prescriptions written at these centers in 2022, 399 (1.7%) were for palliative WBRT. Most frequent primary cancers were lung (42%) and breast (28%). Twenty-seven different dose regimens were used. The most common prescriptions were for 3 Gy daily fractions for 10 fractions (45%) and 4 Gy daily for 5 fractions (37%). Prior CNS SRS was delivered in 32 pts (7%). HA technique was used in 44 pts (10%); this technique was almost exclusively used in the United States. Memantine was prescribed in 93 pts (20%). Survival ranged from zero days to still surviving. The global median overall survival was 84 days after completion of treatment (95% CI: 68.0-104.0). Cumulative 3-month and 6-month actuarial survivals were 48% and 32%. This "moment in time" analysis confirms that pts with poor expected survival are being appropriately selected for WBRT and demonstrates the variance in global practice. Since poor survival precludes these pts from deriving much benefit, memantine and HA may be best suited only for carefully selected cases; use of these is not Standard of Care in the participating European, Asian, and African centers.