P01.07.A Neurocognitive outcomes after proton beam therapy for skull base tumours

Abstract

Abstract Background Evidence suggests that Proton Beam Therapy (PBT) may lessen the risk of neurocognitive decline (NCD) by reducing the dose to the normal brain as compared to conventional photon radiotherapy (XRT). We report the incidence of moderate-severe (Grade ≥3) NCD in adults treated for skull base chordomas and chondrosarcomas within the United Kingdom’s Proton Overseas Programme (POP). Material and Methods Baseline (pre-PBT) and follow-up clinical outcomes data were prospectively collected as part of a national PBT-outcomes registry, which started in 2008 . This registry is curated by a dedicated Proton Clinical Outcomes Unit. Specifically, late toxicities ≥G3 as per CTCAE (Common Terminology Criteria for Adverse Events) v4.0 definition, occurring later than 90 days after treatment completion, were recorded. This study focuses on the incidence of memory impairment (MI) in the adult (≥25 y) cohort. Results Between 2008-2018, 141 adult patients were treated for skull base chordomas (77 patients, 54.6%) and chondrosarcomas (64 patients, 45.4%) via the POP (the majority -62.8%- treated at the University of Florida PBT Institute). Median age at treatment was 51 years (range 26-77). Median prescription dose was 73.8 GyRBE (70-75.6), with a median dose per fraction of 1.8 Gy (1.2-2.1). Of note, the median dose for chondrosarcomas was 70.2 GyRBE (70-75.6), whereas the median dose for chordomas was 73.8 GyRBE (72-75.6). Median follow up was 39 months (0-138). On clinical assessment, 4 patients (2 chordomas, 2 chondrosarcomas) were reported with G3 MI after a median time of 43 months (27-49). None of them had impaired memory at baseline, nor relevant neurological comorbidities. Median age of those who developed G3 MI was 63 y (39-70). Median prescription dose was 72.9 GyRBE (70-73.8). Plans were available for 3 of these 4 patients. Relevant dose statistics to hippocampi and temporal lobes were extracted. Dmean to the omo- and contralateral hippocampi in these 3 patient plans were: patient 1) 33.7 and 11.6 GyRBE; patient 2) 28.1 and 24.4 Gy; patient 3) 8.7 and 8.2 GyRBE, respectively. V20 to the omo- and contralateral temporal lobes in the same patients were: patient 1) 47% and 10%; patient 2) 29% and 28.7%; patient 3) 30% and 28%, respectively. Suggested constraints for these structures are: Dmean < 20 Gy to the hippocampi and V20Gy <10% to the temporal lobes. Conclusion Our results indicate that adult patients undergoing high dose radiation for radioresistant tumours may experience detrimental effects on memory. Neurocognitive baseline and follow-up assessment is not routinely performed in this age group but might be appropriate to explore which domains of cognitive function are mainly affected. Larger cohorts are warranted to establish predictive factors and better understand dose volume effect of brain structures and neurocognitive sequelae.