Proton beam therapy for central nervous system tumours: outcomes from the Proton Overseas Programme

Abstract

Purpose or Objective In 2008, the UK National Health Service (NHS) started the Proton Overseas Programme (POP), to provide access for Proton Beam Therapy (PBT) abroad for selected tumour diagnoses, whilst two national centres were being planned. This work reports the moderate-severe toxicities and their incidence in the patient group treated for Central Nervous System (CNS) malignancies. Materials and Methods Since the start of the NHS POP Programme, an agreement between NHS England and UK referring centres ensured outcomes data collection. Follow-up correspondence has been stored in patient files in a national database and curated by the Proton Clinical Outcomes Unit, established in 2018. Clinical and treatment-related data were extracted from the central patient database. The POP patient cohort was divided into CNS and extracranial diseases. Spinal and skull base (BoS) chordoma and chondrosarcoma were grouped with CNS diseases. Grade (G) ≥3 late toxicities (LT), as per CTCAE (Common Terminology Criteria for Adverse Events) v 4.0 definition, occurring later than 90 days since completion of treatment, were recorded. Where toxicity could not be graded accurately, individualised workbooks were sent to referring centres for clarification. The follow up time is calculated from end of PBT treatment to death or last follow up. Results Between 2008 and September 2020, 830 patients were treated within the POP for CNS malignancies. Their demographics and clinical characteristics are listed in Table 1. After a median follow up of 2.65 years (range 0.03 - 11.59) the overall survival for the whole cohort was 91.33%, and the local control was 75.42%. Of note, the local control was unknown in 12.29% of the patients, and 12.29% experienced disease progression. Toxicity analysis (Table 2) was carried out on 760 patients, with patients excluded due to short follow-up (<90 days) and/or inadequate toxicity data available. Median follow up in this population is 2.8 years (0.26 - 11.59), and median radiotherapy prescription dose 54 GyRBE (34.8-79.2). In total, 69 patients (9.1%) experienced G≥3 LT, with 18 (2.4%) experiencing more than one toxicity. Of note, G≥3 LT are more common in those tumour groups (such as Chordomas and Chondrosarcomas) receiving dose-escalated treatments, and in those (such as Craniopharyngiomas and Ependymoma) commonly located in close proximity to critical organs at risk and background of multiple surgical procedures. Conclusion The results of this study indicate safety of PBT for CNS tumours, with predominantly passive scattering. Clinical outcomes from this cohort will be compared with the newest Pencil Beam Scanning technology, in the UK NHS National PBT service. Baseline toxicity assessment is essential for the correct interpretation of radiotherapy toxicities and longer follow up is needed to evaluate endpoints, such as secondary malignancies, which have a long latency period.