Late toxicity outcomes of the NHS Proton Overseas Program since 2008

Abstract

Purpose/Objective(s) The Proton Overseas Program (POP) was begun by the National Health Service (NHS) in England in 2008, to fund eligible patients, including from the rest of the United Kingdom, for proton beam therapy (PBT) abroad. The first NHS PBT center was set up in 2018 and all POP patients’ data were transferred to its central repository for tracking and analysis. Outcomes are reported for POP patients diagnosed with non-neuroaxial tumors treated from 2008 to 2020. Materials/Methods Each patient's data are stored in the center's Proton Clinical Outcomes database. Clinical follow-up correspondence, last follow-up date, survival data, etc. are continuously updated when received. All non-neuroaxial tumors as of 2nd March 2020 were retrieved. Each patient's information from follow-up letters, assessment forms, etc. was reviewed, for incidence, type and onset time of grade 3-5 toxicities. CTCAE version 4 was used for toxicity nomenclature and grading. If needed, a patient's local UK follow-up center was contacted, sending individualized forms to record the most recent outcomes data. Results 495 patients met the eligibility criteria, with median follow-up 2.1 years (range 0-9.3 years), of which 89% were treated at the University of Florida (68%) and the Oklahoma Procure Center (21%). 70% of patients were pediatric (< 16 years), median age 11 (0-69 years). The most common diagnoses were rhabdomyosarcoma (RMS) (43%) and Ewing sarcoma (34%). The main disease site was the Head & Neck (H&N) region (51%). 69 patients had died by March 2020 (13.9%), with the highest risk in spindle cell carcinoma (60% mortality), osteosarcoma (38%) and neural/vascular tumors (25%). The 2-year actuarial survival was 88.3%. Patients with < 90 days follow-up (n = 26) or with insufficient toxicity data (n = 33) were excluded, leaving 436 patients for analysis. Following multimodality therapy, 55 patients (13%) had at least one grade 3 toxicity, 7 patients (1.6%) at least one grade 4, and none with grade 5. Most grade 3 (64%) and all grade 4 occurred in the H&N region, and most were for RMS patients (62%, N = 34 and 71%, N = 5 respectively). The most common grade 3 toxicity was cataract (51%, N = 18), then musculoskeletal deformity (11%, N = 6), premature menopause (11%, N = 6) and hearing impairment (7%, N = 4). Half of the grade 4 toxicities were secondary to hearing impairment. Median time from treatment end to onset was 2.3 years for grade 3 and 5 years for grade 4. Conclusion This study provides a large well-defined cohort of patients diagnosed with uncommon non-neuroaxial tumors undergoing multimodality therapy including PBT. The NHS approach to vigilant collection and tracking of patient data over time is feasible and provides valuable analysis of PBT patient outcomes. Despite difficulties with international patient transfer, this preliminary data suggests acceptable survival and toxicity rates in the POP cohort.