P18.43.A THE APPROACH TRIAL (ANALYSIS OF PROTON VS PHOTON RADIOTHERAPY IN OLIGODENDROGLIOMA AND ASSESSMENT OF COGNITIVE HEALTH): OPEN AND RECRUITING IN THE UK
Authors: Murray L J , Boele F , Brown S , Powell J , Borland M , Bruce A , Bulbeck H , Burnet N , Chang Y , Colaco R , Currie S , Egleston D , Fersht N , Hudson E , Klein M , Lilley J , Lowe M , Murray R D , Norris M , Noutch S , O’Hara D , Parbutt C , Smith A , Smith C , Whitfield G A , Short S 
Published: October 2024

Abstract

BACKGROUND
Proton beam radiotherapy (PBT), when used in the brain, may spare healthy tissue and preserve neurocognitive function (NCF) compared to photon radiotherapy (RT). Even small deficits in NCF may impact negatively on health-related quality of life (HRQoL) and are especially relevant for patients with oligodendroglioma (ODG), due to their young age and favourable prognosis. Randomised evidence for PBT remains limited. APPROACH is a UK multicentre randomised controlled phase III trial assessing PBT vs photon RT in patients with ODG.

MATERIALS AND METHODS
Procedures: Adult ODG patients will be randomised 1:1 between PBT (delivered at the NHS PBT centre in London or Manchester) and photon RT (delivered locally). Participants will receive 54Gy(Relative Biological Effectiveness; RBE) in 30 fractions (Grade 2 ODG) or 59.4Gy(RBE) in 33 fractions (Grade 3 ODG). Following RT, participants will receive Procarbazine, Lomustine and Vincristine chemotherapy. Patient and public involvement: To guide trial design, a focus group was held with ODG patients and carers in November 2018. Participants welcomed the opportunity to access PBT in a trial. Randomisation, travel/relocation for treatment, and completion of NCF and HRQoL assessments were deemed acceptable. Endpoints: The primary endpoint is NCF at 5 years, assessed using a standard neurocognitive test battery (EORTC Core Clinical Trial Battery Composite score). Secondary endpoints include additional NCF outcomes, HRQoL, endocrinopathy, work and economic impact, caregiver distress, toxicity, radiological response and, progression-free and overall survival. Trial design: Stage 1: internal pilot: assessing feasibility of recruitment over the first 12 months; Stage 2: first interim analysis: NCF at 2 years, after all participants reach 2-year follow-up, allowing potential early dissemination; Stage 3: second interim analysis: NCF at 5 years, when 50% of participants reach 5 years, assessing futility; Stage 4: final analysis: NCF at 5 years, once all participants reach 5 years. Sample size: For NCF at 5 years, based on a two-sample t-test with 5% two-sided significance and 90% power, 172 patients are required to detect a moderate effect size (Cohen’s d 0.5) between PBT and photon RT. Assuming 30% loss to follow-up, 246 patients are required. We aim to recruit from 18-25 UK centres over 3.5 years.

RESULTS
Set up began in April 2021. The trial opened to recruitment in January 2024. As of April 2024, 16 centres have completed the Radiotherapy Trials Quality Assurance (RTTQA) contouring and planning exercises, 8 centres are open, and 9 patients have been registered.

CONCLUSION
The APPROACH trial is one of the first randomised controlled trials of PBT vs photon RT in ODG patients. It aims to evaluate if the dosimetric advantages of PBT translate into clinical or patient benefits regarding NCF, other side effects and HRQoL. Funder: NIHR EME (131082)