RADAR sample collection: a randomised phase III study with a PET response-adapted design comparing ABVD +/- ISRT with A2VD +/- ISRT in patients with previously untreated stage IA/IIA Hodgkin lymphoma

Background: Late effects of treatment, particularly second cancers and cardiovascular disease, are the leading cause of morbidity and mortality in highly curable cancers such as early-stage (ES) Hodgkin lymphoma (HL), especially for the majority of patients treated at a young age.

Trials of risk-adapted therapy aimed at reducing the burden of chemo-radiation treatment responsible for these late effects have had limited success because current methods of risk stratification are suboptimal.

Development of biomarkers to improve risk prediction has been hampered by a lack of systematic sample collection within clinical trials.

The international, phase 3 RADAR study will be the first clinical trial in ES-HL to concurrently assess serum, tissue and imaging biomarkers in ES-HL, forming the largest co-ordinated research effort and tissue collection of its kind.

Aims: 1) to facilitate biomarker discovery and improve risk stratification in ES-HL 2) to explore the biology of ES-HL at diagnosis and relapse and its interaction with the immune microenvironment Methods: RADAR will recruit 1042 patients aged 16-69-years with stage IA/IIA HL globally. Patients are randomised to receive one of two chemotherapy regimens (ABVD or A2VD), with or without radiotherapy.

This award will support sample collection from 272 UK patients, as part of an international effort to collect standardised samples from all RADAR participants.

Archival tissue biopsies will be collected at baseline and relapse for tissue microarray construction and extraction of RNA and DNA.

Serum and plasma samples will be collected at 4 time points, before, during and after treatment, coinciding with PET response assessment, and at relapse. Samples will be processed and stored at the University of Liverpool GCP Laboratory Facility. The CRUK and University College London Cancer Trials Centre will oversee trial conduct and data management.

RADAR recruitment commenced in April 2022 and will continue until 2027. An international consortium of leading clinician scientists will develop proposals for RADAR translational research.

How the results of this research will be used: validated biomarkers in ES-HL will allow more accurate patient risk stratification, to enable design of personalised, risk-adapted treatment pathways in future.

Novel insights into the biology of Hodgkin lymphoma at diagnosis and relapse will inform the development of targeted treatment strategies and application of immune therapies, such as checkpoint inhibition.

Together, these will support our overarching goal of reducing late treatment morbidity and mortality for the majority of HL survivors, and improving cure rates for high-risk patients.