5-year report of the E²-RADIatE Platform:
Executive summary

The E²-RADIatE Platform (EORTC-ESTRO RADiotherapy InfrAstrucTure for Europe) is a collaborative initiative launched in 2019 by EORTC and ESTRO to enhance radiotherapy research across Europe. The project aims to address critical radiotherapy-related questions through prospective real-world data collection, generating robust data on the role of radiotherapy in cancer treatment, focusing on survival, toxicity, quality of life, and resource use. In addition, the collected evidence is expected to generate new hypotheses to be investigated in future clinical trials, or may be a starting point to test new research methodologies, such as Trials within Cohorts (TwiCs).

The platform is structured as an observational multi-cohort study, collecting data from cancer patients treated with radiotherapy across Europe. It uses a unified protocol for data capture, ensuring streamlined regulatory processes and broad participation from various radiation oncology centers.

Following cohorts are ongoing, or in development:

• OligoCare (EORTC-1822): Since its launch in 2019, this cohort has enrolled over 3000 oligometastatic cancer patients from 58 European centers. Patients are eligible irrespective of whether oligometastatic disease is diagnosed synchronously or metachronously as long as all active cancer lesions were or will be treated with radical intent. The primary objective is to identify patient and tumor characteristics and therapeutic patterns-of-care, impacting overall survival in patients with oligometastatic disease of breast, non-small cell lung, prostate, and colorectal cancers. The cohort has already produced significant scientific output, including multiple abstracts and peer-reviewed papers focusing on the doses delivered in metastasis-directed stereotactic radiotherapy, its toxicity and impact on quality of life. In addition, two consensus papers addressing the characterization and classification of oligometastatic disease and the safety of combining stereotactic radiotherapy with novel systemic therapies, have been published.

Based on the finding in the OligoCare cohort that more than 90% of stereotactic treatments for oligometastatic disease use a multi-fraction regimen, a next step has been set by initiating the SPRINT study. This randomised trial embedded in the prospective cohort will primarily asses the safety and toxicity of single-fraction stereotactic radiotherapy, compared to the current fractionated standard-of-care.

• ReCare (EORTC-2011): Initiated in May 2023, this cohort focuses on high-dose reirradiation for various primary tumors. It has already surpassed recruitment projections with over 350 patients enrolled by the end of 2024. The ReCare study prospectively generates a multimodal real-world dataset – including clinical data, imaging, and radiotherapy plans – curated by the EORTC and its RTQA team to ensure the highest data fidelity. Doing so, ReCare will allow analysing pivotal uncertainties on dose constraints in the context of reirradiation, thus minimizing the risk of toxicity, guiding treatment decisions for an ever-growing patient population, and ultimately supporting the design of the next generation of randomized trials in reirradiation.
• AlphaCare (EORTC-2352): This upcoming cohort aims to assess the safety of combining metastasis-directed radiotherapy with novel anti-cancer drugs. In this prospective non-interventional registry, initial evidence will be generated on severe toxicity associated with the concomitant use of stereotactic body radiotherapy and selected, newly approved, systemic therapies in patients with (oligo)metastatic cancer. In case of a positive safety profile, AlphaCare will provide reassurance for the clinical use of combined modality approach, yet help design future efficacy trials if any safety concerns would arise. As such, it will ultimately lead to improved treatment strategies for metastatic cancer patients requiring combined modality treatment.

Challenges, opportunities and future directions: The platform requires substantial investment to curate the data, maintain the database and ensure compliance with regulations. Securing long-term funding and compensating participating centers for their work remain critical issues. Despite these challenges, the E²-RADIatE platform continues to generate highly valuable data at a rapid pace while fostering collaboration within the radiation oncology community. Without the dedicated work of this large group of academic and non-academic radiation oncology centers alike, this achievement would not have been possible.

In summary, the E²-RADIatE platform has made significant strides in enhancing radiotherapy research across Europe. With its comprehensive approach to data collection and collaboration, it continues to address critical questions in radiotherapy, test innovative study designs and ultimately aims to improve patient outcomes and advance the field of radiation oncology.