Radiotherapy is a cornerstone of cancer care, but radiation oncology research still represents only a small part of the global oncology research portfolio.
A new article published in Radiotherapy and Oncology highlights how prospective registries and real-world data can help close this evidence gap.
The paper reports five years of experience from E2-RADIatE, the EORTC-ESTRO Radiotherapy Infrastructure for Europe, a collaborative project launched in 2019 by the European Organisation for Research and Treatment of Cancer and the European Society for Radiotherapy and Oncology.
The platform was created to collect prospective real-world data on cancer patients, radiotherapy treatments, and outcomes across Europe.
Why This Project Matters
Radiotherapy continues to evolve rapidly.
New technologies, treatment techniques, clinical indications, combinations with systemic therapies, and workflow innovations are constantly entering practice.
However, generating evidence for radiotherapy innovations is often difficult.
Randomized controlled trials remain essential, but they are not always easy to conduct in radiation oncology. Many radiotherapy advances are incremental, depend on technology and operator experience, require long-term endpoints, and often involve high upfront costs for hospitals.
As a result, radiotherapy research accounts for only a small fraction of oncology research activity.
This creates a need for complementary approaches to evidence generation, including prospective registries, real-world cohorts, pragmatic trials, and trial designs embedded in routine care.
E2-RADIatE was built to address this need.
What Is E2-RADIatE?
E2-RADIatE is a pragmatic, observational, prospective multi-cohort platform.
It collects real-world data from patients treated with radiotherapy across Europe through a centralized database.
The platform is designed to be disease- and technology-agnostic, meaning it can support different radiotherapy questions, indications, and treatment approaches.
It captures clinical outcomes, radiotherapy planning and delivery data, imaging information, patient-reported outcomes, patient experiences, resource use, and economic data.
This makes it broader than many traditional oncology trials, which often focus mainly on survival, progression, or toxicity.
The EORTC and ESTRO Partnership
The project brings together the strengths of EORTC and ESTRO.
EORTC provides long-standing clinical trial infrastructure and expertise in multicenter oncology research.
ESTRO brings the radiation oncology community, professional networks, education, and strategic focus on equitable access to high-quality radiotherapy.
Together, the two organizations created a pan-European framework to support radiotherapy-specific research questions and build evidence from daily clinical practice.
Five Years of Progress
After five years, two active cohorts are recruiting patients within E2-RADIatE.
The first is OligoCare, which focuses on metastasis-directed radiotherapy for oligometastatic disease.
The second is ReCare, which focuses on re-irradiation, an increasingly common but under-studied clinical situation.
Together, these cohorts show how prospective real-world registries can capture complex radiotherapy practice across different countries, tumor types, treatment sites, technologies, and clinical scenarios.
The platform has also supported scientific outputs, consensus recommendations, new hypotheses, and innovative trial methodology.
OligoCare and Oligometastatic Disease
OligoCare is the first and most mature E2-RADIatE cohort.
It evaluates radical metastasis-directed radiotherapy in patients with oligometastatic disease from breast, non-small cell lung, prostate, or colorectal cancer.
The cohort includes patients treated with local ablative intent, with at least one lesion treated using stereotactic body radiotherapy.
By November 2025, OligoCare had enrolled 3,768 patients across 67 centers in 13 European countries.
Early analyses have already provided important insights into real-world SBRT practice.
One analysis of the first 1,004 patients showed that prostate cancer was the most common primary tumor, followed by non-small cell lung cancer, colorectal cancer, and breast cancer.
The most frequently treated sites were non-vertebral bone, lung, and distant lymph node metastases.
Most patients were treated for a single metastasis, and SBRT was usually delivered using multiple fractions.
Early Safety and Quality-of-Life Data
OligoCare has also generated early outcome data.
In an interim analysis of 1,468 patients, acute grade 3 or higher SBRT-related adverse events within six months were rare, occurring in 0.5% of patients.
Fatal events were reported in 0.1%.
These findings support the short-term safety of metastasis-directed SBRT in routine European practice.
Another analysis focused on health-related quality of life in men with oligometastatic prostate cancer.
Most patients had good baseline global health status, and overall quality of life remained largely stable during the first six months after SBRT.
These findings are important because metastasis-directed treatment should not only aim for tumor control, but also preserve patient well-being.
ReCare and the Evidence Gap in Re-Irradiation
ReCare focuses on high-dose re-irradiation.
This is a growing area in radiation oncology, but prospective evidence remains limited.
Clinicians often face difficult questions about cumulative dose, organ-at-risk tolerance, fractionation, retreatment safety, integration with systemic therapy, and patient selection.
ReCare aims to collect high-quality data on tumor control, toxicity, imaging, radiotherapy plans, and quality-of-life outcomes.
Launched in 2023, ReCare had enrolled 653 patients from 19 centers across 9 countries by November 2025.
The first interim analysis included 290 patients with 348 lesions.
Most re-irradiations occurred in the thorax and pelvis, with prostate, lung, and breast cancers among the most common primary tumors.
More than 80% of cases involved overlap between the first and second radiotherapy volumes, and treatment intent was curative in more than two-thirds of patients.
These early data confirm both the feasibility of large-scale re-irradiation data collection and the heterogeneity of current clinical practice.
From Registry Data to New Trials
A major strength of E2-RADIatE is that it does not only describe current practice.
It also generates new hypotheses for future trials.
One example is SPRINT, a trial embedded within the OligoCare cohort.
OligoCare showed that more than 90% of SBRT treatments in Europe are delivered using multiple fractions. This raised the question of whether single-fraction SBRT could be a safe and efficient alternative for selected patients.
SPRINT uses a Trial Within Cohorts design, known as TwiCs, to compare single-fraction SBRT with multi-fraction SBRT.
This is the first international oncology TwiCs trial run through the platform.
The design allows randomization to be embedded within an ongoing real-world cohort, reducing patient burden and improving external validity compared with many traditional trial designs.
ALPHA-Care and Combining SBRT With Novel Drugs
Another planned cohort is ALPHA-Care.
This cohort will address a major practical question in oncology: how to safely combine SBRT with newly approved systemic therapies.
In daily practice, clinicians often pause systemic treatment during SBRT because of toxicity concerns, while others may reduce radiotherapy intensity or avoid treatment.
Both approaches may affect patient outcomes.
ALPHA-Care is designed to generate early safety data on combinations of SBRT with novel anti-cancer drugs in patients with metastatic disease.
This could help guide multidisciplinary decision-making and inform future efficacy trials.
Key Lessons From E2-RADIatE
The five-year experience shows that a prospective pan-European radiotherapy registry is feasible.
It also shows that such platforms require strong community engagement, standardized data collection, quality assurance, sustainable funding, and clear governance.
E2-RADIatE has already supported multiple abstracts, publications, consensus statements, and methodological innovations.
It has also highlighted important challenges.
These include funding limitations, hidden workload for participating centers, differences in ethics and data-protection requirements across countries, difficulty collecting complex DICOM radiotherapy data, and the need to harmonize registry infrastructure across Europe.
Why Real-World Evidence Matters in Radiation Oncology
Real-world evidence cannot replace randomized trials, but it can complement them.
This is especially important in radiation oncology, where clinical practice is technically complex, rapidly evolving, and highly dependent on treatment delivery, imaging, planning, and local expertise.
Prospective registries can help capture what happens in routine care, evaluate patterns of practice, identify variation, support benchmarking, generate hypotheses, and inform future trial design.
They can also provide evidence for settings that are difficult to study through traditional randomized trials alone, such as oligometastatic disease, re-irradiation, rare subgroups, or technology-driven innovations.
Clinical Takeaway
The first five years of E2-RADIatE show that prospective real-world registries can become powerful research infrastructure for radiation oncology.
Through OligoCare and ReCare, the platform is already helping describe European radiotherapy practice, evaluate safety and quality-of-life outcomes, develop consensus guidance, and generate new trial questions.
Its experience also highlights what is needed for success: sustainable funding, standardized data structures, community engagement, regulatory harmonization, and integration of patient-centered outcomes.
E2-RADIatE demonstrates that radiation oncology can learn systematically from routine care.
For a field where innovation often moves faster than traditional evidence generation, this kind of infrastructure may become essential for building stronger, more relevant, and more patient-centered evidence.
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