THE INTERNATIONAL CONSENSUS ON PALLIATIVE RADIOTHERAPY ENDPOINTS FOR FUTURE CLINICAL TRIALS IN BONE METASTASES: A SECOND UPDATE

Purpose:

External beam radiotherapy (EBRT) is a well-established palliative treatment for symptomatic bone metastases. As radiation techniques and clinical practices evolve standardized endpoints are essential for ensuring accurate reporting and facilitate comparability across clinical trials. To address this, the International Bone Metastases Consensus Group developed consensus guidelines for EBRT trial endpoints. This study presents the latest revision of these guidelines, incorporating advancements in clinical practice and technology to further refine consensus-based endpoints for future clinical trials.

Materials and Methods:

Applying the Delphi Method, a structured, two-phase electronic survey was conducted to update the consensus. Expert participants, including prior consensus contributors and globally recognized specialists in bone irradiation, provided input. Statements required a consensus threshold of >75% agreement. Consensus was defined as ≥75% agreement. Statements that did not reach consensus in Phase I were revised and reassessed in Phase II after Working Panel discussions. Descriptive statistics summarized the results, categorizing statements by consensus level.

Results:

A total of 58 experts participated in Phase I, 44 in Phase II. Consensus was achieved 38 of 47 (81%) of statements, including 18 newly introduced or modified items. Key consensus areas included eligibility criteria, pain and analgesic assessments, radiation techniques and dose specifications, follow-up protocols, assessment timing, and cost-effectiveness considerations. Notably, net pain relief was introduced as a critical endpoint, quality of life measures were recommended for all trials, and skeletal-related events were deemed as essential additional endpoints. Despite broad consensus, several areas remained unresolved. Debate persisted over the optimal duration for pain assessment (3-day versus 7-day) and whether worst pain, mean pain or both should be reported. Additionally, the timeframe for pre-treatment assessment could not be agreed upon. While pain response evaluations at 1, 2, and 3 months were widely accepted, alternative assessment intervals generated discussion. And while de-intensification of follow-up after 6 months was thought to be a consideration, the optimal follow-up duration beyond those 6 months remained a point of contention, with some advocating for extended monitoring to assess long-term outcomes.

Conclusions:

This updated consensus provides a refined framework for the design of clinical trials in EBRT for bone metastases, promoting standardized reporting and identifying research priorities. The inclusion of new endpoints, such as standardized dose thresholds, reflects contemporary clinical practice. Ongoing re-evaluation is planned to maintain relevance with evolving treatment paradigms.