Does the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS v1 .1) Apply to Radiation Oncology? A Constructive Critique

Abstract

<h3>Purpose/Objective(s)</h3> There is an ongoing desire to define "value" in clinical research. ESMO-MCBS is a commonly used framework, endorsed by ESMO and used by several governments in their health technology assessments in various settings. Such value frameworks have not been validated for assessing benefit derived from radiotherapy (RT). We herein assess the applicability of the ESMO-MCBS in radiation oncology, using breast cancer as a test-case. <h3>Materials/Methods</h3> We reviewed the supportive literature used by the ASTRO Evidence-Based Guideline on Radiation Therapy for the Whole Breast for adjuvant whole breast Radiation Therapy. We delineated a pool of "core" (112 studies) and "supplemental" articles (additional 65 studies). Among these, we identified a subset of 15 randomized trials, 1 systematic review and 1 big data study. The goals of our exercise were (1) to evaluate the "scorability" of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version of the ESMO-MCBS tool, and (3) to identify shortcomings in the instrument when applied to RT approaches, and suggest amendments to improve the efficacy and validity of the ESMO-MCBS tool. <h3>Results</h3> Few studies met the ESMO-MCBS criteria for crediting clinical benefit; i.e., in (1) superiority of the trials in overall survival (OS) or disease-free survival (DFS), or, (2) non-inferiority in OS or DFS with benefit in either life quality (QOL) or toxicity or reduced treatment costs as secondary end-points. OS was the primary end point in only one trial (which was a negative study). However, that study (EORTC boost trial) was practice-changing because it showed a significant improvement in local control (LC) which was a secondary outcome. Since the ESMO-MCBS does not credit local control (i.e., "local DFS"), superiority studies using this endpoint were not scoreable. Arguably, the 4 non-inferiority studies and one meta-analysis comparing hypo-fractionation with standard fractionation (that demonstrated non-inferior disease control with reduced acute and late toxicity) could be scored. Finally, reports describing cosmetic, clever technical or dosimetric advances, without verification of improved patient outcomes nor associated with clinical benefit, were not scoreable. <h3>Conclusion</h3> Currently, ESMO-MCBS does not credit LC as distinct from DFS or RFS. Since local recurrence results in a cascade of adverse events for patients, this is a clinically meaningful outcome, albeit often not always a good surrogate for OS. For consistency in research design and description of results, we propose replacing the conventional nomenclature of LC with Local-DFS (L-DFS)- a subtype of DFS most-relevant to local treatments (e.g., RT and surgery). The utility of the ESMO-MCBS in studies involving RT and surgery would be improved by incorporation of credit for statistically and clinically significant improvements in L-DFS.