NIRA-03 THE EFFECT OF INDIVIDUAL CLINICAL FACTORS ON RANO ASSESSMENT IN BRAIN METASTASES
Jeffrey DiPaolo, Beatriz Lega, Amir Elbahnasawi, Ann MorstadAbstract
Background
RANO-BM integrates radiographic measurements with clinical factors including corticosteroid use and neurologic status, making response assessment a composite endpoint rather than an imaging-only determination. We evaluated how specific clinical factors, including steroid escalation, neurologic decline, on-study surgery or radiation, and missing clinical data, affect final RANO-BM response classification.
Methods
We retrospectively analyzed four RANO-BM clinical trial datasets including 242 subjects with measurable baseline brain metastases and 1,079 assessed timepoints. Two response classifications were compared: (1) imaging-only response based on unidimensional percent change thresholds and (2) final RANO-BM response incorporating protocol-defined clinical factors, including corticosteroid dose, neurologic status, on-study surgery/radiation, and data completeness. Discordant assessments were analyzed to determine the impact of each clinical component.
Results
Discordance between imaging-only and final RANO-BM response occurred in 6.2% of time point assessments (66/1,079), including 63 downgrades and 3 upgrades. Steroid escalation accounted for 9% of downgrades and clinical decline for 3%, while combined clinical effects accounted for additional cases. Missing clinical data was the leading cause of downgrade (52%), followed by surgical information (22%). At the subject level, 10% of subjects (24/242) had at least one downgraded timepoint, largely due to missing clinical data and on-study surgery/radiation. The 3 upgraded timepoints reclassified radiographic progressive disease as composite stable disease or non-evaluable.
Conclusions
Clinical factors meaningfully change radiographic response classification in RANO-BM, reinforcing that it functions as a composite endpoint rather than an imaging-only framework. Imaging-only assessment may overestimate response relative to full RANO-BM evaluation. Missing clinical data was the dominant driver of downgraded responses, with greater impact than all other individual factors combined.