135 - Evaluation of 68Ga-NYM 096 CAIX PET/CT for Systemic Therapy-Radiotherapy Integration and Target Definition in Metastatic ccRCC (NYCRRT)

Purpose/Objective(s): Radiotherapy (RT) is increasingly used in metastatic clear cell renal cell carcinoma (mccRCC) to control oligometastatic/oligoprogressive/symptomatic or high-risk sites. Decisions on whether and how to integrate RT require accurate definition of biologically active and feasibly treatable disease burden.We evaluated whether CAIX-targeted PET/CT (68Ga-NY096) adds clinical utility beyond conventional imaging (FDG-PET/CT plus CT/MRI/bone assessment) by changing systemic therapy–RT strategy, RT intent, and RT target definition in mccRCC patients.

Materials/Methods: This exploratory paired decision-impact analysis was embedded in NYCRRT study. Histology-proven ccRCC patients with potentially coverable or indeterminate metastatic extent on conventional imaging underwent 68Ga-NY096 CAIX PET/CT. An MDT documented intended integrated strategy and RT plan. Primary endpoints were changes in integrated strategy and RT intent. Secondary endpoints included changes in the comprehensively treated lesion set among post-CAIX all-site RT candidates and lesion-edge sharpness assessed by paired lesion-to-background SUV edge gradients (?SUV/mm) (CAIX vs FDG). McNemar tests were used for paired proportions; paired Wilcoxon tests for gradients (two-sided a=0.05).

Results: 69 patients were included. CAIX-PET/CT eliminated baseline uncertainty in integrated strategy (16/69, 23.2%?0%) and RT intent (18/69, 26.1%?0%) by reclassifying equivocal cases into actionable pathways. Integrated strategy shifted from systemic therapy+RT 53/69 (76.8%) to 45/69 (65.2%), driven by (1) rule-out of active targets (no convincing CAIX-avid disease) and (2) identification of widespread active burden in which all-site RT was unlikely to be beneficial or feasible. RT intent shifted away from all-site RT+systemic therapy (51/69, 73.9%) to 39/69 (56.5%) after CAIX, with reallocation to selective RT targeting dominant lesions (7/69, 10.1%) and no RT (21/69, 30.4%). Definitive local therapy was selected in 2/69 (2.9%) after CAIX excluded metastatic disease and supported curative-intent local management. Among patients remaining candidates for all-site RT after CAIX (n=35), CAIX changed the intended comprehensively treated lesion set: expanded in 14 (40.0%) due to additional CAIX-avid lesions and reduced in 10 (28.6%) due to lack of CAIX activity in conventionally suspected sites(unchanged in 11, 31.4%). Lesion-to-background SUV edge gradients were steeper on CAIX than FDG (paired p<0.001), consistent with sharper lesion boundaries that may support more reproducible target delineation.

Conclusion: Against a stringent FDG-based real-world pathway, 68Ga-NY096 CAIX-PET/CT provided incremental utility by resolving uncertainty, reallocating RT intent toward activity- and feasibility-aligned pathways, and refining lesion selection and GTV boundary definition. COSTAR-001 follow-up is ongoing to link these CAIX-informed decisions with toxicity and outcomes. (NCT06613269)