Pretreatment 18 F-FDG uptake heterogeneity predicts response to CDK4/6 inhibitors in metastatic hormone receptor-positive breast cancer

Background: Intratumoral heterogeneity in 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake has been shown to serve as an alternative biomarker for predicting treatment outcomes across various tumors. This study aims to explore the potential value of 18 F-FDG uptake heterogeneity in predicting the efficacy of cyclin-dependent kinases 4/6 (CDK4/6) inhibitor therapy for metastatic hormone receptor-positive breast cancer (MHBC). Methods: A retrospective analysis was conducted on 127 patients with MHBC who underwent 18 F-FDG positron emission tomography/computed tomography (PET/CT) scans before CDK4/6 inhibitor therapy. The volume of interest (VOI) was delineated for each lesion. The sum of maximum standardized uptake value for all lesions (SUV max -T), the sum of total lesion glycolysis (TLG-T), the sum of metabolic tumor volume (MTV-T), and the heterogeneity index (HI) were recorded using a 50% SUV max threshold. Spearman's rank correlation test was employed to analyze the correlation between PET/CT parameters and treatment outcomes. The predictive ability for prognosis was determined using time-dependent survival receiver operating characteristic (ROC) analysis. The survival analysis was estimated using the Kaplan-Meier method, and comparisons were made using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression models, respectively. Results: Survival analysis demonstrated that HI was an independent prognostic factor for CDK4/6 inhibitor treatment in MHBC patients. Patients with HI ≥1.446 exhibited significantly lower progression-free survival (PFS) (9.1 vs. not reached, P <0.001). The area under the curve (AUC) for PFS was 0.762 (95% CI : 0.674–0.850), with a sensitivity of 86.2% and a specificity of 71.0%. Conclusion: The HI of 18 F-FDG uptake may help to assist the prognostication for MHBC patients receiving CDK4/6 inhibitor therapy.