18F-FDG-PET/CT-guided Stereotactic Body Radiation Therapy in Advanced Breast Cancer Patients Treated with Cyclin-Dependent Kinase 4/6 Inhibitors

Introduction.Cyclin-dependent kinase (CDK) 4/6 inhibitors have transformed treatment of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer, yet resistance remains common.Metabolic response assessed by fluorine-18-labeled deoxyglucose might identify patients at risk of treatment failure earlier than conventional imaging.We evaluated the safety, feasibility, and efficacy of 18 F-FDG-PET/CT-guided stereotactic body radiotherapy (SBRT) combined with CDK4/6 inhibitors. Materials andMethods.This retrospective study included twenty-nine patients monitored with 18 F-FDG PET/CT, who received SBRT concurrently with CDK4/6 inhibitors treatment or before CDK4/6 inhibitors commencement.Median age was 61 years (IQR 53-68).Ten patients had de novo disease.The median disease-free interval for patients with recurrent disease was 66.9 months (IQR 34.5-108.5).The majority of patients (72%) were treated in the first-line setting; 11 received ribociclib, 15 palbociclib, and three abemaciclib.Fifty-nine radiation treatments were delivered to 70 lesions: 41 before or concomitantly with the 1 st CDK4/6 inhibitors cycle and 18 for oligoprogressive disease.Twenty-six treatments used single-fraction SBRT (SF-SBRT) and 33 hypofractionated SBRT (HF-SBRT).Results.Post-SBRT SUVmax reduction was observed in all but one lesion.Metabolic complete response (mCR) occurred in 33 sites (56%), more frequently after SF-SBRT than HF-SBRT (p=0.03), in smaller lesions (<14 cm 3 , p=0.002), and in lesions with lower SUVmax (<6.3, p=0.008).Each unit increase in SUVmax reduced odds of mCR by ~18% (OR 0.824, p=0.04).Median progression-free survival (PFS) was 48.2 months; 2-year PFS was 71.5% (95% CI 50.9-84.6).Conclusions. 18F-FDG-PET/CT-guided SBRT, particularly single-fraction, added to CDK 4/6 inhibitors, is a valuable treatment modality resulting in substantial rates of metabolic complete response.Whether this translates into deferring disease progression requires randomized studies with larger treatment groups.To our knowledge, this study represents the first analysis evaluating 18 F-FDG-PET/CT-guided SBRT in combination with CDK4/6-inhibitor-based therapy in patients with metastatic breast cancer.