S967
Clinical - Oligometastatic cancer
ESTRO 2026
marker of micrometastatic disease burden and cancer progression, ctDNA may optimize the management of oligometastatic disease across tumor types. Future trials are being planned to validate these hypotheses. References: 1. Ludmir EB, Sherry AD, Fellman BM, et al. Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial. J Clin Oncol. 2024;42(32):3795-3805.2. Sherry AD, Siddiqui BA, Haymaker C, et al. Continuous Androgen Deprivation Therapy with or Without Metastasis- directed Therapy for Oligometastatic Prostate Cancer: The Multicenter Phase 2 Randomized EXTEND Trial. Eur Urol. 2025;88(5):496-509.3. Tang C, Sherry AD, Haymaker C, et al. Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023;9(6):825- 834. Keywords: ctDNA, metastasis-directed therapy, randomized Digital Poster 1289 Progression-Directed Ablative Radiotherapy Improves Event-Free Survival in Oligoprogressive NSCLC Lorenzo De Sanctis 1 , Riccardo Ray Colciago 1 , Giulia Rossano 1 , Matteo Ferrari 1 , Matteo Mombelli 1 , Ilenia Manno 1 , Federica Ferrario 2 , Valeria Faccenda 3 , Denis Panizza 3 , Stefano Arcangeli 1,2 1 Medicine and Surgery Department, University of Milan Bicocca, Milan, Italy. 2 Radiation Oncology, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy. 3 Medical Physics, Fondazione IRCCS San Gerardo Dei Tintori, Monza, Italy Purpose/Objective: To evaluate the efficacy of progression-directed radiation therapy (PDRT) in patients with oligoprogressive non-small cell lung cancer (NSCLC), focusing on disease progression and changes in systemic therapy. Material/Methods: From January 2020 to October 2025, a retrospective single-centre analysis was conducted at our Institution, including NSCLC patients treated with PDRT for oligoprogressive disease. Oligoprogression was defined as progression involving fewer than five extracranial lesions or up to a total intracranial disease volume of 14 cc, following an initial response to systemic treatment. The primary endpoint was event- free survival (EFS), defined as the occurrence of any of the following: change in systemic therapy, progression within six months, or development of more than three
progressive lesions. Multivariate Cox regression models were applied to identify predictors of oncological outcomes. Results: Eighty-seven patients were included, with a median age of 68 years (range: 43–87) and a median follow-up of 14 months. Adenocarcinoma was the predominant histology (75 cases, 86.2%), followed by squamous cell carcinoma (12 cases, 13.8%). PDRT was administered after first-line systemic therapy in 61 patients (70.1%). At the last assessment, 12 (13.8%) patients achieved complete response, 29 (33.3%) partial response, and 46 (52.9%) stable disease.The median EFS was 5 months (range: 1–48), with a one-year actuarial EFS rate of 52.1% (95% CI: 46.4–57.8%). Median time to next treatment (TTNT) was 8 months (range: 1–68), while median progression-free survival (PFS) was 5 months (range: 1–39).On multivariate analysis, both PDRT directed at the primary tumor (HR = 0.28, 95% CI: 0.12–0.66; p < 0.01) and a complete response prior to oligoprogression (HR = 0.31, 95% CI: 0.10–0.95; p = 0.04) were significantly associated with improved EFS. Conversely, use of chemotherapy (HR = 2.33, 95% CI: 1.21–4.48; p = 0.02) and larger CTV volumes (HR = 1.01, 95% CI: 1.0004–1.0111; p = 0.03) were associated with worse outcomes.
Conclusion: PDRT effectively delayed oncological events, resulting in a median EFS of 5 months and postponing the initiation of a new systemic therapy by a median of 8 months. These findings suggest that PDRT may represent a viable therapeutic strategy for prolonging disease stability and deferring systemic treatment in oligoprogressive NSCLC. Larger, prospective studies with extended follow-up are warranted to confirm these results. Keywords: NSCLC, Oligoprogression, PDRT
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