Long-Term Outcomes in Patients With Lung Metastases Treated With Ablative Radiotherapy in the Modern Era.

Purpose/Objective(s) Metastasis-directed radiotherapy (RT) may improve disease free and overall survival (OS) in select patients with lung metastases (LM). Long-term toxicity and cancer outcome data in patients with LM treated with ablative RT is limited, particularly in patients treated concurrently with novel systemic therapies. This is a retrospective, multi-hospital analysis of ablative RT for LM. Materials/Methods From 2015-2020, 343 LM-directed ablative RT treatment courses were delivered in 301 patients. Second primary lung cancers and non-parenchymal lesions were excluded. Medical records were reviewed retrospectively, and local progression (LP) was determined by evaluation of serial CT and/or PET scans. Univariate associations of clinical and radiographic parameters with clinical outcomes were evaluated using Cox proportional hazard models. Acute and late adverse events (AEs) were defined using CTCAE v.4.0. Results Median age was 64 years with 51% of patients being female. Median lesion size was 1.6 cm (range 0.3-9.4 cm). Seventy-four (22%) courses involved treatment of > 1 LM. Most common primary tumor histologies included melanoma (18%), colorectal adenocarcinoma (15%), urothelial/renal cell carcinoma (11%), and sarcoma (9%). Median physical dose was 5000 cGy. Median number of fractions delivered was 5, and 27 (8%) courses were > 5 fractions. Concurrent systemic therapies included immuno-, targeted, hormone, and cytotoxic therapy in 16%, 8%, 2%, and 1% of courses, respectively. Treatment to prior lung LM included surgery, RT, and ablation in 25%, 22%, and 2% of courses, respectively. With a median follow-up of 2.8 years, median and 5-year estimated OS were 3.0 years and 43% (95% confidence interval [CI] 34-52%), respectively. Factors associated with shorter OS included larger lesion size (P 2 LM (P = 0.016; HR 1.6), and > 5 fraction treatment (P = 0.024; HR 2.0). Fifteen patients experienced LP with a 5-year estimated cumulative incidence of 5.7% (95% CI 3.4-9.3%). Factors associated with increased risk of LP included larger lesion size (P = 0.004; HR 1.4 per cm), > 5 fraction treatment (P = 0.040; HR 3.8), and colorectal histology (P = 0.011; HR 3.9). Acute and late grade 2-3 AEs were 13% and 5%, respectively. There were no grade 4+ AEs. Increased toxicity was associated with larger size (P = 0.007; odds ratio 1.3 per cm) but not concurrent systemic therapy (P = 0.546) or prior treatment to other LM (P = 0.694). Conclusion These data confirm the efficacy and safety of ablative RT for LM in well-selected patients. 5-year OS and LP were 43% and 6%, respectively. AEs were infrequent, even in the setting of 24% of courses delivered concurrently with systemic therapy and 40% of courses delivered subsequent to other local therapies for LM. Given the excellent OS, these data are suggestive of improved local control as a factor for improved OS.