Radioresistant Lung Oligometastases: Impact of Histology and Dose on Local Control

Abstract

<h3>Purpose/Objective(s)</h3> While a prescribed biologically effective dose (BED) of 100 Gy optimizes local control in early-stage non-small cell lung cancer (NSCLC), pulmonary oligometastases from radioresistant primary tumors such as colorectal cancer are associated with higher local failure rates despite similar radiotherapy (RT) regimens. We hypothesized that (1) metastases from radioresistant primaries would have inferior local control than those from non-radioresistant non-NSCLC primaries, and that (2) higher BED would be associated with superior local control among radioresistant metastases. <h3>Materials/Methods</h3> We identified 102 patients treated with radiotherapy for oligometastatic pulmonary disease (1-3 lung metastases from non-NSCLC primaries) in 2013-2020 at a single institution. Radioresistant primary cancers included colorectal carcinoma, endometrial carcinoma, renal cell carcinoma, melanoma, and sarcoma. Non-radioresistant primary cancers included breast, bladder, esophageal, pancreas, and head and neck carcinomas. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare local recurrence-free survival (LRFS) and overall survival (OS) between radioresistant vs. non-radioresistant metastases, as well as between BED10≥100 Gy vs. BED10<100 Gy among radioresistant metastases. <h3>Results</h3> Among the 94 patients with complete records, 60 were identified as having pulmonary oligometastases from radioresistant primary cancers. The median total dose was 52 Gy (interquartile range [IQR] 50-54 Gy), and the median number of fractions was 5 (IQR 3-5). Median follow-up time was 62.9 months. 1 of 34 patients (2.9%) with a non-radioresistant metastasis experienced local failure compared to 14 of 60 (23.3%) patients with radiosensitive metastasis (log-rank p=0.038). Multivariable Cox regression analysis showed that radioresistant histology was associated with an increased risk of LRFS following lung RT (hazard ratio [HR]: 4.20, 95% CI: 1.11-15.9, p=0.034). Escalation of the lung RT dose (BED10≥100 vs. BED10<100) was associated with improved LRFS among patients with radioresistant tumors (HR 0.32, 95% CI 0.11-0.96, p=0.04, 1-year LRFS 93.7% vs. 66.7%, 2-year LRFS 78.3% vs. 50.0%). <h3>Conclusion</h3> For oligometastatic patients with lung metastases from non-NSCLC primaries, radioresistant histology was associated with an increased risk of local failure following lung RT. Among these patients, BED10≥100 Gy is associated with decreased risk of local recurrence, suggesting that dose escalation above this threshold should be strongly considered when feasible. In the context of ongoing oligometastatic trials that seek to increase the number of sites treated, our results emphasize that maintaining ablative doses may be necessary to optimize local disease control in this subset of patients.