Multi-Target Thoracic Stereotactic Body Radiotherapy – Toxicity and Efficacy Analysis

Abstract

<h3>Purpose/Objective(s)</h3> With the increasing utilization of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multi-target thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data on MTT, the purpose of this study was to report the experience of this strategy from a large academic center. <h3>Materials/Methods</h3> Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets within 1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included late grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0) apart from pneumonitis, local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival (PFS), and overall survival (OS). Competing risk analysis was used to evaluate the cumulative incidence (CI) of CSRP, LF, and ICST. PFS and OS were estimated using the Kaplan-Meier method. Univariate analyses (UVA) and multivariable analyses (MVA) were performed to look for clinical and dosimetric predictive factors of CSRP. <h3>Results</h3> One-hundred and ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Primary histologies included colorectal (29.9%), lung (28.1%), kidney (17.5%), and breast (6.0%). Indications for SBRT were oligoprogression (n=180; 37.4%), oligometastases (n=164; 34.1%), curative intent (n=81; 16.9%), and control of dominant areas of progression (n=56; 11.6%). Thirty-two patients (16.8%) had systemic therapy within 3 months of SBRT. Number of irradiated tumors ranged from 2-7 and the majority of SBRT courses were delivered concurrently (88.2%). Of concurrent courses, 157 (62.3%) used multiple isocenters and 95 (37.7%) used a single isocenter. Median SBRT dose was 50 Gy (range: 25-60 Gy) delivered in 1-8 fractions, with a median biological effective dose of 105.6 Gy (range: 37.5-150 Gy). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The CI of CSRP at 6 and 12 months was 5.3% and 7.7%, respectively. Two other patients had late grade ≥3 toxicity: 1 grade 3 rib fracture and 1 grade 4 esophageal perforation. The CI of LF at 2 years was 10.5%. The CI of ICST at 2 years was 44.0%. Median PFS was 9.9 months and median OS was 47.4 months. On UVA, shorter time between SBRT treatments (HR=62.50; p<0.01), ≥3 tumor targets (HR=2.96; p=0.04), and a higher V35Gy (HR=2.60; p=0.02) were predictive for a higher risk of CSRP. On MVA, shorter time between SBRT treatments (HR=55.56; p<0.01) and a higher V35Gy (HR=2.58; p=0.02) remained as statistically significant predictors. <h3>Conclusion</h3> In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Increasing the time between SBRT treatments and optimizing plans to lower the V35Gy may decrease the risk of CSRP.