Stereotactic Body Radiation Therapy to Multiple Sites of Intrathoracic Disease: A Multi-Institutional Analysis

Abstract

There are limited data regarding the safety of stereotactic body radiotherapy (SBRT) to multiple sites of intrathoracic disease. We sought to assess rates of radiation pneumonitis (RP) and outcomes for patients treated with SBRT to multiple intrathoracic tumors. Thirty-eight patients with 84 synchronous (within 3 months) or metachronous lung nodules were treated with a total of 72 courses of SBRT between 2009 and 2017 at three tertiary hospitals. Clinical and dosimetric data were collected. Rates of RP (graded per CTCAE v4.0) and Kaplan-Meier estimates of oncological outcomes were calculated. Thirty-one patients were treated to 2 sites of disease, while six patients were treated to 3 sites, and one patient was treated to 4 sites. Nine patients received SBRT to two lesions simultaneously with one plan, while 13 and 9 patients received SBRT to synchronous or metachronous lesions, respectively. The median time interval between SBRT courses was 28.5 days (IQR: 18.5-43 days) for synchronous lesions and 14.7 months (IQR: 8.5-24.8) for metachronous lesions. Fifty-six (66.7%) of the treated lesions were primary lung cancers, while 28 (33.3%) were metastatic nodules (included for RP endpoint only). The most common fractionation scheme was 50 Gy in 5 fractions. Seventy-nine (94.0%) nodules received a biological effective dose of at least 100Gy. The median treated nodule size was 1.8 cm (IQR: 1.2-2.7). Median follow-up from the first SBRT course was 29.0 months. Grade 2 RP was diagnosed in 2 patients (5.2%) following the first SBRT course and 1 patient (2.6%) following the second SBRT course. Grade 3 RP was diagnosed in 2 patients following the second SBRT course (5.2%). Neither the number of treated sites nor the number of SBRT courses was associated with development of RP (P=0.48 and P=0.15, respectively) or grade of radiation pneumonitis (P=0.64 and P=0.16, respectively). Eighteen patients with a median age of 74 years (IQR: 67-80) received at least 2 courses of SBRT to a total of 40 primary Stage IA-IIB non-small cell lung cancers (NSCLC). At a median of 22.8 months (IQR: 14.0-40.9), the in-site recurrence rate was 5.6% (N=1), the ipsilateral lung recurrence rate was 27.8% (N=5), and the distant recurrence rate was 38.9% (N=7). The Kaplan-Meier estimate for 3-year freedom from in-site recurrence was 91.7% (95% CI: 77.3-100.0), 3-year freedom from locoregional recurrence was 63.1% (95% CI: 39.0-100.0), and 3-year overall survival was 62.5% (95% CI: 40.7-95.9). In this series of patients, more than one course of SBRT to synchronous or metachronous intrathoracic tumors was not associated with higher rates of RP. Excellent locoregional control was achieved among patients treated for early stage NSCLC. While larger studies are required, receipt of previous SBRT should not necessarily preclude consideration of further SBRT.