Comprehensive Analysis of Toxicity and Pulmonary Function Tests in Patients Undergoing Repeat Lung Stereotactic Body Radiation Therapy (SBRT) After Initial Lung SBRT

Abstract

There is a paucity of data on the role of repeat lung SBRT in patients who have undergone a prior course of SBRT. We performed a comprehensive analysis of toxicity and pulmonary function tests in patients who underwent repeat lung SBRT. Using an institutional lung SBRT database (2003-2016), we identified patients who underwent two separate courses of SBRT for early stage lung cancer or oligometastatic disease. We included patients treated with repeat SBRT for local failure, for new primaries or new sites of oligometastasis. Toxicities were graded according to CTCAE v4. Pulmonary function tests (PFTs) were obtained prior to SBRT and at follow-up. Changes in PFTs were evaluated using Repeated Measures Analysis of Variance. Local failure was assessed using Kaplan-Meier estimates and association with clinical and treatment variables was assessed using competing risk regression with death as the competing risk. We identified 111 patients who underwent repeat SBRT, of whom 32 (28.8%) were for local failure, 60 (54.1%) for a new primary and 19 (17.1%) for a new site of oligometastases. Median time between initial and repeat SBRT was 17.9 mo (range, 3.7-86.3) and the median follow-up after repeat SBRT was 16.6 mo (range, 0-64). Median overall survival after repeat lung SBRT was 28.3 mo. At time of initial SBRT, 11 (9.9%) patients underwent other synchronous SBRT treatments and 4 (3.6%) patients had received prior thoracic radiotherapy. Majority (64%) of patients received 50 Gy/5 fx or 48 Gy/4 fx at repeat lung SBRT. Chest wall (CW) toxicity occurred in 10 (9%) patients of whom 3 developed Grade 1, 5 developed Grade 2, and 3 developed Grade 3; one patient developed a rib fracture. All patients with CW toxicity had peripheral tumors. Older age (p=0.03) and peripheral location (p<0.01) were associated with increased risk for CW toxicity. Pneumonitis occurred in 7 (6.3%) patients of whom 3 developed Grade 1, 2 developed Grade 2 and 2 developed Grade 3. No variables predicted for pneumonitis (all p>0.05). Pre-treatment and post-treatment PFTs were available in 51 patients. Median FEV1(L)/FEV1%/DLCO at baseline, prior to repeat SBRT and post-repeat SBRT were 1.3/67%/57, 1.3/59%/51, 1.3/62%/51, respectively. Changes in FEV1 and FEV1% were not statistically significant. DLCO decline after the first course of SBRT was statistically significant (p<0.01), however, there was no statistically significant decline noted after repeat SBRT (p>0.05). At last follow-up, 13 (11.8%) patients developed local failure, 3 (2.7%) developed lobar failure, 13 (11.8%) developed nodal failure and 32 (28.8%) developed distant failure after repeat SBRT. Repeat lung SBRT was well tolerated and associated with a low risk for toxicity. There were no clinically significant PFT changes after repeat lung SBRT and the primary pattern of failure in cases of repeat SBRT was distant failure.