Cardiac Toxicity in Central Non-Small Cell Lung Tumors treated with Stereotactic Body Radiation Therapy (SBRT) – Is there a “No-Flutter Zone”?

Abstract

Cardiac toxicity has been well-described following conventional radiotherapy to the thorax; however, the long-term cardiac effects of ablative stereotactic body radiotherapy (SBRT) doses are unknown. Furthermore, appropriate dose constraints to the heart to minimize long-term cardiac toxicity have not been well characterized, nor has the potential effect of pre-existing cardiac disease on toxicity risk. We conducted an institutional database review to assess cardiac events in patients treated with SBRT for central early-stage lung cancer or metastasis within 5 cm of the heart, prior to the year 2017 to allow sufficient follow up. Descriptive statistics were used to report patient and treatment information, and cardiac events. Linear regression was used to assess the relationship between cardiac events and age, gender, cardiac history, smoking history, tumor size, and cardiac dose (mean, maximum, volume receiving, 5Gy, 10Gy and 30Gy). Forty-seven patients met criteria, 39 patients with primary NSCLC, and 8 with central lung metastasis. Median follow up time after SBRT was 21.5 months (range 2.1-61). Mean tumor diameter was 4.3 cm (range 2.5-7.4). Seventeen (36.2%) patients had a pre-existing cardiac history, most commonly ischemia or MI. Median distance from the tumor to heart in all included patients was 1.8 cm (range 0.0-4.9). Eight of 47 patients (12.1%) had a cardiac event following SBRT (2 de novo, 6 in patients with cardiac history), at a median time of 30 months (range 17-34). Six of the 8 patients had tumors located within 1 cm of the heart. Maximum heart doses ranged from 20.8Gy to 61.7Gy (median 51 Gy), while MHD ranged from 2.3-7.8Gy (median 5.6Gy). Only one cardiac death attributed to atrial fibrillation causing stroke occurred, in a patient with a prior history of atrial fibrillation. On univariate analysis, previous history of cardiac disease (OR 4.4; p = 0.03) was with an increased risk of cardiac events. On multivariate analysis, there was a trend towards association between cardiac history and cardiac events, however this was not statistically significant (OR 5.2, p = 0.1). Mean and maximum heart dose, V5, V10, V30, were not significantly associated with cardiac disease (see Tables 5 and 6). Overall, current SBRT dose constraints for the heart appear to be safe with low risk of cardiac events, and our findings do not support previous reports of an association between cardiac events, death and SBRT dose. Cardiac history was the main predictor of cardiac event post-SBRT, and this should be considered when treating patients with SBRT for central tumors in close proximity to the heart.