Cardiac Maximum Point Dose Predicts for Patient Survival in Early Stage Non–small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Abstract

RTOG 0617 identified cardiac dose as an important predictor for survival in NSCLC patients treated with standard fractionation 3D conformal radiation therapy. Due to the increasing utilization of stereotactic body radiation therapy (SBRT) for early stage NSCLC, the aim of this study is to examine cardiac dose and survival outcomes for early stage NSCLC patients treated with SBRT. We identified 107 non-operable early stage NSCLC patients treated with SBRT between 2008 and 2015 within our multi-facility integrated health care system. The median age was 79 [61-89] years old, 97% of patients were smokers with median 40 [3.5-160] pack-years, and median Karnofsky Performance Status was 70 [50-100]. The median dose delivered was 50 [37.5 - 60] Gy to the isocenter in a range of 3 to 5 fractions using 8 to 11 co-planar beams. The patient’s heart was retrospectively contoured per RTOG guidelines. Dose-volume histogram (DVH) analysis was used to extract cardiac dose parameters. Survival analysis was then conducted using Kaplan-Meier method with log-rank test. After identifying patients with significant cardiac maximum point dose (CMPD), their heart V5, V10, V20, V30, and V40 values were recorded. In regards to this subgroups tumor location, 95% were in the left thorax, 95% were at the level of the heart base, and 50% were centrally located. The median time of follow-up was 26 [6-80] months. The five-year overall survival (OS) for the cohort was 24%. The median mean cardiac dose was 2.21 [0 – 18.62] Gy and was not associated with survival. The median CMPD was 13.6 [0.24-58] Gy. The CMPD was continuously analyzed and demonstrated an inverse relationship with survival; 5-year OS decreased as the CMPD increased: ≥20 Gy vs <20 Gy (19% vs 38%, P = 0.074), ≥25 Gy vs <25 Gy (9% vs 34%, P = 0.047), ≥30 Gy vs <30 Gy (10% vs 35%, P = 0.011), and ≥35 Gy vs <35 Gy (12% vs 34%, P = 0.027). The 5-year overall survival met a threshold dose of 25 Gy, where further increase in CMPD remained statistically detrimental but survival rates plateaued. Twenty patients were identified with a CMPD greater than 25 Gy. This sub-groups median cardiac DVH values were CMPD = 41.66 Gy, mean heart dose = 4.90 Gy, V20 = 13.94 cc, V25 = 9.70 cc, V30 = 2.69 cc, and V35 = 0.37 cc. In this cohort of non-operable early stage NSCLC patients treated with SBRT, maximum cardiac dose was found to be a predictor for survival. This inverse relationship became significant at point doses of 25 Gy and greater. The RTOG and the AAPM task group 101 recommend a CMPD less than 30 – 38 Gy, depending on SBRT fractionation. The results of this study warrant the further investigation into SBRT cardiac dose parameters and cardiac-specific mortality, particularly in elderly patients with significant cardiovascular comorbidities. Additionally, patients with left sided tumors located at the level of the heart base seem to be at highest risk for excessive dose to the heart; alternative treatment delivery techniques or dose modifications should also be investigated.