Grade 4 Lymphopenia Induced by High Cardiac Radiation Exposure Predicted the Poor Prognosis in Left Non-Small Cell Lung Cancer Receiving Postoperative Radiotherapy

Abstract

Aimed to investigate the correlation between grade 4 (G4) lymphopenia and cardiac dosimetric and the role of G4 lymphopenia in predicting prognosis in left non-small cell lung cancer (NSCLC) receiving postoperative radiotherapy (PORT). Between 2009 and 2018, the clinical characteristics and radiation parameters of patients with PORT for left NSCLC were reviewed retrospectively. Lymphopenia was graded according to the CTCAE 4.0. Absolute lymphocyte count (ALC) nadir < 0.2 × 103/ul was defined as grade 4 (G4) lymphopenia. Logistic regressions were performed to analyzed potential related factors of lymphopenia. The overall survival (OS) was measured from the date of RT started to the date of death from any cause or the follow-up date. Kaplan-Meier was performed to calculate survival, and log-rank test was used to compare survival between the G4 and non-G4 group. Two-sided p values < 0.05 were considered statistically significant. A total of 151 patients were reviewed in this study. The major patients were female (52.3%), age ≥ 60 (60.3%), former/current smoker (74.8%), lobectomy (79.5%), stage III (84.1%), postoperative chemotherapy (75.5%) and intensity-modulated radiotherapy (IMRT, 64.2%). The clinical characteristics (e.g. Cardiac disease, body mass index, baseline ALC) and radiation dosimetric (PTV dose, and Heart/Lung RT dosimetric) of G4 (18 pts., 11.9%) and non-G4 (133 pts., 88.1%) were well balanced. The median PTV dose was 60 Gy in G4, whereas it was 54 Gy in non-G4. However, the PTV of G4 was significantly larger than that of non-G4 (563.51 ± 276.07 vs. 395.86 ± 254.58, p = 0.005). Multivariate logistic regression indicated PTV volume (HR 1.00, p = 0.01), PTV dose (HR 1.08, p = 0.04), RT fraction size (HR 0.23, p = 0.02), and Heart V5 (HR 1.09, p = 0.03) were associated with G4 lymphopenia. The median survival time of the whole cohorts was 36.8 months, while it was 23.2 months in the G4 group and 37.5 months in the non-G4 group (p = 0.01). The 1- and 3-year survival in G4 were 77.8% and 33.3%, respectively, compared to 85.2% and 53.1%, respectively, in non-G4. Multivariate analysis revealed former/current smoker (HR 1.57, p = 0.04), postoperative chemotherapy (HR 0.58, p = 0.02) and G4 lymphopenia (HR 1.78, p = 0.04) were significant prognostic factors for OS. Grade 4 lymphopenia was common in left NSCLC patients with PORT and correlated with heart V5. Grade 4 lymphopenia could predict poor survival in this population.