Can Dosimetry Affect Overall Survival in Patients with Medically Inoperable Peripheral Early Stage Lung Cancer Treated with Stereotactic Ablative Radiotherapy (SABR)? An Analysis of 1300 Patients

Abstract

SABR is an established treatment option for early stage medically inoperable peripheral lung cancer. Recent studies have shown that tight conformity of radiotherapy plans i.e., reducing the radiation dose outside the target volume might worsen loco-regional control and can predict more distant metastases. The aim of the study is to report overall survival and dosimetry of early stage peripheral lung cancer patients treated with SABR and to try to explore if any dosimetric parameters can predict overall survival. Patients treated with SABR in a single institute in UK between May 2009 and August 2018 were included. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. Dosimetric data was extracted from software. For the planning target volume (PTV), plan conformity was assessed using three indices, i.e., R100-volume receiving the 100% dose /volume (PTV), R50- volume receiving the 50% dose/volume (PTV), and maximum dose to >2 cm of PTV(D2cm). Patients were treated according to the UK SABR consortium guidelines. Kaplan Meier survival analysis was done for univariate analysis and Cox regression model was used for multivariate analysis, using IBM software. 1300 patients received SABR treatment for 1357 tumors. Median age of the patients were 75 years (range 38-97 years). Median follow up was 26 months. Median overall survival was 37 months with 1,2,3,4 and 5 years survival rates of 84.4%, 65%, 50.7%, 39.5% and 30.8%, respectively. Median PTV volume was 30 cc ((range 5.5-213.4 cc, Inter quartile range (IQR)-29.6). Median values of R100, R50 and D2cm were 1.1(range 0.68-3.19, IQR-0.08), 5.6(range 2.2-16.2, IQR- 2.08), 32.7Gy (range 9.3-56.3Gy, IQR-5.9Gy). Median value of mean lung dose, V20 and V12.5 were 3.9Gy (range 0.6-11.5Gy, IQR-2Gy), 5 %( range 0.2-19.3%, IQR-3.4%) and 9.3% (range 1.4-30.8%, IQR-5.4%). On univariate analysis, only R100 of ≤ 1.10 was found to be significantly associated with improved survival (median survival 40 months vs 33 months, hazard ratio 0.85, 95% confidence interval 0.73-0.98) which was also confirmed in multivariate cox regression analysis. Although treatments with R50 of ≤ 6 have shown to have better survival (38 months vs 35 months) but that was not significant in univariate or multivariate analysis. A more conformal plan with high dose matching to the PTV with R100 of < 1.10 is associated with improved survival in medically inoperable early stage lung cancer patients treated with SABR, which emphasizes the importance of plan conformity. However, this data needs to be interpreted cautiously taking into account other possible confounding variables, particularly higher dose to heart +/- lung with less conformal SABR plans.