Our study sought to identify a cut-off on FEV1 or DLCO that could be associated with increased toxicity. We also evaluated the incidence of acute toxicities grade ≥ 2 by stratifying patients according to FEV1 into subgroups: FEV1 < 1.0 L, FEV1 < 1.5 L, FEV1 < 30% of predicted and FEV1 < 35% of predicted. However, similar to other studies, we did not find any value that was significantly associated with increased toxicity that could preclude empiric SABR. One possible reason is that no treatment is offered for patients with extremely poor lung function as deemed by clinical judgement, therefore data on these patients is unavailable. In contradiction to other studies, our study found that oxygen dependence before treatment was significantly associated with development of acute toxicities. The exact mechanism for this association is unknown and could not be elucidated by baseline PFT. One possible explanation is that SABR could lead to oxygen free radical generation. In addition, our study indicated that those who developed acute toxicities had worse OS.
Limitations
Our study is limited by caveats of a retrospective study and its small sample size, but is in line with the reported literature (ranging from 33 to 88 patients).1,7,8 Another limitation is that data on pretreatment DLCO was missing in 37 patients and the lack of statistical robustness in terms of the smaller inoperable cohort, which limits the analyses of these factors in regards to anticipated morbidity from SABR. Also, given this is data collected from the US Department of Veterans Affairs, only 3% of our sample was female.
Conclusions
Empiric SABR for patients with presumed early-stage NSCLC appears to be safe and might positively impact OS. Development of any acute toxicity grade ≥ 2 was significantly associated with dependence on supplemental oxygen before treatment, central tumor location, and development of new oxygen requirement. No association was found in patients with poor pulmonary function before treatment because we could not find a FEV1 or DLCO cutoff that could preclude patients from empiric SABR. Considering the poor survival of untreated early-stage NSCLC, coupled with the efficacy and safety of empiric SABR for those with presumed disease, definitive SABR should be offered selectively within this patient population.
Acknowledgments
Drs. Park, Whiting and Castillo contributed to data collection. Drs. Park, Govindan and Castillo contributed to the statistical analysis and writing the first draft and final manuscript. Drs. Park, Govindan, Huang, and Reddy contributed to the discussion section.
