Could Poor Outcomes for Patients with Limited Lung Function Treated with SAbR Necessitate PULSAR?

Stereotactic ablative radiotherapy (SAbR) employs precise targeting and delivery of ablative radiation doses in patients with medically inoperable early-stage non-small cell lung cancer, as well as patients with pulmonary metastases. SAbR is well tolerated with few studies reporting a minimal decline in pulmonary function tests (PFTs). However, poor pulmonary function is considered a risk factor for radiation induced lung toxicity. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) is an adaptive radiation therapy regimen where radiation pulses are delivered over longer periods of time, thereby allowing for modification of the treatment based on the patient's response, as well as limiting toxicities. As such, we hypothesize that treating patients with poor pulmonary function using a PULSAR approach is better tolerated in when compared to patients treated with SAbR.We performed a retrospective review of our institutional database of patients treated with SAbR to lung lesions from 2005 to 2022. We assessed the overall survival in stage-matched patients with normal vs poor lung function who received SAbR (40 patients in each cohort). Patients with decreased lung function included those with a diagnosis of moderate/severe COPD, restrictive lung disease, or patients needing home oxygen at the time of treatment. We then analyzed PFTs changes for patients receiving SAbR, and evaluated these changes relative to treatment delivery.Stage-matched Kaplan-Meier analysis of patients with normal vs poor lung function receiving SAbR revealed a statistically significant difference in survival with Log-rank test p = 0.007. Of the patients with PFTs, 45 (90%) received SAbR with two to three treatments weekly, while 5 (10%) were treated on a PULSAR regimen with one fraction every week to three weeks. No trends or significant differences are observed in the changes of total lung capacity (TLC), the first second of exhalation (FEV1), forced vital capacity (FVC) or FEV1/FVC ratios. However, we did note variations in the diffusing capacity of the lung for carbon monoxide (DLCO). The mean difference in DLCO for the SAbR and PULSAR groups were -26.07% (95% CI: -31.28 to -20.87, p < 0.0001), and -10.52% (95% CI: -40.74 to 19.69, p = 0.388), respectively.We observed a significant difference in overall survival between patients with normal vs poor lung function receiving SAbR. In a preliminary analysis, we discovered a small decline in DLCO for patients treated with regularly scheduled SAbR treatments. In the patients treated on the PULSAR regimen, however, this change in DLCO is not statistically significant. While this data suggests that increasing the time frame between individual doses of radiation may result in better toleration of radiotherapy in this patient population, the sample size of patients treated via PULSAR is limited, and longer follow-up is needed to further evaluate the potential benefits.