The Impact Of "Low-Dose Lung Bath" On The Sensitivity Of The Lung To Radiation: Are There Neighborhood Effects In The Lung?

Increasing interest in IMRT, which often increases the volume of normal tissue at low dose, raises concerns regarding the impact of “low-dose baths” on normal tissue. We herein assess the impact of the irradiated “low-dose lung volume” on the response of the entire lung to RT. As part of an IRB approved-prospective clinical study, patients underwent pre-and serial post-RT lung SPECT (single photon emission computed tomography) scans providing quantitative assessments of regional lung perfusion. By registering pre-and post-RT SPECT scans to 3D doses (reflecting tissue density corrections), we can define an individual's dose response curve (DRC) for RT-induced regional lung injury. Population DRCs are computed as weighted averages of individual patient's DRCs. For the overall population and different subgroups, DRCs were fitted with a linear regression model, and hence described by their slope (% regional perfusion reduction per Gy). Patient subgroups were defined based on the percentage lung volume at low RT doses; e.g., V5, V10; and also the percent of lung receiving between 1–5 Gy (V1–5), 5–10 Gy (V5–10), and 5–15 (V5–15). The DRC slopes between subgroups were compared (t test). As prior studies suggested, DRC slopes stabilize at ≥6-month post-RT, data from 6-month post-RT scans were herein considered. 68 patients with SPECT DRCs at ∼6-mos post-RT were considered; overall population DRC slope = 0.86% per Gy. The slopes for patients with a V5 less than, or greater than, the mean V5 were 0.96 and 0.75 respectively p = 0.02. The results were similar for V10 (0.95 vs. 0.80, p = 0.04), V15 (0.99 vs. 0.79, p = 0.01), V5-10 (0.95 vs. 0.78, p = 0.07), and V5-15 (0.95 vs. 0.79, p = 0.07). The slopes of population DRCs appear steeper in patients with a smaller “low dose lung bath” compared to those with more. The differences in absolute terms are modest (≈0.77% per Gy vs. ≈0.94% per Gy; corresponding to a 15-20% relative increase in slope). This argues against the presence of a meaningful “neighborhood effect” in the lung, and suggests that IMRT may not alter the lung's sensitivity to radiation. Additional study is needed.