Purpose: Stereotactic body radiation therapy has been associated with increased toxicity when delivered to patients with early-stage non-small cell lung cancer with a tumor within 2 cm of the proximal bronchial tree (PBT). We investigated noncancer deaths for these patients as related to gross tumor volume (GTV) proximity to the PBT, compared with peripheral tumors. Methods and Materials: We included 765 patients with early-stage non-small cell lung cancer who were treated with stereotactic body radiation therapy to a median of 3 × 18 Gy. Central tumors were treated with a risk-adapted (less-intense) schedule (mostly 8 fractions) in 55% of the patients in the first-centimeter group and 27% of the patients in the second-centimeter group. An average anatomy with contouring of PBT and organs at risk (OARs) was deformed onto each patient to obtain the distance of the GTV to the PBT and doses to OARs. Log-rank, 1-way analysis of variance, and Cox regressions were performed to assess differences in the first-centimeter, second centimeter, and peripheral groups and associations with noncancer deaths. Results: The median overall survival was 42.7 months, the median noncancer death occurred in 57.3 months, and the median follow-up was 34.8 months. Noncancer death in the first-centimeter group (31 patients) was significantly different from noncancer death in the other groups, with a hazard ratio of 3.175 (P <.001). Noncancer death in the second-centimeter group (71 patients) was not different from noncancer death in the peripheral group (P =.53). Doses to OARs were higher in the first- and second-centimeter groups than in the peripheral group for all OARs. High dose to the PBT was associated with noncancer death (D1%; hazard ratio, 1.006 Gy−1; P =.003). Conclusions: Patients with a GTV in the first centimeter surrounding the PBT died more often from causes other than cancer compared with other patients. Noncancer death in patients with a GTV in the second centimeter, who partly received a risk-adapted schedule, was comparable to that in patients with a peripheral tumor.
Stam, B., Kwint, M., Guckenberger, M., Mantel, F., Hope, A., Giuliani, M., … Belderbos, J. (2019). Subgroup Survival Analysis in Stage I-II NSCLC Patients With a Central Tumor Partly Treated With Risk-Adapted SBRT. International Journal of Radiation Oncology Biology Physics, 103(1), 132–141. https://doi.org/10.1016/j.ijrobp.2018.08.040