Objectives: The role of Stereotactic body radiation therapy (SBRT) in centrally located non-small cell lung cancer (NSCLC) remains controversial because of the potentially severe toxicity, especially for the optimal dose-fractionation regimen. This study was to evaluate the effect of dose-location relationship on safety and efficacy in centrally located NSCLC using SBRT.

Methods: Eighty patients (56 male and 24 female) with within 2 cm of the bronchial tree, centrally located early-stage NSCLC treated with SBRT were retrospectively enrolled between January 2006 and December 2015. All included patients were conformed by histologically and PET-CT or CT. The PTV dose was prescribed with a median 74% (range, 58%-80%) isodose line, which covered at least 95% of the PTV. Here, we adopted two kinds of classification: all lesions are divided into two groups (overlapping-O; Non-overlapping-N) according to overlapping volume between PTV and the proximal bronchus tree (PBT), or the distance between GTV and PBT (≤5mm-T≤5; 5-20mm-T>5). The primary endpoint was the toxicity. The second endpoints were overall survival (OS), local control rate (LC).

Results: The median age of all patients was 71 years (range, 51-85). Thirty-seven patients had T1 cancer, 33 had T2a, and 10 had T2b. The median PTV volume was 52.2 mL (range, 2.8-264.5), the median prescription dose was 56 Gy (range, 48-60) in 6 fractions (range, 3-10), and the median BED10 was 102.6 Gy (range, 81.3-151.2). Median follow-up was 22.6 months (range, 2.6-68.2). CTCAE v4.0 = Grade 3 toxicities occurred in only one patient, who died from radiation pneumonitis. The median OS, 3-year, and 5-year OS were 37.9 months, 51.7%, and 36.8%, respectively. The 3-year and 5-year cancer-specific OS were 63.6% and 52.5%, respectively. The 1-year and 5-year LC rates were 97.1% and 95.6%, respectively. There are 53, 27, 50, 30 patients in Group O, Group N, T≤5 and Group T>5, respectively. The median PTV volume was 55.0 mL, 48.7 mL, 54.7 mL, and 48.9 mL (range, 9.9-264.5, 2.8-125.4, 9.9-264.5, 2.8-125.4), median prescription dose was 56 Gy, 60 Gy, 56 Gy, and 60 Gy (range, 48-60, 48-60, 48-60, 48-60) in 7, 6, 7, 6, fractions (range, 5-10, 3-8, 5-10, 3-8) with per dose 8 Gy, 10 Gy, 8 Gy, 10 Gy, and median BED10 was 100.8 Gy, 120 Gy, 100 Gy, 120 Gy, (range, 81.3-132, 94.4-151.2, 81.3-132, 94.4-151.2) in Group O, Group N, T≤5 and Group T>5, respectively. One patient with Grade 5 radiation pneumonitis occurred in Group N and Group T>5,and there were no Grade 3 and more toxicities occurred in Group O and T≤5. And, 54.7%, 37.0%, 40%, and 56% toxicities occurred in Group O, Group N, T≤5 and Group T>5, respectively. Furthermore, there has no significant difference in OS and LC between Group O and Group N  (p=0.36, p=0.22), or Group T≤5 and Group T>5 (p=0.39, p=0.27).

Conclusions: SBRT is a safe and efficacious treatment strategy for central NSCLC. For those tumors within 5 mm of PBT or PTV overlapping PBT, 7 fractions with 8 Gy per dose might be an option and outer of them be with higher per dose, which may achieve the acceptable survival and attenuate the toxicities. Given the potential risks and survival, we recommend that the different dose fractionation regimen could be tried depending on the distance between tumors and PBT. Further studies should be warranted.