Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Cancer: A Systematic Review

Abstract

The safety and effectiveness of stereotactic ablative radiotherapy (SABR) for patients with ultra-central lung tumors is currently unclear. We performed a systematic review to summarize existing data and identify trends in treatment-related toxicity and local control following SABR in patients with ultra-central lung lesions. We performed a systematic review using the PRISMA guidelines. The PubMed and Embase databases were queried from dates of inception until September 2018. Studies in the English language that reported treatment-related toxicity and local control outcomes post-SABR for patients with ultra-central lung lesions were included. Ultra-central lung lesions were defined as lesion whose gross tumor volume (GTV) or planning target volume (PTV) abutted or invaded the proximal tracheo-bronchial tree (PBT) or other mediastinal structures such as the great vessels or esophagus. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation and studies with fewer than 5 patients were excluded. A total of 446 studies were identified, with 10 meeting all criteria for inclusion. A total of 250 patients with ultra-central lung lesions were included. All studies were retrospective in design. Radiotherapy dose and fractionation ranged from 30-60 Gy in 3-12 fractions, with median biologically-effective doses (BED10) ranging from 78-103 Gy10 in individual studies. Median treatment-related grade ≥3 toxicity was 10% (range: 0-50%). Median treatment-related mortality was 5% (range: 0-22%). The most common form of treatment-related mortality was pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the PBT ≥180 Gy3 (BED3, corresponding to 45 Gy in 5 fractions or 55 Gy in 8 fractions), peri-SABR bevacizumab use, and antiplatelet/anticoagulant use. Median 1-year local control rate was 96% (range: 63-100%) and 2-year local control rate was 92% (range: 57-100%). SABR for ultra-central lung lesions appears feasible with good local control outcomes. There is a potential for severe toxicity in patients receiving high doses to the PBT, those with endobronchial disease, and those receiving bevacizumab or anticoagulants around the time of SABR. Prospective studies are required to establish the optimal doses, volumes and normal tissue tolerances for SABR in this patient population.