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

Abstract

Introduction: The safety and effectiveness of stereotactic ablative radiotherapy (SABR) in 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. Methods: We performed a systematic review based on the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines using the PubMed and Embase databases. The databases were queried from dates of inception until September 27, 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. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation, and studies with fewer than five patients were excluded. Results: A total of 446 studies were identified, with 10 meeting all criteria for inclusion. The total sample size from the identified studies was 250 ultra-central lung patients and all studies were retrospective in design. Radiotherapy dose and fractionation ranged from 30 to 60 Gy in 3 to 12 fractions, with biologically effective doses (BED 10) ranging from 48 to 138 Gy 10 (median, 78-103 Gy 10). Median treatment-related grade 3 or greater toxicity was 10% (range, 0-50%). Median treatmentrelated mortality was 5% (range, 0-22%), most commonly from pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the proximal bronchial tree greater than or equal to 180 Gy 3 (BED 3 , 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%). Conclusions: SABR for ultra-central lung lesions appears feasible but there is a potential for severe toxicity in patients receiving high doses to the proximal bronchial tree, 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.

Toxicity and Efficacy of Stereotactic Body Radiotherapy for Ultra-central Lung Tumours: a Single Institution Real Life Experience

“…Yet, we obtained a local control rate of 96.7% at 1 year and 87.6% at 2 years; 10.8% of patients had a primary local relapse. Similar results were reported by Yang et al and in the meta-analysis by Chen et al [15,29]. In the present study, a prescribed BED 10 < 50 Gy was correlated with an increasing risk of local recurrence.…”

Stereotactic Radiotherapy for Ultra-Central Lung Oligometastases in Non-Small-Cell Lung Cancer

“…The author found no difference in LC, OS, and grade ≥3 toxicity comparing patients with central and ultra-central tumors [34]. A recent review analyzed data from 10 studies focusing on SBRT for ultra-central lung tumors, for a total number of 250 treated patients [19]. Despite obvious limitations linked to the retrospective nature of the study and the heterogeneity of delivered doses (BED ranging from 48 to 138 Gy), safety was confirmed.…”

“…Conversely, use of more protracted dose schedules (4-12 fractions) showed an acceptable toxicity incidence with satisfying oncologic outcomes [14][15][16][17][18]. Recently, a subset of proximally-seated central tumors, dubbed "ultra-central", has been reported as a separate clinical entity due to possible additional increased risk of fatal toxicity [19]. However there is no consensual definition of "ultra-central" tumors.…”

Optimizing lung cancer radiation treatment worldwide in COVID-19 outbreak

“…More mild hypofractionation could be considered in very select patients (i.e. ultra-central lung lesions), akin to treatment approaches in NSCLC [13]. [32,33].…”