Stereotactic Ablative Radiotherapy for Mediastinal and Hilar Lymphadenopathy: A Systematic Review

Abstract

Stereotactic ablative radiotherapy (SABR) is a form of high dose hypofractionated radiotherapy typically delivered ≤ 5 fractions and a desired BED10 ≥ 100 Gy10. While established for parenchymal lung tumors, its safety and effectiveness for mediastinal and hilar lymphadenopathy (MHL), is not well established, given the potential for toxicity due to proximity of nearby organs at risk. Therefore, the objective of this study was to summarize reported outcomes following SABR for MHL. A systematic review, based on the PRISMA guidelines, was performed using MEDLINE® (PubMed®), EMBASE and Cochrane Library databases from inception until December 2018. Studies reporting outcomes from SABR specifically for MHL from all primary malignancies were included. Studies were not excluded based on SABR dosage and fractionation prescribed. Non-English studies, guidelines, reviews, non-peer reviewed correspondences, and studies with fewer than 5 patients were excluded. If multiple publications were found from the same institution, only the most recent publication and/or largest cohort were included for data abstraction. From the 223 studies initially identified, 4 studies totaling 196 unique patients met all inclusion criteria. All studies were retrospective in design, and from single institutions. The majority (65%) of patients (n=127) had a diagnosis of non-small cell lung cancer, and breast was the second most common with 16 patients (8%). Median follow-up periods ranged between 12.0-32.2 months. SABR dose and fractionation ranged from 21 Gy to 60 Gy in 3-11 fractions, which corresponded to a median BED10 ranging from 46-106 Gy10. Planning tumor volume (PTV) margins employed ranged from 3 to 5 mm. Three studies reported local control (LC) rates, which were: study I) 97% (1-year) and 77% (5-year); study II) 66% (16-month) and study III) 88% (2-year). Overall survival (OS) was calculated from time of treatment in 3 studies, with a weighted median OS of 24.3 (18.0-27.2) months. Weighted progression-free survival (PFS) calculated from 2 studies were 11.4 (9.0-13.1) months. Overall, SABR was well tolerated; with a weighted Grade 3-5 toxicity rate of 6% (n = 11). The weighted treatment-related mortality (i.e. Grade 5 toxicity) rate was 2% (n=4). Despite the potential for serious toxicity, SABR for MHL appears to be feasible and effective. Considering the inconsistency of reported patients, SABR prescriptions, treatments, and outcome variables, both multi-institutional and/or prospective data would be helpful to determine the relative therapeutic benefit of SABR in this high-risk treatment scenario.