Dose-response relationship of stereotactic body radiotherapy for ultracentral tumor and comparison of efficacy with central tumor: A meta-analysis

Background: Ultracentral (UC) tumors, a subset of central lung tumors defined as those that abut the proximal bronchial tree (PBT), have been contraindicated for stereotactic body radiotherapy (SBRT). The present meta-analysis evaluated the efficacy of SBRT for UC and central tumors, and dose-response for local control (LC) of UC tumors. Methods: Databases including MEDLINE and EMBASE were searched up to March, 2020, to identify studies regarding SBRT for UC and/or central tumors. The primary endpoints were LC and overall survival (OS), while secondary endpoints were grade =3 and 5 complications. Results: Fourteen studies including 892 patients were included. In the UC and central tumor groups, the 1-year OS rates were 82.2% and 85.4% (P=0.556), respectively, and the 2-year OS rates were 66.4% and 71.9% (P=0.522), respectively. The 1- and 2-year LC rates in the UC and central tumor groups were 93.9% and 97.8% (P=0.023) and 90.4% and 93.7% (P=0.459), respectively. The pooled grade =3 complication rates in the UC and central tumor groups were 9.0% and 4.4% (P=0.06), while the corresponding grade 5 complication rates were 5.7% and 2.1% (P=0.087). The dose-response for LC was shown in the metaregression (P<0.0001), and 1-year LC rates were significantly different (94.4% vs. 59.3%, P<0.001) with very low heterogeneities in both subgroups, with threshold of 85 Gy10. Of the 28 fatalities, 12 (42.8%) were caused by hemorrhage or bronchial stenosis, and another 12 (42.8%) by pneumonia or respiratory failure. Conclusions: The oncologic outcomes of patients with UC and central tumors were comparable post- SBRT. A dose of at least =85 Gy10 is recommended for SBRT of UC tumors. Causes of complications should be further studied as UC tumors are more prone to serious toxicities.