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

Abstract

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 meta-regression (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.

Keywords: Lung cancer; central tumor; stereotactic ablative body radiotherapy; stereotactic body radiotherapy (SBRT); ultracentral (UC) tumor.

Figure 1

Forest plots for the pooled analyses of controlled studies (comparison between the ultracentral and central tumor groups). (A) 1-year local control rate; (B) 2-year local control rate; (C) 1-year overall survival rate; (D) 2-year overall survival rate; (E) Grade ≥3 complication rate; (F) Grade 5 complication rate.

Figure 2

Dose-response relationship for local control in the scatterplot. (A) Meta-regression scatterplot for BED_10Gy and 1-year local control; (B) Forest plot of subgroup pooled analysis for 1-year local control with threshold of 85 Gy_10.

Figure S1

Study inclusion plot.

Figure S2

Forest plots and scatter plots of pooled analyses among all ultracentral cohorts. (A) 1-year local control rate (top to bottom: all cohort; subgroup comparison according to planning target volume; subgroup comparison according to the proportion of metastases or recurrence; scatterplot of meta-regression according to biologically equivalent dose); (B) 1-year overall survival rate (top to bottom: same order with above); (C) grade ≥3 complication rate (top to bottom: same order with above); (D) grade 5 complication rate (top to bottom: same order with above).