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 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.

Ultra-central lung tumors: safety and efficacy of protracted stereotactic body radiotherapy

“…The most recent meta-analysis of 72 studies of Rim et al demonstrated pooled 1-and 2-year local control rates of 93.3% (95% CI 95.6-8.9%) and 90.4% (95% CI 77.8-96.2%) after SBRT for ultra-central lung tumors, respectively. The corresponding pooled 1-and 2-year overall survival rates were 82.2% (95% CI 71.7-89.7%) and 66.4% (95% CI 51.4-78.7%), respectively [34]. These numbers are in line with our results.…”

“…These numbers are in line with our results. When comparing the local control and overall survival rates with the rates for central tumors, to which higher fractionation doses are described in most studies, no differences were found [34]. So, despite the knowledge that a BED 10 of !100 Gy leads to a low local failure rate of 8% compared to a local failure rate of 26% for a BED 10 of <100 Gy [4], our protracted SBRT regimen with a BED 10 of 90-150 Gy leads to somewhat limited, but very decent local tumor control, comparable with that for central tumors.…”

“…Besides, the updated meta-analysis of Rim et al (2020) demonstrated a pooled grade !3 toxicity rate of 10.4%, much lower than revealed in their previous meta-analysis in 2019. This is mainly due to inclusion of more recent trials which found lower rates of grade !3 toxicity (0À8%) [30][31][32][33], potentially because of avoidance of such risk factors as described in the previous studies and improved radiotherapy techniques [34].…”

“…These favorable local control rates might be the result of the higher accepted PTV max doses up to a median of 147 Gy BED 10 . However, it was also stated that with a threshold of BED 10 60 Gy for lymph node metastases and 85 Gy for primary tumors, a favorable 1-year regional control rate of 92% and a pooled 1-year local control rate of 94.3% with low heterogeneity was found respectively, suggesting that BED 10 over 100 Gy is not always necessary and should be carefully administered, taking the risk factors for fatal hemorrhage into account [34,35]. In addition, we found a lower overall survival rate (36% at 3 years) in our cohort, compared to that for peripheral tumors (about 56% at 3 years [4]).…”

Dosimetric Analysis of Proximal Bronchial Tree Subsegments to Assess The Risk of Severe Toxicity After Stereotactic Body Radiation Therapy of Ultra-central Lung Tumors

“… [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] After SBRT, local control (LC) rates of 80.0 % to 97.0 % after two years are comparable to surgical resection. [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] Furthermore, SBRT is increasingly used in oligometastatic cancer patients. [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] Despite major progress in the field of radiation-oncology, the safety and efficacy of SBRT in ultra-central lung tumors remains controversial.…”