Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design.

We performed a systematic review and meta-analysis of studies reporting the incidence of radiation induced brachial plexopathy (RIBP) and the associated radiotherapy doses to this structure. Databases were queried without language restriction for cohort studies reporting RIBP incidence and associated brachial plexus dose maximum dose (bpDmax). Studies specifying RIBP relative risk (RR) effect size were selected for meta-analysis. RRs for RIBP from each study were converted to a regression coefficient (β) and standard error corresponding to a continuous representation of bpDmax. The adjusted β from individual studies were combined using a random effects model and weighted by inverse variance (1/SE2). The trim and fill approach was used to assess publication bias. We identified 25 studies that included 37 unique patient cohorts eligible for analysis. Seventeen cohorts experienced an RIBP incidence ≤5%, of which 6 cohorts exceeded conventional plexus constraints of 60 Gy for bpDmax. Five of the 6 cohorts were simulated with 3D-CT techniques. Meta-analysis of eligible studies demonstrated a significant increase in RIBP risk for each Gy increase in bpDmax (RR, 1.11; 95% CI 1.07-1.15). Results remained significant after adjustment for publication bias and when sensitivity analysis was performed. Our results suggest that current brachial plexus constraints of 60-66 Gy are safe. Meta-analysis provides a log-linear model to quantify the association of brachial plexus dose and RIBP risk, and thus inform the therapeutic ratio for dose escalation. Further prospective studies reporting dosimetric data can better refine this model and inform brachial plexus constraint guidelines.

Objective: In contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment. There is mounting evidence in support of the role of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer (OMPC). Methods: MEDLINE and EMBASE were queried for prospective cohort studies reporting the outcomes of metachronous OMPC treated with SBRT. The primary outcome was overall local control. Secondary outcomes included androgen deprivation therapy-free survival (ADTFS), biochemical recurrence free survival (BCFS), and progression-free survival (PFS). When appropriate, these endpoints were combined in a meta-analysis. Results: We screened 356 abstracts and identified 10 studies to include in our analysis, with a total of 653 patients and 1,111 lesions. The maximum number of lesions included in any single study ranged from 3 to 5. PET-CT staging occurred in 92.4% of all patients. SBRT dose varied, with BED_1.5 ranging from 152 to 408. Only one Grade 3 bone toxicity was observed. Meta-analysis reported an overall local control rate of 97% (95% CI, 94–100). Median ADTFS was 24.7 months (95% CI, 20.1–29.2 months). Two-year BCFS, PFS, and ADTFS were 33% (95% CI, 11–55), 39% (95% CI, 24–54), and 52% (95%CI, 41–62), respectively. Patients treated with SBRT were half as likely to experience PSA progression than those on observation when looking at randomized control trial data alone. Conclusion: SBRT appears to be effective in controlling overall disease burden in metachronous OMPC patients and is associated with minimal significant toxicity. The current prospective literature is scarce, and further prospective data are needed to guide treatment recommendations. Advances in knowledge: This study provides a comprehensive summary of the prospective evidence reporting the outcomes of SBRT in the management of OMPC patients. We quantify the rates of local control, biochemical-free recurrence, progression-free survival, and ADT-free survival through meta-analysis.

Objective: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. Results: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). Conclusions: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery. Keywords: Carcinoma, Non-Small-Cell Lung/surgery; Radiosurgery; Meta-analysis.