Stereotactic body radiotherapy is widely used as a curative-intent treatment for medically inoperable early-stage non-small cell lung cancer and selected lung metastases. However, when tumors are located close to critical mediastinal structures, the balance between tumor control and treatment-related toxicity becomes much more delicate.
A new PRISMA-based systematic review and meta-analysis published in Clinical and Translational Radiation Oncology evaluated outcomes and safety of SBRT in centrally and ultra-centrally located lung tumors.
The analysis included 69 studies published between 2006 and 2025. In total, the authors evaluated 3,672 patients with centrally located lung tumors and 1,509 patients with ultra-centrally located tumors.
Why Central and Ultra-Central Tumors Are Challenging
Peripheral lung tumors can often be treated with highly ablative SBRT regimens because they are farther from critical thoracic organs.
Central and ultra-central tumors are different.
They may be close to or overlap with the proximal bronchial tree, trachea, esophagus, heart, major vessels, or other mediastinal structures. These organs are sensitive to high dose per fraction, and excessive exposure can lead to severe toxicity.
Historically, the region within 2 cm of the proximal bronchial tree was described as a “no-fly zone” because early SBRT experiences showed higher rates of severe and sometimes fatal events, including hemorrhage, pneumonitis, and airway necrosis.
Modern SBRT planning has improved substantially, but the anatomical risk remains real. This is why dose, fractionation, target coverage, organ-at-risk constraints, and patient-specific factors all matter.
Study Design
The authors performed a PRISMA-based systematic review and meta-analysis using PubMed/MEDLINE.
Eligible studies reported SBRT for centrally or ultra-centrally located lung tumors and included outcomes such as overall survival, progression-free survival, local control, or toxicity.
The final analysis included 57 retrospective and 12 prospective trials.
One important challenge was that definitions of ultra-central tumors varied across studies. Tumors abutting the proximal bronchial tree were consistently classified as ultra-central, but other definitions included overlap with the trachea, esophagus, major vessels, heart, or pericardial pleura.
This variation is important because even small differences in tumor location can strongly affect toxicity risk.
Main Outcomes
Median follow-up was 22.7 months for centrally located tumors and 21.2 months for ultra-centrally located tumors.
For central tumors, median overall survival was 39.4 months.
For ultra-central tumors, median overall survival was 28.0 months.
Median 1-year overall survival was 80.9% for central tumors and 78.6% for ultra-central tumors.
Median 2-year overall survival was 63.9% for central tumors and 57.0% for ultra-central tumors.
Local control was generally favorable.
Median 1-year local control was 92% for central tumors and 87.9% for ultra-central tumors.
Median 2-year local control was 85.2% for central tumors and 88% for ultra-central tumors.
These results support the role of SBRT as an effective local treatment option, even in anatomically complex thoracic locations.
Toxicity Findings
Overall, pooled grade 3 to 5 toxicity was low for both central and ultra-central tumors.
For ultra-central tumors, pooled grade 3 to 5 toxicity estimates were:
Pulmonary events: 1.75%
Pneumonitis: 0.71%
Esophagitis: 0.00%
Bleeding: 1.02%
For central tumors, pooled grade 3 to 5 toxicity estimates were:
Pulmonary events: 1.51%
Pneumonitis: 0.70%
Esophagitis: 0.01%
Bleeding: 0.17%
Grade 5 toxicity was uncommon, but clinically very important.
The most frequently reported fatal complication was hemorrhage. This was more relevant in ultra-central tumors, where tumors may abut or overlap central airways and major vessels.
The estimated proportion of fatal hemorrhage was 0.48% for ultra-central tumors and 0.12% for central tumors.
Fractionation Signal
Across the included studies, the regimen that appeared to offer the most favorable balance between tumor control and toxicity was 60 Gy in 8 fractions.
This dose schedule was associated with promising outcomes in both central and ultra-central tumors.
However, the authors were careful in their interpretation.
This regimen should not be viewed as automatically safe for every patient. In many studies using 60 Gy in 8 fractions, organ-at-risk constraints were prioritized over complete planning target volume coverage.
That detail matters.
In central and ultra-central lung SBRT, safety depends not only on prescription dose, but also on dose distribution, overlap with critical structures, planning technique, motion management, and patient-specific risk factors.
Risk Factors to Consider
Several factors may increase the risk of severe or fatal toxicity.
These include tumor overlap with the proximal bronchial tree, high dose to central airways or major vessels, large planning target volumes, prior bronchial interventions, re-irradiation, pre-existing interstitial lung disease, and concurrent use of anti-angiogenic drugs.
These risks are especially relevant for ultra-central tumors.
The study also notes that the absence of a clear correlation between biologically effective dose and toxicity should be interpreted cautiously, because organ-at-risk dose reporting was inconsistent across studies.
In other words, BED alone is not enough to predict safety.
Limitations
The authors highlight several limitations.
Most included studies were retrospective, and reporting standards varied.
Definitions of ultra-central tumors were inconsistent.
Toxicity timing was not always clearly reported, so acute and late toxicities were pooled.
Detailed dosimetric information, planning target volume coverage, and organ-at-risk dose parameters were often incomplete.
Because of this, the results support feasibility but should not be used as a one-size-fits-all treatment recommendation.
Prospective trials are still needed to refine dose constraints, treatment selection, and optimal fractionation.
Clinical Takeaway
SBRT appears to be a feasible and effective treatment option for centrally and ultra-centrally located lung tumors, with favorable local control and generally low pooled rates of severe toxicity.
The regimen of 60 Gy in 8 fractions appears promising, but careful interpretation is essential.
For these tumors, the goal is not simply to deliver an ablative dose.
The goal is to deliver enough dose for durable tumor control while protecting the proximal bronchial tree, esophagus, large vessels, and other critical structures.
The main message from this meta-analysis is clear:
SBRT can be used in central and ultra-central lung tumors, but only with individualized planning, strict organ-at-risk constraints, and careful attention to the risk of rare but potentially fatal toxicity.
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