Stereotactic Body Radiation Therapy Can Be Delivered Safely to Ultracentral Lung Tumors with Excellent Local Control: A Single-Institution Experience

Purpose: Hypofractionated radiation therapy (HFRT) and stereotactic body radiation therapy (SBRT) are promising treatment options for lung cancers. Early SBRT studies suggested increased complications for tumors treated near mediastinal organs at risk, termed as ‘ultracentral’. Our study assessed outcomes and toxicities in lung tumors treated using HFRT or SBRT.

Methodology: Ultracentral tumors were defined as those invading, directly abutting, or having an overlapping planning target volume (PTV) with the trachea, proximal bronchial tree, heart, great vessels, or esophagus. HFRT was defined as radiation delivered in 6-15 fractions, while SBRT as ≤5 fractions. Eighty-six patients with ultracentral non-small cell lung cancer (NSCLC) or lung metastases who underwent 94 separate radiotherapy treatments between 2014-2023 were retrospectively analyzed for toxicities, overall survival (OS), and local control (LC). Univariate and multivariate Cox regression, as well as the Mann-Whitney U test, were used for analysis.

Results: The median follow-up time was 17.3 months. Of the 86 patients, 20 were categorized as primary localized, while 66 who had recurrent NSCLC or lung metastases were categorized as late-stage.

38.3% of patients experienced radiation pneumonitis (RP), the majority of which were Grade 1 (22.3%) and Grade 2 (12.8%), with only three (3.2%) Grade 3. 14.9% of patients experienced esophagitis, all of which were Grade 1 (4.3%) and Grade 2 (10.6%). 2.2% of patients experienced pulmonary hemorrhage, including one Grade 1 and one Grade 3. There were no incidents of airway fistula, perforation, or necrosis. Patients with RP had a higher V20Gy and PTV (both p< 0.01).

Median OS was 37.7 months, and 1-, 2-, and 3-year OS were 77.7%, 63.7%, and 50.9% respectively. 30-day mortality was 0.0% while the 90-day mortality was 2.3%. Univariate Cox regression analysis identified biologically effective dose (BED10) ≥100Gy and delivering ≤5 fractions as treatment parameters associated with improved OS (both p< 0.01) with HRs of 0.23 (95% CI: 0.11-0.47) and 0.36 (95% CI: 0.17-0.76) respectively. After adjusting for age, sex, clinical staging, and PTV volume, only BED10 ≥100Gy was associated with significantly improved OS (p=0.01) with a HR of 0.189 (95% CI: 0.07-0.51).

1-, 2-, and 3-year LC rates were 93.1%, 82.3%, and 78.1% respectively. Univariate Cox regression identified RP as a risk factor for local failure (p=0.005, HR=19.0 [95% CI: 2.42-149.8]).

Conclusions: HFRT and SBRT can be delivered to ultracentral lung tumors with low toxicity rates. Higher BED10 and fewer fractions were associated with improved OS. A larger PTV was linked to increased rates of RP, which was identified as a risk factor for local failure. Clinicians should aim to deliver radiation with a high BED10 while minimizing doses to organs at risk for optimal treatment outcomes.

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