In NSCLC, Personalized Radiotherapy Effective for Ultra-Central Tumors

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Tailored radiotherapy with nonuniform target compromises and stringent constraints delivered excellent local control and low toxicity for ultra‑central NSCLC.

Ultra-central non-small cell lung cancer (NSCLC), defined as tumors abutting or overlapping critical mediastinal structures, has long posed a treatment challenge due to the risk for toxicity when using stereotactic body radiation therapy (SBRT). New evidence presented at the 2025 ASCO Annual Meeting suggests that highly individualized SBRT planning can overcome this challenge, providing disease control while minimizing complications.

“SBRT has shown exceptional efficacy for early-stage NSCLC. However, treating ultra-central NSCLC tumors located near critical organs at risk remains a challenge due to potential toxicities,” wrote lead author Di Liu and colleagues. “Advances in personalized radiotherapy planning may enable safe and effective treatment for these patients.”

The researchers retrospectively evaluated 66 patients with unresectable stage I or II ultra-central NSCLC treated between 2020 and 2023. They defined ultra-central disease by a planning target volume (PTV) abutting or overlapping the proximal bronchial tree, esophagus, heart, great vessels, or pulmonary vessels, or located within 1 cm of these critical structures.

“The organ at risk constraints in this study included both maximum dose and volumetric thresholds to ensure comprehensive protection of critical structures,” the researchers noted. “To facilitate safe dose delivery under these stringent constraints, nonuniform PTV compromises were applied in 45.5% of patients, allowing 53.3% to achieve a BED₁₀ of 100 Gy.”

With a median follow-up of 23.7 months, the 1- and 3-year progression-free survival rates were 93.9% and 67.0%, respectively. The 1- and 3-year local control rates were 98.5% and 81.4%, respectively. Overall survival at 1 and 3 years was 98.5% and 92.8%, respectively.

Toxicity was low, with acute grade 1 pneumonitis occurring in 28.8% of patients, and grade 2 pneumonitis in 7.6%; only one patient (1.5%) developed grade 3 pneumonitis. Late toxicities were similarly mild, with 9% of patients experiencing grade 1 pulmonary fibrosis and one patient presenting with grade 2 disease. The researchers did not observe any severe toxicities (greater than grade 3).

The researchers emphasized that the use of individualized, nonuniform PTV compromises did not compromise clinical efficacy, yielding outcomes comparable with those achieved in less challenging cases of early-stage NSCLC.

“Tailored SBRT, utilizing nonuniform PTV compromises and stringent organ at risk constraints, demonstrated excellent tumor control and minimal toxicity in [ultra-central NSCLC]. These personalized treatment plans effectively managed ultra-central tumors, even in the most challenging cases,” Liu and colleagues concluded. “These results highlight the feasibility and effectiveness of individualized radiotherapy approaches, reinforcing SBRT as a safe and viable treatment option.”