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February 8, 2026Journal of Clinical Medicine0 citationsOpen Access

Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) for Patients with Lung Tumors and Severe Pulmonary Disease

KWKenneth D. WestoverThe University of Texas Southwestern Medical Center RLRuiqi LiThe University of Texas Southwestern Medical Center STStetler TannerThe University of Texas Southwestern Medical Center

Key Points

To assess the effectiveness of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) in high-risk lung cancer patients.
Evaluated PULSAR treatment delivered every three weeks to patients with lung tumors smaller than 5 cm.
Utilized online adaptive radiotherapy (o-ART) for treatment planning adaptations in 80% of patients.
Monitored both primary outcomes, such as tumor volumetric response, and secondary outcomes, including overall survival.
Approximately 50% of patients showed a volumetric tumor response with a median residual volume of 70%.
Significant reductions in organ at risk dosimetry were observed, particularly for the heart and lung tissues.
Median progression-free survival reached 21.1 months, with a 1-year overall survival rate of 74%.

Abstract

Background/Objectives: Patients with early-stage non-small cell lung cancer (NSCLC) or limited lung metastases and compromised lung function, such as those with interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD), or other factors rendering them high-risk for surgery or medically inoperable, face increased risks of treatment-related toxicity from stereotactic ablative radiation therapy (SABR). This study evaluated a novel treatment approach to mitigate these risks. Methods: We investigated Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR), delivered as pulsed radiation every three weeks, in patients with <5 cm lung tumors and ILD, COPD, or prior therapy. Treatment occurred between 2022 and 2024. Online adaptive radiotherapy (o-ART) was employed in 20 patients (80%) to modify treatment plans when anatomical changes warranted replanning. Primary outcomes included volumetric tumor response, changes in dose to organs at risk (OARs) and acute events, while secondary outcomes included local and tumor control, and overall survival. Results: Twenty-three patients received PULSAR treatment at doses between 40 Gy and 60 Gy in 5 fractions and one patient received 54 Gy in 3 fractions, with a median follow-up time of 16.2 months. Approximately half of treated patients demonstrated volumetric tumor response, with median residual volume of 70% (range 36–100%) at maximal response. Among the 20 patients (80%) who underwent online adaptive replanning, significant reductions in OAR dosimetry were observed for all organs assessed including the Dmax for heart (p = 0.0053), bronchus (p = 0.0003), esophagus (p = 0.0005), spinal cord (p = 0.025), and the lung V20 Gy and V12.5 Gy (p < 0.0001). Treatment-related toxicity included two grade 1–2 adverse events and six grade 3 events consisting of pneumonitis, dyspnea or lung infection, with no grade 4 or 5 events. Median progression-free survival was 21.1 months, with 1-year overall survival of 74% and 1-year local control of 100%. Conclusions: PULSAR shows promise as a feasible treatment option for high-risk patients with NSCLC or lung metastases, demonstrating no grade 5 events and complete tumor control. Additional research is needed to fully evaluate the safety profile of PULSAR in the high-risk subgroups and whether PULSAR’s treatment intervals and adaptive planning advantages lead to improved long-term outcomes compared to conventional, uninterrupted SABR regimens.

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