Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy in Lung Cancer and Lung Metastases: A Systematic Review.

BACKGROUND/

OBJECTIVES

Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) delivers high-dose stereotactic radiation as temporally separated pulses, permitting interval response assessment, adaptive replanning, and integration with systemic therapy. Its role in lung cancer and lung metastases remains uncertain. This systematic review synthesizes evidence for PULSAR and PULSAR-like approaches in these settings.

METHODS

Embase, MEDLINE, and Cochrane Central were searched from inception to 27 May 2026. Eligible records included clinical studies, trial registries, dosimetric simulations, and preclinical studies. Evidence was stratified into five tiers, with lung-target clinical studies considered direct evidence. Design-appropriate tools were used to assess risk of bias, and certainty was evaluated using a GRADE-informed approach.

RESULTS

Fifteen records were included: five lung-target clinical reports, one brain-metastasis clinical report, one patient-derived dosimetric simulation, five trial registry records, and three preclinical or computational modelling reports. Clinical evidence comprised small cohorts, case reports, and abstracts. True PULSAR regimens used three to five high-dose pulses separated by three- to four-week intervals with CBCT- or MRI-guided adaptive replanning. Studies suggested technical deliverability, interval tumour regression, and organ-at-risk dose reductions. One lung cohort reported 100% 1-year local control, but comparative safety and efficacy were not established. Pulmonary-function and quality-of-life data were sparse. Preclinical studies supported schedule-dependent interactions between pulsed radiation and PD-L1 blockade. Risk of bias was high to critical, and certainty was very low overall.

CONCLUSIONS

PULSAR is technically deliverable in high-risk patients, but evidence remains preliminary. Prospective comparative trials are needed to define optimal schedules, adaptation triggers, safety, quality of life, and patient selection.