Study protocol for the TROG 21.08 VITaL trial: a randomized controlled trial investigating ventilation imaging to improve the quality of life for patients with lung cancer treated with radiation therapy

BACKGROUND: Radiation therapy (RT) is indicated for 77% of patients with lung cancer. Over 20% of patients are affected by radiation-induced lung injury. Computed tomography ventilation imaging (CTVI) estimates high and low functioning lung regions. During RT planning, CTVI can guide preferential avoidance of higher ventilated regions by redirecting dose to less well ventilated regions, sparing healthy lung tissue. The double-masked randomized Trans-Tasman Radiation Oncology Group (TROG) 21.08 VITaL trial will investigate if sparing healthy lung can improve the quality of life (QoL) for patients with stage 3 non-small cell lung cancer (NSCLC) treated with RT. METHODS: 165 patients will be recruited to test the hypothesis that patients receiving healthy lung-sparing RT have better QoL than patients receiving standard RT. CTVI will be generated from exhale and inhale breath-hold CT scan pairs. A healthy lung-sparing plan and a standard treatment plan will be created for each patient and randomly assigned in a 1:1 ratio for the patient's treatment. QoL will be assessed with the Functional Assessment of Cancer Therapy-Lung questionnaire before and after treatment. Secondary hypotheses include that patients in the healthy lung-sparing arm will have fewer treatment side effects, better lung function, be more likely to receive and complete adjuvant immunotherapy, and healthy lung-sparing treatment will be cost-effective. Patient follow-up will continue for three years. DISCUSSION: This prospective randomized trial will determine whether the incorporation of healthy lung-sparing RT based on CTVI improves QoL, reduces pulmonary toxicity, and increases eligibility to receive curative immunotherapy for patients with stage 3 NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06127654).