A Phase I Study of Cyclical Hypofractionated Palliative Radiation Therapy (Quad Shot) for Central Lung Tumors in Patients With Stage IV Non-Small Cell Lung Cancer: Results From the PROMISE 006 Trial.

PURPOSE: Patients with stage IV non-small cell lung cancer (NSCLC) often present with substantial symptom burden that impairs quality of life and tolerance of systemic therapy. Quad Shot (QS), a cyclical hypofractionated radiation therapy (RT) regimen, could provide effective symptom palliation while allowing concurrent systemic therapy. We evaluated the safety, feasibility, and patient-reported outcomes of delivering up to 3 cycles of QS concurrently with systemic therapy.

METHODS AND MATERIALS: This prospective phase I dose-escalation trial enrolled patients with stage IV NSCLC from June 2020 to February 2024. Allowable systemic therapy included immunotherapy alone, immunotherapy plus chemotherapy, or chemotherapy alone at the treating medical oncologist's discretion. Each QS cycle consisted of 14.8 Gy in 4 fractions delivered twice daily over 2 consecutive days within 1 week of systemic therapy. The primary endpoint was to determine the maximum tolerated number of QS cycles using a modified 3 + 3 design, defined as a dose-limiting toxicity rate ≤17% (1 of 6 patients). Secondary endpoints included feasibility, systemic therapy disruptions, RT-related toxicities, and patient-reported outcomes.

RESULTS

Forty-five patients were enrolled in this study. One dose-limiting toxicity occurred in the 2-cycle cohort, and none occurred with 3 cycles, establishing 3 cycles as the maximum tolerated dose. In the expansion cohort, 3 patients developed grade 3 RT-related toxicities. All systemic therapies were administered without any interruptions. Among symptomatic patients, patient-reported outcomes demonstrated improvement in dyspnea (67%), cough (62%), and hemoptysis (100%).

CONCLUSIONS

Three cycles of QS were associated with limited high-grade toxicities, no disruption of systemic therapy, and high rates of patient-reported symptom improvement, supporting its use as a palliative option within multidisciplinary care for advanced NSCLC.