A Phase I Study of Cyclical Hypofractionated Palliative Radiotherapy (Quad Shot) for Central Lung Tumors in Patients with Stage IV Non-Small Cell Lung Cancer (NSCLC): Results from the PROMISE 006 Trial Thoracic Quad Shot RT in Stage IV NSCLC.

Authors

Y Helen Zhang, Afsheen Iqbal, Daphna Gelblum, Jennifer Ma, Ellen Yorke, Jonathan T Yang, Erin F Gillespie, Nicolas Toumbacaris, Zhigang Zhang, Paige Brooks, Emali Khalyat, Narek Shaverdian, Victoria Brennan, David M Guttmann, Brandon S Imber, Puneeth Iyengar, Jacob Shin, Charles B Simone, Abraham J Wu, Andreas Rimner, Daniel Gomez, Annemarie Shepherd

Published in

International journal of radiation oncology, biology, physics. Aug 18, 2026. Epub Aug 18, 2026.

Abstract

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 radiotherapy (RT) regimen, could provide effective symptom palliation while allowing concurrent systemic therapy. We evaluated the safety, feasibility, and patient-reported outcomes (PROs) of delivering up to three cycles of QS concurrently with systemic therapy.
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 (MTD) using a modified 3+3 design, defined as a dose-limiting toxicity (DLT) rate ≤17% (1 of 6 patients). Secondary endpoints included feasibility, systemic therapy disruptions, RT-related toxicities, and PROs.
Forty-five patients were enrolled in this study. One DLT occurred in the two-cycle cohort, and none occurred with three cycles, establishing three cycles as the MTD. In the expansion cohort, three patients developed grade 3 RT-related toxicities. All systemic therapies were administered without any interruptions. Among symptomatic patients, PROs demonstrated improvement in dyspnea (67%), cough (62%), and hemoptysis (100%).
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.

PMID:
42612834
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.

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