KEY POINTS
- PROMISE 006 (NCT04384146) was a prospective single-institution phase I dose-escalation study enrolling 45 patients with stage IV NSCLC and symptomatic or near-symptomatic central thoracic tumors. Thirty-nine patients ultimately received at least one radiotherapy cycle.
- Each Quad Shot cycle consisted of 14.8 Gy in four 3.7-Gy fractions, delivered twice daily over two consecutive days with ≥6 hours between same-day fractions. Cycles were separated by 21–28 days and were intentionally delivered within one week of systemic therapy, including chemotherapy, immunotherapy or chemoimmunotherapy.
- The trial escalated the number of cycles rather than dose per cycle. Among six evaluable patients assigned two cycles, one dose-limiting toxicity occurred—grade 3 esophagitis. Among six evaluable patients at the next level, no dose-limiting toxicity occurred with three cycles, establishing three cycles as the protocol maximum tolerated regimen.
- Treatment was logistically compatible with systemic therapy: no patient experienced a systemic-therapy delay >7 days attributable to radiation. Two-cycle completion was 88%, while 74% of patients assigned three cycles completed all three; most incomplete courses resulted from clinical decline or extracranial disease progression rather than radiotherapy toxicity.
- High-grade toxicity was uncommon but clinically important. Beyond the initial grade 3 esophagitis, three grade 3 events occurred among patients receiving three cycles: pneumonitis, a cavitary lung infection considered possibly radiation-related, and a delayed tracheal-mediastinal fistula in a patient receiving immunotherapy. No signal suggested routine interruption of systemic treatment was necessary.
- Patient-reported symptoms improved frequently: cough improved in 62%, dyspnea in 67% and hemoptysis in 100% of symptomatic patients at some point after treatment. At one month, average cough and dyspnea scores were lower in both treatment groups, and hemoptysis scores fell to zero.
- Median overall survival among the 39 treated patients was 6.2 months. No local failures were recorded among patients receiving three cycles during available follow-up; after two cycles, cumulative local failure was 6.3% at six months and 14% at 12 months. The study was not designed or powered to compare two versus three cycles for efficacy.
CLINICAL TAKEAWAY
For patients with metastatic NSCLC who need rapid palliation of a central thoracic mass without putting systemic therapy on hold, cyclical Quad Shot is an attractive option. PROMISE 006 establishes prospective feasibility of up to three cycles, but the small phase I sample and serious though uncommon thoracic toxicities argue for careful anatomy-based selection rather than routine adoption in every patient.
SOURCE
International Journal of Radiation Oncology, Biology, Physics