Chemoradiation with a pulsed low-dose–rate technique led to lower-than-usual rates of severe esophagitis without compromising efficacy in patients with esophageal and non–small cell lung cancer (NSCLC), according to findings from a single-arm phase I study presented as a poster during the American Society for Radiation Oncology (ASTRO) 67th Annual Meeting (Abstract 3437).
These findings are an important step toward the validation of pulsed low-dose–rate chemoradiation as a first-line treatment option for patients prior to surgery.
“Historically, we’ve been limited in how much radiation we could safely deliver to these patients because of severe side effects, particularly painful swallowing problems,” said lead study investigator Joshua Meyer, MD, FASTRO, Vice Chair of Translational Research and Professor in the Department of Radiation Oncology at Fox Chase Cancer Center. “The beauty of this technique is that we’re not compromising on cancer treatment. We’re delivering the same effective dose, just in a smarter way that minimizes damage to healthy tissue.”
Background and Study Methods
Chemoradiation can lead to high rates of severe esophagitis during and immediately after treatment for patients with esophageal cancer and NSCLC. Pulsed low-dose–rate radiation has been used to decrease toxicity, but there are no prospective data to date for safety of the technique in combination with radiosensitizing chemotherapy.
The single-arm phase I prospective study explored the use of pulsed low-dose–rate radiation plus weekly carboplatin and paclitaxel in the first-line, curative setting for patients with esophageal cancer or NSCLC. Patients with esophageal cancer received 50.4 Gy and patients with NSCLC received 60 Gy, both delivered in 1.8 to 2 Gy fractions using pulses of 0.2 Gy every 3 minutes.
For the purpose of the study, severe esophagitis was defined as the start of or increase by 25% of narcotic doses, or dysphagia necessitating the transition from solids to liquids or to minimal oral intake within 1 week of treatment and up to 4 weeks after the completion of treatment.
The primary endpoint of the study was the proportion of patients experiencing severe esophagitis; quality of life was also assessed using QLQ-C30.
Although the study was designed to include 20 patients with esophageal cancer and 20 with NSCLC, it was amended after poor accrual figures for patients with NSCLC to include flexible proportions of patients with each cancer type, and was later closed to patients with NSCLC.
Key Study Findings
Of the 39 enrolled patients, only 10 developed severe esophagitis, which compared well vs historical controls (26% vs 38%; P = .075). Among patients with esophageal cancer specifically, 20% developed severe esophagitis.
In terms of pathologic outcomes, six patients with esophageal cancer had pathologic complete responses, seven had near-complete pathologic response, and 18 had poor responses. Two patients with NSCLC were pathologically lymph node–negative and two were positive.
“We were very pleased to see that not only did we cut severe esophagitis roughly in half, but we also preserved the treatment effectiveness we expect,” said Dr. Meyer.
The median progression-free and overall survival were each 45 months.
Quality-of-life analysis also demonstrated general stability, except for small decreases following surgery.
Disclosure: For full disclosures of the study authors, visit amportal.astro.org.
