Researchers at Fox Chase Cancer Center have demonstrated that pulsed low dose rate (PLDR) chemoradiation therapy can significantly reduce side effects while maintaining treatment effectiveness for patients with esophageal cancer and non-small cell lung cancer.
The phase I trial results, presented on Tuesday, Sept. 30 at the American Society for Radiation Oncology (ASTRO) 2025 Annual Meeting, mark an important step toward validating PLDR as a first-line treatment option before 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 Joshua Meyer, MD, FASTRO , Vice Chair of Translational Research and Professor in the Department of Radiation Oncology at Fox Chase, and lead investigator of the study.
"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."
Key Findings
- Reduced Side Effects: Severe esophagitis — inflammation which causes pain and difficulty swallowing significant enough that feeding tubes or IV hydration are sometimes required — dropped from the typical 40% rate seen with standard chemoradiation to just 26%.
- Strong Survival Outcomes: Patients achieved a median overall survival of 45 months.
- Comparable Response Rates: Among esophageal cancer patients who later had surgery, 19% achieved a complete pathologic response and another 23% had near-complete responses.
How PLDR Works
Unlike conventional radiation, which delivers the dose all at once, PLDR breaks the dose into short pulses spaced a few minutes apart. This slower delivery allows healthy cells nearby to better repair DNA damage from radiation. Cancer cells, which are not as capable of repairing DNA damage, cannot take advantage of this repair window as effectively.
About the Study
- The phase I trial enrolled 39 patients with locally advanced disease (35 esophageal, 4 non-small cell lung cancer).
- All patients received standard chemotherapy (carboplatin + paclitaxel) with PLDR radiation over 5.5-6 weeks.
- Results showed that toxicity was reduced while therapy effectiveness was maintained.
"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 Meyer, who conducted the research with other colleagues at Fox Chase.
A Legacy of Innovation at Fox Chase
PLDR radiation was pioneered at Fox Chase by Chang-Ming Charlie Ma, PhD, FASTRO , Vice Chair of Radiation Oncology and Director of Radiation Physics. He developed much of the methodology for ensuring optimal delivery.
This marks the first time PLDR has been systematically tested as an initial treatment approach at Fox Chase, building on earlier success with recurrent cancers requiring retreatment.
The study, " PLDR Chemoradiation for Esophageal and Lung Cancer Is Associated With Low Rates of Severe Esophagitis ," was presented at the ASTRO 2025 Annual Meeting, held September 27 through October 1 in San Francisco.
