Safety and efficacy of pulsed low-dose rate radiotherapy for local recurrent esophageal squamous cell carcinoma after radiotherapy

Abstract

Introduction: Re-irradiation after radiotherapy is a common treatment for locally recurrent esophageal cancer. However, the side effects of re-irradiation are serious. The most serious adverse reactions of re-irradiation include esophageal perforation and hemorrhage caused by esophageal perforation. Studies have shown that pulsed low-dose rate radiotherapy (PLDR) induces a hypersensitivity effect on tumor tissue and a hyper-repair effect on normal tissue, which can simultaneously reduce damage on the normal tissue and increase the therapeutic effect on the tumor. The objective of this study is to explore whether PLDR can reduce rate of esophageal perforation and improve efficacy in patients with recurrent esophageal squamous cell carcinoma (ESCC) after radiotherapy. Methods and analysis: This study is a prospective, multi-center, open, single-arm clinical trial designed to enroll 27 patients with locally recurrent ESCC after radiotherapy with or without chemotherapy. Re-irradiation will be performed using intensity modulated radiation therapy in 50 Gy/25 fractions. The strategy of PLDR includes dividing 2 Gy into 10 fractions, and administering each irradiating dose of 20 cGy at an interval of 3 minutes before the next low-dose irradiation. The actual dose rate of administration each time will be 16.67 cGy /minute. The primary endpoint in this study is the rate of esophageal perforation. The secondary endpoints are the objective remission rate, the palliative effect on quality of life and pain, and the time of disease progression. The observation time is 2 years after the end of the study. Trial registration: Clinical trial number: ChiCTR1900020609.

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

“…The use of PLDR irradiation in local recurrent HNSCC has been recently tested in a clinical trial in order to evaluate safety and treatment efficacy. [31][32][33] PLDR irradiation was initially proposed for the treatment of recurrent radioresistant gliomas. 13,16 It exploits two phenomena, LDHRS, and the inverse dose-rate effect.…”

<p>LOC441178 Overexpression Inhibits the Proliferation and Migration of Esophageal Carcinoma Cells via Methylation of miR-182</p>

“…7 However, the serious side effects and unexpected risks are not uncommon, including esophageal perforation, hemorrhage, dysphagia. 8,9 Therefore, exploring the promising therapeutic molecular targets may help to understand the diagnosis and treatment of EC.…”

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies

“…The implementation strategy for PLDR involves dividing 2.00 Gy into ten fractions and administering each irradiating dose of 20 cGy at an interval of 3 min before the next low-dose radiation (Li et al, 2019). The pulse dose is within the dose range for tumor radiosensitivity and normal tissue radioresistance, which can contribute to a higher rate of tumor cell apoptosis while better protecting normal tissues from radiation damage.…”

“…The pulse dose is within the dose range for tumor radiosensitivity and normal tissue radioresistance, which can contribute to a higher rate of tumor cell apoptosis while better protecting normal tissues from radiation damage. Relevant basic and clinical studies have shown that PLDR improves the local control rate and the quality of life of cancer patients (Li et al, 2019).…”

“…Next, we studied the time interval in PLDR in terms of the sublethal repair half-time (t 1/2 ) of peripheral normal cells. According to previous study (Li et al, 2019), time interval in PLDR is calculated by the following formulae: t=t 1/2 /(m−1), m=D/d (t is the time interval, t 1/2 is the sublethal repair half-time, D is radiation dose, d is pulse dose, and m is pulse number). The normal tissues around pancreatic cancer include pancreas, small intestine, and liver; the normal tissues around prostate cancer include prostate, rectum, and bladder.…”