Use Of Pulsed Low-Dose Rate Radiation Therapy In Refractory Malignances

Most tumor cell lines exhibited hyper-radiosensitivity (HRS) to radiation doses low than 0.3Gy, while tumor cells became radioresistant when the unit radiation dose escalates to 1Gy. Pulsed low-dose rate radiotherapy (PLDR) took advantage of HRS and maximized the normal tissue repair process. In this study, we retrospectively analyzed patients receiving PLDR for refractory malignances. The radiation treatment was delivered using a series of 0.2 Gy pulses separated by 3 minutes time intervals. In total, twenty patients were included in our study, with 13 male and 7 female. There were 8 patients with gastric cancer, 3 patients with lung cancer, 3 patients with esophageal cancer, 2 patients with colorectal cancer, 1 patient with bladder cancer, 2 patients with glioma, 1 patient with chondrosarcoma, and 1 patient with cholangiocarcinoma. The irradiation treatment was delivered using 10 fractions of 2Gy/day, interval 3 minutes and 5 days per week. Approximately 30 minutes were taken to apply the treatment every day. The dose rate was 6.67 cGy/min. The median age was 63 years old. The ECOG performance status varied from 0 to 3. Seven patients had in-field recurrence and the previously delivered total dose range was 45Gy-112Gy (One patient with glioma received twice cerebral irradiation with total doses of 54Gy and 60Gy respectively within five years.). Fourteen patients had bulky tumors and were evaluated to be intolerant to the conventional radiotherapy. The time interval from last irradiation was 11months-28months. The concurrent treatments included chemotherapy, targeted therapy, and immunotherapy. Nine patients received merely radiotherapy. The irradiated sites included abdominal cavity (12 patients), thoracic cavity (6 patients), brain (1 patient), vertebral metastases (1 patient), and multiple metastatic foci in thoracic cavity and abdominal cavity (1 patient). Three patients discontinued the treatment due to the rapid progression of disease. The other seventeen patients completed the PLDR successfully. Response rates were evaluated one month after the treatment-end. RECIST evaluation criteria were referred. The partial remission rate was 41% (7/17) and the stable disease rate was 53% (9/17). Six patients (35%) did not develop treatment related toxicities. Seven patients (41%) had grade 1-2 toxicities and four patients (23%) with grade 3-4 toxicities. The median follow-up was one year (range 8-14months). Four patients had in-field recurrence. The one-year local control rate was 76.4%. PLDR was an effective treatment option with acceptable toxicities for patents with refractory malignancies. A prospective clinical trial is undergoing to validate our results.