Use of Pulsed Low-Dose Rate Radiotherapy in Refractory Malignancies

Most tumor cell lines exhibited low-dose hyperradiosensitivity (LDHRS) to radiation doses lower than 0.3 Gy. Pulsed low-dose rate radiotherapy (PLDR) took advantage of LDHRS and maximized the tumor control process. In this study, we retrospectively analyzed patients receiving PLDR for refractory malignancies.

In total, 22 patients were included in our study: 9 females and 13 males. The median age was 61 years old. All the patients previously received multiline treatments and failed with an estimated survival less than 6 months. Thus, palliative PLDR was given. The PLDR was delivered using 10 fractions of 2 Gy/day, with an interval of 3 minutes, for 5 days per week. The dose rate was 6.67 cGy/min. The median follow-up was 1 year (range 8-30 months). Nine patients underwent PLDR for reirradiation due to locally recurrent diseases. The time interval from last irradiation was 11 to 168 months. Ten patients received PLDR due to poor performance status. Three patients were given PLDR for bulky tumor. The irradiated sites included primary disease (seven patients), locally recurrent disease (nine patients), and retroperitoneal adenopathy (six patients).

Five patients developed grade 3 or 4 toxicities. No grade 5 toxicities occurred. All the toxicities recovered after treatments. In general, the 1-year local-regional control rate was approximately 40%, and almost all the patients developed progression at the second year after PLDR. The 6-month survival rate was 76%, and the 1-year survival rate was 69%. For the three patients given PLDR for bulky tumor, all of them achieved partial remission 1 month after the PLDR, and one patient achieved complete response at the fourth month.

PLDR is an effective and safe option not only for reirradiation but also for patients with poor performance status or bulky tumors. A prospective clinical trial (NCT03061162) is ongoing to validate our results.