Abstract P4-11-14: Pulsed Reduced Dose-Rate Radiotherapy: A Re-Irradiation Strategy for Breast Cancer Patients with Brain and Spinal Cord Metastasis

Abstract Background: Radiotherapy delivered at reduced dose-rates has the potential to preferentially reduce normal tissue toxicity, while still yielding almost identical tumor cell kill due to the superior repair capacity of late responding normal tissue. In conventional radiotherapy a 2 Gy dose is delivered at a dose-rate of 4-6Gy/min. A reduced dose-rate can be obtained by dividing a standard treatment fraction into a number of sub-fractions delivered in a pulsed manner separated by a fixed time interval. This increases the overall treatment time, allowing normal tissue repair during these sessions. Radiobiological modeling shows that a 2 Gy fraction can be delivered in a series of 0.2 Gy pulses separated by 3-minute intervals, creating an effective dose-rate of 0.0667 Gy/min. We have termed this re-irradiation technique pulsed reduced dose-rate radiotherapy (PRDR).* Methods: Between November 2000 and April 2010, 21 previously irradiated and heavily pretreated patients (pts) with progressive metastatic breast cancer were re-irradiated with PRDR to the whole brain (WB) (15) or spinal cord (SC) (6). The mean prior RT dose to the whole brain was 34.5 Gy (range 30-40 Gy) and the spinal cord was 39.9 Gy (range 30-50 Gy). A mean PRDR dose to the WB of 27.8 Gy (range 18-36 Gy) and SC of 31.3 Gy (range 28-40 Gy) was delivered in 1.8 or 2.0 Gy per fraction. Results: Mean overall survival (OS) of pts treated to the WB was 5.9 months (M) (range 0.5-21.3 M) and for pts treated to the SC was 18.9 M (range 5.6-43 M); 2 pts remain alive as of this report. Treatment was well tolerated: no grade 4 or 5 acute toxicities or grade 3 or 4 late toxicities were observed. Despite a mean cumulative dose of 64.9 Gy (range 54-80 Gy), there was no clinical or radiographic evidence of radionecrosis and/or neurological sequela. There appeared to be a correlation between KPS and OS. Conclusions: PRDR is a well-tolerated and effective radio-therapeutic method for the treatment of breast cancer patients with progressive metastatic CNS disease that have received prior radiotherapy. * Reirradiation of Large-Volume Recurrent Glioma with Pulsed Reduced- Dose-Rate Radiotherapy. Adkison JB, Tome W, Seo S, Richards GM, Robins HI, Rassmussen K, Welsh JS, Mahler PA, Howard SP. Int J Radiat Oncol Biol Phys. 2010 May 14. [Epub ahead of print] PMID: 20472350 Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-14.