Prospective phase I/II trial of dose-painting prostate brachytherapy guided by cancer-specific ultrasound-based tissue-type imaging (TTI).

Abstract

246 Background: Standard treatments treat the entire prostate gland uniformly, while focal treatments target only the dominant tumor. We propose an alternative approach wherein tumor areas are treated with an escalated dose of radiation while the remainder of the prostate with dose de-escalation. Tissue-type images (TTIs), which identify intraprostatic tumors via ultrasound spectral analysis, were used to identify tumors. Methods: 14 low risk patients were enrolled. TTIs and standard B-mode ultrasound images were generated and fused intraoperatively. Based on TTIs, plans were developed to deliver 200% prescription dose to the tumors and 100% to the prostate. Doses above 100% to non-tumor regions were minimized and standard normal tissue constraints were respected. Results: 12 patients were successfully treated. Technical problems occurred in the first patient and another received a standard implant due to discordance of TTIs with MRI and biopsy findings. One patient passed away soon after the procedure of unrelated cause. A total of 28 tumors were identified in these 12 patients (median 2 tumors/patient, range 1-4). Mean tumor volume was 0.72cc (range 0.03cc -4.07cc). Tumor dose was significantly higher in TTI-based plans, with mean tumor V200%: TTI vs. standard 97% vs. 48%, p<0.05. Modest dose reduction of the whole prostate was also achieved. Median follow-up was 25.7 months (range 21.3-48 months). A low incidence of grade 2 toxicities and no grade 3-4 toxicities were seen (Table). Two patients experienced a biochemical failure per the nadir+2 definition, both failures are attributable to PSA bounce (PSA down to 1.0 and 0.59 at 42 and 30 mos., respectively). Post-treatment biopsies have been performed on 5/11 patients (4 refused), with 2 patients with pending biopsies. 4/5 available biopsies are negative, with 1 patient having a small focus of residual cancer. Conclusions: Dose-painting prostate brachytherapy is technically feasible. This tumor-directed approach, more rational than uniform whole gland treatments, offers the promise of excellent cancer control, low toxicity and low risk of re-treatment. Clinical trial information: NCT01227642. [Table: see text]