Elsevier

Brachytherapy

Volume 5, Issue 4, October–December 2006, Pages 256-261
Brachytherapy

A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy?

https://doi.org/10.1016/j.brachy.2006.08.007Get rights and content

Abstract

Purpose

The study aimed to evaluate mature outcomes of a Phase I/II high-dose-rate brachytherapy (HDRB) boost protocol.

Methods and materials

We analyzed data from 88 patients with T1a–T3a, N0, M0 prostate adenocarcinoma treated on a prospective Phase I/II HDRB boost protocol of 16 (n = 47) or 20 Gy (n = 41) in four fractions, without planned androgen deprivation therapy. HDRB was added to 46 Gy of external beam radiotherapy (EBRT). Outcomes were compared to a contemporaneous retrospective cohort of 104 patients receiving 66 Gy EBRT monotherapy. The primary endpoint was freedom from biochemical failure, defined as a 2 ng/mL rise above the lowest prostate-specific antigen (PSA) (FFbFn2), whereas the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) was used for comparative purposes.

Results

For the HDRB cohort, the overall actuarial 5-year FFbFn2 was 67.4% (95% CI: 58.2–75.5%). For the HDRB doses of 16 and 20 Gy, the 5-year FFbFn2 rates were 58.8% (95% CI: 41.9–72.5%) and 77.3% (95% CI: 64.4–88.3%), respectively (log-rank test p = 0.07). Compared to men treated with 66 Gy EBRT, using multivariate analysis, there was no significant benefit to using HDRB with the FFbFn2 outcome (p = 0.52), yet the ACD suggested a significant advantage (hazard ratio 0.50, 95% CI: 0.29–0.86, p = 0.011). There was a trend to better FFbFn2 outcomes with increasing biologically effective doses (p = 0.09), which was significant using the ACD (p = 0.0003).

Conclusions

The data support HDRB boost as a potential means of dose escalation in prostate cancer. Significant findings using the ACD need to be validated with contemporary biochemical failure definitions. Prospective trials to optimize fractionation and evaluate outcomes in comparison to contemporary EBRT techniques are warranted.

Introduction

Previous studies have debated the α/β ratio for prostate cancer, with recent studies suggesting a low ratio [1], [2], [3]. Based on the assumption of a low α/β ratio, hypofractionation should theoretically improve local control rates (4). High-dose-rate brachytherapy (HDRB) boost seems to be a safe and efficient means of delivering a hypofractionated schedule, with recent studies reporting good biochemical and clinical outcomes with long-term follow-up (5). Hence we hypothesize that, given a low α/β ratio for prostate cancer, combined external beam radiotherapy (EBRT) with a hypofractionated HDRB boost compared to EBRT to the same total dose would prove to be biologically more effective.

The primary aim of this report is to summarize the mature biochemical outcome of an ongoing Phase I/II HDRB boost protocol. Secondarily, we will compare the outcomes to those of a retrospective cohort treated with EBRT monotherapy to a dose of 66 Gy over the same period, to which the HDRB regimen was initially designed to be isoeffective.

Section snippets

Patient cohort

This study included patients with clinical T1a–T3a, N0, M0 [TNM 1997 classification (6)] adenocarcinoma of the prostate who were treated with curative intent at Peter MacCallum Cancer Centre, Melbourne, Victoria, between September 1997 and December 1999. Investigation for the presence of metastatic disease was performed using whole body radioisotope bone scanning and CT of the abdomen and pelvis at the discretion of the treating physician. Gleason Score (GS) was available for all cases and was

HDRB boost outcomes

Patient characteristics are shown in Table 1. Forty-seven patients were enrolled in the 16 Gy HDRB boost arm and 41 patients in the 20-Gy HDRB boost arm. Four men had undergone previous transurethral resection of the prostate.

The PSA nadir in the HDRB cohort was achieved at a median time of 36 months, at a median PSA of 0.45 ng/mL. There were 32 biochemical failures, with an overall actuarial FFbF (using Phoenix nadir + 2 ng/mL definition [FFbFn2]) of 67.4% (95% CI: 58.2–75.5%) at 5 years. Divided

Discussion

We have demonstrated acceptable results of a prospective Phase I/II trial of HDRB as a boost to 46 Gy EBRT, with an approximate 5-year risk of bF of 30% in a predominately low and intermediate risk cohort. As this protocol was designed to have an approximately equal biological effect to 66 Gy of EBRT (typical of that time), we compared the HDRB results to those of a retrospective EBRT patients concurrently treated to this dose. The similarity of the results for the HDRB boost and the EBRT-only

Conclusion

Combined EBRT with HDRB boost seems to be an effective treatment alternative option, which may be able to provide higher biologically equivalent doses than conventional EBRT, potentially resulting in better tumor control rates. The mechanism by which these intensive local therapies impact on PSA and clinical biology is yet to be fully defined. Randomized trials to clarify the role of this treatment are required, particularly comparing HDRB schedules to dose-escalated EBRT using contemporary

References (17)

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This study was presented at the Royal Australian and New Zealand College of Radiologists annual scientific meeting, Sydney, 2005.

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