A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy?
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
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Image-guided high-dose-rate brachytherapy boost to the dominant intraprostatic lesion using multiparametric magnetic resonance imaging including spectroscopy: Results of a prospective study
2016, BrachytherapyCitation Excerpt :Indeed, in our institution, Bachand et al. reported a 5-year biochemical failure-free survival of 96% according to ASTRO or Phoenix consensus definitions in patients treated with external beam pelvic radiation followed by an HDR Ir-192 prostate boost (8). In 49 NCCN intermediate-risk prostate cancers treated with 46 Gy of EBRT followed by 16 or 20 Gy of HDR boost, the actuarial 5-year freedom from biochemical failure was reported at 68.4% (28). In a randomized trial of EBRT alone or combined with HDR boost for all-risk group patients, Hoskin et al. (9) reported a 5-year biochemical relapse-free survival rate of 75% in an EBRT + HDR brachytherapy group, compared with 61% in an EBRT-only group.
Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer
2016, Cancer Treatment ReviewsCitation Excerpt :Supplementary Table 2 lists those of external beam RT dose escalation with conventionally fractionated RT [7–14], those of hypofractionated RT vs. conventionally fractionated RT [15–19], and those of SBRT [20–23]. Supplementary Table 4 lists studies of BT [24–34]. Comparisons, based on levels of evidence (from Supplementary Table 1), were used to compare outcomes and toxicities for the various forms of RT (Table 2).
Brachytherapy for Prostate Cancer: An Overview
2016, Prostate Cancer: Science and Clinical Practice: Second EditionHigh dose rate brachytherapy boost for prostate cancer: A systematic review
2014, Cancer Treatment ReviewsCitation Excerpt :Non-dosimetric patient and treatment characteristics predicting late toxicity include older age (> ∼65 years) [40,43], ADT use [43,79], initial presence of symptoms [43], use of EBRT alone vs. HDR-BT boost [79], high-risk status [79], prior trans-urethral resection of the prostate [44,52], hypertension [52], and high dose per fraction of HDR-BT [52]. Studies that compare HDR-BT boost to conventional therapies are summarized in Table 4 [72–77,79]. Multiple studies report improved FFBF rates with HDR-BT boost with either CFRT [79,77] or HFRT [72,74,79].
Direct 2-arm comparison shows benefit of high-dose-rate brachytherapy boost vs external beam radiation therapy alone for prostate cancer
2013, International Journal of Radiation Oncology Biology PhysicsDosimetric effect of external beam planning preceding combined high-dose-rate brachytherapy of the prostate
2011, BrachytherapyCitation Excerpt :Improved techniques, such as image-guided radiotherapy and intensity-modulated radiotherapy reduce the late toxicity of dose-escalated EBRT, although thus far only Level 3 evidence exists to support this (6–9). Furthermore, high-dose-rate brachytherapy (HDRB) boosting and modern dose-escalated EBRT are yet to be compared in a completed randomized trial; hence, head-to-head comparisons regarding toxicity and efficacy are usually based on single-institution experience (10, 11). Overall, HDRB boosting is an option for men treated with dose-escalated radiotherapy.
This study was presented at the Royal Australian and New Zealand College of Radiologists annual scientific meeting, Sydney, 2005.