A sector-based dosimetric analysis of dose heterogeneity in high-dose-rate prostate brachytherapy, "Beyond the Abstract," by Shane Mesko, BS and Mitchell Kamrava, MD

BERKELEY, CA (UroToday.com) - At the GU Cancers Symposium this year, the results of the Phase II/III Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) trial demonstrated that a low-dose-rate (LDR) brachytherapy boost resulted in a 50% reduction in biochemical relapse compared with dose-escalated external beam radiation therapy.[1] This provides Level 1 evidence that higher risk prostate cancer patients significantly benefit from a level of dose escalation that can only safely be achieved with brachytherapy. While this study used a LDR boost there are similar encouraging outcomes using high-dose-rate (HDR) brachytherapy as a boost.[2] In addition there is a growing body of literature demonstrating high PSA control and low toxicity outcomes using HDR monotherapy (i.e., without external beam radiation therapy).[3]

HDR is unique in that it delivers a hypofractionated treatment (i.e., doses higher than 1.8-2.0 Gy per day) that helps take advantage of the low alpha/beta ratio of prostate cancer. The dose of HDR is also very heterogeneous because the iridium-192 brachytherapy source delivers radiation from within the prostate. It is not known how much of the excellent clinical results being seen with HDR brachytherapy are a consequence of the hypofractionated dose escalation versus the heterogeneous dose delivery.

 bta mesko fig1
Figure 1. Isodose colorwash distribution of prostate stereotactic body radiation therapy (A - Axial, B - sagittal) and high dose rate brachytherapy (C – axial, D - sagittal). One can see while the distribution of the 50% isodose line (blue for SBRT and yellow for HDR) is similar that the dose within the prostate gland is homogeneous for SBRT while there are many small hot-spots in the HDR plan.

It is important to investigate which is most important as newer external beam treatment modalities such as stereotactic body radiation therapy (SBRT) can deliver “HDR-like” hypofractionated doses in a non-invasive manner, but typically with a homogeneous dose distribution. Data going out to about 6-7 years in low-risk and favorable intermediate-risk patients treated with SBRT demonstrates high PSA control rates and low late term toxicities.[4] Given its non-invasive platform, SBRT has appeal over HDR brachytherapy. However, if the heterogeneity of HDR is responsible for a significant portion of the treatment efficacy, then SBRT, at least when delivered homogeneously, may be an inferior treatment in some patients.

Multiple dosimetric comparisons between HDR and SBRT prostate treatment have been published, mostly demonstrating that the overall doses to the surrounding organs at risk (bladder and rectum) may be slightly in favor of HDR but in a magnitude that makes clinical relevance difficult to discern. Furthermore, most of these studies did not attempt to account for the dose heterogeneity of HDR. The few that tried did not effectively mimic the spatial distribution of HDR heterogeneity, partly because it has never been well described.

To this end we wanted to quantify the spatial distribution of dose heterogeneity of HDR prostate brachytherapy. We determined that the “hot-spots” that are inherent to prostate brachytherapy result in the lateral portions of the gland receiving 1.57 times higher dose compared with the medial sections. This is meaningful as the lateral sections are where the peripheral zone is located. HDR brachytherapy is able to achieve this with acceptable dosimetry despite the fact that these areas are in close proximity to the rectum. This study demonstrates that the intra-prostatic dose heterogeneity from HDR treatment results in much higher doses to the lateral portions of the prostate than just what the prescription would suggest. It is unlikely that a treatment that is delivered from the outside, like SBRT, could safely mimic this exact dose distribution.

What this paper cannot answer is whether or not this really matters clinically. It is not known whether HDR and SBRT achieve similar clinical outcomes and/or have similar acute/long term impacts on patient quality of life. It will take longer clinical follow-up and perhaps a randomized trial to determine this.

References:

  1. Morris WJ TS, Pai H, et al. ASCENDE-RT*: A multicenter, randomized trial of dose-escalated external beam radiation therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer. J Clin Oncol 33, 2015 (suppl 7; abstr 3), 2015
  2. Boladeras A, Santorsa L, Gutierrez C, et al. External beam radiotherapy plus single-fraction high dose rate brachytherapy in the treatment of locally advanced prostate cancer. Radiother Oncol 112:227-32, 2014
  3. BolZamboglou N, Tselis N, Baltas D, et al. High-dose-rate interstitial brachytherapy as monotherapy for clinically localized prostate cancer: treatment evolution and mature results. Int J Radiat Oncol Biol Phys 85:672-8, 2013
  4. BolKatz AJ, Kang J. Stereotactic body radiotherapy as treatment for organ confined low- and intermediate-risk prostate carcinoma, a 7-year study. Front Oncol 4:240, 2014

Written by:
Shane Mesko, BSa and Mitchell Kamrava, MDb as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

aUC Irvine School of Medicine/Paul Merage School of Business, Irvine, CA USA
bUCLA Department of Radiation Oncology, UCLA Health System, Los Angeles, CA USA

A sector-based dosimetric analysis of dose heterogeneity in high-dose-rate prostate brachytherapy - Abstract

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