August, 2018
A Message From the President
Welcome to the August 2018 edition of the American Brachytherapy Society’s BrachyBlast newsletter.

Our longstanding and dedicated BrachyBlast editor, Daniel Petereit, MD is preparing to ascend to the President of American Brachytherapy Society in 2019. As such, we are soliciting members who are interested in participating in the production of our monthly BrachyBlast and taking us into the future. If you are interested in participating, we encourage you to please reach out to us . During this transition year, each month we will feature a Guest Editor from the Board of Directors. It is my hope that featuring Guest Editors will allow you to become immersed in the topics that the leaders of the ABS find to be of the greatest importance to the society, and that this will give members of the ABS a glimpse at the innerworkings of the ABS as we navigate this next year together.

This month, Guest Editor Christopher Deufel, PhD, has produced a thought provoking newsletter with all kinds of information pertinent to our practices. We are featuring a review of the NEW and appoved Nuclear Regulatory Commission (NRC) definitions for Medical Event Reporting for permanent prostate brachytherapy and we have a piece on brachytherapy as a boost for high risk prostate cancer in the context of the recent publication by Kishan et al in JAMA. In this article we are including for our membership a brief commentary on the evidence and considerations for LDR vs HDR and even the potential to perform the boost prior to as opposed to after EBRT. 

Enjoy the final days of summer, and keep an eye out for the Summer 2018 BrachyNews , coming to your inbox in the next few weeks. 

Thank you,
Peter F. Orio III, DO, MS
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David M. Routman, MD and Bradley J. Stish, MD
Mayo Clinic, Rochester, MN
Dose matters and extreme dose escalation with the combination of external beam radiation therapy (EBRT) and brachytherapy (BT) boost for subsets of high risk prostate cancer patients may improve clinically meaningful endpoints including distant metastasis free survival (DMFS), and potentially prostate cancer specific mortality (PSCM).

Kishan et al. recently published in JAMA on outcomes of over 1800 patients with Gleason 9 and 10 disease treated at 12 different institutions. In a propensity score adjusted analysis, EBRT + BT was associated with a significant improvement in DMFS and PSCM as compared to EBRT or radical prostatectomy. Interestingly, an additional subset analysis comparing patients receiving EBRT + BT to those receiving “optimal” EBRT management, comprised of at least 78 Gy and 24 months of androgen deprivation therapy, revealed EBRT + BT was still associated with improved DMFS [1]. The authors, and a recent commentary by Ong et al., note the limitations of this analysis.  Limitations include biases inherent to a retrospective design such as; non-standardized treatment selection, the fact not all centers contributed patients in each category of treatment, and the potential for differential time to imaging amongst the cohorts [2, 3]. However, these data remain congruent with population based studies and prior retrospective studies investigating high risk patients.

Stone et al. previously analyzed the association of BED and outcomes for over a thousand patients treated across six institutions, focusing on Gleason 7 – 10 patients and including a substantial number of patients with Gleason 8 – 10 (n=233). For Gleason 8 – 10 patients, receipt of a BED >220 was associated with better biochemical failure free survival, DMFS, and overall survival (OS) [4]. Johnson et al. found a similar result when analyzing the NCDB for patients treated between 2004 to 2012 with EBRT versus EBRT + BT in the setting of unfavorable risk prostate cancer. Brachytherapy boost was independently associated with improved OS on multivariate analysis. This advantage for EBRT+BT persisted even when the analysis was restricted to patients less than 60 years old without recorded comorbidities[5].

Are the existing data enough to accept brachytherapy boost as the treatment of choice for Gleason 9 and 10 disease? If not, we are left to await longer term results of ASCENDE-RT for level I evidence. One limitation of this study, like all previously published studies assessing the role of BT boost, is that it is underpowered in regards to PCSM or DMFS due to a somewhat heterogeneous patient cohort and relatively small sample size. PIVOTALBoost, a recently initiated trial sponsored by the Institute of Cancer Research in the United Kingdom, is investigating the role of both HDR and IMRT boost and plans to enroll over 1900 patients [6]. This study promises to add important data to this discussion, but results are not expected for approximately 10 years. In the interim, we are also left to determine what we consider a meaningful endpoint, if not biochemical failure free survival, as Dr. Petereit previously discussed in a Brachyblast [7]. 

Emerging technologies, such as advanced imaging techniques and genomic classifiers (GC), may improve patient selection and outcomes in future studies of men with Gleason 9 and 10 (ISUP Grade Group 5) prostate cancer. In the initial report of ASCENDE-RT trial, 86% of the metastatic events were noted to occur within 2 years of biochemical failure, with a median interval of time to metastasis after biochemical failure of only 4 months, representing a cohort of patients who likely had occult metastatic disease at initial presentation [8]. Using prostate cancer-specific PET radiotracers [9] may help identify a portion of patients with occult metastases prior to treatment. For example, an analysis of PSMA based imaging in the primary setting showed a detection rate of nodal or distant metastases in 48% of patients with Grade Group 5 [10]. Novel biomarkers such as GC may identify patients with a significantly higher risk for early metastatic progression. These patients may derive less benefit from intensification of local therapy and instead have their outcomes improve by augmented systemic therapies such as novel androgen axis drugs or cytotoxic chemotherapy. 

If we accept EBRT with BT boost as the treatment of choice for appropriately selected high risk prostate cancer patients based on the available data, important questions remain to be answered. Additional studies are needed to minimize the modest increase in toxicity that has been associated with BT boost. Determining the optimal boost technique (LDR versus HDR) [11] and ideal organ at risk dosimetric constraints will help optimize the therapeutic window. Additionally, the appropriate duration of ADT in the setting of extreme dose escalation remains uncertain, and warrants further investigation. However, designing and conducting research in order to optimize the efficacy of BT boost may be hindered by the concerning trends being reported of declining BT utilization and trainee exposure to these techniques. In the words of Dr. Crook,

“If the addition of a brachytherapy boost is indeed indispensable in the optimal management of unfavorable prostate cancer, meeting the training demands of a nation so that optimal treatment can be offered to all who require it will be a major challenge.” [12]

In our opinion, there is a group of patients where the superior biochemical and local control offered by EBRT + BT outweighs the small risk for intermediate grade toxicity and the advantages may translate into meaningful improvements in quality, and potentially, quantity of life. Uncertainty remains in precisely defining these patients, and further prospective trials are warranted.

1.   Kishan, A.U., et al., Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer. Jama, 2018. 319(9): p. 896-905.
2.  Kishan, A.U., R.R. Cook, and C.R. King, Optimal Treatment for High-Risk Prostate Cancer-Reply. Jama, 2018. 320(4): p. 405.
3. Ong, W.L., T.L. Koh, and J. Millar, Optimal Treatment for High-Risk Prostate Cancer. Jama, 2018. 320(4): p. 404-405.
4. Stone, N.N., et al., Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys, 2009. 73(2): p. 341-6.
5. Johnson, S.B., et al., Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer. European Urology, 2017. 72(5): p. 738-744.
6.   Institute of Cancer Research in the United Kingdom [Internet]. PIVOTALBoost: A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost . Available from:
7.  D’Amico, A.V., Active Surveillance Versus Treatment of Prostate Cancer: Should Metastasis Be the Primary End Point? Journal of Clinical Oncology, 2017. 35(15): p. 1638-1640.
8. Morris, W.J., et al., Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Radiat Oncol Biol Phys, 2017. 98(2): p. 275-285.
9.  Evans, J.D., et al., Prostate cancer-specific PET radiotracers: A review on the clinical utility in recurrent disease. Pract Radiat Oncol, 2018. 8(1): p. 28-39.
10. Meyrick, D.P., et al., The role of 68Ga-PSMA-I&T PET/CT in the pretreatment staging of primary prostate cancer. Nuclear Medicine Communications, 2017. 38(11): p. 956-963.
11.  British Columbia Cancer Agency [Internet]. H13-02139 (NCT01936883): Improving Quality of Life After Prostate Brachytherapy: a Comparison of HDR and LDR Brachytherapy (BrachyQOL) . Available from: .
12. Crook, J., Optimal Radiotherapy for Unfavorable-risk Prostate Cancer. Eur Urol, 2017. 72(5): p. 745-746.
The NRC has revised the requirements for a written directive and the definition of a medical event. The changes are effective on January 14, 2019. The NRC revisions can be viewed at:
Purpose for the revisions
The NRC staff concluded that dose-based criteria are problematic for permanent implant brachytherapy, and that clinically acceptable therapies were being reported as medical events. The NRC also noted that a total source strength-based criterion would allow for recognition of medical events earlier than a dose-based criterion, thus allowing timelier corrective actions.

Revised Written Directive requirements

The revised rule establishes separate WD requirements in § 35.40, “Written directives,” that are appropriate for permanent implant brachytherapy.

This rule requires that the WD for permanent implant brachytherapy consist of two portions. The first portion of the WD must be prepared before the implantation, and the second portion of the WD must be completed after the procedure but before the patient leaves the post-treatment recovery area. For permanent implant brachytherapy, this rule requires that the WD portion prepared before the implantation include documentation of the treatment site, the radionuclide, and the total source strength. This final rule requires that the post-implantation portion of the WD contain documentation of the treatment site, the number of sources implanted, the total source strength implanted, and the date. This information must be entered after implantation but before the patient leaves the post-treatment recovery area.

For permanent implant brachytherapy, the user must also determine within 60 calendar days from the date the implant was performed, the total source strength administered outside of the treatment site compared to the total source strength documented in the post-implantation portion of the written directive, unless a written justification of patient unavailability is documented. This is required to show compliance with the new permanent implant medical event definition (see below).

Revised Medical Event Definition
The revised medical event definition replaces dose requirements with total source strength requirements. The user is no longer required to calculate dose, however the user must evaluate whether the administered source strength was 20 percent or more different than the written directive or 20 percent or more of the source strength was administered outside of the treatment site.  The revised language is provided below:

For permanent implant brachytherapy, the administration of byproduct material or radiation from byproduct material (excluding sources that were implanted in the correct site but migrated outside the treatment site) that results in—
(i) The total source strength administered differing by 20 percent or more from the total source strength documented in the post-implantation portion of the written directive;
(ii) The total source strength administered outside of the treatment site exceeding 20 percent of the total source strength documented in the post-implantation portion of the written directive; or
(iii) An administration that includes any of the following:
(A) The wrong radionuclide;
(B) The wrong individual or human research subject;
(C) Sealed source(s) implanted directly into a location discontiguous from the treatment site, as documented in the post-implantation portion of the written directive; or
(D) A leaking sealed source resulting in a dose that exceeds 0.5 Sv (50 rem) to an organ or tissue.”
Sarah Price, Graduate Student
Panagiota Galanakou, Graduate Student
Florida Atlantic University
As promised in our case 0001 posted on the Brachyblast on July 31 st 2018, we are eager to present the feedback (corrective and preventive measures) that we have collected from several colleagues (medical physicists and radiation oncologists). As a reminder to readers, this is a case of an HDR procedure where the use of an incorrect length (incorrect click-fits and wrong input into the TPS) has led to a medical event.
Independent manual measurement check to verify treatment length matches planning length

When a different than manufacturer recommended click-fit is to be used as a substitute with any applicator, a commissioning should be performed in advance using manufacturer recommended length (confirmed with measurement by the user).
P olicies and procedures that require the medical physicist to be directly involved with the treatment set up when there are any alterations to the plan, HDR equipment, or treatment devices.

All members of the brachytherapy team should be directly informed regarding any modifications to the use of device or treatment plan. In addition to verbal instructions, written ones with photos of selected click-fit set used for planning should be provided for treatment setup verification and delivery.
In-service for the brachytherapy team regarding the use of “Click-fit” with all applicators and the clinical impact when using the non-planned one .
The physicist involved in the modification of any treatment plan should directly be involved in the patient setup prior to treatment. The resulting set up should be independently be verified by the treatment team.  
When there is any doubt about proper set up and use of brachytherapy device, time-out should be performed and manufacturer should be contacted for clarification and recommendation prior to treatment 
When having two different sets of click-fit (A and B) consider retiring one set to eliminate the use of the wrong one. The resulting total length when connected to this selected click-fit set remains a variable and one should consider a table of total length for all applicators as a reference for treatment planning.
  • Manufacturers should consider redesigning the afterloader to measure (in the dummy sequence) each treatment length and stop treatment if the measured value is not within 1mm of the planning length.

  • Manufacturers should remove the legacy ‘magic’ numbers (the 1.4 cm difference between the actual measurement of treatment length with a Quick Connect for VariSource iX and the actual treatment length).

  • Manufacturer should remove the default treatment length from the BrachyVision TPS. The user should be forced to enter the length and there should be an authorization popup requiring initials (or password) to proceed. This will ensure measurements were performed.

  • Click-fits should be designed and sold such that they have the same length for all applicators.

  • Manufacturers should provide illustrations or demonstrations of the possible ramifications of improper use of devices and various click-fit set. For this specific example, demonstrate how using an incorrect click-fit set will result in a medical event. During training, emphasis should not only be on how things work well but also how things can lead to medical events. Reported events should be part of the education with demonstration.

  • Manufacturers should provide detailed illustrations or demonstrations of the procedures the staff should follow for proper treatment.

  • Treatment summary generated by the plan that will include all critical parameters for treatment setup and delivery will be useful. Parameters such as patient name, applicator model, “click-fit” set, planning length, fraction #, and dose.

We would like to thank Wesley Culberson PhD, Robert Ebeling III MD, Stephen J. Klash, Dorin Todor PhD, Daniel Scanderbeg PhD, Christopher L. Deufel PhD, and William Bice PhD for their valuable feedback.

We encourage our readers to continue to submit their ideas to as there may have been preventive and corrective actions we did not identify. Be sure to check out next month’s BrachyBlast where we will present case 0002.
The ABS Wants You!
Want to get more involved with the ABS? Here's your chance! Our goal to reshape the vision and future of the ABS to best serve the industry continues to guide how we approach every aspect of the organization. We've revamped our volunteer opportunities to better meet your needs. If you're interested in being part of one our committees, please feel free to fill out an interest form and return to Melissa Pomerene .
We look forward to working with you!
of Directors 
  2018-2019 ABS Board of Directors

Peter F. Orio, III, DO, MS , President
Daniel G. Petereit, MD, President Elect
Firas Mourtada, PhD, Vice President
Ann Klopp, MD, PhD, Treasurer
Zoubir Ouhib, MS, Secretary
Catheryn Yashar, MD, Chairwoman of the Board
Steven J. Frank, MD, Past Chairman of the Board

Sushil Beriwal, MD
Christopher L. Deufel, PhD
Peter J. Rossi, MD
Timothy Showalter, MD