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Advisory Committee on the Medical Use of Isotopes (ACMUI) 

Permanent Implant Brachytherapy Revised Final Report 

February 7, 2012 

Permanent Implant Brachytherapy Subcommittee Members

Susan Langhorst, Ph.D. 

John Suh, M.D. 

Bruce Thomadsen, Ph.D. 

James Welsh, M.D., Chairman 

Recommendations

A. Proposed Definition for Medical Event for Macroscopic Permanent Implants 

1. For the target, greater than 20% of the sources fall outside of the treatment site 

(not resulting from patient-related causes such as edema or source migration 

after placement)

OR

2. For normal-tissue structures,

a. For neighboring structures (such as the bladder or rectum in prostate 

implants as an example), the dose to at least 5 contiguous cm3 exceeds 

150% of the dose prescribed to the CTV or PTV; 

OR

b. For intra-target structures (such as the urethra in prostate implants as an 

example), the dose to at least 5 contiguous cm3

 exceeds 150% of that 

structure’s expected dose based on the approved pre-implant, dose 

distribution. 

OR

3. A treatment is executed

a. Using the wrong radionuclide;

b. Using the wrong activity or source strength (+/- 20%) as specified in the 

Written Directive;

c. Delivered to the wrong patient;

d. Delivered directly to the wrong site or body part, with the exceptions of seed 

migration, edema and other patient-related factors or source displacement 

following placement, as long as the criteria in 1. is not violated;

e. Delivered using the wrong modality or

f. Using leaking sources, 
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B. Written Directive Completion 

After implantation but before the patient is released from the Authorized User’s control, 

the Authorized User shall complete the Written Directive to include the radionuclide, 

treatment site, number of sources, and the total source strength permanently implanted 

in accordance with 10 CFR 35.40(b)(6). Unusual aspects of the procedure, including 

patient-related limitations should be documented in this Written Directive completion. 

The Authorized User should provide a statement in this Written Directive Completion 

attesting that the permanently implanted sources have been placed in accordance with 

the final planned distribution. 

The permanent implant procedure shall be considered complete once the patient is 

released from the Authorized User’s control. 

Terminology 

Gross Tumor Volume, GTV – The volume of the tumor proper as detected on imaging, 

visual observation or manual palpation on physical examination. 

Clinical Target Volume, CTV – The volume containing the gross tumor and a margin 

that may contain malignant cells from the tumor. In the case of prostate 

implants, this usually is the whole prostate but can be more if there is “extracapsular extension” of disease. 

Planning Target Volume, PTV – The volume within which the sources are placed to 

deliver the prescribed dose to the CTV. This would include the CTV plus any 

additional margin used to assure adequate coverage. 

D90 – The dose to 90% of the CTV 

Treatment site – The anatomical description of the tissue intended to receive a radiation 

dose, as described in a written directive [10 CFR 35.2]. The Subcommittee 

recommends the description include the concept of GTV, CTV, or PTV. 

Report Modification 

Please note that a significant minority of the Subcommittee holds an opinion that 

differs substantially from the general body of this modified report. An additional 

section (“Minority Report” vide infra) details key aspects of this minority 

viewpoint. 

In the period since the approval of the ACMUI Permanent Implant Brachytherapy 

Final Report dated October 18, 2011, several comments have been received regarding 

the practicality of the recommendations that report contained. Based on several follow-
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up teleconferences and discussions on the subject, the Subcommittee has modified the 

final report into the form contained herein. The essential adjustments are: 

1) Omission of the use of D90 to the treatment site as a criterion for Medical Event 

definition. Upon reflection, most members of the Subcommittee felt that after 

years of arguing against the use of dose to the treatment site as a metric for 

defining Medical Events, it was imprudent to resurrect its use presently. 

2) Omission of the octet concept. While some members of the Subcommittee liked 

the concept, others felt this may prove too challenging in real, daily practice for 

the Authorized User to document and the regulator to effectively inspect. 

3) Inclusion of the attestation by the Authorized User in the Written Directive 

Completion. This, along with A2a,b – overdosing of normal tissues, is meant to 

address the concern about bunched sources. 

The rationale for these recommendations is discussed below. Importantly however, 

there was not complete agreement within the Subcommittee on several issues and this 

modified report does not reflect a unanimous opinion on the issues discussed. At the 

end of this document is a section entitled, Minority Report, which explains the 

dissenting perspective. 

Discussion 

The ACMUI has previously issued three reports providing recommendations on the 

definition of Medical Event for permanent implant brachytherapy. In the 2008 report1

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ACMUI provided comments and recommendations on the proposed rule2

 to redefine 

Medical Event for permanent implants. The ACMUI issued an interim report3 in 2010 

at the NRC’s charge to provide recommendations on regulatory changes or 

improvements to the NRC’s processes for permanent implant brachytherapy programs. 

ACMUI’s interim recommendations reiterated the principle that “a Medical Event 

should be potentially of true medical significance to a patient.” In the time since the 

2008 rulemaking2

, NRC and the medical community have discussed4 possible Medical 

Event definitions that would identify those permanent implants (and ideally only those 

implants), that fall below clinically acceptable tolerances. Most recently, the ACMUI 

 

1 Advisory Committee on the Medical Use of Isotopes (ACMUI) comments on the Proposed Rule for 

Medical Use of Byproduct Material – Amendment/Medical Event Definitions (RIN 3150-AI26, NRC2008-0071-0058, November 5, 2008; 

http://pbadupws.nrc.gov/docs/ML0922/ML092220766.pdf). 2 73 FR 45635, Proposed Rule for Medical Use of Byproduct Material – Amendment/Medical Event 

Definitions (RIN 3150-AI26, NRC-2008-0071, August 6, 2008; 

http://edocket.access.gpo.gov/2008/pdf/E8-18014.pdf). 3 Advisory Committee on the Medical Use of Isotopes (ACMUI) Permanent Implant Brachytherapy 

Interim Report (October 20, 2010; http://pbadupws.nrc.gov/docs/ML1035/ML103540385.pdf). 4 Medical Rulemaking Workshops for Discussion of Topics Related to Medical Part 35 Regulations 

(New York, NY, June 20-21, 2011; Houston, TX, August 11-12, 2011; 

http://www.blsmeetings.net/NRCMedicalRulemakingWorkshop/presentations.cfm) 
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Permanent Implant Brachytherapy Subcommittee issued another report in October 

2011, which was subsequently reviewed by the entire ACMUI and designated as 

"final". Since finalizing that report, a number of concerns were raised by experienced 

practitioners and stakeholder organizations including the American Society for 

Radiation Oncology (ASTRO). Upon review of these concerns, some members of this 

Subcommittee now believe that although the recommendations within the October 2011 

report would work in an ideal world, there could be difficulties with some of these 

recommendations in the "real world" of brachytherapy. Therefore, this modified report 

contains different criteria defining Medical Event from the October 2011 report that 

some members of the Subcommittee feel will be more practical yet fully effective in the 

aim of capturing events that are truly clinically significant or of radiological 

importance. However, see the section entitled Minority Report at the end of this 

document, which reveals that the vote on this matter was not unanimous. 

This modified ACMUI report proposes a definition that would capture appropriate 

Medical Events, utilizing metrics consistent with information currently required on the 

Written Directive and using standard medical guidelines for permanent implant 

brachytherapy. This proposed definition would identify cases where less-than-desirable 

dosimetry results from poor source distribution. Unlike previous definitions, dose 

changes due to edema or other patient-related factors would not trigger a Medical 

Event. 

Because the vast majority of permanent implants are performed to treat prostate cancer, 

examples and guidance for these recommendations have drawn heavily on that 

procedure. However, the proposed definition (and everything else in this Subcommittee 

report) is intended to apply generally to all forms of permanent implants. 

The Medical Event definition proposed in this modified report would catch an event 

where an inappropriate number of sources are bunched together through the 

requirement that the Authorized User provide an attestation in the Written Directive 

Completion that the final distribution of sources has been placed in accordance with 

that called for by the computer-calculated plan, or medical description why the surgical 

implant varied from the plan. As the computer-generated plan will invariably call for a 

source distribution that will be spread out within the treatment site (except for areas to 

be spared or dose-escalated as called for in the prescription), the final source 

distribution should reflect a reasonable approximation to that computer-generated 

source distribution. The Authorized User must attest in the Written Directive 

Completion that this aim has been achieved. For cases in which areas within the 

treatment site are physically unreachable (e.g., the pubic arch limited access to the 

anterior prostate) in which octants might therefore be underrepresented, the Written 

Directive Completion should reflect the clinical limitations encountered. Such cases 

should not be classified as Medical Events as long as the completed Written Directive 

documents why there might be octants with fewer sources than initially planned. 

The Subcommittee feels that dose is an acceptable parameter for defining Medical 

Events that are due to overdoses to normal tissues and structures. For normal tissues 
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and structures, some form of dose-volume specification is needed for realistic 

regulatory implementation. The suggested D5cc contiguous dose-volume specification 

avoids the high variation in dose sometimes seen in point doses and has literature to 

support it being a relevant quantity for toxicity. In the case of prostate therapy, the 

rationale for the distinction between the bladder and rectum versus the urethra is that 

the latter falls within the target volume. Thus, the suggestion for categorizing normal 

structures as neighboring normal tissues or intra-target normal tissues is included in this 

report. 

This modified report also provides recommendations of how the NRC should apply the 

current requirements for a permanent implant Written Directive. As stated in 10 CFR 

35.40(b)(6), a Written Directive must contain for permanent implants: 

“(i) Before implantation: treatment site, the radionuclide, and dose; and 

(ii) After implantation but before completion of the procedure: the radionuclide, 

treatment site, number of sources, and total source strength and exposure time 

(or the total dose).” 

The Subcommittee recommends use of the current NRC definition for prescribed dose 

in manual brachytherapy which allows the Authorized User to use total source strength 

(number of sources) and exposure time (permanent). Completion of the Written 

Directive after implantation reflects NRC’s recognition of the need to allow final 

Written Directive documentation based on the medical situation encountered during the 

surgical procedure. The Subcommittee recommends that “completion” of the 

procedure should be considered the point when the patient is released from the 

Authorized User’s control. This time frame is consistent with other surgical 

procedures, allowing the physician to complete surgical documentation while the 

patient is in the surgical recovery area. 

 Adequate treatments require appropriate source-strength distributions that have been 

correlated over decades with successful clinical outcomes. As discussed in previous 

reports from this Subcommittee, post-implant evaluation constitutes an important 

component of Authorized User (and other members of the treatment team) selfassessment for correlating how actual source distributions compare with that on the preimplant plan, and as modified by the Written Directive completion. It is acknowledged 

that dose distributions calculated on such post-implant dosimetry studies are fraught 

with problems, making calculated dose an unreliable metric for regulatory compliance 

purposes with regards to the treatment site. Nonetheless, post-implant evaluation of this 

type provides some valuable medical feedback to the Authorized User. Post-implant 

evaluation of the number of seeds located in the treatment site, as modified by the 

Written Directive completion, does provide the Authorized User and the regulating 

community with a more objective basis for inspecting implant compliance. Therefore, 

the Subcommittee has recommended that post-implant assessment be a mandatory 

component of the overall treatment process and is required implicitly through the 

requirement of an assessment of dose to the normal structures. 
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Basis for the Previous Subcommittee Recommendations 

The Subcommittee has reaffirmed the principles that guided the definitions from the 

previous reports. The definition of a permanent implant brachytherapy Medical Event 

should be based on the following concepts: 

A Medical Event ideally should be of true medical significance to a patient. The 

definition should be sensitive enough to detect any implant that is truly of 

potential harm to a patient from an unintended action during the surgical 

implantation, but not so rigid as to prevent an Authorized User from exercising 

his/her medical judgment for the benefit of the patient in changing where to 

implant seed during the surgical implant procedure. 

NRC regulations categorize “harm” to a patient in these two ways: 

1.) Radiological and medical harm medically due to overdosing of 

sensitive normal structures and tissues 

2.) Medical harm due to unintended under-dosing the cancer and not 

curing the patient 

An appropriate Medical Event definition for permanent implant brachytherapy must 

reasonably balance the identification of these potential ways of patient harm, but 

without causing the real harm of reducing or eliminating the patient’s access to this 

type of therapy, which historically has been proven effective in treating cancer, such as 

prostate cancer, with little to no side effects. This is a difficult task and the 

Subcommittee feels the proposed definition in this modified report reasonably meets 

this balance. 

Meeting this reasonable balance is made even more difficult when attempting to 

encompass all forms of permanent implant brachytherapy under one Medical Event 

definition. The Subcommittee was previously in favor of proposing separate medical 

event definitions for prostate vs. non-prostate permanent implants. But, with the 

Medical Event definition proposed here, the Subcommittee no longer feels it is 

imperative to create separate definitions. 

However, since overdose (item 1. immediately above) is irreversible whereas 

underdosing (item 2.) can be medically corrected (in some cases), the Subcommittee is 

not in full agreement with NRC’s traditional stance on the equivalence of these two 

forms of “harm”. It is felt by some Subcommittee members that, while overdosing of 

normal tissues remains clearly within the realm of NRC purview (protection of the 

public from inappropriate use/application of byproduct material), underdosing (to the 

target) falls into the realm of “practice of medicine” and should not remain a basis for 

NRC regulation. Furthermore, during the Summer 2011 Workshops, yet another 

concept of "harm" was introduced - psychological harm to the patient if his/her 

brachytherapy procedure has been labeled as a Medical Event. Despite the fact that 
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NRC has always insisted that the appellation, “Medical Event” does not necessarily 

imply clinically significant problems with the procedure, exaggerated negative media 

coverage may have spoiled the original NRC intent of this terminology and 

Subcommittee members now acknowledge the possibility of this additional form of 

"harm" as an unintended consequence of the Medical Event reporting process. This 

emphasizes the importance of developing a truly appropriate and relevant definition of 

Medical Events for permanent implant brachytherapy and all other brachytherapy 

procedures. 

The Subcommittee recognizes that a dose-based definition for the treatment site, 

especially in prostate permanent implant brachytherapy, suffers from several 

limitations: 

1.) True anatomic prostate volume or shape changes can occur during and after 

the implant procedure, particularly due to edema, 

2.) Spurious differences in estimated prostate volumes can occur due to inherent 

limitations of identifying organ or target boundaries using CT and ultrasound 

(or any other modality), 

3.) Volume estimate uncertainties due to artifacts caused by the seeds and the 

resultant indistinct prostate boundaries seen on post-implant CT images. 

For these reasons, the Subcommittee opposes the use of dose to the treatment site (but 

is not opposed to appropriate use of absorbed dose to normal tissues) in defining 

Medical Events (however, please see the Minority Report at the conclusion of this 

modified report since not all Subcommittee members entirely oppose the use of dose to 

the target). The October 2011 report did use absorbed dose to the target in a limited 

fashion and some Subcommittee members are still in favor of that particular limited 

application). The Subcommittee also recommended in previous reports that if an 

apparent Medical Event were found to be due to true anatomic prostate volume changes 

(item 1. immediately above) after the administration, it should not be deemed a Medical 

Event. Such cases should be addressed in the fashion of other patient-related or 

patient-specific factors equivalent to a patient removing a temporary implant, migration 

of properly implanted radioactive seeds, or termination of a 90Y microsphere 

administration because of stasis. Finally, consistent with the Subcommittee’s opinion 

regarding target underdosing (an occasionally correctable situation), an implant with 

potentially undertreated regions should not be considered a Medical Event if imaging 

identifies regions requiring additional radiation therapy. 

The previous reports also reviewed aspects of the old definition that dealt with normal 

tissues. Consider the part of §35.3045 that reads, “A dose to the skin or an organ or 

tissue other than the treatment site that exceeds by 0.5 Sv (50 rem) to an organ or tissue 

and 50 percent or more of the dose expected from the administration defined in the 

Written Directive.” The Subcommittee feels that this definition is obsolete and 

inappropriate for use in modern permanent implant brachytherapy. 
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With the very high gradients in the dose distributions, small and clinically insignificant 

shifts in: 

a.) the source distribution, 

b.) the target organ, or 

c.) the normal tissues in question 

can cause much larger changes than 0.5 Sv or 50% of the expected dose, with no 

consequences to the patient. For example, a 1-cm shift in the position of the prostate 

due to gas in the bowel (a common amount of movement) can produce a 94% change in 

the calculated dose to the skin. It is worth noting that the difficulties in post-implant 

dose reconstruction for the prostate might also affect dose calculations for certain 

normal tissues – for instance, the above example of a 94% increase in the dose to the 

skin might not be seen if the same procedure were done the very next day if the bowel 

gas resolved. Such perfectly normal and clinically acceptable implants should not be 

categorized as Medical Events. 

Thus, if this §35.3045 criterion were applied strictly, some (perhaps many) properly 

executed and medically acceptable implants might inappropriately be categorized as 

Medical Events. This underscores the concept that, ideally, Medical Events should be 

of potential medical significance or at least should identify trends that could lead to 

consequences of medical significance if not identified and acted upon. The proposed 

Medical Event definition herein adheres to these principles. 

Minority Report

One of the four members of the subcommittee preferred the definition for a permanent 

implant medical event in the 2011 draft of the report presented to the ACMUI to that 

definition in this draft. The reasons were: 

1. The ambiguity of the term, “treatment site” in the new proposed draft. In 

the previous draft, the evaluation of the source placement explicitly tied with the 

“planning target volume (PTV).” Treatment site in the new draft is taken to 

mean the volume in which the sources are to be placed. In the prescription, the 

treatment site usually would mean the volume to receive the target dose, which 

would be the clinical target volume (CTV). This sets up a situation where the 

treatment site in the written directive and the treatment prescription are 

different, potentially leading to confusion and misunderstanding. 

2. The dissociation of the definition with potential harm to the patient. The 

principle elucidated in the previous draft was that a medical event should be 

related to a situation that potentially could lead to harm to a patient. In many 

situations, an implant with more than 20% of the sources outside of the PTV can 

lead to a perfectly good implant with the proper dose coverage to the CTV, 

particularly in a case where just over 20% fall outside. The was the reason to 
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have the exclusion criterion in the previous draft that specified if the dose to 

90% of the CTV (D90) was greater than 60% of the prescribed dose, the case 

would not be a medical event, preventing excessive reporting of adequate cases 

as medical events. Contrary to the interpretations of some members of the 

subcommittee, the criterion of D90<60% would not trigger a medical event 

classification for any case unless the source distribution fell into the criteria of 

>20% of the sources outside of the PTV or 5% not in each octant. The dose 

specification is an exclusionary criterion to narrow the application of the 

geometric criteria, not to expand and add another criterion. The dissenting 

member did prefer the use of 70% as the cut-off value for the D90, but the 

ACMUI changed that to 60%. The principle is still sound with either value. 

Another objection to the use of this exclusionary clause was that the 

radiotherapy community has demonstrated that D90 should not be used to 

trigger a medical event for many reasons (e.g., edema, atrophy, timing of 

assessment different imaging modalities,) discussed very well in the 2008 report 

of the Permanent Implant Subcommittee. Those reasons still hold. There was 

concern in discussions about the current draft that the use of this quantity in any 

form could lead to the use of D90 as a criterion for a medical event rather than 

an exclusionary criterion. The dissenter felt that the NRC now understands the 

problems associated with the use of D90 to define a medical event, and as the 

2011 draft was written, this hypothetical problem would not be realized. 

3. The lack of a distribution criterion in the current draft. In the previous draft, 

the criterion for a minimal amount of source distribution was to catch egregious 

implants where a very large number of the sources unintentionally bunched 

within the target, and thus would not be caught in the 20%-outside-the-target 

criterion. 

a. While the criterion specified 5% in each of the target’s octants, it 

explicitly excepted cases where a non-uniform distribution was 

prescribed, for example to reduce or accentuate the dose in particular 

regions, or where the patient’s anatomy precluded such a distribution. 

b. Some discussion in the subcommittee focused on the complexity of 

octants. Octants are simply cutting the target in half on each of the three 

axes, which is very simple. Equivalently, it could be stated that 20% of 

the sources would occupy either half of the target, regardless of how the 

target was cut (again, except by prescribed differential distributions or 

due to anatomical constraints.) 

c. The subcommittee had some discussion about potential disagreements 

between regulators and practitioners based on differing axes used for the 

evaluation. This could be solved by allowing this criterion to be satisfied 

if the distribution would exist for any set of orthogonal axes. 

d. Again as with the 20% criterion, failure to satisfy this criterion only 

would have triggered a medical event if the D90 fell below 60%, i.e., if 

the poor distribution was clinically significant. The distribution need not 

be determined for any implant with the D90>60%, which means most 

practices would never perform this determination. 
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4. The attestation in the current draft. In place of the criterion for a minimal 

distribution of the sources, the current draft has an attestation by the authorized 

user that the sources were placed as intended. The dissenting member felt that 

this was not good regulation, neither holding the user responsible for possibly 

harmful sources placement and encouraging some users faced with a potentially 

harmful implant to prevaricate. While this attestation was to replace the minimal 

distribution criterion, it could just as well replace the 20%-outside-the-target 

criterion, since the user could say that where ever the sources lie is the treatment 

site, now defined as the desired location of the sources. The attestation makes 

enforcement of this medical event definition mostly useless, unenforceable and 

a potential source of contention between users and regulators. There was 

discussion in the subcommittee asserting that the distribution of sources in the 

target was practice of medicine, and thus should not be included in the medical 

event definition. If that were the case, the attestation is unnecessary. Also if that 

were the case, holding the placement of the sources around the target, and 

possible outside of any defined target, would also be practice of medicine and 

outside the charge of the NRC. This assertion has been discussed many times in 

the ACMUI, always to be decided that the NRC does have the obligation to 

protect the public when practitioners fail to do so, and not to leave such cases to 

credentialing committees, where they exist.