Advisory Committee on the Medical Uses of Isotopes (ACMUI) 

 Permanent Implant Brachytherapy Interim Report 

October 20, 2010 

Note: The ACMUI unanimously voted to approve this report at the October 20, 2010 

meeting with the caveat that this is an interim report that may be revised in the future to 

consider additional input such as that received from stakeholders at public workshops. 

Permanent Implant Brachytherapy Subcommittee Members

Debbie Gilley 

Darrell Fisher, Ph.D. 

Susan Langhorst, Ph.D. 

Bruce Thomadsen, Ph.D. 

James Welsh, M.D. 

Introduction

At the ACMUI meeting on October 27, 2008, the ACMUI and NRC staff 

discussed the proposed rule on medical use of byproduct material for permanent 

brachytherapy procedures (“permanent implants”). Several suggestions made at that 

meeting were incorporated into a formal Subcommittee report. On November 5, 2008 

the formal report (Advisory Committee on the Medical Uses of Isotopes (ACMUI) 

comments on the Proposed Rule for Medical Use of Byproduct Material—

Amendments/Medical Event Definitions (RIN 3150-AI26, NRC-2008-0071)) of the 

ACMUI Permanent Implant Brachytherapy Rulemaking Subcommittee was made 

available. (Report available on NRC's ACMUI web page at: http://www.nrc.gov/aboutnrc/regulatory/advisory/acmui.html ) 

Since the time of the November 5, 2008 report, NRC has made extensive review 

of medical events involving permanent implant brachytherapy at the Department of 

Veterans Affairs (DVA) hospitals. As a result, NRC decided it was necessary to reevaluate the proposed rules. This led NRC Staff to issue the following charge to the 

ACMUI permanent brachytherapy subcommittee: 

Charge: The subcommittee should draft a report to provide recommendations on 

regulatory changes or improvements to the NRC's processes for permanent implant 

brachytherapy programs, as an outgrowth of the investigation of the Department of 

Veterans Affairs medical events. 

In the interim, a re-proposed rule based partly on analysis of the medical events 

involving the VA was submitted for the Commission to consider. Thus, this 

Subcommittee Report addresses not only the above charge but also various aspects of 

the re-proposed rule. 

Subcommittee Recommendations
The definition of a permanent implant brachytherapy medical event should be 

based on the following concepts: 

I. A medical event ideally should be of true medical significance to a patient. 

If this requirement is not fundamental, there is the risk of being overly sensitive and 

designating as “Medical Events” many cases that are of no potential harm to a patient 

and thereby inundating the regulatory and health care systems with many unnecessary 

investigations. The NRC definition of a “medical event” for permanent implant 

brachytherapy should be based on medical actions that could either cause harm to the 

patient, result in grossly inadequate treatment or identify patterns or trends that could 

lead to patient harm or inadequate treatment. 

II. This concept should be balanced by the concept that: The definition should be 

sensitive enough to detect any implant that is truly of potential harm to a patient.

Furthermore, “harm” to a patient can be of two forms: 

1.) Harm due to overdosing of sensitive normal structures and tissues 

2.) Harm due to under-dosing the cancer and not curing the patient 

III. Procedures with expected large changes in the source positions, such as permanent 

intra-operative lung implants, should be considered separately form more stable 

procedures, such as prostate implants. An appropriate Medical Event definition must 

balance the factors discussed above. This is a difficult task and could be even more 

difficult if an attempt is made at encompassing ALL forms of permanent implant 

brachytherapy under one set of Medical Event criteria. Therefore, the Subcommittee 

recommends that unless an activity-based (as opposed to dose-based) Medical Event set 

of criteria is adopted, consideration be given to separation of permanent brachytherapy 

procedures into various categories, e.g. permanent implant brachytherapy procedures 

which result in significant rearrangement of implant location during completion of the 

surgical implant procedure (such as operative lung implants) and those procedures that 

do not generally experience this phenomenon (such as prostate implants). The 

Subcommittee suggests that the former implant procedures be covered under separate 

categories within 10 CFR 35.400 or perhaps 10 CFR 35.1000 for the present. 

IV. The Subcommittee strongly recommends that NRC seek specific help from 

stakeholders, particularly the medical community with expertise in permanent implant 

brachytherapy to discuss the definition of Medical Event for permanent implants, due to 

the complex nature of the issues. 

 

V. The event metric should be source-strength based as opposed to dose based. The 

Subcommittee has focused on its primary charge above but is also aware of the recently 

re-proposed rule and has devoted considerable deliberation to this closely related 

subject. The Subcommittee is aware of certain circumstances in which the original 
recommendations of ACMUI may be inadequate. Previously, the ACMUI was in favor 

of abandoning a dose-based metric in favor of an exclusively source-strength-based 

definition. The Subcommittee remains in favor of not using a dose-based metric for 

defining medical events. However, the Subcommittee is aware of certain clinical 

scenarios in which the ACMUI-proposed source-strength-based definition may fall 

short. For instance, the extremely unusual and unlikely situation in which all seeds are 

placed within the prostate but not distributed in the intended fashion. If they are all 

clumped into one location, this would not be a Medical Event under the sourcestrength-based proposed definitions. Consideration of this particular situation has 

caused the Subcommittee to reconsider its initial position on fully endorsing and 

advocating the previous activity-based definition. 

V. If any dose-based criteria are to be applied, these criteria must be able to account 

for: 

1.) True anatomic prostate volume or shape changes during and after the implant 

procedure, 

2.) Differences in prostate volumes identified on CT vs. ultrasound (or any other 

modality), 

3.) Inherent inter- and intra-observer differences in prostate contours (and thus 

volume estimates, which go into dose calculations), and 

4.) Volume estimate uncertainties due to artifacts from the seeds and the 

indistinct prostate boundaries seen on post-implant CT images. 

 We recommend that if an apparent medical event were found to be due to 

anatomic prostate volume changes (item 1. above) after the administration, it would not 

be deemed a Medical Event, and that such cases be addressed in the fashion of other 

patient-related or patient-specific factors such as a patient removing a temporary 

implant, migration of properly implanted radioactive seeds, or incompletion of a Y-90 

administration because of stasis. 

 Additionally, it should be kept in mind that brachytherapy is an art as well as 

a science and on occasion, skilled, experienced practitioners may intentionally “doseintensify” certain regions within a target. Conversely, practitioners my elect to “dose 

de-escalate” in areas such as the urethra in a patient who has had a TURP (transurethral 

resection of the prostate) for example. Such aspects of the art and science of 

brachytherapy must be accommodated in any dose-based definitions of Medical Events 

and further strengthen the argument in favor of exclusively activity-based Medical 

Event definitions. 

Discussion

 In general, the Subcommittee finds that much of the intent of the Permanent 

Implant Brachytherapy Rulemaking Subcommittee Report of November 5, 2008 

remains valid. The 97 medical events in 2008-09 within the Department of Veterans 

Affairs and the subsequent investigation of those medical events have not changed the 
general recommendations of the ACMUI Permanent Implant Brachytherapy 

Rulemaking Subcommittee. Some relevant points include: 

1.) Part § 35.3045(a)(3) 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 

(excluding, for permanent implants, seeds that were implanted in the correct site but 

migrated outside the treatment site.” In otherwise normal cases, this 0.5 Sv is a very

small amount compared to therapeutic doses prescribed in most of these permanent 

brachytherapy cases (amounting typically to 0.35%). Also, a 50% overdose (as 

described in §35.3045(a)(3) could be medically inconsequential if the original expected 

dose to that normal tissue was very low (for example, the predicted skin dose in most 

permanent brachytherapy procedures or the penile bulb dose in prostate brachytherapy). 

With the very high gradients in the dose distributions and the inverse square law, very 

small 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 and constituting a perfectly normal and appropriate 

implant. A typical prostate implant may give 6 Gy to the skin 5 cm anterior to the 

prostate. If at the time of CT the prostate falls only 4 cm form the skin, not an 

uncommon occurrence, the dose to the skin would be twice that expected. Thus, if 

this criterion is applied strictly, some and perhaps many properly executed, medically 

acceptable implants could be inappropriately categorized as medical events. This 

underscores the concept that ideally Medical events should be of potential medical 

significance (or perhaps should identify trends that could lead to consequences of 

medical significance if not identified and acted upon). The 0.5 Sv threshold/20% 

definition of “Medical Event” is problematic when one considers the variability and 

inherent uncertainty in current medical practice, with dose uncertainties as high as 50% 

possible and medically acceptable. The inherently high level of uncertainty for many 

brachytherapy procedures in absorbed dose estimation is due to the variability of the 

tumor border, which is dependent on the imaging modality and imaging technique, 

normal movement of organs in the body, and significant volumetric changes associated 

with the surgical procedure itself resulting in inflammation and subsequent biological 

response. 

 Implanted amounts of radioactivity are not fully equivalent to absorbed dose 

and an appreciation that the spatial rearrangement of the same constant amount of 

activity can result in very different values of radiation dose. In current medical 

practice, the uncertainty in defining treatment volumes due to different imaging 

modalities and procedures and temporal variations due to the effects of the invasive 

procedures (e.g. edema) makes the 20% Medical Event criteria unrealistic. 

The Subcommittee suggests defining specific volumes or areas of organs, 

tissues and skin if §35.3045(a)(3) is to remain. The Subcommittee suggests revision of 

§35.3045(a)(3) to adjust the nominal 0.5 Sv dose and the 50 percent figure to more 

appropriate figures and/or to specify an area of maximally irradiated skin and volume 

of maximally irradiated organ or tissues (e.g. 30 cm2

 of maximally irradiated skin or 5 
cm3

 of maximally irradiated organs or tissues, based on Perera F, Chisela F, Stitt L, et 

al, TLD skin dose measurements and acute and late effects after lumpectomy and highdose-rate brachytherapy only for early breast cancer. Int J Radiat Oncol Biol Phys. 

62,1283-90; 2005 and S. L. Schoeppel, M. L. LaVigne, M. K. Martel et al., “Threedimensional treatment planning of intracavitary gynecologic implants: analysis of ten 

cases and implications for dose specification,” Int J Radiat Oncol Biol Phys 28 (1), 

277-83 (1994).). 

 The Subcommittee maintains that the units in the language above remain 

inconsistent and confusing in that absorbed dose (Gy or rads) and equivalent dose (Sv 

or rem) are used almost interchangeably. It is suggested that the final rule use 

appropriate units in a consistent manner. 

2.) In the previous Subcommittee report, the ACMUI recommended that section § 

35.3045(a)(2) (ii) be modified to “The total source strength implanted outside the 

treatment site (including the gross tumor, the clinical target volume plus a variable 

planning margin as defined by the AU) exceeding 20 percent of the total source 

strength documented in the written directive”. This would take into account source 

migrations, seeds that become dislodged and seeds suctioned out of position but would 

still hold accountable cases in which the target organ was grossly misidentified and the 

wrong area was implanted. 

The Subcommittee is aware of the preference for regulatory language that will broadly 

encompass all organs/situations rather than design regulations for each organ/situation. 

However, it would be prudent to devise separate categories for: 1) permanent 

implant brachytherapy procedures that result in significant rearrangement of 

implant location during completion of the surgical implant procedure, e.g., mesh 

lung implants and 2) those procedures that do not generally experience this 

phenomenon, such as prostate or breast implants. This would take into account the 

vast differences in sophistication and technology for pre-implantation treatment 

planning and post-implant dose distribution assessment between the two categories. 

Such separate classification could hopefully obviate the unnecessary assignment of the 

title of medical event to numerous medically acceptable non-prostate implants because 

of modifications to source geometries with the closing of surgery. The question of 

where to put such procedures in which implant relocation does occur was the subject of 

discussion within the Subcommittee with some favoring placement into 10CFR 

35.1000 and others suggesting a revision within 10CFR 35.400. 

3.) The Subcommittee felt that the old definition of “treatment site” (described in §35.2 

as “the anatomical description of the tissue intended to receive a radiation dose, as 

described in a written directive”) could lead to some uncertainty regarding the exact 

volume to which “treatment site” refers in §35.3045(a)(2)(ii). The Subcommittee 

recommends refinement of the previously ambiguous term “treatment site” to 

encompass the more rigorously defined concepts of gross tumor volume (GTV), 

clinical target volume (CTV) and planning target volume (PTV) (ICRU Report 62: 

Prescribing, Recording, and Reporting Photon Beam Therapy. Bethesda, MD: 
International Commission on Radiation Units and Measurements (ICRU), 1999). The 

Subcommittee recommends that any revised rule and all subsequent matters 

dealing with this subject adopt the currently accepted nomenclature. If a sourcestrength-based criterion is used, the basis for defining a medical event should be of the 

form of 20% of the source strength fall outside of the planning target volume, whereas 

a dose-based criterion should relate to the clinical target volume, both according to 

conventional clinical practice. 

4.) The Subcommittee is in agreement that post-implant dosimetry is important and 

should be required. There was some discussion about the proposed requirement of 

licensees assessing the dose within 60 days from when the patient leaves the posttreatment recovery area. While imposing a timeline for such dosimetric evaluation may 

be challenging or difficult for some licensees, it is acknowledged that NRC desires 

some defined timeline for regulatory purposes. The 60-day timeline is acceptable as it 

is in alignment with recommendations of national organizations and guidelines. 

Situations in which a patient refuses or doesn’t show up within the defined time-frame 

should be considered patient related factors and excluded from classification as Medical 

Events. 

 There was some discussion within the Subcommittee regarding the idea of 

using this post-implant dosimetry rule for regulatory purposes. Not all were in 

agreement that this requirement is appropriate for regulatory purposes (i.e. that if a 

licensee does not perform post-implant dosimetry within 60 days it would be a Medical 

Event). The decision of when to image and which modality to use for such imaging 

may be a medical decision. The main point is that after the treatment, there should be 

some imaging-based assessment with which dose can be re-estimated. Current practice 

varies enough that an NRC imposed regulatory requirement specifying the imaging 

modality could impede the development of good practice. 

5.) Devising a truly acceptable, universally appropriate dose-based criterion for 

medical events remains challenging. One challenge is the potential for difference in 

the prostate anatomy between the pre-procedure images and those performed 

afterwards that will affect the calculated total dose. 

 Prostate volume can be affected by: 

1.) Anatomic changes such as edema or atrophy 

2.) Contouring differences due to: 

a. different modalities (e.g CT vs ultrasound) 

b. inter- and intra-user contouring differences, 

c. artifacts introduced by the metallic seeds on CT, and 

d. Organ motion, which can be several centimeters, between the 

ultrasound and the CT. 

Based on factor 1.) above, anatomic changes, depending on exactly when in the edemaresolution time course the post-implant dosimetric analysis is performed, the 

calculation of total dose can vary, although in general, the variations seem to fall in the 

range of less than 10% (AAPM recommendations on dose prescription and reporting 

methods for permanent interstitial brachytherapy for prostate cancer: report of Task 
Group 137. Nath R, Bice WS, Butler WM, Chen Z, Meigooni AS, Narayana V, Rivard 

MJ, Yu Y; American Association of Physicists in Medicine. Med Phys. 2009 

Nov;36(11):5310-22). Therefore, the Subcommittee continues to feel that dose-based 

assessments are not be ideal for regulatory purposes. 

A dose-based definition must be capable of addressing all of the factors above that can 

affect prostate volume and calculated absorbed dose. To design a truly appropriate a 

dose-based criterion, it may be reasonable to introduce the concept of normalization to 

Vinit, the initial pre-implant volume, so that any subsequent calculations of total dose 

afterwards are related back to this volume that the Authorized User based his/her initial 

dose prescription on. Thus, if in a prostate brachytherapy procedure, the prostate 

volume on which planned dose calculations are made is Vinit but the post-implant 

dosimetry is done during the edematous period and the measured volume is 140% Vinit, 

any deviations from the written directive prescribed dose due to this volume-related 

dose discrepancy should not be considered a Medical Event. The same concept would 

hold should the prostate shrink considerably following the implant due to the actions of 

hormonal therapy. In addition to addressing the concern about anatomic volume 

changes that affect dose calculations, the concept of normalizing back to V(init) also 

addresses the problems posed by the non-anatomic, contouring-related volume 

estimations. Any dose-based criteria for Medical Events must refer back to Vinit, not the 

volume measured during the post-implant dosimetry procedure if there is a volume 

change. It is noted that normalization to Vinit will eliminate categorization of many 

perfectly acceptable implants as Medical Events, but would not preclude identification 

of truly sub-standard implants irrespective of edema, atrophy or contouring 

discrepancies. In other words, a volume change should not be the basis for a Medical 

Event, but conversely just because a volume change occurred does not exclude the 

possibility of a Medical Event. 

 In general, alterations of a final brachytherapy dose due to “patient factors” 

such as a patient removing a temporary implant, migration of properly implanted 

radioactive seeds, or incompletion of a Y-90 administration because of stasis are not 

considered Medical Events. It is highly recommended that prostate volume changes 

due to edema, hematoma, hormone therapy-induced shrinkage, etc. also be 

considered “patient factors.” Thus, item 1.) above, anatomic changes that cause 

alterations in volume that affect dose calculations should not be cause for the label of 

Medical Event. 

 Additionally, brachytherapy dose is not homogenous. Authorized User 

brachytherapists often intentionally intensify dose (to perhaps 125-150%of the 

prescribed dose) to the high-risk areas of the prostate (e.g. the peripheral lobe where 

many tumors are located). In the opinion of many experts, the reason why 

brachytherapy is so effective is precisely because of this much higher dose to the tumor 

areas than stated in the prescription dose. This reality creates an intrinsic challenge to 

the use of dose-based criteria for regulatory purposes. The concept of intentional 

underdosing to certain areas within the clinical target volume (CTV) also poses a 

challenge to most dose-based criteria including those previously proposed by NRC. 
 

 The Subcommittee has decided to not put forth a proposition explicitly in 

writing at this time. But if requested the Subcommittee would be pleased to engage in 

further discussion with NRC staff on this complicated, important and sensitive matter in 

a highly efficient manner to help develop the regulatory wording. 

Final Comments

 Medical events are defined by the specific situations that constitute medical 

events. NRC’s Policy Statement on Medical Uses (August 2000) states, “NRC will, 

when justified by the risk to patients, regulate the radiation safety of patients primarily 

to assure the use of radionuclides is in accordance with the physician's directions.” 

Therefore, it is important that the situations chosen to define a medical event for 

permanent implant brachytherapy be justified as having the potential of causing patient 

harm. In order to determine whether the use of the permanent implant is in accordance 

with the physician’s directions, the requirements need to be understandable and 

unambiguously measurable for proper implementation and inspection and compatible 

with good medical practice. 

 Permanent implant brachytherapy is an effective, safe and convenient medical 

procedure that addresses a potentially lethal disease, cancer. Compared to other 

potentially cancer-curing treatment such as surgery and chemotherapy, permanent 

implant brachytherapy maintains a very safe overall clinical profile. Because of its 

safety, effectiveness and convenience, permanent implant brachytherapy is often the 

preferred first choice therapy. NRC should remain aware that compared to other 

modalities such as surgery and chemotherapy, permanent implant brachytherapy 

maintains its standing as a low-risk yet highly effective treatment. It would defeat our 

purpose if through overly restrictive regulations this treatment alternative were to fall 

out of fashion and become unavailable to those who could benefit. In the estimation of 

some, strict enforcement of the event rule could lead to many thousands of perfectly 

acceptable permanent brachytherapy cases (in prostate alone) being considered Medical 

Events. This would have obvious consequences on the practice and future availability 

of this proven effective medical option. 

 The Subcommittee recommends that the Subcommittee and all of ACMUI review 

any changes made to the rule before the Commission approves it for publication. It is 

also strongly recommended that NRC seek specific input from the medical community 

with expertise in permanent implant brachytherapy. 

 Finally, this Subcommittee has crafted what it believes is an important first step 

towards an understandable, unambiguously measurable and carefully considered 

solution for a dose-based criterion. The Subcommittee has decided to not put this 

proposition explicitly in proposed regulatory language within this report, but if 

requested, would be pleased to engage in further discussion on this complicated, 

important and sensitive matter in a highly efficient manner. 
Addendum

 

 This subject is presently hotly debated matter not just within the 

Subcommittee but in the radiation oncology community as a whole. Several points in 

the above report were not unanimously favored. Examples include: 

 The point about an exclusively activity-based metric rather than adding or 

switching to dose-based criteria was controversial. Three members were opposed to 

any dose-based criteria for the purposes of a medical event definition. 

 Two members felt strongly that this Subcommittee report should include a 

specific recommendation with regards to a dose-based metric. Three were opposed to 

dose-based criteria and did not wish to spell out any dose-based recommendations for 

fear that these would then be implemented when the preference was to steer clear of 

dose-based criteria altogether. 

 One member was opposed to the statement that brachytherapy is an “art” as 

well as science. Others were not opposed to such labeling. Three members felt that IF a 

dose-based definition were implemented, it would be more critical to emphasize this 

point about the art of medicine. Another member mentioned that this IS an art and 

therefore it will always be challenging for NRC to not encroach upon the practice of 

medicine in permanent implant brachytherapy. This difficulty in avoiding such 

encroachment will be compounded by attempts towards dose-based criteria. 

 One member was opposed to the concept of separating prostate brachytherapy 

(and other permanent brachytherapy procedures that do not typically experience 

significant rearrangement of seed location during completion of the procedure) from 

other permanent implant brachytherapy procedures that do result in significant 

rearrangement of implant location during completion of the surgical implant procedure, 

such as mesh lung implants. 

 One member was opposed to the requirement of post-implant dosimetry as a 

basis for medical events. Two others were not opposed to the requirement of postimplant dosimetry but were opposed to the idea of placing a 60-day limit for 

performing this. 

 Because three members were opposed to any dose-based criteria, (two 

adamant, the other not adamant), all matters related to dose-based criteria (such as 

including a specific recommendation) were controversial and one member suggested 

not including any discussion of the concept at all in this report.