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Advisory Committee on the Medical Use of Isotopes (ACMUI) 

Permanent Implant Brachytherapy Final Report 

October 18, 2011 

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,

a. For the source locations (not resulting from patient-related causes such as 

edema or source migration after placement)

(i) 20% or more of the sources fall outside of the intended locations 

(planning target volume, PTV);

OR

(ii) Less than 5% of the sources occupy any octant of the PTV, except

(a) by design for preservation of normal tissue; or 

(b) intentional dose escalation to a particular region; or 

(c) cases in which patient anatomy or technical limitations preclude 

physically reaching certain areas,

as specified in the Written Directive; 

AND

b. Calculated dose to 90% of the clinical target volume (CTV) is less than 60% 

of the dose prescribed to the CTV (D90<60%) within a timeframe to be 

determined by the Authorized User consistent with prevailing medical 

practice but not to exceed 60 days unless accompanied by written 

justification.

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 cm3 (contiguously) 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 cm3 (contiguously) exceeds 150% of that 
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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;

e. Delivered using the wrong modality or

f. Using leaking sources, 

with the exceptions of seed migration, edema and other patient-related factors or 

source displacement following placement, as long as the criteria in 1a(i) is not 

violated.

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 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 minimum dose to 90% of the CTV 
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Discussion 

The ACMUI has previously issued two reports providing recommendations on the 

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

, 

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. This current 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 report would catch an event where all the 

sources are bunched together. Using a template that limits source placement, the 

requirement of 5% of the sources occupy each octant (except by plan) is generally 

 

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) 

5 Concept from “Sector analysis of prostate implants.” William S. Bice, Jr., Bradley R. Prestidge, 

Michael F. Sarosdy. Medical Physics, Vol. 28, No. 12, December 2001. 6 RTOG 0232: “A Phase III Study Comparing Combined External Beam Radiation And Transperineal 

Interstitial Permanent Brachytherapy With Brachytherapy Alone For Selected Patients With 

Intermediate Risk Prostatic Carcinoma,” Radiation Therapy Oncology Group Protocol 

(9/6/2011 Version; 

http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0232). 
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practical. Octants simply define the prostate in half along each of the three axes and are 

unambiguous. The idea stems from a paper by Bice, Prestidge and Sarosdy.5

Importantly, it would not identify as a Medical Event an implant with the sources 

missing an octant as long as the D90 is above 60%. The 60% criterion is recommended 

to prevent labeling as a Medical Event a less-than-ideal implant that is not medically 

significant to the treatment of that site. 

This last criterion is based on the RTOG 0232,6 a phase III trial comparing combined 

external beam radiation therapy and permanent implant with implant alone for selected 

patients with intermediate risk prostate cancer, where D90<80% was considered an 

unacceptable deviation. Since a Medical Event should be more significant than a 

deviation in a clinical trial, a D90 threshold of 60% would be approximately 20% below 

the medically acceptable doses, which is consistent with other regulations. 

Additionally, for cases in which areas within the target are physically unreachable 

(because of patient anatomy or template and needle geometric limitations, such as the 

pubic arch limiting access to the anterior prostate) in which octants might therefore be 

underrepresented, the Written Directive (which should be completed after the implant 

but before the patient is released from control of the Authorized User) 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. 

For the normal tissue, the 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. The rationale for the distinction between the bladder and 

rectum versus the urethra is that the latter falls within the target volume. 

This final ACMUI 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).” 

Completion of the written directive after implantation reflects the need to document the 

implant based on the medical situation encountered during the procedure, for example 

adding sources where the source distribution appears to need additional coverage or 

noting that some sources could not be placed due to anatomical limitations. The 

completion of the procedure should be considered at the point when the patient is 

released from the Authorized User’s control. This time frame is consistent with other 

types of surgical procedures allowing the physician to complete surgical documentation 

while the patient is in the surgical recovery area. 
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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 forms an important part of 

Authorized User (and other members of the treatment team) self-assessment for 

correlating how actual source distributions compare with that on the pre-implant plan. 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. Nonetheless, post-implant evaluation of this type 

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

evaluation provides the Authorized User and the regulating community with a more 

objective basis for inspecting implant compliance. 

 

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. 

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

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

sensitive normal structures and tissues 

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

patient 

An appropriate Medical Event definition must balance the above factors. This is a 

difficult task and is made even more difficult when attempting to encompass all forms 

of permanent implant brachytherapy under one set of Medical Event criteria. The 

Subcommittee was previously in favor of separating prostate from non-prostate 

permanent implants. With the presently proposed Medical Event definition, the 

Subcommittee no longer feels it is imperative to create such distinct categories. 

The Subcommittee recognizes that a dose-based definition for the target, 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, 
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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. 

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 patientspecific factors equivalent to a patient removing a temporary implant, migration of 

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

administration because of stasis. 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.” With the very high gradients in the dose distributions, very 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 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 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 perhaps 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.