Submission via the Federal eRulemaking Portal November 5, 2008 

 

 

Re: 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) [See 73 FR 45635 (August 6, 2008)] 

 

At their meeting on October 27, 2008, the ACMUI reviewed the proposed rule on 

medical use of byproduct material for permanent implants. The ACMUI notes that these 

rules were developed based primarily on the preplanned technique of prostate 

brachytherapy whereas the rules will nonetheless apply to all types and techniques of 

permanent brachytherapy in any organ of the body. This could create some unforeseen 

unintended consequences. 

General comments: 

The ACMUI supports rule § 35.40 for the written directive (WD) to be source strengthbased rather than being dose based. The ACMUI recommends that the word “activity” 

be replaced by the more technically acceptable term “source strength” whenever it is 

applied to permanent brachytherapy in the document. The ACMUI also notes that 

although the proposed rules were based on the recommendations of the ACMUI, the 

ACMUI was not offered an opportunity to review the proposed rules before the 

proposed rules were published in the Federal Register. The ACMUI requests that, in 

future, the ACMUI be given an opportunity to review proposed rules before publication. 

Specific concerns: 

The ACMUI is concerned that the proposed language §35.3045(a)(2) could result 

in inadvertently and inappropriately categorizing some properly executed, medically 

acceptable, implants as “medical events” (ME) as follows: 

1. The proposed language for § 35.3045(a)(2) (i) on page 45643, column 3 would 

deem it an ME if the total source strength administered differed by 20 percent or more 

from the total source strength documented in the preimplantation WD. Further, it is 

noted that the preimplantation WD cannot be changed since the preimplantation WD 

serves as the basis for determining if an ME has occurred. 

The ACMUI wishes to clarify that many Authorized Users (AU) perform real-time 

adaptive interactive planning whereby the written directive and the source strength to be 

implanted are based on the actual volume dynamically obtained during the procedure 

rather than be based on the preimplant volume (Reference: Nag S, Ciezki JP, Cormack 

R, Doggett S, DeWyngaert K, Edmundson GK, Stock RG, Stone NN, Yu Y, Zelefsky M. 

Intraoperative Planning and Dosimetry for Permanent Prostate Brachytherapy: Report 

of The American Brachytherapy Society. Int J Radiat Oncol Biol Phys 2001;51:1422-

30). Real-time planning is a more accurate method of implantation as it takes into 

account any alterations in the prostate volume and shape that occur between the time 

of the preplan and the implant procedure and therefore represents the actual prostate 

volume and implant situation. Hence for those performing real-time adaptive planning 
implantation, the total source strength to be implanted is determined intraoperatively 

during the implantation procedure and not preimplant. Further, even those performing 

permanent brachytherapy using preplanned techniques will often modify their plan if, 

intraoperatively, they find that the gland volume differs markedly from the volumes 

determined during the preplan. Hence the basis for ME should be the total source 

strength implanted after administration but before the patient leaves the post-treatment 

recovery area. 

The ACMUI therefore recommends that: § 35.3045 (a)(2)(i) be modified to read 

“The administration of byproduct material or radiation from byproduct material for 

permanent implant brachytherapy (excluding sources that were implanted in the correct 

site but migrated outside the treatment site) results in the total source strength 

administered differing by 20 percent or more from the total source strength documented 

in the written directive.” {i.e. delete “preimplantation”} It should be clarified that, in the 

WD, the source strength implanted refers to the source strength implanted after 

administration but before the patient leaves the post-treatment recovery area. This 

wording would therefore apply both to those using the preplanned technique and those 

using real time adaptive technique. Similarly, the word “preimplantation” should be 

deleted from “preimplantation written directive” in sections § 35.3045 (a)(2)(ii), (iii) and 

(iv). 

2. The proposed language for § 35.3045(a)(2) (ii) ) on page 45643, column 3 would 

deem it an ME if the total source strength implanted outside the treatment site and 

within 3 cm (1.2 in) of the boundary of the treatment site exceeded 20 percent of the 

total source strength documented in the preimplantation WD. 

The 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” leads to some ambiguity regarding the exact volume that “treatment site” 

refers to in § 35.3045(a)(2)(ii). There are various standard radiation oncology volumes 

already defined in International Commission on Radiation Units and Measurements 

(ICRU) report #62, including the 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 GTV is the gross demonstrable 

extent and location of tumor growth as determined by clinical examination and/or by 

imaging techniques. The CTV is the tissue volume that contains the GTV and 

surrounding subclinical microscopic malignant disease. The PTV adds a margin to the 

CTV account for uncertainties in source positioning, set up errors, internal organ motion, 

isodose constrictions, etc to ensure that the CTV will be fully covered by the treatment 

plan. These expansion margins are non-uniform and depend on the clinical situation 

and treatment modality. Radiation oncologists use a larger margin if there is high 

degree of uncertainty and/or if there are no adjacent critical structures. Conversely, the 

margins are smaller if the boundary is distinct and/or if there are adjacent critical 

structures as illustrated in the following diagram. 
Therefore, it is apparent that using the definition of “treatment site” in § 35.2 as 

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

described in a written directive” raises ambiguities in terms of the proposed ME reports 

as it is unclear whether the “treatment site” refers to the gross tumor volume or includes 

the margins in the clinical target volume or those in the planning target volume. Further, 

the NRC will be interfering into medical judgment if it dictates the amount of source 

strength the authorized user can place in the expansion margin, which is a clinical 

decision. The ACMUI therefore recommends that the definition of “treatment site” in § 

35.2 and § 35.3045(a)(2)(ii) be clarified to reflect that it is the planning target volume 

and includes the gross tumor, the clinical target volume, plus a planning target margin 

as defined by the AU. 

 

3. The proposed language for § 35.3045 (a)(2)(iii) on page 45643, column 3 would 

deem it an ME if any brachytherapy source(s) were implanted beyond 3 cm (1.2 in) 

from the outside boundary of the treatment site, except for brachytherapy source(s) 

at other sites noted in the preimplantation written directive. Further in page 45638 

column 2 it is noted that with the exception of sealed sources that migrate after 

implantation, even a single brachytherapy source implanted beyond 3 cm from the 

outside boundary of the treatment site would constitute an ME. 

The ACMUI wishes to emphasize that in the normal course of some brachytherapy 

implants, a few seeds can end up beyond 3 cm (1.2 in) from the outside boundary of 

the treatment site due to a number of factors. 

a. In the prostate, seeds can be deposited into the periprostatic blood vessels and 

then travel to distant organs such as the lung. This is correctly recognized by the 

NRC, which excludes sources that were implanted in the correct site but have 

migrated outside the treatment site from medical event criteria. However, the 

deposited seeds could also travel to the adjacent pelvic area via the pelvic 

vessels and be more than 3 cm away from the prostate. This case could be 

determined to be an ME as it would be impossible to distinguish whether it was 

wrongly deposited there or was correctly placed but migrated there. 

PTV 

CTV 

CRITICAL 

STRUCTURE 

GTV 

Volume abbreviations: 

GTV = gross tumor volume 

CTV = clinical target volume 

PTV = planning target 
b. In prostate implants, a few seeds can sometimes be implanted into the urethra or 

adjacent bladder. Most of these seeds normally are excreted in the urine. 

However, sometimes they move within the bladder or urethra and lodge more 

than 3 cm from the prostate. 

c. In permanent implants of any organ, some seeds can be unknowingly sucked 

along the needle track while the needle is being retracted and may end up more 

than 3 cm from the organ in the direction of the needle track. In the prostate, they 

would end up inferior to the prostate. 

d. In permanent implants of any organ, patients could inadvertently move during the 

needle retraction causing some seeds to be deposited more than 3 cm from the 

treatment site. 

e. While most permanent brachytherapy is done in the prostate, these rules will 

apply to other sites of permanent implant in addition to prostate. At other sites, 

for example the tumor beds after resection and deep seated liver tumors, the 

margins are indistinct and there are greater uncertainties. Therefore clinicians 

routinely implant beyond the tumor or tumor bed if there are no critical structures 

in that area. Further, sometimes (especially after tumor resection) there may be 

no tissues to anchor the seeds to and so they are placed in gelfoam or vicryl 

mesh and attached to the tumor bed. Some of these seeds do dislodge and then 

can travel in an adjacent free cavity and be deposited more than 3 cm away 

(e.g., in the abdominal, pelvic, or thoracic cavity). It would be virtually impossible 

to determine whether they were implanted there or were dislodged and migrated 

there and therefore could be deemed to be an ME. 

The ACMUI recommends 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 being dislodged, sucked out, etc, but would 

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

wrong area was implanted. Accordingly, § 35.3045 (a)(2)(iii) will become superfluous 

and therefore would be eliminated. 

Other comments: 

1. In §35.40(B)(6), it should be clarified that for any two part WD, an AU (rather 

than the AU) needs to sign and date both the before administration and after 

implantation parts of the WD. This would clarify the intent of the regulation that an AU 

(and not necessarily the same AU) needs to approve all required information on the 

WD. 

2. In §35.3045(a), the ACMUI wishes to comment on new wording that potentially 

affects any administration of byproduct material requiring a WD. The proposed 

language for §35.3045(a) on Federal Register, page 45643, column 2 currently reads, 

“A licensee shall report as a medical event any administration requiring a written 

directive if a written directive was not prepared or any event...” Not having a written 

directive prior to administration of byproduct material is already a violation of NRC 
regulations. 10 CFR §§35.40(a) and 35.41 require having a WD prior to administration 

and the program and procedures to provide “high confidence” for verifying the written 

directive is done. Creating MEs that are already regulatory violations serves only to add 

the number of reported deviations and establishes a undesirable precedent for making 

any medical regulation violation an ME. 

Therefore, the ACMUI recommends that when a WD is required, administrations without 

a WD are to be reported as regulatory violations and may or may not constitute an 

ME. 

Summary: 

The ACMUI is very much concerned that the proposed rules may inadvertently result 

in the unintended consequence that some properly executed, medically acceptable, 

brachytherapy implants may be inappropriately deemed to be medical events when, in 

reality, they sometimes occur in the course of normal medical practice, and are beyond 

the control of the AU. Further, the ACMUI is concerned that some practitioners will 

simply abandon permanent brachytherapy procedures rather than risk having medical 

events. This will be detrimental to patient care. Specifically, the ACMUI recommends 

that: 

1. The word “preimplantation” be deleted from “preimplantation written directive” in 

sections § 35.3045 (a)(2) (i), (ii), (iii) and (iv). 

2. § 35.3045(a)(2) (ii) ) be clarified to read “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 Authorized User exceeding 20 percent of 

the total source strength documented in the written directive”. 

3. § 35.3045 (a)(2)(iii) will become superfluous and therefore should be eliminated. 

4. The word “activity” should be replaced by the term “source strength” whenever it is 

applied to permanent brachytherapy in the document. 

5. §35.40(B)(6) should be clarified that for any two part WD, an AU (though not 

necessarily the same AU) needs to approve all required information on both parts of 

the WD. 

6. The ACMUI should be given an opportunity to review proposed rules before they are 

published. 

7. When a WD is required, administrations without a WD are to be reported as 

regulatory violations and may or may not constitute an ME. 

 

Thank you for affording us this opportunity to provide comments on the NRC’s 

preliminary draft rule changes to 10 CFR 35.40 and 35.3045 related to medical 

events in brachytherapy. 

 Leon S. Malmud, M.D. /RA/ 

 Chairman, Advisory Committee 

 on the Medical Uses of Isotopes