ML18075A408

Draft Transcript of Advisory Committee on the Medical Uses of Isotopes (ACMUI) Teleconference Meeting, February 15, 2018

ML18075A408
Person / Time
Issue date:	02/15/2018
From:	Advisory Committee on the Medical Uses of Isotopes
To:
Holiday, Sophie
References
NRC-3522
Download: ML18075A408 (67)

Text

DRAFT Official Transcript of Proceedings NUCLEAR REGULATORY COMMISSION

Title:

Meeting of the Advisory Committee on the Medical Uses of Isotopes:

Docket Number:

N/A Location:

Teleconference Date:

February 15, 2018 Work Order No.:

NRC-3522 Pages 1-67 NEAL R. GROSS AND CO., INC.

Court Reporters and Transcribers 1323 Rhode Island Avenue, N.W.

Washington, D.C. 20005 (202) 234-4433

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 UNITED STATES OF AMERICA NUCLEAR REGULATORY COMMISSION

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ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES

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TELECONFERENCE

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THURSDAY, FEBRUARY 15, 2018

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The meeting was convened at 9:06 a.m.,

Philip Alderson, ACMUI Chairman, presiding.

MEMBERS PRESENT:

PHILIP O. ALDERSON, M.D., Chairman VASKEN DILSIZIAN, M.D., Nuclear Cardiologist RONALD D. ENNIS, M.D., Radiation Oncologist DARLENE F. METTER, M.D., Diagnostic Radiologist MICHAEL OHARA, Ph.D., FDA Representative CHRISTOPHER J. PALESTRO, M.D., Nuclear Medicine Physician MICHAEL A. SHEETZ, Radiation Safety Officer JOHN J. SUH, M.D., Radiation Oncologist LAURA M. WEIL, Patients Rights Advocate PAT B. ZANZONICO, Ph.D., Vice Chairman

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 NON-VOTING MEMBERS PRESENT:

RICHARD GREEN MEGAN SHOBER ZOUBIR OUHIB NRC STAFF PRESENT:

CHRISTIAN EINBERG, Acting Deputy Director, NMSS/MSST DOUGLAS BOLLOCK, ACMUI Designated Federal Officer SOPHIE HOLIDAY, ACMUI Alternate Designated Official and ACMUI Coordinator MARYANN AYOADE, NMSS/MSTR/MSEB JENNIFER BISHOP, R-III/DNMS SAID DAIBES, Ph.D., NMSS/MSST/MSEB JASON DRAPER, R-III SARA FORSTER, R-III/DNMS CASSANDRA FRAZIER, R-III/DNMS MICHELLE HAMMOND, R-IV/DNMS VINCENT HOLAHAN, Ph.D., NMSS/MSST PATRICIA JEHLE, OGC JAN NGUYEN, RI/DNMS PATTY PELKE, R-III/DNMS GRETCHEN RIVERA-CAPELLA, NMSS/MSST/MSEB VERED SHAFFER, RES

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 NRC STAFF PRESENT (CONT.):

LAURA SHRUM, OGC DANIEL STROHMEYER, R-III/DNMS KATHERINE TAPP, Ph.D., NMSS/MSTR/MSEB FRANK TRAN, R-III/DNMS LESTER TRIPP, R-I/DNMS IRENE WU, NMSS/MSST/MSEB MEMBERS OF THE PUBLIC:

BETTE BLANKENSHIP, American Association of Physicists in Medicine (AAPM)

KELLY CLASSIC, Mayo Clinic CHARLES CODLEMAN, VA Radioactive Materials Program THOMAS CONLEY, University of Kansas Medical Center Whitney Cox, Illinois (IL) Emergency Management Agency ROBERT DANSEREAU, New York State (NYS)

Department of Health ARIEL DOUCET, Virtua Health ADAM EKSTEDT, IL Emergency Management Agency ASFAW FENTA, Virginia (VA) Radioactive Materials Program MICHAEL FULLER, VA Radioactive Materials Program MIGUEL DE LA GUARDIA, Cook Childrens Health Care System

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 MEMBERS OF THE PUBLIC (CONT.):

SANDRA GABRIEL, unaffiliated JERRY GEORGE, Baptist Health South Florida KIMBERLY GILLIAM, VA Radioactive Materials Program THEODORE GODFREY, Elekta, Inc.

BENNETT GREENSPAN, Society of Nuclear Medicine and Molecular Imaging (SNMMI)

STANLEY HAMPTON, Eli Lilly and Company STEVE HARRISON, VA Radioactive Materials Program DESIREE KENNEDY, Elekta, Inc.

RICHARD KENNEY, unaffiliated TIM KLEYN, Indiana University JANAKI KRISHNAMOOTHY, NYS Department of Health SUSAN LOHMAN, Elekta, Inc.

LANCHU LU, Ohio State University Medical Center CAROL MARCUS, University of California at Los Angeles RICHARD MARTIN, American Association of Physicists in Medicine (AAPM)

BARBARA MATTHEWS, Baptist Memorial Health Care Corporation CATHERINE PERHAM, Maine Radiation Control Program RICHARD PEROS, New Jersey Radioactive Materials Program

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 MEMBERS OF THE PUBLIC (CONT.):

ERIC PERRY, Kentucky Radioactive Materials Section MICHAEL PETERS, American College of Radiology (ACR)

BRUCE PROCTOR, Elekta.Inc.

BRAD READ, Elekta, Inc.

SLYVIA REVELL, University of Texas Southwestern Medical School DANIEL SAMSON, NYS Department of Health BETH SCHILKE, VA Radioactive Materials Program A. ROBERT SCHLEIPMAN, Partners Healthcare LOU SHIMABUKU, unaffiliated EUGENIO SILVERSTRINI, Northwell Health MICHAEL STABIN, Vanderbilt University CINDY TOMLINSON, American Society of Radiation Oncology (ASTRO)

MICHAEL WELLING, University of Virginia

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 TABLE OF CONTENTS Nursing Mother Guidelines14 Physical Presence Requirements for Leksell Gamma Knife Icon35 Public Comments Submitted In Advance of Meeting Dr. Carol Marcus and Dr. Michael Stabin61 Society of Nuclear Medicine and Molecular Imaging64

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 P-R-O-C-E-E-D-I-N-G-S 1

(9:06 a.m.)

2 CHAIRMAN ALDERSON: Well, good morning, 3

and welcome to today's ACMUI public teleconference.

4 We'll discuss two topics today: nursing mothers 5

guidelines, the subcommittee report; and the physical 6

presence requirements for the gamma knife, also a 7

subcommittee report.

8 I will now turn it over to Mr. Doug Bollock 9

from the NRC for some opening remarks.

10 MR. BOLLOCK:

Thank you, Dr. Alderson.

11 Good morning. As the designated federal officer for 12 this meeting, I am pleased to welcome you to the public 13 meeting of the Advisory Committee on Medical Uses of 14 Isotopes.

15 My name is Doug Bollock. I am the chief 16 of the Medical Safety and Events Assessment Branch, 17 and I have been designated as the federal officer for 18 this Advisory Committee in accordance with 10 CFR Part 19 7.11.

20 Present today as the alternate designated 21 federal officer is Sophie Holiday, our ACMUI 22 coordinator.

23 This announced meeting of the Committee is 24

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 being held in accordance with the rules and regulations 1

of the Federal Advisory Committee Act and the Nuclear 2

Regulatory Commission. This meeting is being 3

transcribed by the NRC, and it may also be transcribed 4

or recorded by others. This meeting was announced in 5

the January 23, 2018, edition of the Federal Register 6

on 83 page 3191.

7 The function of the Committee is to advise 8

the staff on issues and questions that arise on medical 9

uses of byproduct material. The Committee provides 10 counsel to the staff but not determine or direct the 11 actual decisions of the staff or the Commission. The 12 NRC solicits the view of the Committee and values their 13 opinion.

14 I request that whenever possible we try to 15 reach a consensus on the various issues that we will 16 discuss today. But I also recognize there may be 17 minority or dissenting opinions. If you have such 18 opinions, please allow them to be read into the record.

19 At this point, I'd like to perform a roll 20 call of the ACMUI members participating today. Dr.

21 Philip Alderson?

22 CHAIRMAN ALDERSON: Here.

23 MR. BOLLOCK: Thank you. Dr. Pat 24 Zanzonico?

25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 VICE CHAIRMAN ZANZONICO: Yes.

1 MR. BOLLOCK: Thank you. Dr. Vasken 2

Dilsizian?

3 MEMBER DILSIZIAN: Here.

4 MR. BOLLOCK: Dr. Ronald Ennis?

5 MEMBER ENNIS: Here.

6 MR. BOLLOCK: Thank you. Dr. Darlene 7

Metter?

8 MEMBER METTER: Here.

9 MR. BOLLOCK: Thank you. Dr. Michael 10 O'Hara?

11 MEMBER O'HARA: Here.

12 MR. BOLLOCK: Thank you. Dr. Christopher 13 Palestro?

14 MEMBER PALESTRO: Here.

15 MR. BOLLOCK: Thank you. Mr. Michael 16 Sheetz?

17 MEMBER SHEETZ: Here.

18 MR. BOLLOCK: Thank you. Dr. John Suh?

19 MEMBER SUH: Here.

20 MR. BOLLOCK: Thank you. And Ms. Laura 21 Weil.

22 MEMBER WEIL: Here.

23 MR. BOLLOCK: Thank you. I've confirmed 24 that a quorum is met by the presence of at least six 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 members.

1 Also, on the phone do we have Mr. Zoubir 2

Ohib?

3 MR. OUHIB: Here.

4 MR. BOLLOCK: Thank you. Mr. Richard 5

Green?

6 MR. GREEN: Here.

7 MR. BOLLOCK: Thank you. And Ms. Megan 8

Shober?

9 MS. SHOBER: Here.

10 MR. BOLLOCK: All right. Thank you.

11 Mr. Ouhib has been selected as ACMUI's 12 therapy medical physicist. Mr. Green has been selected 13 as the ACMUI nuclear pharmacist. And Ms. Shober has 14 been selected as the ACMUI Agreement State 15 Representative.

16 At this time, Mr. Ouhib, Mr. Green, and Ms.

17 Shober are pending security clearance but may 18 participate in the meeting. However, they do not have 19 voting rights at this time.

20 I now ask NRC staff members who are present 21 to identify themselves. I'll start with individuals 22 in the room here.

23 MS. HOLIDAY: Sophie Holiday, ACMUI 24 coordinator.

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 DR. TAPP: Dr. Katie Tapp with the medical 1

team.

2 MS. WU: Irene Wu with the medical team.

3 DR. HOLAHAN: Dr. Vincent Holahan, senior 4

advisor.

5 MR. BOLLOCK: Okay. Now we go to NRC 6

employees on the phone.

7 MR. BOLLOCK: Maryann, are you with us?

8 MS. AYOADE: Yes, I am. I had you on mute.

9 Here.

10 MR. BOLLOCK: Okay. That's Maryann 11 Ayoade, also with the medical team.

12 MS. AYOADE: That's correct.

13 MR. BOLLOCK: Anyone else? Any other NRC 14 headquarters employees on the phone?

15 Okay. Are there any NRC regional employees 16 on the phone?

17 Okay. Thank you all. Members of the 18 public who notified Ms. Holiday that they would be 19 participating on the teleconference will be captured 20 in the transcripts. Those of you who did not provide 21 prior notification, please contact Ms. Holiday at 22 sophie.holiday@nrc.gov. That's S-O-P-H-I-E dot 23 H-O-L-I-D-A-Y at N-R-C dot G-O-V. Or call her at 24 (301) 415-7865.

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 We have a bridge line available, and that 1

phone number is (888) 790-6447. The passcode to access 2

the bridge line is 279-0867 followed by the pound key.

3 This meeting is also using to the GoTo 4

webinar application to view the presentation handouts 5

real time. You can access this by going to 6

www.gotowebinar.com, G-O-T-O-W-E-B-I-N-A-R dot com and 7

searching for the meeting ID 563-775-347.

8 The purpose of this meeting is to discuss 9

the revised draft report for the ACMUI nursing mother 10 guidelines for the medical administration of 11 radioactive materials, and the revised draft report 12 for the ACMUI physical presence requirements for the 13 Leksell Gamma Knife Icon'.

14 Individuals who would like to ask a question 15 or make a comment regarding a specific issue the 16 committee has discussed should request permission to 17 be recognized by the ACMUI chairperson, Dr. Philip 18 Alderson. Dr. Alderson, at his option, may entertain 19 comments or questions from members of the public who 20 are participating with us today.

21 Comments and questions are usually 22 addressed by the Committee near the end of the 23 presentation after the Committee has fully discussed 24 the topic. We ask that one person speak at a time as 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 this meeting is also closed caption.

1 I would also like to add that handouts and 2

an agenda for this meeting are available on the NRC's 3

public website.

4 At this time, I'd ask that everyone on the 5

call who is not speaking to place their phones on mute.

6 If you do not have the capability to mute your phone, 7

please press star six to utilize the conference line 8

mute and unmute function.

9 I would ask everyone to exercise care to 10 ensure that background noise is kept at a minimum, as 11 any stray background sounds can be very disruptive on 12 a conference call this large.

13 At this point, I would like to turn the 14 meeting back over to Dr. Alderson.

15 CHAIRMAN ALDERSON:

Thank

you, Mr.

16 Bollock. So I will then start the meeting by turning 17 it to Dr. Darlene Metter, who is the chair of the Nursing 18 Mothers Guidelines Subcommittee. Dr. Metter?

19 MEMBER METTER: Thank you, Dr. Alderson.

20 And I'd like to first thank the work of my subcommittee 21 members, Dr. Vasken Dilsizian, Dr. Christopher 22 Palestro, and Dr. Pat Zanzonico.

23 The subcommittee charge was to review the 24 radiation exposure from diagnostic and therapeutic 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 radiopharmaceuticals, including brachytherapy, to the 1

nursing mother and child.

2 Now, as a summary of our report in 3

September, we know that many drugs and 4

radiopharmaceuticals administered to the nursing 5

mother can enter her milk, and then, therefore, be 6

ingested by the nursing child. The subcommittee 7

recommendations regarding the radiation exposure to 8

the nursing child follows current existing 9

recommendations for the nursing mother by reputable 10 expert sources such as the NRC, ICRP, Dr. Michael 11 Stabin's paper, and others.

12 Therefore, our subcommittee 13 recommended -- recommendations mirrored the sources 14 with the use of a maximum dose of 100 millirem to the 15 nursing child. The current literature at times had 16 variable recommendations on the temporary interruption 17 of breastfeeding due to radiopharmaceuticals in the 18 mother's milk, and the subcommittee generally opted 19 to choose the most conservative, which was usually the 20 longest interruption period.

21 The subcommittee results and 22 recommendations are summarized in a table reviewed at 23 the September 2017 ACMUI meeting. Since that time, 24 there have been comments from Dr. Carol Marcus and Dr.

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Michael Stabin, and Dr. Bennett Greenspan and the SNMMI.

1 To review these comments, Dr. Pat Zanzonico will 2

address them and the associated report revisions.

3 Dr. Zanzonico?

4 VICE CHAIRMAN ZANZONICO: Thank you, Dr.

5 Metter. So as Dr. Metter just said, we received a 6

number of comments, both from Drs. Marcus and Stabin, 7

and independent from Dr. Greenspan and the Society of 8

Nuclear Medicine and Molecular Imaging. So what I was 9

going to do was step through their respective comments 10 and summarize our responses.

11 This was an information-dense report, and 12 so there were a number of comments, so please bear with 13 me. The first comment from Drs. Marcus and Stabin was 14 that the draft report failed to describe or at least 15 acknowledge the real and significant benefits of 16 breastfeeding to both the infant and the nursing mother, 17 and they include a statement from the American Academy 18 of Pediatrics to that effect.

19 And that point is well taken, and in our 20 subsequent revision of the report we think it would 21 be reasonable to include a statement explicitly 22 acknowledging the benefits of breastfeeding to the 23 mother and child, and so we plan to do that in the revised 24

-- the subsequent revision of our report.

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 The second point was that the so-called 1

specific gamma ray factors cited in Table 2 are 2

incorrect. They indicate by a factor of 1,000. And 3

this was a units transcription error. The values in 4

the table, and as used in our calculations, are in 5

roentgen centimeters squared per microcurie hour.

6 The mu for micro when it went to hard copy 7

became an m for milli inadvertently. And so the 8

factor of 1,000 error was apparent. We will correct 9

that, of course, in the subsequent revision, but I want 10 to assure everyone that the actual calculations and 11 analyses were based on the actual correct values.

12 I will just also address the related point 13 of a comment by Dr. Greenspan and the SNMMI. They state 14 in their comments that the specific gamma ray constant, 15 the quantities I'm referring to right now, were in 16 error, and they provided a number of different values 17 with variable units being used.

18 And of course if we have numerical or other 19 factual errors in the report, those will be corrected 20 and reflected in a revised analysis. However, we asked 21 that Dr. Greenspan and the SNMMI provide a reference 22 for their values. No such reference was provided with 23 their written comments, and so we have no way at this 24 point of verifying their veracity, their accuracy.

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Our specific gamma ray constants were taken 1

from a classic textbook in medical physics, Johns and 2

Cunningham, which many of you may be familiar with.

3 So that's the source of our data, but we understand 4

that specific gamma ray constants, like other physical 5

quantities, are periodically updated, and we certainly 6

want to use the most current and most accurate values 7

in our analysis.

8 And if Dr. Greenspan and the Society can 9

provide a reference, so that we can verify the accuracy 10 of their stated values, we will amend our report 11 accordingly.

12 The next point from Drs. Marcus and Stabin 13 was they found a number of typos and editorial errors, 14 and we appreciate, of course, their careful reading 15 of the report as we appreciate all their comments and 16 insights, and we will certainly correct these editorial 17 errors in the subsequent revision. Likewise, Dr.

18 Greenspan and the Society noted a number of editorial 19 errors, and we will correct those as well, of course.

20 One issue that arose, which is always a 21 thorny one, is the system of units to use. We use 22 essentially conventional units because, frankly, 23 that's the system of units most of us, including myself, 24 are most familiar with and most comfortable with. But 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 we certainly appreciate that we should be transitioning 1

to use of SI units.

2 And we will confirm with the NRC staff to 3

verify that that's an appropriate thing to do, and we'll 4

amend our report accordingly to use SI rather than 5

conventional units or perhaps SI units primarily with 6

conventional units presented parenthetically. But we 7

will address that point.

8 A fourth point raised by Drs. Marcus and 9

Stabin was that the dosimetry analysis for 10 radioiodines, specifically with respect to the thyroid, 11 used worst-case factors in terms of maximal uptakes 12 of radioiodine by the thyroid and minimal thyroid gland 13 masses. Both of those conservative assumptions would 14 lead to maximal estimates of dosimetry.

15 And Drs. Marcus and Stabin recommended that 16 we perform this thyroid dosimetry analysis for all 17 medically used radioiodines, not just I-131. So that 18 would include, of course, I-123, nowadays I-124, 19 perhaps even I-125. And they also suggested that in 20 that analysis we use a range of uptakes, not simply 21 maximal uptake, and a range of age-dependent uptakes 22 and age-dependent thyroid masses. And we can certainly 23 do that.

24 And, immodestly, I cite my own paper, 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Age-Dependent Thyroid-Absorbed Doses for 1

Radiobiologically Significant Radioisotopes of Iodine 2

from Health Physics, 2000. So we can extract dose 3

estimates or -- in the dosimetry analysis from that 4

paper and incorporate the suggested, augmented analysis 5

in the subsequent revision of our report.

6 Drs. Marcus and Stabin also point out that 7

two significant literature references were not cited 8

in the paper, and certainly we want to be as 9

comprehensive and thorough as possible in incorporating 10 the pertinent scientific literature into our 11 recommendations. And we will certainly review these 12 papers and incorporate them, at least cite them, in 13 our report and, if necessary, make whatever adjustments 14 those dictate.

15 And they also point out that perhaps an 16 ill-advised phrase was included in the report 17 referencing the available scientific literature on 18 breastfeeding, dosimetry, and so forth; namely, the 19 phrase being the general lack of pertinent data in the 20 literature. And on further reflection, I think we all 21 acknowledge -- and you can verify this by looking at 22 the bibliography -- the references in our report, there 23 actually is already significant literature on the 24 subject. So we will eliminate that phrase as well as 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 include these additional references.

1 A further point that was made is that rather 2

than using or modeling he mother and the mother's breast 3

as point sources -- and that is often done, frankly, 4

for simplicity purposes in dose calculations -- we 5

modeled those source regions in terms of the external 6

dose to the nursing baby. We modeled those as line 7

sources based on a paper in the literature, and that 8

yields a more realistic estimate of the external dose 9

to the infant that does a point source model.

10 Drs. Marcus and Stabin point out, however, 11 that there are so-called humanized gamma ray constants 12 available, certainly at least for I-131. However, we 13 point out -- or we would like to point out that in our 14 calculation we not only model the mother's body and 15 breast as line sources, but we also incorporated the 16 self-absorption of extant gamma rays by those 17 respective source regions, and we also -- well, we 18 modeled those, as I say, as attempting to count the 19 self-absorption.

20 So we think that our approach, even though 21 we use specific gamma ray constants which implicitly 22 implies -- which implies a point source, we think we've 23 made the necessary adjustments to appropriately 24 quote/unquote "humanize our specific gamma ray constant 25

22 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 values."

1 I'm just thumbing through my notes.

2 Another point that was made -- and this was a lengthy, 3

very scholarly comment, indicating that basing 4

recommendations with regard to cessation of 5

breastfeeding for mothers who undergo a nuclear 6

medicine procedure, basing that on a 100 millirem limit 7

to the nursing infant is overly conservative, and Drs.

8 Marcus and Stabin recommend a dose limit of five 9

millisieverts instead.

10 And incorporated into that comment was a 11 strong reputation of the linear non-threshold dose 12 response model for cancer induction by radiation. And 13 I think many of us, myself included, are very empathetic 14 so to speak to that point, and I think many of us have 15 well-founded skepticism about the biological validity 16 of the linear non-threshold model.

17 But having said that, really, a discussion 18 of that model, as important and interesting as it is 19 certainly, is really beyond the scope of our report.

20 And as Dr. Metter pointed out, we deferred to the 21 prevailing recommendations made by authoritative 22 bodies like the ICRP, NCRP, and so forth.

23 And we also noted that in their original 24 analysis, in the really seminal and widely cited paper 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 by Dr. Stabin and Dr. Bryce, that they based their 1

analysis on a one millisievert effective dose 2

quote/unquote limit to the nursing infant.

3 So based on all of those considerations, 4

and despite our misgivings of the linear non-threshold 5

dose-response models, we decided, as Dr. Metter 6

indicated, to use a one millisievert limit upon which 7

to base our recommendations.

8 Proceeding now to the comments submitted 9

by Dr. Greenspan and the Society, to address their 10 comment on the possible -- possibly erroneous specific 11 gamma ray constant values, and we will ask them and 12 await the literature citation of the values they cite, 13 and based on our subsequent review of these values in 14 that literature adjust the specific gamma ray constants 15 and our values and our calculations accordingly.

16 I mentioned that they also had a number of 17 editorial corrections which we will certainly address 18 in a subsequent revision of the paper. And there was 19 a question or a disagreement with our recommendation 20 for discontinuing of breastfeeding following 21 administration of I-123 labeled radiopharmaceuticals, 22 not only sodium iodide but also ortho-iodohippurate 23 and MIGB, metaiodobenzylguanidine, which are all used 24 clinically labeled with I-123.

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 And I think there may have been a 1

misunderstanding, understandably, given all of the 2

numbers and so forth in the paper, in the report rather, 3

but in Table 2 -- I'm sorry, in Table 5 of the report, 4

in which we include our recommendations on cessation, 5

the penultimate column, the next-to-last column, which 6

use the -- which list the current recommendations of 7

-- that we use here at Memorial Sloan Kettering, 8

indicated a seven-day discontinuation following 9

administration of at least certain I-123 10 radiopharmaceuticals.

11 But if you looked at the recommendations 12 for -- from the Committee, which is actually in the 13 very last column of that table, our recommendations 14 are much shorter, no more than 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />, and in the 15 case of I-123, iodohippurate, not recommending any 16 interruption of breastfeeding.

17 So I think we have all -- I think what we 18

-- what the committee or subcommittee has recommended 19 is perfectly consistent with the point that Dr.

20 Greenspan and the Society were making. So, yes, as 21 you see what's on the screen now, in the very last 22 column, the fourth, fifth, and sixth lines refer to 23 cessation of I-123, sodium iodide; 24 metaiodobenzylguanidine, MIGB; and the last of those 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 three lines, line 6, to ortho-iodohippurate labeled 1

with I-123. So I think our recommendations are 2

consistent with what the Society is recommending.

3 Dr. Greenspan and the Society are also 4

recommending a more thorough, a more complete 5

dosimetric analysis of radioiodine as a function of 6

age, child age, and thyroid mass. And as I alluded 7

to earlier, we will provide an expanded dosimetric 8

analysis as also recommended by Drs. Marcus and Stabin.

9 And Dr. Greenspan and the Society also 10 forcefully endorsed the recommendation of Drs. Marcus 11 and Stabin that, number one, a 500 millirem rather than 12 a 100 millirem dose limit or dose benchmark upon which 13 to base recommendations is more appropriate, and that 14 the linear non-threshold model is really not only 15 inappropriate but incorrect.

16 So I have already addressed that point in 17 my earlier comments. And so that actually completes 18 our point-by-point response to the submitted comments, 19 both by Drs. Marcus and Stabin, and by Dr. Greenspan 20 and the Society. We very much appreciate their careful 21 and thoughtful -- their careful reading of the report 22 and their thoughtful comments. And we have tried to 23 address them as comprehensively as possible. And I 24 think we've done so and will revise the report 25

26 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 accordingly.

1 So that concludes my comments in terms of 2

our responses to the submitted comments. So, Dr.

3 Metter, I will turn it back to you.

4 MEMBER METTER: Thank you, Dr. Zanzonico, 5

for a very thorough review and work on the comments 6

from Drs. Marcus, Stabin, Greenspan, and the Society 7

of Nuclear Medicine.

8 Do I have other comments from our 9

subcommittee members?

10 Okay. Hearing none --

11 MEMBER WEIL: Dr. Metter?

12 MEMBER METTER: Yes.

13 MEMBER WEIL: This is Laura Weil.

I do 14 have a comment, and I'd like to apologize for not 15 submitting it in advance. The subcommittee report 16 recommends the complete cessation of -- states that 17 the cessation of milk production generally occurs about 18 six weeks after the last breastfeeding.

19 And I encountered a report from the APA, 20 which recommends a longer period of cessation, and I'd 21 like to -- this is from the ATA from 2009 in Thyroid.

22 If I might just briefly read this paragraph and ask 23 for an evaluation of it, basically.

24 Let's see. Breastfeeding must be stopped 25

27 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 at least six weeks before administration of I-131 1

therapy, and a delay of three months will more reliably 2

ensure that lactation-associated increase in breast 3

sodium iodide symporter activity has returned to 4

normal.

5 I wonder if six weeks in our -- in the 6

subcommittee report could be amended to at least six 7

weeks in order to acknowledge the potential for a longer 8

period of time being necessary. I don't know how one 9

would assess how long a period of time between six weeks 10 and three months should be recommended, but certainly 11 for the provision of information to patients, in 12 accordance with the ALARA principles, so that 13 breastfeeding women would have time to allow at least 14 six weeks' cessation of breastfeeding before 15 administration of Iodine-131. Would you comment on 16 that?

17 MEMBER METTER: Yes. Actually, thanks for 18 bringing that up. There was a comment as far as the 19 minimal timeframe in regards to notifying the nursing 20 mother regarding her I-131 therapy issue with nursing, 21 and we did say it was going to be at six weeks. I have 22 no problem saying at least six weeks prior to the 23 radioiodine administration. Does anybody else on the 24 subcommittee have any comments?

25

28 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 VICE CHAIRMAN ZANZONICO: This is Pat 1

Zanzonico. I have no problem either with that 2

language, meaning specifically at least six weeks.

3 I think we all recognize that both medically and 4

logistically the longer that period of discontinuation 5

of breastfeeding begins prior to therapy, the more 6

problematic it becomes.

7 And so I think six weeks itself may be 8

somewhat problematic, but I have no problem at all with 9

that language, at least -- at least six weeks for 10 cessation prior to therapy.

11 MEMBER METTER: Thank you, Dr. Zanzonico.

12 Thank you as well for your comment on that. And any 13 other comments?

14 Okay. Dr. Alderson, I'll turn it back to 15 you.

16 CHAIRMAN ALDERSON: Well, thank you. I 17 believe that must conclude this report and discussion.

18 Are there other comments from people who are online?

19 OPERATOR: And if you have a question or 20 a comment from the phones, you may press star one at 21 this time. Make sure your phone is unmuted and record 22 your name. And to withdraw that request, you may press 23 star two. Once again, press star one for questions 24 or comments from the phones, and I'll stand by for 25

29 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 questions or comments.

1 One moment. And we do have a question or 2

comment coming from Carol Marcus. Your line is open.

3 DR. MARCUS: Thank you. Pat, I think we're 4

in complete agreement on everything except the 500 5

millirem calculations. And I think it would be really 6

helpful to have both the 100 millirem and the 500 7

millirem, recognizing that for 21 years the limit has 8

been 500 millirem, and then the physician and the 9

lactating mother decide what ALARA provision is 10 appropriate.

11 Otherwise, what we have is something so 12 conservative that I think a lot of people won't want 13 to use it. I know that Mike and Hazel's paper 14 originally used 100 millirem, but Mike has changed his 15 mind and thinks 500 millirem calculations would be good.

16 And I think having both might be the best way to do 17 it. Then licensees can choose what seems most 18 appropriate, and we'll have at least the calculations 19 with which to make a good choice.

20 Thank you.

21 OPERATOR: Does that conclude the question 22 or comment?

23 DR. MARCUS: Yes, it does.

24 MEMBER METTER: May I say something on this 25

30 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 regarding -- in our paper, the first part as far as 1

the current guidance, it does allude to a nursing mother 2

who has received, until byproduct material can be 3

released by a licensee, the total effective dose 4

equivalent to any other individual, including her 5

nursing child, is projected to not exceed five 6

millisieverts. But she must give guidance if it's 7

going to exceed one millisievert. So we have that in 8

our paper.

9 DR. MARCUS: Yes. But you don't have the 10 calculations.

11 VICE CHAIRMAN ZANZONICO: This is Pat 12 Zanzonico. I personally have no objections to 13 including a

essentially a

dual set of 14 recommendations. I mean, the heart of the report and 15 the key recommendations, of

course, are the 16 recommendations for the duration of discontinuing 17 breastfeeding.

18 And we can certainly add an additional 19 column which gives those periods of time for a 20 100 millirem dose to the nursing infant and a 500 21 millirem dose to the nursing infant.

22 If I

understand correctly, the NRC 23 obviously doesn't regulate breastfeeding, and we can 24 provide, as points of information, the recommended 25

31 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 discontinuation periods for 100 and 500 millirem 1

limits, and the patient and their caregivers can then 2

choose as appropriate.

3 I

have no objection, scientific or 4

otherwise, to that approach. I don't know if -- if 5

having dual recommendations in effect is problematic 6

from the NRC's point of view. But from a logistical, 7

scientific point of view, I have no objection to that 8

approach.

9 MS. HOLIDAY: Dr. Zanzonico and Dr. Metter, 10 NRC does not object to, if you want to amend the 11 subcommittee report to reflect these dual 12 recommendations, that's at your discretion.

13 MEMBER METTER: Thank you, Sophie. I 14 think if that's okay, we'll go ahead. Any other 15 comments from the subcommittee? Because I think we'll 16 go ahead and make those two recommendations as far as 17 listing on the table as Dr. Zanzonico had reflected.

18 MEMBER WEIL: This is Laura Weil. Dr.

19 Metter, may I comment on that?

20 MEMBER METTER: Yes.

21 MEMBER WEIL: I have no objection to 22 listing both sets of recommendations, but I would like 23 to know that they would be labeled with the agency that 24 recommends both the 100 and the 500 millisieverts 25

32 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 threshold.

1 MEMBER METTER: Okay.

2 MEMBER WEIL: So that the chart or the graph 3

itself is labeled to indicate which agencies recommend 4

which threshold.

5 MEMBER METTER: Okay. I believe most of 6

them are based on the 100 millirem.

7 MEMBER WEIL: I believe that's true, and 8

I'd like to see that noted in the table.

9 MEMBER METTER: Oh, I see. Okay. Thank 10 you.

11 Any other comments?

12 OPERATOR: And I am currently showing no 13 further questions or comments from the phones. Again, 14 as a reminder, if you have further questions or 15 comments, it is star one. Make sure your phone is 16 unmuted and record your name. And it is star two to 17 withdraw that request. And I'll stand by for any 18 further questions or comments at this time.

19 MEMBER METTER: Dr. Alderson, I don't think 20 there are other comments or questions at this time.

21 CHAIRMAN ALDERSON: All right. Thank you 22 very much.

23 OPERATOR: And we did just have one cue up.

24 If you'd like to wait one moment, I'll get that party's 25

33 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 name.

1 CHAIRMAN ALDERSON: Certainly.

2 OPERATOR: One moment. Thank you.

3 Excuse me. Dr. Greenspan, your line is open for your 4

question or comment.

5 DR. GREENSPAN: Thank you very much. I 6

just had a quick comment as a follow up to 7

Dr. Zanzonico's request for references for gamma ray 8

constants. I'm traveling this week, but I will be glad 9

to provide them next week. I hope that won't be too 10 late. Thank you.

11 VICE CHAIRMAN ZANZONICO: This is Pat 12 Zanzonico. Yes, Dr. Greenspan, that would be certainly 13 soon enough. The additional analyses I'm committing 14 to are going to take a bit of time, and they certainly 15 won't be concluded by next week, so next week will be 16 soon enough.

17 DR. GREENSPAN: Thank you very much.

18 OPERATOR: Thank you. And I'm currently 19 showing no further questions or comments at this time.

20 CHAIRMAN ALDERSON: Good. Thank you.

21 That means that we will now proceed with the next part 22 of this public conference call. That will be the report 23 from Dr. John Suh's subcommittee on the physical 24 presence requirements for the Gamma Knife Icon. I will 25

34 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 turn the conversation over to Dr. Suh.

1 MS. HOLIDAY: Dr. Alderson and Dr. Suh, 2

before you launch into the next topic, if I may, can 3

I ask if the Committee will be making a motion to endorse 4

this report with the reflected amendments?

5 CHAIRMAN ALDERSON:

Yes, certainly.

6 That's fine. Let's do that.

7 MEMBER METTER: Can I make a motion to 8

endorse the amended reports?

9 PARTICIPANT: Second.

10 MS. HOLIDAY: And then if you could state 11 for me what the amendments will be, so that we can 12 capture that on the record?

13 MEMBER METTER: Okay. Dr. Zanzonico?

14 VICE CHAIRMAN ZANZONICO: Yes. The 15 amendments will include acknowledgment of the benefits 16 of breastfeeding. They will include correction as 17 needed of the specific gamma ray constant values. They 18 will include conversion of the system of units from 19 conventional to SI. There will be an expanded 20 dosimetric analysis of radioiodines as a function of 21 the age and thyroid mass of the child, and also include 22 other medical radionuclides -- radioisotopes of iodine.

23 We will include at least two additional 24 references as cited by Drs. Marcus and Sabin. And we 25

35 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 will include recommendations or recommended cessation 1

periods of time based on both a 100 and a 500 millirem 2

effective dose to the nursing child.

3 MS. HOLIDAY: Okay. Thank you, Dr.

4 Zanzonico.

5 CHAIRMAN ALDERSON: This is Dr. Alderson.

6 I think we should just mention that the transcription 7

errors/typos also will be corrected as recommended.

8 MS. HOLIDAY: Thank you. Okay. Dr.

9 Alderson, now that there is a motion, can you call for 10 the vote?

11 CHAIRMAN ALDERSON: All right. All in 12 favor?

13 (Chorus of ayes.)

14 CHAIRMAN ALDERSON: Any opposed? (pause) 15 Hearing none, that passes unanimously.

16 CHAIRMAN ALDERSON: All right. So as I 17 stated a moment ago, I'll repeat now, it is now time 18 for us to consider the report on the physical presence 19 requirements for the Gamma Knife

Icon, that 20 subcommittee report. That subcommittee is led by 21 Dr. John Suh. Dr. Suh, you're on.

22 MEMBER SUH: Okay. Thank you, Dr. Alderson.

23 I want to first thank the subcommittee members, Dr.

24 Ron Ennis and Laura Weil, and also thank Sophie Holiday 25

36 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 for her staff resource support.

1 So I will -- the charge to the subcommittee 2

was to propose the appropriate physical presence 3

requirements for Leksell Gamma Knife Icon' 4

radiosurgery units. And I just want to go through just 5

a little bit about the gamma knife. The gamma knife 6

is a very well-established treatment for patients with 7

various benign and malignant brain tumors, vascular 8

malformations, and functional disorders, including 9

trigeminal neuralgia.

10 The first gamma knife in the United States 11 was installed at the University of Pittsburgh in 1987, 12 and over the years the gamma knife has evolved and in 13 2006 the Perfexion' unit was introduced, which allowed 14 for the authorized users to be inside the treatment 15 unit.

16 And given the differences between the 17 Perfexion' versus the models U, B, and C, the Perfexion' 18 was licensed under 10 CFR 35.1000. And as of the 19 reports, based on information collected, there are 77 20 Perfexion' units and 22 Icon' units in the United States, 21 and worldwide over a million patients have been treated 22 with the gamma knife.

23 In terms of the current physical presence 24 requirements in 10 CFR part 35, it requires an 25

37 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 authorized user with appropriate training and 1

experience in radiation oncology and an authorized 2

medical physicist to be physically present throughout 3

all treatments involving the unit. And physical 4

presence has undergone some evolution. Initially, it 5

was defined as within hearing distance of normal voice, 6

and as part of a regulatory issue summary it was further 7

defined to be speaking in a normal conversational tone, 8

not a raised voice. And they made a comment that a 9

distance of 20 feet may not be close enough to adequately 10 hear and respond to an emergent situation.

11 The rationale for changing the physical 12 presence requirements is that the gamma knife unit, 13 as I mentioned, has evolved through the years. It is 14 important that any change we make allow the authorized 15 user to address an emergent situation and also to verify 16 that a correct dose was delivered.

17 If you look at the past 10 years of the NMED 18 report, there have been 10 reportable events involving 19 the Perfexion', and only a minority of these events 20 occurred during a treatment.

21 So from the Perfexion' in -- there has been 22 an evolution to a newer unit called the Icon' system.

23 Some of the fundamental differences with the Icon' 24 system is that it does allow for the option of a 25

38 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 thermoplastic frameless mask rather than a frame. The 1

majority of centers using the Icon' system still use 2

a frame-based system rather than a mask-based system.

3 It does give the option for those patients who may 4

benefit from some type of fractionated approach.

5 Number two is it allows the ability to perform 6

integrated stereotactic cone beam CT, which provides 7

stereotactic reference for patient setups.

8 And number three is it also has a high 9

definition motion management for mask-based 10 treatments, which allows us to confirm that the 11 treatment is being delivered to the target itself.

12 There was a proposal from Elekta on 13 April 26th about the Gamma Knife Icon', and their 14 proposal is that an authorized user and authorized 15 medical physicist be physically present during the 16 initiation of all treatment involving a unit.

17 Number two is to have an authorized medical 18 physicist present throughout all patient treatments.

19 And number three is that an authorized user 20 physically be present in the department during patient 21 treatment and immediately be able to come to the 22 treatment room in case of emergency.

23 Based on the -- looking at the current 24 physical presence requirements, the evolution of the 25

39 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Icon unit, the recommendations from the subcommittee 1

is that the authorized user and authorized medical 2

physicist be physically present during the initiation 3

of all treatments involving the Icon', and that the 4

authorized medical physicist be physically present 5

throughout all treatments of the unit itself.

6 We have made a recommendation that the 7

current physical presence requirements for the 8

authorized user be modified to allow the authorized 9

user to be close enough to the console area to respond 10 quickly to any issues that may arise.

11 The definition we came up with is that within 12 a two-minute walk of the Icon console area and 13 immediately available to come to the treatment room.

14 So it is very important that with this definition of 15 physical presence, the authorized user cannot be 16 involved in another procedure that would prevent him 17 or her to come immediately to the gamma knife in case 18 of an emergency.

19 In addition, we felt that it was important 20 that we do not use the definition of a department as 21 "department" can have different meanings to different 22 centers. So one could be stated that it's part of a 23 department, but the department could be physically a 24 long walk away. So we felt that there should be some 25

40 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 time restraint in terms of what constitutes being 1

physical presence in terms of this newer definition.

2 If there is an interruption of treatment 3

secondary to a medical or mechanical event, the 4

authorized user must return to the Gamma Knife Icon' 5

console area to evaluate patient and to review any of 6

the medical -- mechanical issues along with the medical 7

physicist.

8 And at the conclusion of treatment, the 9

authorized user must be present at the Icon console 10 to discuss any treatment or patient issues with the 11 patient, physicist, and a nurse.

12 The subcommittee felt that with these 13 modifications, in terms of current physical presence 14 requirements, it would allow more flexibility to the 15 authorized user.

16 In closing, we felt that it was very important 17 that the committee report did not encroach on the 18 practice of medicine, also allowed for the regulator 19 to inspect the regulated gamma knife center, and also 20 be consistent with regulations governing a physician's 21 supervision.

22 Any change that occurs to the current 23 physical presence requirements should take into account 24 that the culture of safety quality be supported, given 25

41 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 the superb track record for quality and safety with 1

the gamma knife.

2 Thank you. That concludes my report, Dr.

3 Alderson.

4 CHAIRMAN ALDERSON: All right. Thank you.

5 Are there comments?

6 MEMBER SHEETZ: John, this is Mike Sheetz.

7 I have some comments.

8 CHAIRMAN ALDERSON: Please.

9 MEMBER SHEETZ: I think the subcommittee 10 provided an excellent report and overview of the 11 technological advances in gamma knife treatment since 12 the process has become more efficient allowing for more 13 treatments, and multiple targets can be treated in a 14 single session.

15 And they pointed out, based on the small 16 number of medical events involving modern gamma knife 17 models, it is, therefore, appropriate to evaluate the 18 required physical presence requirements for gamma knife 19 to see if they should be revised.

20 Based on our experience here at the 21 University of Pittsburgh where we have had every model 22 like the gamma knife, and we were the first to license 23 the U model in 1987, I have some comments with respect 24 to the recommendations of the subcommittee, if I may 25

42 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 proceed with those.

1 CHAIRMAN ALDERSON: Please.

2 MEMBER SHEETZ:

I agree with the 3

recommendation number one that the AU and AMP need to 4

be physically present at the initiation of all 5

treatments.

6 With respect to recommendation two, I think 7

the definition of "within a two-minute walk from a gamma 8

knife treatment console" will create ambiguity for the 9

regulatory compliance with licensees, and the 10 recommendation for the appropriately trained staff to 11 be present to respond to patient medical issues is not 12 really enforceable by the NRC.

13 So I would suggest consideration of this 14 recommendation to be modified to something that 15 actually is in current regulation for HDR right after 16 the initiation of treatment, an authorized medical 17 physicist and either an authorized user or a physician 18 under the supervision of an authorized user who has 19 been trained in the operation of emergency procedures 20 for response of the unit, to be physically present 21 during continuation of all patient treatments involving 22 the unit.

23 So I'll throw that up for consideration.

24 Again, it would be consistent with the HDR requirements, 25

43 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 and it would eliminate any ambiguity in response times, 1

and it would assure that appropriate personnel are 2

present to respond to any patient medical issues.

3 I agree with recommendation three that the 4

AU must return to the gamma knife console for the 5

interruption of treatment secondary to medical or 6

mechanical issues.

7 With respect to recommendation four that 8

requires the AU to be present at the gamma knife 9

treatment console at the conclusion of the treatment 10 to discuss any treatment of patient issues, if the 11 patient treatment has been completed without any 12 issues, I question whether this would be necessary.

13 And if you have eliminated this requirement, it would 14 provide greater relief to the authorized user.

15 And then the last slide on this, if the 16 subcommittee report -- not specifically saying, but 17 implies some modified physical presence requirements 18 should only be applicable to the Icon' unit when using 19 the thermoplastic mask for patient treatment and not 20 the stereotactic beam, while the Icon' utilizes an 21 integrated cone beam CT for stereotactic reference and 22 high-definition motion management systems, these 23 features are only required when using mask-based 24 treatments. They are not required for frame-based 25

44 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 treatments.

1 In our experience, less than 10 percent of 2

the gamma knife patient cases qualify for mask-based 3

treatments. There have been an extremely low number 4

of medical events with Perfexion' that have been pointed 5

out involving thousands of patient treatments 6

demonstrating a highly reliable treatment technology.

7 And so when using the Icon for frame-based 8

treatments, it is identical to the Perfexion' unit for 9

frame based. So, therefore, I would suggest that the 10 revised physical presence requirements should also be 11 applicable to frame-based treatments on either the Icon 12 or the Perfexion'.

13 And that concludes my comments.

14 CHAIRMAN ALDERSON: Thank you. Dr. Suh?

15 MEMBER SUH: Thank you, Michael, for those 16 very thoughtful comments. So in terms of your second 17 recommendation about whether or not the physical 18 presence requirement of the two-minute walk, this is 19 something that the subcommittee grappled with in terms 20 of what would constitute appropriate physical presence 21 requirements with the Gamma Knife Icon', and the number 22 we came up with -- initially, there was some discussion 23 about whether or not being physically present in the 24 department would be adequate, and we all agreed that 25

45 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 that is too -- that is too ambiguous. So we felt that 1

was not a good starting point.

2 And we grappled at the time -- we needed some 3

type of time standpoint. And I do agree with you that 4

there could be some ambiguity in terms of regulatory 5

compliance. I actually have looked at your comments.

6 I actually thought about it.

7 And thinking about the HDR model, the current 8

proposal of either an authorized user or a physician 9

under the supervision of an authorized user who has 10 been trained in the operation of emergency response 11 to the unit be physically present during the 12 continuation of all patient treatments involving the 13 unit is a better definition, in my opinion, because 14 it then allows a physician to be present at the console 15 area or within voice distance during the entire 16 treatment.

17 As you mentioned, the NRC does not regulate 18 the ancillary staff such as nursing support, so that 19 is a consideration that I am certainly open to. I would 20 be curious to see what the other subcommittee members 21 think and also the rest of the committee as well on 22 that particular point.

23 In terms of point -- so in terms of authorized 24 user returning, I'm glad that you agree with that 25

46 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 comment. I do think it's important for the authorized 1

user to return.

2 In terms of recommendation number four, I 3

am probably not as strong of an advocate for that.

4 I do believe that the gamma knife does require an 5

authorized user to know what happened during the 6

treatment, and one of my concerns is that if the 7

authorized user does not know that the patient --

8 because, again, there could be a situation where the 9

treatment is "completed," but things may not have gone 10 as planned. And I think this is an opportunity for 11 the authorized user to deal with the medical physicist 12 to ensure everything has occurred correctly.

13 Also, from a patient care standpoint, having 14 the authorized user there to let the patient know that 15 everything went well I think is a greater assurance 16 in terms of that the treatment actually did go according 17 to plan rather than having a surrogate physician who 18 has been trained to say, well, treatment went well.

19 I have found that from a patient standpoint 20 it -- there is a better confidence when the physician 21 is actually there, the one who is actually involved 22 with the actual treatment.

23 In terms of number five, in terms of whether 24 or not the Icon' and the Perfexion' are similar units, 25

47 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 although the fundamental makings of the Icon' are very 1

similar to the Perfexion' unit, there is the opportunity 2

to use a cone beam CT device for the frame-based 3

treatments.

4 What I can share with you is that at our 5

institution about 20 percent of our patients are 6

undergoing frame-based treatments right now, typically 7

up to five treatments -- of treatment. And for our 8

functional cases and for those cases that we -- we have 9

actually started to use the cone beam CT to ensure that 10 the alignment of what we saw on the computer screen 11 aligns with the frame attached to the treatment machine.

12 So I don't feel that the Perfexion' and the 13 Icon' are similar. So I am not in support of modifying 14 physical presence requirements for both Perfexion' and 15 Icon'. I would propose that we change the physical 16 presence requirements for just the Icon' unit itself.

17 MEMBER ENNIS: This is Ron. Just to follow 18 up, being on the subcommittee, my thoughts to Mr.

19 Sheetz's comments. So in terms of the ambiguity of 20 the two-minute walk, well, certainly, there is a little 21 bit of ambiguity with that, although I don't think it 22 will be a lot because it does specify a time which you 23 can measure and walk. And of course people can walk 24 slightly faster or slower, but I don't think it's 25

48 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 tremendously ambiguous.

1 So I'm comfortable with that. The notion 2

of instead requiring another physician to be there under 3

the supervision, I would be comfortable with that, too.

4 That is more restrictive on our users, I think, than 5

the proposed definition that our subcommittee came up 6

with.

7 And I think part of our charge was to see 8

whether we could provide safe relief to the authorized 9

user. So I don't know that our constituents, if you 10 will, or the people asking for some relief would feel 11 that we have provided any relief with that. We could 12 maybe hear what those constituents had to say.

13 But I am comfortable with either, but I do 14 feel like the -- as written in the subcommittee report 15 is kind of aligned with providing some level of relief 16 while still being, you know, conservative in terms of 17 patient safety.

18 In terms of the other issues, the return at 19 the end I feel is an important component to this as 20 well. In my mind, it's kind of akin at the end of a 21 brachy procedure, kind of -- although we're not 22 requiring formal documentation, that the authorized 23 user documents that everything went as planned, or, 24 if not, what kind of changes.

25

49 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 I do feel like it's really important to close 1

that loop. More subtle things that aren't quite events 2

might not be raised or you might forget about them an 3

hour later when you see each other in the hall. But 4

at that moment, the physicist and/or the nurse or 5

whoever might be there might be able to share some issue 6

about slight patient movement or things like that that 7

could be safety concerns that I think will be lost if 8

there is not that closure at the end.

9 In terms of the nurse issue, and whether it's 10 appropriate for these guidelines or not, I can kind 11 of certainly see the perspective that it's not something 12 NRC can regulate or does regulate, so it's not 13 appropriate for our subcommittee report. On the other 14 hand, it seems like a good practice advice.

15 I don't have a good sense of whether good 16 practice advice like this is appropriate or not. I 17 would turn to NRC staff for their comments on that.

18 It feels like a good idea to me, but I do get the argument 19 that it's a little bit more medical than regulatory.

20 And on the final point of Perfexion' versus 21 Icon', frankly, I would defer to Dr. Suh's judgment.

22 He has a lot more experience with these units than 23 I. So I don't have any particular opinion beyond his 24 on that.

25

50 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 I think I covered all the points. But if 1

there is something else, Mr. Sheetz, please remind me.

2 MEMBER SHEETZ: This is Mike Sheetz. Thank 3

you for your consideration and responding to those --

4 all of my comments.

5 So I guess, for clarity, you are recommending 6

these revisions for the Icon' unit for both frame-based 7

and mask-based treatments. Is that correct?

8 MEMBER ENNIS: That is correct. Yes.

9 MEMBER SHEETZ: Okay. The other comment is 10 we -- we do use the cone beam CT with frame based as 11 a replacement for the MRI or co-registration. But 12 otherwise, if we have a frame and an MRI image, we would 13 not repeat the cone beam CT, you know, as a secondary 14 check. And I'm not sure that's standard.

15 So, again, I guess I still go back to 16 frame-based treatments on Icon' and Perfexion' are 17 identical in practice.

18 MR. OUHIB: Hi. This is Zoubir.

19 CHAIRMAN ALDERSON: Go ahead.

20 MR. OUHIB: On item number two, you know, 21 trying to use the HDR regulation type of thing, I think 22 it's a good idea. However, there are institutions that 23 might not be as fortunate to have the luxury of a 24 physician under the direct supervision of an authorized 25

51 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 user.

1 So perhaps consideration would be to use one 2

or the other; in other words, to keep the two-minute 3

option and perhaps -- or the presence of a physician 4

under the direct supervision of an authorized user.

5 CHAIRMAN ALDERSON: Are there further 6

comments? Is there anyone that would like to comment 7

on that statement?

8 MEMBER SUH: This is John Suh. So I can see 9

both points. So in terms of being less restrictive, 10 the two-minute walk from a gamma knife treatment console 11 area is certainly less restrictive. Again, as Ron 12 mentioned, you know, one can walk faster or slower, 13 but, again, I think if someone says two minutes, that's 14 something that the authorized user could work with in 15 terms of what is considered a two-minute walk.

16 Physicians would need to decide what constitutes that 17 as a safety parameter.

18 You know, in terms of this proposal of either 19 an authorized user or physician under the supervision 20 of authorized user be present, it does -- it's probably 21 a clearer definition, although it is somewhat more 22 restrictive. And for a smaller center that may not 23 have the luxury of having another physician involved, 24 I can see this being a more restrictive definition for 25

52 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 gamma knife.

1 Not all gamma knife centers have multiple 2

physicians who are: a) trained, and b) have an interest 3

in being involved in gamma knife.

4 In terms of doing both, I guess I have mixed 5

feelings about whether or not both is a good option.

6 I think we should stick with one option if we are going 7

to go ahead with changing the current physical presence 8

requirements, which was the charge of the subcommittee 9

to begin with.

10 CHAIRMAN ALDERSON: Further comments? I 11 think we still need to work to clarify this a bit.

12 I'm going to take the prerogative here to indicate what 13 I think is being said, and then I'd like to get, John, 14 your comments and that of the Committee to clarify this.

15 So I am hearing that regarding the comment 16 of extending this new approach to both the Icon' and 17 the Perfexion', I believe that the Committee is saying 18 that it would choose to stay with the Icon' alone, that 19 there should be -- the physician should be present at 20 the end of the treatment, so that they can talk to the 21 patient.

22 Am I correct on the Committee's position on 23 those two issues?

24 MEMBER SUH: This is John Suh speaking again.

25

53 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Yes, I do believe that the Icon' and Perfexion' are 1

different units.

2 CHAIRMAN ALDERSON: Yes.

3 MEMBER SUH: And your second point about 4

being present at the conclusion of treatment, like Ron, 5

I feel very strongly that it is important to close the 6

loop when treating patients with high dose/high 7

precision radiation that is offered with the Icon' Gamma 8

Knife unit.

9 CHAIRMAN ALDERSON: Right. Am I correct 10 that Dr. Ennis and Laura Weil agree with those 11 positions?

12 MEMBER ENNIS: This is Ron. So just to 13 clarify, on the second position of being there at the 14 end, I agree with the position. But to clarify the 15 rationale, for me, it's not just about patient -- you 16 know, good for the patient, the patient will like that, 17 and all that, which I totally agree, but that's really 18 a medical thing.

19 But I do feel like there could be more subtle 20 or minor safety concerns, issues that might have 21 happened that would not stop the treatment and would 22 not be a misadministration, but might be helpful for 23 the team to know going forward for the next case or 24 the next patient, where things weren't perfect, that 25

54 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 it's really important to have that kind of -- well, 1

they call it a huddle nowadays, right? Doing 2

essentially a mandated huddle from a safety point of 3

view at the end of treatment, which will only really 4

happen efficiently and effectively, in my opinion, if 5

we mandate that everyone gets together at the end.

6 CHAIRMAN ALDERSON: Yes. Good. Any 7

disagreement with that from Dr. Suh or Ms. Weil?

8 MEMBER WEIL: No.

9 MEMBER SUH: No.

10 CHAIRMAN ALDERSON: Okay. So I think that 11 we have resolved those two issues in terms of the 12 committee's response to the comments. And that leaves 13 us with the comment regarding the two-minute walk versus 14 someone, being the AU or an AU-trained person, being 15 physically present at all times.

16 I'm going to turn this back to Dr. Suh to 17 try to see if we can navigate our way through that 18 particular concern, which seems to be the significant 19 one remaining in this discussion.

20 MEMBER SUH: So I have been thinking about 21 this since, you know, Michael sent this to me. As I 22 said, I am -- I like his suggestion, but I do agree 23 that it is more restrictive. And, again, it should 24 be very apparent. You know, a two-minute walk I don't 25

55 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 think should be that ambiguous in terms of responding 1

to an emergency or if there is an issue with a patient.

2 But my personal feeling, my recommendation, 3

is that the subcommittee report of the altered current 4

physical presence to allow for the authorized user to 5

be within a two-minute walk of the gamma knife console 6

area is appropriate and will allow the authorized user 7

to respond to any immediate medical needs.

8 CHAIRMAN ALDERSON: Okay. Good. That's 9

definitive. Do Dr. Ennis and Ms. Weil agree?

10 MEMBER ENNIS: I do.

11 CHAIRMAN ALDERSON: Laura?

12 MEMBER WEIL: Yes, I do.

13 CHAIRMAN ALDERSON: Okay. So that's also 14 clear from the standpoint of the subcommittee. Are 15 there other comments before we open this up to people 16 who might be on the phone lines?

17 So with the help of the operator, we will 18 now take comments on any of these issues from people 19 who are on the phone?

20 OPERATOR: Thank you. And, again, as a 21 reminder, if you have a question or a comment from the 22 phone, please press star one at this time. Make sure 23 your phone is unmuted and record your name to introduce 24 your question. And to withdraw that request, you may 25

56 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 press star two. Once again, for questions or comments, 1

press star one and record your name at this time.

2 And one moment. We'll stand by for questions 3

or comments. One moment, please. And we do have a 4

question or comment from Susan Lohman. Your line is 5

open.

6 MS. LOHMAN: Thank you. This is Susan 7

Lohman. I am neuroscience applications manager with 8

Elekta. And, first, I'd like to thank the subcommittee 9

for their long and thorough review of this issue, the 10 process that they have gone through.

11 And at this time, I would like to urge the 12 subcommittee and Committee to move forward with the 13 subcommittee's recommendation as it was proposed and 14 possibly in the future come back to look at the inclusion 15 or continued exclusion of Perfexion'.

16 And myself, as a representative of Elekta, 17 would be more than willing to provide any subject 18 material necessary to proceed as such.

19 Thank you.

20 CHAIRMAN ALDERSON: Do we have other 21 comments?

22 OPERATOR: Yes, we do have another question 23 or comment. And our next question or comment is from 24 Frank Tran. Your line is open.

25

57 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 MR. TRAN: Yes. This is Frank Tran in 1

Region III, NRC. I have a comment on the rule with 2

the HDR of exactly they -- they didn't require direct 3

supervision from an authorized user or a trained person.

4 It just says under supervision. So I believe the key 5

is not that. So I just want to comment on that.

6 CHAIRMAN ALDERSON: This is Dr. Alderson.

7 I'd like to ask the commenter to repeat some of what 8

he said, because I don't know how other -- I didn't 9

actually hear all those words very clearly.

10 MR. TRAN: Okay. So earlier I believe that 11 Mike mentioned about the rule under -- that required 12 authorizer user to be -- or a trained person to be 13 present over the -- under the rule for the HDR. Another 14 person mentioned that there should be direct 15 supervision.

16 However, under the rule for the HDR, it is 17 not a direct supervision, just a supervision, either 18 direct or not direct. So there's the comment for that.

19 CHAIRMAN ALDERSON: All right. Did people 20 understand the comment?

21 PARTICIPANT: Yes.

22 CHAIRMAN ALDERSON: Okay. Are there 23 further comments?

24 OPERATOR: I am currently showing no further 25

58 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 questions or comments at this time. And, again, as 1

a reminder, that is star one. Make sure your phone 2

is unmuted and record your name. And it is star two 3

to withdraw that request.

4 Again, for further questions or comments at 5

this time, please press star one and record your name, 6

and I'll stand by for further questions or comments.

7 CHAIRMAN ALDERSON: So, Dr. Suh, I'm going 8

to summarize here how I think this conversation has 9

evolved. I think we are -- we have accepted the --

10 we have listened to all of the comments. We have made 11 comments in return. I believe that we're at the point 12 where we are ready to accept the proposal as it was 13 originally recommended. Is that how you also 14 understand the comments?

15 MEMBER SUH: Yes, Dr. Alderson.

16 CHAIRMAN ALDERSON: Okay. Well, in that 17 case, are we in fact ready to -- is the subcommittee 18 and the -- are the ACMUI recommended as -- to accept 19 the report as it was originally proposed? All those 20 in favor?

21 (Chorus of ayes.)

22 CHAIRMAN ALDERSON: Any opposed? Thank 23 you. This report is accepted in its original proposed 24 form.

25

59 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 MS. HOLIDAY: Dr. Alderson, if I may, I'm 1

sorry, I didn't catch who made the motion and who 2

seconded the motion.

3 CHAIRMAN ALDERSON: I believe it was implied 4

that Dr. Suh was making the recommendation, I believe.

5 MEMBER SUH: Yes. On behalf of the 6

subcommittee, I propose that we accept the current --

7 sorry, the physical presence requirements of the 8

Leksell Gamma Knife Icon' that as submitted on behalf 9

of the subcommittee members.

10 VICE CHAIRMAN ZANZONICO: Sophie, this is 11 Pat. I'll second it.

12 MS. HOLIDAY: Thank you.

13 CHAIRMAN ALDERSON: Good.

14 MS. HOLIDAY: And then, if I understand, was 15 this a unanimous endorsement, or were there any 16 dissentions or abstentions?

17 CHAIRMAN ALDERSON: I did ask for that, I 18 believe, and it is a unanimous endorsement.

19 MS. HOLIDAY: Okay. Thank you.

20 CHAIRMAN ALDERSON: So is there any other 21 business that we need to conduct this morning?

22 MS. HOLIDAY: No. I would just like to thank 23 the subcommittee members for putting forth all of the 24 effort for both Dr. Metter's subcommittee and Dr. Suh's 25

60 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 subcommittee, for their thorough reviews and their 1

reports. I would also like to remind the ACMUI members 2

and other participants on the phone that ACMUI will 3

be holding another public teleconference in two weeks 4

on March 1st from 2:00 p.m. to 4:00 p.m. eastern.

5 The topic of that teleconference will be the 6

subcommittee report for the training and experience 7

requirements under all modalities in 10 CFR part 35 8

with a focus on 35.300 uses.

9 The ACMUI will also be holding their spring 10 meeting here at NRC headquarters on March 7th and 8th.

11 Thank you.

12 CHAIRMAN ALDERSON: Well, thank for everyone 13 who was on the call today.

14 Mr. Bollock, anything you would like to say 15 in the end?

16 MR. BOLLOCK: No, thank you, Dr. Alderson.

17 Appreciate everyone's time.

18 CHAIRMAN ALDERSON: I believe, Sophie, that 19 we have concluded our business. Thank you all, 20 everyone.

21 (Whereupon, the discussion of the draft 22 report concluded at 10:19 a.m.)

23

1 Carol S. Marcus, Ph.D., M.D.

1877 Comstock Avenue Los Angeles, CA 90025-5014

<csmarcus@ucla.edu>

Michael Stabin, Ph.D., CHP 3878 Stevens Lane Nashville, TN 37218

<michael.g.stabin@vanderbilt.edu>

February 7, 2018 Advisory Committee on Medical Uses of Isotopes (ACMUI)

U.S. Nuclear Regulatory Commission 11555 Rockville Pike Rockville, MD 20852 c/o Ms. Sophie Holiday, Sophie.Holiday@nrc.gov

Dear Ms. Holiday and Members of the ACMUI:

We have reviewed the ACMUI subcommittee draft on Nursing Mother Guidelines for the Medical Administration of Radioactive Materials, which is to be discussed at the Feb. 15, 2018 ACMUI meeting. We have a number of comments which we believe should be addressed in the next draft of this document which should make the final document more useful.

1. The draft guidance document assumes theoretical risk to the infant but fails to include information on the benefits of breastfeeding, which are real and significant. According to the American Academy of Pediatrics (AAP):

Most health professionals are familiar with the benefits of breastfeeding. The AAP continues to support the unequivocal evidence that breastfeeding protects against a variety of diseases and conditions in the infant such as: bacteremia, diarrhea, respiratory tract infection, necrotizing enterocolitis, otitis media, urinary tract infection, late-onset sepsis in preterm infants, type 1 and type 2 diabetes, lymphoma, leukemia, and Hodgkins disease, childhood overweight and obesity. There are also maternal health benefits to breastfeeding such as: decreased postpartum bleeding and more rapid uterine involution, decreased menstrual blood loss and increased child spacing (lactational amenorrhea), earlier return to prepregnancy weight, decreased risk of breast and ovarian cancers."

2

2. We note that the specific gamma ray factors cited in Table 2 are incorrect, by a factor of 1000(!) We hope that this is an error in the table, and that erroneous gamma factors were not used in the calculations given in the document.

3. We note a number of typos that suggest that the document was not carefully reviewed:

a. In Table 5, the heading "Hazel and Breitz" should be "Stabin and Breitz". "Hazel" is Breitz's first name.

b. The reference Stabin and Breitz is repeated as references 10, 26, 31, 36, 54, 71, and 73.

c. The proper spelling of Lu is "lutetium", not "lutecium", but this is misspelled several times in the document.

d. The word radioisotope is substituted for radionuclide twice. Radionuclide is the general term for a radioactive species; isotope refers to different radioactive species of a given element.

e. In all cases et al should be et al. (abbreviation mark included).

f. The name of the computer program is OLINDA/EXM.

g. Page 8: generallyless is given as one word.

h. Table 1 - do not capitalize rad.

i. On page 4 last line and in Table 2 the half-life of F-18 is given as 1.2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br />. The half-life of F-18 is 110 minutes, or 1.83 hours9.606481e-4 days <br />0.0231 hours <br />1.372354e-4 weeks <br />3.15815e-5 months <br />.

j. It is odd that non-SI units are used preferentially in a 2018 document.

4. For ingestion of radioiodinated pharmaceuticals, the document should contain thyroid dosimetry for all radionuclides of iodine to the infant thyroid as a function of infant uptake and thyroid mass/infant age. Choosing the worst possible case of a newborn with extremely high uptake and a tiny thyroid gland is not useful once the uptake falls from 75%-100% to about 15% and the thyroid mass increases, so a whole range of values needs to be presented. This information is important not only when considering advice to the mother but in evaluating accidents as well, of which there have been a number over the years.

5. We were pleased to see the calculations for external dose to the infant using the mother as a line source instead of a point source. We have two issues, however, with the calculations:

a. The authors appear to be unaware of important literature on the subject, noting the general lack of pertinent data in the literature. We note, for example:

i. J. G. Hunt, D. Nosske, D. S. dos Santos. Estimation of the dose to the nursing infant due to direct irradiation from activity present in maternal organs and tissues. Radiation Protection Dosimetry, Volume 113, Issue 3, 28 April 2005, Pages 290-299.

ii. Mountford PJ and Coakley AJ. Radiopharmaceuticals in breast milk.

Proceedings, Fourth International Radiopharmaceutical Dosimetry Symposium, Oak Ridge Associated Universities, Oak Ridge, TN, 1986; 167-180.

b. In calculating external dose to the infant from the radioactive mother, humanized gamma ray constants should be used or estimated, as the specific gamma ray

3 constants significantly overestimate infant dose. For example, the humanized gamma ray constant for I-131, with a 364 kev photon, is 1.3, not 2.2 (RADAR Exposure and Dose Calculator, http://www.doseinfo-radar.com/ExposureCalculator.html). For radionuclides with lower photon energy, the humanized gamma ray constants would reflect even more self-absorption by the mother. In the case of a mother with thyroid cancer who has stopped breastfeeding entirely and who has no thyroid of her own (it has been surgically removed), an accurate external dose to the infant after a 5 mCi administration for a metastatic survey and after a 150 mCi administration of a therapy dose should be calculated and appear in this guidance document, so the physician can offer accurate advice about holding the infant and feeding him formula or other milk product.

6. We appreciate that 10CFR35.75 notes a dose limit of 5 mSv (500 mrem) for exposure to members of the public, but requires that guidance be given regarding interruption of breast feeding if the dose to an infant or child may exceed 1 mSv (100 mrem). We strongly suggest that this second requirement be changed (in the statute) to 5 mSv, and the calculations be redone. The calculations performed were already conservative, but the application of an additional factor of 5 has no scientific basis. There are no scientifically valid data showing harm to infants at a dose of 500 mrem, and it is therefore unreasonable to reduce the dose far below the legal limit. Every baby conceived and born in Denver, CO has received an extra 500 mrem from background radiation by the age of 15 months, over and above the United States average which is 300 mrem/y. (Background radiation in Denver is about 550 mrem/y). Year after year, the State of Colorado tends to be tied for the third lowest cancer death rate in America, despite the fact that residents receive an extra 250 mrem/y, every year. Some receive even higher doses (Copper City, CO has a background rate of about 890 mrem/y.). By clinging to the Linear No-Threshold (LNT) myth that says any amount of radiation is dangerous and can cause death from cancer, 500 mrem seems five times more dangerous than 100 mrem, but the LNT premise itself has been soundly denounced on various fronts for low dose and dose rates. First, the LNT states that there is no such thing as radiation repair, but we have found over 150 genes that are active in the repair of lesions caused by radiation and metabolism using oxygen, and we know that these repair mechanisms are stimulated by low dose radiation and that they repair more damage than what was caused by the low dose radiation to begin with. We know that one mutation cannot cause a cancer, fatal or otherwise, as assumed by the LNT. If it could, we would see three-year old boys with prostate cancer, five-year old boys and girls with breast cancer, and six-year olds with lung cancer. This does not happen. The LNT states that all doses are additive, and that dose rate is irrelevant. We know that radiation delivered chronically in low doses is much less damaging than the same dose delivered instantaneously. The whole field of radiation oncology is mainly based on the fact that normal tissues can repair if the radiation doses delivered are not too high and repair mechanisms are stimulated, whereas aberrant cancer tissue cannot repair as well as normal tissue. That is why radiation therapy is delivered multiple times over weeks, permitting normal tissue to preferentially repair. If 6000 rad were delivered all at once, you would burn a hole in the patient. It is time to stop using the LNT at low doses as a basis for anything.

4 Thank you for your attention and consideration. We look forward to reviewing the improved draft.

Sincerely, Carol S. Marcus, Ph.D., M.D.

Professor of Radiation Oncology, of Molecular and Medical Pharmacology (Nuclear Medicine),

and of Radiological Sciences, David Geffen School of Medicine at the University of California at Los Angeles (UCLA) and past two-term member of the ACMUI.

Michael G. Stabin Chair, RAdiation Dose Assessment Resource (RADAR) Committee of the Society of Nuclear Medicine and Molecular Imaging, and Associate Professor of Radiology and Radiological Sciences Department of Radiology and Radiological Sciences Vanderbilt University

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) appreciates the opportunity to comment on the Sub-Committee on Nursing Mother Guidelines for the Medical Administration of Radioactive Materials report drafted by Vasken Dilsizian, MD, Darlene Metter, MD (Chair), Christopher Palestro, MD, and Pat Zanzonico, Ph.D, dated February 1, 2018.

The Society of Nuclear Medicine and Molecular Imagings more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings, and leading advocacy on key issues that affect molecular imaging and therapy research and practice.

February 12, 2018 U.S. Nuclear Regulatory Commission (NRC) 11555 Rockville Pike Rockville, MD 20852 Washington, DC 20555-0001 Re: Nursing Mother Guidelines for the Medical Administration of Radioactive Materials Dear members of the ACMUI F-18: 6.952E-4 mrem/hr per uCi at 1 m Ga-67: 1.1 x 10-1 mR/hr/mCi at 1 m Tc-99m: 1.2 x 10-1 mrem/hr/mCi at 1 m I-131: 2.2 R-cm2/mCi-hr Page 8, line 1, "generallyless" should be two words.

Page 11, #6 (and possibly elsewhere), "lutecium" is correctly spelled "lutetium".

Table 1, "Rad" should be "rad"

U.S. Nuclear Regulatory Commission (NRC)

February 12, 2018 Page 2 of 2 Table 2 half life of F-18 is 109 or 110 minutes (depending on the reference, and is therefore 1.82 or 1.83 hours9.606481e-4 days <br />0.0231 hours <br />1.372354e-4 weeks <br />3.15815e-5 months <br /> (not 1.2). This is also mentioned incorrectly in the last line of page 4.

Table 5, 3rd column, the reference should be Stabin and Breitz.

References 10, 26, 31, 36, 54, 71 and 73 are all the same reference (Stabin and Breitz).

Additionally, the report offers some debatable recommendations. For example, interrupting breast feeding for 7 days for I-123 400 microcurie capsules. That is significantly longer than 10 half-lives (even though the risk of contamination with other isotopes is no longer present - the previous rationale for interrupting breast feeding). Also, most sources say no interruption of breast feeding is necessary including the NRC regulatory guide 8.39 https://www.nrc.gov/docs/ML0833/ML083300045.pdf (no cessation needed even for doses of 3 mCi) https://www.nrc.gov/materials/miau/miau-reg-initiatives/guide_2002.pdf.

There are certain assumptions of the LNT hypothesis that are lacking in supportive scientific evidence. For one, LNT assumes that there is no DNA repair at low doses. However, the scientific evidence suggests otherwise. There have been over 150 genes identified by radiation biologists that are involved in the repair of DNA radiation damage. There are known to be three types of repair:

1) anti-oxidant prevention

2) enzymatic repair of DNA damage

3) removal of DNA alterations by apoptosis.

Another assumption of the LNT that needs to be addressed is that the dose rate does not matter.

However, that supposition is also not supported by scientific evidence. In fact, the entire field of Radiation Oncology is based on repair of radiation damage, and particularly that the repair mechanisms of normal tissue are more efficient than those of cancerous tissue.

SNMMI appreciates the opportunity to comment on this report. As always, SNMMI is ready to discuss any of its comments or meet with NRC on the above issues. In this regard, please contact Caitlin Kubler, Senior Manager, Regulatory Affairs, by email at ckubler@snmmi.org or by phone at 703-326-1190.

Sincerely, Bennett S. Greenspan, MD, FACNM, FACR President, SNMMI

U.S. Nuclear Regulatory Commission (NRC)

February 12, 2018 Page 2 of 2