ML18088B413

Transcript of the Advisory Committee on the Medical Uses of Isotopes (ACMUI) Teleconference Meeting, February 15, 2018, Pages 1-68

ML18088B413
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Issue date:	03/29/2018
From:	Advisory Committee on the Medical Uses of Isotopes
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Holiday, Sophie
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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 1-68 NEAL R. GROSS AND CO., INC.

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

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

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

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

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

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

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6 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.

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

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7 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 Stabin63 Society of Nuclear Medicine and Molecular Imaging67 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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8 1 P-R-O-C-E-E-D-I-N-G-S 2 (9:06 a.m.)

3 CHAIRMAN ALDERSON: Well, good morning, 4 and welcome to today's ACMUI public teleconference.

5 We'll discuss two topics today: nursing mothers 6 guidelines, the subcommittee report; and the physical 7 presence requirements for the gamma knife, also a 8 subcommittee report.

9 I will now turn it over to Mr. Doug 10 Bollock from the NRC for some opening remarks.

11 MR. BOLLOCK: Thank you, Dr. Alderson.

12 Good morning. As the designated federal officer for 13 this meeting, I am pleased to welcome you to the 14 public meeting of the Advisory Committee on Medical 15 Uses of Isotopes.

16 My name is Doug Bollock. I am the chief 17 of the Medical Safety and Events Assessment Branch, 18 and I have been designated as the federal officer for 19 this Advisory Committee in accordance with 10 CFR 20 Part 7.11.

21 Present today as the alternate designated 22 federal officer is Sophie Holiday, our ACMUI 23 coordinator.

24 This announced meeting of the Committee 25 is being held in accordance with the rules and NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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9 1 regulations of the Federal Advisory Committee Act and 2 the Nuclear Regulatory Commission. This meeting is 3 being transcribed by the NRC, and it may also be 4 transcribed or recorded by others. This meeting was 5 announced in the January 23, 2018, edition of the 6 Federal Register on 83 page 3191.

7 The function of the Committee is to advise 8 the staff on issues and questions that arise on 9 medical uses of byproduct material. The Committee 10 provides counsel to the staff but not determine or 11 direct the actual decisions of the staff or the 12 Commission. The NRC solicits the view of the 13 Committee and values their opinion.

14 I request that whenever possible we try 15 to reach a consensus on the various issues that we 16 will discuss today. But I also recognize there may 17 be minority or dissenting opinions. If you have such 18 opinions, please allow them to be read into the 19 record.

20 At this point, I'd like to perform a roll 21 call of the ACMUI members participating today. Dr.

22 Philip Alderson?

23 CHAIRMAN ALDERSON: Here.

24 MR. BOLLOCK: Thank you. Dr. Pat 25 Zanzonico?

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10 1 VICE CHAIRMAN ZANZONICO: Yes.

2 MR. BOLLOCK: Thank you. Dr. Vasken 3 Dilsizian?

4 MEMBER DILSIZIAN: Here.

5 MR. BOLLOCK: Dr. Ronald Ennis?

6 MEMBER ENNIS: Here.

7 MR. BOLLOCK: Thank you. Dr. Darlene 8 Metter?

9 MEMBER METTER: Here.

10 MR. BOLLOCK: Thank you. Dr. Michael 11 O'Hara?

12 MEMBER O'HARA: Here.

13 MR. BOLLOCK: Thank you. Dr. Christopher 14 Palestro?

15 MEMBER PALESTRO: Here.

16 MR. BOLLOCK: Thank you. Mr. Michael 17 Sheetz?

18 MEMBER SHEETZ: Here.

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

20 MEMBER SUH: Here.

21 MR. BOLLOCK: Thank you. And Ms. Laura 22 Weil.

23 MEMBER WEIL: Here.

24 MR. BOLLOCK: Thank you. I've confirmed 25 that a quorum is met by the presence of at least six NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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11 1 members.

2 Also, on the phone do we have Mr. Zoubir 3 Ohib?

4 MR. OUHIB: Here.

5 MR. BOLLOCK: Thank you. Mr. Richard 6 Green?

7 MR. GREEN: Here.

8 MR. BOLLOCK: Thank you. And Ms. Megan 9 Shober?

10 MS. SHOBER: Here.

11 MR. BOLLOCK: All right. Thank you.

12 Mr. Ouhib has been selected as ACMUI's 13 therapy medical physicist. Mr. Green has been 14 selected as the ACMUI nuclear pharmacist. And Ms.

15 Shober has been selected as the ACMUI Agreement State 16 Representative.

17 At this time, Mr. Ouhib, Mr. Green, and 18 Ms. Shober are pending security clearance but may 19 participate in the meeting. However, they do not 20 have voting rights at this time.

21 I now ask NRC staff members who are 22 present to identify themselves. I'll start with 23 individuals in the room here.

24 MS. HOLIDAY: Sophie Holiday, ACMUI 25 coordinator.

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12 1 DR. TAPP: Dr. Katie Tapp with the medical 2 team.

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

4 DR. HOLAHAN: Dr. Vincent Holahan, senior 5 advisor.

6 MR. BOLLOCK: Okay. Now we go to NRC 7 employees on the phone.

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

9 MS. AYOADE: Yes, I am. I had you on 10 mute. Here.

11 MR. BOLLOCK: Okay. That's Maryann 12 Ayoade, also with the medical team.

13 MS. AYOADE: That's correct.

14 MR. BOLLOCK: Anyone else? Any other NRC 15 headquarters employees on the phone?

16 Okay. Are there any NRC regional 17 employees on the phone?

18 Okay. Thank you all. Members of the 19 public who notified Ms. Holiday that they would be 20 participating on the teleconference will be captured 21 in the transcripts. Those of you who did not provide 22 prior notification, please contact Ms. Holiday at 23 sophie.holiday@nrc.gov. That's S-O-P-H-I-E dot H-O-24 L-I-D-A-Y at N-R-C dot G-O-V. Or call her at 25 (301) 415-7865.

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13 1 We have a bridge line available, and that 2 phone number is (888) 790-6447. The passcode to 3 access the bridge line is 279-0867 followed by the 4 pound key.

5 This meeting is also using to the GoTo 6 webinar application to view the presentation handouts 7 real time. You can access this by going to 8 www.gotowebinar.com, G-O-T-O-W-E-B-I-N-A-R dot com 9 and searching for the meeting ID 563-775-347.

10 The purpose of this meeting is to discuss 11 the revised draft report for the ACMUI nursing mother 12 guidelines for the medical administration of 13 radioactive materials, and the revised draft report 14 for the ACMUI physical presence requirements for the 15 Leksell Gamma Knife Icon'.

16 Individuals who would like to ask a 17 question or make a comment regarding a specific issue 18 the committee has discussed should request permission 19 to be recognized by the ACMUI chairperson, Dr. Philip 20 Alderson. Dr. Alderson, at his option, may entertain 21 comments or questions from members of the public who 22 are participating with us today.

23 Comments and questions are usually 24 addressed by the Committee near the end of the 25 presentation after the Committee has fully discussed NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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14 1 the topic. We ask that one person speak at a time as 2 this meeting is also closed caption.

3 I would also like to add that handouts and 4 an agenda for this meeting are available on the NRC's 5 public website.

6 At this time, I'd ask that everyone on the 7 call who is not speaking to place their phones on 8 mute. If you do not have the capability to mute your 9 phone, please press star six to utilize the 10 conference line mute and unmute function.

11 I would ask everyone to exercise care to 12 ensure that background noise is kept at a minimum, as 13 any stray background sounds can be very disruptive on 14 a conference call this large.

15 At this point, I would like to turn the 16 meeting back over to Dr. Alderson.

17 CHAIRMAN ALDERSON: Thank you, Mr.

18 Bollock. So I will then start the meeting by turning 19 it to Dr. Darlene Metter, who is the chair of the 20 Nursing Mothers Guidelines Subcommittee. Dr. Metter?

21 MEMBER METTER: Thank you, Dr. Alderson.

22 And I'd like to first thank the work of my 23 subcommittee members, Dr. Vasken Dilsizian, Dr.

24 Christopher Palestro, and Dr. Pat Zanzonico.

25 The subcommittee charge was to review the NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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15 1 radiation exposure from diagnostic and therapeutic 2 radiopharmaceuticals, including brachytherapy, to 3 the nursing mother and child.

4 Now, as a summary of our report in 5 September, we know that many drugs and 6 radiopharmaceuticals administered to the nursing 7 mother can enter her milk, and then, therefore, be 8 ingested by the nursing child. The subcommittee 9 recommendations regarding the radiation exposure to 10 the nursing child follows current existing 11 recommendations for the nursing mother by reputable 12 expert sources such as the NRC, ICRP, Dr. Michael 13 Stabin's paper, and others.

14 Therefore, our subcommittee 15 recommended -- recommendations mirrored the sources 16 with the use of a maximum dose of 100 millirem to the 17 nursing child. The current literature at times had 18 variable recommendations on the temporary 19 interruption of breastfeeding due to 20 radiopharmaceuticals in the mother's milk, and the 21 subcommittee generally opted to choose the most 22 conservative, which was usually the longest 23 interruption period.

24 The subcommittee results and 25 recommendations are summarized in a table reviewed at NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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16 1 the September 2017 ACMUI meeting. Since that time, 2 there have been comments from Dr. Carol Marcus and 3 Dr. Michael Stabin, and Dr. Bennett Greenspan and the 4 SNMMI. To review these comments, Dr. Pat Zanzonico 5 will address them and the associated report 6 revisions.

7 Dr. Zanzonico?

8 VICE CHAIRMAN ZANZONICO: Thank you, Dr.

9 Metter. So as Dr. Metter just said, we received a 10 number of comments, both from Drs. Marcus and Stabin, 11 and independent from Dr. Greenspan and the Society of 12 Nuclear Medicine and Molecular Imaging. So what I 13 was going to do was step through their respective 14 comments and summarize our responses.

15 This was an information-dense report, and 16 so there were a number of comments, so please bear 17 with me. The first comment from Drs. Marcus and 18 Stabin was that the draft report failed to describe 19 or at least acknowledge the real and significant 20 benefits of breastfeeding to both the infant and the 21 nursing mother, and they include a statement from the 22 American Academy of Pediatrics to that effect.

23 And that point is well taken, and in our 24 subsequent revision of the report we think it would 25 be reasonable to include a statement explicitly NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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17 1 acknowledging the benefits of breastfeeding to the 2 mother and child, and so we plan to do that in the 3 revised -- the subsequent revision of our report.

4 The second point was that the so-called 5 specific gamma ray factors cited in Table 2 are 6 incorrect. They indicate by a factor of 1,000. And 7 this was a units transcription error. The values in 8 the table, and as used in our calculations, are in 9 roentgen centimeters squared per microcurie hour.

10 The mu for micro when it went to hard copy 11 became an m for milli inadvertently. And so the 12 factor of 1,000 error was apparent. We will correct 13 that, of course, in the subsequent revision, but I 14 want to assure everyone that the actual calculations 15 and analyses were based on the actual correct values.

16 I will just also address the related point 17 of a comment by Dr. Greenspan and the SNMMI. They 18 state in their comments that the specific gamma ray 19 constant, the quantities I'm referring to right now, 20 were in error, and they provided a number of different 21 values with variable units being used.

22 And of course if we have numerical or 23 other factual errors in the report, those will be 24 corrected and reflected in a revised analysis.

25 However, we asked that Dr. Greenspan and the SNMMI NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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18 1 provide a reference for their values. No such 2 reference was provided with their written comments, 3 and so we have no way at this point of verifying their 4 veracity, their accuracy.

5 Our specific gamma ray constants were 6 taken from a classic textbook in medical physics, 7 Johns and Cunningham, which many of you may be 8 familiar with. So that's the source of our data, but 9 we understand that specific gamma ray constants, like 10 other physical quantities, are periodically updated, 11 and we certainly want to use the most current and 12 most accurate values in our analysis.

13 And if Dr. Greenspan and the Society can 14 provide a reference, so that we can verify the 15 accuracy of their stated values, we will amend our 16 report accordingly.

17 The next point from Drs. Marcus and Stabin 18 was they found a number of typos and editorial errors, 19 and we appreciate, of course, their careful reading 20 of the report as we appreciate all their comments and 21 insights, and we will certainly correct these 22 editorial errors in the subsequent revision.

23 Likewise, Dr. Greenspan and the Society noted a 24 number of editorial errors, and we will correct those 25 as well, of course.

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19 1 One issue that arose, which is always a 2 thorny one, is the system of units to use. We use 3 essentially conventional units because, frankly, 4 that's the system of units most of us, including 5 myself, are most familiar with and most comfortable 6 with. But we certainly appreciate that we should be 7 transitioning to use of SI units.

8 And we will confirm with the NRC staff to 9 verify that that's an appropriate thing to do, and 10 we'll amend our report accordingly to use SI rather 11 than conventional units or perhaps SI units primarily 12 with conventional units presented parenthetically.

13 But we will address that point.

14 A fourth point raised by Drs. Marcus and 15 Stabin was that the dosimetry analysis for 16 radioiodines, specifically with respect to the 17 thyroid, used worst-case factors in terms of maximal 18 uptakes of radioiodine by the thyroid and minimal 19 thyroid gland masses. Both of those conservative 20 assumptions would lead to maximal estimates of 21 dosimetry.

22 And Drs. Marcus and Stabin recommended 23 that we perform this thyroid dosimetry analysis for 24 all medically used radioiodines, not just I-131. So 25 that would include, of course, I-123, nowadays I-124, NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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20 1 perhaps even I-125. And they also suggested that in 2 that analysis we use a range of uptakes, not simply 3 maximal uptake, and a range of age-dependent uptakes 4 and age-dependent thyroid masses. And we can 5 certainly do that.

6 And, immodestly, I cite my own paper, Age-7 Dependent Thyroid-Absorbed Doses for 8 Radiobiologically Significant Radioisotopes of 9 Iodine from Health Physics, 2000. So we can extract 10 dose estimates or -- in the dosimetry analysis from 11 that paper and incorporate the suggested, augmented 12 analysis in the subsequent revision of our report.

13 Drs. Marcus and Stabin also point out that 14 two significant literature references were not cited 15 in the paper, and certainly we want to be as 16 comprehensive and thorough as possible in 17 incorporating the pertinent scientific literature 18 into our recommendations. And we will certainly 19 review these papers and incorporate them, at least 20 cite them, in our report and, if necessary, make 21 whatever adjustments those dictate.

22 And they also point out that perhaps an 23 ill-advised phrase was included in the report 24 referencing the available scientific literature on 25 breastfeeding, dosimetry, and so forth; namely, the NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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21 1 phrase being the general lack of pertinent data in 2 the literature. And on further reflection, I think 3 we all acknowledge -- and you can verify this by 4 looking at the bibliography -- the references in our 5 report, there actually is already significant 6 literature on the subject. So we will eliminate that 7 phrase as well as include these additional 8 references.

9 A further point that was made is that 10 rather than using or modeling the mother and the 11 mother's breast as point sources -- and that is often 12 done, frankly, for simplicity purposes in dose 13 calculations -- we modeled those source regions in 14 terms of the external dose to the nursing baby. We 15 modeled those as line sources based on a paper in the 16 literature, and that yields a more realistic estimate 17 of the external dose to the infant than does a point 18 source model.

19 Drs. Marcus and Stabin point out, however, 20 that there are so-called humanized gamma ray 21 constants available, certainly at least for I-131.

22 However, we point out -- or we would like to point 23 out that in our calculation we not only model the 24 mother's body and breast as line sources, but we also 25 incorporated the self-absorption of extant gamma rays NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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22 1 by those respective source regions, and we also --

2 well, we modeled those, as I say, as attempting to 3 count the self-absorption.

4 So we think that our approach, even though 5 we use specific gamma ray constants which implicitly 6 implies -- which implies a point source, we think 7 we've made the necessary adjustments to appropriately 8 quote/unquote "humanize our specific gamma ray 9 constant values."

10 I'm just thumbing through my notes.

11 Another point that was made -- and this was a lengthy, 12 very scholarly comment, indicating that basing 13 recommendations with regard to cessation of 14 breastfeeding for mothers who undergo a nuclear 15 medicine procedure, basing that on a 100 millirem 16 limit to the nursing infant is overly conservative, 17 and Drs. Marcus and Stabin recommend a dose limit of 18 five millisieverts instead.

19 And incorporated into that comment was a 20 strong reputation of the linear non-threshold dose 21 response model for cancer induction by radiation.

22 And I think many of us, myself included, are very 23 empathetic so to speak to that point, and I think 24 many of us have well-founded skepticism about the 25 biological validity of the linear non-threshold NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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23 1 model.

2 But having said that, really, a discussion 3 of that model, as important and interesting as it is 4 certainly, is really beyond the scope of our report.

5 And as Dr. Metter pointed out, we deferred to the 6 prevailing recommendations made by authoritative 7 bodies like the ICRP, NCRP, and so forth.

8 And we also noted that in their original 9 analysis, in the really seminal and widely cited 10 paper by Dr. Stabin and Dr. Bryce, that they based 11 their analysis on a one millisievert effective dose 12 quote/unquote limit to the nursing infant.

13 So based on all of those considerations, 14 and despite our misgivings of the linear non-15 threshold dose-response models, we decided, as 16 Dr. Metter indicated, to use a one millisievert limit 17 upon which to base our recommendations.

18 Proceeding now to the comments submitted 19 by Dr. Greenspan and the Society, to address their 20 comment on the possible -- possibly erroneous 21 specific gamma ray constant values, and we will ask 22 them and await the literature citation of the values 23 they cite, and based on our subsequent review of these 24 values in that literature adjust the specific gamma 25 ray constants and our values and our calculations NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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24 1 accordingly.

2 I mentioned that they also had a number 3 of editorial corrections which we will certainly 4 address in a subsequent revision of the paper. And 5 there was a question or a disagreement with our 6 recommendation for discontinuing of breastfeeding 7 following administration of I-123 labeled 8 radiopharmaceuticals, not only sodium iodide but also 9 ortho-iodohippurate and MIGB, 10 metaiodobenzylguanidine, which are all used 11 clinically labeled with I-123.

12 And I think there may have been a 13 misunderstanding, understandably, given all of the 14 numbers and so forth in the paper, in the report 15 rather, but in Table 2 -- I'm sorry, in Table 5 of 16 the report, in which we include our recommendations 17 on cessation, the penultimate column, the next-to-18 last column, which uses the -- which lists the current 19 recommendations of -- that we use here at Memorial 20 Sloan Kettering, indicated a seven-day 21 discontinuation following administration of at least 22 certain I-123 radiopharmaceuticals.

23 But if you looked at the recommendations 24 for -- from the Committee, which is actually in the 25 very last column of that table, our recommendations NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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25 1 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 2 case of I-123, iodohippurate, not recommending any 3 interruption of breastfeeding.

4 So I think we have all -- I think what we 5 -- what the committee or subcommittee has recommended 6 is perfectly consistent with the point that Dr.

7 Greenspan and the Society were making. So, yes, as 8 you see what's on the screen now, in the very last 9 column, the fourth, fifth, and sixth lines refer to 10 cessation of I-123, sodium iodide; 11 metaiodobenzylguanidine, MIGB; and the last of those 12 three lines, line 6, to ortho-iodohippurate labeled 13 with I-123. So I think our recommendations are 14 consistent with what the Society is recommending.

15 Dr. Greenspan and the Society are also 16 recommending a more thorough, a more complete 17 dosimetric analysis of radioiodine as a function of 18 age, child age, and thyroid mass. And as I alluded 19 to earlier, we will provide an expanded dosimetric 20 analysis as also recommended by Drs. Marcus and 21 Stabin.

22 And Dr. Greenspan and the Society also 23 forcefully endorsed the recommendation of Drs. Marcus 24 and Stabin that, number one, a 500 millirem rather 25 than a 100 millirem dose limit or dose benchmark upon NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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26 1 which to base recommendations is more appropriate, 2 and that the linear non-threshold model is really not 3 only inappropriate but incorrect.

4 So I have already addressed that point in 5 my earlier comments. And so that actually completes 6 our point-by-point response to the submitted 7 comments, both by Drs. Marcus and Stabin, and by Dr.

8 Greenspan and the Society. We very much appreciate 9 their careful and thoughtful -- their careful reading 10 of the report and their thoughtful comments. And we 11 have tried to address them as comprehensively as 12 possible. And I think we've done so and will revise 13 the report accordingly.

14 So that concludes my comments in terms of 15 our responses to the submitted comments. So, Dr.

16 Metter, I will turn it back to you.

17 MEMBER METTER: Thank you, Dr. Zanzonico, 18 for a very thorough review and work on the comments 19 from Drs. Marcus, Stabin, Greenspan, and the Society 20 of Nuclear Medicine.

21 Do I have other comments from our 22 subcommittee members?

23 Okay. Hearing none --

24 MEMBER WEIL: Dr. Metter?

25 MEMBER METTER: Yes.

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27 1 MEMBER WEIL: This is Laura Weil. I do 2 have a comment, and I'd like to apologize for not 3 submitting it in advance. The subcommittee report 4 recommends the complete cessation of -- states that 5 the cessation of milk production generally occurs 6 about six weeks after the last breastfeeding.

7 And I encountered a report from the ATA, 8 which recommends a longer period of cessation, and 9 I'd like to -- this is from the ATA from 2009 in 10 Thyroid. If I might just briefly read this paragraph 11 and ask for an evaluation of it, basically.

12 Let's see. Breastfeeding must be stopped 13 at least six weeks before administration of I-131 14 therapy, and a delay of three months will more 15 reliably ensure that lactation-associated increase in 16 breast sodium iodide symporter activity has returned 17 to normal.

18 I wonder if six weeks in our -- in the 19 subcommittee report could be amended to at least six 20 weeks in order to acknowledge the potential for a 21 longer period of time being necessary. I don't know 22 how one would assess how long a period of time between 23 six weeks and three months should be recommended, but 24 certainly for the provision of information to 25 patients, in accordance with the ALARA principles, so NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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28 1 that breastfeeding women would have time to allow at 2 least six weeks' cessation of breastfeeding before 3 administration of Iodine-131. Would you comment on 4 that?

5 MEMBER METTER: Yes. Actually, thanks for 6 bringing that up. There was a comment as far as the 7 minimal timeframe in regards to notifying the nursing 8 mother regarding her I-131 therapy issue with 9 nursing, and we did say it was going to be at six 10 weeks. I have no problem saying at least six weeks 11 prior to the radioiodine administration. Does 12 anybody else on the subcommittee have any comments?

13 VICE CHAIRMAN ZANZONICO: This is Pat 14 Zanzonico. I have no problem either with that 15 language, meaning specifically at least six weeks.

16 I think we all recognize that both medically and 17 logistically the longer that period of 18 discontinuation of breastfeeding begins prior to 19 therapy, the more problematic it becomes.

20 And so I think six weeks itself may be 21 somewhat problematic, but I have no problem at all 22 with that language, at least -- at least six weeks 23 for cessation prior to therapy.

24 MEMBER METTER: Thank you, Dr. Zanzonico.

25 Thank you as well for your comment on that. And any NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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29 1 other comments?

2 Okay. Dr. Alderson, I'll turn it back to 3 you.

4 CHAIRMAN ALDERSON: Well, thank you. I 5 believe that must conclude this report and 6 discussion. Are there other comments from people who 7 are online?

8 OPERATOR: And if you have a question or 9 a comment from the phones, you may press star one at 10 this time. Make sure your phone is unmuted and record 11 your name. And to withdraw that request, you may 12 press star two. Once again, press star one for 13 questions or comments from the phones, and I'll stand 14 by for questions or comments.

15 One moment. And we do have a question or 16 comment coming from Carol Marcus. Your line is open.

17 DR. MARCUS: Thank you. Pat, I think 18 we're in complete agreement on everything except the 19 500 millirem calculations. And I think it would be 20 really helpful to have both the 100 millirem and the 21 500 millirem, recognizing that for 21 years the limit 22 has been 500 millirem, and then the physician and the 23 lactating mother decide what ALARA provision is 24 appropriate.

25 Otherwise, what we have is something so NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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30 1 conservative that I think a lot of people won't want 2 to use it. I know that Mike and Hazel's paper 3 originally used 100 millirem, but Mike has changed 4 his mind and thinks 500 millirem calculations would 5 be good. And I think having both might be the best 6 way to do it. Then licensees can choose what seems 7 most appropriate, and we'll have at least the 8 calculations with which to make a good choice.

9 Thank you.

10 OPERATOR: Does that conclude the question 11 or comment?

12 DR. MARCUS: Yes, it does.

13 MEMBER METTER: May I say something on 14 this regarding -- in our paper, the first part as far 15 as the current guidance, it does allude to a nursing 16 mother who has received information that until 17 byproduct material can be released by a licensee, the 18 total effective dose equivalent to any other 19 individual, including her nursing child, is projected 20 to not exceed five millisieverts. But she must give 21 guidance if it's going to exceed one millisievert.

22 So we have that in our paper.

23 DR. MARCUS: Yes. But you don't have the 24 calculations.

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31 1 Zanzonico. I personally have no objections to 2 including a -- essentially a dual set of 3 recommendations. I mean, the heart of the report and 4 the key recommendations, of course, are the 5 recommendations for the duration of discontinuing 6 breastfeeding.

7 And we can certainly add an additional 8 column which gives those periods of time for a 9 100 millirem dose to the nursing infant and a 500 10 millirem dose to the nursing infant.

11 If I understand correctly, the NRC 12 obviously doesn't regulate breastfeeding, and we can 13 provide, as points of information, the recommended 14 discontinuation periods for 100 and 500 millirem 15 limits, and the patient and their caregivers can then 16 choose as appropriate.

17 I have no objection, scientific or 18 otherwise, to that approach. I don't know if -- if 19 having dual recommendations in effect is problematic 20 from the NRC's point of view. But from a logistical, 21 scientific point of view, I have no objection to that 22 approach.

23 MS. HOLIDAY: Dr. Zanzonico and Dr.

24 Metter, NRC does not object to, if you want to amend 25 the subcommittee report to reflect these dual NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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32 1 recommendations, that's at your discretion.

2 MEMBER METTER: Thank you, Sophie. I 3 think if that's okay, we'll go ahead. Any other 4 comments from the subcommittee? Because I think 5 we'll go ahead and make those two recommendations as 6 far as listing on the table as Dr. Zanzonico had 7 reflected.

8 MEMBER WEIL: This is Laura Weil. Dr.

9 Metter, may I comment on that?

10 MEMBER METTER: Yes.

11 MEMBER WEIL: I have no objection to 12 listing both sets of recommendations, but I would 13 like to know that they would be labeled with the 14 agency that recommends both the 100 and the 500 15 millisieverts threshold.

16 MEMBER METTER: Okay.

17 MEMBER WEIL: So that the chart or the 18 graph itself is labeled to indicate which agencies 19 recommend which threshold.

20 MEMBER METTER: Okay. I believe most of 21 them are based on the 100 millirem.

22 MEMBER WEIL: I believe that's true, and 23 I'd like to see that noted in the table.

24 MEMBER METTER: Oh, I see. Okay. Thank 25 you.

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33 1 Any other comments?

2 OPERATOR: And I am currently showing no 3 further questions or comments from the phones.

4 Again, as a reminder, if you have further questions 5 or comments, it is star one. Make sure your phone is 6 unmuted and record your name. And it is star two to 7 withdraw that request. And I'll stand by for any 8 further questions or comments at this time.

9 MEMBER METTER: Dr. Alderson, I don't 10 think there are other comments or questions at this 11 time.

12 CHAIRMAN ALDERSON: All right. Thank you 13 very much.

14 OPERATOR: And we did just have one cue 15 up. If you'd like to wait one moment, I'll get that 16 party's name.

17 CHAIRMAN ALDERSON: Certainly.

18 OPERATOR: One moment. Thank you. Excuse 19 me. Dr. Greenspan, your line is open for your 20 question or comment.

21 DR. GREENSPAN: Thank you very much. I 22 just had a quick comment as a follow up to 23 Dr. Zanzonico's request for references for gamma ray 24 constants. I'm traveling this week, but I will be 25 glad to provide them next week. I hope that won't be NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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34 1 too late. Thank you.

2 VICE CHAIRMAN ZANZONICO: This is Pat 3 Zanzonico. Yes, Dr. Greenspan, that would be 4 certainly soon enough. The additional analyses I'm 5 committing to are going to take a bit of time, and 6 they certainly won't be concluded by next week, so 7 next week will be soon enough.

8 DR. GREENSPAN: Thank you very much.

9 OPERATOR: Thank you. And I'm currently 10 showing no further questions or comments at this 11 time.

12 CHAIRMAN ALDERSON: Good. Thank you.

13 That means that we will now proceed with the next 14 part of this public conference call. That will be 15 the report from Dr. John Suh's subcommittee on the 16 physical presence requirements for the Gamma Knife 17 Icon. I will turn the conversation over to Dr. Suh.

18 MS. HOLIDAY: Dr. Alderson and Dr. Suh, 19 before you launch into the next topic, if I may, can 20 I ask if the Committee will be making a motion to 21 endorse this report with the reflected amendments?

22 CHAIRMAN ALDERSON: Yes, certainly.

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

24 MEMBER METTER: Can I make a motion to 25 endorse the amended reports?

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35 1 PARTICIPANT: Second.

2 MS. HOLIDAY: And then if you could state 3 for me what the amendments will be, so that we can 4 capture that on the record?

5 MEMBER METTER: Okay. Dr. Zanzonico?

6 VICE CHAIRMAN ZANZONICO: Yes. The 7 amendments will include acknowledgment of the 8 benefits of breastfeeding. They will include 9 correction as needed of the specific gamma ray 10 constant values. They will include conversion of the 11 system of units from conventional to SI. There will 12 be an expanded dosimetric analysis of radioiodines as 13 a function of the age and thyroid mass of the child, 14 and also include other medical radionuclides --

15 radioisotopes of iodine.

16 We will include at least two additional 17 references as cited by Drs. Marcus and Sabin. And we 18 will include recommendations or recommended cessation 19 periods of time based on both a 100 and a 500 millirem 20 effective dose to the nursing child.

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

22 Zanzonico.

23 CHAIRMAN ALDERSON: This is Dr. Alderson.

24 I think we should just mention that the transcription 25 errors/typos also will be corrected as recommended.

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36 1 MS. HOLIDAY: Thank you. Okay. Dr.

2 Alderson, now that there is a motion, can you call 3 for the vote?

4 CHAIRMAN ALDERSON: All right. All in 5 favor?

6 (Chorus of ayes.)

7 CHAIRMAN ALDERSON: Any opposed? (pause) 8 Hearing none, that passes unanimously.

9 CHAIRMAN ALDERSON: All right. So as I 10 stated a moment ago, I'll repeat now, it is now time 11 for us to consider the report on the physical presence 12 requirements for the Gamma Knife Icon, that 13 subcommittee report. That subcommittee is led by 14 Dr. John Suh. Dr. Suh, you're on.

15 MEMBER SUH: Okay. Thank you, Dr.

16 Alderson. I want to first thank the subcommittee 17 members, Dr. Ron Ennis and Laura Weil, and also thank 18 Sophie Holiday for her staff resource support.

19 So I will -- the charge to the subcommittee 20 was to propose the appropriate physical presence 21 requirements for Leksell Gamma Knife Icon' 22 radiosurgery units. And I just want to go through 23 just a little bit about the gamma knife. The gamma 24 knife is a very well-established treatment for 25 patients with various benign and malignant brain NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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37 1 tumors, vascular malformations, and functional 2 disorders, including trigeminal neuralgia.

3 The first gamma knife in the United States 4 was installed at the University of Pittsburgh in 5 1987, and over the years the gamma knife has evolved 6 and in 2006 the Perfexion' unit was introduced, which 7 allowed for the authorized users to be inside the 8 treatment unit.

9 And given the differences between the 10 Perfexion' versus the models U, B, and C, the 11 Perfexion' was licensed under 10 CFR 35.1000. And as 12 of the reports, based on information collected, there 13 are 77 Perfexion' units and 22 Icon' units in the 14 United States, and worldwide over a million patients 15 have been treated with the gamma knife.

16 In terms of the current physical presence 17 requirements in 10 CFR part 35, it requires an 18 authorized user with appropriate training and 19 experience in radiation oncology and an authorized 20 medical physicist to be physically present throughout 21 all treatments involving the unit. And physical 22 presence has undergone some evolution. Initially, it 23 was defined as within hearing distance of normal 24 voice, and as part of a regulatory issue summary it 25 was further defined to be speaking in a normal NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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38 1 conversational tone, not a raised voice. And they 2 made a comment that a distance of 20 feet may not be 3 close enough to adequately hear and respond to an 4 emergent situation.

5 The rationale for changing the physical 6 presence requirements is that the gamma knife unit, 7 as I mentioned, has evolved through the years. It is 8 important that any change we make allow the 9 authorized user to address an emergent situation and 10 also to verify that a correct dose was delivered.

11 If you look at the past 10 years of the 12 NMED report, there have been 10 reportable events 13 involving the Perfexion', and only a minority of these 14 events occurred during a treatment.

15 So from the Perfexion' there has been an 16 evolution to a newer unit called the Icon' system.

17 Some of the fundamental differences with the Icon' 18 system is that it does allow for the option of a 19 thermoplastic frameless mask rather than a frame.

20 The majority of centers using the Icon' system still 21 use a frame-based system rather than a mask-based 22 system. It does give the option for those patients 23 who may benefit from some type of fractionated 24 approach.

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39 1 perform integrated stereotactic cone beam CT, which 2 provides stereotactic reference for patient setups.

3 And number three is it also has a high 4 definition motion management for mask-based 5 treatments, which allows us to confirm that the 6 treatment is being delivered to the target itself.

7 There was a proposal from Elekta on 8 April 26th about the Gamma Knife Icon', and their 9 proposal is that an authorized user and authorized 10 medical physicist be physically present during the 11 initiation of all treatment involving a unit.

12 Number two is to have an authorized medical 13 physicist present throughout all patient treatments.

14 And number three is that an authorized user 15 physically be present in the department during 16 patient treatment and immediately be able to come to 17 the treatment room in case of emergency.

18 Based on the -- looking at the current 19 physical presence requirements, the evolution of the 20 Icon unit, the recommendations from the subcommittee 21 are that the authorized user and authorized medical 22 physicist be physically present during the initiation 23 of all treatments involving the Icon', and that the 24 authorized medical physicist be physically present 25 throughout all treatments of the unit itself.

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40 1 We have made a recommendation that the 2 current physical presence requirements for the 3 authorized user be modified to allow the authorized 4 user to be close enough to the console area to respond 5 quickly to any issues that may arise.

6 The definition we came up with is that 7 within a two-minute walk of the Icon console area and 8 immediately available to come to the treatment room.

9 So it is very important that with this definition of 10 physical presence, the authorized user cannot be 11 involved in another procedure that would prevent him 12 or her to come immediately to the gamma knife in case 13 of an emergency.

14 In addition, we felt that it was important 15 that we do not use the definition of a department ,

16 as "department" can have different meanings to 17 different centers. So one could be stated that it's 18 part of a department, but the department could be 19 physically a long walk away. So we felt that there 20 should be some time restraint in terms of what 21 constitutes being physical present in terms of this 22 newer definition.

23 If there is an interruption of treatment 24 secondary to a medical or mechanical event, the 25 authorized user must return to the Gamma Knife Icon' NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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41 1 console area to evaluate patient and to review any of 2 the medical -- mechanical issues along with the 3 medical physicist.

4 And at the conclusion of treatment, the 5 authorized user must be present at the Icon console 6 to discuss any treatment or patient issues with the 7 patient, physicist, and a nurse.

8 The subcommittee felt that with these 9 modifications, in terms of current physical presence 10 requirements, it would allow more flexibility to the 11 authorized user.

12 In closing, we felt that it was very 13 important that the committee report did not encroach 14 on the practice of medicine, also allowed for the 15 regulator to inspect the regulated gamma knife 16 center, and also be consistent with regulations 17 governing a physician's supervision.

18 Any change that occurs to the current 19 physical presence requirements should take into 20 account that the culture of safety quality be 21 supported, given the superb track record for quality 22 and safety with the gamma knife.

23 Thank you. That concludes my report, Dr.

24 Alderson.

25 CHAIRMAN ALDERSON: All right. Thank you.

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42 1 Are there comments?

2 MEMBER SHEETZ: John, this is Mike Sheetz.

3 I have some comments.

4 CHAIRMAN ALDERSON: Please.

5 MEMBER SHEETZ: I think the subcommittee 6 provided an excellent report and overview of the 7 technological advances in gamma knife treatment since 8 the process has become more efficient allowing for 9 more treatments, and multiple targets can be treated 10 in a single session.

11 And they pointed out, based on the small 12 number of medical events involving modern gamma knife 13 models, it is, therefore, appropriate to evaluate the 14 required physical presence requirements for gamma 15 knife to see if they should be revised.

16 Based on our experience here at the 17 University of Pittsburgh where we have had every 18 model of the gamma knife, and we were the first to 19 license the U model in 1987, I have some comments 20 with respect to the recommendations of the 21 subcommittee, if I may proceed with those.

22 CHAIRMAN ALDERSON: Please.

23 MEMBER SHEETZ: I agree with the 24 recommendation number one that the AU and AMP need to 25 be physically present at the initiation of all NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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43 1 treatments.

2 With respect to recommendation two, I think 3 the definition of "within a two-minute walk from a 4 gamma knife treatment console" will create ambiguity 5 for the regulatory compliance with licensees, and the 6 recommendation for the appropriately trained staff to 7 be present to respond to patient medical issues is 8 not really enforceable by the NRC.

9 So I would suggest consideration of this 10 recommendation to be modified to something that 11 actually is in current regulation for HDR right after 12 the initiation of treatment, an authorized medical 13 physicist and either an authorized user or a 14 physician under the supervision of an authorized user 15 who has been trained in the operation of emergency 16 procedures for response of the unit, to be physically 17 present during continuation of all patient treatments 18 involving the unit.

19 So I'll throw that up for consideration.

20 Again, it would be consistent with the HDR 21 requirements, and it would eliminate any ambiguity in 22 response times, and it would assure that appropriate 23 personnel are present to respond to any patient 24 medical issues.

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44 1 AU must return to the gamma knife console for the 2 interruption of treatment secondary to medical or 3 mechanical issues.

4 With respect to recommendation four that 5 requires the AU to be present at the gamma knife 6 treatment console at the conclusion of the treatment 7 to discuss any treatment or patient issues, if the 8 patient treatment has been completed without any 9 issues, I question whether this would be necessary.

10 And if you have eliminated this requirement, it would 11 provide greater relief to the authorized user.

12 And then the last slide on this, if the 13 subcommittee report -- not specifically saying, but 14 implies some modified physical presence requirements 15 should only be applicable to the Icon' unit when using 16 the thermoplastic mask for patient treatment and not 17 the stereotactic beam, while the Icon' utilizes an 18 integrated cone beam CT for stereotactic reference 19 and high-definition motion management systems, these 20 features are only required when using mask-based 21 treatments. They are not required for frame-based 22 treatments.

23 In our experience, less than 10 percent of 24 the gamma knife patient cases qualify for mask-based 25 treatments. There have been an extremely low number NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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45 1 of medical events with Perfexion' that have been 2 pointed out involving thousands of patient treatments 3 demonstrating a highly reliable treatment technology.

4 And so when using the Icon for frame-based 5 treatments, it is identical to the Perfexion' unit 6 for frame based. So, therefore, I would suggest that 7 the revised physical presence requirements should 8 also be applicable to frame-based treatments on 9 either the Icon or the Perfexion'.

10 And that concludes my comments.

11 CHAIRMAN ALDERSON: Thank you. Dr. Suh?

12 MEMBER SUH: Thank you, Michael, for those 13 very thoughtful comments. So in terms of your second 14 recommendation about whether or not to support the 15 physical presence requirement of the two-minute walk, 16 this is something that the subcommittee grappled with 17 in terms of what would constitute appropriate 18 physical presence requirements with the Gamma Knife 19 Icon', and the number we came up with -- initially, 20 there was some discussion about whether or not being 21 physically present in the department would be 22 adequate, and we all agreed that that is too -- that 23 is too ambiguous. So we felt that was not a good 24 starting point.

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46 1 some type of time standpoint. And I do agree with 2 you that there could be some ambiguity in terms of 3 regulatory compliance. I actually have looked at 4 your comments. I actually thought about it.

5 And thinking about the HDR model, the 6 current proposal of either an authorized user or a 7 physician under the supervision of an authorized user 8 who has been trained in the operation of emergency 9 response to the unit be physically present during the 10 continuation of all patient treatments involving the 11 unit is a better definition, in my opinion, because 12 it then allows a physician to be present at the 13 console area or within voice distance during the 14 entire treatment.

15 As you mentioned, the NRC does not regulate 16 the ancillary staff such as nursing support, so that 17 is a consideration that I am certainly open to. I 18 would be curious to see what the other subcommittee 19 members think and also the rest of the committee as 20 well on that particular point.

21 In terms of the authorized user returning, 22 I'm glad that you agree with that comment. I do think 23 it's important for the authorized user to return.

24 In terms of recommendation number four, I 25 am probably not as strong an advocate for that. I do NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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47 1 believe that the gamma knife does require an 2 authorized user to know what happened during the 3 treatment, and one of my concerns is that if the 4 authorized user does not know about the patient --

5 because, again, there could be a situation where the 6 treatment is "completed," but things may not have 7 gone as planned. And I think this is an opportunity 8 for the authorized user to deal with the medical 9 physicist to ensure everything has occurred 10 correctly.

11 Also, from a patient care standpoint, 12 having the authorized user there to let the patient 13 know that everything went well I think is a greater 14 assurance in terms of that the treatment actually did 15 go according to plan rather than having a surrogate 16 physician who has been trained to say, well, 17 treatment went well.

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

22 In terms of number five, in terms of 23 whether or not the Icon' and the Perfexion' are 24 similar units, although the fundamental makings of 25 the Icon' are very similar to the Perfexion' unit, NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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48 1 there is the opportunity to use a cone beam CT device 2 for the frame-based treatments.

3 What I can share with you is that at our 4 institution about 20 percent of our patients are 5 undergoing frame-based treatments right now, 6 typically up to five treatments sessions. And for 7 our functional cases and for those cases that we --

8 we have actually started to use the cone beam CT to 9 ensure that the alignment of what we saw on the 10 computer screen aligns with the frame attached to the 11 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' 15 and Icon'. I would propose that we change the 16 physical presence requirements for just the Icon' unit 17 itself.

18 MEMBER ENNIS: This is Ron. Just to follow 19 up, being on the subcommittee, my thoughts to Mr.

20 Sheetz's comments. So in terms of the ambiguity of 21 the two-minute walk, well, certainly, there is a 22 little bit of ambiguity with that, although I don't 23 think it will be a lot because it does specify a time 24 which you can measure and walk. And of course people 25 can walk slightly faster or slower, but I don't think NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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49 1 it's tremendously ambiguous.

2 So I'm comfortable with that. The notion 3 of instead requiring another physician to be there 4 under the supervision, I would be comfortable with 5 that, too. That is more restrictive on our users, I 6 think, than the proposed definition that our 7 subcommittee came up with.

8 And I think part of our charge was to see 9 whether we could provide safe relief to the 10 authorized user. So I don't know that our 11 constituents, if you will, or the people asking for 12 some relief would feel that we have provided any 13 relief with that. We could maybe hear what those 14 constituents had to say.

15 But I am comfortable with either, but I do 16 feel like what is written in the subcommittee report 17 is kind of aligned with providing some level of relief 18 while still being, you know, conservative in terms of 19 patient safety.

20 In terms of the other issues, the return at 21 the end I feel is an important component to this as 22 well. In my mind, it's kind of akin at the end of a 23 brachy procedure, kind of -- although we're not 24 requiring formal documentation, that the authorized 25 user documents that everything went as planned, or, NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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50 1 if not, what kind of changes.

2 I do feel like it's really important to 3 close that loop. More subtle things that aren't quite 4 events might not be raised or you might forget about 5 them an hour later when you see each other in the 6 hall. But at that moment, the physicist and/or the 7 nurse or whoever might be there might be able to share 8 some issue about slight patient movement or things 9 like that that could be safety concerns that I think 10 will be lost if there is not that closure at the end.

11 In terms of the nurse issue, and whether 12 it's appropriate for these guidelines or not, I can 13 kind of certainly see the perspective that it's not 14 something NRC can regulate or does regulate, so it's 15 not appropriate for our subcommittee report. On the 16 other hand, it seems like a good practice advice.

17 I don't have a good sense of whether good 18 practice advice like this is appropriate or not. I 19 would turn to NRC staff for their comments on that.

20 It feels like a good idea to me, but I do get the 21 argument that it's a little bit more medical than 22 regulatory.

23 And on the final point of Perfexion' versus 24 Icon', frankly, I would defer to Dr. Suh's judgment.

25 He has a lot more experience with these units than I.

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51 1 So I don't have any particular opinion beyond his on 2 that.

3 I think I covered all the points. But if 4 there is something else, Mr. Sheetz, please remind 5 me.

6 MEMBER SHEETZ: This is Mike Sheetz. Thank 7 you for your consideration and responding to those -

8 - all of my comments.

9 So I guess, for clarity, you are 10 recommending these revisions for the Icon' unit for 11 both frame-based and mask-based treatments. Is that 12 correct?

13 MEMBER ENNIS: That is correct. Yes.

14 MEMBER SHEETZ: Okay. The other comment is 15 we -- we do use the cone beam CT with frame based as 16 a replacement for the MRI or co-registration. But 17 otherwise, if we have a frame and an MRI image, we 18 would not repeat the cone beam CT, you know, as a 19 secondary check. And I'm not sure that's standard.

20 So, again, I guess I still go back to frame-21 based treatments on Icon' and Perfexion' are identical 22 in practice.

23 MR. OUHIB: Hi. This is Zoubir.

24 CHAIRMAN ALDERSON: Go ahead.

25 MR. OUHIB: On item number two, you know, NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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52 1 trying to use the HDR regulation type of thing, I 2 think it's a good idea. However, there are 3 institutions that might not be as fortunate to have 4 the luxury of a physician under the direct 5 supervision of an authorized user.

6 So perhaps consideration would be to use 7 one or the other; in other words, to keep the two-8 minute option and perhaps -- or the presence of a 9 physician under the direct supervision of an 10 authorized user.

11 CHAIRMAN ALDERSON: Are there further 12 comments? Is there anyone that would like to comment 13 on that statement?

14 MEMBER SUH: This is John Suh. So I can 15 see both points. So in terms of being less 16 restrictive, the two-minute walk from a gamma knife 17 treatment console area is certainly less restrictive.

18 Again, as Ron mentioned, you know, one can walk faster 19 or slower, but, again, I think if someone says two 20 minutes, that's something that the authorized user 21 could work with in terms of what is considered a two-22 minute walk. Physicians would need to decide what 23 constitutes that as a safety parameter.

24 You know, in terms of this proposal of 25 either an authorized user or physician under the NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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53 1 supervision of authorized user be present, it does -

2 - it's probably a clearer definition, although it is 3 somewhat more restrictive. And for a smaller center 4 that may not have the luxury of having another 5 physician involved, I can see this being a more 6 restrictive definition for gamma knife.

7 Not all gamma knife centers have multiple 8 physicians who are: a) trained, and b) have an 9 interest in being involved in gamma knife.

10 In terms of doing both, I guess I have mixed 11 feelings about whether or not both is a good option.

12 I think we should stick with one option if we are 13 going to go ahead with changing the current physical 14 presence requirements, which was the charge of the 15 subcommittee to begin with.

16 CHAIRMAN ALDERSON: Further comments? I 17 think we still need to work to clarify this a bit.

18 I'm going to take the prerogative here to indicate 19 what I think is being said, and then I'd like to get, 20 John, your comments and that of the Committee to 21 clarify this.

22 So I am hearing that regarding the comment 23 of extending this new approach to both the Icon' and 24 the Perfexion', I believe that the Committee is saying 25 that it would choose to stay with the Icon' alone, NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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54 1 that there should be -- the physician should be 2 present at the end of the treatment, so that they can 3 talk to the patient.

4 Am I correct on the Committee's position on 5 those two issues?

6 MEMBER SUH: This is John Suh speaking 7 again. Yes, I do believe that the Icon' and Perfexion' 8 are different units.

9 CHAIRMAN ALDERSON: Yes.

10 MEMBER SUH: And your second point about 11 being present at the conclusion of treatment, like 12 Ron, I feel very strongly that it is important to 13 close the loop when treating patients with high 14 dose/high precision radiation that is offered with 15 the Icon' Gamma Knife unit.

16 CHAIRMAN ALDERSON: Right. Am I correct 17 that Dr. Ennis and Laura Weil agree with those 18 positions?

19 MEMBER ENNIS: This is Ron. So just to 20 clarify, on the second position of being there at the 21 end, I agree with the position. But to clarify the 22 rationale, for me, it's not just about the patient -

23 - you know, good for the patient, the patient will 24 like that, and all that, which I totally agree, but 25 that's really a medical thing.

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55 1 But I do feel like there could be more 2 subtle or minor safety concerns, issues that might 3 have happened that would not stop the treatment and 4 would not be a misadministration, but might be 5 helpful for the team to know going forward for the 6 next case or the next patient, where things weren't 7 perfect, that it's really important to have that kind 8 of -- well, they call it a huddle nowadays, right?

9 Doing essentially a mandated huddle from a safety 10 point of view at the end of treatment, which will 11 only really happen efficiently and effectively, in my 12 opinion, if we mandate that everyone gets together at 13 the end.

14 CHAIRMAN ALDERSON: Yes. Good. Any 15 disagreement with that from Dr. Suh or Ms. Weil?

16 MEMBER WEIL: No.

17 MEMBER SUH: No.

18 CHAIRMAN ALDERSON: Okay. So I think that 19 we have resolved those two issues in terms of the 20 committee's response to the comments. And that 21 leaves us with the comment regarding the two-minute 22 walk versus someone, being the AU or an AU-trained 23 person, being physically present at all times.

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56 1 particular concern, which seems to be the significant 2 one remaining in this discussion.

3 MEMBER SUH: So I have been thinking about 4 this since, you know, Michael sent this to me. As I 5 said, I am -- I like his suggestion, but I do agree 6 that it is more restrictive. And, again, it should 7 be very apparent. You know, a two-minute walk I don't 8 think should be that ambiguous in terms of responding 9 to an emergency or if there is an issue with a 10 patient.

11 But my personal feeling, my recommendation, 12 is that the subcommittee report of the altered 13 current physical presence to allow for the authorized 14 user to be within a two-minute walk of the gamma knife 15 console area is appropriate and will allow the 16 authorized user to respond to any immediate medical 17 needs.

18 CHAIRMAN ALDERSON: Okay. Good. That's 19 definitive. Do Dr. Ennis and Ms. Weil agree?

20 MEMBER ENNIS: I do.

21 CHAIRMAN ALDERSON: Laura?

22 MEMBER WEIL: Yes, I do.

23 CHAIRMAN ALDERSON: Okay. So that's also 24 clear from the standpoint of the subcommittee. Are 25 there other comments before we open this up to people NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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57 1 who might be on the phone lines?

2 So with the help of the operator, we will 3 now take comments on any of these issues from people 4 who are on the phone?

5 OPERATOR: Thank you. And, again, as a 6 reminder, if you have a question or a comment from 7 the phone, please press star one at this time. Make 8 sure your phone is unmuted and record your name to 9 introduce your question. And to withdraw that 10 request, you may press star two. Once again, for 11 questions or comments, press star one and record your 12 name at this time.

13 And one moment. We'll stand by for 14 questions or comments. One moment, please. And we 15 do have a question or comment from Susan Lohman. Your 16 line is open.

17 MS. LOHMAN: Thank you. This is Susan 18 Lohman. I am neuroscience applications manager with 19 Elekta. And, first, I'd like to thank the 20 subcommittee for their long and thorough review of 21 this issue, the process that they have gone through.

22 And at this time, I would like to urge the 23 subcommittee and Committee to move forward with the 24 subcommittee's recommendation as it was proposed and 25 possibly in the future come back to look at the NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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58 1 inclusion or continued exclusion of Perfexion'.

2 And myself, as a representative of Elekta, 3 would be more than willing to provide any subject 4 material necessary to proceed as such.

5 Thank you.

6 CHAIRMAN ALDERSON: Do we have other 7 comments?

8 OPERATOR: Yes, we do have another question 9 or comment. And our next question or comment is from 10 Frank Tran. Your line is open.

11 MR. TRAN: Yes. This is Frank Tran in 12 Region III, NRC. I have a comment on the rule with 13 the HDR of exactly they -- they didn't require direct 14 supervision from an authorized user or a trained 15 person. It just says under supervision. So I believe 16 the key is not that. So I just want to comment on 17 that.

18 CHAIRMAN ALDERSON: This is Dr. Alderson.

19 I'd like to ask the commenter to repeat some of what 20 he said, because I don't know how other -- I didn't 21 actually hear all those words very clearly.

22 MR. TRAN: Okay. So earlier I believe that 23 Mike mentioned about the rule under -- that required 24 authorizer user to be -- or a trained person to be 25 present over the -- under the rule for the HDR.

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59 1 Another person mentioned that there should be direct 2 supervision.

3 However, under the rule for the HDR, it is 4 not a direct supervision, just a supervision, either 5 direct or not direct. So there's the comment for 6 that.

7 CHAIRMAN ALDERSON: All right. Did people 8 understand the comment?

9 PARTICIPANT: Yes.

10 CHAIRMAN ALDERSON: Okay. Are there 11 further comments?

12 OPERATOR: I am currently showing no 13 further questions or comments at this time. And, 14 again, as a reminder, that is star one. Make sure 15 your phone is unmuted and record your name. And it 16 is star two to withdraw that request.

17 Again, for further questions or comments at 18 this time, please press star one and record your name, 19 and I'll stand by for further questions or comments.

20 CHAIRMAN ALDERSON: So, Dr. Suh, I'm going 21 to summarize here how I think this conversation has 22 evolved. I think we have listened to all of the 23 comments. We have made comments in return. I believe 24 that we're at the point where we are ready to accept 25 the proposal as it was originally recommended. Is NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

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60 1 that how you also understand the comments?

2 MEMBER SUH: Yes, Dr. Alderson.

3 CHAIRMAN ALDERSON: Okay. Well, in that 4 case, are we in fact ready to -- is the subcommittee 5 and the -- are the ACMUI members ready -- to accept 6 the report as it was originally proposed? All those 7 in favor?

8 (Chorus of ayes.)

9 CHAIRMAN ALDERSON: Any opposed? Thank 10 you. This report is accepted in its original proposed 11 form.

12 MS. HOLIDAY: Dr. Alderson, if I may, I'm 13 sorry, I didn't catch who made the motion and who 14 seconded the motion.

15 CHAIRMAN ALDERSON: I believe it was 16 implied that Dr. Suh was making the recommendation, 17 I believe.

18 MEMBER SUH: Yes. On behalf of the 19 subcommittee, I propose that we accept the current -

20 - sorry, the physical presence requirements of the 21 Leksell Gamma Knife Icon' as submitted on behalf of 22 the subcommittee members.

23 VICE CHAIRMAN ZANZONICO: Sophie, this is 24 Pat. I'll second it.

25 MS. HOLIDAY: Thank you.

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61 1 CHAIRMAN ALDERSON: Good.

2 MS. HOLIDAY: And then, if I understand, 3 was this a unanimous endorsement, or were there any 4 dissentions or abstentions?

5 CHAIRMAN ALDERSON: I did ask for that, I 6 believe, and it is a unanimous endorsement.

7 MS. HOLIDAY: Okay. Thank you.

8 CHAIRMAN ALDERSON: So is there any other 9 business that we need to conduct this morning?

10 MS. HOLIDAY: No. I would just like to 11 thank the subcommittee members for putting forth all 12 of the effort for both Dr. Metter's subcommittee and 13 Dr. Suh's subcommittee, for their thorough reviews 14 and their reports. I would also like to remind the 15 ACMUI members and other participants on the phone 16 that ACMUI will be holding another public 17 teleconference in two weeks on March 1st from 18 2:00 p.m. to 4:00 p.m. eastern.

19 The topic of that teleconference will be 20 the subcommittee report for the training and 21 experience requirements under all modalities in 22 10 CFR part 35 with a focus on 35.300 uses.

23 The ACMUI will also be holding their spring 24 meeting here at NRC headquarters on March 7th and 25 8th.

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62 1 Thank you.

2 CHAIRMAN ALDERSON: Well, thank for 3 everyone who was on the call today.

4 Mr. Bollock, anything you would like to say 5 in the end?

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

7 Appreciate everyone's time.

8 CHAIRMAN ALDERSON: I believe, Sophie, that 9 we have concluded our business. Thank you all, 10 everyone.

11 (Whereupon, the discussion of the draft 12 report concluded at 10:19 a.m.)

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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."

1

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 2

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.

3

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 4

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:

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.

SNMMI has reviewed the draft on Nursing Mother Guidelines for the Medical Administration of Radioactive Materials. We believe this is an excellent first draft, however, there are some few errors that should be corrected.

First, while not an error, the benefits of breastfeeding to the infant and to the mother should be mentioned.

Specific gamma ray constants are markedly incorrect, and should be:

• 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