ML20081G156

Discussess Historical Info on Approval Process for Use of Mit Research Reactor Medical Beam Therapy Facility

ML20081G156
Person / Time
Site:	MIT Nuclear Research Reactor
Issue date:	06/06/1991
From:	Bernard J MASSACHUSETTS INSTITUTE OF TECHNOLOGY, CAMBRIDGE
To:	NRC OFFICE OF INFORMATION RESOURCES MANAGEMENT (IRM)
References
NUDOCS 9106120266
Download: ML20081G156 (9)

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8 NUCLEAR REACTOR LABORATORY h, ,.N AN INTERDEPARTMENTAL CENTF.R OF MASSACHUSETT S INSTITUT E OF T ECHNOLOGY OK HARUNG 138 Aba y S9eet Camtroge, Mass 02139 J A BERN ARD .R Dwecto, Te.e'as No i6 t h253- 7300 Dacctor of Aca:ty Opeatoes Te'en No 9214g, g g*g Tel No c6171 June 6,1991 U.S. Nuclear Regulatory Commissic-Washington, DC 20555 Attn: Document Contml Desk

Subject:

Historical Inturmatio,. on Soproval Process for Use of MIT Research Reactor Medical Beam herapy Facu..y Gentlemen:

This letter is submitted in response to the request of the NRC's Gmce of Nuclear Reactor Regulation (Project Manager, Standardization and Non Power Reactor Project Directorate) for historical information on the approval process for use of the MIT Research Reactor Medical Beam Therapy Facility. This material is submitted as an item of information and not as the result of any specific regulation. In reviewing the information contained herein, reference should be made to our communications of 3 April 91 and 16 April 91. The former outlined 3 resent practice at MIT for obtaining approval to use neutron beams for patient therapy; the ,atter summarized the history of the 1960-1962 patient trials at MIT.

Two MIT and several hospital committees had jurisdiction over the approval process for the 1960-1962 trials of neutron capture therapy at the MIT Research Reactor.

This letter provides information on only the MIT committ.9s which were the Committee on Reactor Safeguards and the Biomedical Advisory Committee. The former is, as NRC is well aware, still active. The latter is not. Its functions are now pe-fermed by the MIT Committee on Radiation Exposure to Human Subjects, the MIT Radiation Protection Committee, and the MIT Committee on the Use of Humans as Experimental Subjects.

(Nme.: Please refer to our letter of 3 April 91 for the specific functions of these committees.) Records of the Reactor Safeguards Committee are on file at the MIT Research Reactor. The official records of the MIT Reactor Biomedical Advisory Committee are missing and a search of both the MIT libraries and archives has failed to locate them. De information coritained in this letter is based on an unofficial and possibly iricom? lete compilation that was kept by an individual member of the committee. Appendix A to tais letter lists the available documents. Appendix B gives a retyped copy of the original Charter of the MIT Reactor Biomedical Advisory Committee.

In addition.to searching for documents, both Dr. Sweet and Dr. Brownell were contacted relative to the regulations that may have governed the 1960 trials of neutron capture therapy. Dr. Sweet directed the 1960 trials of neutron capture therapy at the MIT 9106120266 910606 PDR ORG EEIMTT ,

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U.S. Nuclear Regulatory Commission 4 Page 2 Research Reactor. Dr. Brownell has conducted much research in this field. Incider, sily, botl) are still very active in their respective fields. Both indicated that the approval process waMjt(rely a function of MIT and hospital (Massachusetts General) committees.

Given here is a summary of the contents of the documents contained in Appendix A to this letter. The empha.;is is on regulatory considerations. l l

1) On 10 May 1957, the MIT Radiation Protection Of0cer wrote to the Reactor Director concerning the need for manual operation of the MIT Reactor Medical Therapy Room's door from the inside. Ile cited the following regulations as supporting this requirement:

i) From Title 10 - Atomic Energy, Chapter 1 - Atomic Energy Commission, Part 20- Standards for Protection against Radiation, Section 20.101,

" Exposure to individuals in restricted areas - (a) Exposure to radiation (1) Except as provided in subparagraph (2) of this paragraph, no licensee shall possess, use, or transfer licensed material in such a manner as to cause any individual in a restricted area to receive in any period of seven consecutive days from radioactive materials and other sources of radiation in the licensee's possession a dose in excess of the limits specined in Appendix A of this part."

ii) From the New York State Code - The Industrial Code, Rule No. 38,

" Radiation Protection," Board of Staridards and Appeals, Department of Labor, State of New York, Section %-5.8, " Doors from Shielded Enclosures.

Shielded enclosures of radiation areas with access openings large enough for the entry of personnel shall have at least one exit door easily and quickly openable manually from the inside."

The reason for quoting the New York State Code was that Massachusetts was at that

time considering adopting a similar statute. The door to the MIT Reactor Medical Room Facility has ever since met and presently does meet the above requirement.

21 On 22 March 1958, a charter was prepared for the MIT Reactor Biomedical Advisory Committee (see Ap aendix B to this letter). Also, a description of the Medical Herapy Room was issued. 'entures noted in that description are retained in the room's present ecnfiguration which is given in Section 10.13 of MIT Research Reactor's current Safety Analysis Report. (Note: Refer to our letter of 3 April 1991 for a copy.)

3) On 13 April 1960, Dr. W. H. Sweet formally requested approval for use of the medical therapy room for three purposes. Dese were neutron capture therapy for brain tumors, treatment of pituitary gland disorders with a form of neutron capture therapy, and the treatment of cephalic neoplasms by perfusion of the head with radioisotopes.

Dr. Sweet's request had been previously approved at the Massachusetts General Hospital (MGH) by its Surgical Executive Committee, its General Executive Committee, and its Board of Trustees. Dr. Sweet's letter of application notes that

". . the prospective program is to be laid before a group of eight members of the Atomic Energy Commission from 9 a.m. until 2 p.m. on 21 April 1960... in the pathology conference room of the Warren Building at MGH." No regulatory issues were raised in Dr. Sweet's letter. Ir' f.hct, the only issues raised were those of medical 4

liability. No record of the meeting with the AEC is presently available. Also, Dr.

Sweet does not recall the meeting.

U.S. Nuclear Regulatory Commission

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4) On 2 June 1960, the MIT Reactor Biomedical Advisory Committee approved the first two of Dr. Sweet's three requests. A requirement was imposed on the neutron capture therapy trials for brain cancer (Request #1) that " animal experiments be conducted to test out the adequacy of the radiation dose measuring devices contemplated for use." (Epic: Efficacy trials of neutron cap re therapy using animal models are an integral part of the present MIT program.)

5) On 8 June 1960, the MIT Reactor Biomedical Advisory Committee issued a draft summary of the legal aspects of the medical uses of the MIT Research Reactor. Most of the issues raised concerned medicalliability and the respcasrailities of the t.ospital (not MIT) for patient transportation. Of possible regulatory interest were the j following:

a) Non-licensed personnel (the attending physician) should be qualified for operation of the medical therapy room's controls.

b) A procedure should be established for use by the physician.

These requirements are still in effect at MIT. Reactor Administrative Procedure l PM 1.10.10 covers qualification of non licensed personnel for ase of the medical  :

therapy facility, it also describes the protocol for use of the room. l 1

6) On 22 June 1960, the MIT Reactor Biomedical Advisory Committee approved the third of Dr. Sweet's three requests. The approval contained nothing rel:vant to neutron capture therapy or to the use of beams for medical purposes.

7) On 18 July 1960, a guideline was circulated for the selection of human volunteers in experiments at MIT involving either radioactive materials or radiation exposure.

Paragraph Ore of that procedure is of regulatory interest and is therefore cited here in full:

"A committee will be appointed by the Medical Director to pass on any proposed experiment. The approval of the A.E.C. will be sought after the Medical Department Committee acts. It is to be understood that the Radiological Safety Officer and the secretary of t',e M.I.T. Radiation Protection Committee will always serve with this committee."

The other paragraphs of this procedure concern only medical liability issues. No records are on file concerning the 'AEC appreval' mentioned in the above paragraph.

It is not clear if this guideline was ever adopad. In any event, patient selection criteria are now far more rigorous.

8) On 28 July 1950, a procedure was issued for the taking of cultures from the medical therapy room. The intent was to be certain of medically hygienic conditions.

9) On 10 August 1960, a form entitled " Irradiation Reque:;t for Medical Use of MIT Reactor" was circulated. Most of the form is devoted to medical liability issues.

However, it also required that medical personnel agree to abide by the reactor's working and safety regulations. This requirement remains in effect and is currently a condition agreed to oy any experimenter prior to his or her being issued a reactor access card and dosimeter.

U.S. Nuclear Regulatory Commission o Page 4

10) On 24 August 1960, the MITR Staff issued a memo in which the legal aspects of medicalirradiations were summar; zed. Input to this memo was solicited from both Dr. Sweet at MGli and Dr. Exc Farr, Medical Director r' Se Brookhavea National Laboratory (BNL). ne following appear to be relevant:

a) Dr. Sweet was operating under an AEC contract at the time of the 1960-1962 trials of neutron capture therapy, b) Dr. Fanr, whose organization had already done trials of neutron ca ature thera ay at its reactor, said (and here the memo is quoted), "that notiing has xen pmmulgated on this subject and there are no stated legal requirements which have to be met. The AEC is aware that MIT (and others) are doing or planning this type of work but has issued no regulations." Dr. Farr went on to say that the physician was responsible for patient treatment, for determining the dose that shonid be administered, and for specifying how that dose should be delivered.

The reactor's responsibility was to know accurately the dose given. Specifically, the reactor facility had an obligation to:

Exercise care and prudence in dose delivery.

-- Eliminate undesired radiation whenever possible.

Be certain of the neuuun spectra and the gamma exposure levels.

,Be capable of correlating beam strength with reactor power or other mstruments.

It should be noted that relative to the present MIT medical progmm, great care is being exe4cised in these areas. For example, MIT and BNL have each measured the other's beam and dosimetry experts are being asked to convene at MIT to review the MIT measurements.

1!) On 25 August 1960, a formula for a disinfectant for the medical facility was issued.

12) On 10 January 1961 Dr. W. H. Sweet wrote a letter to the Reactor Director in which he amplified his earlier irradiation request. Specifically, he provided an oatline of the major steps in the neutron captum therapy process. No regulatory issues were raised.

13) The last item in the MIT Reactor Biomedical Advisory Committee file is a copy of the form used to authorize non licensed personnel to operate the medical room controls.

This has since been supplanted by a far more detailed qualification card (MITR PM

1. id.10).

l 14) On 18 December 1961, the MIT Reactor Safeguards Committee (MffRSC) approved l MIT Reactor Experiment Safeguard Report No.14, ' General Use of the Medical Therapy Room and Beam Irradiation Facility.' (The findings of this report were reaffirmed by the MITRSC following the modification of the MIT Research Reactor in the early 1970s.) The report's major findings anc or mquirements were:

l a) Use of the medical facility cannot cause a direct safety problem to the reactor.

l De facility's only effect is the reactivity associated with cycling of the water shutter. T' tis effect is small, b) Proper control must be exercised of the medical fa::ility in order to ensure that radiation exposure limits are not exceeded.

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U.S. Nuclear Regulatory Commission i Page5 c) Non licensed personnel who wish to use the facility should first be instructed in radiation protection procedures, operation of the medical room controls, the process of experiment approval and scheduling, and ase of the reactor intercom.

d) A record is to te kept of all non licensed personnel qualified to use the medical room facility, e) Medical use (presumably involving humans) of the reactor's medical room must be approved by the MIT Reactor Biomedical Advisory Committee. All other types of experiments will be subject to only the standard review process, f) The medical room radiation monitor, position alarm on the facility door, and intercom (or their equivalent in function) shall be operable.

15) On 10 August 1973, a memo war, sent to the MIT Reactor safeguards Committee notifying that group of a possible near tenn use of the medical therapy room for neutron capture therapy. That use did not materialize. Nevenheless, the memo is of interest because it refers to a technical specification that required the Biomedical Advisory Committee. Acccrding to the memo, the specification gave the functions of i the MIT Reactor Biomedical Advisory Committee as: )

I "To review the biomedical experiments using reactor products and l irradiation facilities at the reactor from the point of view of provision of maximum safety to investigators, patients, or any human beings on whom tracer experiments, diagnosis, or therapy is to be perfonned."

"To consider the justification of the use of the reactor for the proposed i biomedical experimems."

This requirement, with different wording, was Erst established in July 1965 when it l appears that the original MIT Research Reactor's technical specincations were nrst issued (see letter dated 8 July 1965 from T. J. Thompson to Dr. Morris Mann, US AEC Task Force on Technical Specifications). Accordingly, this requirement was not in effect at the time of the 1960-1962 trials. (Note: No reactor was using technical sxcifications at that time. The technical specificatica concept originated with Dr. Tacos J. nompson, who was the Designer and first Director of the MIT Research Reactor and later an Atomic Energy Commissioner.) Also this requirement was not part of the MIT Research Reactor's technical specifications when they were reissued in their entirety following the redesign of the reactor in the early 1970s. The basis for its deletion is not known. Ilowever, one possible reason is that the specifications were written to comply with promulgated guidance and that guidance did not include medical usage. Were this specification to be in effect at arcsent,it would be ineffective because it is too broad to be practical. For examp'e, does it cover reactor products in general or only reactor products at the reactor? The wonling is sufficiently vague to allow either interpretauon. The former meaning would be most impractical because biomedical use of the MIT Research Reactor is extensive and growing with isotopes supplied to many local area hospitals. An MIT committee would have neither the time nor the authority to oversee all such uses. The present system under which materials made at MIT are tran:ferred to the byproduct license of the recipient is preferable because the recipient's oversight committ:es are then responsible for the safe use of the material, if a specification of this type were to be reinstituted today, its scope should be clearly limited to the on-site use of the MIT Research Reactor's irradiation facilities. The use of reactor produced byproduct

U.S. Nuclear Regulatory Commission i Page 6 material either elsewhere at MIT or at another organization should not be considered as a reactor tes pnsibility once that material has been proper;y transferred to another licensee. Another issue that warrants noting with regard to any consideration of such a technical specification is that reactor personnel and investigators are govemed by the 10 CFR 20 radiation exposure limits. Patients are not, in fact, those undergoing neutron capture therapy (NCT) for glioblastoma multifonne (the most virulent form of brain cancer) will require doses to tumor of grhaps 4000 RBE cGy. (Noic: That figure may seem high to those unfamiliar with the treatment. It should be realimi that a major advantage of NC r is that dose is localized in the cancerous cells because a neutron beam is used to fission boron that is localized in those cells. Adjacent healthy cells are spared. With conventional X-ray therapy, all cells are equally irradiated.)

The above completes our response to the request from the NRC's Office of Nuclear Reactor Regulation for infonnation on the approval process used for the 1960-1962 trials of neutmn captured therapy at the MIT Research Reactor. As regards our use of a neutron beam for patient therapy, we are still of the opinion given in our letter of 3 April 1991.

Namely, the MIT Research Reactor is licensed under both $0.21(a) and 50.21(c) of 10 CFR and hence the use of a neutron beam for medical therapy is allowed. Moreover, an internal administrative structure with the expertise and authonty appropriate to review the design and us: of such a beam for medical therapy is in place and functional. Finally, the mechanisms exist and are operative whereby NRC may monitor decisions made conceming the design and use of this beam. For these reasons, we de, not feel that furtbr regulation by NRC of MITfrufts NEMC's planned use of a neutron therapy beam is necessary.

Sincerely, cL Q A -

Iohn A. Bernard, Ph.D.

Director of Reactcc Operations MIT Research Reactor JAB:DKE Enclosures cc: USNRC - Dr. J. Glenn, Medical and Commercial Use Safety Branch USNRC - Region 1 - Radiation Specialist Division of Radiation Safety and Safeguards USNRC - Project Manager, Standardization and Non-Power Reactor Pmject Directorate Chairmen, MIT/rufts-NEMC Committees on Medical Uses of Radiation l

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e Al-i Annendlyd List of Avallnble Documents Pertaining to NCT Trials at MIT in 1960-1962

1. Memo on mant.al operation of MIT Reactor Medical Therapy Room door dated 05/10/57.

2. Description of MIT Reactor Medical Therapy Room and Charter of MIT Reactor Biomedical Advisory Committee dated 03/22/58.

3. Request by Dr. William 11. Sweet (Harvard Medical School and Massachusetts General llospital) for use of the MIT Reactor Medical Therapy Room for patient therapy dated 04/13/60. Approval was requested for three separate medical protocols. These were neutron capture therapy, a pituitary gland treatment, and the treatment of cephalic neoplasms. (Hg.ig: Document is in poor condition, would require transcribing in order to obtain a copy.)

4. Approval from MIT Reactor Biomedical Advi:,ory Committee of Proposals #1 and #2.

(of the 04/13/60 request by Dr. Sweet) dated 06/02/60. (Neic: Approval refers to a meeting held 05/03/60; but no minutes are available.)

5. Draft memo summarizing legal issues in use of MIT Reactor Medical Therapy Room dated 06A)8/60.

6. Approval from the MIT Reactor Biomedical Advisory Committee of Proposal #3 (of the 04/13/60 request by Dr. Sweet) dated 05/22/60.

7. Guidelines for identifying potential human volunteers for experiments at MIT involving the use of radioactive materials dated 07/18/60.

8. Memo on the taking of cultures from the MIT Reactor Medical Therapy Room dated l 07/28/60.

9. Form entitled ' Irradiation Request for Medical Use of MIT Reactor' dated 08/10/60.

His includes statements limiting liability and a patient release form.

10. Staff memo outlining MIT understanding of regulatory requirements for medical uses of isotopes and humans dated 08/24/60.

I1. Chemical composition of disinfectant used for MIT Reactor Medical Therapy Room dated 08/25/60.

12. Letter dated 01/10/61 from Dr. William H. Sweet that supplemented material contained in his irradiation request of 04/13/60.

13. Certification form for non-licensed personnel to utilize the MIT Reactor Medical Facility (no specific date).

14. MIT Reactor Experiment Safeguard Report No.14 on ' General Use of the Medical Therapy Room and Beam Irradiation Facility' dated 12/18/61.

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15. Staff memo dated 08/10/73 which addressed possible renewed use of the MIT Reactor Medical Therapy Room. This contains a brief review of the procedures followed for the 1960-1962 trials of neutron capture therapy plus a reference to a technical specification requiring review of medical experiments by a Biomedical Advisory Committee.

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Anoendix B Charter of the MIT Reactor Biomedical Advisory Committee (03/22/58)

The ultimate responsibility for the perfomiance and conduct of biotaedical experiments at the MIT Reactor rests with MIT. However, since MIT is not a medical school, a committee has been fonned to act in an advisory capacity for the review and l approval of biomedical experiments to be conducted at the reactor. l This committee, the MIT Reactor Biomedical Advisory Committee, is composed of representatives from the three medical schools in the area, Boston University School of Medicine, Harvard Medical School, Tufts Medical School, and representatives from MIT.

The functions of the committee are:

1. To review the biomedical experiments using the reactor products and irradiation facilities at ti reactor from the point of view of provision of maximum safety to investigatnra, stients, or any human beings on whom tracer experiments, diagnosis, or therapy is to be perfonned.

2. To co,nsider the justification of the use of the reactor for the proposed biomedical expenments.

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3. To acquaint the research and clinical groups in the surrounding area of the l potentialities of the reactor and to encourage the use of reactor products and 1 trradiation facilities by these groups at the reactor.  !

Proposals for biomedical experiments to be conducted at the reactor are to be submitted to the committee for review and approval. After review and formal approval of the proposal by the committee, the aroposal will be submitted to the MIT Medical Department (Dr. James M. Faulkner, Jirector) for approval. The proposal will then be referred to the director and operating staff of the reactor project for furmer review and iinal approval.

Use of reactor products and irradiation facilities at the reactor for biomedical experiments involving human beings will not be authorized by the reactor project without the prior appmval of the advisory comndttee and of the MIT Medical Department.

The advisory committee was formed early in 1957. The non-MIT members we c appointed to the committee by the deans of the respective medical schools at the request of Dr. James M. Faulkner, Director, MIT Medical Department. The present membership of l

the committee is as follows:

l Dr. Arthur K. Solomon, Chaimian l

Associate Professor of Biophysics, Harvard Medical Schcol: Consultant in Biophysics, Peter Bent Brigham Hospital; Coasultant, Los i lamos Scientific Laboratory Dr. Constantine Maletskos, Secretary Radiation Biophysicist, Massachusetts Institute of Technology Medical Department:

Radiatior. Protection Officer, Massachusetts Institute of Technology Reactor; Research Physicist, Radioactivity Center, Department of Physics, Massachusetts j Institute of Technology 1

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D2-i Dr. Belt"n Burrows Chief, Radioisotope Sen'.ce, Boston Veteran's Administration llospital; Assistant Professor of Medicine, Boston University School of Medicine; Associate Member, Evans Memorial Laboratory; Visiting Physician, Massachusetts Memorial llospital Dr. Charles F. Emerson Associate Pmfessor of Medicine, Boston University School of Medicine; Director of llematology, Evans Memorial llospital; Associate Director, Radioisotope Laboratory, Massachusetts Memorial llospital; llematology Consultant, United States Public Health }{ospital, Brighton, Massachusetts Dr. Harriet Hardy Assistant Medical Director, Massachusetts Institute of Technology; Head, Occus.-'.ional Medical Service, Massachusetts Institute of Technology; Former Health Division Group Leader, Los Alamos Scientific Laboratory; Consultant.

Division of Biology and Medicine, Atomic Energy Commission; Consultant, Los Alamos Scientific Laboratory; Consultant, Atomic Research Center, Ames, Iowa Dr. William Moloney Clinical Professor of Medicine, Tufts; Director, Tufts llematology Laboratory; ,

Director, Clinical Laboratories, Boston City llospital l l

Dr. William Sweet l Associate Professor of Surgery. Harvard Medical School; Visiting Neurosurgeon, 1 Massachusetts General Hospital: Former Regional Consultant, Midland Region and Neurosurgeon-in-chief, Queen Elizabeth Hospital, Birmingham, England Dr. Shields Wa'ren l I

Profesor of Pathology, Harvard Medical School; Director of Laboratory , New England Deaconess Hospital; Member, Advisory Committee on Biology nd Medicine, Atom!c Energy Commission; Formerly IIead of Division of Biology and ,

Medicine, Atomic Energy Commission, United States Representative to United Nations Science Committee on Effects of Atomic Radiation Dr. Manson Benedict Professor of Nuclear Engineering, Massachusetts Institute of Technology; Head, Nuclear Engineering Division, Depart.nent of Chemical Engineering, Massachusetts Institute of Technology; Member, Advisory Committee on Reactor Safeguards, Atomic Energy Commission Ex-officio member Professor and Medical Director, Massachusetts Institute of Technology Medical Department: Former Dean, Boston University School of Medicine; Professor of Clinical Medicine, Doston University School of Medicine; Diplomat, American Board of Internal Medicine; Fellow, American College of Physicians; Vice Chairman, Council on Medical Education and Hospitals, American Medical Association l

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