C7U.S.NRCUNITED STATES NUCLEAR REGULATORY COMMISSION

Protecting People and the Environment

Part 35 Medical Events Definitions-Permanent Implant Brachytherapy

Advisory Committee on the Medical Usesof Isotopes Recommendations

James S. Welsh, M.S., M.D., FACROAdvisory Committee on the Medical Uses of Isotopes

Radiation Oncologist

April 24, 2012

Need for New Definition ofMedical Event?

* Edema or atrophy alter prostateshape or volume and affectdose calculations possiblyleading to cases beinginappropriately labeled as ME's

* 3 retracted MEs in FY2011

2

2012 ACMUI RecommendationsSource-Strength Based Criteria

* Greater than 20% of thesources fall outside of thetreatment site

3

2012 ACMUI RecommendationsDose-Based Criterion

* For normal-tissue structures" For neighboring structures the dose to at

least 5 contiguous cm 3 exceeds 150% ofthe dose prescribed to the treatment site

OR" For intra-target structures, the dose to at

least 5 contiguous cm 3 exceeds 150% ofthat structure's expected dose based onthe approved pre-implant, dose distribution

4

2012 ACMUI RecommendationsOther Existing Criteria

Or if a treatment is executed

* Using the wrong radionuclide

* Using the wrong activity or sourcestrength (>20% different from the WD)

* Delivered to the wrong patient- Delivered directly to the wrong site or

body part• Delivered using the wrong modality* Using leaking sources

5

2012 ACMUI RecommendationsWritten Directive Completion

• At completion of procedure" Document unusual aspects

6

2012 ACMUI RecommendationsWritten Directive Completion.

AU Attestation* AU should provide a statement in the WD

attesting that the permanently implantedsources have been placed in accordancewith the plan

7

ACMUI Dissenting Opinion

* Ambiguity of the term, treatment site, mayprove impractical*Dissociation of definition with potential harmto patient*Lack of distribution criterion*eAttestation may cause regulatory ambiguity

8

2012 ACMUI RecommendationsTreatment Site

Recommendation to NRC - Definition fortreatment site in 10 CFR 35.2 shouldinclude the modern concepts of GTV, CTVand PTV- Non-specific, could be GTV, CTV or PTV- AU can create written directive to volume

of choice

9

2012 ACMUI RecommendationsBunching

* AU Attestation on WD

* ACMUI Dissenting Opinion - Octants

* Post-implant imaging

10

Summary

*Need for new ME definition

92012 ACMUI Recommendations-Source-strength based criteria for treatment site-Dose based criterion for neighboring and intra-targetstructures-Other existing criteria-No change to definition of treatment site-Completion of written directive-AU attestation-Post-implant imaging and dosimetry

11

Definitions/Abbreviations° ACMUI - Advisory Committee on the Medical Uses of

Isotopes* AU - Authorized User• CFR - Code of Federal Regulations0 CTV - Clinical target volume, where microscopic

extension of disease might exist0 D30- Dose that covers 90% of CTV* GTV - Gross tumor volume, the visible or palpable target" ME - Medical Event* PTV - Planning target volume, which includes factors

such as set-up variability and patient movement inexternal beam radiotherapy and normal internal organmotion in brachytherapy and which is where the sourcesare to be within

* WD - Written Directive

12

CU.S.NRCUNITED STATES NUCLEAR REGULATORY COMMISSION

Protecting People and the Environment

Part 35 Medical Events Definitions-Permanent Implant Brachytherapy

Fundamental Concepts inPatient Advocacy

Laura WeilAdvisory Committee on the Medical Uses of Isotopes

Patients' Rights Advocate

April- 24, 2012

Defining patient advocacy

* Supporting choice

* Enabling and facilitating autonomousdecision-making via transparency, culturallyand linguistically appropriate information

* Promoting patient and public safety

" Increasing access and quality

2

Underpinnings UU Ethics

3

Underpinnings: Rights

4

Choice: Enablers and Barriers

Barriers

" Geography

" Payment issues

" Provider Bias

Enablers

* Full information

* Transparency

° Access

5

Current Issues

• Permanent Implant Brachytherapy- Medical event definition- Disclosureltransparency

• Iodine 131- Patient release instructions- Public protection

* CardioGen

6

Referenceshttp://ohsr.od.nih.gov/guidelines/belmont.htmlSchulman, K et al. "The Effect of Race and Sex on Physicians'

Recommendations for Cardiac Catheterization" N Engl J Med-1999; 340:618-626

http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics.page

Engel, KG et al. "Patient comprehension of emergency departmentcare and instructions: are patients aware of when they do notunderstand?" Ann Emerg Med. 2009 Apr; 53(4):454-461

Hobgood,C et al. "Medical errors-what and when: what do patientswant to know?" Acad Emerg Med. 2002 Nov; 9(11):1156-61.

Witman, A et al." How do Patients Want Physicians to HandleMistakes? A survey of Internal Medicine Patients in anAcademic Setting." Archives of Internal Medicine. 1996,156(22) 2565-2569

7

UNITED STATES NUCLEAR REGULATORY COMMISSION

Protecting People and the Environment

Part 35 Medical EventDefinitions- PermanentImplant Brachytherapy

April 24, 2012

Agenda

" Opening Comments- Bill Borchardt, Executive Director for Operations

- Brian McDermott, Director, MSSA/FSME

" Presentation- Ronald Zelac, Ph.D., Senior Health Physicist,

MSSA/FSME

Main Objectives ofRecommendations

" Change treatment site medicalevent (ME) criterion from dose-based to source-strength-based.

" Remove ambiguity from writtendirective (WD) and MErequirements.

3

Reasons for Change

* Authorized User physicians (AUs)can't control patient-relatedfactors.

" Use of available absorbed dosemetrics causes much concern.

" Current rule is worded towardtemporary implants.

4

Basis For CurrentRecommendations

" ACMUI revised final report.

" Stakeholder input fromworkshops and public meetings.

" ASTRO recommendations.

" OAS recommendations.

5

Recommendations,10 CFR 35.3045, Reporting MEs

* Define separate ME criteria forpermanent implant brachytherapyutilizing radioactive seeds.

* Treatment site ME if 20% or moreof implanted seeds are outsidethe intended implant location.

6

Neighboring Structures

te'mpl&te used tog-dde seed

prostatem t

p.tt.kded seed( ~ needle

7

University Hospital- 10R008 1156-01 PM

lame:SPID:.

)t. ID:

ocea-ur Date: 16/2008I

Study: PoSt Plan Average ActVariation: Defatult

Images7 67

.Preascr•ption Dose: 160.0 Qy

Source: 1-126 (6711) (NIST 99]Comment:

So:urcem: 48Antsotropy- Famtors (Pount Model)

Source A 30 0.soR UJ -.-SOomcjCA -__mta__1 At:v t 30.3_60 U[ 23S•06 nm•i 3 2I-

Cincinnati VA

Prescribed dcose= 144 Gray

13L-AA

Dose Administered= 148 Gray

DDER

4 -- P ROSTATE

Recom mendations,10 CFR 35.3045 (cont.)

• For normal tissue in neighboringstructures - ME if dose tocontiguous >5 cc exceeds 150%of the absorbed dose prescribedfor the treatment site.

9

Recom mendations,10 CFR 35.3045 (cont.)

• For normal tissue structureswithin treatment site- ME if doseto contiguous >5 cc exceeds150% of the expected absorbeddose for that tissue.

10

Recommendations,.10 CFR 35.3045 (cont.)* ME if treatment is administered:

- using wrong radionuclide;

- using wrong source strength(+1- 20%) as specified in the WD;

- with delivery to the wrongpatient;

11

Recommendations,10 CFR 35.3045 (cont.)* ME if treatment is administered:

- with implantation directly intothe wrong site or body part;

- with delivery using the wrongmodality;

- using leaking sources.

12

Recommendations,10 CFR 35.3045 (cont.)

o All of the proposed ME criteriareflect circumstances in whichthere is actual or potential harmto patients being treated.

13

Recommendations,10 CFR 35.40, WDs* Define separate criteria for

permanent implant brachytherapy

e Delete "total dose" as an optionfor completing the WD

* Replace "before completion of theprocedure"

14

Variance of recommendationsfrom ACMU I report.

e No requirement for an AUattestation on source distribution

15

Variance from ASTROrecommendations

* Inclusion of dose-based ME-criteria for normal tissues andstructures

16

Variance from OASrecommendations

* Not having a dose-based MEcriterion for the treatment site

• Having set dose threshold MEcriteria for normal tissues andstructures

17

Staff position re: its currentrecommendations

" Patient interests would beprotected.

" Physicians would be able to takemedically necessary actions.

18

Staff position re: its currentrecommendations (cont.)• NRC would be able to continue

detecting failures in process,procedures, and training plusmisapplications by AUs.

* Stakeholder input is reflected inthese recommendations.

19

Acronyms. ACMUI - Advisory Committee on the Medical Uses of Isotopes. ASTRO - American Society for Radiation Oncology• AU - Authorized Usero cc - cubic centimeter* FSME - Office of Federal and State Materials and

Environmental Management Programso ME - Medical Event* MSSA - Division of Materials Safety and State Agreements. OAS - Organization of Agreement States* SRM - Staff Requirements Memorandum* WD - Written Directive

20

Presentation of Chris Timmerman, OASNRC Commission Meeting on April 24, 2012

Good morning Chairman Jaczko and Commissioners, I am pleased to be here

today representing the Organization of Agreement States and briefing you on the

Organization's position on the Part 35 Medical Definition as it pertains.to

permanent implant manual bracytherapy.

There are three primary areas that I will be focusing my time on today. First, I

will describe the Organization of Agreement States position on the recently

submitted SECY paper 12-0053 on the Recommendations on Regulatory

Changes for Permanent Implant Brachytherapy Programs. Next, I will discuss

what some of the Agreement States have done in the interim awaiting guidance

from the NRC concerning these types of implants since the inspection of the VA

Hospital. Finally, I will cover the work completed by a joint NRC/OAS Working

Group tasked to create a supplement to the Inspection Manual Chapter 2800

"Material Inspection Program" and the Inspection Procedure 87132

"Brachytherapy Programs" as based on current Part 35.

The Organization of Agreement States Executive Board has reviewed the SECY

paper 12-0053 and supports the stated goal of the Commission (SRM-SECY

paper 10-0062) to clarify the medical event definition to protect the interests of

the patient, allow physicians to take actions that they deem medically necessary,

while continuing to enable the NRC and agreement states to detect failures in

process, procedure, and training. However, the Board does not support using

only activity based medical event criteria as recommended in the SECY paper

12-0053. All other therapy treatments utilize dose based criteria, thus, it is

inconsistent to have one radioactive material therapy treatment that does not

utilize dose based criteria. OAS recommends retention of dose based criteria. If

dose based criteria is not retained, OAS requests that the Agreement States be

allowed the flexibility to utilize dose based criteria for these types of implants.

The OAS also performed a survey of the Agreement States concerning medical

event criteria for prostate brachytherapy implants and 14 states responded. The

Presentation of Chris Timmerman, OASNRC Commission Meeting on April 24, 2012

results of the survey were briefed at the stake-holder workshops held in New

York City and Houston last year as well as at the OAS Annual meeting. All of the

14 states that responded have the same "current" medical event definition as the

NRC or a definition that is more restrictive than the NRC's.

Now I will discuss what Wisconsin has done. Wisconsin has inspected the

majority of their medical licensees that perform manual brachytherapy implants

and all of the licensees have established dose based criteria. These inspections

were conducted utilizing the Wisconsin's Information Notice, issued July 21, 2010

which reminded licensees that they are required to have written procedures to

verify that each administration is performed in accordance with the provisions of

the written directive, and a Regulatory Information Summary, issued February

18, 2011 which detailed additional guidance, requested licensees to respond with

the criteria currently used and provided some lessons learned from previous

inspections. Additionally, during this time frame Wisconsin completed 29

inspections and compiled the number of implants performed and the number of

medical events reported. A retrospective review was conducted by the licensees

to determine if any process improvements could be made by the licensees

concerning their prostate manual brachytherapy programs. Out of 1970 prostate

implants performed (since 2003) there have been only 35 reported medical

events, which is 1.78%. Many of the reported medical events could have easily

been prevented (i.e. planning errors, not documenting the correct number of

seeds, etc.). Therefore, as seen in Wisconsin, if licensees use a dose based

medical event definition, there will not be a huge surge of medical events, as

some people have projected.

Now moving on to the Joint NRC/OAS working group, it was assembled in

August 2011. The working group was comprised of personnel from the Office of

Federal and State Materials and Environmental Managements Programs, 2

Agreement States, all NRC Regions, Office of General Counsel, Office of

Enforcement and the Division of Intergovernmental Liaison and Rulemaking. As

Presentation of Chris Timmerman, OASNRC Commission Meeting on April 24, 2012

you may know the Inspection Procedure 87132 is in the final steps of the

approval process and the training will be conducted for all NRC Regions and all

Agreement States this Thursday April 26, 2012 via webcast and webinar. This

training will go over the changes made to the Inspection Procedure based on the"current" 10 CFR 35.40, "Written Directives" and 10 CFR 35.3045, "Report and

Notification of Medical Events". This Inspection Procedure will be used until the

new Part 35 is finalized.

As the co-chair of the Working Group, the group worked hard to find common

ground that would benefit not only the NRC Regions but also the Agreement

States as pertaining to inspection guidance for manual brachytherapy programs.

In the NRC Regions as well as the Agreement States there is a big difference

when it comes to licensees using dose based criteria or activity based criteria or

even how licensees are performing these implants. In providing interim guidance

for inspectors, we had to work within the constraints of the current rule. We

identified some areas that can be improved. The revised rule should define key

terms (e.g., Completion of procedure, Prescribed Dose, Administered Dose,

Absorbed Dose, etc.) and, unlike the current Part 35, it should use the defined

terms consistently throughout the revised rule and associated guidance.

One consistent message from the Working Group is that training and guidance

needs to be given to the licensees and the inspectors on'the current and new

medical event definition.

In closing the OAS would also like to submit the following recommendations

concerning the new Part 35 rulemaking process:

* Consider listing Authorized Medical Physicist (AMP) on the license for

Manual Brachytherapy based on the Medical Physicist's involvement

with treatment plans and post treatment plans. Similar to the

requirement for SR-90 eye applicators;

" Incorporate treatment planning;

Presentation of Chris Timmerman, OASNRC Commission Meeting on April 24, 2012

* Incorporate post treatment evaluation steps (most licensees do a 30

day follow-up); and

* Do not remove the 'total dose" as an option for completion of the

Written Directive or at a minimum allow Agreement States flexibility in

this area.

Thank you again for allowing me to talk with you today. This concludes my

remarks.

Definition of MedicalEvent in Permanent

Implant Brachytherapy

April 24, 2012

Dr. Anthony Zietman

On behalf of the AmericanSociety for Radiation Oncology

(ASTRO)

Current Definition

* It is deemed to be a medicalevent if "the total dose delivereddiffers from the prescribed doseby 20% or more."

* This definition relies onestimates of absorbed dosewhich is hard to quantify.

Problems with Definition

* Permanent implant prostatebrachytherapy is a dynamicprocedure impacted by:

" Changes in size and shape ofprostate

* Imaging modalities used --

Ultrasound and CT

Urethra

Neurovascularbundle

Ejaculatory ducts

~cD~0

Ii "-

i j

ASTRO Recommendation

• Target-based definition

* It is deemed to be a medicalevent if more than 20% ofsource strength is implantedoutside the planning targetvolume

Rationale

• The total source strengthimplanted within and around theprostate is under control of theauthorized user.

• The subsequent prostate volumeand the resultant dose to theprostate is not.

Conclusion

* It is important to capture thoseevents that could cause seriouspatient harm.

* Target-based definition wouldidentify true errors and weed outmedically acceptable implants.

Definition of Medical Event inPermanent Implant Brachytherapy

NRC-April 24, 2012

W. Robert Lee, MD, MS, MEd

On behalf of the AmericanBrachytherapy Society (ABS)

CFR 10 Part 35Medical Event:

° Wrong patient

• Wrong site-

* Wrong isotope

* Wrong dose

Medical Event

"total dose delivered differs

from the prescribed dose

by 20 percent or more"

Absorbed Dose

° Volume changes

° Timing of Imaging

° Modality of Imaging

° Contouring variation

Inter-observer Variability

52 cc 80 ccv • v v

Lee, ABS 2002

RTOG 0019-Postimplant DosimetryD90 %Rx Dose

35

30

25

20

15

10

5

0<70 70-80 80-90 90-100 100-110 110-120 120-130 130-140 >140

35% of cases ME!Lee, Brachytherapy 2006

"Expert" contours ?7

P-roposed Changes

The new changes puts theonus on the AU for thingsthat they can control; notthe things they cannot.

Proposed Changes

S

S

i.mple, relevant

upported by ABS

Clarity will increase use

Opportunity to educate