1. Bruce Thomadsen University of Wisconsin Madison Some Current Regulatory issues from the ACMUI

2. The ACMUI The Advisory Committee on Medical Uses of Isotopes for the U.S. Nuclear Regulatory Commission

3. ACMUI Patient Advocacy Patient Advocacy State Government Radiation Programs State Government Radiation Programs Radiation Safety Officers Radiation Safety Officers Healthcare Administration Healthcare Administration Nuclear Pharmacists Nuclear Pharmacists Nuclear Medicine Physicians Nuclear Medicine Physicians Nuclear Cardiologist Nuclear Cardiologist Radiation Oncologist – Brachytherapy Radiation Oncologist – GammaKnife FDA Medical Physicist – Radiotherapy Medical Physicist – Nuclear Medicine Members representative of (not representing):

4. ACMUI Agenda April 2011 1. Medical Events Subcommittee Report 2. Rulemaking 3. Part 35 Expanded Rulemaking 4. Permanent Implant Brachytherapy Rulemaking 5. Permanent Implant Brachytherapy Rulemaking 6. Permanent Implant Brachytherapy Rulemaking 7. Grandfathering 8. Preceptor Attestation 9. Patient Release 10. Patient Release

5. Patient Release Criteria Between 1986 and 1997 131 I thyroid patients receiving more than 30 mCi had to be hospitalized. Between 1986 and 1997 131 I thyroid patients receiving more than 30 mCi had to be hospitalized. This limit was based on: This limit was based on: The assumption that the source material acted like a point source, The assumption that the source material acted like a point source, There was no attenuation in the patient, There was no attenuation in the patient, Use of the physical half-life instead of the effective half-life. Use of the physical half-life instead of the effective half-life. Keeping the exposure < 5 mR/h @ 1 m. Keeping the exposure < 5 mR/h @ 1 m.

6. Revised Patient Release Criterion In 1997 the criterion changed from a fixed activity to a dose. In 1997 the criterion changed from a fixed activity to a dose. The new criterion: Family at home <5 mSv for complete decay. The new criterion: Family at home <5 mSv for complete decay. Other persons still <1 mSv*. Other persons still <1 mSv*. Includes external and internal exposures. Includes external and internal exposures. Requires User to know living conditions and calculate projected doses. Requires User to know living conditions and calculate projected doses.

7. Projected Doses Where: D(∞)= 500 mrem G= Exposure-rate constant=2.2 R cm 2 /(mCi h) for 131 I Q o = Activity administered in mCi, O= Occupancy = 0.25 if not known better, F= fraction of the administered activity taken up by the thyroid or rest of body, T= Effective half-life for either the thyroidal or extrathyriodal activity

8. Or Based on Measured Exposure Rates Where D(∞)= 500 mrem D(∞)= 500 mrem 103h= Effective life in h for 131 I 103h= Effective life in h for 131 I O= Occupancy = 0.25 if not known better, O= Occupancy = 0.25 if not known better, R o = Initial exposure rate at 1 m, R o = Initial exposure rate at 1 m,

9. The Controversies 1. Moves to go back to the 30 mCi release criteria. Initiated by a petition from Peter Crain. Demanded by Congressman Markey 2. Questions about having patients go directly to a hotel. a hotel. 3. Questions about patients going to nursing homes. homes.

11. The Arguments for 30 mCi Releasing patients with over 30 mCi exposes family members to unsafe levels of radiation and radioactive contamination. Releasing patients with over 30 mCi exposes family members to unsafe levels of radiation and radioactive contamination. Patients may take public transportation and expose unwitting bystanders to excessive doses. Patients may take public transportation and expose unwitting bystanders to excessive doses. Patients may vomit soon after taking the NaI and spread contamination. Patients may vomit soon after taking the NaI and spread contamination. Some users may not give adequate instructions. Some users may not give adequate instructions.

12. The Arguments for the Current Rule Studies with family members badged have show that they receive considerably less than calculated doses. Studies with family members badged have show that they receive considerably less than calculated doses. Other passengers at 50 cm would get 1 mSv in about 2.2 h from a patient containing 200 mCi (no attenuation) – So no long plane trips. Other passengers at 50 cm would get 1 mSv in about 2.2 h from a patient containing 200 mCi (no attenuation) – So no long plane trips. Most practitioners keep patients for an hour for the radionuclide to get absorbed, and give antiemetics. Most practitioners keep patients for an hour for the radionuclide to get absorbed, and give antiemetics.

13. The Arguments for the Current Rule Surveys show that users do give instructions. Anyway, that should only lead to regulators checking that instructions are given. Surveys show that users do give instructions. Anyway, that should only lead to regulators checking that instructions are given. Insurance companies will not pay for hospitalization. Insurance companies will not pay for hospitalization. Increase the dose to hospital staff who would care for such patients repeatedly. Increase the dose to hospital staff who would care for such patients repeatedly. National and International bodies have recommended a dose-base release criterion if feasible. National and International bodies have recommended a dose-base release criterion if feasible.

14. Hotels Hotel stays for radioactive patients are more controversial. Hotel stays for radioactive patients are more controversial. Calculation of dose to workers indicate they would be unlikely to receive >1 mSv for a patient’s stay. Calculation of dose to workers indicate they would be unlikely to receive >1 mSv for a patient’s stay. But, they may from multiple patients, such as may happen for major referral centers. But, they may from multiple patients, such as may happen for major referral centers. Vomiting seems not to be an issue. Vomiting seems not to be an issue. Not as dangerous as hepatitis patients. Not as dangerous as hepatitis patients.

15. Release Criterion Note The 30 mCi rule is just a special case of the current rule with: No attenuation in the patient No attenuation in the patient No information on the biological half-life (the physical is used) No information on the biological half-life (the physical is used) The default occupancy (0.25) The default occupancy (0.25) Why not use the best information available?

16. 99 Mo Production The ACMUI has discussed this but is not in a position to do anything about it other than recommend that the NRC facilitate US production. We can talk about this later if there is interest. The ACMUI has discussed this but is not in a position to do anything about it other than recommend that the NRC facilitate US production. We can talk about this later if there is interest.

17. Medical Event Definition for Prostate Implants Current ME definition (1) A dose that differs from the prescribed dose or dose… by more than 0.05 Sv (5 rem) effective dose equivalent, 0.5 Sv (50 rem) to an organ or tissue, or 0.5 Sv (50 rem) shallow dose equivalent to the skin; and (1) A dose that differs from the prescribed dose or dose… by more than 0.05 Sv (5 rem) effective dose equivalent, 0.5 Sv (50 rem) to an organ or tissue, or 0.5 Sv (50 rem) shallow dose equivalent to the skin; and  (i) The total dose delivered differs from the prescribed dose by 20 percent or more;

18. Medical Event Definition for Prostate Implants Current ME definition (3) A dose to the skin or an organ or tissue other than the treatment site that exceeds (3) A dose to the skin or an organ or tissue other than the treatment site that exceeds  by 0.5 Sv (50 rem) to an organ or tissue and  50 percent or more of the dose expected from the administration defined in the written directive  (excluding, for permanent implants, seeds that were implanted in the correct site but migrated outside the treatment site).

19. ME Definition Problem Many acceptable implants have doses to some parts of the target <80% of the prescribed dose. Many acceptable implants have doses to some parts of the target <80% of the prescribed dose. ALL implants have doses >120% of the prescribed. (Near the sources D=>∞.) ALL implants have doses >120% of the prescribed. (Near the sources D=>∞.) Dose to nearby organs can easily change by >50% through movement. (The prostate moves cm over short periods of time.) Dose to nearby organs can easily change by >50% through movement. (The prostate moves cm over short periods of time.)

20. Utility and Price The current definition works well for temporary implants where there is good control over source placement and treatment duration. The current definition works well for temporary implants where there is good control over source placement and treatment duration. Not so well for permanent implants. Not so well for permanent implants. Classifying adequate implants has its prices: Classifying adequate implants has its prices:  Time and expense of dealing with an ME  Law suits  Publicity  Practitioners forgoing the practice. (This has happened!)

21. Commissions’ Comments They have rejected these definition, saying that they do not know what is right, but the current definition isn’t. They have rejected these definition, saying that they do not know what is right, but the current definition isn’t.

22. Background Some of this is fueled by the situation at the Philadelphia VA. Some of this is fueled by the situation at the Philadelphia VA. There there were 107 implants identified as ME. Some were very bad. There there were 107 implants identified as ME. Some were very bad.

23. Target Volumes: ICRU 62 GTVCTVIMSMPTVOARPRV The IM and the SM do not just add – that gives too much margin. May combine as uncertainties, which is why the PTV is smaller than the SM added to the IM The OAR may limit the expansion to the PTV.

24. Target Volume So what is the target volume? So what is the target volume? If the CTV (i.e., prostate), then seeds placed in the margin are out of the target and so is the dose. If the CTV (i.e., prostate), then seeds placed in the margin are out of the target and so is the dose. If the PTV (where seeds may be placed to cover the prostate) then the dose to the PTV will be low. If the PTV (where seeds may be placed to cover the prostate) then the dose to the PTV will be low. RTOG uses D 90, the dose that covers 90% of the target, and a protocol violation is D 90 <80%D script. That is not a real event, just less than the protocol accepts. RTOG uses D 90, the dose that covers 90% of the target, and a protocol violation is D 90 <80%D script. That is not a real event, just less than the protocol accepts. This is different from D 100 <80%D script. This is different from D 100 <80%D script.

25. Target Volume Dose Many implants fail the D<80% based on CT the day of or day following the implant. Many implants fail the D<80% based on CT the day of or day following the implant. This is due to edema (swelling) from the trauma, separating the sources and lowering the dose. This is due to edema (swelling) from the trauma, separating the sources and lowering the dose. This clears up a little on scans done after four weeks. This clears up a little on scans done after four weeks. It is often very hard to get patients back in four weeks. It is often very hard to get patients back in four weeks. Also, identifying a gap in sources at four weeks is too late. Also, identifying a gap in sources at four weeks is too late. Even with edema, gaps can be identified and fixed. Even with edema, gaps can be identified and fixed.

26. Effects on the VA Events Correcting for edema, reduced the number of events from 107 to just over a handful. More in the next presentation. Correcting for edema, reduced the number of events from 107 to just over a handful. More in the next presentation.

27. Current Definition for Other Organs The 50% increase in dose is a problem also. The 50% increase in dose is a problem also. Take the skin at maybe 6 cm deep. The dose is roughly 45U x (1cGy/h)/U x 0.272 x (1cm/6cm) 2 = 0.34 cGy/h Take the skin at maybe 6 cm deep. The dose is roughly 45U x (1cGy/h)/U x 0.272 x (1cm/6cm) 2 = 0.34 cGy/h If, due to gas at the time of the CT the distance is 5 cm (a common change) the dose becomes 45U x (1cGy/h)/U x 0.367 x (1cm/5cm) 2 = 0.66 cGy/h If, due to gas at the time of the CT the distance is 5 cm (a common change) the dose becomes 45U x (1cGy/h)/U x 0.367 x (1cm/5cm) 2 = 0.66 cGy/h That is an increase of 94% That is an increase of 94%

28. Another Option discussed ME when >20% sources outside the target. ME when >20% sources outside the target. Of course, this would have to be the PTV. Of course, this would have to be the PTV. This correlates well with bad implants, but would not identify problems where all sources are in the prostate but bunched. This correlates well with bad implants, but would not identify problems where all sources are in the prostate but bunched. The ACMUI endorsed the ASTRO definition, discussed in the next presentation. The ACMUI endorsed the ASTRO definition, discussed in the next presentation.

29. Other Organs The rectum contacts the prostate, and lies at the edge of the high dose gradient. The rectum contacts the prostate, and lies at the edge of the high dose gradient. Millimeters of motion can make more than 50% changes in dose. Millimeters of motion can make more than 50% changes in dose. The currents regulations have no volume component, so even one pixel with a dose change >50% is an ME. The currents regulations have no volume component, so even one pixel with a dose change >50% is an ME.

30. Summary These issues are not easy. These issues are not easy. Patient release itself is pretty straight forward until hotel stays or nursing homes come into the picture. Patient release itself is pretty straight forward until hotel stays or nursing homes come into the picture. Medical event definition has many unintended consequences. Medical event definition has many unintended consequences. Sculpting a ME definition that covers everything is challenging. Sculpting a ME definition that covers everything is challenging.