ML22094A102
| ML22094A102 | |
| Person / Time | |
|---|---|
| Issue date: | 04/05/2022 |
| From: | Advisory Committee on the Medical Uses of Isotopes, Office of Nuclear Material Safety and Safeguards |
| To: | |
| Valentin-Rodriguez C | |
| References | |
| Download: ML22094A102 (216) | |
Text
Advisory Committee on the Medical Uses of Isotopes Spring Meeting April 5, 2022 Meeting Handout
MEETING AGENDA ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES April 5, 2022 Virtual Meeting NOTE: Sessions of the meeting may be closed pursuant to 5 U.S.C. 552(b) to discuss organizational and personnel matters that relate solely to internal personnel rules and practices of the ACMUI; information the release of which would constitute a clearly unwarranted invasion of personal privacy; information the premature disclosure of which would be likely to significantly frustrate implementation of a proposed agency action; and disclosure of information which would risk circumvention of an agency regulation or statute.
TUESDAY, APRIL 5, 2022 OPEN SESSION
- 1. Opening Remarks C. Einberg, NRC Mr. Einberg will formally open the meeting and Mr. Williams will provide K. Williams, NRC opening remarks.
- 2. Old Business D. Lowman, NRC Mr. Lowman will review past ACMUI recommendations and provide NRC 10:00am to responses.
12:15pm EST
- 4. Medical Related Events D. Dimarco, NRC Mr. Dimarco will provide an overview of the NRC staffs assessment of FY21 medical events.
12:15pm to LUNCH 12:45pm EST
- 5. ACMUI Reporting Structure D. Lowman, NRC Mr. Lowman will provide an overview of the current reporting structure.
Members will discuss the reporting structure of the Committee and provide feedback to the NRC.
- 6. Special Presentation to Dr. Vasken Dilsizian J. Lubinski, NRC
- 7. TheraSphere' Y-90 Glass Microspheres Ashley Cockerham, 12:45pm to A representative from Boston Scientific will provide an overview of the Boston Scientific 3:15pm EST TheraSphere' Y-90 glass microspheres.
- 8. SIR-Spheres Y-90 Resin Microspheres Diana Thompson, A representative from Sirtex Medical will provide an overview of the SIR- Sirtex Medical Spheres Y-90 resin microspheres.
- 9. Minimizing Risk of Medical Events J. Angle, NRC Dr. Angle will provide an overview institutional processes and team approaches to reducing errors.
- 10. CORAR Comments on the NIST Radioisotope Measurement M. Guastella, Assurance Program CORAR Mr. Guastella will discuss CORARs request that NIST facilitate the restart of NRMAP and provide sufficient resources to NRMAP and Radioactivity Measurement Group.
- 11. Update on NIST Radioisotope Measurement Assurance Program B. Zimmerman, Dr. Zimmerman will provide an update on the NRMAP program and an PhD, NIST overview of NISTs plan to reorganize the program.
3:15pm to BREAK 3:30pm EST
- 12. Non-Medical Events M. Sheetz, NRC Mr. Sheetz will provide an analysis of FY20-FY21 non-medical events reported by medical use facility and commercial pharmacies.
- 13. Medical Team Updates C. Valentin-Dr. Valentin-Rodriguez will provide an update on Medical Radiation Safety Rodriguez, PhD, Team activities. NRC 3:30pm to 5:00pm EST 14. Open Forum ACMUI The ACMUI will continue discussion on medical topics of interest.
- 15. Administrative Closing D. Lowman, NRC Mr. Lowman will provide a meeting summary and propose dates for the fall 2022 meeting.
5:00pm EST ADJOURN
2019 ACMUI Recommendations and Action Items Target Completion ITEM DATE STATUS Date for NRC Action The ACMUI endorsed the Appropriateness of Medical Event 17 Reporting Subcommittee report and the recommendations 9/10/2019 Propose Open May 2022 provided therein. to Close The ACMUI endorsed the Evaluation of Extravasations Subcommittee Report, as amended, to note that under future 18 9/10/2019 Accepted Open Spring 2023 revisions to Part 35 rulemakings, extravasations be captured as a type of passive patient intervention in the definition of patient intervention.
2020 ACMUI Recommendations and Action Items Target Completion ITEM DATE STATUS Date for NRC Action The ACMUI endorsed the Patient Intervention subcommittee report, as presented, and the recommendations provided therein to re-4 3/30/2020 Accepted Open Spring 2023 interpret current definition of patient intervention and to report medical events resulting from patient intervention which result in unintended permanent functional damage under 10 CFR 35.3045(b).
As part of the Non-Medical Events report, the ACMUI recommended to the NRC staff and/or NMP to evaluate the issue 11 9/21/2020 Accepted Open Spring 2023 of detection of short-lived medical isotopes in municipal waste (waste from nuclear medicine patients that might be triggering the landfill alarms) and provide some level of guidance, best practices, or additional instructions.
2021 ACMUI Recommendations and Action Items Target Completion ITEM DATE STATUS Date for NRC Action The ACMUI tentatively scheduled the fall meeting for October 4-5, 3/16/2021 Propose Open 1 2021. The alternate meeting date is September 13-14, 2021. A October 2021 to close virtual or in-person meeting for fall 2021 is to be determined.
The ACMUI endorsed the ACMUI Abnormal Occurrence 5/27/2021 Propose to Open May 2022 2
Subcommittee report, and the recommendations provided therein. close The ACMUI formed a new subcommittee on the Radionuclide Generator Training and Experience. The subcommittee is Propose to 3 5/27/2021 Open Fall 2021 expected to provide a draft report and any recommendations at close the fall 2021 ACMUI meeting.
The ACMUI formed a new subcommittee on Emerging Radionuclide Therapy Training. The subcommittee is expected to Propose to 4 5/27/2021 Open Fall 2021 provide a draft report and any recommendations at the fall 2021 close ACMUI meeting.
The ACMUI formed a new subcommittee on the Diffusing Alpha-emitter Radiation Therapy (DaRT) Manual Brachytherapy Source. Propose to 5 9/02/2021 Open December 2021 The subcommittee is expected to provide a draft report and any Close recommendations at the spring 2022 ACMUI meeting.
The ACMUI endorsed the Extravasation Subcommittee report, as 6 9/02/2021 Accepted Open Spring 2023 amended, to support option 4 of the Subcommittee Report.
The ACMUI formed a new subcommittee on the Liberty Vision Y-90 Manual Brachytherapy source. The subcommittee is expected 7 10/04/2021 Accepted Open Fall 2022 to provide a draft report and any recommendations at the spring 2022 ACMUI meeting.
The ACMUI tentatively scheduled the spring meeting for April 4-5, Propose to 8 2022. The alternate meeting date is March 21-22, 2022. The 10/04/2021 Open Spring 2022 close Spring 2022 meeting is planned to be in-person.
The ACMUI formed a new subcommittee to review the NRC staffs draft proposed revision to Regulatory Guide (RG) 8.39, Release of Patients Administered Radioactive Materials and Propose to 9 review and comment on the NRCs staff additional draft patient 10/04/2021 Open December 2021 close release licensing guidance for CivaDerm. The subcommittee is expected to provide a draft report and any recommendations at the spring 2022 ACMUI meeting.
The ACMUI endorsed the Radionuclide Generator Knowledge 10 and Practice Requirements Subcommittee Report and the 10/04/2021 Accepted Open March 2026 recommendations provided therein.
The ACMUI endorsed the Medical Event Subcommittee report Propose to 11 10/04/2021 Open Spring 2022 and the recommendations provided therein. close
The ACMUI formed a new subcommittee on Y-90 microspheres in medical events. The subcommittee is expected to provide a draft 12 10/04/2021 Accepted Open Fall 2022 report and any recommendations at the spring 2022 ACMUI meeting.
The ACMUI endorsed the Emerging Radiopharmaceutical Propose to 13 Therapy Knowledge Requirements in Theranostics Subcommittee 10/04/2021 Open October 2021 close report and the recommendations provided therein.
The ACMUI endorsed the ACMUI Alpha DaRT Subcommittee Propose to 14 12/15/2021 Open March 2022 report and the recommendations therein. close The ACMUI endorsed the ACMUI RG. 8.39 Subcommittee report 15 12/15/2021 Accepted Open Summer 2022 on CivaDerm and the recommendations therein.
The ACMUI endorsed the ACMUI RG. 8.39 Subcommittee report 16 on the proposed revision to RG 8.39 and the recommendations 12/15/2021 Accepted Open Fall 2022 therein.
OPEN FORUM (No Handout)
Status of Medical Events FY 2021 Daniel DiMarco Medical Radiation Safety Team April 5, 2022
Medical Events The dose threshold for diagnostic events precludes reportable events most years.
Each year, there are approximately 150,000 therapeutic procedures performed utilizing radioactive materials.
2
Medical Events FY 2016 - 2018
- 50 Medical events reported - FY 2016
- 43 Medical events reported - FY 2017
- 48 Medical events reported - FY 2018 FY16 FY17 FY18 35.200 4 0 0 35.300 4 4 2 35.400 6 (18*) 7 11 (13*)
35.600 6 8 (14*) 10 35.1000 30 24 25 (26*)
- The total number of patients involved if greater than the number of reports 3
Medical Events FY 2019 - 2021
- 56 Medical events reported - FY 2019
- 48 Medical events reported - FY 2020
- 64 Medical events reported - FY 2021 FY19 FY20 FY21 35.200 1 (8*) 0 4 35.300 9 2 10 35.400 5 6 4 35.600 9 (10*) 13 5 35.1000 32 27 41
- The total number of patients involved if greater than the number of reports 4
Medical Events 2021 35.200 Medical events 4 FDG Overdose 1 Wrong radiopharmaceutical 3 5
35.200 FDG
- Patient overdose
- Prescribed 0.37 GBq (10 mCi), administered 3.85 GBq (104 mCi)
- Technician realized he administered the wrong dosage after the treatment 6
35.200 I-123
- Wrong Drug
- Patient called back to the hospital and given KI
- Stayed at hospital for four days under I-131 safety protocols
- Planned dose to thyroid was 2.37 cGy (rad)
- Early estimates of the dose received ranged from 1,220 cGy (rad) to 155,000 cGy (rad)
- Dose estimates could not accurately account for KI administration
- Patient lost sense of taste and was given Synthroid medication 7
35.200 I-123 (cont)
- Root cause determined to be several errors by NMT
- The containers are also very different and are kept in separate rooms
- Patients name and DOB are visible on outside labels for all doses
- Doses are checked in a dose calibrator to ensure correct dosage
- All iodine procedures now require two NMTs to sign off before administration
- NMT initial competency will be evaluated between diagnostic and therapeutic doses
- Involved NMT had their employment terminated
- Safety Event Analysis was scheduled to review the incident 8
35.200 Tc-99m
- Wrong Drug
- Patient was prescribed 1.11 GBq (30 mCi) of Tc-99m Sestamibi, administered 4.42 GBq (119.49 mCi) of Tc-99m Sodium Pertechnetate
- Effective dose estimated to be 5.7474 cSv (rem) 9
35.200 MDP
- Wrong Radiopharmaceutical
- Anonymous allegation that patient injected with MDP during a stress test
- The same patient was also injected with Tc-99m Sestamibi at a later time
- More information has been requested 10
Medical Events 2021 35.300 Medical events 10 Targeted Thorium Therapy 1 Lutetium-177 3 I-131 NaI 3 I-131 Iomab-B 2 Xofigo 1 11
35.300 Targeted Thorium Therapy
- Wrong Drug
- Prescribed 0.0405 mCi of Th-227 epidermal growth factor receptor 2 (HER-2) Target Thorium Conjugate (TTC), received 0.046 mCi of Th-227 mesothelin (MSLN) TTC
- Investigative study involving novel TTC intended to deliver radioisotope to HER-2 antigen expressing tumor tissue
- Incorrectly labelled by manufacturer
- Both drugs are processed the same in the body
- Estimated doses are : 609 cGy (rad) to liver, 164 cGy (rad) to small intestine, 174 cGy (rad) to kidneys, and 85.3 cGy (rad) to red marrow
- No toxicities were noted after six weeks of monitoring 12
35.300 I-131 NaI
- Patient overdose
- Patient prescribed 1.11 GBq (30 mCi), received 3.7 GBq (100 mCi)
- Expected whole body dose of 26.64 cSv (rem) and dose to the bladder wall of 225.7 cGy (rad)
- Dosage of 3.7 GBq (100 mCi) was verbally given to technologist
- Did not check written directive prescription of 30 mCi
- NMT was using a worksheet with the incorrect dosage of 100 mCi
- Root cause was determined to be human error
- Corrective actions included new personnel hires, improved supervision, and procedure modifications 13
35.300 I-131 NaI
- Patient underdose
- Patient prescribed 7.4 GBq (200mCi), received 2.22 GBq (60 mCi)
- Dose was divided into two capsules
- Patient only received one of two capsules
- Second capsule stuck in shipping vial, discovered by radiopharmacy in the returned vial
- Subsequent dose was administered to complete thyroid cancer treatment 14
35.300 I-131 NaI
- Patient underdose
- Patient prescribed 3.7 GBq (100mCi), received 0.7215 GBq (19.5 mCi)
- Dose prescribed was 10,000 cGy (rad), dose administered was 3,900 cGy (rad)
- Patient only received one capsule of a two-capsule treatment
- Remaining capsule was accounted for in the original vial
- Root cause determined to be human error, did not follow written handling and survey procedures
- Procedures were updated for radiotherapy isotope administrations
- DOT/HAZMAT training and supplementary radiation protection training was administered to all technologists 15
35.300 Lu-177 Dotatate
- Patient underdose
- Patient prescribed 7.4 GBq (200 mCi), received 5.06 GBq (136.64 mCi)
- Leakage in adaptor/needle connection
- No personnel or area contamination
- No adverse effects to the patient were expected
- Root cause determined to be defective part of the assembly, specifically the dual male adaptor
>> Lack of vacuum seal at the septum from re-puncturing with the new assembly setup was also a contributing factor 16
35.300 Lu-177 Lutathera
- Patient underdose
- Patient was prescribed 7.4 GBq (200 mCi) of Lu-177
- Patient received 1.04 GBq (28 mCi), 14% of prescribed
- Procedure stopped after the patient stated they had a chemotherapy injection the day before, instead of after the radiopharmaceutical therapy
- The prescribed dose was 479 cGy (rad) but estimated delivered dose to the kidney was 67 cGy (rad)
- No medical impact expected
- Root cause was determined to be inadequate review of patient records by authorized user 17
35.300 Lu-177 Lutathera
- Patient underdose
- Patient prescribed 7.4 GBq (200 mCi), received 0.666 GBq (18 mCi)
- Technician had difficulty establishing IV injection site and flow
- No adverse effects were noted and none were expected
- Cause was determined to be poor venous access and incorrect gauge needle 18
35.300 I-131 Iomab-B
- Patient underdose
- Prescribed 414.4 MBq (11.2 mCi) (measured at 388.5 MBq (10.5 mCi) prior to administration)
- Delivered 212.38 MBq (5.74 mCi); 51% of the prescribed dose (residual activity in vial and tubing was 176.12 MBq (4.76 mCi))
- Considerable air in tubing required replacement of infusion set
- Problem persisted with the second set of tubing, so the administration was stopped 19
35.300 I-131 Iomab-B (cont.)
- 38 mL of the 43 mL dosage was administered
- Approximately 0.111 Sv (11.1 rem) difference in prescribed and actual effective dose
- No re-administration of diagnostic dose was required, and the therapy dose was readministered without incident
- Corrective actions included procedure modifications 20
35.300 I-131 Iomab-B
- Patient underdose
- Patient prescribed 35.11 GBq (949 mCi), received 18.76 GBq (507 mCi)
- Dose administered was 1,900 cGy (rad)
- Leaking tube from infusion system, nurse inadvertently removed a tube occluding clamp and opened the roller clamp on the flush bag line at the beginning of the infusion
- No adverse effects expected, bone marrow dose was considered to be sufficient
- Supplemental training was provided to the radiopharmacist and nuclear medicine supervisor on operating and setting up the infusion pump
>> Solely responsible for setting up and operating the pump for all future patients
- Checklist developed for pump operation 21
35.300 Ra-223 Xofigo
- Patient underdose
- Patient prescribed 3.47MBq (93.65 µCi), received 0.63 MBq (17.1
µCi)
- Procedure was cancelled due to low blood pressure, dose kept in hot lab for decay
- New dose ordered, however the decayed, original dose was delivered
- Patient brought back after the event; remaining dose delivered
- Administrative actions taken to prevent reoccurrence 22
Medical Events 2021 35.400 Medical events 4 Prostate 3 Mammosite 1 23
35.400 I-125 Prostate
- Wrong Site
- Prescribed 1.013 GBq (27.378 mCi), 54 seeds, prescribed dose of 14,500 cGy (rad)
- Follow-up CT revealed that all seeds were implanted in penile bulb
- Malfunction of ultrasound ruled out
- Review indicated that if the foley catheter was not fully visible on images it could result in incorrect implantation
- Root cause was human error
- Changes to prostate brachytherapy protocol implemented an additional step to ensure clear identification of prostate gland and surrounding anatomy
- Follow-up scans from previous cases involving this type of procedure indicated this was not a repeated event 24
35.400 Cs-131 Prostate
- Wrong site
- Patient prescribed 7.34 GBq (198.26 mCi), received 1.41 GBq (38.12 mCi)
- Prostate D90 dose was 26.26% of the prescribed dose
- Perineal region received a V100 dose of 11,500 cGy (rad)
- Urethra and rectum received approx. 50% of expected dose
- Plan to insert stranded seeds around the prostate periphery and individual seeds at the apex, base, and interior of the prostate
- Ultrasound probe was not accurately advanced on sagittal imaging to see the prostate
- 63 of 78 stranded seeds were implanted in the perineum below the prostate, 15 loose seeds were implanted in the prostate 25
35.400 Cs-131 Prostate (cont.)
- Corrective actions included frame of reference establishing using the stepper position to identify base and apex of prostate
- During the procedure, a timeout will be performed to identify both the prostate and the bladder
- Retraining program was planned to include retraining and proctoring by a qualified radiation oncology physician and physicist
- External beam radiotherapy was performed to boost treatment to areas that received less dose
- Patient was scheduled for long-term follow-up 26
35.400 I-125 Prostate
- Patient Overdose
- Patient prescribed 845.38 MBq (22.848 mCi) total activity for 64 prostate brachytherapy seeds
- Authorized user discovered a mistake when entering the source strength into the treatment planning system
- Inadvertently entered the seed strength of 13.21 MBq (0.357 mCi) into the air-kerma strength field
- Prescribed dose was 110,000 cGy (rad), delivered dose was 140,000 cGy (rad)
- No negative effects were expected, start of a two-part treatment plan
>> Second part was a linear accelerator treatment, which was adjusted to accommodate the overdose
- Corrective actions included procedure revision 27
35.400 Mammosite
- Wrong Patient
- Wrong patient received breast cancer treatment
- Determined not to be medical event in 2001, reevaluated after inspection
- No details of the event were saved except that the patient dose exceeded 5 cSv (rem) EDE, or 50 cSv (rem) to an organ or tissue, or 50 cSv (rem) SDE to the skin
- No related records could be obtained, past record retention period 28
Medical Events 2021 35.600 Medical events 5 Gynecological 4 Skin 1 29
35.600 HDR
- Patient overdose
- Patient prescribed 5000 cGy (rad) in 20 fractions at 250 cGy (rad) per fraction
- Treatment for skin cancer using 35mm cone
- Treatment occurred at correct site but without the 35mm cone for one fraction
- Unintended skin dose was approx. 70 cGy (rad) above expected
- No effects were expected to the patient
- Corrective actions included
- Advance preparation of treatment room with correct cone sizes
- Physicist verification of applicator size and treatment site
- Cone placed on skin and outline drawn by physician or physicist
- Treatment outline and placement of applicator re confirmed before treatment is administered 30
35.600 HDR
- Wrong site
- Patient was treated with fraction 2 of 3 with a vaginal cylinder
- After treatment, the physician noted that the cylinder had been displaced 6 cm
- Exact cause was unknown but could have been due to patient movement or loosening of the cylinder holder
- Estimated dose difference of approximately 558 cGy (rad)
- Patient did not experience any irregular toxicities
- Corrective actions included removing the device from service 31
- Wrong site
- Patient being treated with a 190.04 GBq (5.14 Ci) Ir-192 source
- Source transfer tube was 12 cm too long, maximum shallow dose of 800 to 900 cGy (rad) to vagina
- Root cause was determined to be failure of medical staff to follow established procedures
- Also a failure to identify a difference in planned and measured transfer tube lengths
- No adverse health effects are expected 32
- Corrective actions included addition of expected lengths of different channels in the HDR pre-treatment delivery checklist
- Also added measured length with the source position check ruler for each channel to checklist, to be completed and signed off on by the treating RTT prior to physicist review for all HDR cases
- Checklist approved by physicist prior to treatment to allow enough time for physician to verify accuracy 33
35.600 HDR
- Wrong site
- Patient prescribed five fractions of 600 cGy (rad) during an HDR gynecological treatment
- After the third treatment, it was determined that a 125 cm transfer tube was used instead of the expected 113 cm transfer tube
- Dose was delivered 12 cm away from expected site
- Exposed tissue was largely fatty tissue, max dose to any tissue was 600 cGy (rad)
- Authorized medical physicist did not identify the correct tube length during the verification process
- Corrective actions included removal of all 113 cm transfer tubes, only 125 cm tubes will be used for all future treatments
- All physicists were reminded of mandatory checks before all treatments and re-educated on procedural process 34
35.600 HDR
- 462.87 GBq (12.51 Ci) HDR unit
- Patient prescribed single 700 cGy (rad) fraction, received 525 cGy (rad)
- Sometime during planning process dose scalar was adjusted by 25%
- Most likely occurred when user was rotating/panning through images
- Root cause was determined to be human error
- No adverse effects are expected
- Corrective actions included modifying procedures to include an additional step in the pre-check procedure to verify the correct dose and dwell times
- Training was also conducted on the incident and procedure changes with all staff and users 35
Medical Events 2021 35.1000 Medical events 41 Y-90 Microspheres
- TheraSphere' 31
- SIR-Spheres 10 36
35.1000 TheraSphere'
- Y-90 TheraSphere' wrong location
- Patient prescribed 2.55 GBq (68.92 mCi) to the left lobe, received 2.48 GBq (66.96 mCi) to right lobe
- Catheter placement was verified prior to treatment by angiography and fluoroscopy
- AU believes the catheter was kicked out during treatment, but no definitive cause was determined
- No adverse effects were expected
- Corrective actions included a new written procedure 37
35.1000 TheraSphere'
- Patient prescribed 3.841 GBq (103.8 mCi), received 4.751 GBq (128.4 mCi)
- Event was discovered by the RSO after a records review
- Dose was calibrated for administration the day after the administration took place
- Resulting activity was higher at administration
- Root cause was determined to be human error
- Corrective actions included secondary review of written directive, addition of another pre-administration form, and updated procedures 38
35.1000 TheraSphere'
- Patient prescribed 1.75 GBq (47.3 mCi), received 2.224 GBq (60.11 mCi)
- Event discovered after treatment by RSO during a review of therapies
- Dose was administered a day too early, calibrated for the day after 39
35.1000 TheraSphere'
- Y-90 TheraSphere' overdose (cont.)
- Several corrective actions were taken
- Operating procedures were revised to clarify responsibilities of involved participants
- Dose will not be ordered until a microsphere treatment window illustrator is received, a complete written directive is received, there are no discrepancies between to two, NM verifies that the written directive is complete, and NM confirms the dose is appropriate for the date and time of administration
- Second verification after receipt of dose
- Time-out process was formalized
- NM staff and AUs were trained on the changes
- All AUs received a memo reminding them of their reporting responsibility
- Office of Radiation Safety continued quarterly audits
- Refresher training was performed 40
35.1000 TheraSphere'
- Patient prescribed 1.73 GBq (46.7 mCi), received 0.9324 GBq (25.2 mCi)
- During treatment the physician noted that microspheres were visibly clogged in the catheter, discontinued the administration
- Physician requested a larger catheter but was only able to find a smaller catheter
- Noted the full dose might not be able to be delivered but elected to continue
- Manufacturer review of the equipment found microspheres throughout the device and high back pressure and low flow rate
- No adverse effects were expected, and follow-up treatment was successfully delivered 41
35.1000 TheraSphere'
- Patient prescribed 72,000 cGy (rad), received 36,620 cGy (rad)
- Remaining microspheres remained in microsphere kit
- Physician stated the patient received an adequate therapeutic dose 42
35.1000 TheraSphere'
- Patient prescribed 1.23 GBq (mCi), received 0.88 GBq (mCi)
- No personnel or area contamination was noted
- Leaky connections ruled out and no root cause was determined
- Later inspections showed that the microspheres likely clumped in the vial
- Saline was administered successfully, and scans showed bulk of material remained in the vial
- May be due to inadequate tilting of the vial, tapping on a firm surface, or not taking those actions immediately prior to administration 43
35.1000 TheraSphere'
- Patient prescribed 12,000 cGy (rad), received 9,200 cGy (rad)
- No personnel or area contamination was noted
- Suspected kink in delivery system
- Later inspection determined the root cause to be tortuous anatomy of the patient
- The patient was also receiving chemotherapy treatment simultaneously, which was not recommended by the vendor representative
- No corrective actions were taken 44
35.1000 TheraSphere'
- Patient prescribed 4.05 GBq (109.5 mCi) to liver lobes 5 and 8, 5.66 GBq (153 mCi) to lobes 6 and 7
- Patient only received 2.53 GBq (68.5 mCi) to lobes 6 and 7
- Blockage occurred in the microcatheter, unable to be cleared
- Post procedure survey indicated residual activity in the microcatheter
- Microcatheter used (d = 0.49mm) was smaller than recommended size (d = 0.5mm)
- Corrective actions included using a larger catheter for subsequent treatment 45
35.1000 TheraSphere'
- Patient prescribed 547.6 MBq (14.8 mCi), received 344.84 MBq (9.32 mCi)
- No adverse effects expected, likely the tumor was adequately treated
- Investigation identified possible kink in microcatheter as root cause
- Corrective actions included additional checks for kinks in catheters and tubing 46
35.1000 TheraSphere'
- Patient prescribed 2.876 GBq (77.73 mCi), received 1.34 GBq (36.22 mCi)
- Also 0.027 GBq (0.73 mCi) to lungs
- Prior to treatment saline flush had slight resistance but all the flush went through
- Pressure increased appreciably during the procedure and administration was stopped
- Post-treatment survey of the catheter indicated greater than normal radioactivity
- Cause determined to be kink in catheter, but AU stated the treatment area was tortuous
- No corrective actions taken because proper procedures were followed 47
35.1000 TheraSphere'
- Patient prescribed 1.14 GBq (30.8 mCi), received 0.8094 GBq (21.868 mCi)
- Mechanical blockage occurred in the delivery system
- All material contained in delivery system, lines, and patient
- Post treatment imaging indicated activity in the vial
- No adverse effects were anticipated 48
35.1000 TheraSphere'
- Patient prescribed 1.067 GBq (28.84 mCi), received 0.522 GBq (14.11 mCi)
- Microsphere vial was empty, likely held up in microcatheter
- AU also believed that the high residual waste reading was due to a slower infusion of treatment dose and flushing saline
- Normal flow rate was not able to be attained due to small patient vasculature
- Investigation determined the delivery set worked as intended 49
35.1000 TheraSphere'
- Patient prescribed 2.31 GBq (62.43 mCi), received 1.572 GBq (42.49 mCi)
- Microsphere vial was empty, likely held up in microcatheter
- Needed more saline flushes than normal to complete procedure (4 vs. 1-2)
- Microsphere apparatus was new, first-time use
- Manufacturer issued a product advisory concerning a possible leak point near catheter connection 50
35.1000 TheraSphere'
- Patient prescribed 2 doses of 2.4 GBq (64.86 mCi), received 1.067 GBq (28.84 mCi) and 2.374 GBq (64.16 mCi)
- During first administration the AU noticed leakage from the microcatheter and stopped the infusion to check the connection
- Continued with the procedure and performed surveys around the room
- Contamination was found on their hands, performed decontamination procedures and continued with second dose
- Second dose delivered without incident 51
35.1000 TheraSphere'
- Y-90 TheraSphere' underdose (cont.)
- RSO contacted to ensure containment of radioactive material
- Personnel were surveyed and access to the room was restricted in order to decontaminate
- Decontamination of room proceeded without incident 52
35.1000 TheraSphere'
- Patient prescribed 1.067 GBq (28.86 mCi), received 0.799 GBq (21.62 mCi)
- Pinch clamp remained online during infusion, discovered after AU noticed more pressure when pushing syringe
- Clamp removed and treatment resumed
- Flushed five times to ensure no microspheres remained in tubing
- Images of the waste container indicated microspheres in inlet and outlet lines
- AU believes the patient was delivered a clinically effective dose 53
35.1000 TheraSphere'
- Y-90 TheraSphere' underdose (cont.)
- Root cause was determined to be failure to follow procedures
- Checklist was not followed to remove clamp prior to treatment
- Corrective actions included procedure modification 54
35.1000 TheraSphere'
- Patient prescribed 2.46 GBq (66.36 mCi), received 0.47 GBq (12.8 mCi)
- Microspheres became visually clumped in tubing distal to the box prior to microcatheter connection
- Multiple saline flushes were not effective in clearing the clump
- Infusion was stopped after 33 minutes
- Measurement of the tubing and microcatheter indicated only 20% of dose was delivered to the patient 55
35.1000 TheraSphere'
- Patient prescribed 2.95 GBq (79.73 mCi), received 1.15 GBq (31.08 mCi)
- During treatment, the dosimeter used to measure the spheres remaining in the container indicated a lower than expected rate of decrease in microspheres remaining in the container
- The device and tubing were flushed more times than normal to remove any residual activity
- Post-treatment surveys indicated the remaining activity remained in tubing
- Suspected blockage in the tubing due to small portion of the septum lodged in needle after being pierced 56
35.1000 TheraSphere'
- Patient prescribed 2 doses of 0.79 GBq (21.35 mCi) to left lobe segments 4A and 4B, received 0.465 and 0.594 GBq (12.57 and 16.05 mCi) to segments 4A and 4B
- Radiation surveys of the vials post treatment revealed that some microspheres adhered to the tubing
- Standard protocol was followed yet no root cause was identified during discussions with the manufacturer
- Flushing with saline 3 times
- Known risk that microspheres can be stuck in device in rare occasions 57
35.1000 TheraSphere'
- Patient prescribed 640.1 MBq (17.3 mCi), received 401.82 MBq (10.86 mCi)
- Root cause was leakage of microspheres at the connection between tubing and microcatheter
- Leakage resulted in personnel and area contamination
- Addressed by Radiation Safety staff, no skin effects were reported or expected
- No adverse effects to the patient
- Corrective actions included procedure modifications 58
35.1000 TheraSphere'
- Patient prescribed 1.33 GBq (35.9 mCi), received 0.75 GBq (20.2 mCi)
- Two doses were prepared for two separate sites of the liver
- Doses were correctly labeled and prepared, but the smaller dose was administered to the site that needed the higher dose
- The second dose was not administered
- Root cause was determined to be miscommunication between NMT and AU 59
35.1000 TheraSphere'
- Y-90 TheraSphere' underdose (cont.)
- No adverse effects occurred, and the dose was determined to be clinically effective
- Corrective actions included updates to the administration checklist, discussion of the use of a closed loop communication between the administrator of the dose and the physician requesting the dose, and increased training for applicable personnel 60
35.1000 TheraSphere'
- Patient prescribed 888 MBq (24 mCi), received less than 710.4 MBq (19.2 mCi)
- A significant amount of microspheres leaked out of the tubing/catheter connection during the procedure
- Sterile, non-radioactive solution was able to be pushed through the tubing without incident
- Several drops were noticed at the connection during the administration and were cleaned off
- Contamination was detected on the gloves, patients drape, and towels after the treatment
- No contamination was detected on the floor, patient, or staff 61
35.1000 TheraSphere'
- Y-90 TheraSphere' underdose (cont.)
- Imaging indicated radioactivity in the patients liver
- No adverse effects were expected
- Physician stated connecting the catheters took more force than normal, indicating a possible defect
- Corrective actions included update procedures so two people check the connection between catheters
- The procedure was repeated at a later date to accomplish the prescribed dose 62
35.1000 TheraSphere'
- Patient prescribed 828 MBq (22.379 mCi), received 624 MBq (16.865 mCi)
- No contamination was detected in the room or on staff members
- No issues were found with the delivery system or setup
- No unusual resistance was felt on the syringe during treatment
- On the day of the treatment an angiogram demonstrated brisk arterial supply to the tumor and verified catheter position
- No cause was identified
- No adverse effects were expected 63
35.1000 TheraSphere'
- Patient prescribed 688.2 MBq (18.6 mCi), received 144.5 MBq (3.9 mCi)
- Patient received 21% less dose than prescribed
- Residual activity remained in delivery system 64
35.1000 TheraSphere'
- Patient prescribed 2.36 GBq (63.7 mCi), received 0.074 GBq (2 mCi)
- Connection between delivery apparatus and catheter failed when the injection started
- All contamination was contained in the pads below the connection
- No adverse effects were expected 65
35.1000 TheraSphere'
- Y-90 TheraSphere' underdose (cont.)
- Inspection revealed a manufacturing defect in the administration kit
- Leakage at the Leur outlet
- Product advisory was issued, and all kits associated with the involved lot numbers were disposed of
- Corrective actions included staff training 66
35.1000 TheraSphere'
- Patient prescribed 2.76 GBq (74.46 mCi), received 1.32 GBq (35.6 mCi)
- Microcatheter disconnected from the Luer lock during injection
- Lock was tightened and treatment was completed
- Leaked microspheres were contained in absorbent towels
- Underdose was estimated from measurement of tubing, towels, and microcatheter
- Patient was scheduled for imaging to determine if follow-up treatment was necessary
- Corrective actions included checklist training, with a focus on the Luer lock connection 67
35.1000 TheraSphere'
- Patient prescribed 860 MBq (23.24 mCi), received 359.738 MBq (9.72 mCi)
- Patient prescribed same dose to four lobes of liver
- Three lobes received correct dose; one was underdosed
- Analysis of the delivery kit found residual microspheres in the last few inches of tubing, in the microcatheter hub, and in the initial length of the microcatheter
- Indication of obstruction downstream of administration set
- Catheter was in good condition but only a limited flow rate could be achieved 68
35.1000 TheraSphere'
- Y-90 TheraSphere' underdose (cont.)
- Microcatheter did not meet size requirements for TheraSphere' administration
- No adverse effects were expected
- Follow-up imaging determined the treatment was clinically effective
- Corrective actions included use of correct microcatheters, and notification of physicians of the correct microcatheter to use 69
35.1000 TheraSphere'
- Patient prescribed 1.79 GBq (48.38 mCi), received 0.716 GBq (19.35 mCi)
- Root cause was not clear but likely due to selection of a distal arterial branch for administration
- 3 hairpin turns may have resulted in ovalization of the microcatheter lumen
- Location was checked multiple times during treatment and flow was established with saline and contrast
- Ovalization may have resulted in greater pressure on administration set
- Corrective actions included cessation of treatment on patients with a significant number of tight turns 70
35.1000 TheraSphere'
- Patient prescribed 592 MBq (16 mCi), received 368 MBq (9.95 mCi)
- Leak was identified between administration kit and microcatheter
- Spill was confined to patient drape, confirmed by follow-up surveys of the room and staff
- Root cause was determined to be mismatch between the administration set received from manufacturer and previous kits used, resulting in a leaky junction 71
35.1000 TheraSphere'
- Patient prescribed 594.94 MBq (16.08 mCi), received 270.1 MBq (7.3 mCi)
- Treatment appeared to be correct, survey of items used determined the patient had been underdosed
- Experiments to find the root cause determined that if the connection between the delivery set and the microcatheter was not vertically oriented, the microspheres would become stuck
- These findings were communicated to all AUs
- Corrective actions included amending checklist to specify that the connection must be oriented vertically
- Patient will be followed to determine if further treatment is needed 72
35.1000 TheraSphere'
- Patient prescribed 1.56 GBq (42.24 mCi), received 1.04 GBq (28.1 mCi)
- Treatment appeared to be correct, survey of catheter indicated higher than normal residual activity
- Experiments to find the root cause determined that if the connection between the delivery set and the microcatheter was not vertically oriented, the microspheres would become stuck
- These findings were communicated to all AUs
- Corrective actions included amending checklist to specify that the connection must be oriented vertically
- Patient will be followed to determine if further treatment is needed 73
35.1000 TheraSphere'
- Patient prescribed 13.65 GBq (368.92 mCi),
received 10.51 GBq (284.07 mCi)
- Patient received 77% of expected dose, which was determined to be medically appropriate
- No spill or contamination was detected after surveys
- Root cause was decay of dose due to multiple treatment reschedules
- The healthcare center has implemented a program to review accuracy prior to patient scheduling and dose ordered 74
35.1000 SIR-Spheres
- Y-90 SIR-Spheres wrong site
- Patient prescribed 0.29 - 0.83 GBq (7.84 - 22.43 mCi) to left lobe of liver
- The activity was a range because treatment would be stopped if the left lobe became saturated
- Post treatment survey indicated the right lobe had received between 33% and 67% of the dose intended for the left lobe
- Treatment was not intended for the right lobe (patient had been treated for the right lobe previously)
- Periodic flushing and fluoroscopy was performed and indicated the catheter had moved during the treatment
- Suspected respiratory motion and vascular pulsations moved the catheter to the right branch
- No adverse effects were anticipated 75
35.1000 SIR-Spheres
- Patient prescribed 489.14 MBq (13.22 mCi), received 1,168.09 MBq (31.57 mCi)
- Two different treatments were prepared for different lobes of the liver
- Higher dose was administered to the wrong lobe
- Error discovered after treatment of the first lobe
- The other lobe was correctly treated
- Root cause was determined to be incorrect labelling and failure to compare dosage to written directive 76
35.1000 SIR-Spheres
- Corrective actions included revised procedure that specifies labelling to only include patient initials, radionuclide, activity, and date
- A time-out was also incorporated to compare each dose to the written directive, signed by the AU 77
35.1000 SIR-Spheres
- Prescribed 13,000 cGy (rad) to lobes 2,3 and another 13,000 cGy (rad) to lobes 4,5
- Complex vascular flow pattern complicated the treatment delivery
- Microspheres intended for lobe 2,3 went to segment 4
- Dose intended for lobes 4 and 5 only went to lobe 5
- Segment 4 received a dose of 2,500 cGy (rad), and segemtn 5 received a dose of 13,500 cGy (rad)
- Root cause determined to be incorrect placement of delivery catheter
- Corrective actions included a review by a quality control committee 78
35.1000 SIR-Spheres
- Patient prescribed 599.4 MBq (mCi), received 140.6 MBq (mCi)
- During treatment a microcatheter almost immediately clogged
- No adverse effects were expected
- Root cause was determined to be clogs in the microcatheter
- Imaging of the delivery system determined the potential clumping was in the delivery box or the microcatheter 79
35.1000 SIR-Spheres
- Patient prescribed 2.697 GBq (72.9 mCi), received 0.93 GBq (25.16 mCi)
- No contamination was reported
- Delivered dose was clinically effective
- No changes to the catheter or procedures during this administration from prior administrations
- Root cause was determined to be a clog in the catheter
- Corrective actions taken included procedure modifications 80
35.1000 SIR-Spheres
- Patient prescribed 3.5 GBq (94.6 mCi), received 2.66 GBq (71.9 mCi)
- Catheter clogged due to high volume of microspheres
- Catheter was replaced and no stasis was observed, treatment continued
- No adverse effects on patient, no additional treatment was required 81
35.1000 SIR-Spheres
- Patient prescribed 1.6 GBq (43.2 mCi), received 0.17 GBq (4.53 mCi)
- Procedure was stopped after encountering resistance, intended to complete administration at a later time
- AU disconnected the line before releasing pressure
- Microspheres were expelled onto administration table and floor covering
- All coverings were disposed of and the room was decontaminated
- Root cause was suspected to be clogged microcatheter
- No adverse effects to the patient, follow-up treatment was administered 82
35.1000 SIR-Spheres
- Patient prescribed 299.7 MBq (8.1 mCi), received 229.4 MBq (6.2 mCi)
- Root cause was determined to be retention of microspheres in delivery device
- The relatively large percentage of activity retained in the delivery apparatus may be related to the small activity and volume prescribed
- No adverse effects were expected; the procedure was expected to be clinically effective
- Corrective actions included drawing low activity doses (555 MBq [15mCi] or less) using a delivery fraction of 0.90 instead of 0.095
- Better accommodate the larger residual percentages observed for low activities 83
35.1000 SIR-Spheres
- Patient prescribed 3.6 GBq (97.3 mCi), received 2.46 GBq (66.5 mCi)
- Full dose was separated into 2 administrations through 2 arteries
- First administered successfully, second encountered catheter occlusion
- Root cause was determined to be a deformed catheter with a significant kink point on the inner catheter body
- Reduced flow rate and allowed for full occlusion of the proximal segment of the catheter 84
35.1000 SIR-Spheres
- No adverse effects were expected
- Patient returned for remainder of the dose at a later time 85
35.1000 SIR-Spheres
- Patient prescribed 1.1174 GBq (30.2 mCi), received 0.8854 GBq (23.93 mCi)
- NMT encountered increasing resistance during treatment, leading them to believe stasis had been achieved
- Root cause was a clogged microcatheter discovered post treatment
- Subsequent treatment was given to make up for underdose
- Corrective actions included obtaining new equipment 86
- µCi - microcurie
- AMP - authorized medical physicist
- AU - Authorized User
- Cs-131 - Cesium-131
- cGy - centiGray
- CT - Computed tomography
- FY - Fiscal Year
- GBq - Giga Becquerel
- Gy - Gray
- HDR - High Dose Rate Remote Afterloader 87
- I-192 -Iridium-192
- IVB - Intravascular Brachytherapy
- MBq - Mega Becquerel
- µCi - microcurie
- mCi - millicurie
- NMT - Nuclear Medicine Technologist
- RSO - Radiation Safety Officer
- SI units - International System of Units
- Y Yttrium-90 88
QUESTIONS?
89
ACMUI Reporting Structure Don Lowman, ACMUI Coordinator Medical Radiation Safety Team April 5, 2022
Outline
- Current Reporting Structure
- Annual Review
- Meetings
- Discussion 2
Current Reporting Structure The Commission EDO Dan Dorman Director, NMSS John Lubinski Director, MSST Kevin Williams Chief, MSEB ACMUI Christian Einberg 3
Annual Review In September 2012, the ACMUI recommended to have an annual review of reporting structure.
4
Meetings Two meetings each year
- March/April
- September/October Approximately 2-3 teleconferences (as needed) 5
ACMUI Discussion 6
Points of Contact
- Kevin Williams - MSST Director
- Kevin.Williams@nrc.gov
- Christian Einberg - Designated Federal Officer (DFO), Chief, MSEB
- Christian.Einberg@nrc.gov
- Don Lowman -ACMUI Coordinator (acting)
- Don.Lowman@nrc.gov 7
- DFO - Designated Federal Officer
- EDO - Executive Director for Operations
- MSST - Division of Materials Safety, Security, States, and Tribal Programs
- MSEB - Medical Safety and Events Assessment Branch
- NMSS - Office of Nuclear Material Safety and Safeguards 8
TheraSphere Yttrium-90 Glass Microspheres TM Ashley Cockerham Advisory Committee on the Medical Uses of Isotopes Meeting April 5, 2022
Disclosure
- Consultant for Boston Scientific
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 2
Overview
- Product Information
- Ordering
- Setup
- Administration
- Disassembly
- Waste
- Written Directive
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved.
What is TheraSphere?
- Insoluble glass microspheres with a mean diameter of 15-35 µm1
- 1. Package Insert - TheraSphere Yttrium-90 Glass Microspheres - Rev.1. Biocompatibles UK Ltd, a BTG International group company.
- 2. Kennedy A et al. Int J Radiat Oncol Biol Phys 2007;68(1):13-23.
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 4
How does TheraSphere work?
- Delivered to tumor vasculature through the hepatic artery1,3
- 100% pure beta emitter
- Half-life of 64.1 h
- Average tissue penetration range of 2.5 mm
- 1. Package Insert - TheraSphere Yttrium-90 Glass Microspheres - Rev.1. Biocompatibles UK Ltd, a BTG International group company.
- 3. U.S. TheraSphere Reference Manual (PI-1001304-AA).
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 5
Recommended Treatment Algorithm
- The use of CBCT can improve assessment of tumor perfusion with the intent to minimize non-target deposition CBCT = Cone-Beam Computed Tomography; CT = Computed Tomography; GI = Gastrointestinal; MRI = Magnetic Resonance Imaging; Tc-99m MAA = Technetium-99 Macroaggregated Albumin
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved.
Ordering - Treatment Window Illustrator
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 7
Ordering - Online
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 8
Setup
- 1. Administration Set (Tubing)
- 2. Administration Accessory Kit 3 (Acrylic Box) 1 2
- 3. Nalgene Waste Container w/
Beta Shield
- 4. Radiation Meter 4 5. Saline Bag
- 6. RADOS Meter 8 7. TheraSphere Dose Vial 7 6 5 8. Additional Supplies
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 9
Administration Checklist
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 10
Setup - Contamination Precautions Three Separate Contamination Barriers:
- Drape/absorbent pad on floor underneath TheraSphere table/delivery path
- Second drape beneath outline line and catheter hub
- Third drape bridging administration box and patient Other Precautions:
- Recommend use of double gloves/shoe covers for staff involved in administration
- Establish contamination control point at exit of room to monitor hands and feet of all personnel
- Wrap catheter tip in gauze/small towel to control contamination when removing from patient
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved.
Setup - Administration Set Priming Once primed, connect needle system to dose vial Flush tubing set with saline, Place tubing set through ensuring two steady streams labeled slots in acrylic box through needle system
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 12
Administration - Optimize Delivery Dose Vial Handling
- Dose vial may have been inverted during shipment causing microspheres to become lodged around septum
- Gently rock lead pot 90° to wet microspheres and firmly tap bottom on hard surface
- Maintain vial in upright position until infused into patient Pinch Clamps
- Relieve dent in pinch clamp when opening prior to administration
- Minimize potential for air bubbles in outlet line Infusion Pressure
- Constant syringe pressure is important
- Recommended flow rate 20 cc/min (appropriate to flow of native vessel; slower rate may decrease delivery efficiency)
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 13
Administration - Optimize Delivery
- Infuse TheraSphere dose vial by pushing on syringe plunger
- Applying pressure >30 psi will cause saline to divert into 20 mL overflow vial (reduce pressure, if seen)
- Once completed, refill syringe by pulling plunger back
- A minimum of three flushes of 20 cc of saline are recommended
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 14
Administration - RADOS Meter
- Allow RADOS meter to stabilize for 15-30 seconds following delivery or x-ray use
- RADOS meter should be measuring in mR/h
- Typically reads 0.0 mR/h when all microspheres have cleared the vial
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 15
Disassembly - Waste Containment
- On final disassembly, pull microcatheter into base catheter and slowly remove both from the patient while controlling the tip with gauze or a towel
- Carefully cut and remove TheraSphere tubing, including attached catheters and acrylic dose vial, along with top set of gloves into waste container
- Survey remaining TheraSphere system materials for contamination
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 16
Waste Measurement All waste components inserted in 2L Nalgene waste jar
- Handling treatment waste involves mitigating:
- Hazards of patient blood
- High radiation fields
- Potential radioactive contamination
- Radiation safety considerations have driven the approach to estimating residual waste activity Waste Template Measurement (mR/h)
- Measure waste at 30 cm (12 in) from detector at four rotational positions
- Average these four measurements and subtract background radiation
- Calculate % difference between pre- and post-treatment template measurements to determine % vial delivered
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved reserved. 17
Written Directive The written directive captures all pre- and post-treatment measurements and automatically tracks and calculates TheraSphere % delivery
© 2022 Boston Scientific Corporation or its affiliates. All rights reserved. 18
SIR-Spheres Y-90 Resin Microspheres An Overview SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd Do not copy or distribute
Overview
- Preparation
- Delivery Box set up
- Delivery principle and infusion
- Potential abort points
- Post-procedure information 2
SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd Do not copy or distribute
Training Resources - New Account Resource Kit Training Education and Certification Program A Sirtex program designed to ensure site and users are adequately trained to use SIR-Spheres yttrium-90 resin microspheres, designed to mitigate risk to patients, users, the environment.
- Spills (Nuclear Medicine Technologists/Radiopharmacist/IR techs)
- Users (how to use Sirtex shielding devices (i.e. box, syringe shield, v-vial shield, SIROS)
- Patient (significance of patient selection, mapping and catheter placement to Adverse Events (i.e. REILD, RILD, Radiation pneumonitis))
Preparation 5
SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd TRN-TEC-001 rev # : 1 (CR 2860) Issued: 28 Sept 2021 Do not copy or distribute
Preparation Preparation Preparation Preparation Preparation Delivery Box Set Up 11 SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd TRN-TEC-001 rev # : 1 (CR 2860) Issued: 28 Sept 2021 Do not copy or distribute
Delivery Box Components SIR-Spheres Y-90 resin microspheres are delivered using a specialized Delivery Box. This box shields from beta radiation and prevents contamination in the unlikely event of a spill.
Delivery Set Delivery Box v-vial holder v-vial 12 SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd TRN-TEC-001 rev # : 1 (CR 2860) Issued: 28 Sept 2021 Do not copy or distribute
Delivery Box Components Continued Delivery Set There are one-way valves fitted to the tubes B and D to prevent any possibility of SIR-Spheres microspheres being injected back into either of the syringes with water for injection or D5W.
13 SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd TRN-TEC-001 rev # : 1 (CR 2860) Issued: 28 Sept 2021 Do not copy or distribute
Delivery Box Assembly Delivery Box Assembly Needle Positions Delivery Principle and Infusion Infusion Potential Abort Points Potential Abort Points Post-Procedure Checklist 21 SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd TRN-TEC-001 rev # : 1 (CR 2860) Issued: 28 Sept 2021 Do not copy or distribute
Post-Procedure Checklist Collect v-vial and other residually contaminated materials in mayo jar and measure residual.
Check personnel for contamination before leaving suite.
Check suite for contamination after patient leaves.
22 SIR-Spheres is a registered trademark of Sirtex SIR-Spheres Pty Ltd TRN-TEC-001 rev # : 1 (CR 2860) Issued: 28 Sept 2021 Do not copy or distribute
Patient Release Questions?
Thank you for your attention!
Checklists: Reducing Mis-Administration and Other Events During Y90 Radioembolization J. Fritz Angle, M.D.
University of Virginia
Collaborators
- Robert Mulder, PhD
- Andrew Polemi, PhD
- Paul W. Read MD, PhD
- Einsley-Marie Janowski MD, PhD
Stubborn Floor To The Number of Reportable Events in USA Annual Y90 Reported Medical Events 30 25 20 15 10 5
0 2017 2018 2019 2020 Therasphere SIR-sphere Dr .Ronald D. Ennis, ACMUI Fall Meeting. October 4, 2021
The Most Common Unexpected Events Are A Relatively Short List
- Incomplete delivery of prescribed dose (device or technique related)
- Delivered dose larger than planned or desired for intended target
- Administration into the wrong lobe or segment
- Treatment does not adequately treat all feeding arteries (planning or delivery)
- GI or other extra-hepatic mesenteric dose delivery (planning or delivery)
- Arterial-venous shunting with lung injury
- Arterial-portal shunting with liver, GI or lung injury
- Wrong patient
- Spills, splashes, or improper disposal
- Unexpected exposure to fetus, family, caregivers, Y90 team members or pathologists (autopsy)
Breaking The Medical Training Is Useful But There Is No Hierarchy Substitute For Experience
- Speak up for safety (event reporting without repercussion)
- Chain of command responds to reporting
- Events lead to durable change
- Institutions can also be relatively isolated in implementing safety measures Peadon R (R), Hurley J, Hutchinson M. Safety Sci. Character Colonel Rosa Klebb played by Lotta 2020;125:104648 Lenya in From Russia With Love (1963)
Common Medical Error Reduction Methodology
- Team approach to identifying steps in the process and high-risk steps
- Review of events (internal and external) with process analysis
- Develop actions and outcome measures
- Time out
- Checklists
- Data collection with regular analysis, communication, and process updates Chiossa ML, Ponzetti C. FMEA: a model for reducing medical errors. Clnca Chimica Acta 2009; 404: 75-78
UVA Y90 Planning Initiation Identification of potential patient by liver tumor board MAA study with hepatic artery branch pruning If shunt fraction low and anatomy favorable: Y90 team activation Standardized Y90 administration
Y90 Planning Initiated by Interventional Radiologists
- Defines tumor vascularity
- Measures liver, lobar and tumor volumes (stored in PACS)
- Defines which segments or lobes to be treated and in what sequence
- Suggest a target dose
- Suggests Therasphere or SIR-sphere (mostly based on desired number of particles)
- Forwards the tentative plan to radiation oncology and radiation physics
Checklists As Essential As For Flying A Plane
- Set pause points at which the checklist is supposed to be used
- DO-CONFIRM versus READ-DO checklist:
- READ-DO tasks are checked off as they are performed
- In DO-CONFIRM tasks are performed from memory and then confirmed at key stopping points
- We started with READ-DO and evolved to DO-CONFIRM Atul Gawande, 2009. Metropolitan Books
Pre-Procedure Checklist
Intra-procedure Checklist
Post Procedure Checklist Troubleshooting Troubleshooting Checklist
- Current list of problems at our institution was developed from personal experience, NRC notifications, and communication at meetings
- Ideally, we would also have a process for all commonly encountered problems
- Check lists remain a great opportunity to standardize how we manage known problems
Summary
- Most important tool to preventing adverse events is having a defined team with established communication
- Checklists seem ideally suited to Y90 planning and administration
- Opportunity for standardization of these checklists across institutions
- Maintaining compliance with check lists presents a challenge
RAR Council on Radionuclides and Radiopharmaceuticals, Inc.
CORAR ACMUI Presentation Comments to NIST - re: NRMAP April 5, 2022 CORAR Council on Radionuclides and Radiopharmaceuticals, Inc.
CORAR
- The Council on Radionuclides and Radiopharmaceuticals, Inc.
(CORAR) is a Washington, DC based trade association of companies that manufacture radiopharmaceuticals, radionuclides, and other radioactive products used in medicine, research, and industry.
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 2
CORAR Comments to NIST
- On January 13, 2022, CORAR submitted comments to James K. Olthoff, PhD, Acting Director, National Institute of Standards and Technology (NIST).
- Restart of the NIST Radioisotope Measurement Assurance Program (NRMAP) and provide sufficient resources for the NRMAP and the NIST Radioactivity Group.
- The NRMAP has provided Standard Reference Materials (SRMs) and Reference Materials (RMs) to medical and industrial stakeholders for the past 47 years.
- Participants in the NRMAP receive SRMs and RMs to ensure their radiation measurements are NIST traceable.
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 3
CORAR Comments to NIST
- An extended interruption in the NRMAP service began in late 2019.
- The NRMAP was unable to provide the required calibration standards for more than 24 months; and
- no clear resolution to the ongoing shutdown of the NRMAP.
- In nuclear medicine, radiopharmaceuticals are used in the diagnosis and treatment of disease.
- Devices that measure the radioactivity of a dose must use calibration sources that can be traced to NIST SRMs and RMs that have been provided by the NRMAP.
- Accurate dose measurement could have Medicare reimbursement implications for radiopharmaceutical dose payment based on activity (e.g. mCi, uCi).
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 4
CORAR Comments to NIST
- The NRMAP shutdown occurs at a time when exciting new radiotherapies are being developed exploiting alpha-emitting and beta-emitting characteristics such as:
- lutetium-177 (Lu-177) - actinium-225 (Ac-225)
- copper-67 (Cu-67) - lead-212 (Pb-212)
- Medical and industrial licensees require NIST traceability making the restart of the NRMAP a high priority for radiopharmaceutical and industrial radioisotope industries.
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 5
CORAR Comments to NIST
- CORAR expressed concerns that further delays in restarting the NRMAP could result in several challenges:
- complying with FDA and NRC regulatory requirements (10 CFR 32.72(c), 10 CFR 35.60, and 10 CFR 35.63);
- providing radiation detection measurement standards that ensure patient and worker safety;
- supplying short-lived diagnostic and therapeutic standards traceable to NIST SRMs and RMs;
- having NIST traceable SRMs and RMs available in the development of new radiopharmaceuticals.
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 6
CORAR Comments to NIST
- CORAR closed with an urgent request; that NIST facilitate the restart of the NRMAP as soon as safely possible and re-invigorate with sufficient resources both the Radioactivity Measurement Group and the NRMAP, to ensure that required NIST traceability needed by U.S. healthcare and industry is consistently available in CY 2022 and beyond.
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 7
NIST Response to CORAR
- Dr. Olthoff responded on February 2nd and thanked CORAR for its comments. With regard to the NRMAP services, Dr. Olthoff mentioned:
- NIST remains fully committed to delivering high quality radioactivity metrology services;
- NIST has embarked on a restructuring of the existing the NRMAP; and
- NIST is working expeditiously to restore the essential functions of the NRMAP.
- CORAR appreciates the follow-up from Dr. Olthoff, and we look forward to learning more about the return of services provided by the NRMAP.
CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 8
- CORAR - Council on Radionuclides and Radiopharmaceuticals
- FDA - Food and Drug Administration
- NIST - National Institute of standards and Technology
- NRC - Nuclear Regulatory Commission
- NRMAP - NIST Radioisotope Measurement Assurance Program
- RMs - Reference Materials
- SRMs - Standard Reference Materials CORAR Council on Radionuclides and Radiopharmaceuticals, Inc. 9
Changes to the NRMAP Program Brian E. Zimmerman, PhD Leader, Radioactivity Group Radiation Physics Division, Physical Measurement Laboratory National Institute of Standards and Technology NRC Advisory Committee on Medical Uses of Isotopes 5 April 2022 via Teams
Why?
- Decision made by NIST Senior Management after complete review of program following a safety-related incident
- Many considerations, but overarching one is that establishing and maintaining standards is an inherently Governmental function that must be done by Federal employees
- Program has grown in complexity
- Increased administrative burden
- Greater need for Government oversight to ensure safety and integrity of traceability chain
- Changes in Program will provide:
- Increased safety
- Enhanced integrity
- Greater accountability
Planning Considerations
- At its height in late 1990s, the Program supported 2 FT professionals, a FT technician, and 0.5 secretary/shipping clerk (shared with Radioactivity Group) .
- Gas standards were distributed through the Program, but were conducted by NIST staff (without compensation back to NIST).
- Gamma-ray spectrometry support was provided (uncompensated) by NIST staff dedicated 100 % to those types of measurements (and metrology research in that field).
- Ongoing commitment to development of new standards (89Zr, 212Pb, 227Th, 225Ac).
Important legal factors
- Establishing and maintaining standards is a government function
- US Constitution, Article 1, Sec. 8.
- Organic Act and National Institute of Standards and Technology Act (15 USC 271, ff)
- Promoting transfer is specifically called out in the above, but mechanism is not defined
- Federal Policy (OMB Circular A-76) prohibits NIST from competing directly with private industry for same services
- NIST must recover all costs associated with its programs (Antideficiency Act (Pub. L.97-258, 96 Stat. 923))
How we will proceed
- All-Fed program
- Support for changes from NIST Office of Associate Director for Laboratory Programs
- Direct Government supervision, funding of program/cost recovery
- Safety and security are paramount
- Reduction in risk to NIST re: radiation hazards
- Source accountability
- Sufficient staff to perform duties
- Steps will be taken slowly and deliberately in order to ensure safety and compliance with Federal law
- Continue to meet customer needs to whatever degree possible, given current constraints
Immediate significant changes
- Blind distributions are suspended
- Traceability instead through Radioactivity Groups Calibrations Program
- Reports of Traceability are suspended
- Information needed for traceability claims will be provided in calibration reports
- NIST policy states:
- Entity making traceability claim is responsible for documenting, providing proof
- Interpretation of traceability claim is responsibility of customer
- NIST only provides data to support claims, but makes no judgement
Phase 1
- T=0 to T=6 months (approximate)
- Communicate plan to stakeholders
- Address critical calibration needs
- Clear backlog of outstanding certificates, reports
- Work with stakeholders to prioritize submissions
- Shift existing personnel to calibrations as much as possible
- Make necessary changes to QMS
- Begin hiring process for new personnel
- Goal: enable essential services using existing mechanisms
- Realistic throughput: max 2 calibrations/month
Phase 1: Assumptions
- The level of rigor will be raised since the NIST Radioactivity Group is directly making the measurements, therefore the time required for calibrations will initially be greater.
- NRMAP submissions will be done through 43010C, 43020C, 43060S, or 43090S* as appropriate
- We can currently only accept submission rate of up to 2 sources per month
- Standard Reports of Test can be modified to include difference from NIST value for traceability documentation
- Service is currently suspended, but is being restarted
Phase 2
- T=6 to T=18 months (approximate)
- Complete hiring process
- Training of new personnel
- Gradually increase throughput as new personnel become independent
- Continue to work with stakeholders to prioritize submissions
- Previously re-assigned personnel gradually return to former duties
- Continue to make necessary changes to QMS
- Realistic throughput: max 4 calibrations/month
- Investigate use of new measurement geometry for this program
- Investigate secondary calibrations lab concept to extend traceability with need for direct NIST calibrations
Phase 3 (overlap with Phase 2)
- T=12 to T = 24+ months (approximate)
- Continue training of new personnel
- Gradually increase throughput as new personnel become independent
- Develop new Measurement Service to cover all MAPs, including environmental
- Some limited samples may be sent as blinds
- Realistic throughput: max 6 calibrations/month
- Implement inclusion of second measurement geometry
Major changes to Program
- Greater reliance on companies internal QA/QC capabilities (1 site providing standards to subsidiaries)
- Most work will be done as calibration, not distribution; calibrations may be coordinated so work is done on 1 or 2 radionuclides at a given time
- Number of SRMs offered across all programs will likely decrease
- Limited number of nuclides may be sent as blinds (mid-Year 2 at earliest)
- Costs to participants may increase due to overhead on government salaries
- Gases will finally be re-incorporated into the Program
- Special Test may be created specifically for NRMAP and other PT/MAP programs during Year 2
- Program will now be completely covered fully under NIST QMS, compliant with ISO 17025, ISO 17034, and ISO 17043
This program is a critical component of our mission
- NIST Management has indicated their commitment to this transition
- We are not getting out of the calibrations/SRM business
- Not competing with private industry
- Providing new opportunities for business to provide traceability
- Success in transition relies on program members prioritizing their needs
- Expanding capabilities
- Gases
- More convenient geometry
- More flexibility for members
Questions?
Non-Medical Byproduct Material Events: FY20 and FY21 ACMUI Meeting April 5, 2022 Michael Sheetz 1
Non-Medical Events Reported by Medical Licensees
- NMED events reported by medical licensees
- Does not include medical events under 10 CFR 35.3045 or 35.3047
- Includes event types reported under:
- Leaking sealed source (10 CFR 35.3067)
- Lost, abandoned, or stolen material (10 CFR 20.2201)
- Radiation over exposure (10 CFR 20.2202)
- Release of material or contamination (10 CFR 30.50)
- Equipment malfunction (10 CFR 30.50)
- Transportation incidents (49 CFR 171.15)
Non-Medical Event Categories Identified in FY20 and FY21 Category FY20 FY21 Lost, Abandoned, or Stolen Material 17 23 Leaking Sealed Source 2 5 Equipment Malfunction 5 2 Transportation of Radioactive Material 1 4 Radiation Overexposure 1 3 Radioactive Contamination 3 1 Total 29 38 3
Total NMED Events (All Categories)
FY20 and FY21 67 838 Non-Medical Events from Medical Licensees All Other Events 4
Lost, Abandoned, or Stolen Sources FY20 and FY21
- Licensee lost medical sources - 6
- Missing I-125/Pd-103 brachy seeds - 3
- Temporary loss of RAM shipment - 3
- Incomplete shipment of I-125 brachy seeds - 2
- Lost RAM shipment - 2
- Delivery vehicle stolen - 2
- Abandoned calibration sources - 1
- Ir-192 sources delivery to wrong location - 1
- Lu-177 vials in medical waste - 1 5
Leaking Sealed Source FY20 and FY21
- Cs-137 dose calibrator vial - 6
Equipment Malfunction FY20 and FY21
- Sr-90 IVB device source retraction failure - 4
- Co-60 Gamma Knife device treatment interruption - 1 7
Transportation of Radioactive Material FY20 and FY21
- Contaminated package - 4
- Delivery vehicle accident - 1 8
Radiation Overexposure FY20 and FY21
- Interventional radiologist using Y-90 microspheres - 2
- PET radiochemist researcher - 1
- (800 mSv SDE)
- Non-patient nuclear medicine procedure - 1
- (8.5 mSv EDE) 9
Radioactive Contamination FY20 and FY21
- Inpatient room contamination from patient receiving I-131 MIBG - 1
- Hot lab contamination from breaking open I-131 capsules - 1
- Nuc med tech contamination during administration of Tc-99m - 1
- Rb-82 generator system contamination - 1 10
Other Events - Landfill Alarms
- Detection of short-lived medical isotopes in municipal waste
- No standard reporting requirement
- Varying number of events reported FY17 FY18 FY19 FY20 FY21 18 17 6 9 9
- Can result in significant response effort 11
Conclusions
- Relatively small number of Non-Medical events
- Type of events occurring have minimal health and safety impact
- Need for continued effort to address short-lived medical isotope landfill alarm responses to reduce burden on regulators, licensees, and patients 12
- ACMUI - Advisory Committee on the Medical Use of Isotopes
- CFR - Code of Federal Regulations
- Co cobalt-60
- EDE - Effective Dose Equivalent
- F flourine-18
- FY - Fiscal Year
- Ge germanium-68
- HDR - High dose-rate 1
3
- I-125/131 - iodine-125/131
- IR - Interventional Radiology
- IVB - Intravascular Brachytherapy
- LDE - Lens Dose Equivalent
- MIBG - metaiodobenzylguanidine
- mSv - milliSievert
- NMED - Nuclear Material Events Database 1
4
- Pd-103 - palladium-103
- PET - Positon Emission Tomography
- RAM - Radioactive Material
- Rb rubidium-82
- RSL - Radioactive Seed Localization
- SDE - Shallow Dose Equivalent
- Sr strontium-90
- Sv - Sievert
- Tc-99m - technetium-99 metastable
- Y yittruim-90 15
Updates from the Medical Radiation Safety Team Celimar Valentin-Rodriguez, Ph.D.
Medical Radiation Safety Team Leader (acting)
Medical Safety and Events Assessment Branch Division of Materials Safety, Security, State, and Tribal Programs Office of Nuclear Material Safety and Safeguards
Abnormal Occurrence Criteria
- SECY-22-0009, Proposed Limited Revision to Policy Statement on Criteria for Reporting Abnormal Occurrences, February 1, 2022 (ML21217A201)
- Proposed revisions to medical AO criteria:
- Step 1: Quantitative (dose-based) Assessment Criterion
- Step 2: Qualitative (deterministic effects) Assessment Criterion
Abnormal Occurrence Criteria Step 1 - Quantitative Assessment (Criterion III.C.1)
Dose-based threshold values remain the same. Proposed revisions:
- Clarify that AO include medical events reported under 10 CFR 35.3045 and in specific license conditions.
- Clarify dose to be unintended rather than expected.
- Removed written directives as a necessary requirement for an AO since some medical administrations do not require it.
- Include unintended dose that would have resulted from delivery of prescribed dose, prescribed dosage, or prescribed activity.
Abnormal Occurrence Criteria Step 2 - Qualitative Assessment (Criterion III.C.2)
Add qualitative consideration based on physiological harm which promptly manifests following treatment (deterministic effects)
- Explored in SECY-19-0088
- Compared NRC approach to HHS
- Medical Team staff provided its evaluation of whether extravasations should be reported as medical events to the ACMUI.
- The ACMUI supported the staffs recommended Extravasations option 4, to report extravasation events that require medical attention.
- The NRC staff will provide a package to the Commission in April 2022 to disposition PRM-35-22.
Emerging Medical Technologies
- The Medical Team continues to implement a streamlined review and guidance development process.
- The staff has evaluated several EMTs with this streamlined process.
Liberty Vision Y-90 Alpha DaRT' CivaDerm Disc Source
The staff established a joint NRC/Agreement State working group in February 2022.
Emerging Medical Technologies Rulemaking SCHEDULE REGULATORY PROPOSED BASIS RULE FINAL RULE March 2023 AND AND DRAFT GUIDANCE 90-day public GUIDANCE comment August 2026 period August 2024
Training and Experience Rulemaking
- SRM-SECY-20-0005, Training and Experience Requirements for Unsealed Byproduct Material, January 27, 2022 (ML22027A519)
- The Commission maintained the NRCs current T&E requirements for use of unsealed byproduct material in 10 CFR Part 35.
Training and Experience Rulemaking Reconsider the full complement of T&E requirements and obtain stakeholder comments, as part of the EMT/Rb-82 Generator Rulemaking Complete an evaluation of whether each specialty board still satisfies the board recognition criteria Develop implementation guidance to clarify expectations on how individuals fulfill T&E requirements and clarify the roles and responsibilities of persons subject to T&E requirements.
Veterinary Release Oct. 2021 Feb.-Mar. 2022 Sept. 2022 Working Group established Alignment on Rulemaking Plan to the recommendations Commission Draft Rulemaking Plan to Agreement States for comment G2G with Agreement States G2G with Agreement States Dec. 2021 Spring 2022
- AO - Abnormal Occurrence
- CFR - Code of Federal Regulations
- EMT - Emerging Medical Technologies
- G2G - Government-to-Government Meeting
- HHS - US Department of Health and Human Services
- PRM - Petition for Rulemaking
- Rb Rubidium-82
- T&E - Training and Experience
OPEN FORUM (No Handout)
ADMINISTRATIVE CLOSING
September 2022 SUN MON TUES WED THUR FRI SAT 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 November 2022 SUN MON TUES WED THUR FRI SAT 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 December 2022 SUN MON TUES WED THUR FRI SAT 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31