Information Notice 2019-12, Recent Reported Medical Events Involving the Administration of Yttrium-90 Microspheres for Therapeutic Medical Procedure

Recent Reported Medical Events Involving the Administration of Yttrium-90 Microspheres for Therapeutic Medical Procedure

ML19262G231
Person / Time
Issue date:	12/31/2019
From:	Michael Layton, Chris Miller Office of Nuclear Material Safety and Safeguards, NRC/NRR/DRO
To:
Benney B
References
IN-19-012
Download: ML19262G231 (4)

UNITED STATES

NUCLEAR REGULATORY COMMISSION

OFFICE OF NUCLEAR MATERIAL SAFETY AND SAFEGUARDS

WASHINGTON, DC 20555-0001 December 31, 2019 NRC INFORMATION NOTICE 2019-12: RECENT REPORTED MEDICAL EVENTS

INVOLVING THE ADMINISTRATION OF

YTTRIUM-90 MICROSPHERES FOR

THERAPEUTIC MEDICAL PROCEDURES

ADDRESSEES

All U.S. Nuclear Regulatory Commission (NRC) medical-use licensees and NRC master

materials licensees that are authorized for yttrium-90 (Y-90) microspheres in accordance with

Title 10 of the Code of Federal Regulations (10 CFR) 35.1000, Other Medical Uses of

Byproduct Material or Radiation from Byproduct Material. All Agreement State Radiation

Control Program Directors and State Liaison Officers.

PURPOSE

The NRC is issuing this information notice (IN) to inform licensees of recent reported medical

events that involved the administration of Y-90 microspheres. The NRC expects that recipients

will review the information for applicability to their facilities and consider actions, as appropriate, to avoid similar medical events. INs may not impose new requirements, and nothing in this IN

should be interpreted to require specific action. The NRC is providing this IN to the Agreement

States for their information and for distribution to their medical licensees, as appropriate.

DESCRIPTION OF CIRCUMSTANCES

From 2016-2018, the NRC received reports of 71 medical events involving NRC or Agreement

State licensees regarding the administration of Y-90 microspheres. Although 2019 data is not

yet available, these medical events continue and are monitored. These reported medical events

resulted from a variety of causes, such as errors with the written directive; clogging and kinking

in the catheters causing the administration of a reduced amount of microspheres to the patient;

and treatment of the wrong location, such as the wrong lobe of the liver. Events involving

treatment of the wrong location were identified when licensees used post-treatment imaging. It

is important to note that some of the events are associated with the inherent risks of the

treatment such as shunting to wrong treatment sites and may not be prevented by using the

current standard of care. The NRC requires reporting of events that meet medical events

criteria per 10 CFR 35.3045 and licensees approved conditions per 10 CFR 35.1000.

Of the reported medical events, seven events involved dose or activity going to the target organ

that exceeded the written directive by more than 20 percent as a result of human errors not

related to the physical delivery of the microspheres. The causes of these medical events

involved errors in measuring the activity before administration, improper control of vials

containing the microspheres, and failure to consult the written directive. One example occurred

on June 14, 2017, when the licensee delivered an activity of 8.55 gigabecquerels (GBq)

(231 millicurie (mCi)) to a patient instead of the prescribed activity of 1.71 GBq because the

ML19262G231 licensee did not verify the measured activity of the dosage with the written directive (Event

Notification [EN] 52807). Another example occurred on December 29, 2016, when a licensee

delivered an activity of 816.85 megabecquerels (MBq) (22.1 mCi) to a patient instead of the

prescribed activity of 90.76 MBq because the licensee used a vial intended for treatment of a

different area of the patients liver (EN 52473).

Of the Y-90 microspheres medical events that occurred from 2016 through 2018, 27 appear to

have involved blockages of the microspheres in the delivery system. Specifically, five events

involved kinks or dents in the catheter. In these events, the Y-90 microspheres built up and

caused a blockage around the kink or dent. The majority of the remaining 22 events occurred

because of suspected clumping of the Y-90 microspheres in the catheter. Clumping is a known

phenomenon which can occur for both of the Y-90 microsphere manufacturers (SIR-Spheres

and TheraSphere). Many events occurred during unique administrations, such as unusually

large or small doses or use of a slower flow rate. In one example, on October 27, 2017, a

licensee delivered an activity of 0.4255 GBq to a patient instead of the prescribed activity of

2.22 GBq because the microcatheter apparently clogged as a result of the large number of

microspheres being administered (EN 53040). Another example occurred on April 12, 2016, when the licensee delivered an activity of 0.04 GBq to a patient instead of the prescribed activity

of 1.29 GBq because of apparent clumping of the microspheres in the microcatheter (EN 51868).

In addition, there were eight other events that involved treatment to the wrong location, such as

the wrong lobe of the liver. Of these events, four involved an administrative error that caused

the microspheres to be delivered to a site other than prescribed location. In another event that

occurred on June 6, 2018, the interventional radiologist delivered the microspheres through the

wrong hepatic artery. A different interventional radiologist had previously performed

pretreatment mapping and identified the patient had atypical hepatic arterial anatomy, however, this was not reported to the radiologist preforming the treatment. This event resulted in a dose

of 11,086 centigray (rad) to the wrong liver lobe (EN 53448). The remaining three events

involved microspheres that traveled to the wrong liver lobe for unknown reasons. The four

events not associated with administrative errors were identified through post-treatment imaging.

Although the NRC regulations do not require post-treatment imaging, licensees must report

medical events identified by these images per 10 CFR 35.3045 and licensees approved

conditions per 10 CFR 35.1000.

DISCUSSION

Administrative errors involving the written directive for several of the above examples of medical

events, demonstrate the importance of licensees having a signed and dated written directive as

described in the Y-90 microsphere licensing guidance document, and licensees reviewing the

written directive before the administration of the Y-90 microspheres. The written directive shall

include the name of the patient or human research subject, the treatment site, the radionuclide

including the physical form (Y-90 microspheres), the model of spheres (i.e., TheraSphere or

SIR-spheres) or manufacturer (i.e., Nordion or Sirtex) and the prescribed dose or activity as

described in the Y-90 microsphere licensing guidance document. In addition, licensees should

determine and record the activity of the dosage before use, and only use it if it falls within 20

percent of the prescribed dosage. Finally, these medical events demonstrate the importance of

licensees developing, implementing, and maintaining written procedures to provide high

confidence that each administration is in accordance with the written directive. The NRC

recommends the use of timeouts in these procedures to ensure that planned administration

aligns with the written directive immediately before administration for Y-90 microspheres. In summary, this IN is intended to provide licensees with a heightened awareness of numerous

medical events involving incorrect administration of a prescribed dose or activity of Y-90

microspheres in the past several years. Licensees should be aware that small kinks in the

catheter can lead to an underdose, and the NRC recommends visual inspection of all tubing

before starting the procedure. Licensees should review manufacturer recommendations to

avoid clumping. Licensees are encouraged to communicate with their peers in the industry or

Y-90 microsphere vendors to identify best practices with respect to the administration of the

microspheres, especially in unique administrations such as when unusually large or small doses

or use of a slower flow rate is necessary for the patient.

CONTACT

S

This information notice requires no specific action or written response. Please direct any

questions about this matter to the technical contact listed below or to the appropriate regional

office.

/RA/ for /RA/

Christopher G. Miller, Director Michael C. Layton, Director

Division of Reactor Oversight Division of Materials Safety, Security, State, Office of Nuclear Reactor Regulation and Tribal Programs

Office of Nuclear Material Safety

and Safeguards

Katie Tapp, NMSS

301-415-0236 E-mail: Katherine.Tapp@nrc.gov

ML19262G231 EPIDS No.

OFFICE NMSS/MSST/MSEB QTE NMSS/MSST/MSEB NMSS/MSST/MSEB

NAME KTapp KAzariah-Kribbs LDimmick CEinberg

DATE 10 / 21 /19 9/23/19 10/22/19 11/6/19 OFFICE NMSS/MSST/MSEB NRR/DIRS/IRGB/PM NRR/DIRS/IRGB/LA NRR/DIRS/IRGB/BC

NAME MLayton BBenney IBetts LRegner

DATE 11/12/19 11/13/19 11/14/19 11/25/19 OFFICE NRR/DIRS/D

NAME CMiller for

DATE 12/31/19