Medical Device Daily Washington Editor
BETHESADA Maryland – The Nuclear Regulatory Commission hosted a meeting of the Advisory Committee on the Medical Uses of Isotopes (ACMUI) April 25 to review a number of issues, including the training requirements for medical uses of radioactive byproduct materials. The training issues centered on the use of microspheres made with yttrium-90 (Y-90) for radiation oncologists and nuclear physicians, but interventional radiologists also sought a place at the table.
Some controversy arose over the duration of training for Y-90 use –typically provided by proctors who are sponsored by the manufacturers. Several comments heard during the afternoon briefing indicated an interest in more demanding training regimes, but the panel did not pass on to NRC a recommendation for more stringent requirements than are already in place.
Microspheres made with Y-90 are currently the subject of an investigational device exemption by FDA for treatment of unresectable hepatocellular carcinoma. At present, two firms engaged in the manufacture of Y-90, MDS Nordion (Ottawa, Canada), and Sirtex Medical (Lake Forest, Illinois), are sponsoring their use in this area.
Douglas Eggli, MD, the chief of the Division of Nuclear Medicine at Penn State University (University Park) gave a nuclear physician perspective on therapy with Y-90 microspheres, during which he pointed out that Y-90s are registered as brachytherapy sources, but that the units do not have serial numbers and due to their small size, are too numerous to count. Y-90 microspheres, which can be encapsulated in glass or resin, tend to behave much like “large particles,“ giving the example of macroaggregated albumin as a comparison.
On the subject of training requirements, Eggli remarked that “any experienced therapeutic physician trained under 10 CFR 35 part 300 or part 400 can be readily further trained to safely handle therapeutic microspheres,“ specifying that nuclear medicine physicians can “learn appropriate dosimetry techniques“ and that radiation oncologists can learn “to manage administration and spills similar“ to the requirements for unsealed sources.
However, Eggli added that while “the bottom line“ is that many can be appropriately trained, he questioned whether three supervised procedures was enough to qualify a practitioner to use Y-90 to treat cases of unresectable hepatocellular carcinoma because the procedure “is more complicated than I-131 (iodine 131) use“ for thyroid carcinomas.
Eggli's references are to 10 CFR 35, the section of the code that addresses medical use of byproduct materials. Subsection 490 states that an authorized user is one who has completed “a minimum of three years of residency training“ in an approved radiation oncology program and who has “completed a structured educational program in basic radionuclide handling techniques applicable to the use of manual brachytherapy sources.“
Subsection 390 addresses training for “use of unsealed byproduct material for which a written directive is required,“ directing that practitioners “successfully complete residency training in a radiation therapy or nuclear medicine training program or a program in a related medical specialty.“ This includes the requirement of “700 hours of training and experience, including a minimum of 200 hours of classroom and laboratory training, in basic radionuclide handling techniques.“ Subsection 490 calls for 200 hours of classroom and laboratory training and 500 hours of work experience under the supervision of an authorized user.
David Diamond, MD, of Florida Hospital Cancer Institute (Orlando) drew essentially the same conclusion as Eggli on the overall training/experience question, albeit from the perspective of a radiation oncologist. He noted that categorizing Y-90 microspheres presented problems in terms of categorizing their use under the manual brachytherapy rubric because “one cannot count the individual sources“ due to the fact that each spherical container of Y90 contains several million microspheres, making them too numerous to count. He also pointed out that technetium-99 microspheres “used for decades in nuclear medicine have never been regulated as such.“
After Diamond and Eggli finished their presentations, Riad Salem, MD, director of interventional radiology at Northwestern University (Chicago), stated that “it does not appear that interventional radiologists had any input“ into the rules addressing the use of Y-90 microspheres.
Salem said that his experience with the microspheres includes “850 infusions of Y-90 microsphere therapy as the authorized user,“ including the performance of “clinical patient assessment, eligibility for treatment, dosimetry, and long-term follow-up.“ (Interventional radiology is essentially treatment of diseases by means of small catheters and catheter-based instruments. Many of the common procedures include arteriograms and insertion of vascular access devices, but this field has also moved into radioablation of tumors.)
Speaking for the Society for Interventional Radiology (Fairfax, Virginia), Salem commented that interventional radiologists (IRs) must undertake 960 hours of training in nuclear medicine during their residencies and that “[o]f the last 50 peer-reviewed publications and book chapters [addressing Y-90], more than 55% were generated“ by IRs.
Salem added that while the FDA classifies Y-90 microspheres as a sealed source or radiation delivery device, this regime ignores “the unique delivery methodology for the device.“ He argued that the delivery method “depends on knowledge of the vascular system“ as well as a working knowledge of “the anatomy and dynamic changes in the capacitance of the hepatic vascular bed, catheter infusion pressure and angiographic endpoints,“ which he described as “skills [that] are intrinsic to the practice of interventional radiology.“
Salem closed his comments with the statement that IRs are qualified to handle this procedure because of the training and experience required to obtain certification, which is in turn “ultimately supported by the fact that as of today, radiation oncologists and nuclear medicine physicians are being trained by interventional radiologists.“
Among the representatives of NRC was Donna Beth Howe, PhD, who made the case that IRs might need three training sessons and another three proctored procedures before going into Y-90 work alone because “this is a complicated procedure that has many places where things can go wrong.“
Salem rebutted that “problems have not been conspicuous“ but admitted that “significant handholding“ is nonetheless required of the manufacturer due to the complexities involved.