American Thyroid Association 86th Annual Meeting:
RAI: Beyond Evidence-Based Medicine to Manage Thyroid Cancer
Using personalized medicine, not simply evidence-based medicine, can help physicians to better decide which patients with thyroid cancer can safely avoid radioactive iodine (RAI) treatment, according to Paul Walfish, MD, professor emeritus of medicine, pediatrics, otolaryngology, pathology and laboratory medicine at the University of Toronto, Ontario, Canada, at the American Thyroid Association (ATA) annual meeting.
Dr. Walfish challenged the ATA Guidelines for post-operative management of thyroid cancer1 at a symposium hosted by Sanofi Genzyme, manufacturer of Thyrogen (thyrotropin alfa for injection), genetically engineered human thyroid stimulating hormone (TSH), during the American Thyroid Association annual meeting.
Evidence-based guidelines, Dr. Walfish told EndocrineWeb, ''are based on groups and metaanalyses; however, the evidence is not necessarily strong based on the individual."
Personalizing treatment decisions for the post-surgical management of low and intermediate risk papillary thyroid cancer patients,” he said, “can help the vast majority of [these] patients avoid RAI, even though under evidence-based guidelines they would not."2
In challenging evidence over personalization of care, Dr. Walfish reviewed his team's 2015 findings for a cohort of 129 patients with primary thyroid tumors of 1 centimeter or more.2,3 All patients were enrolled in a personalized risk stratification and radiation selection protocol with post-op stimulated thyroglobulin (Stim-tg) and neck ultrasound. The mean follow up was 5.6 years.
“The follow up has been extended to 8 years, with the goal to republish the data after the 10 year mark,” Dr. Walfish told EndocrineWeb. He added, “To date, there have been no surprises, and only one false negative, since the 5-year mark.”
The findings as published,2 showed the following:
- 84 (65%) had undetectable Stim-Tg after initial surgery
- 40 (31 %) had Stim-Tg of 1-5 µg/L
- 5 (4 %) had Stim-Tg >5 µg/L
- RAI was given to 8 (20 %) patients with Stim-Tg 1-5 µg/L, and 5 (100 %) with Stim-Tg >5 µg/L
- RAI therapy was avoided in 17/20 (85%) patients with tumors >4 cm, while 72/81 (89%) patients over age 45
- 6/9 (67%) patients with central lymph node involve-ment avoided it
Of the 129, 116 (90%) have not received RAI therapy, and have no evidence of residual or recurrent disease,2 according to Dr. Walfish. Among the 13 who received RAI, 1 patient had residual/recurrence.2
The characteristics of the cohort2 was: 78% (100) were female, 63% were age 45 or older. The average tumor size was 2.49 (+-1.44 cm). Twenty had tumors more than 4 cm.
"Overall, in this group of patients, only 10% needed RAI,"2 Dr. Walfish said. ''As we showed, it didn’t matter what your age or tumor status was.''
Challenging Current Guidelines
"Eighty to 90% of low to intermediate risk thyroid cancer patients do not need radioactive remnant ablation routinely.''3 Dr. Walfish said. "The ATA is now beginning to recognize this."
Dr. Walfish added that he had one patient in the very low risk group, who could have avoided RAI based on the results, but who opted for it anyway, citing a family history of thyroid cancer. "That patient was the exception," he said.
"Most patients welcome the thought they don't have to get radiated and [instead] can be watched," Dr. Walfish said.
Among the protocol limitations,2 he mentioned the following:
- Applies only to low and intermediate risk, well-differentiated thyroid cancer patients
- Surgeon must have strong expertise
- Measurement of serum Tg must be accurate
- Anti-tg antibody positivity must be ruled out
- Requires long-term Tg (stimulated or ultrasensitive basal) and neck ultrasound surveillance.
"There are other limitations to the approach,"3 said Richard Weiss, MD, Sanofi Genzyme's global medical director of endocrinology/rare disease. Among them:
- Tg levels stimulated by Thyrogen are typically lower (and don't correlate with) those after thyroid hormone withdrawal.
- Risk of missing a diagnosis of thyroid cancer or underestimating the extent of disease remains.
- Anti-Tg antibodies may confound the Tg assay, making Tg levels not interpretable. Further evaluation should be considered.
“The protocol did have side effects”, Andrew Bauman, MD, an endocrinologist and assistant professor of medicine at Geisel School of Medicine at Dartmouth University, in New Hampshire, told EndocrineWeb.
"According to Sanofi Genzyme, headaches and nausea have been the most commonly reported adverse effects," said Dr. Bauman. "However, central nervous system problems, such as stroke in young women at elevated risk, also have been reported."
However, Dr. Bauman continued, ''the side effects of Thyrogen are [typically] minor compared to [those of] having radiation you don't require." Dr. Bauman said he has referred some patients to the treatment.
“Patients appreciated not having to go off their thyroid hormone and become hypothyroid," he said. "I've had patients who are freezing in July.”
Another concern, Dr. Bauman added: “cost can be a downside”. On average, according to Dr. Weiss, the two injections of Thyrogen required cost about $3,000, but he acknowledged that some centers charged much more.
This presentation was well timed; the emergence of personalized medicine was also discussed in a lecture by Nobel Prize winner, Thomas Cech, PhD, who spoke about the place for personalized medicine in current clinical care.
Dr. Walfish is a consultant to Genzyme Canada, reports being a shareholder in Proteocyte Diagnostics, Inc, and he is senior endocrine consultant at Sonshine Centre for Head & Neck Diseases, Toronto, Ontario, Canada.