Hashimoto Thyroiditis Lessens Recurrence Risk of BRAF-positive Differentiated Thyroid Tumors

Daniel M. Keller, PhD

September 13, 2022

PHILADELPHIA — The presence of Hashimoto thyroiditis (HT) has a protective effect against recurrence for patients with differentiated thyroid cancer (DTC). Even in the presence of a BRAF mutation, "[i]t significantly reduces the rate of recurrence compared to patients with no history of Hashimoto thyroiditis," Mohamed Aboueisha, MD, a pre-residency clinical fellow at Beth Israel Deaconess Medical Center in Boston, reported here at the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 2022 Annual Meeting.

He said that papillary thyroid carcinoma is the most common form of DTC and that its incidence among patients with HT is greater than in the general population. Presence of the BRAF V600E mutation in the tumor leads to higher tumor/nodes/metastases (TNM) staging, an increased risk of cancer recurrence, and decreased 10-year survival.

In a retrospective study conducted at Tulane University Hospital on the effect of HT in DTC, investigators assembled a cohort of patients (N = 469) from 2008 to 2020 with papillary cancer (n = 427) or follicular thyroid cancer (n = 25) or both (n = 17). Patients were aged 18 years or older, and all were evaluated for HT and for BRAF status.

A diagnosis of HT was made preoperatively on the basis of the presence of subclinical hypothyroidism and elevated biochemical markers and postoperatively by histopathology. Investigators determined BRAF status preoperatively through commercial testing for molecular markers on fine-needle aspiration and after surgery by next-generation sequencing at Tulane.

There were no significant differences between the HT and non-HT patients by age, body mass index, or radiation exposure. There were significantly more women in the HT group (85.0%) compared with the non-HT group (72.6%; P = .04). There were more Blacks in the non-HT group (37.7% vs 26.4%; P = .01), and more patients in the HT group had a family history of thyroid cancer (14.3% vs 8.2%; P = .04).

During a median follow-up of 2.84 years (interquartile range [IQR], 0.58 – 6.64 years) for the non-HT group and 2.08 years (IQR, 0.49 – 6.03 years) for the HT group, 11.9% of the non-HT patients experienced a recurrence compared with only 2.9% of patients with HT.

Risk of Recurrence

In a multivariate analysis, the presence of HT vs no HT predicted a 70% lower risk of recurrence (hazard ratio [HR], 0.3; 95% CI, 0.11 – 0.88; P = .028).

Two factors predicted an elevated risk of recurrence: extranodal extension vs no extranodal extension (HR, 5.99; 95% CI, 2.43 – 14.77; P < .001) and lymph node metastasis vs no lymph node metastasis (HR, 2.88; 95% CI, 1.2 – 6.86; P = .017).

The presence of the BRAF mutation raised the risk of recurrence. However, the presence of HT ameliorated this risk (see table below). "These findings can influence periodic follow-up times and decision-making for endocrinologists, oncologists, and surgeons alike," Aboueisha said.

Table: Effect of Hashimoto Thyroiditis and BRAF on Risk of Cancer Recurrence (P < .001)

BRAF status HT positive (n = 140) HT negative (n = 329)
BRAF positive 6.8% (n = 44) 18.3% (n = 104)
BRAF negative 1% (n = 96) 8.9% (n = 225)

 

Speaking with Medscape Medical News after the session in which Aboiueisha spoke, co-moderator Linda Lee, MD, a facial plastic and reconstructive surgeon at Massachusetts Eye and Ear in Boston, cautioned that "we have to be careful that we don't...follow up or change surgical guidelines until we know for sure that [HT's being a protective factor] is not just a trend but that it truly is protective in a significant way."

Co-moderator Anil Lalwani, MD, professor of otolaryngology at Columbia University in New York City, agreed, adding, "How are the team managing their patient differently when they have Hashimoto vs not Hashimoto? And I think that question still needs to be answered. I think it's kind of early." (Lee and Lalwani were not involved in the study.)

As with other cancers, genotyping "is becoming increasingly common in head and neck cancers, whether it's squamous cell, or whether people [are] looking at HPV status, whether it's BRAF," Lalwani said. He noted that thyroid cancer is "one of the best-studied cancers out there. There are actually prospective studies.... The clinical studies can serve as a model for all the other cancers because it is one of the few areas where we have really good data because it's very common...and it's well studied."

The study received no commercial funding. Aboueisha has disclosed no relevant financial relationships. Lalwani is on the medical advisory board of Spiral Therapeutics and is a co-founder of Haystack Medical, Inc. He reported no conflicts of interest relevant to this presentation. Lee has disclosed no relevant financial relationships.

American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 2022 Annual Meeting.

Daniel M. Keller, PhD, is a medical journalist based in Philadelphia.

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