NTRK Gene Fusion Thyroid Cancer: Incidence and Prognosis


Jochen H. Lorch, MD, MS: This is a little bit of an odd case. To have a presentation with a thyroid nodule that’s palpable is very typical, and for this to be papillary thyroid cancer is also completely unremarkable. That is frequently the case. Where this case is a little bit unusual is that, first, the papillary thyroid cancer, which was 3.8 cm in diameter, had already metastasized to several lymph nodes in the central neck compartment. That can happen. But the brain metastases were definitely unusual. We only see brain metastases in about 15% of all patients with papillary thyroid cancer or with iodine-refractory thyroid cancer, which is not necessarily what this patient has. So this is definitely an unusually aggressive thyroid cancer.

Having brain metastases obviously raises the stakes of treatment in this considerably, since the prognosis for cancer in general that has spread to the brain is generally much less favorable than without brain metastases. The classical treatment for this would be evaluation by neurosurgery. It sounds like there were multiple brain lesions, so it’s likely not a case that would be amenable to resection of these multiple nodules. But whole brain radiation or stereotactic radiation to these individual brain lesions is also something that could classically be considered.

Now, this tumor being NTRK fusion positive obviously gives us another option to treat with larotrectinib or a similar drug, which is entrectinib, and has a very similar profile. The incidence of NTRK fusion positive thyroid cancer is relatively high compared to other types of cancers. Across the board of all cancer types, the incidence is roughly 1%. But with thyroid cancer, it’s in the order of 10% to 15%. There also seem to be some geographical variations; for example, in Japan, the incidence seems to be a little bit higher. There’s also a higher incidence of fusion NTRK3, which is related to radiation exposure and has been described in people who were exposed to radioactive iodine and radiation during the Chernobyl disaster in Ukraine.

Transcript edited for clarity.

Case: A 71-Year-Old Woman With Thyroid NTRK Gene Fusion Cancer

Initial Presentation

  • A 71-year-old woman presents with a painless “ball on his neck”
  • PMH: hypercholesterolemia, medically controlled
  • PE: palpable, non-tender solitary left-of-the midline neck mass; otherwise unremarkable

Clinical Workup and Initial Treatment

  • Labs: including TSH, anti-Tg antibodies WNL
  • Ultrasound of the neck revealed a 3.8 cm suspicious mass arising from the left thyroid; 4 suspicious submandibular lymph nodes, largest 2.2 cm in size
  • Ultrasound-guided FNAB of the thyroid mass and the largest lymph node confirmed undifferentiated papillary thyroid carcinoma
  • Chest/abdominal/pelvic CT showed no evidence of distant metastases
  • Patient underwent total thyroidectomy with therapeutic central compartment and left selective neck dissection
    • Pathology: 3.8 cm undifferentiated papillary thyroid cancer arising in left lobe of thyroid, 2 of 7 positive central compartment lymph nodes, largest 1.3 cm, no extra nodal extension
  • StageT2N1M1; ECOG PS 0

Follow-Up and Additional Treatment

  • She was treated with radioactive iodine 150 millicuries
    • Whole body scan showed uptake in neck only consistent with thyroid remnant
    • Added levothyroxine to regimen
  • Follow-up at 2 months TSH 0.2 mU/L; thyroglobulin 26 ng/mL
    • MRI of the brain revealed multiple small lesions
  • Biomarkers testing:NTRK fusion+, RET-, BRAF-, NRAS-,KRAS-
  • Initiated treatment with larotrectinib 100 mg PO BID
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