Molecular Testing in Patients With Advanced RAI-Refractory DTC
Lori Wirth, MD, discusses molecular testing practices for patients with advanced RAI-refractory differentiated thyroid cancer.
Case: A 64-Year-Old Woman with DTC
Initial presentation
- A 64-year-old woman presents with a painless “lump on her neck” with occasional swelling. She states she noticed this just a few days after returning from vacation.
- PMH: Hyperlipidemia managed with medication; COPD
- PE: palpable, non-tender solitary right-of-the midline neck mass; mobile supraclavicular mass on the same side; otherwise unremarkable
Clinical workup and initial treatment
- Labs: TSH WNL
- Ultrasound of the neck revealed a 3.3-cm suspicious right mass in the lobe of the thyroid; 2 suspicious supraclavicular lymph nodes (LNs), largest 2.0 cm in size.
- Ultrasound-guided FNAB of the thyroid mass and the largest LN confirmed papillary thyroid carcinoma.
- Patient underwent total thyroidectomy with central compartment node dissection and right selective neck dissection.
- Pathology: 3.0-cm papillary thyroid cancer, columnar cell variant; 4/14 lateral positive LN, 3/3 central positive LN
- Largest lateral node was 2.2 cm with no extra-nodal extension
- Margins were negative
- Microscopic extrathyroidal extension present
- Probable stage II; T2N1bM0 papillary thyroid cancer
Subsequent treatment and follow-up
- She was treated with radioactive iodine 150 millicuries
- Whole body scan showed uptake in the neck, consistent with remnant thyroid tissue
- She was started on levothyroxine suppression therapy
- Follow-up at 6 months
- TSH 0.1 µU/mL, thyroglobulin 24 ng/mL (negative anti-thyroglobulin antibodies)
- Chest CT scan showed 8 small bilateral lung nodules only several mm in size
- Next-generation sequencing was negative for mutations, rearrangements
- Follow-up CT chest scan and blood tests 3 months later
- Thyroglobulin increased
- Lung nodules had increased by up to 1 cm in size
- Lenvatinib 24mg po qd was initiated
This is a video synopsis/summary of a Case-Based Peer Perspective featuring: Lori Wirth, MD.
Wirth emphasizes the importance of molecular testing in patients with radioactive iodine (RAI)–refractory differentiated thyroid cancer (DTC), as a majority harbor potentially actionable gene alterations. BRAF V600E mutations are present in approximately 60% of papillary thyroid cancers (PTCs). Although dabrafenib and trametinib have an FDA approval as tissue-agnostic therapy for patients without other treatment options, Wirth tends to consider lenvatinib in the first-line setting and dabrafenib/trametinib in the second-line setting for BRAF V600E–mutated, RAI-refractory PTC.
Oncogenic gene fusions are less frequent in DTC, with RET fusions in 10% to 15% of patient cases, NTRK1 and NTRK3 fusions in 2% to 5% of patient cases, and rare instances of ALK and ROS1 fusions. Selecting the best next-generation sequencing (NGS) platform is challenging due to the various options available. Wirth emphasizes the importance of using an NGS platform with robust detection for oncogenic gene fusions, given their high frequency in advanced thyroid cancers. She recommends the Archer assay as the most robust for detecting oncogenic gene fusions. However, she also stresses the importance of a platform capable of detecting point mutations.
Video synopsis is AI-generated and reviewed by Targeted Oncology® editorial staff.
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