A 56 year-old Samoan man underwent thyroidectomy in 2015 for a suspicious thyroid nodule. Comorbidities included obesity, diabetes, hypertension, CKD with proteinuria and IgA paraprotein. Histopathology showed a 50mm follicular carcinoma with vascular invasion and areas of poorly differentiated thyroid cancer. Mutation testing revealed NRAS Q61R mutation.
He was treated with 100mCi of radioiodine (RAI) with recombinant TSH stimulation. The post-dose scan showed iodine uptake in the thyroid bed with two 3mm non-avid lung nodules.
Subsequently, he was treated with 148mCi of RAI due to rising thyroglobulin and progressive subcentimetre lung metastases. The post-dose scan showed iodine avidity in the majority of pulmonary nodules. Imaging 6 months post-therapy indicated stability of pulmonary nodules.
However, rapidly rising thyroglobulin was noted 12 months post-therapy. CT-scan showed recurrence underlying the thyroidectomy scar, nodal enlargement and progression of pulmonary metastases. He underwent resection of local recurrence and a large lymph node metastasis. Unstimulated thyroglobulin fell from 503 preoperatively to 220. Subsequent imaging demonstrated further progression of pulmonary metastases.
Taking into account small volume metastases, mutation status and multiple comorbidities, a trial of redifferentiation therapy was initiated with trametinib 2mg daily for 4 weeks. Apart from lethargy and myalgias necessitating brief dose interruption, this was well tolerated. Pre and post redifferentiation therapy I-124 PET/CT scans performed following thyroxine withdrawal demonstrated significantly increased iodine avidity post-therapy in thyroid bed, left nodal and pulmonary metastases. The patient was treated with 192mCi RAI.
Restaging PET/CT scan 6 months post-therapy showed a favourable response with interval reduction in a majority of pulmonary nodules and nodal metastases. Unstimulated Tg fell from 220 to 153.
Conclusion
RAI following redifferentiation therapy should be considered in appropriately selected thyroid cancer patients with seemingly iodine refractory progressive disease. It can delay disease progression and avoids side effects associated with long-term tyrosine kinase inhibitor therapy.