Blogs Details

Blog with Images and Youtube video

The mainstays of therapy for differentiated thyroid cancer cases include surgery, selective use of radioactive iodine (RAI) based on risk of tumor recurrence, and TSH suppression therapy with levothyroxine[1]. Although most patients have a favorable prognosis, a subset develop distant metastases (<10%), of which approximately two-thirds result in radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) [2]. Depending on the extent of metastatic disease, active surveillance under TSH suppression and localized therapies, including surgery, radiation, ablative therapies, and bone modulating agents for bone metastases, may assist in controlling the disease. Nevertheless, patients may require long-term systemic treatment for progressive RAIR-DTC. Evaluation for systemic therapy includes radiographic staging (including brain imaging), tumor testing for targetable mutations, comprehensive laboratories, cardiac function assessment, and close monitoring of comorbidities such as hypertension, diabetes, etc.

 

Initial systemic therapies approved for RAIR-DTC included multikinase inhibitors (MKIs) Lenvatinib and Sorafenib, which target multiple tumorigenic kinase pathways, including vascular endothelial growth factor receptors. Lenvatinib demonstrated impressive response rates of 65% and survival improvement in patients 65 years and older, leading to FDA approval in 2015 [3-5]. However, since tumors almost inevitably develop resistance mechanisms, additional therapies are being studied to expand the management options for RAIR-DTC; for example, Cabozantinib has recently been approved as a second line MKI [6].

 

Improved understanding of the molecular pathogenesis of thyroid cancer, coupled with increasingly comprehensive molecular testing platforms, has led to new insights. In fact, molecular testing has developed over time into an informative tool for prognostic and therapeutic implications. For example, BRAF V600E is the most common alteration in papillary thyroid cancer (PTC), present in at least 60% of cases [7]. BRAF inhibitors alone (e.g., Dabrafenib) or in combination with a MEK inhibitor (e.g., Trametinib) have shown overall responses between 42-54% in RAIR-DTC [8, 9]. A recent FDA approval in the summer of 2022, supported dabrafenib and trametinib combination for unresectable or metastatic BRAF V600E solid tumors with progression despite prior treatments. In addition, recently approved selective inhibitor options include Selpercatinib and Pralsetinib for RET fusion-driven thyroid cancer, and Larotrectinib and Entrectinib for tumors harboring NTRK fusions. Together, both MKI’s and selective inhibitors have brought a ray of hope for patients with RAIR-DTC[10]. However, practice variability still exists in terms of a) timing of initiation of systemic therapy, b) the definition criteria for RAI-refractory thyroid cancer, and c) decision regarding the first line of therapy when a targetable mutation is present.

But the load will be too heavy for us if we the a carry yesterday’s burden over again today

asdasd