Fusion-Positive Thyroid Carcinoma: From Diagnosis to Targeted Therapy.

Purpose: Neurotrophic tropomyosin receptor kinase () fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States.

Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer: A Potential Strategy for Systemic Therapy Deferral.

Background: Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer.

Methods: This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.

Efficacy and Safety of Selective RET Inhibitors in Patients with Advanced Hereditary Medullary Thyroid Carcinoma.

Two selective RET inhibitors (RETis) are effective in treating ()-altered medullary thyroid carcinoma (MTC), but clinical trials did not distinguish responses between hereditary MTC (hMTC) and sporadic MTC (sMTC) cases. We reviewed our single-center experience using a RETi to treat advanced hMTC. We conducted a retrospective cohort study of patients with hMTC treated with a selective RETi at a tertiary cancer center.

Paraneoplastic Diarrhea From Medullary Thyroid Carcinoma Resolved With Yttrium-90 Radioembolization of Liver Metastases.

Medullary thyroid carcinoma (MTC) can often have an indolent course despite distant metastatic disease. Additionally, given that metastatic MTC is incurable and systemic therapies have non-negligeable toxicities, localized treatments are often favored in presence of oligo-progressive disease. Transarterial radioembolization (TARE) with yttrium-90 (Y90) has emerged as a safe and efficacious treatment for nonresectable primary and metastatic liver tumors, yet data supporting its use in metastatic MTC are limited.

The Multi-Institutional Medullary Thyroid Cancer Collaborative Registry: Can a Rare Tumor Registry Accurately Represent the Real-World Patient Population?

Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries.

Next-Generation Sequencing in Sporadic Medullary Thyroid Cancer Patients: Mutation Profile and Disease Aggressiveness.

Context: Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including M918T, which has been considered a negative prognostic indicator.

Objective: This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS.

Methods: In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified.

RET kinase inhibitors for the treatment of RET-altered thyroid cancers: Current knowledge and future directions.

RET gain-of-function mutations are the most common drivers in medullary thyroid carcinoma, while RET fusions are identified in 5-10% of papillary thyroid carcinomas. Thus, RET plays a major role in the tumorigenesis of thyroid neoplasia, making it a valuable therapeutic target. Over a decade ago, multikinase inhibitors (MKIs) were first shown to have variable degrees of anti-RET activity.

Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers.

The US Food and Drug Administration (FDA) approval of the selective RET inhibitors selpercatinib and pralsetinib has led to a paradigm change in the treatment of RET-altered lung and thyroid cancers through a higher response rate and a more tolerable safety and toxicity profile than multi-kinase inhibitors. Recently, selpercatinib has received a tissue-agnostic FDA approval for all RET-fusion-positive cancers, and pralsetinib has shown pan-cancer activity as well. Given the anticipated increase in the use of both drugs across multiple tumor types, it is crucial to recognize the possible side effects and approaches for their optimal management in order to maximize the clinical benefit for treated patients.

Decreasing utilization for postoperative radiation therapy in locoregionally advanced medullary thyroid cancer.

Background: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS).

Methods: Retrospective cohort study of 346 MTC patients separated into PORT and no-PORT cohorts.

Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study.

Rearranged during transfection () alterations are targetable oncogenic drivers in thyroid cancer. Primary data from the open-label, phase 1/2 ARROW study demonstrated clinical activity and manageable safety with pralsetinib, a selective RET inhibitor, in patients with advanced/metastatic -altered thyroid cancer. We present an updated analysis with more patients and longer follow-up.

Phase 3 Trial of Selpercatinib in Advanced -Mutant Medullary Thyroid Cancer.

Background: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced -mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear.

Methods: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment.

Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance.

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for -mutated solid tumors and are routinely used in RR-DTCs in many centers.

Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline.

Background: Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking.

LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve -mutant medullary thyroid cancer.

Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with -mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic -mutant MTC.

RET kinase inhibitors for -altered thyroid cancers.

Precision oncology has opened a new era in cancer treatment focused on targeting specific cellular pathways directly involved in tumorigenesis. The REarrangement during Transfection () proto-oncogene is involved in the pathogenesis of various thyroid cancer subtypes. Mutations in give rise to both hereditary and sporadic medullary thyroid cancer (MTC).

Hypercalcemia of Malignancy.

Hypercalcemia of malignancy (HCM) is considered an oncologic emergency associated with significant symptom burden and increased comorbid conditions and mortality. Underlying pathologic processes most often stimulate osteoclast-mediated bone resorption. Although long-term control of HCM depends on effective management of the underlying cancer, temporizing management strategies for acute and/or symptomatic HCM include hydration and antiresorptive bone-modifying agents.

Medullary thyroid carcinoma.

Purpose Of Review: To summarize recent developments in the diagnosis and management of patients with medullary thyroid cancer (MTC), with a focus on pathogenesis, systemic therapy, and future directions.

Recent Findings: The addition of mutational analysis to cytological assessment of thyroid nodules has improved the diagnostic accuracy of MTC. The discovery of new genomic alterations and overexpression of certain factors allows for improved prognostication in MTC and provides potentially new therapeutic agents.

Decision Making When Cancer Becomes Chronic: Needs Assessment for a Web-Based Medullary Thyroid Carcinoma Patient Decision Aid.

Background: In cancers with a chronic phase, patients and family caregivers face difficult decisions such as whether to start a novel therapy, whether to enroll in a clinical trial, and when to stop treatment. These decisions are complex, require an understanding of uncertainty, and necessitate the consideration of patients' informed preferences. For some cancers, such as medullary thyroid carcinoma, these decisions may also involve significant out-of-pocket costs and effects on family members.