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Recent findings in thyroid cancer treatment, including laser ablation therapy, lenvatinib, and guidelines for treating pediatric patients, are shown in the following slides.
Thyroid cancer is a relatively rare disease that is mostly curable with treatment. Recent news reveals that ultrasound-guided laser ablation therapy can be an effective, well-tolerated treatment for benign solid and mixed thyroid nodules. Also, patients with advanced, radioiodine-refractory, differentiated thyroid cancer appear to respond to the tyrosine kinase inhibitor lenvatinib. And for the first time, the American Thyroid Association has released guidelines for treating pediatric patients with thyroid nodules and thyroid cancer.
Ultrasound-guided Laser Ablation Therapy of Benign Thyroid Nodules.
• Ultrasound-guided laser ablation therapy (LAT) of benign thyroid nodules has demonstrated favorable results in prospective randomized trials.
• These researchers conducted a retrospective, multicenter study to assess LAT in a large consecutive series of patients in a real-world setting.
• The study included patients with solid or mixed nodules with up to 40% fluid composition, benign cytological findings, and normal thyroid function.
• Clinical records of 1534 thyroid nodules in 1531 patients were collected from 8 Italian thyroid referral centers. All patients were treated in the last 10 years.
Laser Ablation Significantly Reduces Nodule Volume.
• A total of 1837 LAT procedures were performed on these nodules. The majority (83%) were treated in a single session. All nodules were treated in no more than 3 consecutive sessions, with a fixed output power of 3 watts.
• Mean nodule volume significantly decreased following LAT, from 27 ± 24 mL at baseline to 8 ± 8 mL at 12 months after treatment.
• Mean nodule volume reduction was 72% ± 11%, with an overall range of 48%-100%.
• Mixed nodules experienced significantly larger decreases than solid ones. On average, mixed nodule volume decreased 79% ± 7%, versus 72% ± 11% for solid nodules.
Laser Ablation Therapy Is Clinically Effective and Well-tolerated.
• Symptoms decreased from 49% to 10% of cases and evidence of cosmetic signs from 86% to 8% of cases.
• Only 17 patients experienced complications, including 8 patients with transitory voice changes, which completely resolved within 2-84 days, and 9 patients with minor complications, such as skin burn and hematoma.
• No changes in thyroid function or autoimmunity were observed.
• In real practice, laser ablative therapy is clinically effective and well-tolerated, both in solid and mixed nodules. The risk of major complications is low due to the use of fine needles and constant ultrasound monitoring.ReferencePapini E, et al. Outcomes, side effects and risk factors for complications of ultrasound-guided laser ablation for thyroid nodules. A multicenter study on 1531 patients. Presentation at the American Association of Clinical Endocrinologists Annual Meeting in Nashville, TN, May 13-17, 2015, Abstract 1260. See abstract here.
Lenvatinib for Radioiodine-refractory Differentiated Thyroid Cancer.
• Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor (VEGF) receptors 1 through 3, fibroblast growth factor receptors 1 through 4, and others. It has shown activity in solid tumors in a phase 1 trial.
• These researchers conducted a phase 2 trial in patients with advanced, radioiodine-refractory, differentiated thyroid cancer.
• The study included 58 patients who had disease progression during the previous 12 months.
• They received lenvatinib 24 mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Previous VEGFR-targeted therapy was permitted.
Lenvatinib Active in Thyroid Cancer.
• After a minimum follow-up of 14 months, patients had an overall response rate (ORR) of 50%, with only partial responses reported.
• The median time to response was 3.6 months, the median response duration was 12.7 months, and the median progression-free survival (PFS) was 12.6 months.
• The ORR for the 17 patients who had received previous VEGF therapy was 59%.
Lenvatinib Shows Encouraging Responses.
• Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS.
• Grade 3 and 4 treatment-emergent adverse events, regardless of their relation to treatment, occurred in 72% of patients. The most frequent were weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%).
• The researchers concluded that in patients with and without prior exposure to VEGF therapy, lenvatinib leads to encouraging response rates, median time to response, and PFS.
• The drug will be further investigated in a phase 3 trial in this setting.ReferenceCabanillas ME, et al. Cancer. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment. Published online 24 Apr. 2015. See abstract here.
American Thyroid Association (ATA) Announces First Pediatric Guidelines.
• Guidelines for the management of thyroid nodules and cancers have been geared toward adults. However, thyroid cancers in children exhibit differences in pathophysiology, clinical presentation, and long-term outcomes.
• Therapy recommended for an adult may not be appropriate for a child who is at low risk for death, but at higher risk for long-term harm from over-aggressive treatment.
• For these reasons, the American Thyroid Association decided to issue new guidelines for children and adolescents with thyroid tumors.
Task Force Makes Recommendations.
• An ATA task force developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC).
• After a literature search, the task force identified and reviewed relevant articles through April 2014.
• Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force.
Recommended Evaluations and Treatments for Children and Adolescents.
• The guidelines recommend evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine needle aspiration cytology, and the management of benign nodules.
• Also outlined are recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC that include pre-operative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression.
• The guidelines provide management algorithms and separate recommendations for papillary and follicular thyroid cancers.ReferenceFrancis G, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer. Thyroid. 2015 Apr 21. See abstract here.
Take-home Messages.
• Ultrasound-guided laser ablation therapy is a clinically effective and well-tolerated treatment for benign solid and mixed thyroid nodules.
• Patients with advanced, radioiodine-refractory, differentiated thyroid cancer demonstrated encouraging response rates and PFS when treated with lenvatinib.
• For the first time, the American Thyroid Association has released guidelines for treating children with thyroid nodules and thyroid cancer.
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