NTRK-fusions in pediatric thyroid tumors: Current state and future perspectives

Casado‐Medrano, Victoria; O'Neill, Alison; Halada, Stephen; Laetsch, Theodore W.; Bauer, Andrew J.; Franco, Aime T.

doi:10.1016/j.cancergen.2022.02.009

Cited by 4 publications

(4 citation statements)

References 56 publications

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“…Indeed, the webserver for fusion integrative analysis FPIA 37 shows that for each NTRK gene, considering 33 cancer types from The Cancer Genome Atlas Program data, breaks occur at different exonic, splicing (within 2-bp of a splicing junction), non-coding RNA (overlaps a transcript without coding annotation in the gene definition), intronic, and intergenic locations (Fig 4A). The literature revealed 127 different fusion partners 5,25,34,35,38,39 from which 90 (70.9%) were associated with adult tumor histologies, 22 (17.3%) were restricted to pediatric tumors, and 15 (11.8%) are shared by both settings (Fig 4B). When examining the recombinational background of each fusion partner, 78% of them translocate with all NTRK members in adult tumors.…”

Section: Discussionmentioning

confidence: 99%

“…25 Moreover, fusions presented a certain tissue tropism: pediatric thyroid tumors predominantly involved NTRK1 and NTRK3, whereas CNS tumors primarily have fusions associated with NTRK2. 25,35,36 In this regard, as more tumors are being studied for fusions, higher the number of partners and different breakpoints. Indeed, the webserver for fusion integrative analysis FPIA 37 shows that for each NTRK gene, considering 33 cancer types from The Cancer Genome Atlas Program data, breaks occur at different exonic, splicing (within 2-bp of a splicing junction), non-coding RNA (overlaps a transcript without coding annotation in the gene definition), intronic, and intergenic locations ( Response rates observed in our study were similar to the literature.…”

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confidence: 99%

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Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology

Vince,

Brassesco,

Mançano

et al. 2024

JCO Precis Oncol

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PURPOSE Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)–fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology

Vince,

Brassesco,

Mançano

et al. 2024

JCO Precis Oncol

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“…The TRK inhibitors Entrectinib and Larotrectinib have been recommended by the FDA for use in both pediatric and adult tumors with NTRK fusions. Larotrectinib is selective for TrkA, TrkB and TrkC, whereas Entrectinib also inhibits ROS1 and ALK [ 125 , 126 ]. Selpercatinib has shown efficacy in RET fusion-positive pediatric PTCs [ 83 ].…”

Section: Targeted Therapy In Pediatric Patientsmentioning

confidence: 99%

“…However, the acquisition of drug resistance is a major obstacle. To overcome this, trials of novel agents such as Selitrectinib (LOXO-195), Repotrectinib (TPX-0 0 05) and Taletrectinib (DS-6051b) are currently underway [ 126 ].…”

Section: Targeted Therapy In Pediatric Patientsmentioning

confidence: 99%

Molecular Landscape of Pediatric Thyroid Cancer: A Review

et al. 2022

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Thyroid carcinomas (TC) are rare in the pediatric population; however, they constitute the most common endocrine malignancy. Despite some similarities with adult carcinomas, they have distinct clinical behavior and responses to therapy due to their unique pathology and molecular characteristics. The age cut-off used for defining the pediatric age group has been variable across different studies, and the universally accepted recommendations influence accurate interpretation of the available data. Moreover, factors such as radiation exposure and germline mutations have greater impact in children than in adults. Papillary TC is the most common and the most evaluated pediatric TC. Others, including follicular, poorly differentiated and medullary carcinomas, are rarer and have limited available literature. Most studies are from the West. Asian studies are primarily from Japan, with few from China, India, Saudi Arabia and South Korea. This review provides a comprehensive account of the well-established and novel biomarkers in the field, including point mutations, fusions, miRNA, and thyroid differentiation genes. Familial and syndromic associations are also discussed. Current management guidelines for pediatric patients are largely derived from those for adults. An awareness of the molecular landscape is essential to acknowledge the uniqueness of these tumors and establish specific diagnostic and therapeutic guidelines.

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Surgical management of rare tumors (Part 1)

Stetson,

Saluja,

Cameron

et al. 2024

Pediatric Blood & Cancer

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With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.

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NTRK-fusions in pediatric thyroid tumors: Current state and future perspectives

Cited by 4 publications

References 56 publications

Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology

Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology

Molecular Landscape of Pediatric Thyroid Cancer: A Review

Surgical management of rare tumors (Part 1)

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