For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
Inviting an author to review:
Starved Guts: Morphologic and Functional Intestinal Changes in Malnutrition.
Find an author and click ‘Invite to review selected article’ near their name.
Search for authorsSearch for similar articles
0
views
22
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      839
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A Misleading Case of NTRK-Rearranged Papillary Thyroid Carcinoma

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Herein, we present a misleading case of advanced papillary thyroid carcinoma with lung, node, and pleural metastases, initially diagnosed as metastatic lung adenocarcinoma with papillary features, based on the histological and immunohistochemical analysis of a pleural biopsy. Between August 2019 and August 2020, the patient received 2 ineffective lines of systemic therapy, including a first line of chemotherapy with cisplatin and pemetrexed, and a second line of immunotherapy with atezolizumab. Comprehensive genomic profiling by next-generation sequencing on the archival pleural biopsy revealed an NTRK1-TMP3 fusion and comutation of the TERT promoter, commonly found in papillary thyroid carcinoma. After palliative partial thyroidectomy that confirmed the diagnosis of papillary thyroid carcinoma, in February 2021, the patient was enrolled in the STARTRK-2 GO40782 basket trial and received entrectinib, an oral pan-TRK inhibitor specifically targeting NTRK-rearranged tumors. After initially experiencing drug-related grade 2 anorexia, dysgeusia, and neurotoxicity and grade 3 asthenia, the dose was reduced, and an excellent and durable objective response was observed.

          Abstract

          This article presents a misleading case of advanced papillary thyroid carcinoma with lung, node, and pleural metastases, initially diagnosed as metastatic lung adenocarcinoma with papillary features. Comprehensive genomic profiling by next-generation sequencing revealed an NTRK1-TMP3 fusion and comutation of the TERT promoter. The patient then achieved meaningful and durable benefit with tailored treatment targeting NTRK fusion.

          Related collections

          Most cited references22

          • Record: found
          • Abstract: found
          • Article: not found

          NTRK fusion-positive cancers and TRK inhibitor therapy

          Emiliano Cocco, Maurizio Scaltriti, Alexander Drilon (2018)
          NTRK gene fusions involving either NTRK1 , NTRK2 , or NTRK3 (encoding the neurotrophin receptors TRKA, TRKB, and TRKC, respectively) are oncogenic drivers of various adult and paediatric tumour types. These fusions can be detected in the clinic using a variety of methods, including tumour DNA and RNA sequencing and plasma cell-free DNA profiling. The treatment of patients with NTRK fusion-positive cancers with a first-generation TRK inhibitor, such as larotrectinib or entrectinib, is associated with high response rates (>75%), regardless of tumour histology. First-generation TRK inhibitors are well tolerated by most patients, with toxicity profiles characterized by occasional off-tumour, on-target adverse events (attributable to TRK inhibition in non-malignant tissues). Despite durable disease control in many patients, advanced-stage NTRK fusion-positive cancers eventually become refractory to TRK inhibition; resistance can be mediated by the acquisition of NTRK kinase domain mutations. Fortunately, certain resistance mutations can be overcome by second-generation TRK inhibitors, including LOXO-195 and TPX-0005 that are being explored in clinical trials. In this Review, we discuss the biology of NTRK fusions, strategies to target these drivers in the treatment-naive and acquired-resistance disease settings, and the unique safety profile of TRK inhibitors.
          Article 0 comments Cited 394 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Lenvatinib versus placebo in radioiodine-refractory thyroid cancer.

            Martin Schlumberger, Makoto Tahara, Lori J Wirth … (2015)
            Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).
            Article 0 comments Cited 387 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Molecular characterization of cancers with NTRK gene fusions

              Zoran Gatalica, Joanne Xiu, Jeffrey J Swensen … (2018)
              Targeted inhibitors of neurotropic tyrosine kinases are highly effective in selected patients with gene fusions involving NTRK1, NTRK2, or NTRK3. These fusions are consistently detected in rare cancer types (e.g., secretory breast carcinoma and congenital infantile fibrosarcoma), but the occurrence of NTRK fusions in common cancers and their relationship to other therapy biomarkers are largely unexplored. Tissue samples from 11,502 patients were analyzed for 53 gene fusions and sequencing of 592 genes, along with an immunohistochemical evaluation of TrkA/B/C and PD-L1. Thirty-one cases (0.27% of the entire cohort) had NTRK fusions. The most common fusions were ETV6:NTRK3 (n = 10) and TPM3:NTRK1 (n = 6). Gliomas had the highest number of NTRK fusions (14/982, 1.4%), most commonly involving NTRK2 (n = 9). Seventeen non-glioma cases with NTRK fusions included carcinomas of the lungs, thyroid, breast, cervix, colon, nasal cavity, cancer of unknown primary and soft tissue sarcomas. Strong and uniform Trk expression detected with a pan-Trk immunohistochemistry characterized 7/8 NTRK1 fusion cases and 8/9 NTRK2 fusion cases, while NTRK3 fused cases were positive in 6/11 (55%) of cases. 29% of NTRK fusion cases had no other pathogenic genomic alteration. PD-L1 expression was observed in 23% of NTRK fused cases while high tumor DNA microsatellite instability was detected in two cases. We confirm the rarity of NTRK genes fusions outside the brain malignancies. NTRK inhibitors alone or combined with immune checkpoint inhibitors may be a therapeutic option for a substantial proportion of these patients. Strategies for detection of the NTRK fusion-driven cancers may include immunohistochemistry, but gene fusion detection remains the most reliable tool.
              Article 0 comments Cited 177 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Marco Maria Germani
                Chiara Boccaccio:
                ORCID: https://orcid.org/0000-0003-1019-5983
                Antonio Matrone
                Eleonora Molinaro
                Greta Alì
                Mirella Giordano
                Rossella Elisei:
                ORCID: https://orcid.org/0000-0002-5333-9257
                Gabriella Fontanini
                Chiara Cremolini:
                ORCID: https://orcid.org/0000-0002-0520-4841
                Journal
                Journal ID (nlm-ta): Oncologist
                Journal ID (iso-abbrev): Oncologist
                Journal ID (publisher-id): oncolo
                Title: The Oncologist
                Publisher: Oxford University Press (US )
                ISSN (Print): 1083-7159
                ISSN (Electronic): 1549-490X
                Publication date Collection: January 2024
                Publication date (Electronic): 30 November 2023
                Publication date PMC-release: 30 November 2023
                Volume: 29
                Issue: 1
                Pages: 84-88
                Affiliations
                Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana , Pisa, Italy
                Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa , Pisa, Italy
                Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana , Pisa, Italy
                Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa , Pisa, Italy
                Unit of Endocrinology, Department of Clinical and Experimental Medicine, Pisa University Hospital , Pisa, Italy
                Unit of Endocrinology, Department of Clinical and Experimental Medicine, Pisa University Hospital , Pisa, Italy
                Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa , Pisa, Italy
                Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa , Pisa, Italy
                Unit of Endocrinology, Department of Clinical and Experimental Medicine, Pisa University Hospital , Pisa, Italy
                Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa , Pisa, Italy
                Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana , Pisa, Italy
                Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa , Pisa, Italy
                Author notes
                Corresponding author: Chiara Cremolini, MD, PhD, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana and Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa , Pisa, Italy. Email: chiaracremolini@ 123456gmail.com
                Author information
                https://orcid.org/0000-0003-1019-5983
                https://orcid.org/0000-0002-5333-9257
                https://orcid.org/0000-0002-0520-4841
                Article
                Publisher ID: oyad310
                DOI: 10.1093/oncolo/oyad310
                PMC ID: 10769806
                PubMed ID: 38037189
                SO-VID: 22484db7-78c2-4b56-987c-2bdb92c75967
                Copyright © © The Author(s) 2023. Published by Oxford University Press.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

                History
                Date received : 23 May 2023
                Date accepted : 01 November 2023
                Page count
                Pages: 5
                Funding
                Funded by: Italian Ministry of University and Research;
                Award ID: PE_00000019
                Funded by: European Union, DOI 10.13039/501100000780;
                Categories
                Subject: Precision Medicine Clinic: Molecular Tumor Board
                Subject: AcademicSubjects/MED00010

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: thyroid carcinoma,next-generation sequencing, ntrk1-tmp3 fusion, tert promoter
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: thyroid carcinoma, next-generation sequencing, ntrk1-tmp3 fusion, tert promoter

                Comments

                Comment on this article