Endocrine-related cancer最新文献_第4页

Molecular clusters and precision medicine in pheochromocytomas and paragangliomas. 嗜铬细胞瘤和副神经节瘤的分子簇与精准医学。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0258

Madson Q Almeida, Patricia L M Dahia, Mercedes Robledo

{"title":"Molecular clusters and precision medicine in pheochromocytomas and paragangliomas.","authors":"Madson Q Almeida, Patricia L M Dahia, Mercedes Robledo","doi":"10.1530/ERC-26-0258","DOIUrl":"10.1530/ERC-26-0258","url":null,"abstract":"Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells of the adrenal medulla and extra-adrenal paraganglia. Over the past two decades, the genomic characterization of PPGLs has profoundly transformed their diagnosis, classification, risk stratification, and therapeutic management. Up to 40% of PPGLs harbor germline pathogenic variants, the highest proportion among human neoplasms, and somatic driver events are identified in a substantial fraction of the remaining cases. Integrative multi-omic studies have established three main molecular clusters: a pseudohypoxic cluster driven by Krebs-cycle alterations (SDHx, FH, MDH2, DLST) and HIF-2α pathway alterations (VHL, EPAS1, EGLN1/2); a kinase-signaling cluster driven by activation of RAS/MAPK and PI3K/AKT pathways (RET, NF1, HRAS, TMEM127, MAX); and a Wnt-signaling cluster characterized primarily by MAML3 fusions. This review summarizes progress in PPGL genomics, highlighting geographic and sex-related particularities. Using EPAS1/HIF-2α and RET as paradigmatic examples, we illustrate how diverse germline, somatic, mosaic, and fusion events converge on common core signaling hubs that can be therapeutically exploited with FDA-approved selective inhibitors for relevant targets (e.g. belzutifan for HIF-2α; selpercatinib and pralsetinib for RET). We further review the genomic determinants of metastatic risk (SDHB, ATRX, TERT, and MAML3 fusions), the immune microenvironment of metastatic disease, and emerging radionuclide theranostics, liquid biopsy biomarkers, and integrative multi-omic approaches that are reshaping precision medicine for PPGLs.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arginine vasopressin deficiency: towards a better characterization. 精氨酸抗利尿激素缺乏症：走向更好的表征。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0090

Cihan Atila, Clara Consoli, Mirjam Christ-Crain

{"title":"Arginine vasopressin deficiency: towards a better characterization.","authors":"Cihan Atila, Clara Consoli, Mirjam Christ-Crain","doi":"10.1530/ERC-26-0090","DOIUrl":"10.1530/ERC-26-0090","url":null,"abstract":"Arginine vasopressin (AVP) deficiency, previously termed central diabetes insipidus, arises from impaired AVP synthesis or secretion by the hypothalamus and/or the posterior pituitary gland and presents with hypotonic polyuria and polydipsia. To differentiate AVP deficiency from AVP resistance and primary polydipsia, a stepwise diagnostic workup is required. In recent years, copeptin, as a reliable surrogate marker of AVP secretion, has been incorporated into diagnostic algorithms, and copeptin-based stimulation tests have substantially improved diagnostic accuracy. Once AVP deficiency has been established, identification of the underlying cause is essential. A wide range of etiologies, including neurosurgical and traumatic injuries, granulomatous, inflammatory and autoimmune diseases, vascular events, infections, and genetic defects, require a diagnostic approach tailored to the suspected diagnosis. Evaluation should include a careful assessment of the patient's personal and family history, clinical examination, laboratory studies, imaging and, when indicated, tissue biopsy. In patients with apparently idiopathic AVP deficiency, a careful longitudinal follow-up is warranted, since it may represent the first manifestation of an underlying pathology. Treatment of AVP deficiency consists of desmopressin replacement combined with etiology-specific management.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting radioiodine therapy response in advanced and recurrent thyroid cancer. 预测晚期和复发甲状腺癌放射碘治疗反应。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0253

Vincenzo Condello, Myrsini Strati, Daniel Thor, Catharina Larsson, C Christofer Juhlin, Joachim N Nilsson

{"title":"Predicting radioiodine therapy response in advanced and recurrent thyroid cancer.","authors":"Vincenzo Condello, Myrsini Strati, Daniel Thor, Catharina Larsson, C Christofer Juhlin, Joachim N Nilsson","doi":"10.1530/ERC-26-0253","DOIUrl":"10.1530/ERC-26-0253","url":null,"abstract":"Radioiodine therapy of differentiated thyroid cancer is effective and possibly curative in patients with metastatic lesions that retain iodine avidity. However, in clinical practice, iodine avidity in any metastatic site is usually unknown at the point of initial treatment. Avidity prediction could enable more tailored initial radioiodine treatment. This work aimed to establish the best predictive factors for iodine avidity and subsequent treatment response. Thirty-one patients with metastatic or recurrent thyroid cancer sites in which iodine avidity could be assessed by image-based analysis were included. In tissue specimens from primary surgery, immunohistochemical expression of thyroglobulin (Tg), thyroid peroxidase (TPO), sodium-iodide symporter (NIS), and Ki67 and mutational status of BRAF, RAS, and the TERT promoter were analyzed. Biochemical and structural responses were assessed by serum Tg response and radiological evaluation. High-risk histology (widely invasive follicular, tall cell subtype papillary, differentiated high-grade, or poorly differentiated thyroid carcinoma) combined with the expression of TPO, Tg, and cytoplasmic NIS performed well in predicting treatment response and iodine avidity. Approximately half of the variation between patients was explained by those variables, outperforming pT stage and mutational status. TPO and Tg expression were the largest contributors to prediction modeling. Radioiodine treatment response and iodine avidity in thyroid cancer can be predicted from histopathological analysis of the primary tumor. High-risk histology and the expression of TPO, Tg, and NIS were robust and informative predictors. This may be used to adapt treatment strategy in adjuvant and metastatic therapy settings.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STING expression in pituitary neuroendocrine tumour immune microenvironments. 垂体神经内分泌肿瘤免疫微环境中STING的表达。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0385

Paul Benjamin Loughrey, Aoife McArdle, Amélie Viratham Pulsawatdi, Kris D McCombe, Christine Greene, Hannah James, Estelle G Healy, Fionn Corr, Ella Ross, Stephen Cooke, Steven J Hunter, Márta Korbonits, Stephanie G Craig, Jacqueline A James

{"title":"STING expression in pituitary neuroendocrine tumour immune microenvironments.","authors":"Paul Benjamin Loughrey, Aoife McArdle, Amélie Viratham Pulsawatdi, Kris D McCombe, Christine Greene, Hannah James, Estelle G Healy, Fionn Corr, Ella Ross, Stephen Cooke, Steven J Hunter, Márta Korbonits, Stephanie G Craig, Jacqueline A James","doi":"10.1530/ERC-26-0385","DOIUrl":"10.1530/ERC-26-0385","url":null,"abstract":"The pituitary neuroendocrine tumour (PitNET) immune microenvironment (IME) has become a recent focus of research interest. Multiplex immunofluorescence combined with digital image analysis is a powerful technique to interrogate the IME. Processes such as DNA damage response and cellular senescence have been implicated in somatotroph tumour pathogenesis, and these have in turn been linked with immunological responses to neoplasia. The objectives of this study were to compare the immune cell infiltrate in PitNETs to normal pituitary, investigate how the PitNET-IME may vary according to treatment with somatostatin receptor ligand, tumour invasiveness, tumour proliferation, and AIP mutation status. Two bespoke multiplex panels were developed and applied to a range of PitNET subtypes before being interrogated with deep learning algorithms and QuPath image analysis software. Tumours had significantly higher total macrophage infiltrate (P < 0.001), STING+ macrophages (P < 0.001) and STING positivity (P < 0.001) compared with normal pituitary tissue. Macrophage infiltration and STING positivity were positively correlated with tumour Ki-67 proliferation index (rs = 0.305, P = 0.003; and rs = 0.263, P = 0.010, respectively). Results suggested that AIP-mutated PitNETs may have higher CD8+ T-lymphocyte infiltrate, macrophage infiltrate, including STING+ macrophages and overall STING positivity compared with AIP-negative tumours. The application of machine learning to multiplex immunofluorescence images identifies macrophages and STING as upregulated in these subgroups of functioning PitNETs. This immunological response may indicate that DNA damage, cellular senescence and autophagy could be features of these tumours.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Forgoing node dissection for desmoplasia-negative hereditary medullary thyroid cancer. 遗传性甲状腺髓样癌行淋巴结清扫术。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0148

Andreas Machens, Claudia Bensch, Claudia Wickenhauser, Henning Dralle, Kerstin Lorenz

{"title":"Forgoing node dissection for desmoplasia-negative hereditary medullary thyroid cancer.","authors":"Andreas Machens, Claudia Bensch, Claudia Wickenhauser, Henning Dralle, Kerstin Lorenz","doi":"10.1530/ERC-26-0148","DOIUrl":"10.1530/ERC-26-0148","url":null,"abstract":"Clinically inapparent node metastases, requiring neck dissection in addition to thyroidectomy, pose a diagnostic challenge in patients with medullary thyroid cancer (MTC). Although desmoplasia negativity has emerged as a powerful marker of node-negative disease, its clinical utility in hereditary MTC remains ill-defined. This cross-sectional investigation employed multivariable logistic regression on, and stratification of clinical variables by, nodal status of 124 RET carriers with MTC who underwent initial total thyroidectomy with at least central neck dissection between 2000 and 2025 at a tertiary center. Unlike tumor size, grade, laterality, index status, and sex, only desmoplasia (>10% vs ≤5%), basal serum calcitonin (>500 pg/mL >> 101-500 pg/mL vs ≤100 pg/mL), and RET category (highest (p.Met918Thr) vs any other) were independently associated with node metastases. In unilateral MTC, desmoplasia ≤5% was always associated with freedom from node metastases (0 of 15 patients), whereas tumor size ≤5 mm and basal serum calcitonin ≤100 pg/mL were associated with node metastases in 4 (18%) of 22 patients and 4 (15%) of 26 patients, respectively. In bilateral MTC, none of the above thresholds were sufficiently discriminatory, suggesting metastatic cross-contamination by the contralateral MTC. In unilateral MTC with desmoplasia ≤5%, node metastases were always absent, regardless of whether basal calcitonin levels were ≤100 (based on 13 patients) or >100 pg/mL (based on 2 patients). This comprehensive proof-of-concept study demonstrates that RET carriers with desmoplasia-negative unilateral MTC may forgo node dissection at specialist centers, similarly to what has been proposed for patients with desmoplasia-negative sporadic MTC.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dickkopf-1 (DKK1) controls papillary and follicular thyroid cancer growth. Dickkopf-1 （DKK1）控制甲状腺乳头状癌和滤泡癌的生长。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0026

Gloria Fiorentino, Beatrice Latiano, Letizia Rinella, Cristina Grange, Massimo Cedrino, Ornella Bosco, Chiara Pighi, Laura Perin, Emanuela Arvat, Maria Graziella Catalano

{"title":"Dickkopf-1 (DKK1) controls papillary and follicular thyroid cancer growth.","authors":"Gloria Fiorentino, Beatrice Latiano, Letizia Rinella, Cristina Grange, Massimo Cedrino, Ornella Bosco, Chiara Pighi, Laura Perin, Emanuela Arvat, Maria Graziella Catalano","doi":"10.1530/ERC-26-0026","DOIUrl":"10.1530/ERC-26-0026","url":null,"abstract":"Thyroid cancer, the most frequent endocrine tumor, has a good prognosis. However, the survival rate of patients with recurrent or metastatic forms that become resistant to conventional treatments drops to <20% at 10 years, with a mean life expectancy of 3-5 years. The molecular mechanisms that drive the advancement of these forms are still largely unknown, and therefore, the identification of disease progression biomarkers is of great clinical relevance. Dickkopf-1 (DKK1) is a regulator of the Wnt signaling cascade that controls several biological processes, including cell proliferation, differentiation, and migration. DKK1 has been associated with progression and poor prognosis in different types of tumors; however, its role in thyroid cancer is still not well defined, and a better characterization is needed. The present study investigated the role of DKK1 in the growth of papillary and follicular thyroid cancers in in vitro and in vivo models. In vitro, DKK1 silencing through siRNA and deletion via CRISPR/Cas9 editing were performed in different papillary and follicular thyroid cancer cell lines. Both silencing and deletion reduced cell growth and migration, with the involvement of β-catenin-dependent Wnt and PI3K/mTOR pathways. In vivo xenograft tumor models showed that DKK1 deletion reduced tumor growth. In conclusion, our findings support the key role of DKK1 in the growth of differentiated thyroid cancers both in vitro and in vivo.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic and therapeutic impact of genomic testing in neuroendocrine neoplasms. 基因组检测在神经内分泌肿瘤中的诊断和治疗作用。

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0225

Emma Boehm, Aidan Flynn, Wing Fai Nip, Leila Varghese, Shannon Nicolson, Shiva Balachander, Camilla B Thornton, Ting Chan, Wenying Layla Zhu, Richard J Rebello, Sarah-Jane Dawson, Rodney J Hicks, Michael Kc Lee, Benjamin J Solomon, Hui-Li Wong, Alison H Trainer, Roderick Clifton-Bligh, Grace Kong, Michael Michael, Joseph Ha Vissers, Stephen Luen, Sean M Grimmond, Richard W Tothill

{"title":"Diagnostic and therapeutic impact of genomic testing in neuroendocrine neoplasms.","authors":"Emma Boehm, Aidan Flynn, Wing Fai Nip, Leila Varghese, Shannon Nicolson, Shiva Balachander, Camilla B Thornton, Ting Chan, Wenying Layla Zhu, Richard J Rebello, Sarah-Jane Dawson, Rodney J Hicks, Michael Kc Lee, Benjamin J Solomon, Hui-Li Wong, Alison H Trainer, Roderick Clifton-Bligh, Grace Kong, Michael Michael, Joseph Ha Vissers, Stephen Luen, Sean M Grimmond, Richard W Tothill","doi":"10.1530/ERC-26-0225","DOIUrl":"10.1530/ERC-26-0225","url":null,"abstract":"Neuroendocrine neoplasms (NENs) are a diverse group of rare cancers with high heritability and limited treatment options for metastatic disease. Genomic testing guidelines for patients with NENs are limited to germline testing in high-risk individuals and tumour mutational burden (TMB) in a subset of patients. Here, we assess the prevalence of clinically actionable somatic variants using gene panel testing in the AACR GENIE database, and our real-world experience using additional genomic testing methodologies such as whole genome sequencing (WGS) and circulating tumour DNA sequencing for patients with NENs. The AACR GENIE database contained large panel data for 2,838 samples representing 26 different NEN subtypes. Of the samples, 19.1% had an OncoKB-defined actionable variant; however, only 1.6% were Level 1. TMB ≥ 10 mut/Mb was found in 21% of the assessable AACR GENIE cohort, mostly in NEC subtypes. Our institutional cohort of 30 patients was analysed using tumour-normal WGS in 24/33 testing episodes. Eight of thirty patients (27%) had variant-based clinical trial recommendations made. Seven of twenty-four WGS cases (29%) had clinically reportable germline variants identified. Circulating tumour DNA testing (n = 5/33) was used to sequence patients with uncontrolled hormone syndromes and when adequate tissue was not available. In selected patients with certain metastatic NET subtypes or NECs, our data support consideration of comprehensive tumour-normal genomic testing.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"33 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SDHC c.397C>T-related pheochromocytomas and paragangliomas: insights from an international study. t相关嗜铬细胞瘤和副神经节瘤：来自一项国际研究的见解

IF 4.6

Endocrine-related cancer Pub Date : 2026-09-01 DOI: 10.1530/ERC-26-0296

S Parisien-La Salle, F Perreault, S Mahrokhian, N Dumas, G Corbeil, A Lacroix, A P Gimenez-Roqueplo, A Vaidya, M St-Jean, I Bourdeau

{"title":"SDHC c.397C>T-related pheochromocytomas and paragangliomas: insights from an international study.","authors":"S Parisien-La Salle, F Perreault, S Mahrokhian, N Dumas, G Corbeil, A Lacroix, A P Gimenez-Roqueplo, A Vaidya, M St-Jean, I Bourdeau","doi":"10.1530/ERC-26-0296","DOIUrl":"10.1530/ERC-26-0296","url":null,"abstract":"The SDHC c.397C>T (p.Arg133Ter) germline pathogenic variant is present in over 40% of mutation-positive paragangliomas in French-Canadian patients, supporting a founder effect. We aimed to characterize pheochromocytomas and paragangliomas (PPGLs) associated with this variant in a large international cohort of European descent. We conducted an international case series of adults with PPGLs carrying the SDHC c.397C>T germline pathogenic variant, treated between 2010 and 2024 at four university hospitals: two in the province of Québec (Canada), one in the Northeastern United States, and one in France. Among the 45 patients confirmed with PPGLs harboring the SDHC c.397C>T pathogenic variant, 46.7% were women, and the mean age at diagnosis was 49.7 years. Forty-four patients (97.8%) had paragangliomas, and one (2.2%) had a pheochromocytoma. The most common paraganglioma sites were the head and neck (26/44, 59.1%), followed by the thoracic (including mediastinal) region (12/44, 27.3%; half located in or near cardiac structures), and finally the abdominal region (6/44, 13.6%). Multiple tumors were present in 15.6% (7/45) of cases, and metastatic disease was identified in 11.1% (5/45). Following surgical resection, four patients (15.4%) experienced recurrence during a mean follow-up of 7.9 years. Loss of SDHB protein expression was confirmed in all available immunohistochemistry samples. The SDHC c.397C>T founder pathogenic variant, likely originating from France, is common in the province of Québec, with probable migration to New England (USA), and appears enriched for thoracic (including mediastinal) paragangliomas. Although based on a limited series, affected patients remain at risk of recurrence and metastasis and should be followed up closely.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RETurn of the Gene. Post scriptum. 基因回归。后记。

IF 4.6

Endocrine-related cancer Pub Date : 2026-08-01 DOI: 10.1530/ERC-26-0178

Tom R Kurzawinski, Kate Newbold, Neil Q McDonald

引用次数: 0

Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data. larorectinib治疗TRK融合分化甲状腺癌：最新的试验数据。

IF 4.6

Endocrine-related cancer Pub Date : 2026-08-01 DOI: 10.1530/ERC-25-0531

Steven G Waguespack, Marcia S Brose, Jessica J Lin, Ray McDermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Shivaani Kummar, Se-Hoon Lee, Damian T Rieke, Do-Youn Oh, Changsong Qi, Natascha Neu, Domnita-Ileana Burcoveanu, Chiara E Mussi, Alexander Drilon, David S Hong, Maria E Cabanillas

{"title":"Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data.","authors":"Steven G Waguespack, Marcia S Brose, Jessica J Lin, Ray McDermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Shivaani Kummar, Se-Hoon Lee, Damian T Rieke, Do-Youn Oh, Changsong Qi, Natascha Neu, Domnita-Ileana Burcoveanu, Chiara E Mussi, Alexander Drilon, David S Hong, Maria E Cabanillas","doi":"10.1530/ERC-25-0531","DOIUrl":"10.1530/ERC-25-0531","url":null,"abstract":"Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per RECIST v1.1. Duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety were also assessed. Twenty-four patients (papillary TC, n = 21; follicular TC, n = 2; poorly DTC, n = 1) were included (data cut-off: 20 July 2024). ORR was 79% (95% confidence interval (CI): 58-93); best responses were complete response in 3 (13%) patients, partial response in 16 (67%), stable disease in 3 (13%), progressive disease in 1 (4%) and not evaluable in 1 (4%). Median DoR and PFS were 35 (95% CI: 22-not estimable (NE)) and 44 (95% CI: 35-NE) months, respectively; 6-year OS rate was 71% (95% CI: 50-91). Six patients remained on treatment. Treatment-related adverse events (TRAEs) were mainly grade 1/2; no patients permanently discontinued treatment due to TRAEs. Larotrectinib continues to demonstrate durable disease control, extended survival and a favourable long-term safety profile in patients with advanced TRK fusion DTC requiring systemic therapy.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0