Limited efficacy of lenvatinib in heavily pretreated anaplastic thyroid cancer: a French overview

2021 ◽  
Vol 28 (1) ◽  
pp. 15-26
Author(s):  
Clotilde Sparano ◽  
Yann Godbert ◽  
Marie Attard ◽  
Christine Do Cao ◽  
Slimane Zerdoud ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Response ◽  
Therapeutic Option ◽  
Anaplastic Thyroid Cancer ◽  
External Beam Irradiation ◽  
Off Label ◽  
Limited Efficacy ◽  
Heavily Pretreated ◽  
Poorly Differentiated ◽  
Mixed Tumors

Anaplastic thyroid cancer (ATC) is a rare lethal disease. Lenvatinib is an off-label therapeutic option for ATC in most countries, except in Japan. The aim of this multicenter retrospective survey was to analyze the efficacy and the toxicity profile of off-label lenvatinib treatment in all adults advanced ATC patients, in France. Of the 23 patients analysed (14 males; mean age 64 years), 15 were pure ATC and 8 were mixed tumors (i.e. with a differentiated or poorly differentiated component). Prior treatments included neck external beam irradiation in 74%, at least one line of chemotherapy in 22 cases, two lines of chemotherapy in 11 patients, other TKI in 4 cases. A central RECIST assessment was performed. Since lenvatinib initiation, median PFS was 2.7 months (95% CI; 1.9–3.5) and median OS was 3.1 months (95% CI; 0.6–5.5). OS was significantly longer in case of mixed tumors compared with pure ATC (6.3 vs 2.7 months, P = 0.026). Best tumor response was partial response in two cases and stable disease in seven. Clinical improvement was achieved in seven patients. Lethal adverse events occurred in three patients, consisting in haemoptysis in two cases and pneumothorax in one case. Among long-surviving ATC patients (>6 months), four underwent biopsy of distant metastasis, revealing poorly differentiated histology; three of them had initial mixed ATC histology. Efficacy of lenvatinib appears limited, although pure vs mixed ATC disclose differences in disease aggressiveness and treatment response. Long-surviving ATC patients might benefit from biopsy of persistent disease, searching for histological transition or molecular target.

scholarly journals Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

2021 ◽  
Vol 22 (6) ◽  
pp. 3117
Author(s):  
Loredana Lorusso ◽  
Virginia Cappagli ◽  
Laura Valerio ◽  
Carlotta Giani ◽  
David Viola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Approved Drugs ◽  
New Generation ◽  
Systemic Therapies

Differentiated thyroid cancers (DTC) are commonly and successfully treated with total thyroidectomy plus/minus radioiodine therapy (RAI). Medullary thyroid cancer (MTC) is only treated with surgery but only intrathyroidal tumors are cured. The worst prognosis is for anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC). Whenever a local or metastatic advanced disease is present, other treatments are required, varying from local to systemic therapies. In the last decade, the efficacy of the targeted therapies and, in particular, tyrosine kinase inhibitors (TKIs) has been demonstrated. They can prolong the disease progression-free survival and represent the most important therapeutic option for the treatment of advanced and progressive thyroid cancer. Currently, lenvatinib and sorafenib are the approved drugs for the treatment of RAI-refractory DTC and PDTC while advanced MTC can be treated with either cabozantinib or vandetanib. Dabrafenib plus trametinib is the only approved treatment by FDA for BRAFV600E mutated ATC. A new generation of TKIs, specifically for single altered oncogenes, is under evaluation in phase 2 and 3 clinical trials. The aim of this review was to provide an overview of the current and future treatments of thyroid cancer with regards to the advanced and progressive cases that require systemic therapies that are becoming more and more targeted on the molecular identity of the tumor.

scholarly journals Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3200
Author(s):  
Alessandro Prete ◽  
Antonio Matrone ◽  
Carla Gambale ◽  
Liborio Torregrossa ◽  
Elisa Minaldi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Median Overall Survival ◽  
Clinical Problem ◽  
Anaplastic Thyroid Cancer ◽  
New Drugs ◽  
Poor Survival ◽  
Tumor Microenvironments ◽  
Genetic Features ◽  
Poorly Differentiated

PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC.

Poorly Differentiated and Anaplastic Thyroid Cancer

2006 ◽  
Vol 13 (2) ◽  
pp. 119-128 ◽  
Author(s):  
Kepal N. Patel ◽  
Ashok R. Shaha
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Poorly Differentiated

scholarly journals Comprehensive gene expression analysis for exploring the association between glucose metabolism and differentiation of thyroid cancer

2020 ◽  
Author(s):  
Hoon Young Suh ◽  
Hongyoon Choi ◽  
Jin Chul Paeng ◽  
Gi Jeong Cheon ◽  
June-Key Chung ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Glucose Metabolism ◽  
Anaplastic Thyroid Cancer ◽  
Biological Properties ◽  
Metabolic Profiles ◽  
Tumor Differentiation ◽  
Independent Prognostic Marker ◽  
Progression Marker ◽  
Poorly Differentiated ◽  
Advanced Thyroid Cancer

Abstract Background: The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC). Methods: We used RNA sequencing of 505 patients with PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival. Results: In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC. Conclusions: As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification.

scholarly journals Comprehensive gene expression analysis for exploring the association between glucose metabolism and differentiation of thyroid cancer

2019 ◽  
Author(s):  
Hoon Young Suh ◽  
Hongyoon Choi ◽  
Jin Chul Paeng ◽  
Gi Jeong Cheon ◽  
June-Key Chung ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Glucose Metabolism ◽  
Anaplastic Thyroid Cancer ◽  
Biological Properties ◽  
Metabolic Profiles ◽  
Tumor Differentiation ◽  
Independent Prognostic Marker ◽  
Progression Marker ◽  
Poorly Differentiated ◽  
Advanced Thyroid Cancer

Abstract Background: The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC). Methods: We used RNA sequencing of 505 patients with PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival. Results: In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC. Conclusions: As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification.

Combined inhibition of cellular pathways as a future therapeutic option in fatal anaplastic thyroid cancer

Endocrine ◽  
2012 ◽  
Vol 42 (3) ◽  
pp. 637-646 ◽  
Author(s):  
Annette Wunderlich ◽  
Silvia Roth ◽  
Annette Ramaswamy ◽  
Brandon H. Greene ◽  
Cornelia Brendel ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Therapeutic Option ◽  
Anaplastic Thyroid Cancer ◽  
Cellular Pathways

scholarly journals Comprehensive gene expression analysis for exploring the association between glucose metabolism and differentiation of thyroid cancer

2019 ◽  
Author(s):  
Hoon Young Suh ◽  
Hongyoon Choi ◽  
Jin Chul Paeng ◽  
Gi Jeong Cheon ◽  
June-Key Chung ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Glucose Metabolism ◽  
Anaplastic Thyroid Cancer ◽  
Biological Properties ◽  
Metabolic Profiles ◽  
Tumor Differentiation ◽  
Independent Prognostic Marker ◽  
Progression Marker ◽  
Poorly Differentiated ◽  
Advanced Thyroid Cancer

Abstract Background The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC). Methods We used RNA sequencing of PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival. Results In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC. Conclusions As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification.

scholarly journals Inhibition of Survivin with YM155 Induces Durable Tumor Response in Anaplastic Thyroid Cancer

2015 ◽  
Vol 21 (18) ◽  
pp. 4123-4132 ◽  
Author(s):  
Amit Mehta ◽  
Lisa Zhang ◽  
Myriem Boufraqech ◽  
Yi Liu-Chittenden ◽  
Yaqin Zhang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Response ◽  
Anaplastic Thyroid Cancer

Lenalidomide Administration in Heavily Pretreated Patients with Non Hodgkin Lymphoma – First Report of the REVEAL Study (REVlimid® Effectiveness of Administration in patients with Lymphoma)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4979-4979
Author(s):  
Luigi Rigacci ◽  
Francesco Zaja ◽  
Alberto Fabbri ◽  
Alice Di Rocco ◽  
Angelo Michele Carella ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hodgkin Lymphoma ◽  
Therapeutic Option ◽  
Stage Iv ◽  
Management Plan ◽  
Off Label Use ◽  
Off Label ◽  
Non Hodgkin Lymphoma ◽  
Heavily Pretreated ◽  
Label Use

Abstract Abstract 4979 Lenalidomide (Revlimid®) is an oral treatment authorized in the US and EU for use in relapse/refractory multiple myeloma. Since March 2008, lenalidomide, in combination with Dexamethasone, is marketed in Italy in the aforementioned indication. The Italian Drug Agency (AIFA) has also granted authorization for the off-label use of lenalidomide in patients with Non Hodgkin Lymphoma (NHL) who have no residual therapeutic option, provided these patients are tracked in a registry, in order to ensure their compliance with the Risk Management Plan (RMP) already in place for the multiple myeloma indication. The authorization was granted based on preliminary published favorable phase 2 data (Wiernik, 2008; Habermann, 2009). April 2008 to November 2010 lenalidomide was prescribed (following the 94/98 Italian law) to over 200 NHL patients, mainly diagnosed as Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL). This retrospective observational study was undertaken to gather clinic-pathological and laboratory data about this cohort of NHL patients, with the objective to evaluate the safety and the efficacy of lenalidomide administered, in the context of routine clinical practice, to a heavily pretreated patient population with no remaining therapeutic alternative. Also, efforts will be done in order to identify prognostic factors which can affect response to lenalidomide treatment. As of today, data on 30 patients treated at 6 sites have been collected and analyzed. Patient demographics and disease characteristics are summarized in Table 1. Patient median age was 70.5 years (range 36.0 – 90.0); median number of previous treatments was 5 (range 1 – 17). Over ninety three per cent (93.3%.) of the patients were previously treated with Rituximab. Forty per cent (40%) had DLBC histology, 16.7% MCL, 13.3% follicular histology and 16.7% were transformed lymphomas. As expected, 60% of the patients had stage IV disease, in keeping with the highly unfavorable characteristics of a heavily pretreated patient population. Responses were assessed according to the International Workshop on Lymphoma Response Criteria (IWRC). The number of lenalidomide cycles administered varied between 1 and 15 in this small patient group; 69.2% of the patients, evaluated at cycle 3, showed an objective response (OR). Table 1 TABLE T3 DEMOGRAPHIC CHARACTERISTICS (EVALUABLE POPULATION) Demographic and Disease Characteristics on evaluable population (N=30) Gender Male 20 (66.7%) Female 10 (33.3%) Age (years) N 30 Mean (SD) 69.8 (11.2) Median 70.5 Range 36.0- 90.0 Time since diagnosis (years) N 22 Mean (SD) 8.82 (8.3) Median 3.30 Range 0.45- 9.0 Histology DLBCL 40% Follicular 13.3% MCL 16.7% Transformed 16.7% Stage Stage III 20% Stage IV 60% Data on approximately 180 patients treated at 46 sites throughout Italy will be analysed and presented. Only subjects who refuse to make their data available for review and analysis, or are currently participating in an interventional clinical study (from the date of enrollment into the interventional study) will be excluded. Although very preliminary, this experience indicates that lenalidomide has interesting anti- lymphoma efficacy, even in patients who have exhausted all available therapeutic options. Disclosures: Off Label Use: The Italian Drug Agency (AIFA) has also granted authorization for the off-label use of lenalidomide in patients with Non Hodgkin Lymphoma (NHL) who have no residual therapeutic option, provided these patients are tracked in a registry, in order to ensure their compliance with the Risk Management Plan (RMP) already in place for the multiple myeloma indication.

scholarly journals Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1094
Author(s):  
Caitlin O. Caperton ◽  
Lee Ann Jolly ◽  
Nicole Massoll ◽  
Andrew J. Bauer ◽  
Aime T. Franco
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
In Vitro Models ◽  
Follicular Thyroid Cancer ◽  
Poorly Differentiated

Recent developments in thyroid cancer research have been hindered by a lack of validated in vitro models, allowing for preclinical experimentation and the screening of prospective therapeutics. The goal of this work is to develop and characterize three novel follicular thyroid cancer (FTC) cell lines developed from relevant animal models. These cell lines recapitulate the genetics and histopathological features of FTC, as well as progression to a poorly differentiated state. We demonstrate that these cell lines can be used for a variety of in vitro applications and maintain the potential for in vivo transplantation into immunocompetent hosts. Further, cell lines exhibit differing degrees of dysregulated growth and invasive behavior that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We believe these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and lead to the development of more personalized diagnostic and treatment strategies.

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