Clinical outcomes and risk stratification for papillary thyroid carcinoma presenting with distant metastasis before the era of tyrosine kinase inhibitors

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

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Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives

Hormone and Metabolic Research ◽

10.1055/a-1380-4154 ◽

2021 ◽

Vol 53 (03) ◽

pp. 149-160

Author(s):

Frederik A. Verburg ◽

Holger Amthauer ◽

Ina Binse ◽

Ingo Brink ◽

Andreas Buck ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Performance Status ◽

Progression Free Survival ◽

Placebo Treatment ◽

Differentiated Thyroid Carcinoma ◽

Future Research ◽

Prospective Comparison

AbstractNotwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

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Assessment of Biomarkers for Clinical Diagnosis of Papillary Thyroid Carcinoma with Distant Metastasis

The International Journal of Biological Markers ◽

10.1177/172460081002500106 ◽

2010 ◽

Vol 25 (1) ◽

pp. 38-45 ◽

Cited By ~ 20

Author(s):

Huasheng Liang ◽

Yuhua Zhong ◽

Zuojie Luo ◽

Yu Huang ◽

Huade Lin ◽

...

Keyword(s):

Growth Factor ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Clinical Diagnosis ◽

Distant Metastasis ◽

Roc Curve ◽

Curve Analysis ◽

Papillary Thyroid ◽

Roc Curve Analysis ◽

Thyroid Carcinomas

Early diagnosis and treatment of thyroid cancers are critical for better prognosis and better survival rates. The purpose of this study was to identify potential diagnostic markers for papillary thyroid carcinomas with distant metastasis. Fifty-eight papillary thyroid tumor specimens (27 papillary thyroid carcinomas with distant metastasis and 31 without metastasis) were examined, and protein expression of pituitary tumor-transforming gene (PTTG), E-cadherin, p27kip1, vascular endothelial growth factor (VEGF)-C, metalloproteinase (MMP) 2, MMP9, chemokine receptor CXCR4, and basic fibroblast growth factor (bFGF) in these tumors was assessed by immunohistochemistry. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and their diagnostic values were evaluated by ROC curve analysis. PTTG, VEGF-C, MMP2, MMP9, CXCR4, and bFGF were overexpressed in metastatic papillary thyroid carcinomas, whereas p27kip1 expression was elevated only in carcinomas lacking metastasis. Multiple-factor binary ordinal logistic regression analysis revealed that PTTG, VEGF-C, MMP2, and bFGF were independently related to biological metastatic behavior in thyroid tumors, suggesting their potential use as biomarkers. ROC curve analysis showed that among these four proteins, VEGF-C and bFGF were the best diagnostic biomarkers. A VEGF-C and bFGF cluster was the most useful factor for the differential diagnosis between metastatic and non-metastatic papillary thyroid cancers. Thus, the combined use of VEGF-C and bFGF as biomarkers may improve the diagnostic accuracy of papillary thyroid carcinoma and may be useful in multimodal screening programs for the clinical diagnosis of papillary thyroid carcinoma and early detection of papillary thyroid carcinoma with distant metastasis.

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Tyrosine-kinase inhibitors to treat radioiodine-refracted, metastatic, or recurred and progressive differentiated thyroid carcinoma [Review]

Endocrine Journal ◽

10.1507/endocrj.ej16-0064 ◽

2016 ◽

Vol 63 (7) ◽

pp. 597-602 ◽

Cited By ~ 19

Author(s):

Yasuhiro Ito ◽

Shinichi Suzuki ◽

Ken-ichi Ito ◽

Tsuneo Imai ◽

Takahiro Okamoto ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Differentiated Thyroid Carcinoma

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Prognostic factors of chronic myeloid leukaemia

Oxford Specialist Handbook: Myeloproliferative Neoplasms ◽

10.1093/med/9780198744214.003.0005 ◽

2020 ◽

pp. 63-78

Author(s):

Michele Baccarani ◽

Fausto Castagnetti ◽

Gabriele Gugliotta ◽

Francesca Palandri ◽

Simona Soverini ◽

...

Keyword(s):

Chronic Myeloid Leukaemia ◽

Risk Stratification ◽

Tyrosine Kinase ◽

Myeloid Leukaemia ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

First Line ◽

Abl Tyrosine Kinase ◽

Baseline Characteristics ◽

Kinase Domain Mutations

Two decades following the successful introduction of the ABL tyrosine kinase inhibitors in clinics for the treatment of patients with chronic myeloid leukaemia (CML), the principal objective of treatment in chronic phase (CP) is survival, preferably without life-long therapy. In tandem, the methodology and tools for assessing the prognosis of the newly diagnosed patient with CML in CP has evolved substantially. Prior to the era of tyrosine kinase inhibitors (TKIs), risk assessment depended more on the response to treatment than on baseline characteristics. The Sokal score, introduced in 1984, was the first one dividing patients into three risk categories based on a mathematical formula taking into account the patient’s age, and baseline characteristics like blast cell count, spleen size, and platelet count. This, and the several other subsequent risk stratification methods developed during the chemotherapy and interferon-alpha era, have remained useful in the first-line TKI treatment, and identifies a variable proportion of high-risk patients with lower response rates and worse outcomes. In second line, the most important risk factors are the absence of haematologic or cytogenetic response on first line, the presence of hematologic toxicity the development of additional cytogenetic abnormities (ACA), and the development of BCR-ABL1 kinase domain mutations. In this chapter, we address the prognosis of CML and the various methods for risk stratification.

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