Diagnostic and prognostic value of preoperative systemic inflammatory markers in anaplastic thyroid cancer.

BACKGROUND: Easily accessible, generalized, and inexpensive methods are expected to differentiate anaplastic thyroid carcinoma (ATC) from advanced differentiated thyroid cancer (aDTC). We aimed to explore potential diagnostic and prognostic value of systematic inflammatory markers (SIMs) in ATC and aDTC. METHODS: About 22 ATC, 101 aDTC, and 100 matched early DTC patients were analyzed retrospectively. SIMs included the comprehensive index, neutrophil-monocyte-platelet-to-lymphocyte ratio (NMPLR) and the previously reported ones. Receiver operating characteristic, Kaplan-Meier, and COX regression analyses were mainly conducted. RESULTS: NMPLR exhibited the highest area under the curve value 0.806 (P < .0001) to diagnose ATC from aDTC. NMPLR was identified as an independent risk factor for overall survival (OS) (hazard ratio [HR]: 47.821, 95% confidence interval [CI], 2.863-798.765, P = .007) in ATC, as well as for OS (HR: 7.360, 95% CI, 1.620-33.430, P = .010) and recurrence-free survival (HR: 4.172, 95% CI, 1.139-15.286, P = .031) in aDTC. Taken both refractory types (ATC and aDTC) together, NMPLR could independently predict OS (HR: 6.470; 95% CI, 2.134-19.616; P = .001). CONCLUSION: NMPLR is a generalized index. It showed excellent potential in differential diagnosis and survival prediction in refractory thyroid cancer. However, it needs to be validated in larger cohort and clinical practice.

Anaplastic Thyroid Cancer: A Rare Entity Presented Clinically Only with Fever and Elevated CRP.

Anaplastic thyroid carcinoma (ATC) is a rare but almost invariably lethal disease. In this manuscript, we present a case where the dominant manifestation of ATC beside the goitre was elevated CRP values and a persistent low-grade fever. The patient underwent surgical removal of the tumour, chemotherapy and radiotherapy treatment. She is still alive and healthy 11 months after the surgery. We aim to demonstrate that ATC can be present with no specific symptoms or findings and to raise awareness towards an earlier diagnosis.

Low Lymphocyte-to-Monocyte Ratios Are Associated with Poor Overall Survival in Anaplastic Thyroid Carcinoma Patients.

Background: The lymphocyte-to-monocyte ratio (LMR), which reflects the tumor-infiltrating immune cell status and host immunity, has been reported as a prognostic marker in various cancers. The aim of the present study was to evaluate the role of the LMR as a prognostic marker in predicting the survival of patients with anaplastic thyroid carcinoma (ATC). Methods: This study retrospectively included 35 ATC patients with available complete blood cell count data. The primary outcome was the overall survival (OS) of patients with ATC. Results: There were no significant differences between the LMR of the baseline and that of the follow-up complete blood cell count data (p = 0.53). The patients were divided into two groups based on their baseline LMR: a low LMR group (<4; n = 23, 66%) and a high LMR group (≥4; n = 12, 34%). The proportion of cervical lymph node metastasis in the low LMR group was significantly higher than that in the high LMR group (p = 0.021). The OS curves were significantly different based on the LMR values, and the median OS of the low and high LMR groups were 3.0 and 9.5 months, respectively (p = 0.004). In multivariate analysis, a low LMR was also an independent risk factor for all-cause mortality in patients with ATC (hazard ratio = 2.55 [confidence interval 1.08-6.00], p = 0.032) after adjusting for sex, tumor size, and distant metastasis. Conclusions: A low LMR is associated with poor survival in patients with ATC. The LMR could be a simple and stable prognostic biomarker reflecting host immunity in patients with ATC. Further studies are needed to confirm the prognostic role of the LMR in ATC.

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma.

BACKGROUND: BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAFV600E assay was reported. The objective of this study was to assess the correlation of BRAFV600E circulating tumor RNA levels with surgical and medical treatment. METHODS: Circulating BRAFV600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAFV600E mutation undergoing BRAFV600E-inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAFV600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAFV600E values were assessed and compared to clinical characteristics and response to therapy. RESULTS: In a murine model of anaplastic thyroid carcinoma with BRAFV600E mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAFV600E-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAFV600E levels declined postoperatively (median 370.0-178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAFV600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. CONCLUSIONS: This study shows the correlation of blood BRAFV600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAFV600E-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.

Real-Time Genomic Characterization Utilizing Circulating Cell-Free DNA in Patients with Anaplastic Thyroid Carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive disease that requires rapid diagnosis and multimodality treatment. Recent advances in targeted therapeutics have provided ATC patients with previously unavailable treatment options, which may improve clinical outcomes in the coming years. Continued development of high-throughput next-generation sequencing provides clinicians with an unparalleled ability to characterize the genomic background of tumors in order to guide treatment selection and clinical trial enrollment. METHODS: Twenty-three patients with ATC treated at the University of Texas MD Anderson Cancer Center between August 2015 and April 2016 were evaluated. All patients underwent next-generation sequencing using an institutional tissue-based DNA platform (50 genes) and a commercially available cell-free circulating DNA (cfDNA) platform (70 genes). RESULTS: Sequencing data were successfully obtained for both platforms on all patients. The most commonly mutated genes noted on both platforms were TP53 (15/23; 65%) and BRAF (11/23; 48%). Concordance between the tumor and cfDNA data was high for BRAF, PIK3CA, NRAS, and PTEN and moderate for TP53. Concordance was highest in patients who underwent dual-platform sequencing prior to initiation of definitive treatment, and lowest in patients who underwent cfDNA analysis following treatment. Nineteen patients had treatment at the University of Texas MD Anderson Cancer Center following cfDNA sequencing. One patient was observed, and three patients opted for hospice. At the time of last contact, 15/23 (65%) patients were alive. CONCLUSIONS: Next-generation sequencing platforms offer clinicians an opportunity to identify targetable oncogenic events in ATC. To the authors' knowledge, this is the largest sequential cohort of ATC patients who have undergone targeted genomic profiling. Based on these data, utilization of both tumor-based and cfDNA analysis in the context of clinical-trial development and application is recommended. Integration of these or similar platforms in clinical-trial implementation may have the potential to transform clinical outcomes for patients with ATC.

Anaplastic thyroid carcinoma accompanied by uncontrollable eosinophilia.

Anaplastic thyroid carcinoma is a rare disease, and cases associated with eosinophilia are even rarer. We herein report a case of anaplastic thyroid carcinoma accompanied by remarkable and uncontrollable eosinophilia. A 71-year-old man was diagnosed with end-stage anaplastic thyroid carcinoma. Throughout the aggressive clinical course of the cancer, eosinophilia dramatically progressed and became extremely refractory to steroid treatment. We measured the serum levels of hematopoietic cytokines potentially involved in eosinophilia, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5. Although the GM-CSF level was moderately elevated, both the IL-3 and IL-5 levels were within the normal ranges. In this case, the patient's eosinophilia may have been related to his severe dyspnea and was likely responsible for the allergic reaction to the anticancer drug. Therefore, it is essential to elucidate the etiology of eosinophilia in patients with thyroid cancer in order to improve the treatment for patients with anaplastic thyroid carcinoma.