Locally Advanced Thyroid Cancer: Can CT Help in Prediction of Extrathyroidal Invasion to Adjacent Structures?

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

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The efficacy and safety of anlotinib in neoadjuvant treatment in locally advanced thyroid cancer: A single-arm phase II clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6069 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6069-6069

Author(s):

Naisi Huang ◽

Guohua Sun ◽

Yulong Wang ◽

Jiaying Chen ◽

Qing Guan ◽

...

Keyword(s):

Clinical Trial ◽

Thyroid Cancer ◽

Adverse Events ◽

Objective Response ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Primary Treatment ◽

Tumor Diameter ◽

Efficacy And Safety ◽

Advanced Thyroid Cancer

6069 Background: Surgery is the primary treatment for locally advanced thyroid cancer (TC). For some locally advanced TC, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. However, there is still little evidence regarding neoadjuvant treatment in locally advanced TC. Methods: This single-arm, phase 2 study investigated the efficacy and safety of Anlotinib (12mg orally daily, for two weeks on/on week off) for 2-6 cycles in patients with locally advanced TC in the neoadjuvant setting. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were included and received an average of 3.5 cycles (range: 3-6 cycles) of Anlotinib treatment. 12 cases were papillary thyroid cancer, and 1 was follicular thyroid cancer. The ORR of Anlotinib was 76.9% with 10 partial response (PR), 2 stable disease (SD), and 1 progressive disease (PD). 8 PR and 1 SD patients received surgery after neoadjuvant treatment, of whom 8 had R0/1 resections and 1 had R2 resection. 2 PR patients refused to have surgery and the rest 2 patients were not operable. The R0/1 resection rate for intent to treat population was 61.5% and for per-protocol population was 72.7%. The maximum reduction in sum of tumor diameter was an average of 34.8% (range: 30.9%-45.5%) for PR patients. Most adverse events were grade 1 or 2. Common adverse events of all grade were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), TSH increase (53.8%), cholesterol elevation (53.8%) and hand-foot syndrome (38.5%). The majority of adverse events discontinued after the neoadjuvant treatment stopped. Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment in locally advanced TC and the majority of patients achieved R0/1 resection. Adverse events were consistent with the known Anlotinib adverse event profile. These results suggest that Anlotinib neoadjuvant treatment represents a new option for locally advanced TC. Clinical trial information: NCT04309136.

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Management of Locally Advanced Thyroid Cancer

Evidence-Based Endocrine Surgery ◽

10.1007/978-981-10-1124-5_8 ◽

2018 ◽

pp. 85-95

Author(s):

Andrea R. Marcadis ◽

Jennifer Cracchiolo ◽

Ashok K. Shaha

Keyword(s):

Thyroid Cancer ◽

Locally Advanced ◽

Advanced Thyroid Cancer

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Intensity modulated radiotherapy in locally advanced thyroid cancer: Outcomes of a sequential phase I dose-escalation study

Radiotherapy and Oncology ◽

10.1016/j.radonc.2018.02.002 ◽

2018 ◽

Vol 127 (1) ◽

pp. 43-48 ◽

Cited By ~ 1

Author(s):

K.P. Rooney ◽

A.B. Miah ◽

S.A. Bhide ◽

M.T. Guerrero-Urbano ◽

M.T. Sharabiani ◽

...

Keyword(s):

Thyroid Cancer ◽

Phase I ◽

Dose Escalation ◽

Locally Advanced ◽

Intensity Modulated Radiotherapy ◽

Cancer Outcomes ◽

Dose Escalation Study ◽

Intensity Modulated ◽

Advanced Thyroid Cancer ◽

Sequential Phase

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A phase II study of axitinib (AG-013736 [AG]) in patients (pts) with advanced thyroid cancers

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.6008 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 6008-6008 ◽

Cited By ~ 11

Author(s):

E. E. Cohen ◽

E. E. Vokes ◽

L. S. Rosen ◽

M. S. Kies ◽

A. A. Forastiere ◽

...

Keyword(s):

Thyroid Cancer ◽

Tumor Regression ◽

Locally Advanced ◽

Thyroid Tumor ◽

External Beam Radiation ◽

Vegf Receptors ◽

Beam Radiation ◽

Thyroid Cancers ◽

Advanced Thyroid Cancer ◽

Multi Center Study

6008 Background: Elevated VEGF-A and VEGF-C have been reported in thyroid tumor tissue compared with normal thyroid. AG is a potent, small molecule inhibitor of VEGF receptors 1, 2 and 3. The efficacy and safety of AG therapy in pts with advanced thyroid cancers was examined in this single-arm, multi-center study. Methods: 60 pts with metastatic or unresectable locally-advanced thyroid cancer refractory to, or not suitable candidates for, 131iodine (131I) treatment, with measurable disease received AG at a starting dose of 5 mg orally BID. The primary endpoint was response rate (RR) by RECIST criteria. A Simon 2-stage minimax design was used (a=0.1; β=0.1; null RR=5%; alternative RR=20%). Samples were collected pretreatment and q8wks to explore relationships between clinical response and plasma soluble proteins. Results: Median age was 59 yrs (26–84), 35 (58%) were male. Histological subtypes included papillary: 29 pts (48%); follicular: 15 pts (25%)-11 (18%) with Hurthle cell variant; medullary: 12 pts (20%); anaplastic: 2 pts (3%), and other/unknown: 2 pts (3%). 53 pts (88%) had prior surgery, 42 (70%) had prior 131I treatment, 27 (45%) had prior external beam radiation, and 9 (15%) had prior chemotherapy. Partial response (PR) by investigator report was achieved in 13 pts (22% CI: 12.1, 34.2), with 31- 68% maximum tumor regression and duration of response (DOR) of 1–16 months. 30 pts (50%) have stable disease with a duration range of 4–13 months and 13–67% maximum tumor regression in 28 pts. Response assessments are ongoing. The treatment duration range is 6–670 days with 38 pts currently on study. Median PFS has not been reached with a median follow up of 273 days. The most common treatment-related adverse events were fatigue (37%), proteinuria (27%), stomatitis/mucositis (25%), diarrhea (22%), hypertension (20%) and nausea (18%). AG therapy consistently decreased soluble VEGFR2 and VEGFR3, and increased VEGF in the blood, demonstrating pharmacodynamic activity against targeted VEGF receptors. Conclusions: AG has substantial anti-tumor activity in advanced thyroid cancer with demonstrated pharmacodynamic activity. A global pivotal trial testing AG in doxorubicin refractory thyroid cancer is ongoing. [Table: see text]

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An Update of the Appropriate Treatment Strategies in Anaplastic Thyroid Cancer: A Population-Based Study of 735 Patients

International Journal of Endocrinology ◽

10.1155/2019/8428547 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Nai-si Huang ◽

Xiao Shi ◽

Bo-wen Lei ◽

Wen-jun Wei ◽

Zhong-wu Lu ◽

...

Keyword(s):

Thyroid Cancer ◽

Distant Metastasis ◽

Cox Regression ◽

Early Stage ◽

Locally Advanced ◽

Treatment Strategies ◽

Anaplastic Thyroid Cancer ◽

Treatment Modalities ◽

Cox Regression Analysis ◽

Adjacent Structures

Background. Anaplastic thyroid cancer (ATC) responds poorly to conventional therapies and requires a multidisciplinary approach to manage. The aim of the current study is to explore whether aggressive treatment is beneficial, especially the appropriate extent of surgery in ATC. Methods. Patients diagnosed with ATC from 2004 to 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database and included in our study. Results. A total of 735 ATC patients were identified. The two-year overall survival (OS) rates for stage IVA, IVB, and IVC patients were 36.5%, 15.6%, and 1.4%, respectively. By directly comparing eight treatment modalities, we found that surgery+radiotherapy RT±chemotherapy was the most effective treatment strategy. surgery+chemotherapy and RT+chemotherapy had comparable results (hazard ratio HR=1.461, 95% confidential interval (CI): 0.843-2.531, P=0.177). Multivariate Cox regression analysis also showed increased mortality risk in patients with increased age (HR=1.022, P<0.001), tumor extension to adjacent structures (HR=1.649, P=0.013), and distant metastasis (HR=2.041, P<0.001), while surgery+RT (HR=0.600, P=0.004) and chemotherapy (HR=0.692, P=0.010) were independently associated with improved OS. Further analysis revealed that patients undergoing total/near-total thyroidectomy (TT) had superior OS to those receiving less than TT (P<0.001). In subgroup analysis, the benefit of TT remained significant in patients with tumors larger than 4.0 cm (HR=0.776, 95% CI: 0.469-0.887, P=0.007), with adjacent structure extension (HR=0.642, 95% CI: 0.472-0.877, P=0.005), including trachea and major vessels, but not in patients with early phase local disease such as tumor≤4.0 cm or tumor within the thyroid or with minimal extrathyroidal extension. Patients with very locally advanced disease or distant metastasis could not benefit from TT as well. Conclusions. In operable cases, surgery+RT±chemotherapy was the optimal treatment modality. Otherwise, RT+chemotherapy was the appropriate strategy. However, TT was not beneficial for very early stage or metastatic ATC.

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