The dilemma of metastatic medullary thyroid carcinoma: when to start systemic treatment

2019 ◽  
Vol 105 (6) ◽  
pp. NP28-NP31
Author(s):  
Marco Siano ◽  
Salvatore Alfieri ◽  
Roberta Granata ◽  
Giuseppina Calareso ◽  
Ester Orlandi ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Lymph Nodes ◽  
Medullary Thyroid Carcinoma ◽  
Systemic Therapy ◽  
Kinase Inhibitors ◽  
Locally Advanced ◽  
Tumor Burden ◽  
Bone Lesions ◽  
Progression Rate ◽  
Medullary Thyroid

Purpose: Two tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib, have been approved for recurrent/metastatic (R/M) medullary thyroid carcinoma (MTC). To date, it is still debated when and which TKI has to be started in R/M MTC patients. This is due to 1) TKI-related toxicity burden, 2) no overall survival benefit for either TKI, and 3) progression-free survival improvement in MTC subgroups ( RETM918T and RAS mutations) treated with cabozantinib. Herein, we present a case of R/M MTC with a discordant disease behavior because of spontaneous regression of some parenchymal sites along with progression of bone metastases, putting into the question the best timing for starting TKIs in R/M MTC. Methods: We report a 46-year-old man with relapse (lymph nodes in the neck and mediastinum) after curative treatment (total thyroidectomy plus central compartment and right neck dissection) for a locally advanced MTC with only somatic RETM918T mutation. Considering the low tumor burden, absence of symptoms, as well as the potential TKI-related side effects, we decided not to start systemic therapy when metastases first appeared. Results: Some lymph nodes spontaneously regressed, while new symptomatic bone lesions appeared with need for palliative radiotherapy. In total, first-line systemic therapy (cabozantinib) was started after 2 years since first distant metastases appearance. Conclusions: Radiologic progression of disease alone seems not to be adequate for MTC patients’ selection to be treated. The progression rate, the tumor burden, and the site of disease should also be taken into account for the clinical decision process.

scholarly journals Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times

2008 ◽  
Vol 158 (2) ◽  
pp. 239-246 ◽  
Author(s):  
Anne Laure Giraudet ◽  
Abir Al Ghulzan ◽  
Anne Aupérin ◽  
Sophie Leboulleux ◽  
Ahmed Chehboun ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Carcinoembryonic Antigen ◽  
Disease Progression ◽  
Medullary Thyroid Carcinoma ◽  
Stable Disease ◽  
Progressive Disease ◽  
Tumor Burden ◽  
Ki 67 ◽  
Medullary Thyroid ◽  
Doubling Times

ObjectiveThe progression of medullary thyroid cancer is difficult to assess with imaging modalities; we studied the interest of calcitonin and carcinoembryonic antigen (CEA) doubling times and of Ki-67 labeling and mitotic index (MI).Patients and methodsFifty-five consecutive medullary thyroid carcinoma (MTC) patients with elevated calcitonin levels underwent repeated imaging studies in order to assess tumor burden and progression status. We looked for relationships between tumor burden and levels of calcitonin and CEA and between progression status according to the response evaluation criteria in solid tumors (RECIST) and calcitonin and CEA doubling times, and Ki-67 labeling and MI.ResultsThe calcitonin and CEA levels were correlated with tumor burden. Ten patients with calcitonin levels below 816 pg/ml had no imaged tumor foci. Among the 45 patients with imaged tumor foci, 19 had stable disease and 26 had progressive disease, according to the RECIST. The calcitonin and CEA doubling times were strongly related to disease progression, with very few overlaps: 94% of patients with doubling times shorter than 25 months had progressive disease and 86% of patients with doubling times longer than 24 months had stable disease. Ki-67 labeling and MI were not significantly associated with disease progression.ConclusionFor MTC patients, the doubling times of both calcitonin and CEA are efficient tools for assessing tumor progression.

Anlotinib treatment in locally advanced or metastatic medullary thyroid carcinoma: A multicenter, randomized, double-blind, placebo-controlled phase IIB trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6019-6019 ◽  
Author(s):  
Dapeng Li ◽  
Ping Zhang Tang ◽  
Xiaohong Chen ◽  
Minghua Ge ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Primary Endpoint ◽  
Target Therapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Double Blind ◽  
Medullary Thyroid ◽  
Therapy Strategy

6019 Background: Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferative signaling. Our previous single-arm phase 2 ALTN/MTC trial (NCT01874873) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic medullary thyroid carcinoma (MTC). Here we report results of the phase IIB trial (ALTER01031, NCT02586350) of anlotinib for locally advanced or metastatic MTC with a larger samples. Methods: Between September 2015 and September 2018, 91 patients were enrolled in China. Eligible patients have diagnosed as phase IV MTC with relapsed and measurable disease and without antiangiogenetic target therapy. The patients were randomly assigned in a 2:1 ratio to receive anlotinib or a matched placebo (12 mg QD from day 1 to 14 of a 21-day cycle). Patients who have been diagnosed with disease progression by the Independent Imaging Committee could be unblinded and crossed to the treatment group if the patient previous treated by placebo. The primary endpoint was progression-free survival (PFS). Results: 91 patients were randomized 62 to anlotinib arm and 29 to placebo arm. Until the data cutoff date (1 Feb 2019), median PFS was 20.67 months (95%CI, 14.03-34.63) in anlotinib arm vs 11.07 (95%CI, 5.82-14.32) months in placebo arm (HR 0.53, p = 0.0289). The OS data were not sufficiently mature for analysis. Considerable improvement in ORR was observed over the two arms (48.39% vs 3.45%, p < 0.0001). The adverse events (AEs) were 100% in anlotinib arm and 89.66% in placebo arm. The most common AEs in anlotinib arm were hand-foot syndrome, hypertension, hypertriglyceridemia and diarrhea. Conclusion: ALTER01031 met its primary endpoint of PFS shows that anlotinib treatment is effective and well tolerated. The safety profile was consistent and no new adverse events were identified. These data potentially extend the role of anlotinib monotherapy as a new therapy strategy for MTC patients. Clinical trial information: NCT02586350.

scholarly journals Advances in the management of MEN2: from improved surgical and medical treatment to novel kinase inhibitors

2018 ◽  
Vol 25 (2) ◽  
pp. T1-T13 ◽  
Author(s):  
Samuel A Wells
Keyword(s):  
Pharmaceutical Industry ◽  
Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Kinase Inhibitors ◽  
Locally Advanced ◽  
Targeted Therapeutics ◽  
Medullary Thyroid ◽  
Dominant Component ◽  
Endocrine Neoplasia

Medullary thyroid carcinoma (MTC), a tumor derived from the neural crest, occurs either sporadically or as the dominant component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B. The discovery that mutations in the RET protooncogene cause hereditary MTC was of great importance, since it led to the development of novel methods of diagnosis and treatment. For example, the detection of a mutated RET allele in family members at risk for inheriting MEN2A or MEN2B signaled that they would develop MTC, and possibly other components of the syndromes. Furthermore, the detection of a mutated allele created the opportunity, especially in young children, to remove the thyroid before MTC developed, or while it was confined to the gland. The discovery also led to the development of molecular targeted therapeutics (MTTs), mainly tyrosine kinase inhibitors, which were effective in the treatment of patients with locally advanced or metastatic MTC. While responses to MTTs are often dramatic, they are highly variable, and almost always transient, because the tumor cells become resistant to the drugs. Clinical investigators and the pharmaceutical industry are focusing on the development of the next generation of MTTs, which have minimal toxicity and greater specificity for mutated RET.

scholarly journals Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma

Thyroid ◽  
2017 ◽  
Vol 27 (9) ◽  
pp. 1142-1148 ◽  
Author(s):  
Yasuhiro Ito ◽  
Naoyoshi Onoda ◽  
Ken-ichi Ito ◽  
Iwao Sugitani ◽  
Shunji Takahashi ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Locally Advanced ◽  
Japanese Patients ◽  
Anaplastic Thyroid Carcinoma ◽  
Medullary Thyroid

scholarly journals Correlation between Preoperative Ultrasonic Features of Medullary Thyroid Carcinoma and Postoperative Recurrence

2021 ◽  
Author(s):  
Qiaodan Zhu ◽  
Dong Xu
Keyword(s):  
Thyroid Carcinoma ◽  
Lymph Nodes ◽  
Medullary Thyroid Carcinoma ◽  
Postoperative Recurrence ◽  
Capsular Invasion ◽  
Calcitonin Level ◽  
Medullary Thyroid ◽  
Metastatic Lymph Nodes ◽  
Recurrence Group

Abstract Background: To investigate the factors that affect postoperative recurrence in medullary thyroid carcinoma (MTC) patients, including preoperative ultrasonic characteristics and other factors. Method: A retrospective analysis of seventy four MTC patients who underwent the first thyroid surgery from 2009 to 2018 and who had complete follow-up data was conducted. According to the follow-up results, these patients were divided into the recurrence group (17 cases) and non-recurrence group (57 cases). The preoperative ultrasound characteristics, preoperative and postoperative calcitonin levels, and general informations of the two groups were recorded, respectively. Univariate and multivariate analyses were performed. Results: Single factor Kaplan-Meier (K-M) analysis showed that: ① Preoperative ultrasonic characteristics including tumor size > 40.0 mm, capsular invasion, and metastatic cervical lymph nodes, as well as preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin (within one week) level > 45.0 pg/ml were positively correlated with the risk of postoperative recurrence of MTC (P <0.05); ② There was no evidence to show that gender and age had a statistically significant effect on postoperative recurrence of MTC (P> 0.05). Multivariate Cox regression analysis showed that metastatic lymph nodes shown by ultrasound (HR=5.368, 95%CI 1.063-27.104, P=0.042) was an independent risk factor for postoperative recurrence of MTC. Conclusions: MTC patients with metastatic lymph nodes shown by ultrasound are prone to postoperative recurrence of MTC. In addition, MTC patients with a tumor > 40.0 mm, capsular invasion, preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin level > 45.0 pg/ml are more likely to have postoperative recurrence.

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