Prognostic Factors Improving ATA Risk System and Dynamic Risk Stratification in Low- and Intermediate-Risk DTC Patients.

CONTEXT: American Thyroid Association (ATA) guidelines do not consider age at diagnosis as a prognostic factor on the estimation of the risk of persistent/recurrent disease in differentiated thyroid carcinoma (DTC) patients. While age at diagnosis has already been assessed in high-risk patients, it remains to be established in low- and intermediate-risk patients. OBJECTIVE: The aim of our study was to investigate the role of age as a prognostic factor in the short- and long-term outcome of DTC patients classified at low and intermediate risk according to the ATA stratification risk system. METHODS: We retrospectively evaluated 863 DTC patients (mean follow-up: 10 ± 6.2 years) 52% classified as low (449/863) and 48% as intermediate risk (414/863). For each ATA-risk class patients were divided into subgroups based on age at diagnosis (<55 or ≥55 years). RESULTS: In the intermediate-risk group, patients aged 55 years or older had a higher rate of structural disease (11.6% vs 8.9%), recurrent disease (4.1% vs 0.7%), and death (4.1% vs 1%) when compared with younger patients (<55 years) (P = .007). Multivariate analysis confirmed that older age at diagnosis (odds ratio [OR] = 3.9; 95% CI, 1.9-8.6; P < .001) was an independent risk factor for worse long-term outcome together with response to initial therapy (OR = 13.0; 95% CI, 6.3-27.9; P < .001), and T (OR = 32; 95% CI, 1.4-7.1; P = .005) and N category (OR = 2.3; 95% CI, 1.1-5.0; P = .03). Nevertheless, a negative effect of older age was documented only in the subgroup of intermediate DTC patients with persistent structural disease after initial therapy. Indeed, the rate of worse long-term outcome rose from 13.3% in the whole population of intermediate DTC patients to 47.8% in patients with persistent structural disease after initial therapy (P < .001) and to 80% in patients older than 55 years and persistent structural disease after initial therapy (P = .02). CONCLUSION: Our results suggest that age at diagnosis further predict individual outcomes in Intermediate-Risk DTC allowing ongoing management to be tailored accordingly.

Dynamic Risk Stratification Integrated with ATA Risk System for Predicting Long-Term Outcome in Papillary Thyroid Cancer.

BACKGROUND: In recent years, there has been a renewed interest in thyroid cancer management paradigms that use individualized risk assessments as the basis for treatment and follow-up recommendations. In this study, we assumed that the long-term follow-up of differentiated thyroid cancer patients might be better tailored by integrating the response to initial therapy with the America Thyroid Association (ATA) risk classes. METHODS: This retrospective study included low- and intermediate-risk papillary thyroid cancer (PTC) patients followed up for a median time of 8 years and classified according to the response to initial therapy assessed 6-12 months after initial treatment. RESULTS: After a median follow-up of 8 years, in the initial excellent response subgroup of PTC patients (n = 522), the rate of recurrent disease was significantly higher in intermediate-risk patients than in low-risk PTC patients (6.9% versus 1.2%, p = 0.0005). Similarly, in the initial biochemical incomplete response subgroup (n = 82), the rate of excellent response was significantly higher in low-risk PTC patients (58.0%) than in intermediate-risk PTC patients (33.3%) (p = 0.007). Finally, in the initial structural incomplete response subgroup (n = 66), the rate of excellent response was higher in low-risk patients (80.0%) than in intermediate-risk patients (46.4%) (p = 0.08). Moreover, all patients with initial indeterminate response had an excellent response at the last follow-up visit. ATA risk classes were independently associated with long-term outcome in each subgroup of patients classified dynamically after initial therapy and the overall prognostic performance, defined via ROC curve analysis, of response to initial therapy integrated with the ATA risk system (AUC: 0.89; 95% CI: 0.86-0.92) was significantly higher compared to the ATA risk stratification (AUC 0.69; 95% CI: 0.65-0.74, p < 0.001) or the dynamic risk stratification (DRS) systems alone (AUC: 0.86 95% CI: 0.82-0.90, p = 0.007). CONCLUSIONS: This study of a large cohort of PTC patients showed that the initial ATA risk criteria may be useful for improving the risk-adapted management of PTC patients based on the response to initial therapy.

Enlargement of a metastatic lymph node from differentiated thyroid cancer after COVID-19 vaccination.

BACKGROUND: The massive vaccination campaign against COVID-19 has granted a high level of protection against the severe forms of the disease at the price of some mild adverse events. OBJECTIVE: To underline that COVID-19 vaccination can induce a transient enlargement of lymph-node metastases in differentiated thyroid cancer patients. CASE PRESENTATION: We describe the clinical, laboratory, and imaging features of a 60-year-old woman affected by paratracheal lymph-node relapse of Hurtle Cell Carcinoma who came to our attention after full COVID-19 vaccination because of neck swelling and pain. In April 2021, after 5 years of stable structural disease, the patient presented an enlargement of the metastatic lymph node, associated with a rise of serum thyroglobulin (from 4.6 to 14.7 pg/mL). Anti-inflammatory treatment was started and pain and swelling remitted after 15 days. At the subsequent evaluation, at neck ultrasound, the right paratracheal lesion was smaller and thyroglobulin dropped to 3.9 pg/mL. CONCLUSIONS: We report the case of an enlargement of metastatic lymph node from differentiated thyroid cancer after COVID-19 vaccination. We warn clinicians to identify features of inflammatory response due to COVID-19 vaccination in order to prevent unwarranted surgical treatment.

Pilot Study on the Impact of Polymorphisms Linked to Multi-Kinase Inhibitor Metabolism on Lenvatinib Side Effects in Patients with Advanced Thyroid Cancer.

Multi-kinase inhibitors (MKIs) represent the best therapeutic option in advanced thyroid cancer patients. The therapeutic efficacy and toxicity of MKIs are very heterogeneous and are difficult to predict before starting treatment. Moreover, due to the development of severe adverse events, it is necessary to interrupt the therapy some patients. Using a pharmacogenetic approach, we evaluated polymorphisms in genes coding for proteins involved with the absorption and elimination of the drug in 18 advanced thyroid cancer patients treated with lenvatinib, and correlated the genetic background with (1) diarrhea, nausea, vomiting and epigastric pain; (2) oral mucositis and xerostomia; (3) hypertension and proteinuria; (4) asthenia; (5) anorexia and weight loss; (6) hand foot syndrome. Analyzed variants belong to cytochrome P450 (CYP3A4 rs2242480 and rs2687116 and CYP3A5 rs776746) genes and to ATP-binding cassette transporters (ABCB1 rs1045642, rs2032582 and rs2235048 and ABCG2 rs2231142). Our results suggest that the GG genotype for rs2242480 in CYP3A4 and CC genotype in rs776746 for CYP3A5 were both associated with the presence of hypertension. Being heterozygous for SNPs in the ABCB1 gene (rs1045642 and 2235048) implicated a higher grade of weight loss. The ABCG2 rs2231142 statistically correlated with a higher extent of mucositis and xerostomia (CC genotype). Heterozygous and rare homozygous genotypes for rs2242480 in CYP3A4 and for rs776746 for CYP3A5 were found to be statistically linked to a worse outcome. Evaluating the genetic profile before starting lenvatinib treatment may help to predict the occurrence and grade of some side effects, and may contribute to improving patient management.

Radioiodine therapy in the different stages of differentiated thyroid cancer.

Differentiated thyroid cancer is the most frequent type of thyroid cancer with an increasing incidence in the last decades. The initial management is represented by surgical treatment followed by radioactive iodine therapy that includes remnant ablation, adjuvant treatment or treatment of metastatic disease. Radioactive iodine treatment is performed only in selected cases based on the risk of recurrence and mortality during follow up, according to American Joint Committee on Cancer Union for international Cancer Control Tumor, Node, Metastasis (AJCC/TNM) staging system and the 2015 American Thyroid Association (ATA) risk stratification system. This article will review the key factors to consider when planning radioactive iodine therapy in differentiated thyroid cancer patients after surgery and during follow up.

Effect of Pre-Existent Sarcopenia on Oncological Outcome of Advanced Thyroid Cancer Patients Treated with Tyrosine Kinase Inhibitors.

(1) Background: Sarcopenia is associated with poor survival and treatment outcomes in several human cancers. The aim of the study was to investigate the prevalence of sarcopenia in a cohort of 58 Caucasian patients with advanced thyroid cancer before and during TKI treatment. The impact of this condition on the outcome of patients was also evaluated. (2) Methods: Sarcopenia was evaluated using the Skeletal Muscle Index (SMI). (3) Results: Pre-treatment sarcopenia was found in 20.7% of patients and this condition significantly affected treatment outcome, emerging as the parameter that has the greatest impact on Progression Free Survival (PFS) (HR 4.29; 95% CI, 1.21−15.11, p = 0.02). A significant reduction in SMI values was observed 3 (p = 0.002) and 12 months (p < 0.0001) after TKI treatment. At a 12-month follow-up, sarcopenia prevalence increased up to 38.5%. Here, 12-month sarcopenia was predicted by a lower SMI (p = 0.029), BMI (p = 0.02) and weight (p = 0.04) and by the presence of bone metastases (p = 0.02). (4) Conclusions: This is the first study that evaluated sarcopenia prevalence and its change over time in Caucasian patients with advanced thyroid cancer under TKI therapy. Sarcopenia seems to be a prognostic factor of TKI treatment outcome, suggesting the importance of the assessment of the nutritional status and body composition in advanced thyroid cancer patients.

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer.

In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial ß-oxidation of oleic acid. In this review, we discuss the current knowledge of the effects of palmitoleic acid and, where available, sapienic acid and hypogeic acid, on metabolic diseases such as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and cancer. The results have shown diverse effects among studies in cell lines, animal models and humans. Palmitoleic acid was described as a lipokine able to regulate different metabolic processes such as an increase in insulin sensitivity in muscle, ß cell proliferation, prevention of endoplasmic reticulum stress and lipogenic activity in white adipocytes. Numerous beneficial effects have been attributed to palmitoleic acid, both in mouse models and in cell lines. However, its role in humans is not fully understood, and is sometimes controversial. Regarding sapienic acid and hypogeic acid, studies on their biological effects are still scarce, but accumulating evidence suggests that they also play important roles in metabolic regulation. The multiplicity of effects reported for palmitoleic acid and the compartmentalized manner in which they often occur, may suggest the overlapping actions of multiple isomers being present at the same or neighboring locations.

Active Surveillance in RET Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia.

Multiple Endocrine Neoplasia 2 (MEN2) is a hereditary cancer syndrome for developing medullary thyroid cancer (MTC) due to germline mutations of RET gene. Subjects harboring a germline RET mutation without any clinical signs of MTC are defined as gene carriers (GCs), for whom guidelines propose a prophylactic thyroid surgery. We evaluate if active surveillance of GCs, pursuing early thyroid surgery, can be safely proposed and if it allows safely delaying thyroid surgery in children until adolescence/adulthood. We prospectively followed 189 GCs with moderate or high risk germline RET mutation. Surgery was planned in case of: elevated basal calcitonin (bCT) and/or stimulated CT (sCT); surgery preference of subjects (or parents, if subject less than 18 years old); other reasons for thyroid surgery. Accordingly, at RET screening, we sub-grouped GCs in subjects who promptly were submitted to thyroid surgery (Group A, n = 67) and who were not (Group B, n = 122). Group B was further sub-grouped in subjects who were submitted to surgery during their active surveillance (Group B1, n = 22) and who are still in follow-up (Group B2, n = 100). Group A subjects presented significantly more advanced age, bCT and sCT compared to Group B. Mutation RETV804M was the most common variant in both groups but it was significantly less frequent in Group A than B. Analyzing age, bCT, sCT and genetic landscape, Group B1 subjects differed from Group B2 only for sCT at last evaluation. Group A subjects presented more frequently MTC foci than Group B1. Moreover, Group A MTCs presented more aggressive features (size, T and N) than Group B1. Accordingly, at the end of follow-up, all Group B1 subjects presented clinical remission, while 6 and 12 Group A MTC patients had structural and biochemical persistent disease, respectively. Thank to active surveillance, only 13/63 subjects younger than 18 years at RET screening have been operated on during childhood and/or adolescence. In Group B1, three patients, while actively surveilled, had the possibility to reach the age of 18 (or older) and two patients the age of 15, before being submitted to thyroid surgery. In Group B2, 12 patients become older than 18 years and 17 older than 15 years. In conclusion, we demonstrated that an active surveillance pursuing an early thyroid surgery could be safely recommended in GCs. This patient-centered approach permits postponing thyroid surgery in children until their adolescence/adulthood. At the same time, we confirmed that genetic screening allows finding hidden MTC cases that otherwise would be diagnosed much later.

Prevalence and Risk Factors of Developing Fistula or Organ Perforation in Patients Treated with Lenvatinib for Radioiodine-Refractory Thyroid Cancer.

INTRODUCTION: Tyrosine kinase inhibitors represent a better treatment in patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). Lenvatinib is usually well-tolerated, but sometimes, it is associated with serious and even life-threatening side effects. The aim of this study was to evaluate the prevalence of and the potential risk factors for fistula and/or organ perforation in RAI-R DTC patients treated with lenvatinib. METHODS: This study included data from advanced and progressive RAI-R DTC patients treated with lenvatinib from February 2011 to February 2020 who were followed up at a single center. The clinical-pathological features and the biochemical and morphological results of the patients were collected at the time of starting lenvatinib and during the follow-up. RESULTS: Fourteen of 95 (14.7%) locally advanced or metastatic RAI-R DTC patients treated with lenvatinib developed a fistula or organ perforation. Nine of 14 (64.3%) patients had tumor infiltration of the trachea, bronchus, esophagus, pleura, or bladder. Five of 14 (35.7%) had a bowel perforation, but only 2 had preexisting diverticulosis. Evaluation of the risk factors for developing a fistula or organ perforation showed that the presence of tumor infiltration and the tumor histology (papillary and poorly differentiated vs. follicular and Hurthle thyroid cancer) were significantly correlated with the development of a fistula or organ perforation (p = 0.003 and p = 0.02, respectively). In the subgroup of patients with tumor infiltration, we found that the papillary thyroid cancer histotype was the only potential predictor of fistula development. External beam radiation therapy (EBRT), the starting dose of lenvatinib, and the duration of treatment were not relevant for the development of fistula. CONCLUSIONS: In metastatic thyroid cancer patients treated with lenvatinib, the presence of tumor infiltration and histological type should be considered as potential risk factors for the development of fistula or organ perforation, although they do not represent an absolute contraindication. Although EBRT and the presence of diverticulosis were not significantly associated with the development of fistula and organ perforation, they should be regarded as potential additional reasons for the development of these complications. According to our findings, there is no reason to start lenvatinib at a lower daily dose when tumor infiltration is present.

Clinical pharmacology and drug-drug interactions of lenvatinib in thyroid cancer.

Lenvatinib is a non-selective tyrosine kinase inhibitor (TKI) with high in vitro potency against vascular endothelial growth factor receptors. Although this drug is used to treat several cancer types, it is the most effective TKI used in patients with thyroid cancer. Lenvatinib is well tolerated and the most common adverse drug reactions can be adequately managed by dose adjustment. Particularly, blood pressure and cardiac function monitoring, as well as antihypertensive treatment optimization, may be required in patients treated with lenvatinib. Dose reduction should be taken into account in patients with body weight <60 kg or severe hepatic failure. No significant change in lenvatinib pharmacokinetics has been observed with other patient-related factors and very few data are available on lenvatinib pharmacogenetics. Lenvatinib can be administered orally regardless of food and no clinically relevant drug-drug interactions have been reported.

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

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.

[18F]-FDG-PET/CT Correlates With the Response of Radiorefractory Thyroid Cancer to Lenvatinib and Patient Survival.

CONTEXT: 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ([18F]-FDG-PET/CT)-positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. OBJECTIVE: We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. METHODS: Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. RESULTS: Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). CONCLUSIONS: Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.

Thyroid cancer and COVID-19: experience at one single thyroid disease referral center.

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is challenging health systems all over the world. Cancer patients have a higher risk of being infected by SARS-Cov-2 and higher coronavirus disease 2019 (COVID-19) severity and mortality. Up to date, there were no data about COVID-19 in patients with thyroid cancer (TCs). The aim of the study was to describe the prevalence of COVID-19 in a well-characterized series of TC patients evaluated for the persistence of the neoplastic disease from March to September 2020; as secondary objective, we looked for the COVID-19 disease severity in a subgroup of multimetastatic TC patients. METHODS: We evaluated 1464 patients affected by persistent TC: 67 patients who were taking multikinase inhibitors (MKIs) and 1397 under active surveillance for a persistent but stable disease. During the clinical evaluation, all patients were specifically investigated about a positive history of Sars-Cov-2 infection. RESULTS: SARS-Cov-2 infection was identified in 4/1464 (0.3%) cases of patients affected by TC. We identified three cases among patients under active surveillance (0.2%), and one case among patients treated with MKI systemic therapy (1/67, 1.5%). This patient was taking vandetanib for metastatic medullary thyroid cancer (MTC), when he came to our attention referring severe fatigue, dyspnea for light physical activities. He presented a mild COVID-19 and he received exclusively supportive care. After a multidisciplinary consultation, we decided against the discontinuation of vandetanib. After 2 months from the infection, he did not present any signs of active infection, and the MTC metastatic disease was stable. CONCLUSIONS: We showed that COVID-19 is not more frequent in TC patients than in general population, although a relatively higher prevalence in the group of TC patients treated with MKIs. A single patient with advanced TC and SARS-Cov-2 infection during MKIs treatment had a mild COVID-19 and did not require the discontinuation of MKI therapy. In cases of more severe COVID-19, an accurate evaluation from a multidisciplinary team would consider risks and benefits in taking the decision to continue or stop MKI treatment.

Safety and Quality-of-Life Data from an Italian Expanded Access Program of Lenvatinib for Treatment of Thyroid Cancer.

Background: Lenvatinib, a multikinase inhibitor, is for progressive radioiodine-refractory-differentiated thyroid cancer (RR-DTC) patients. However, there are a lot of drug-related adverse events (AEs) that can affect the quality of life (QoL) of patients. The aims of this study were (a) to evaluate, and compared with other series, the safety of lenvatinib used in RR-DTC patients enrolled in an Italian expanded access program (EAP), and (b) to evaluate their QoL during treatment with lenvatinib. Methods: To evaluate the safety, we recorded and graded all AEs during the 6 months of lenvatinib treatment in 39 RR-DTC patients. We compared the safety profile of lenvatinib observed in our patients with that reported in the study of (E7080) levatinib in differentiated cancer of the thyroid (SELECT) and tumeurs thyroidiennes refractaires (TUTHYREF) network studies. Moreover, we evaluated the QoL in our series by using the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 and the pain visual analogue scale (VAS). Results: The most frequent AEs among our 39 RR-DTC patients were hypertension (80.5%), fatigue (58.3%), diarrhea (36.1%), stomatitis (33.3%), hand/foot syndrome (33.3%), and weight loss (30.5%). The most prevalent grade 3/4 AE was hypertension (25%). When compared with previous studies (i.e., SELECT and TUTHYREF), a significantly lower percentage of our patients experienced diarrhea, nausea, proteinuria, and weight loss. No statistically significant differences in the QoL of our patients evaluated before, during, and at the end of follow-up (6 months after starting the therapy) were found. However, a slight improvement of the general health and emotional and cognitive status associated with a slightly worsening of physical role and social functioning was observed during these 6 months. Pain, dyspnea, insomnia, and constipation moved toward better values, while fatigue, nausea and vomiting, appetite loss, and diarrhea worsened. By comparing the pain VAS, an overall reduction of the level of pain was found. Conclusions: The safety profile of the drug was similar to that already reported with some differences in the prevalence and severity of the AEs. Regarding the QoL, the EAP showed a trend of improvement of the global health status and a reduction of symptoms correlated to the disease. The clinical impact of fatigue, anorexia/weight loss and stomatitis, mainly due to the drug itself, continues to represent the major issue in the management of these patients.

A New MEN2 Syndrome with Clinical Features of Both MEN2A and MEN2B Associated with a New RET Germline Deletion.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by RET proto-oncogene mutation. Two different clinical variants of MEN2 are known (MEN2A and MEN2B): medullary thyroid carcinoma (MTC) almost always present and associated with pheochromocytoma (Pheo), and primary hyperparathyroidism (HPTH) in MEN2A and with Pheo and other nonendocrine diseases in MEN2B. Case Report. A 7-year-old girl, previously treated for a pelvic plexiform neurofibroma, arrived at our observation with a peculiar MEN2B syndrome and with HPTH. The neck ultrasound showed bilateral thyroid nodules, local lymph node lesions, and a suspicious left hyperplastic parathyroid. The CT scan showed a megacolon and described the persistence of the pelvic tumor. A new RET germline deletion in exon 11 (c.1892_1899delCGAGCT; p.Glu632_Leu633del) was found. She underwent total thyroidectomy, central compartment and latero-cervical lymph node dissection, and neck exploration for primary HPTH. The histology confirmed bilateral MTC, multiple lymph node metastases, a hyperplastic parathyroid, and a parathyroid adenoma. CONCLUSIONS: This is the first case of a complex syndrome characterized by peculiar features of MEN2B, without Pheo but with a pelvic plexiform neurofibroma and with HPTH, which is typical of MEN2A. A "de novo" new germline RET deletion located in exon 11 was found.

No difference in the outcome of metastatic thyroid cancer patients when using recombinant or endogenous TSH.

OBJECTIVE: At present, recombinant TSH cannot be used for the treatment of metastatic differentiated thyroid cancer patients. The aim of this study was to evaluate if the type of TSH stimulation, recombinant or endogenous, had an impact on the outcome of these patients. DESIGN AND METHODS: We compared the outcome of two propensity score-matched groups of metastatic patients, stimulated by either only recombinant TSH (n = 43) or only endogenous TSH (n = 34). RESULTS: As expected from the matching procedure, the clinical-pathological features and the cumulative 131-I activities administered to the two groups were very similar. After 4 years of follow-up, 4% of patients were cured, 3% had biochemical disease and 93% had structural disease. However, 91% of patients obtained a clinical benefit from this therapy in terms of stabilization of the disease or complete remission or partial response. When considering the two groups separately, we did not find any difference in their outcome. When considering the response to 131-I therapy of the single type of metastases, 8% of lymph node metastases and 8% of lung metastases disappeared but none of the bone metastases. The response to 131-I therapy of the single type of metastases was similar when we looked at the two groups separately. CONCLUSIONS: This study shows (i) an overall clinical benefit of the 131-I therapy, since the majority of patients remained affected but with a stable disease, and (ii) that the preparation with either recombinant or endogenous TSH has no impact on the 131-I therapy efficacy and the outcome of our two groups of patients.

Role of Prophylactic Central Compartment Lymph Node Dissection on the Outcome Of Patients With Papillary Thyroid Carcinoma and Synchronous Ipsilateral Cervical Lymph Node Metastases.

OBJECTIVE: Prophylactic central compartment lymph node dissection (pCCND) results in a higher percentage of surgical-related complications. To date, no evidence of the impact of pCCND on the clinical outcome of papillary thyroid carcinoma (PTC) patients with synchronous ipsilateral cervical lymph node metastases has been reported. METHODS: We evaluated all consecutive patients affected by PTC and synchronous ipsilateral cervical, but without evidence of central compartment, lymph node metastases. We selected 54 consecutive patients (group A) treated by total thyroidectomy, ipsilateral cervical lymph node dissection, and pCCND and 115 patients (group B) matched for sex, age at diagnosis, number and dimension of the metastatic lateral cervical lymph nodes, without pCCND. Clinical outcome after a median of 5 years and surgical-related complications were assessed. RESULTS: The two groups were completely similar in terms of clinical features. Clinical outcomes showed a higher percentage of biochemical and indeterminate but not structural response in group B. Group B required significantly more radioiodine treatments, but no difference was shown in the need to repeat surgery for recurrences. Conversely, the prevalence of permanent hypoparathyroidism was significantly higher in group A (14.8%) than in group B (4.3%). CONCLUSION: In PTC patients with synchronous ipsilateral cervical lymph node metastases, in absence of clinically evident lymph node metastases of the central compartment, performing pCCND does not improve the 5-year outcome in terms of structural disease, despite a greater number of 131I treatments. However, pCCND is severely affected by a higher percentage of permanent hypoparathyroidism, even in the hands of expert surgeons. ABBREVIATIONS: IQR = interquartile range; pCCND = prophylactic central compartment lymph node dissection; PTC = papillary thyroid carcinoma; Tg = thyroglobulin; US = ultrasound.

DELAYED 131-I FIRST TREATMENT AFTER SURGERY HAS NO IMPACT ON THE MEDIAN TERM OUTCOME OF PATIENTS WITH INTERMEDIATE RISK DIFFERENTIATED THYROID CANCER.

Objective: In intermediate risk (IR) differentiated thyroid cancer (DTC) patients, selective use of radioiodine (131-I) for remnant ablation and/or as adjuvant therapy (RRA) is advocated. The recently suggested postoperative evaluation could delay the use of RRA. The aim of this study was to evaluate if a delayed RRA can worsen the clinical outcome of IR-DTC patients. Methods: Four hundred and fourteen consecutive IR-DTC patients were divided according to the time elapsed from surgery to RRA, <6 months (group A, 186/414 [44.9%]), or ≥6 months (group B, 228/414 [55.1%]). Clinical and biochemical data were collected, and clinical outcome was analyzed at the first evaluation (EV) after RRA (first-EV) and after a median of 6 years of follow-up (last-EV). Results: No difference in the clinical outcome of group A and B was found. Since a different activity of 131-I could have an impact on the outcome, we separately analyzed the groups according to the 131-I activity (low-activity group: 1,110 MBq/30 mCi [n = 320], and high-activity group: 3,700 MBq/100 mCi [n = 94]), further subdivided according to the time elapsed from surgery to RRA. No major differences were found in both the low- and high-activity groups when comparing the features of their subgroups A and B, as far as in their clinical outcome. Conclusion: The time elapsed between surgery and the first 131-I treatment does not influence the clinical outcome of IR-DTC patients. This finding allows a more relaxed attitude in the decision making process whether to perform the RRA in IR-DTC cases in which a selective use of 131-I is recommended. Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; EV = evaluation; HR = high risk; 131-I = radioiodine; IR = intermediate risk; LR = low risk; rhTSH = recombinant human thyroid-stimulating hormone; RRA = radioiodine for remnant ablation; Tg = thyroglobulin; TgAb = thyroglobulin autoantibody; US = ultrasound.