Real-world Data on Intermediate-risk Differentiated Thyroid Cancer Biochemical Response to 3700 or 5550 MBq of [131I]Sodium Iodide.

Effect of metformin on thyroid cancer risk in patients with acromegaly: A preliminary observational study

Recent studies have suggested that a low dose (LD) of radioiodine (RAI) is sufficient to treat differentiated thyroid cancer (DTC) even in patients with intermediate risk. However, these studies evaluated the efficacy of RAI therapy, irrespective of the results of the whole-body scan (WBS). The aim of the present study was to evaluate the response to LD and high-dose (HD) RAI therapy using two different criteria (with and without WBS results) and the reclassification system according to the revised 2015 guidelines of the American Thyroid Association in Korean intermediate-risk DTC patients. In addition, we evaluated the long-term clinical outcomes of treatment with LD and HD RAI. In total, 204 intermediate-risk DTC patients who underwent postoperative RAI therapy at two tertiary referral hospitals from 2003 to 2004 were enrolled in the present retrospective study. One hundred and twenty-four patients were treated with 3.7 and 5.55 GBq (HD) of RAI in one center and 80 patients were treated with 1.11 GBq (LD) in the other center. The success rate of RAI therapy was assessed with or without the inclusion of WBS results in the analysis. In addition, the response to therapy during the first 2 years of follow-up after the initial RAI therapy was categorized according to the reclassification system of 2015 American Thyroid Association guidelines as excellent response, indeterminate response, biochemical incomplete response, or structural incomplete response. Recurrence was defined as a newly detected cytologically or pathologically confirmed lesion. There were no significant differences between the success rates of the HD and LD groups irrespective of the inclusion of WBS results in the analysis (with WBS: 54.84 vs. 45.0%, P=0.23; without WBS: 60.48 vs. 62.5%, P=0.77). The response to HD and LD RAI therapy was excellent in 54.84 and 45.0% of the patients, respectively; indeterminate in 34.68 and 30.0% of the patients, respectively; biochemical incomplete in 4.03 and 13.75% of the patients, respectively; and structural incomplete in 6.45% and in 11.25% of the patients, respectively (P=0.04). In particular, the biochemical or structural incomplete response rate was lower in patients treated with HD than in patients treated with LD (HD, 10.48%; LD, 25.0%, P=0.01). At the last follow-up (HD, median 11 years; LD, median 10 years), patients who achieved an excellent response showed no evidence of disease. After the initial RAI therapy, eight patients in the HD group and 18 patients in the LD group who achieved either indeterminate response or biochemical incomplete response received additional RAI therapy. Seven patients (indeterminate response in five patients; biochemical incomplete response in two patients) in the HD group and seven patients (indeterminate response in five patients; biochemical incomplete response in two patients) in the LD group showed recurrences. LD RAI therapy after thyroidectomy appears to be insufficient in Korean DTC patients with intermediate risk. The patients in the LD group predominantly showed biochemical or structural incomplete response to initial RAI therapy and additional RAI therapy was required.

Prognostic value of liver stiffness measurement vs. biochemical response in primary biliary cholangitis.

Whether human insulin therapy may increase thyroid cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been investigated. The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the Bureau of National Health Insurance. The entry date was set at 1 January 2004, and 968,384 patients with T2DM were followed up for thyroid cancer incidence until the end of 2009. Ever-users, never-users and subgroups of human insulin exposure (using tertile cut-offs of time since starting insulin, duration of therapy and cumulative dose) at entry date were calculated for thyroid cancer incidence. Insulin glargine was not marketed until after the entry date. Therefore, to exclude the potential contamination of insulin glargine, patients who happened to use insulin glargine were censored at the time of its initiation when calculating the period of follow-up. Hazard ratios were estimated by Cox regression. There were 111,121 ever-users and 857,263 never-users of human insulin, with respective numbers of incident thyroid cancer of 118 (0·11%) and 1047 (0·12%), and respective incidences of 23·9 and 23·8 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) did not show a significant association with human insulin in either the age-sex-adjusted or the fully adjusted model: 0·942 (0·778-1·141) and 1·096 (0·888-1·353), respectively. When categorized into tertiles of the dose-response parameters, none of the hazard ratios was significant. This study does not support the role of human insulin therapy in increasing the risk of thyroid cancer in patients with T2DM.

Controversies in Radioiodine Treatment of Low- and Intermediate-risk Thyroid Cancer

Purpose: Computed Tomography (CT) is a fundamental part of diagnosis of diseases. During CT examinations organs in and out of scanned volume are exposed to ionization radiation. The aim of this study was Estimation Thyroid cancer risk in Patients who Underwent 64 Slice brain and paranasal sinuses CT scan. Materials and Methods: with permission from the authors and editor, data related to thyroid dose of 40 patients in Mazyar et al.'s paper was used and by using Biological Effects of Ionizing Radiation (BEIR)VII model thyroid cancer risk was calculated for different ages at exposure in male and female. Results: In both brain and paranasal sinuses CT, ERR values in female patients were twice as many as those in male patients. At age range from 20 to 40 years, ERR was considerably more than at age range 40-60 years since young patients are more radiosensitive than old patients. Conclusion: The calculations of ERR indicate that PNS and brain CT increase the theoretical risk of thyroid cancer incidence. Although the ERR values are low, impacts on the thyroid cancer incidence should not be disregarded.

Medullary thyroid cancer (MTC), a neuroendocrine tumor arising from the parafollicular C cells of the thyroid gland, is rare and accounts for approximately 5% of all thyroid cancers. The majority of cases of MTC are sporadic, and in roughly 25% of cases, MTC is part of a hereditary cancer syndrome with a well-characterized germline RET mutation: multiple endocrine neoplasia 2A, multiple endocrine neoplasia (MEN) 2B, or familial MTC. Patients with newly diagnosed disease are treated with surgery. Calcitonin and carcinoembryonic antigen (CEA) are useful blood markers and are often used to monitor patients after surgery. Systemic chemotherapy and radiation therapy are not believed to represent important or useful options for most patients with MTC. Patients with metastatic disease are not curable and are often monitored with serial scans and biochemical markers. Metastatic MTC can be quite indolent, and timing to initiate therapy varies greatly among physicians and practices. Until recently, no satisfactory options existed for treating patients with metastatic disease in need of therapy. In 2011, the US Food and Drug Administration approved vandetanib (which targets RET, epidermal growth factor receptor, and vascular endothelial growth factor receptor) for the treatment of patients with symptomatic or progressive, locally advanced, or metastatic MTC. This approval was based on the Zactima Efficacy in Thyroid Cancer Assessment (ZETA) phase III study. In 2012, the US Food and Drug Administration also approved cabozantinib for the same indication on the basis of the Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial reported in the article that accompanies this editorial. The ZETA study was a randomized double-blind phase III trial in which patients were randomly assigned in a 2:1 fashion to receive oral vandetanib 300 mg per day (n 231) or a placebo (n 100) until disease progression. The primary end point was progression-free survival (PFS), and relevant secondary end points were objective response rate, overall survival, biochemical response, safety, and tolerability. Patients who were enrolled onto the ZETA trial were not required to have progressive disease before enrollment but were required to have measurable disease at baseline and a calcitonin level of at least 500 pg/mL. The study showed a significant prolongation of PFS with vandetanib versus the placebo (hazard ratio, 0.46; 95% CI, 0.31 to 0.69; P .001). Statistically significant advantages for vandetanib were also seen for objective response rate, disease control rate, and biochemical response. This study allowed patients receiving the placebo to cross over to vandetanib, and an overall survival advantage was not seen at the time of the initial report. The median duration of treatment in the randomized phase was 90.1 weeks for vandetanib and 39.9 weeks for the placebo. The ZETA trial clearly included many patients with indolent disease, as evidenced by a PFS of 19.3 months in the placebo group (with an estimated PFS of 30 months in the vandetanib group). Adverse events such as diarrhea, rash, nausea, and hypertension occurred in more than 30% of patients receiving vandetanib. More patients required dose reduction of vandetanib compared with the placebo for adverse events or QTc prolongation (35% v 3%). Nineteen patients (8%) developed protocol-defined QTc prolongation, but there were no reports of torsades de pointes. The rate of treatment discontinuation because of toxicity was 12%. Because of this risk of QT prolongation, vandetanib is currently only available through the US Food and Drug Administration Vandetanib Risk Evaluation Mitigation Strategy Program. This program is meant to educate practitioners about the risk, appropriate monitoring, and management of QT prolongation should it occur during vandetanib therapy. The EXAM study that is reported in the article that accompanies this editorial sought to examine the effect of cabozantinib in progressive MTC. Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets three potentially important pathways in MTC: MET, vascular endothelial growth factor receptor 2, and RET. EXAM is a double-blind phase III trial comparing oral cabozantinib at 140 mg per day with a placebo in 330 patients with documented radiographic progression of metastatic MTC. The primary end point is PFS. Other end points are response rate, overall survival, and safety. This study also used a 2:1 randomization schema, but unlike the ZETA trial, the EXAM study did not allow cross over to the active drug. The study met its primary end point of prolongation of PFS: 11.2 months for cabozantinib versus 4 months for the placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.4; P .001). There is no survival advantage noted so far, and analysis is ongoing for the overall survival end point. Objective tumor response rates and biochemical responses were also significantly improved with cabozantinib. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 29 OCTOBER 1

Clinical, Biochemical, and Radiographic Responses to Rituximab Combined with Liposomal Doxorubicin (R-Dox) in HIV-Infected Patients with Severe Kaposi Sarcoma-Associated Herpes Virus (KSHV) – Associated Multicentric Castleman's Disease.

BACKGROUNDThyroglobulin (Tg) is one of the markers of thyroid cancer, and its concentration may be elevated in patients with malignant thyroid tumors. Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland, which has a significant impact on thyroid gland function. Excessively high or low TSH levels may be associated with an increased risk of thyroid cancer. Thus, in-depth studies on the association of serum Tg and TSH levels with thyroid cancer risk in patients with thyroid nodules are warranted. This can help determine whether Tg and TSH levels can predict the degree of malignancy of thyroid nodules, which can in turn guide doctors in making accurate diagnoses and treatment decisions. Furthermore, such studies can provide more accurate diagnostic methods for thyroid nodules and help patients become aware of the presence of thyroid cancer as early as possible, thereby improving the success rate of treatment and prognosis.AIMTo investigate the association of serum Tg and TSH levels with the risk of thyroid cancer in patients undergoing thyroid nodule surgery.METHODSThe clinical data and laboratory examination results of 130 patients who underwent thyroid nodule surgery were retrospectively analyzed. Furthermore, their preoperative serum Tg and TSH levels were recorded. Histopathological examination conducted during follow-up revealed the presence of thyroid cancer. Correlation analysis were used to analyze the association of Tg and TSH levels with the risk of thyroid cancer.RESULTSOf the 130 patients, 60 were diagnosed with thyroid cancer. Statistical analysis revealed a significant positive correlation between serum Tg levels and the risk of thyroid cancer (P < 0.05). This suggests that high serum Tg levels are associated with an increased risk of thyroid cancer. However, no significant correlation was observed between serum TSH levels and the risk of thyroid cancer (P > 0.05).CONCLUSIONIn patients who underwent thyroid nodule surgery, serum Tg levels exhibited a significant correlation with the risk of thyroid cancer but serum TSH levels did not. These findings suggest that serum Tg can serve as an important biomarker for assessing the risk of thyroid cancer in these patients.

Previous research has explored the demands of amateur boxing-specific activity; however, no holistic review of the acute responses to such activity currently exists. This paper aimed to provide a systematic review of the available literature on the acute physiological, endocrine, biochemical, and performance responses to amateur boxing-specific activity. Following a search of EBSCOhost, SPORTDiscus, PubMed and Google Scholar databases, 25 studies were identified as meeting the inclusion criteria for the review. The methodological quality of the included studies was assessed via a modified Downs and Black checklist. Random-effects meta-analysis of standardised mean differences (SMD) revealed large (SMD = 4.62) increases in pre-post blood lactate (BLa), cortisol (SMD = 1.33), myoglobin (Mb) (SMD = 1.43), aspartate transaminase (AST) (SMD = 1.37), and alanine aminotransferase (ALT) (SMD = 0.97), in addition to moderate increases in creatine kinase (CK) (SMD = 0.65). Small pre–post increases in counter-movement jump (CMJ) height (SMD = 0.33) were observed. Consistently greater pre–post alterations were observed in competitive bouts, followed by sparring, and less so in boxing-specific simulations. Considerable physiological, endocrine, and biochemical responses are elicited following amateur boxing. Interestingly, neuromuscular and task-specific performance may not deteriorate following boxing-specific activity. The findings of the review may assist in the designing and periodising of boxing-specific training, dependent on the desired physical adaptations, training phase, and recovery status of the amateur boxer. Highlights Amateur boxing elicits a considerable acute physiological, hormonal, and biochemical response. Such responses are typically greater in competitive bouts, followed by sparring, and less so in simulated activity. The considerable demands of amateur boxing-specific activity do not appear to negatively affect neuromuscular or task-specific performance. Amateur boxers may be conditioned to preserve performance despite the acute demands of the sport, or the lack of performance decrement may reflect the short duration of amateur boxing.

Context: Acromegaly has long been blamed to portend an increased risk for benign and malignant thyroid neoplasia. Growth hormone (GH) and consequent insulin-like growth factor 1 (IGF-1) hypersecretion are implicated in cancer promotion. Metformin, a biguanide derived from the French lilac, is gaining considerable interest because of its plausible anti-tumor properties. Besides, metformin has been shown to inhibit somatotroph proliferation and decrease GH secretion in in vivo studies. Patients with acromegaly have high incidence of diabetes and were thereof treated with metformin. We hypothesized metformin use may be linked to decreased thyroid cancer incidence in patients with acromegaly. Study Design and Methods: The medical records of 508 patients with acromegaly followed at our tertiary referral center between 1969 and 2019 were retrospectively reviewed. The inclusion criteria were having a follow-up duration for at least 12 months and being regularly screened for nodular thyroid disease and thyroid cancer by ultrasonography as indicated in respective guidelines. Patients with acromegaly were evaluated based on ongoing or prior history of metformin use or thyroid cancer diagnosis. Metformin exposure was defined as use of metformin for at least 12 months on a regular basis between initial date of acromegaly and time prior to cancer diagnosis date. Considering the long patency period of cancer of interest, we excluded exposures in the year immediately prior to index cancer date. We evaluated the effect of metformin exposure on risk of thyroid cancer using Kaplan-Meier analysis. Results: Final analysis included 377 patients with acromegaly. Mean age at acromegaly diagnosis was 41.6 ± 11.7 and 60.5% of the patients were female. Three hundred twenty-two patients (85.4%) had undergone transsphenoidal surgery as primary therapy, 73 patients (19.4%) needed radiotherapy and 178 patients (46%) received post-operative medical therapy. Median follow-up duration was 73.5 months (IQR [31.0-137.7]). One hundred twenty patients (31.9%) had an ongoing or prior use of metformin, and total of 19 patients (5%) had thyroidcancer. Age at acromegaly diagnosis, gender distribution, baseline GH and IGF-1 levels, pituitary tumor size and invasiveness, biological aggressiveness, curative therapy options, treatment responses didn’t differ between metformin users and non-users, as well as between those having and not having thyroid cancer. Kaplan-Meier estimates for 1 year, 3 years and 5 years of metformin exposure showed decreased probability of thyroid cancer incidence (p<0.05 for all). Conclusion: Although our results imply decreased thyroid cancer risk upon metformin exposure, prospective study designs with larger cohorts are obliged in order to fully elucidate the effect of metformin use on thyroid cancer.

The palliative role of 131I-MIBG and 111In-octreotide therapy in patients with metastatic progressive neuroendocrine neoplasms

Frontiers in Thyroid Cancer: December 2009

Part I. The Thyroid Nodule. The Thyroid Nodule: Pathogenesis, Evaluation, and Risk of Malignancy, Leonard Wartofsky. Nonisotopic Imaging of the Neck in Patients with Thyroid Nodules or Cancer, Manfred Blum. The Thyroid Nodule: Fine Needle Aspiration Biopsy, Yolanda C. Oertel. The Thyroid Nodule: Medical Management, Leonard Wartofsky. Thyroid Nodules and Cancer Risk: Surgical Management, Orlo H. Clark. Part II. Thyroid Cancer: General Considerations. Molecular Pathogenesis of Thyroid Cancer, James Figge. Epidemiology of Thyroid Cancer, James Figge. Radiation and Thyroid Cancer, James Figge, Timothy Jennings, and Gregory Gerasimov. Classification of Thyroid Malignancies, James Oertel and Yolanda Oertel. Thyroid Cancer in Children and Adolescents, Merrily Poth. Immunologic Aspects of Thyroid Follicular Neoplasms, James R. Baker, Jr. Radioiodine Therapy of Thyroid Cancer: General Considerations-I, Gerald Johnston and Diane Sweeney. Radioiodine Therapy of Thyroid Cancer: General Considerations-II Side Effects of Radioiodine Therapy for Thyroid Cancer, Diane Sweeney and Gerald Johnston. Recombinant Human Thyrotropin, Matthew D. Ringel. Chemotherapy for Thyroid Cancer, Lawrence S. Lessin and Myo Min. Part III. Differentiated Tumors of the Thyroid Gland: A. Papillary Carcinoma. Papillary Carcinoma: Clinical Aspects, Leonard Wartofsky. Papillary Carcinoma: Cytology and Pathology, James Oertel and Yolanda Oertel. Surgical Approach to Papillary Carcinoma, Orlo H. Clark. Differentiated Thyroid Carcinoma: Radioiodine Therapy-I, Gerald Johnston and Diane Sweeney. Chemotherapy of Differentiated (Papillary or Follicular) Thyroid Carcinoma, Lawrence S. Lessin and Myo Min. Management of Papillary Thyroid Carcinoma: External Radiation Therapy, Robert L. White. Papillary Thyroid Cancer: Follow-Up, Henry B. Burch. Radioiodine Treatment of Thyroid Cancer-II: Maximizing Therapeutic and Diagnostic 131I Uptake, Diane Sweeney and Gerald Johnston. An Approach to the Management of Patients with Scan Negative, Thyroglobulin Positive, Differentiated Thyroid Cancer: Alternative Imaging Procedures, Leonard Wartofsky. Papillary Thyroid Cancer: Prognosis, Henry B. Burch. Papillary Cancer: Special Aspects in Children, Merrily Poth. Part IV. Differentiated Tumors of the Thyroid Gland: B. Follicular Carcinoma. Follicular Thyroid Carcinoma: Clinical Aspects, Leonard Wartofsky. Pathology of Follicular Cancer, James Oertel and Yolanda Oertel. Surgical Management of Follicular Cancer, Orlo H. Clark. Follicular Carcinoma of the Thyroid: External Radiation Therapy, Robert L. White and Leonard Wartofsky. Follicular Thyroid Cancer: Follow-Up, Henry B. Burch. Follicular Thyroid Cancer: Prognosis, Henry B. Burch. Follicular Thyroid Cancer: Special Aspects in Children and Adolescents, Merrily Poth. Part V. Undifferentiated Cancers: A. Anaplastic Carcinoma. Anaplastic Carcinoma: Clinical Aspects, Steven I. Sherman. Anaplastic Carcinoma: Pathology, James Oertel and Yolanda Oertel. Anaplastic Carcinoma Management: Surgery, Orlo H. Clark. Chemotherapy of Anaplastic Thyroid Cancer, Lawrence S. Lessin and Myo Min. Management of Anaplastic Carcinoma: External Radiation Therapy, Robert L. White and Leonard Wartofsky. Anaplastic Carcinoma: Prognosis, Steven I. Sherman. Part VI. Undifferentiated Cancers: B. Lymphoma. Thyroid Lymphoma, Steven I. Sherman. Thyroid Lymphoma: Pathology, James Oertel and Yolanda Oertel. Part VII. Undifferentiated Cancers: C. Medullary Carcinoma. Medullary Thyroid Carcinoma, Douglas W. Ball. Medullary Thyroid Cancer: Pathology, James Oertel and Yolanda Oertel. Medullary Carcinoma of the Thyroid: Nuclear Medicine Imaging and Treatment, Diane Sweeney and Gerald Johnston. Management of Medullary Carcinoma of the Thyroid: Surgery, Orlo H. Clark. Medullary Carcinoma Management: External Radiation Therapy, Robert L. White and Leonard Wartofsky. Medullary Carcinoma of the Thyroid: Chemotherapy, Lawrence S. Lessin and Myo Min. Part VIII. Miscellaneous and Unusual Cancers of the Thyroid. Pathology of Miscellaneous and Unusual Cancers of the Thyroid, James Oertel and Yolanda Oertel. Clinical Aspects of Miscellaneous and Unusual Types of Thyroid Cancers, Matthew D. Ringel, Kenneth D. Burman, and Barry M. Shmookler. Part IX. Future Directions. Thyroid Cancer: DNA Ploidy, Tumor Markers, and Cancer-Causing Genes, Michael McDermott. New Approaches to Chemotherapy for Thyroid Cancer, Lawrence S. Lessin and Myo Min. Advances in Radiotherapy For Thyroid Cancer, Robert L. White. Index.

Effects of I-131 therapy on gonads and pregnancy outcome in patients with thyroid cancer