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Neha Venkatesh Baylor College of Medicine, Houston, TX, USA

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Rebecca S Tidwell Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Yao Yu Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Ana Aparicio Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Amado J Zurita Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Sumit K Subudhi Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Bilal A Siddiqui Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Sagar S Mukhida Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Justin R Gregg Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Paul G Corn Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Efstratios Koutroumpakis Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Jennifer L McQuade Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Daniel E Frigo Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Patrick G Pilie Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Chad Huff Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Christopher J Logothetis Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Andrew W Hahn Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/− abiraterone acetate (AAP) were eligible if they had: i) CT imaging of L3 prior to and after treatment; and ii) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher losses of SMMi after treatment (−11.1% vs −6.3%, P = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (−1.3% vs −7.1%, P = 0.04). In addition, the HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs 77.9, P = 0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM was associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

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Koji Sakamoto Department of Otorhinolaryngology, Saiseikai Utsunomiya Hospital, Utsunomiya City, Tochigi, Japan
Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Hiroyuki Ozawa Department of Otorhinolaryngology, Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan

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Yoichiro Sato Department of Otorhinolaryngology, Saiseikai Utsunomiya Hospital, Utsunomiya City, Tochigi, Japan

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Masashi Nakaishi Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Atsuko Sakanushi Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Takeshi Matsunobu Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Kimihiro Okubo Department of Otorhinolaryngology, Head and Neck Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan

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Seiichi Shinden Department of Otorhinolaryngology, Saiseikai Utsunomiya Hospital, Utsunomiya City, Tochigi, Japan

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Measurement of thyroglobulin in fine-needle aspirates (FNA-Tg) is useful for the diagnosis of lymph node metastasis in thyroid carcinoma; however, the cutoff value remains unclear, particularly for the differential diagnosis of neck masses. To evaluate the cutoff value of FNA-Tg, we conducted a retrospective study of patients with neck masses outside the thyroid who pre-operatively underwent both FNAC and FNA-Tg, followed by pathological examination at our hospital from October 2015 to September 2020. The cutoff value of FNA-Tg was calculated using the receiver operating characteristic curve. Among 210 lesions, 57 were of thyroid origin and 153 lesions were not of thyroid origin. A high FNA-Tg value was observed in the lesions of thyroid origin (P: 0.001), and the cutoff value at the minimum point of 100% specificity was 32.2 ng/mL with a sensitivity of 87.7%. Regarding the effect of serum anti-Tg antibodies, FNA-Tg values were significantly lower or not significantly different depending on the grouping, warranting further studies. Among the cases with papillary thyroid carcinoma, the sensitivity of FNAC and FNA-Tg was 71.4% and 87.5%, respectively. The cutoff value of FNA-Tg for the differential diagnosis of neck masses was higher compared to previous reports because some metastatic lymph nodes of carcinomas and lesions, other than lymph nodes, exhibited higher FNA-Tg values. Therefore, if FNA-Tg is to be used as a screening test for the differential diagnosis of neck masses in patients without proven thyroid carcinoma, it is necessary to establish a higher cutoff value.

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Marta Villanova Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Sara M Tolaney Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA

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Le Min Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Pembrolizumab-related thyroid dysfunction has been associated with better outcomes in metastatic cancer patients. This study aims to examine the outcomes (pathological complete response (pCR) and event-free survival (EFS)) in early-stage triple-negative breast cancer (TNBC) patients receiving preoperative therapy who developed pembrolizumab-related thyroid dysfunction. Patients were divided into four groups based on the occurrence or not of pembrolizumab-related thyroid dysfunction (group A and D, respectively) and, in case of pre-existing thyroid disorder, based on the need for levothyroxine start/adjustment or not (group B and C, respectively). pCR and EFS in groups A, B, and C were compared to the ones in group D. Sixty-four early-stage TNBC patients were included, and the median follow-up was 16.5 months (IQR 12.0–23.8). Multiple patterns of thyroid irAEs were observed (overt hypothyroidism in 56.3%, subclinical thyrotoxicosis in 28.1%, overt thyrotoxicosis and subclinical hypothyroidism in 21.9%, and 21.9% of patients). No statistical difference was found in pCR (chi-square test, P = 0.611) comparing groups A, B, and C to group D. The median EFS in groups A, B, and C and in group D were 16.5 (IQR 12.0–24.0) and 16.0 (IQR 12.0–22.3) months, respectively (log-rank test, P = 0.671). The percentage of patients obtaining pCR was 85.7% in patients developing pembrolizumab–related overt thyrotoxicosis and 42.1% in remaining patients (chi-square test, P = 0.036). The EFS was 16.0 months (IQR 12.0–25.0) in patients developing pembrolizumab–related overt thyrotoxicosis and 16.0 months (IQR 12.0–23.5) in the remaining patients (log-rank test, P = 0.494). In conclusion, multiple patterns of pembrolizumab-related thyroid dysfunction occur in early-stage TNBC. Patients developing pembrolizumab-related overt thyrotoxicosis are more likely to achieve pCR.

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David Kishlyansky Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

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Alexander A Leung Division of Endocrinology and Metabolism, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Janice L Pasieka Department of Surgery, University of Calgary, Calgary, Alberta, Canada

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Amita Mahajan Division of Endocrinology and Metabolism, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Gregory A Kline Division of Endocrinology and Metabolism, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are rare neuroendocrine tumors that co-secrete excess catecholamines and adrenocorticotropic hormone, resulting in Cushing syndrome (CS). This review aims to summarize important patient characteristics, investigations, and outcomes in all cases reported in the English literature. A literature search was conducted to identify all English-language case reports and case series describing adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas. Relevant characteristics were systematically recorded. Cases that did not provide definitive evidence of an adrenocorticotropin (ACTH)-producing pheochromocytoma/paraganglioma were excluded. Our search strategy identified 93 published cases that met the inclusion criteria. We additionally reported one patient for a total of 94 cases. Details related to patient characteristics, laboratory data, and outcomes were commonly underreported. The median age was 47 years, and females accounted for 72% of cases. A cushingoid appearance was reported in 82% of patients, and hypertension in 86%. Infections were reported in 23% of patients. Urinary metanephrines were elevated at least three-fold above normal in 74% of cases. ACTH levels were high in 88% of patients and inappropriately normal in 12%. The median 24-hour urinary cortisol was 21-fold the upper limit of normal. Adrenalectomy was performed in nearly all patients, with 88% achieving a cure for both catecholamine and glucocorticoid excess. A total of 11 patients died. Metastases were uncommon (6%). Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are associated with considerable morbidity and mortality. It should be considered in the diagnostic workup of all patients with ectopic CS. Surgical cure is achieved in most patients, and infections are the leading cause of peri-operative mortality.

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Dingwen Liu Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Liang Zhou Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Cheng Li Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Youyou Li Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Jiahao Liu Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Lei Zhou Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Jin Tang Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Wei Xiong Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Long Wang Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% CI. Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = −0.83, 95% CI: −0.92 to −0.74), BC (AAPC = −0.48, 95% CI: −0.56 to −0.39), and TC (AAPC = −0.23, 95% CI: −0.29 to −0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. Higher Social Development Index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies.

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Tugba Barlas Department of Endocrinology and Metabolism, Gazi University, Faculty of Medicine, Ankara, Turkey

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Osman Sutcuoglu Department of Medical Oncology, Gazi University, Faculty of Medicine, Ankara, Turkey

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Orhun Akdogan Department of Medical Oncology, Gazi University, Faculty of Medicine, Ankara, Turkey

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Fusun Balos Toruner Department of Endocrinology and Metabolism, Gazi University, Faculty of Medicine, Ankara, Turkey

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Mujde Akturk Department of Endocrinology and Metabolism, Gazi University, Faculty of Medicine, Ankara, Turkey

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Nuriye Ozdemir Department of Medical Oncology, Gazi University, Faculty of Medicine, Ankara, Turkey

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Ozan Yazici Department of Medical Oncology, Gazi University, Faculty of Medicine, Ankara, Turkey

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Alev Eroglu Altinova Department of Endocrinology and Metabolism, Gazi University, Faculty of Medicine, Ankara, Turkey

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Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs). The appearance pattern of irAEs, who is prone to them, and their mechanisms are still uncertain. In this study, we aimed to monitor patients initiated on ICIs for endocrinological aspects and to investigate the potential predictive markers in the development of endocrine-irAEs. The study prospectively included 43 patients with metastatic disease scheduled for anti-PD-1/L1 therapy. Endocrinological follow-up was conducted at specified intervals as well as in response to any additional reported complaints. Serum concentrations of CXCL10, IL-1beta, and IL-17A were measured prior to ICI and during the endocrine-irAEs. A total of 39.5% of the patients experienced endocrine-irAEs, with a median onset time of 3 months. Among patients, 34.9% developed thyroid-related adverse events, and 4.6% experienced hypophysitis. Thyroid autoantibodies were associated with a higher incidence of thyroid-related irAEs (P = 0.004). In the irAE group, median pre-ICI CXCL10 and baseline thyroid stimulating hormone (TSH) levels were significantly higher, baseline total testosterone level in men was lower than in the non-irAE group (P < 0.05), whereas IL-1beta and IL-17A levels did not differ (P > 0.05). Serum CXCL10, IL-1beta, and IL-17A concentrations did not differ significantly pre-ICI and during adverse events (P > 0.05). Pre-ICI CXCL10 concentration was correlated positively with anti-TPO levels in patients with at least one thyroid autoantibody positivity (r = 0.706, P = 0.01) and negatively with baseline total testosterone level of men (r = 0.509, P = 0.002). Our results suggest that higher pre-ICI serum CXCL10 and TSH levels might have a predictive role in the development of endocrinopathies. Besides, baseline thyroid antibody measurements could be beneficial in predicting thyroid dysfunction.

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Rushabh Gujarathi Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Sara Abou Azar Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA

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Joseph Tobias Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA

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Blase N Polite Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Namrata Setia Department of Pathology, University of Chicago, Chicago, Illinois, USA

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Nicholas Feinberg Department of Radiology, University of Chicago, Chicago, Illinois, USA

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Daniel E Appelbaum Department of Radiology, University of Chicago, Chicago, Illinois, USA

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Xavier M Keutgen Section of Endocrine Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA

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Chih-Yi Liao Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Pre-clinical data suggest that mutations in the MEN1, DAXX, and/or ATRX genes may potentially increase radiation efficacy in cancer cells. Herein, we explore the association between response to peptide receptor radionuclide therapy (PRRT) and those mutations in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We analyzed tissue-based next generation sequencing (NGS) assay results and clinicopathologic data from 28 patients with GEP-NETs treated with PRRT. Findings were correlated with progression-free survival (PFS) and objective response rate (ORR). Patients with mutations in MEN1, DAXX, and/or ATRX (n = 13) had a longer median PFS (26.47 vs 12.13 months; P = 0.014) than wild-type (n = 15) patients when adjusted for surgery prior to PRRT, tumor grade, and presence of TP53 mutation. Alterations in MEN1 along with a concurrent mutation in either DAXX or ATRX (n = 6) trended toward longer PFS compared to patients without concurrent mutations (31.53 vs 17.97 months; P = 0.09). ORR was higher in patients with a mutation in MEN1, DAXX, or ATRX (41.67% vs 15.38%). In pancreatic NET patients, these target mutations also showed a longer PFS (28.43 vs 9.83 months; P = 0.04). TP53 alterations showed a shorter PFS than wild-type cases (11.17 vs 20.47 months; P = 0.009). Mutations in MEN1/DAXX/ATRX are associated with improved PFS in patients with GEP-NETs receiving PRRT and might be used as a biomarker for treatment response.

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Maura Fanti Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, California, USA

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Valter D Longo Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, California, USA

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Cancer is the second leading cause of death in the United States and among the most prevalent diseases globally, with an incidence expected to grow because of smoking, pollution, poor dietary habits, obesity, and the rise in the older population. Given their ability to reduce risk factors, albeit with varying efficacy, nutrition and fasting could help prevent cancer and other age-related disorders. Calorie restriction (CR), various forms of intermittent fasting (IF) or periodic fasting (PF), and fasting-mimicking diets (FMDs) have been shown to improve health span, increase lifespan, and prevent or postpone cancer in rodents. The effects of specific diets and fasting regimens on aging and cancer appear to be mediated in part by the reduction in the activity of the growth hormone (GH)/insulin-like-growth-factor-I (IGF-1) axis. Nevertheless, recent data indicate that the alternation of low and normal levels of these hormones and factors may be ideal for optimizing longevity and function. Here, we review the role of nutrition, CR, and fasting/FMD on cancer, focusing on the hypothesis that the modulation of GH, IGF-1, and insulin signaling partly mediates the effect of these dietary interventions on cancer prevention.

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Dong Hyun Seo Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

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Seul Gi Lee Yonsei University Graduate School of Medical Science, Seoul, South Korea

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Soon Min Choi Department of Surgery, Hallym Hospital, Incheon, South Korea

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Ha Yan Kim Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea

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Sunmi Park Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

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Sang Geun Jung Department of Gynecological Oncology, Bundang CHA Medical Center, CHA University Gyeonggi-do, South Korea

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Young Suk Jo Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

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Jandee Lee Department of Surgery, Open NBI Convergence Technology Research Laboratory, Yonsei University College of Medicine, Seoul, South Korea

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Telomerase reverse transcriptase promoter mutation (pTERT MT) promotes human carcinogenesis via aberrant expression of telomerase reverse transcriptase (TERT). However, the tumorigenic impact of TERT expression independent of pTERT MT remains unclear despite numerous mechanisms of TERT being suggested. To tackle this issue, we employed comprehensive bioinformatics to assess biological variations noticed among different TERT expression mechanisms. Papillary thyroid cancer (PTC) with pTERT MT (pTERT MT PTC) presented aggressive clinical behavior and exhibited biological profiles associated with cellular immortality and genomic instability. PTC with TERT expression but without pTERT MT (TERT (+) PTC), also exhibited poor clinicopathological characteristics and was enriched with immune responses. In accordance, c-MYC/E2F and nuclear factor kappa B (NFκB) were dominant transcription factors in pTERT MT PTC and TERT (+) PTC, respectively. Notably, we revealed TERT hypermethylated oncological region (THOR) as a potential TERT expressing mechanism in TERT (+) PTC patients. Furthermore, three unique subtypes of papillary thyroid cancer were deciphered using a combination of machine learning-based scoring systems. Our proposed scoring system was clinically significant, especially in microcarcinoma, predicting survival outcomes and inferring therapeutic responses to radioactive iodine therapy. Finally, our analysis was expanded to endocrine-related cancers, unveiling various regulatory mechanisms of TERT with poor clinical outcomes and biological behaviors.

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Chrysovalantou Mihailidou Department of Biological Chemistry, University of Athens Medical School, Athens Greece

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Ioulia Chatzistamou Department of Basic Sciences, Dental School, University of Athens, Athens Greece
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USA

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Athanasios G Papavassiliou Department of Biological Chemistry, University of Athens Medical School, Athens Greece

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Hippokratis Kiaris Department of Biological Chemistry, University of Athens Medical School, Athens Greece
Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, South Carolina, USA

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