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Department of Oncology, Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland
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Department of Oncology, Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland
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Department of Radiology, HUS Medical Imaging Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Department of Radiology, HUS Medical Imaging Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Endocrinology, Abdominal Centre, University of Helsinki and HUS, Helsinki, Finland
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Department of Oncology, Comprehensive Cancer Centre, Helsinki University Hospital, Helsinki, Finland
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Objective
Immune checkpoint inhibitors (ICI) can cause endocrine adverse events. However, endocrine AEs could be related to better treatment outcomes. Our aim was to investigate whether this holds true in a real-world setting of metastatic melanoma patients.
Design
A retrospective single-institution study.
Methods
We included 140 consecutive metastatic melanoma patients treated with ICI between January 2012 and May 2019. We assessed the endocrine toxicity and the best possible treatment outcomes from electronic patient records, including laboratory parameters and radiological images.
Results
Of the treated patients, 21 patients (15%) were treated with ipilimumab, 46 (33%) with nivolumab, 67 (48%) with pembrolizumab, and 6 (4%) with combination therapy (ipilimumab + nivolumab). Endocrine AEs appeared in 29% (41/140) patients. Three patients had two different endocrine AEs. Thyroid disorders were the most common: 26% (36/140), followed by hypophysitis: 4% (5/140). Three subjects (2%, 3/140) were diagnosed with autoimmune diabetes. Three patients had to terminate treatment due to endocrine toxicity. Radiological manifestations of endocrine AEs were found in 16 patients (39%, 16/41). Endocrine toxicity was associated with significantly better treatment outcomes. Median progression-free survival (8.1 months, range 5.1–11.1 months vs 2.7 months, range 2.4–3.0 months, P < 0.001), and median overall survival (47.5 months, range 15.5–79.5 months vs 23.7 months, range 15.3–32.1 months, P = 0.035) were longer for patients experiencing endocrine AEs.
Conclusions
The higher number of endocrine AEs suggest that regular laboratory monitoring aids in AE detection. Endocrine AEs in metastatic melanoma may correlate with better treatment outcomes.
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Background
Updated epidemiological data of neuroendocrine tumors are currently lacking. Thus, we performed epidemiological and survival analyses on a large cohort of patients with neuroendocrine tumors and developed a new nomogram to predict survival.
Methods
This population-based study examined 112,256 patients with neuroendocrine tumors between 2000 and 2018 using data from the Surveillance, Epidemiology, and End Results program.
Results
The age-adjusted incidence per 100,000 persons of neuroendocrine tumors increased from 4.90 in 2000 to 8.19 in 2018 (annual percentage change, 3.40; 95% confidence interval, 3.13–3.67), with the most significant increases in grade 1, localized stage, and appendix neuroendocrine tumors. The age-adjusted mortality rate increased 3.1-fold from 2000 to 2018 (annual percentage change, 4.14; 95% confidence interval, 3.14–5.15). The 1-, 5-, and 10-year relative survival rates for all neuroendocrine tumors were 80.5%, 68.4%, and 63.5%, respectively. Multivariate analyses showed that male sex; older age; Black, American Indian, and Alaska Native populations; earlier year of diagnosis; lung neuroendocrine tumors; higher grades; and later stage were associated with a worse prognosis and that disease stage and grade were the most important risk factors for prognosis. Furthermore, we established a nomogram to predict the 3-, 5-, and 10-year survival rates, and its discrimination ability was better than that of the TNM classification.
Conclusions
The incidence, prevalence, and mortality rate of neuroendocrine tumors continued to increase over the last two decades. Additionally, the nomogram could accurately quantify the risk of death in patients with neuroendocrine tumors and had good clinical practicability.
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Objective
Multiple endocrine neoplasia type 4 (MEN4) is caused by a CDKN1B germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics.
Methods
A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE® and Web of ScienceTM.
Results
Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different CDKN1B variants, mostly missense (21/48, 44%) and frameshift mutations (17/48, 35%), were reported. The majority of patients were women (36/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10–68, mean 33.7 ± 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5–76, mean 44.8 ± 19.9) (P = 0.25). The most frequently affected endocrine organ was the parathyroid gland (36/48, 75%; uniglandular disease 31/36, 86%), followed by the pituitary gland (21/48, 44%; hormone-secreting 16/21, 76%), the endocrine pancreas (7/48, 15%), and the thyroid gland (4/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27/48, 56%) and the pituitary gland (11/48, 23%). There were one (27/48, 56%), two (13/48, 27%), three (3/48, 6%), or four (5/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively.
Conclusion
MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.
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KORA Study Centre, University Hospital of Augsburg, Augsburg, Augsburg, Germany
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German Centre for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany
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German Heart Centre Munich, Technical University of Munich, Munich, Germany
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
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German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
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Objective
Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography–tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing.
Methods
After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed.
Results
Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples.
Conclusions
The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile.
Significance Statement
Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.
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Objective
Both primary thyroid lymphoma (PTL) and diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) are two rare malignant tumours with different therapies and prognoses. This study compared their clinical features.
Methods
From a retrospective review of the pathologic database at our institute between January 2015 and August 2020, 52 PTL patients and 40 DSVPTC patients were included. Demographic, clinical, laboratory and ultrasound data were extracted from electronic medical records. Statistical analyses were performed using GraphPad Prism 5.0.
Results
Both PTL and DSVPTC were more likely to occur in women (83.7 and 67.5%, respectively), but DSVPTC patients were younger (median age: 36 vs 64.5), had fewer compressive symptoms, and more frequently had neck lymph node metastasis than PTL patients. The prevalence of Hashimoto’s thyroiditis (HT) and hypothyroidism was significantly higher in PTL patients than in DSVPTC patients (31% vs 17.5%). Hyperthyroidism could only be found in DSVPTC patients, which accounted for 7.5%. Heterogeneous echogenicity and irregular edges were frequently observed in both PTL and DSVPTC. However, compared with PTL, DSVPTC exhibited smaller lesion sizes, higher frequencies of diffuse sonographic patterns and calcification and lower frequencies of hypoechoic features and internal blood flow signal. The overall survival rate with PTL was 77.23%, which was lower than that with DSVPTC (90.91%), but this difference was not significant (P = 0.096).
Conclusion
Clinical characteristics such as age, compression symptoms, and sonographic features such as a large mass with heterogeneous echogenicity, hypoechoic, irregular edges, and calcification are helpful for impression diagnosis of PTL and DSVPTC before surgery.
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Amsterdam UMC, Emma’s Children’s Hospital, Amsterdam, The Netherlands
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Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.
Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands
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Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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Netherlands Comprehensive Cancer Organisation, Utrecht, Netherlands
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Department of Epidemiology and Data Science, Amsterdam UMC, Amsterdam, Netherlands
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Objective
Whether an association between oral levothyroxine use, leading to supraphysiological exposure of the colon to thyroid hormones, and risk of colorectal cancer exists in humans is unclear. We therefore aimed to assess whether the use of levothyroxine is associated with a reduced risk of colorectal cancer in a linked cohort of pharmacy and cancer data.
Design
Population-based matched case–control study.
Methods
A total of 28,121 patients diagnosed with colorectal cancer between 1998 and 2014 were matched to 106,086 controls. Multivariable logistic regression was used to estimate the association between levothyroxine use and occurrence of colorectal cancer, adjusted for potential confounders. Results were stratified by gender, age, tumour subtype, and staging, as well as treatment duration and dosing.
Results
A total of 1066 colorectal cancer patients (4%) and 4024 (4%) controls had used levothyroxine at any point before index date (adjusted odds ratio 0.95 (0.88–1.01)). Long-term use of levothyroxine was seen in 323 (30%) colorectal cancer patients and 1111 (28%) controls (adjusted odds ratio 1.00 (0.88–1.13)). Stratification by tumour subsite showed a borderline significant risk reduction of rectal cancer, while this was not seen for proximal colon cancer or distal colon cancer. There was no relationship with treatment duration or with levothyroxine dose.
Conclusions
In this study, no reduced risk of colorectal cancer was seen in levothyroxine users. When stratifying by tumour subsite, a borderline significant risk reduction of rectal cancer was found and may warrant further research.
Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
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Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
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Leeds Institute of Medical Research, University of Leeds, UK
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Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
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Background
Survivors of childhood brain tumours (SCBT) and teenage and young adult cancer survivors have an adverse cardiovascular risk profile, which translates into an increased vascular mortality. Data on cardiovascular risk profiles in SCBT are limited, and furthermore, there are no data in adult-onset (AO) brain tumours.
Patients and
methods: Fasting lipids, glucose, insulin, 24-h blood pressure (BP), and body composition were measured in 36 brain tumour survivors (20 AO; 16 childhood-onset (CO)) and 36 age- and gender-matched controls.
Results
Compared with controls, patients had elevated total cholesterol (5.3 ± 1.1 vs 4.6 ± 1.0 mmol/L, P = 0.007), LDL-C (3.1 ± 0.8 vs 2.7 ± 0.9 mmol/L, P = 0.011), insulin (13.4 ± 13.1 vs 7.6 ± 3.3 miu/L, P = 0.014), and increased insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR) 2.90 ± 2.84 vs 1.66 ± 0.73, P = 0.016). Patients showed adverse body composition, with increased total body fat mass (FM) (24.0 ± 12.2 vs 15.7 ± 6.6 kg, P < 0.001) and truncal FM (13.0 ± 6.7 vs 8.2 ± 3.7 kg, P < 0.001).
After stratification by timing of onset, CO survivors showed significantly increased LDL-C, insulin, and HOMA-IR compared with controls. Body composition was characterized by the increased total body and truncal FM. Truncal fat mass was increased by 84.1% compared with controls. AO survivors showed similar adverse cardiovascular risk profiles, with increased total cholesterol and HOMA-IR. Truncal FM was increased by 41.0% compared with matched controls (P = 0.029). No difference in mean 24-h BP was noted between patients and controls irrespective of the timing of cancer diagnosis.
Conclusion
The phenotype of both CO and AO brain tumour survivors is characterized by an adverse metabolic profile and body composition, putatively placing long-term survivors at increased risk of vascular morbidity and mortality.
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Universidad La Salle, Posgrado de la Facultad de Ciencias Químicas, Ciudad de México, México
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The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan–Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24–0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.
