Hormone replacement in survivors of childhood cancer and brain tumors: safety and controversies

Childhood cancer survivors are at risk for developing endocrine disorders, including deficits in growth hormone, thyroid hormone and sex hormones. Th e influence these hormones have on cell growth and metabolism has raised concerns regarding the safety of their use as treatments in survivors of childhood cancer and brain tumors. This article offers a summary of current knowledge, controversies and areas f or future research pertaining to this area

Аналіз ефективності використання потенціалу матеріальних ресурсів підприємства

Метою даного дослідження виступає пошук аналітичних можливостей комплексної оцінки та аналізу використання потенціалу матеріальних ресурсів та визначення шляхів підвищення ефективності використання матеріальних ресурсів підприємства

Presentation and outcome of subsequent thyroid cancer among childhood cancer survivors compared to sporadic thyroid cancer:a matched national study

Objective: Childhood cancer survivors (CCS) are at increased risk to develop differentiated thyroid cancer predominantly after radiotherapy (subsequent DTC). It is insufficiently known whether subsequent DTC in CCS has a different presentation or outcome than sporadic DTC. Methods: Patients with subsequent DTC (n = 31) were matched to patients with sporadic DTC (n = 93) on gender, age and year of diagnosis to compare presentation and DTC outcomes. Clinical data were collected retrospectively. Results: Among the CCS with subsequent DTC, all but one had received chemotherapy for their childhood cancer, 19 (61.3%) had received radiotherapy including the thyroid region, 3 (9.7%) 131I-MIBG and 8 (25.8%) had received treatment with chemotherapy only. Subsequent DTC was detected by surveillance through neck palpation (46.2%), as a self-identified mass (34.6%), or by chance. Among sporadic DTC patients, self detection predominated (68.8%). CCS with subsequent DTC tended to have on average smaller tumors (1.9 vs 2.4 cm, respectively, (P = 0.051), and more often bilateral (5/25 (60.0%) vs 28/92 (30.4%), P = 0.024). There were no significant differences in the occurrence of surgical complications, recurrence rate or disease-related death. Conclusion: When compared to patients with sporadic DTC, CCS with subsequent DTC seem to present with smaller tumors and more frequent bilateral tumors. Treatment outcome seems to be similar. The finding that one-third of subsequent DTC cases had been treated with chemotherapy only needs further investigation. These results are important for the development of surveillance programs for CCS at risk for DTC and for treatment guidelines of subsequent DTC

Changes in thyroid function parameters 3 months after allogeneic and autologous hematopoietic stem cell transplantation in children

Background: Thyroid dysfunction (hypo- and hyperthyroidism) has been reported as a late effect after hematopoietic stem cell transplantation (HSCT) in children. Short-term effects of HSCT on thyroid function parameters are, however, unclear. Methods: We prospectively evaluated thyroid function parameters before and 3 months after HSCT in all children (&lt;21 years) who underwent HSCT during a 2-year period in the Princess Máxima Center, the Netherlands. Results: Among 72 children, none had thyroidal hypothyroidism or hyperthyroidism 3 months after HSCT. Changes in thyroid function parameters (either aberrant thyroid-stimulating hormone [TSH] or free thyroxine [FT4] concentrations) were found in 16% before and in 10% 3 months after HSCT. Reverse triiodothyronine (rT3) was found elevated in 9.3% before and in 37% 3 months after HSCT, which could be related to poor physical condition. An individual decline in FT4 concentration of ≥20% was found in 10.5% (6/57) 3 months after HSCT. Conclusion: In conclusion, thyroidal hypo- and hyperthyroidism are very rare 3 months after HSCT. These results indicate that surveillance for hypo- and hyperthyroidism may start later in time. The changes in thyroid function parameters found 3 months after HSCT might reflect euthyroid sick syndrome.</p

The Dutch LATER physical outcomes set for self-reported data in survivors of childhood cancer

Purposes: Studies investigating self-reported long-term morbidity in childhood cancer survivors (CCS) are using heterogeneous outcome definitions, which compromises comparability and include (un)treated asymptomatic and symptomatic outcomes. We generated a Dutch LATER core set of clinically relevant physical outcomes, based on self-reported data. Clinically relevant outcomes were defined as outcomes associated with clinical symptoms or requiring medical treatment. Methods: First, we generated a draft outcome set based on existing questionnaires embedded in the Childhood Cancer Survivor Study, British Childhood Cancer Survivor Study, and Dutch LATER study. We added specific outcomes reported by survivors in the Dutch LATER questionnaire. Second, we selected a list of clinical relevant outcomes by agreement among a Dutch LATER experts team. Third, we compared the proposed clinically relevant outcomes to the severity grading of the Common Terminology Criteria for Adverse Events (CTCAE). Results: A core set of 74 self-reported long-term clinically relevant physical morbidity outcomes was established. Comparison to the CTCAE showed that 36% of these clinically relevant outcomes were missing in the CTCAE. Implications for Cancer Survivors: This proposed core outcome set of clinical relevant outcomes for self-reported data will be used to investigate the self-reported morbidity in the Dutch LATER study. Furthermore, this Dutch LATER outcome set can be used as a starting point for international harmonization for long-term outcomes in survivors of childhood cancer

Dextroamphetamine Treatment in Children With Hypothalamic Obesity

INTRODUCTION: Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO. METHODS: A retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment. RESULTS: Nineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up. CONCLUSION: In addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results

Opposite Incidence Trends for Differentiated and Medullary Thyroid Cancer in Young Dutch Patients over a 30-Year Time Span (vol 13, 5104, 2021)

Error in Figure In the original article [1], there was a mistake in Figure 1 as published. In this figure, two years are missing (2000 and 2001). The AAPC values as previously published are correct. The corrected Figure 1 appears below. In addition, in the original article, there was a mistake in Figure 2A–C as published. In these figures, two years are missing (2000 and 2001). The AAPC values were correct and do not require adjustment. The corrected Figure 2A–C appears below. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated. (figure presented)

Opposite incidence trends for differentiated and medullary thyroid cancer in young dutch patients over a 30‐year time span

Thyroid cancer is the most common endocrine malignancy in children. A rising incidence has been reported worldwide. Possible explanations include the increased use of enhanced imaging (leading to incidentalomas) and an increased prevalence of risk factors. We aimed to evaluate the incidence and survival trends of thyroid cancer in Dutch children, adolescents, and young adults (0–24 years) between 1990 and 2019. The age-standardized incidence rates of differentiated thyroid cancer (DTC, including papillary and follicular thyroid cancer (PTC and FTC, respectively)) and medullary thyroid cancer (MTC), the average annual percentage changes (AAPC) in incidence rates, and 10-year overall survival (OS) were calculated based on data obtained from the nationwide cancer registry (Netherlands Cancer Registry). A total of 839 patients aged 0–24 years had been diagnosed with thyroid carcinoma (PTC: 594 (71%), FTC: 128 (15%), MTC: 114 (14%)) between 1990 and 2019. The incidence of PTC increased significantly over time (AAPC +3.6%; 95%CI +2.3 to +4.8), the incidence rate of FTC showed a stable trend ((AAPC −1.1%; 95%CI −3.4 to +1.1), while the incidence of MTC decreased significantly (AAPC: −4.4% (95%CI −7.3 to −1.5). The 10-year OS was 99.5% (1990–1999) and 98.6% (2000–2009) in patients with DTC and 92.4% (1990–1999) and 96.0% (2000–2009) in patients with MTC. In this nationwide study, a rising incidence of PTC and decreasing incidence of MTC were observed. For both groups, in spite of the high proportion of patients with lymph node involvement at diagnosis for DTC and the limited treatment options for MTC, 10-year OS was high

Crystal IS on the move

Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis 18 years and follow-up 5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (emean 14.5 versus 15.8cm/s, P=0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac agin

Clinical considerations for the treatment of secondary differentiated thyroid carcinoma in childhood cancer survivors

The incidence of differentiated thyroid carcinoma (DTC) has increased rapidly over the past several years. Thus far, the only conclusively established risk factor for developing DTC is exposure to ionizing radiation, especially when the exposure occurs in childhood. Since the number of childhood cancer survivors (CCS) is increasing due to improvements in treatment and supportive care, the number of patients who will develop DTC after surviving childhood cancer (secondary thyroid cancer) is also expected to rise. Currently, there are no recommendations for management of thyroid cancer specifically for patients who develop DTC as a consequence of cancer therapy during childhood. Since complications or late effects from prior cancer treatment may elevate the risk of toxicity from DTC therapy, the medical history of CCS should be considered carefully in choosing DTC treatment. In this paper, we emphasize how the occurrence and treatment of the initial childhood malignancy affects the medical and psychosocial factors that will play a role in the diagnosis and treatment of a secondary DTC. We present considerations for clinicians to use in the management of patients with secondary DTC, based on the available evidence combined with experience -based opinions of the authors