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      High Prevalence of Early Endocrine Disorders After Childhood Brain Tumors in a Large Cohort

      1 , 2 , 1 , 1 , 1 , 1 , 3 , 4 , 5 , 3 , 6 , 6 , 7 , 1 , 8 , 8 , 5 , 9 , 6 , 6 , 10 , 6 , 11 , 1 , 1 , 5 , 6 , 12 , 13 , 9 , 9 , 5 , 14 , 9 , 15 , 16 , 3 , 9 , 5 , 14 , 5 , 14 , 1 , 3
      The Journal of Clinical Endocrinology & Metabolism
      The Endocrine Society

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          Abstract

          Context

          Endocrine complications are common in pediatric brain tumor patients.

          Objective

          We aimed to describe the endocrine follow-up of patients with primary brain tumors.

          Methods

          This is a noninterventional observational study based on data collection from medical records of 221 patients followed at a Pediatric Endocrinology Department.

          Results

          Median age at diagnosis was 6.7 years (range, 0-15.9), median follow-up 6.7 years (0.3-26.6), 48.9% female. Main tumor types were medulloblastoma (37.6%), craniopharyngioma (29.0%), and glioma (20.4%). By anatomic location, 48% were suprasellar (SS) and 52% non-suprasellar (NSS). Growth hormone deficiency (GHD) prevalence was similar in both groups (SS: 83.0%, NSS: 76.5%; P = 0.338), appearing at median 1.8 years (−0.8 to 12.4) after diagnosis; postradiotherapy GHD appeared median 1.6 years after radiotherapy (0.2-10.7). Hypothyroidism was more prevalent in SS (76.4%), than NSS (33.9%) (P < 0.001), as well as ACTH deficiency (SS: 69.8%, NSS: 6.1%; P < 0.001). Early puberty was similar in SS (16%) and NSS (12.2%). Hypogonadotropic hypogonadism was predominant in SS (63.1%) vs NSS (1.3%), P < 0.001, and postchemotherapy gonadal toxicity in NSS (29.6%) vs SS (2.8%), P < 0.001. Adult height was lower for NSS compared to target height (−1.0 SD, P < 0.0001) and to SS patients (P < 0.0001). Thyroid nodules were found in 13/45 patients (28.8%), including 4 cancers (4.8-11.5 years after radiotherapy). Last follow-up visit BMI was higher in both groups (P = 0.0001), and obesity incidence was higher for SS (46.2%) than NSS (17.4%).

          Conclusion

          We found a high incidence of early-onset endocrine disorders. An endocrine consultation and nutritional evaluation should be mandatory for all patients with a brain tumor, especially when the tumor is suprasellar or after hypothalamus/pituitary irradiation.

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          Most cited references39

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          Cancer statistics, 2012.

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,638,910 new cancer cases and 577,190 deaths from cancer are projected to occur in the United States in 2012. During the most recent 5 years for which there are data (2004-2008), overall cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.6% per year in women. Over the past 10 years of available data (1999-2008), cancer death rates have declined by more than 1% per year in men and women of every racial/ethnic group with the exception of American Indians/Alaska Natives, among whom rates have remained stable. The most rapid declines in death rates occurred among African American and Hispanic men (2.4% and 2.3% per year, respectively). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate), with lung cancer accounting for almost 40% of the total decline in men and breast cancer accounting for 34% of the total decline in women. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket. Copyright © 2012 American Cancer Society, Inc.
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            Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. Survivors of childhood cancer have a high rate of illness owing to chronic health conditions. Copyright 2006 Massachusetts Medical Society.
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              The present contribution reports childhood cancer incidence and survival rates as well as time trends and geographical variation. The report is based on the databases of population-based cancer registries which joined forces in cooperative projects such as Automated Childhood Cancer Information System (ACCIS) and EUROCARE. According to these data, which refer to the International Classification of Childhood Cancer, leukemias, at 34%, brain tumors, at 23%, and lymphomas, at 12%, represent the largest diagnostic groups among the under 15-year-olds. The most frequent single diagnoses are: acute lymphoblastic leukemia, astrocytoma, neuroblastoma, non-Hodgkin lymphoma, and nephroblastoma. There is considerable variation between countries. Incidence rates range from 130 (British Isles) to 160 cases (Scandinavian countries) per million children. Incidence rates have shown an increase over time since the mid of the last century. In Europe, the yearly increase averages 1.1% for the 1978-1997 period and ranges from 0.6% for the leukemias to 1.8% for soft-tissue sarcomas. The probability of survival has risen considerably over the past decades, with the EUROCARE data showing an improvement of the relative risk of death by 8% when comparing the 2000-2002 time span to the 1995-1999 period. Regarding the years 1995-2002, the data show an overall 5-year survival probability of 81% for Europe and similar values for the USA. The data presented here describe the cancer situation with a specific, European focus. They are drawn from population-based cancer registries that ensure excellent data quality, and as a consequence represent the most valid European population-based data existing at present. It is also apparent that not all countries have data available from nationwide childhood cancer registries, a situation which warrants further improvement. 2010 Elsevier Ltd. All rights reserved.
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                Journal
                The Journal of Clinical Endocrinology & Metabolism
                The Endocrine Society
                0021-972X
                1945-7197
                May 01 2022
                April 19 2022
                December 16 2021
                May 01 2022
                April 19 2022
                December 16 2021
                : 107
                : 5
                : e2156-e2166
                Affiliations
                [1 ]Hôpital Universitaire Necker-Enfants Malades - Assistance Publique Hôpitaux de Paris (APHP), Service d’Endocrinologie, gynécologie et diabétologie pédiatrique, Institut IMAGINE (affiliate), 75015 Paris, France
                [2 ]ESPE Fellowship – European Society for Paediatric Endocrinology
                [3 ]Université de Paris, 75006 Paris, France
                [4 ]Institut Gustave Roussy, Département de radiothérapie-oncologie, 94805 Villejuif, France
                [5 ]Gustave Roussy, Université Paris-Saclay, Department of Pediatric and Adolescent Oncology, 94805 Villejuif, France
                [6 ]Hôpital Universitaire Necker-Enfants Malades - APHP, Service Neurochirurgie, 75015 Paris, France
                [7 ]Institut Curie, Radiation Oncology Department and Proton Center, 75005 Paris, France
                [8 ]Hôpital Necker-Enfants Malades, Explorations Fonctionnelles, 75015 Paris, France
                [9 ]Institut Curie, SIREDO Oncology Center (Care, Innovation and research for children and AYA with cancer), 75005 Paris, France
                [10 ]Hôpital Montpellier, Hôpital Gui de Chauliac, Unité de Neurochirurgie pédiatrique, 34295 Montpellier, France
                [11 ]Hôpital Lyon-Bron, Service Neurochirurgie, 69500 Bron, France
                [12 ]Lausanne University Hospital, Pediatric Endocrinology, Diabetology and Obesity Unit, Lausanne University, 1011 Lausanne, Switzerland
                [13 ]Hôpital André Mignot - Centre Hospitalier de Versailles, Endocrinologie Pédiatrique, 78157 Le Chesnay, France
                [14 ]Team “Genomics and Oncogenesis of Pediatric Brain Tumors”, INSERM U981, Gustave Roussy, University Paris Saclay, 94805 Villejuif, France
                [15 ]PSL Research University, 75006 Paris, France
                [16 ]Hôpital Universitaire La Pitié-Salpêtrière - APHP, Service Endocrinologie et médecine de la reproduction, Sorbonne Université Médecine, 75013 Paris, France
                Article
                10.1210/clinem/dgab893
                08ee91a1-6899-4df4-88f3-fa3004737639
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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