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

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Abstract

Childhood cancer survivors are at risk for developing endocrine disorders, including deficits in growth hormone, thyroid hormone and sex hormones. The 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 for future research pertaining to this area.

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Most cited references 66

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Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

Gary Francis, Steven G Waguespack, Andrew Bauer … (2015)

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed.

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Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

Adda Grimberg, Sara A. DiVall, Constantin Polychronakos … (2017)

Background/Aims: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time. Methods: This guideline was developed following the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation). Results: This guideline provides recommendations for the clinical management of children and adolescents with growth failure from GHD, ISS, or PIGFD using the best available evidence. Conclusion: The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient. In many instances, careful review highlights areas that need further research.

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Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease.

Ethel Gilbert, Tom Wiklund, Lois B. Travis … (2003)

Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk. To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD. Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998. Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents. Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P =.03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P =.003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses. Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.

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Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 08 November 2022

Publication date Collection: 01 January 2023

Volume: 12

Issue: 1

Electronic Location Identifier: e220382

Affiliations

[1 ]Department of Pediatric Endocrinology , Wilhelmina Children's Hospital, University Medical Center Utrecht, AB Utrecht, The Netherlands

[2 ]Princess Máxima Center for Pediatric Oncology , AB Utrecht, The Netherlands

[3 ]Division of Pediatric Endocrinology , UPMC Children’s Hospitalof Pittsburgh, Pittsburgh, Pennsylvania, USA

Author notes

Correspondence should be addressed to W Chemaitilly: chemaitillyw2@ 123456upmc.edu

Author information

Boudewijn Bakker http://orcid.org/0000-0003-0229-1123

Hanneke M van Santen http://orcid.org/0000-0002-6773-6931

Wassim Chemaitilly http://orcid.org/0000-0003-0717-5076

Article

Publisher ID: EC-22-0382

DOI: 10.1530/EC-22-0382

PMC ID: 9782441

PubMed ID: 36347051

SO-VID: 7863b910-e2b1-4142-8b39-6746a9b1a687

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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

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Most cited references 66

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease.

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