Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study
Abstract
BACKGROUND: Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group. METHODS: As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1,607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS. RESULTS: One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (>/= 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1-694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% CI 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7-109.8), blood clots (RR = 5.7; 95% CI 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy. CONCLUSIONS: Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Craniopharyngiomas are the leading cause of acquired central hypothyroidism in children, followed by cranial irradiation for other childhood brain tumours.
“Craniopharyngiomas are the leading cause of acquired central hypothyroidism in children, followed by cranial irradiation for other childhood brain tumours such as dysgerminomas or malignant haematological diseases (Gurney et al., 2003;Lando et al., 2001;Schmiegelow et al., 2003).”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Gurney et al., 2003
Cites
Multiple Imputation for Nonresponse in Surveys
Rubin, D. B. (1987) · Wiley Series in Probability and Statistics · doi:10.1002/9780470316696 · Cited by 20,701 · see citing works
SEER Cancer Statistics Review, 1975-2003
Ries, L. A. G., Harkins, D., Krapcho, M. F., Mariotto, A. B., Miller, B., Feuer, E. J., Clegg, L. X., Eisner, M. P., Horner, M., Howlader, N., et al. (2006) · Digital Archive @ GSU · Cited by 11,404 · see citing works
Modeling Survival Data: Extending the Cox Model
Therneau, T. M., & Grambsch, P. M. (2000) · Statistics for Biology and Health · doi:10.1007/978-1-4757-3294-8 · Cited by 8,674 · see citing works
O'Leary, D. H., Polak, J. F., Kronmal, R. A., Manolio, T. A., Burke, G. L., & Wolfson, S. K. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901073400103 · Cited by 4,685 · see citing works
Principles and Practice of Pediatric Oncology
Labotka, R. J. (2002) · JAMA · doi:10.1001/jama.288.7.894-a · Cited by 1,019 · see citing works
Robison, L. L., Mertens, A. C., Boice, J. D., Breslow, N. E., Donaldson, S. S., Green, D. M., Li, F. P., Meadows, A. T., Mulvihill, J. J., Neglia, J. P., et al. (2002) · Medical and Pediatric Oncology · doi:10.1002/mpo.1316 · Cited by 695 · see citing works
Self-citationStewart, J. R., Fajardo, L. F., Gillette, S. M., & Constine, L. S. (1995) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(94)00656-6 · Cited by 401 · see citing works
Sklar, C. A., Whitton, J. A., Mertens, A. C., Stovall, M., GREEN, D. J., Marina, N. M., Greffe, B. S., Wolden, S. L., & Robison, L. L. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6808 · Cited by 378 · see citing works
Self-citationSklar, C. A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.9.3227 · Cited by 327 · see citing works
Self-citationChronic neuroendocrinological sequelae of radiation therapy
Sklar, C. A., & Constine, L. S. (1995) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(94)00427-m · Cited by 224 · see citing works
Self-citationLong‐term sequelae of cancer treatment on the central nervous system in childhood
Packer, R. J., Meadows, A. T., RORKE, L. B., Goldwein, J. L., & D’Angio, G. J. (1987) · Medical and Pediatric Oncology · doi:10.1002/mpo.2950150505 · Cited by 215 · see citing works
Self-citationDavis, F. G., Kupelian, V. A., Freels, S. A., et al. (2001) · Neuro-Oncology · doi:10.1093/neuonc/3.3.152 · Cited by 196 · see citing works
Endocrine disorders following treatment of childhood brain tumours
Livesey, E., Hindmarsh, P. C., Brook, C. G. D., Whitton, A. C., Bloom, H. J. G., Tobias, J. S., Godlee, J. N., & Britton, J. R. (1990) · British Journal of Cancer · doi:10.1038/bjc.1990.138 · Cited by 133 · see citing works
Oberfield, S. E., Allen, J. C., Pollack, J. M., New, M. I., & Levine, L. S. (1986) · The Journal of Pediatrics · doi:10.1016/s0022-3476(86)80986-6 · Cited by 132 · see citing works
Thyroid function after treatment of brain tumors in children
Ogilvy‐Stuart, A., Shalet, S. M., & Gattamaneni, H. R. (1991) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80288-4 · Cited by 122 · see citing works
Masuya, D., Huang, C., Liu, D., Kameyama, K., Hayashi, E., Yamauchi, A., Kobayashi, S., Haba, R., & Yokomise, H. (2001) · Cancer · doi:10.1002/1097-0142(20011115)92:10 · Cited by 122 · see citing works
Taylor, J. M., Muñoz, A., Bass, S. M., Saah, A. J., Chmiel, J. S., & Kingsley, L. (1990) · PubMed · doi:10.1002/sim.4780090504 · Cited by 97 · see citing works
Thyroid dysfunction after radiotherapy and chemotherapy of brain tumours.
Livesey, E., & Brook, C. G. D. (1989) · Archives of Disease in Childhood · doi:10.1136/adc.64.4.593 · Cited by 92 · see citing works
Cardiac dysfunction following spinal irradiation during childhood.
Jakacki, R. I., Goldwein, J. W., Larsen, R. L., et al. (1993) · Journal of Clinical Oncology · doi:10.1200/jco.1993.11.6.1033 · Cited by 86 · see citing works
Chadburn, A., Cesarman, E., Nádor, R. G., Liu, Y. F., & Knowles, D. M. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970815)80:4 · Cited by 74 · see citing works
Long-term Effects of Treatment for Childhood Brain Tumors
Tomita, T. (1992) · Neurosurgery Clinics of North America · doi:10.1016/s1042-3680(18)30638-7 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Feldt-Rasmussen, U., Effraimidis, G., & Klose, M. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111173 · Cited by 170 · see citing works
Appelman-Dijkstra, N. M., Kokshoorn, N. E., Dekkers, O. M., Neelis, K. J., Biermasz, N. R., Romijn, J. A., Smit, J. W. A., & Pereira, A. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0306 · Cited by 162 · see citing works
Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies
Pappachan, J. M., Raskauskiene, D., Kutty, V. R., & Clayton, R. N. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3787 · Cited by 138 · see citing works
Harvest for health gardening intervention feasibility study in cancer survivors
Blair, C. K., Madan-Swain, A., Locher, J. L., Desmond, R. A., de Los Santos, J., Affuso, O., Glover, T., Smith, K., Carley, J., Lipsitz, M., et al. (2013) · Acta Oncologica · doi:10.3109/0284186x.2013.770165 · Cited by 53 · see citing works
Less known aspects of central hypothyroidism: Part 1- Acquired etiologies
Benvenga, S., Klose, M., Vita, R., & Feldt-Rasmussen, U. (2018) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2018.09.003 · Cited by 19 · see citing works
Interactions between hypothalamic pituitary thyroid axis and other pituitary dysfunctions
Feldt-Rasmussen, U., Klose, M., & Benvenga, S. (2018) · Endocrine · doi:10.1007/s12020-018-1738-6 · Cited by 12 · see citing works
- Authors
- Gurney, J. G., Kadan‐Lottick, N. S., Packer, R. J., Neglia, J. P., Sklar, C. A., Punyko, J. A., Stovall, M., Yasui, Y., Nicholson, H. S., Wolden, S., McNeil, D. E., Mertens, A. C., & Robison, L. L.
- Affiliations
- University of Minnesota (US)
- Children's National (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Fred Hutch Cancer Center (US)
- Oregon Health & Science University (US)
- National Institutes of Health (US)
- Corresponding author
- Gurney, James G.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2003-01-17
- Volume
- 97
- Issue
- 3
- Pages
- 663-673
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W1494071096
- Cited by
- 369
- References
- 22
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 12 · 2021: 15 · 2020: 13 · 2019: 13 · 2018: 18 · 2017: 22 · 2016: 21 · 2015: 24 · 2014: 21 · 2013: 15 · 2012: 18
- FWCI
- 13.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (U24-CA-55727, U24CA055727)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Keywords
- childhood brain tumor survivors, late effects of cancer treatment, endocrine late effects, cardiovascular late effects, hypothyroidism, growth hormone deficiency, puberty induction, osteoporosis, stroke, blood clots, radiotherapy, adjuvant chemotherapy, Childhood Cancer Survivor Study, sibling comparison, long-term cancer survivorship, treatment-related morbidity
- MeSH terms
- Adult, Antineoplastic Agents, Brain Neoplasms, Cardiovascular Diseases, Child, Endocrine System Diseases, Humans, Radiotherapy, Risk, Survivors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
