ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 9.1 | DOI: 10.1530/ey.18.9.1

Cancer Epidemiol Biomarkers Prev. 2021; 30: 133–141.

This retrospective study of 152 patients and 604 matched-controls within the FCCSS (French Childhood Cancer Survivor Study) cohort aimed to identify clinical and therapeutic factors associated with long-term risk of subsequent primary neoplasm (SPN) in the central nervous system (CNS), occurring at least 5 years after the primary cancer diagnosis.

Treatment of CNS tumors predisposes to SPN. In patients treated with cranial irradiation, the risk of SPN increases linearly with radiation doses. Other factors that contribute to this risk are still not completely understood (1–3). A better knowledge of the risk factors for CNS SPN is essential to define guidelines for long-term surveillance of childhood cancer survivors, improve early detection and treatment.

The study included individuals diagnosed in 1946–2000 with a solid cancer or lymphoma at age < 21 years. The type of first cancer and treatment modalities (radiotherapy, chemotherapy, and growth hormone) were analyzed. Genetic syndromes associated with increased risk of carcinogenesis were considered (neurofibromatosis types 1 and 2, Turcot, Gorlin, Li-Fraumeni, Klinefelter, Rubinstein–Taybi, Turner, Bloom syndrome, tuberous sclerosis, colon polyposis, and bilateral or familial retinoblastoma).

The risk of subsequent meningioma was 16x higher among CNS tumor survivors compared with other cancer survivors. Meningioma risk, after adjustment for potentially predisposing syndromes and primary CNS tumor, increased with higher radiation doses and cumulative doses of alkylating agents, but no association was found with growth hormone therapy. Meningioma risk was higher in patients who were younger at the primary cancer diagnosis, but did not vary over time. The risk of subsequent glioma was 10x higher among CNS tumor survivors and those with a predisposing genetic syndrome. There was no or a moderate reduction in these risks after adjustment for cumulative radiation dose. The excess Odds ratio per Gy (EOR/Gy) increased among older individuals at the time of the primary cancer diagnosis and with a shorter follow-up time. The risk of glioma was higher in patients treated with epipodophyllotoxins, without any dose–response relationship. The sample size was too small to investigate the relationship between growth hormone therapy and subsequent glioma.

Follow-up of individuals with genetic growth disorders or acromegaly showed an association between growth factors and carcinogenesis, and thus, indirectly raised concerns about growth hormone treatment in CNS tumor survivors. Cranial irradiation increases CNS SPN risk and can also induce growth hormone deficiency, thus, it represents an important confounding factor. Very few studies have evaluated the effect of growth hormone therapy while accounting for radiation doses (4). The impact of growth hormone therapy in the long-term risk of CNS SPN need to be investigated in large populations with a prolonged follow up. Up to now, no study has included an adequate number of cases to produce statistically robust results.

Reference: 1. Taylor AJ, et al. Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 2010; 28: 5287–93.2. Neglia JP, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 2006; 98: 1528–37.3. Kok JL, et al. Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort: contributions of radiation dose, exposed cranial volume, and age. Neuro Oncol 2019; 21: 392–403.4. Patterson BC, et al. Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2014; 99: 2030–7.

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