Risk Factors of Subsequent Central Nervous System Tumors after Childhood and Adolescent Cancers: Findings from the French Childhood Cancer Survivor Study

Abstract

Background: Childhood or adolescent cancer survivors are at increased risks of subsequent primary neoplasms (SPN) of the central nervous system (CNS) after cranial irradiation. In a large multicentric cohort, we investigated clinical and therapeutic factors associated with the long-term risk of CNS SPN, and quantified the dose–response relationships. Methods: We selected all CNS SPN cases diagnosed up to 2016 among members of the French Childhood Cancer Survivor Study at least 5 years after first cancer diagnosis in 1946–2000. Four controls per case were randomly selected within the cohort and matched by sex, year of/age at first cancer diagnosis, and follow-up time. On the basis of medical and radiological reports, cumulative radiation doses received to the SPN or matched location were retrospectively estimated using mathematical phantoms. We computed conditional logistic regression models. Results: Meningioma risk significantly increased with higher radiation doses [excess OR per Gy (EOR/Gy) = 1.377; P < 0.001; 86 cases; median latency time = 30 years], after adjustment for reported genetic syndromes and first CNS tumor. It was higher among youngest individuals at first cancer diagnosis, but did not vary with follow-up time. On the opposite, radiation-related glioma risk (EOR/Gy = 0.049; P = 0.11; 47 cases; median latency time = 17 years) decreased over time (P for time effect = 0.05). There was a significant association between meningioma risk and cumulative doses of alkylating agents, but no association with growth hormone therapy. Conclusions: The surveillance of patients with cranial irradiation should continue beyond 30 years after treatment. Impact: The identified risk factors may inform long-term surveillance strategies.

Growth Hormone Deficiency and Treatment in Childhood Cancer Survivors

“…Journy et al report the risk specifically of subsequent CNS tumors in the French Childhood Cancer Survivor Study (FCCSS) (68). The FCCSS includes 7,670 patients diagnosed between 1946-2000 with a solid tumor or lymphoma (68).…”

“…Journy et al report the risk specifically of subsequent CNS tumors in the French Childhood Cancer Survivor Study (FCCSS) (68). The FCCSS includes 7,670 patients diagnosed between 1946-2000 with a solid tumor or lymphoma (68). The risk of subsequent meningioma was 16 times higher amongst patients with prior CNS tumor than other cancer diagnoses, and the risk was significantly associated with cumulative radiation dose.…”

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

“…On the contrary, IR-related glioma risk (EOR/Gy = 0.049; median latency time = 17 years) decreased over time. There was a significant association between meningioma risk and cumulative doses of alkylating agents but no association with growth hormone therapy [100].…”

“…The clinical and therapeutic factors associated with the long-term risk of secondary neoplasm (SN) of the CNS after cranial irradiation in childhood or adolescent cancer survivors have been quantified [100]. After adjustment for reported genetic syndromes and first CNS tumor, the meningioma risk significantly increased with higher IR doses (excess OR per Gy (EOR/Gy) = 1.377; median latency time = 30 years).…”

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

“…Again, meningiomas were the most frequent second tumor in the GH-treated groups [ 24 – 26 ]. Female sex, young age at primary cancer diagnosis, a long time period since cranial irradiation [ 2 ], CNS radiation dose ≥ 20 Gy and cumulative doses of multiple alkylating agents [ 142 ] were associated with meningioma development. These reports reinforce the need to interpret cautiously the risk of secondary tumors in GH treated patients.…”