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Cancer Epidemiol Biomarkers Prev ; 30(1): 133-141, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33033142

RESUMO

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.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/epidemiologia , Criança , Irradiação Craniana/efeitos adversos , Relação Dose-Resposta à Radiação , Feminino , França , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco
3.
J Clin Oncol ; 38(16): 1785-1796, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32196392

RESUMO

PURPOSE: Between 10% and 20% of childhood cancer survivors (CCS) experience impaired growth, leading to small adult height (SAH). Our study aimed to quantify risk factors for SAH or growth hormone deficiency among CCS. METHODS: The French CCS Study holds data on 7,670 cancer survivors treated before 2001. We analyzed self-administered questionnaire data from 2,965 CCS with clinical, chemo/radiotherapy data from medical records. SAH was defined as an adult height ≤ 2 standard deviation scores of control values obtained from a French population health study. RESULTS: After exclusion of 189 CCS treated with growth hormone, 9.2% (254 of 2,776) had a SAH. Being young at the time of cancer treatment (relative risk [RR], 0.91 [95% CI, 0.88 to 0.95] by year of age), small height at diagnosis (≤ 2 standard deviation scores; RR, 6.74 [95% CI, 4.61 to 9.86]), pituitary irradiation (5-20 Gy: RR, 4.24 [95% CI, 1.98 to 9.06]; 20-40 Gy: RR, 10.16 [95% CI, 5.18 to 19.94]; and ≥ 40 Gy: RR, 19.48 [95% CI, 8.73 to 43.48]), having received busulfan (RR, 4.53 [95% CI, 2.10 to 9.77]), or > 300 mg/m2 of lomustine (300-600 mg/m2: RR, 4.21 [95% CI, 1.61 to 11.01] and ≥ 600 mg/m2: RR, 9.12 [95% CI, 2.75 to 30.24]) were all independent risk factors for SAH. Irradiation of ≥ 7 vertebrae (≥ 15 Gy on ≥ 90% of their volume) without pituitary irradiation increased the RR of SAH by 4.62 (95% CI, 2.77 to 7.72). If patients had also received pituitary irradiation, this increased the RR by an additional factor of 1.3 to 2.4. CONCLUSION: CCS are at a high risk of SAH. CCS treated with radiotherapy, busulfan, or lomustine should be closely monitored for growth, puberty onset, and potential pituitary deficiency.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Estatura , Bussulfano/efeitos adversos , Sobreviventes de Câncer , Transtornos do Crescimento/epidemiologia , Hormônio do Crescimento Humano/deficiência , Lomustina/efeitos adversos , Neoplasias/terapia , Lesões por Radiação/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , França/epidemiologia , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/fisiopatologia , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Neoplasias/epidemiologia , Puberdade , Lesões por Radiação/diagnóstico , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/fisiopatologia , Radioterapia/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
4.
Radiother Oncol ; 131: 150-159, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30316563

RESUMO

As modern radiotherapy, including intensity-modulated techniques, is associated with high dose gradients to normal tissues and large low-to-moderate dose volumes, the assessment of second primary cancer (SPC) risks requires quantification of dose-volume effects. We conducted a systematic review of clinical and epidemiological studies investigating the effect of the irradiated volume or dose-volume distribution to the remaining volume at risk (RVR) on SPC incidence. We identified eighteen studies comparing SPC risks according to the irradiated volume (i.e., in most studies, the size or number of fields used), and four studies reporting risk estimates according to the dose distribution to the RVR (after whole-body dose reconstruction). An increased risk of SPCs (mainly breast and lung cancers) with extended radiotherapy was observed among patients treated for Hodgkin lymphoma or childhood cancers. However, normal tissue dose distribution was not estimated, limiting the interpretation of those results in terms of volume effects on organs at risk. Studies considering whole-body exposures quantified dose-response relationships for point dose estimates, without accounting for dose-volume distributions. Therefore, they disregarded possible tissue effects (e.g. bystander and abscopal effects, stem cell repopulation) which may play a role in the induction of SPCs. Currently, there is no clinical or epidemiological information about a possible role of high dose gradients in surrounding organs, or increasing volumes of distant tissues exposed to low doses, in the risk of SPCs. Opportunities for future research nevertheless now exist, since methods and tools for estimating individual whole-body dose-volume distributions in large patient populations have been developed.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Neoplasias/radioterapia , Relação Dose-Resposta à Radiação , Doença de Hodgkin/radioterapia , Humanos , Incidência , Segunda Neoplasia Primária/etiologia , Estudos Observacionais como Assunto , Radioterapia/efeitos adversos , Radioterapia/estatística & dados numéricos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco
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