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1.
Radiother Oncol ; 171: 14-21, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35405175

RESUMO

BACKGROUND AND PURPOSE: The Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS. MATERIALS AND METHODS: Patient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated. RESULTS: The mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2-32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS. CONCLUSIONS: This study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34886029

RESUMO

Important in testing services in medical laboratories is the creation of a flexible balance between quality-response time and minimizing the cost of the service. Beyond the different Lean methods implemented so far in the medical sector, each company can adapt the model according to its needs, each company has its own specifics and organizational culture, and Lean implementation will have a unique approach. Therefore, this paper aims to identify the concerns of specialists and laboratory medical services sector initiatives in optimizing medical services by implementing the Lean Six Sigma method in its various variants: a comparative analysis of the implemented models, with emphasis on measuring externalities and delimiting trends in reforming/modernizing the method, a comprehensive approach to the impact of this method implementation, and an analysis of available databases in order to underline the deficit and information asymmetry. The results highlighted that in the case of clinical laboratories, the Lean Six Sigma method is conducive to a reduction of cases of diagnostic errors and saves time but also faces challenges and employees' resistance in implementation.


Assuntos
Eficiência Organizacional , Laboratórios , Cultura Organizacional , Melhoria de Qualidade , Gestão da Qualidade Total
3.
Brain Commun ; 3(2): fcab055, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136809

RESUMO

Long-term sequelae are major limitations of radiation therapy use, especially for childhood brain tumour. Circle of Willis irradiation strongly increases the long-term risk of stroke, but to establish dose-response relationship, anticipating long-term effects of new techniques, requires to perform accurate and reproducible dosimetric estimations in large cohorts of patients having received radiotherapy decades ago. For the accuracy of retrospective dose reconstruction, the topographic variability of the Circle of Willis arteries is crucial. In order to improve retrospective dosimetric studies and dose-volume estimates to the typical Circle of Willis arteries, we aim to study the inter-individual topographic variability of these structures. Thirty-eight time of flight MRI sequences of children aged 2-17 years in both genders were investigated. A region growth algorithm was used for the segmentation of the cerebral arteries. A rigid registration in a common skull was performed following the anatomy of skull base foramina. The Posterior clinoid processes of the sella turcica were used as reference landmark (R0), and 5 key landmarks were chosen in each segmented Circle of Willis, then distances between the 5 landmarks and R0 were calculated for each of the 38 subjects. The distance between R0 and each landmark of the Circle of Willis followed a normal distribution, the average values ranging from 13.6 to 17.0 mm, and the standard deviations ranged from 2.6 to 3.0 mm, i.e. less than a fifth of the average value. The perimeter of the Circle of Willis was longer in older subjects, this increase being isotropic. Our study shows a remarkably low topographic variability of the typical Circle of Willis. An important result, allowing reliable anthropomorphic phantoms-based retrospective estimations of the radiation doses delivered to these arterial structures during radiotherapy treatment.

4.
Bone Marrow Transplant ; 56(8): 1984-1997, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33824435

RESUMO

Intensive treatments including high-dose chemotherapy (HDC) with autologous stem cell rescue have improved high-risk neuroblastoma (HRNB) survival. We report the long-term health status of 145 HRNB survivors, alive and disease-free 5 years post HDC. Median follow-up was 15 years (range = 5-34). Six patients experienced late relapses, 11 developed second malignant neoplasms (SMNs), and 9 died. Event-free and overall survivals 20 years post HDC were 82% (95% CI = 70%-90%) and 89% (78%-95%), respectively. Compared with the French general population, the standardized mortality ratio was 19 (95% CI = 8.7-36.1; p < 0.0001) and the absolute excess risk was 37.6 (19.2-73.5). Late effects were observed in 135/145 patients (median = 3 events/patient); 103 had at least one severe event. SMNs arose at a median of 20 years post HDC and included carcinoma (n = 5), sarcoma (2), acute myeloid leukemia (2), melanoma (1), and malignant glioma (1). Non-oncologic health events included dental maldevelopment (60%), severe hearing loss (20% cumulative probability at 15 years), hepatic focal nodular hyperplasia (14%), thyroid (11%), cardiac (8%), and renal (7%) diseases and growth retardation (height-for-age z-score ≤ -2 for 21%). Gonadal insufficiency was near-universal after busulfan (40/43 females, 33/35 males). Severe late effects are frequent and progressive in HRNB survivors needing systematic very long-term follow-up.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neuroblastoma , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Seguimentos , Humanos , Masculino , Neuroblastoma/terapia , Transplante de Células-Tronco , Sobreviventes , Transplante Autólogo
5.
Int J Cancer ; 148(9): 2079-2089, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33105035

RESUMO

Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but there is little consensus on the magnitude of some risk factors because of the small size of previous studies. We performed a pooled analysis of all published studies with detailed treatment data, including estimated active bone marrow (ABM) dose received during radiation therapy and doses of specific chemotherapeutic agents for childhood cancer diagnosed from 1930 through 2000, in order to more thoroughly investigate treatment-related risks of SPL. A total of 147 SPL cases (of which 69% were acute myeloid leukemia [AML]) were individually matched to 522 controls, all from four case-control studies including patients from six countries (France, United Kingdom, United States, Canada, Italy and Netherlands). Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression, and the excess OR per Gray (EOR/Gy) was also calculated. After accounting for the other therapies received, topoisomerase II inhibitor was associated with an increased SPL risk (highest tertile vs none: OR = 10.0, 95% CI: 3.7-27.3). Radiation dose to the ABM was also associated with increased SPL risk among those not receiving chemotherapy (EOR/Gy = 1.6, 95% CI: 0.1-14.3), but not among those who received chemotherapy (CT). SPL were most likely to occur in the first decade following cancer treatment. Results were similar when analyses were restricted to AML. The evidence of interaction between radiation and CT has implications for leukemogenic mechanism. The results for topoisomerase II inhibitors are particularly important given their increasing use to treat childhood cancer.


Assuntos
Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/dietoterapia , Leucemia Mieloide Aguda/radioterapia , Adolescente , Sobreviventes de Câncer , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/mortalidade
6.
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
7.
Gut ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139271

RESUMO

BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. METHODS: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. RESULTS: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected. CONCLUSIONS: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

8.
Eur J Endocrinol ; 183(4): 471-480, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32738133

RESUMO

CONTEXT: Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of a second neoplasm (SN). OBJECTIVE: To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986. DESIGN AND SETTING: Cohort study and nested case-control study. PARTICIPANTS: Of the 2852 survivors, with a median follow-up of 26 years, 196 had received GH therapy (median delay from cancer diagnosis: 5.5 years). MAIN OUTCOME MEASURES: Occurrence of SN. RESULTS: In total, 374 survivors developed a SN, including 40 who had received GH therapy. In a multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors (RR: 0.6, 95% CI: 0.2-1.5, P = 0.3), secondary non-brain cancer (RR: 0.7, 95% CI: 0.4-1.2, P = 0.2), or meningioma (RR: 1.9, 95% CI: 0.9-4, P = 0.09). Nevertheless, we observed a slight non-significant increase in the risk of meningioma with GH duration: 1.6-fold (95% CI: 1.2-3.0) after an exposure of less than 4 years vs 2.3-fold (95% CI: 0.9-5.6) after a longer exposure (P for trend = 0.07) confirmed by the results of a case-control study. CONCLUSION: This study confirms the overall safety of GH use in survivors of childhood cancer, which does not increase the risk of a SN. The slight excess in the risk of meningioma in patients with long-term GH treatment is non-significant and could be due to difficulties in adjustment on cranial radiation volume/dose and/or undiagnosed meningioma predisposing conditions.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Hormônio do Crescimento Humano/uso terapêutico , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/induzido quimicamente , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Feminino , Seguimentos , França/epidemiologia , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Meníngeas/induzido quimicamente , Neoplasias Meníngeas/epidemiologia , Meningioma/induzido quimicamente , Meningioma/epidemiologia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/induzido quimicamente , Estudos Retrospectivos , Adulto Jovem
9.
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
10.
Eur J Cancer ; 117: 71-83, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31260818

RESUMO

BACKGROUND: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. METHODS: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. RESULTS: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. CONCLUSIONS: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Leucemia/epidemiologia , Segunda Neoplasia Primária/etiologia , Medição de Risco/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Leucemia/diagnóstico , Masculino , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Prognóstico , Sistema de Registros , Fatores de Risco , Adulto Jovem
11.
Eur J Heart Fail ; 21(4): 509-518, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30592114

RESUMO

BACKGROUND: Paediatric cancer survivors have a high risk of developing cardiac diseases, and the most frequent cardiac disease is heart failure (HF). The radiation dose-volume effects in the heart and cardiac substructures have not been explored in childhood cancer survivors (CCS). Therefore, the role of irradiated heart volume in the occurrence of HF among this population remains unclear. The aims of this study were to determine the doses and irradiated volumes of the heart and left ventricle (LV) related to the risk of HF in CCS and to investigate the impact of anthracycline exposure on this risk. METHODS AND RESULTS: A case-control study nested in the French Childhood Cancer Survivors Study cohort. The mean heart and left ventricular doses and volumes indicators were estimated by reconstruction of individual treatments. A total of 239 HF cases and 1042 matched controls were included. The median age of HF diagnosis was 25.1 years. The median volume of the heart that received ≥ 30 Gy was 61.1% for cases and 16.9% for controls. In patients who did not receive anthracycline, the risk of HF was increased 3.6-fold when less than 10% of the LV received ≥ 30 Gy when compared to patients who were not exposed to any cardiac radiation and anthracycline. CONCLUSIONS: Small irradiated volumes of the heart or LV were significantly associated with HF risk. To the author's knowledge, this is the first study to report a dose-response relationship based on dose-volume indicators in CCS, which can be translated efficiently into current clinical practice.


Assuntos
Volume Cardíaco/efeitos da radiação , Cardiotoxicidade/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Coração/efeitos da radiação , Neoplasias/radioterapia , Radioterapia/efeitos adversos , Adulto , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Volume Cardíaco/efeitos dos fármacos , Cardiotoxicidade/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Coração/efeitos dos fármacos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos da radiação , Humanos , Masculino , Doses de Radiação
12.
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
13.
Int J Radiat Oncol Biol Phys ; 102(3): 578-583, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30096470

RESUMO

PURPOSE: Male breast cancer (MBC) is uncommon, accounting for less than 1% of all breast cancers. Secondary breast cancers among childhood cancer survivors have been well described in the literature, but less is known about MBC. METHODS AND MATERIALS: We carried out an analysis in a cohort of 7019 five-year survivors of a solid childhood (aged ≤20 years) cancer treated in France before 2001 and followed for an average of 20 years and compared breast cancers occurring in both men and women. RESULTS: Among the 7019 survivors, 4 out of 3893 male survivors developed breast cancer, compared with 99 out of 3126 female survivors. All of the men had a history of radiation therapy. The 4 men with MBC had estrogen receptors and 3 had progesterone receptors. CONCLUSIONS: MBC is a rare second malignancy among childhood cancer survivors. Receipt of radiation therapy is a recognized risk factor, but more data about eventual genetic mutations are necessary. Regular screening based only on a history of radiation therapy is not recommended; however, attention must be given in the case of suspicious symptoms.


Assuntos
Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/secundário , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Neoplasias Induzidas por Radiação/etiologia , Radioterapia/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , França , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Doses de Radiação , Fatores de Risco , Fatores Sexuais , Sobreviventes , Adulto Jovem
14.
Int J Radiat Oncol Biol Phys ; 97(2): 278-286, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28068236

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to investigate the role of radiation dose received to the circle of Willis (WC) during radiation therapy (RT) and of potential dose-response modifiers on the risk of stroke after treatment of childhood cancer. METHODS: We evaluated the risk factors for stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median time of 26 years. Radiation doses to the WC and brain structures were estimated for each of the 2202 children who received RT. RESULTS: Fifty-four patients experienced a confirmed stroke; 39 were ischemic. Patients not receiving RT had a stroke risk similar to that of the general population, whereas those who received RT had an 8.5-fold increased risk (95% confidence interval [CI]: 6.3-11.0). The excess of incidence of stroke increased yearly. The dose of radiation to the WC, rather than to other brain structures, was found to be the best predictor of stroke. The relative risk was 15.7 (95% CI: 4.9-50.2) for doses of 40 Gy or more. At 45 years of age, the cumulative stroke incidence was 11.3% (95% CI: 7.1%-17.7%) in patients who received 10 Gy or more to the WC, compared with 1% expected from general population data. Radiation doses received to the heart and neck also increased the risk. Surgery for childhood brain cancer was linked to hemorrhagic strokes in these patients. CONCLUSION: The WC should be considered as a major organ at risk during RT for childhood brain cancers. The incidence of radiation-induced ischemic stroke strongly increases with long-term follow-up.


Assuntos
Círculo Arterial do Cérebro/efeitos da radiação , Órgãos em Risco/efeitos da radiação , Acidente Vascular Cerebral/etiologia , Sobreviventes , Adolescente , Adulto , Fatores Etários , Antineoplásicos/administração & dosagem , Antineoplásicos/classificação , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/radioterapia , Causas de Morte , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Transtornos Cerebrovasculares/etiologia , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , França , Coração/efeitos da radiação , Doença de Hodgkin/radioterapia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Pescoço/efeitos da radiação , Doses de Radiação , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Sobreviventes/estatística & dados numéricos , Fatores de Tempo , Reino Unido
15.
Circulation ; 133(1): 31-8, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26487757

RESUMO

BACKGROUND: Cardiac disease (CD) is one of the major side effects of childhood cancer therapy, but until now little has been known about the relationship between the heart radiation dose (HRD) received during childhood and the risk of CD. METHODS AND RESULTS: The cohort comprised 3162 5-year survivors of childhood cancer. Chemotherapy information was collected and HRD was estimated. There were 347 CDs in 234 patients, 156 of them were rated grade ≥3. Cox and Poisson regression models were used. The cumulative incidence of any type of CD at 40 years of age was 11.0% (95% confidence interval [CI], 9.5-12.7) and 7·4% (95% CI, 6.2-8.9) when only the CDs of grade ≥3 were considered. In comparison with patients who received no anthracycline and either no radiotherapy or an HRD<0·1Gy, the risk was multiplied by 18·4 (95% CI, 7.1-48.0) in patients who had received anthracycline and no radiotherapy or a HRD <0.1Gy, by 60.4 (95% CI, 22.4-163.0) in those who had received no anthracycline and an HRD≥30Gy, and 61.5 (95% CI, 19.6-192.8) in those who had received both anthracycline and an HRD≥30Gy. CONCLUSIONS: Survivors of childhood cancers treated with radiotherapy and anthracycline run a high dose-dependent risk of developing CD. CDs develop earlier in patients treated with anthracycline than in those treated without it.


Assuntos
Antineoplásicos/efeitos adversos , Cardiopatias/etiologia , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Adulto , Antraciclinas/efeitos adversos , Protocolos Antineoplásicos , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/epidemiologia , Humanos , Masculino , Neoplasias/epidemiologia , Fatores de Risco
16.
Int J Radiat Oncol Biol Phys ; 93(3): 658-67, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26461008

RESUMO

PURPOSE: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. METHODS AND MATERIALS: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. RESULTS: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m(2). CONCLUSIONS: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.


Assuntos
Antineoplásicos/efeitos adversos , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Leucemia Induzida por Radiação , Leucemia/induzido quimicamente , Neoplasias/terapia , Adolescente , Análise de Variância , Antineoplásicos Alquilantes/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Humanos , Lactente , Masculino , Segunda Neoplasia Primária/etiologia , Razão de Chances , Compostos de Platina/efeitos adversos , Podofilotoxina/efeitos adversos , Doses de Radiação
17.
J Clin Endocrinol Metab ; 100(11): 4282-90, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26327481

RESUMO

CONTEXT: Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. OBJECTIVE: This study aimed to investigate the role of potential modifiers of the dose response. DESIGN: We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. RESULTS: Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). CONCLUSION: Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.


Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Radioterapia/efeitos adversos , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta à Radiação , Humanos , Incidência , Lactente , Recém-Nascido , Compostos de Nitrosoureia/efeitos adversos , Obesidade/complicações , Obesidade/epidemiologia , Hipófise/efeitos da radiação , Doses de Radiação , Estudos Retrospectivos , Fatores de Risco , Esplenectomia , Glândula Tireoide/efeitos da radiação
18.
Int J Radiat Oncol Biol Phys ; 90(5): 1216-24, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25442047

RESUMO

PURPOSE: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. METHODS AND MATERIALS: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. RESULTS: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D50%) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. CONCLUSIONS: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies.


Assuntos
Medula Óssea/anatomia & histologia , Medula Óssea/efeitos da radiação , Leucemia Induzida por Radiação , Doses de Radiação , Adolescente , Adulto , Fatores Etários , Osso e Ossos/anatomia & histologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Análise por Pareamento , Ilustração Médica , Pessoa de Meia-Idade , Neoplasias/radioterapia , Estudos Retrospectivos , Fatores de Tempo
19.
Radiat Environ Biophys ; 53(2): 381-90, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24419490

RESUMO

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.


Assuntos
Neoplasias Ósseas/etiologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia/efeitos adversos , Sarcoma/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/induzido quimicamente , Neoplasias Ósseas/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Neoplasias Induzidas por Radiação/induzido quimicamente , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/epidemiologia , Dosagem Radioterapêutica , Risco , Sarcoma/induzido quimicamente , Sarcoma/epidemiologia , Sobreviventes , Adulto Jovem
20.
Hum Reprod ; 28(2): 488-95, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23154067

RESUMO

STUDY QUESTION: Is the age at menopause in a cohort of childhood cancer survivors earlier and what are the risk factors associated with earlier age at menopause? SUMMARY ANSWER: Menopause occurred at a median age of 44 years in this cohort which is earlier than in the general population, but premature menopause was uncommon. Main risk factors for non-surgical menopause were exposure to and dose of alkylating agents, especially during adolescence, radiation dose to the ovaries and oophorectomy. WHAT IS KNOWN ALREADY: While survivors of childhood cancer are known to be at increased risk for developing premature menopause, data on its risk factors are limited. STUDY DESIGN: A cohort study of 1109 still-living female survivors of childhood solid cancer treated between 1945 and 1985, of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded. PARTICIPANTS AND METHODS: Seven hundred and six women, among whom 32% have attained 40 years of age, were included in this study. A Cox regression model was used to determine risk factors influencing the age at menopause. MAIN RESULTS: Ninety seven women have reached menopause at a median age of 44 years. Menopause has been surgically induced in 36% of women. In multivariate analysis, risk factors for non-surgical menopause included exposure to alkylating agents, increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide dose and unilateral oophorectomy. The highest risk ratio for non-surgical menopause was observed for women treated after the onset of puberty with alkylating agents, either alone (RR = 9, 95% CI: 2.7-28, P = 0.0003) or associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8-108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature menopause and its main risk factors were age at diagnosis, cyclophosphamide dose, exposure to melphalan and radiation dose to the ovaries. LIMITATIONS: The information on menopause was based on self-reported data without confirmation by FSH levels. Participants to this study have been treated for cancer from 1945 to 1985 and one can expect an increase in premature menopause incidence with more recent protocols using high-dose alkylating agents. WIDER IMPLICATIONS OF THE FINDINGS: This study provides data on risk factors for a reduced fertility window in order to inform survivors at risk and help oncologists to design new therapeutic protocols avoiding this risk. This study does not confirm the high rate of premature menopause reported by the Childhood Cancer Survivor Study, but this population differs from theirs (no leukemia and a lower percentage of lymphoma).


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Menopausa Precoce , Menopausa , Neoplasias/complicações , Radioterapia/efeitos adversos , Sobreviventes , Adulto , Fatores Etários , Antineoplásicos Alquilantes/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Ovário/efeitos da radiação , Ovário/cirurgia , Dosagem Radioterapêutica , Análise de Regressão , Fatores de Risco
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