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2.
Vet Radiol Ultrasound ; 60(5): 586-593, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146304

RESUMO

A total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40 × 40 cm field size, wall-mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source-to-axis distance of 338 cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10 Gy divided into two 5 Gy fractions was delivered approximately 16 h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.


Assuntos
Transplante de Medula Óssea/veterinária , Doenças do Cão/radioterapia , Leucemia/veterinária , Linfoma/veterinária , Fótons , Irradiação Corporal Total/veterinária , Animais , Transplante de Medula Óssea/métodos , Cães , Feminino , Leucemia/radioterapia , Linfoma/radioterapia , Masculino , Estudos Prospectivos , Dosagem Radioterapêutica/veterinária , Irradiação Corporal Total/métodos
3.
Int J Radiat Oncol Biol Phys ; 104(2): 415-424, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30769174

RESUMO

PURPOSE: The association of hyperthyroidism with exposure to ionizing radiation is poorly understood. This study addresses the risk of hyperthyroidism in relation to incidental therapeutic radiation dose to the thyroid and pituitary glands in a large cohort of survivors of childhood cancer. METHODS AND MATERIALS: Using the Childhood Cancer Survivor Study's cohort of 5-year survivors of childhood cancer diagnosed at hospitals in the United States and Canada between 1970 and 1986, the occurrence of hyperthyroidism through 2009 was ascertained among 12,183 survivors who responded to serial questionnaires. Radiation doses to the thyroid and pituitary glands were estimated from radiation therapy records, and chemotherapy exposures were abstracted from medical records. Binary outcome regression was used to estimate prevalence odds ratios (ORs) for hyperthyroidism at 5 years from diagnosis of childhood cancer and Poisson regression to estimate incidence rate ratios (RRs) after the first 5 years. RESULTS: Survivors reported 179 cases of hyperthyroidism, of which 148 were diagnosed 5 or more years after their cancer diagnosis. The cumulative proportion of survivors diagnosed with hyperthyroidism by 30 years after the cancer diagnosis was 2.5% (95% confidence interval [CI], 2.0%-2.9%) among those who received radiation therapy. A linear relation adequately described the thyroid radiation dose response for prevalence of self-reported hyperthyroidism 5 years after cancer diagnosis (excess OR/Gy, 0.24; 95% CI, 0.06-0.95) and incidence rate thereafter (excess RR/Gy, 0.06; 95% CI, 0.03-0.14) over the dose range of 0 to 63 Gy. Neither radiation dose to the pituitary gland nor chemotherapy was associated significantly with hyperthyroidism. Radiation-associated risk remained elevated >25 years after exposure. CONCLUSIONS: Risk of hyperthyroidism after radiation therapy during childhood is positively associated with external radiation dose to the thyroid gland, with radiation-related excess risk persisting for >25 years. Neither radiation dose to the pituitary gland nor chemotherapy exposures were associated with hyperthyroidism among childhood cancer survivors through early adulthood.


Assuntos
Sobreviventes de Câncer , Hipertireoidismo/etiologia , Neoplasias/radioterapia , Glândula Tireoide/efeitos da radiação , Adolescente , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias do Sistema Nervoso Central/radioterapia , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/radioterapia , Humanos , Hipertireoidismo/epidemiologia , Lactente , Recém-Nascido , Leucemia/radioterapia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Hipófise/efeitos da radiação , Prevalência , Fatores de Tempo , Adulto Jovem
4.
Radiat Oncol ; 14(1): 17, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691490

RESUMO

BACKGROUND: Helical irradiation of the total skin (HITS) was modified as simultaneous integrated boost (SIB)-helical arc radiotherapy of total skin (HEARTS) technique and applied to an acute myeloid leukemia (AML) patient with disseminated leukemia cutis. METHODS: The original HITS plan was revised for different regimens, i.e. HEARTS, low-dose HEARTS and SIB-HEARTS. The uniformity index (UI), conformity index (CI), and dose of organs at risk (OARs) were used to evaluate the plans. Additionally, the SIB-HEART (21/15 Gy) was delivered to the total skin and chloromas. RESULTS: No significant differences were observed for the CI and UI between HITS and HEARTS regimens. Compared with HITS, the reduced mean doses to various bone marrows ranged from 17 to 88%. The mean OARs doses for the head, chest and abdomen of a patient with AML treated with SIB-HEARTS (21/15 Gy) were 2.1 to 21.9 Gy, 1.8 to 7.8 Gy and 1.7 to 3.3 Gy, respectively. No severe adverse effects were noted except for grade 4 leukocytopenia and thrombocytopenia. CONCLUSION: HEARTS and different regimens reduced the dose to OARs and bone marrow while maintaining the uniformity and conformity. SIB-HEARTS deliveries different doses to the total skin and enlarged tumors simultaneously. TRIAL REGISTRATION: Retrospectively registered and approved by the Institutional Review Board of our hospital ( FEMH-106151-C ).


Assuntos
Leucemia/radioterapia , Linfoma/radioterapia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Cutâneas/radioterapia , Adulto , Seguimentos , Humanos , Leucemia/patologia , Linfoma/patologia , Masculino , Prognóstico , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Neoplasias Cutâneas/patologia
5.
Int J Radiat Biol ; 95(7): 892-899, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30652952

RESUMO

Studies of the responses of hematopoietic stem and progenitor cells (HSPCs) to low doses of ionizing radiation formed an important aspect of the RISK-IR project ( www.risk-ir.eu ). A brief overview of these studies is presented here. The findings confirm the sensitivity of HSPCs to radiation even at low doses, and illustrate the substantial impact that differentiation state has upon cell sensitivity. The work provides mechanistic support for epidemiological findings of leukemia risk at dose levels used in diagnostic CT imaging, and further suggests that low-dose irradiation may facilitate bone marrow transplantation, a finding that could lead to refinements in clinical practice.


Assuntos
Células-Tronco Hematopoéticas/citologia , Leucemia/etiologia , Leucemia/radioterapia , Doses de Radiação , Radiação Ionizante , Células-Tronco/citologia , Animais , Diferenciação Celular/efeitos da radiação , Células Cultivadas , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Humanos , Camundongos , Neoplasias Induzidas por Radiação , Tolerância a Radiação , Tomografia Computadorizada por Raios X
6.
Int J Radiat Oncol Biol Phys ; 102(2): 314-319, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30191865

RESUMO

Survival times for patients with leukemia generally have improved in recent decades, and this improvement has been attributed to an enhanced understanding of the genetics driving the cause of the disease and improved combinations of chemotherapy and targeted therapy. Durable control of systemic disease in blood and bone marrow has significantly improved survival, but extramedullary relapse can pose therapeutic challenges for which radiation therapy can have an important role. This report discusses the current role of radiation therapy for patients with leukemia, specifically the extramedullary manifestations of leukemia.


Assuntos
Leucemia/radioterapia , Sarcoma Mieloide/radioterapia , Neoplasias Cutâneas/radioterapia , Doença Aguda , Consenso , Humanos , Posicionamento do Paciente/métodos , Guias de Prática Clínica como Assunto , Radioterapia/efeitos adversos , Dosagem Radioterapêutica
8.
Int J Radiat Oncol Biol Phys ; 101(4): 860-874, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29976498

RESUMO

PURPOSE: Our aim was to review the advances in radiation therapy for the management of pediatric cancers made by the Children's Oncology Group (COG) radiation oncology discipline since its inception in 2000. METHODS AND MATERIALS: The various radiation oncology disease site leaders reviewed the contributions and advances in pediatric oncology made through the work of the COG. They have presented outcomes of relevant studies and summarized current treatment policies developed by consensus from experts in the field. RESULTS: The indications and techniques for pediatric radiation therapy have evolved considerably over the years for virtually all pediatric tumor types, resulting in improved cure rates together with the potential for decreased treatment-related morbidity and mortality. CONCLUSIONS: The COG radiation oncology discipline has made significant contributions toward the treatment of childhood cancer. Our discipline is committed to continuing research to refine and modernize the use of radiation therapy in current and future protocols with the goal of further improving the cure rates and quality of life of children with cancer.


Assuntos
Neoplasias/radioterapia , Radioterapia (Especialidade)/organização & administração , Neoplasias Ósseas/radioterapia , Neoplasias do Sistema Nervoso Central/radioterapia , Criança , Doença de Hodgkin/radioterapia , Humanos , Cooperação Internacional , Neoplasias Renais/radioterapia , Leucemia/radioterapia , Neuroblastoma/radioterapia , Terapia com Prótons , Radioterapia (Especialidade)/educação , Radioterapia (Especialidade)/tendências , Doenças Raras/radioterapia , Sarcoma/radioterapia , Sarcoma de Ewing/radioterapia , Fatores de Tempo
9.
Tidsskr Nor Laegeforen ; 138(11)2018 06 26.
Artigo em Inglês, No | MEDLINE | ID: mdl-29947203

RESUMO

BAKGRUNN: Kryopreservering av ovarialvev som fertilitetsbevarende metode tilbys prepubertale jenter og kvinner i reproduktiv alder med høy risiko for å utvikle prematur ovarialsvikt i forbindelse med medisinsk eller kirurgisk behandling. I denne studien ønsket vi å kartlegge fertilitet og prematur ovarialsvikt hos kvinner som har fått gjort kryopreservering av ovarialvev i forbindelse med kreftbehandling. MATERIALE OG METODE: Et spørreskjema ble i 2014 sendt til 94 kvinner over 18 år som i perioden 2004-12 hadde fått kryopreservert ovarialvev i forbindelse med behandling for en malign tilstand. Skjemaet inneholdt spørsmål om menstruasjonsfrekvens, prevensjonsbruk, fertilitet, fremtidig barneønske og sannsynlighet for at de ville benytte ovarialvevet senere. Av de 77 kvinnene som returnerte spørreskjemaet, ble 74 kvinner inkludert i studien. RESULTATER: Totalt 20 av 74 kvinner (27 %) hadde prematur ovarialsvikt definert som opphør av ovarialfunksjonen før 40 års alder. Risikoen var lavest hos kvinner behandlet for brystkreft (5 %) og høyest hos kvinner behandlet for leukemi (75 %). Størst risiko for prematur ovarialsvikt fant man i pasientgruppene som hadde gjennomgått stamcelletransplantasjon, strålebehandling mot helkropp og/eller abdomen og bekken. Til sammen hadde 22 kvinner født 31 barn etter kreftbehandlingen, hvorav to etter reimplantasjon av ovarialvev. FORTOLKNING: Risikoen for å utvikle prematur ovarialsvikt er avhengig av pasientens kreftdiagnose. Hvilke fertilitetsbevarende tiltak som anbefales, bør differensieres avhengig av pasienten kreftdiagnose og planlagt behandling.


Assuntos
Antineoplásicos/efeitos adversos , Criopreservação , Preservação da Fertilidade , Fertilidade , Ovário , Insuficiência Ovariana Primária/etiologia , Radioterapia/efeitos adversos , Transplante de Células-Tronco/efeitos adversos , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Feminino , Humanos , Leucemia/radioterapia , Leucemia/terapia , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Linfoma/terapia , Gravidez , Fatores de Risco , Sarcoma/radioterapia , Sarcoma/terapia , Inquéritos e Questionários , Adulto Jovem
10.
Int J Cardiovasc Imaging ; 34(9): 1373-1381, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29611048

RESUMO

Heart disease is the leading cause of non-cancer death in childhood cancer survivors. to determine the prevalence of subclinical cardiac dysfunction using speckle tracking and compare its results with those obtained by classical methods of assessing left ventricular function and its relationship with different factors to identify the population at higher risk. Echocardiographic assessment of left ventricular function included ejection fraction, tissue Doppler, longitudinal/circumferential strains and biochemical parameters (troponin-T and Pro-BNP) in a cohort of 57 survivors of childhood acute leukaemia with at least 10 years since diagnosis. Ventricular dysfunction was found in 5.2% of patients in M-mode (ejection fraction-EF < 53% with a reduction in the EF ≥ 10%) and in 7% of patients with Simpson's method, compared with 21.05 and 8.8% with suboptimal global longitudinal strain (GLS) and global circumferential strain, respectively. The GLS alteration was significantly correlated with lower values of left ventricular systolic function and was associated with high tumour risk (odds ratio [OR] 13.8), cumulative doses of anthracyclines ≥ 250 mg/m2 (OR 7.6) and radiotherapy (OR 7.19). Biomarkers were not useful for the diagnosis of subclinical cardiomyopathy. Good reproducibility was obtained, with an intraobserver correlation of 93.6% and an interobserver correlation of 89.2% in the GLS. The alteration of the GLS was more prevalent than the alteration in the EF and was associated with the treatment received and high tumour risk. strain imaging seems to be a powerful tool to identify an increased number of survivor with an early myocardial injury.


Assuntos
Ecocardiografia/métodos , Leucemia/tratamento farmacológico , Leucemia/radioterapia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adolescente , Adulto , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Antineoplásicos/efeitos adversos , Criança , Estudos Transversais , Feminino , Humanos , Leucemia/complicações , Masculino , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
11.
Am J Clin Nutr ; 107(1): 3-11, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29381792

RESUMO

Background: An increased risk of becoming overweight has been reported for childhood cancer survivors (CCSs), in particular leukemia survivors, although the evidence is inconclusive. Objective: We assessed the prevalence of overweight in CCSs, with a focus on leukemia survivors, compared it with their peers, and determined potential risk factors. Design: As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire between 2007 and 2013 to all Swiss resident CCSs aged <21 y at diagnosis who had survived ≥5 y. We calculated body mass index (BMI) from medical records at diagnosis and self-reported heights and weights at survey. We calculated BMI z scores by using Swiss references for children and compared overweight prevalence in CCSs, their siblings, and the general population with the use of the Swiss Health Survey (SHS) and assessed risk factors for being overweight by using multivariable logistic regression. Results: The study included 2365 CCSs, 819 siblings, and 9591 SHS participants. At survey, at an average of 15 y after diagnosis, the prevalence of overweight in CCSs overall (26%) and in leukemia survivors (26%) was similar to that in siblings (22%) and the general population (25%). Risk factors for being overweight in CCSs were male sex (OR: 1.8; 95% CI: 1.5, 2.1), both young (OR for ages 5-14 y: 1.6; 95% CI: 1.2, 2.3) and older (range-OR for ages 25-29 y: 1.7; 95% CI: 1.2, 2.4; OR for ages 40-45 y: 4.0; 95% CI: 2.5, 6.5) age at study, lower education (OR: 1.4; 95% CI: 1.1, 1.8), migration background (OR: 1.3; 95% CI: 1.1, 1.7), and no sports participation (OR: 1.4; 95% CI: 1.1, 1.7). Risk factors for overweight were similar in peers. CCSs treated with cranial radiotherapy (≥20 Gy) were more likely to be overweight than their peers (OR: 1.6; 95% CI: 1.2, 2.2). Conclusions: The prevalence of and risk factors for being overweight are similar in long-term CCSs and their peers. This suggests that prevention methods can be the same as in the general population. An important exception is CCSs treated with cranial radiotherapy ≥20 Gy who may need extra attention during follow-up care. This study was registered at clinicaltrials.gov as NCT03297034.


Assuntos
Sobreviventes de Câncer , Sobrepeso/epidemiologia , Adolescente , Adulto , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Leucemia/diagnóstico , Leucemia/radioterapia , Modelos Logísticos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Suíça/epidemiologia , Adulto Jovem
12.
Leuk Lymphoma ; 59(2): 381-397, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28728448

RESUMO

As long-term survival is high for children and young adults diagnosed with leukemia and lymphoma, delineating maternal, fetal and offspring health risks is important to their family planning. This systematic review examined data comparing these health risks between leukemia and lymphoma survivors and women without a history of cancer. Following a search of Embase, PubMed, CINAHL, Cochrane, and Web of Science, 142 articles were screened and 18 were included in this review. No higher risks of spontaneous abortion, maternal diabetes and anemia, stillbirth, birth defects, or childhood cancer in offspring were observed in survivors compared to controls. Important to counseling and clinical care, live birth rates were lower, while preterm birth and low birth weight risks were modestly higher in survivors compared to controls. Findings were largely reassuring but highlight the lack of data on maternal cardiopulmonary risks, differential risk by cancer treatment type, and interventions to decrease these risks.


Assuntos
Sobreviventes de Câncer , Saúde da Criança , Leucemia/epidemiologia , Linfoma/epidemiologia , Adolescente , Criança , Comorbidade , Feminino , Humanos , Recém-Nascido , Leucemia/tratamento farmacológico , Leucemia/radioterapia , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Gravidez , Resultado da Gravidez , Adulto Jovem
13.
J Natl Cancer Inst ; 109(11)2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29059430

RESUMO

Background: Childhood cancer survivors treated with chest-directed radiotherapy have substantially elevated risk for developing breast cancer. Although genetic susceptibility to breast cancer in the general population is well studied, large-scale evaluation of breast cancer susceptibility after chest-directed radiotherapy for childhood cancer is lacking. Methods: We conducted a genome-wide association study of breast cancer in female survivors of childhood cancer, pooling two cohorts with detailed treatment data and systematic, long-term follow-up: the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. The study population comprised 207 survivors who developed breast cancer and 2774 who had not developed any subsequent neoplasm as of last follow-up. Genotyping and subsequent imputation yielded 16 958 466 high-quality variants for analysis. We tested associations in the overall population and in subgroups stratified by receipt of lower than 10 and 10 or higher gray breast radiation exposure. We report P values and pooled per-allele risk estimates from Cox proportional hazards regression models. All statistical tests were two-sided. Results: Among survivors who received 10 or higher gray breast radiation exposure, a locus on 1q41 was associated with subsequent breast cancer risk (rs4342822, nearest gene PROX1 , risk allele frequency in control subjects [RAF controls ] = 0.46, hazard ratio = 1.92, 95% confidence interval = 1.49 to 2.44, P = 7.09 × 10 -9 ). Two rare variants also showed potentially promising associations (breast radiation ≥10 gray: rs74949440, 11q23, TAGLN , RAF controls = 0.02, P = 5.84 × 10 -8 ; <10 gray: rs17020562, 1q32.3, RPS6KC1 , RAF controls = 0.0005, P = 6.68 × 10 -8 ). Associations were restricted to these dose subgroups, with consistent findings in the two survivor cohorts. Conclusions: Our study provides strong evidence that germline genetics outside high-risk syndromes could modify the effect of radiation exposure on breast cancer risk after childhood cancer.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas de Homeodomínio/genética , Proteínas dos Microfilamentos/genética , Proteínas Musculares/genética , Neoplasias Induzidas por Radiação/genética , Segunda Neoplasia Primária/genética , Proteínas Quinases S6 Ribossômicas/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Mama/efeitos da radiação , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença de Hodgkin/radioterapia , Humanos , Lactente , Leucemia/radioterapia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Estudos Retrospectivos , Sobreviventes , Adulto Jovem , Quinases raf/genética
14.
Nat Commun ; 8(1): 186, 2017 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-28775249

RESUMO

Cranial radiotherapy improves survival of the most common childhood cancers, including brain tumors and leukemia. Unfortunately, long-term survivors are faced with consequences of secondary neoplasia, including radiation-induced meningiomas (RIMs). We characterized 31 RIMs with exome/NF2 intronic sequencing, RNA sequencing and methylation profiling, and found NF2 gene rearrangements in 12/31 of RIMs, an observation previously unreported in sporadic meningioma (SM). Additionally, known recurrent mutations characteristic of SM, including AKT1, KLF4, TRAF7 and SMO, were not observed in RIMs. Combined losses of chromosomes 1p and 22q were common in RIMs (16/18 cases) and overall, chromosomal aberrations were more complex than that observed in SM. Patterns of DNA methylation profiling supported similar cell of origin between RIMs and SMs. The findings indicate that the mutational landscape of RIMs is distinct from SMs, and have significant therapeutic implications for survivors of childhood cranial radiation and the elucidation of the molecular pathogenesis of meningiomas.Radiation-induced meningiomas are often more aggressive than sporadic ones. In this study, the authors perform an exome, methylation and RNA-seq analysis of 31 cases of radiation-induced meningioma and show NF2 rearrangement, an observation previously unreported in the sporadic tumors.


Assuntos
Irradiação Craniana/efeitos adversos , Rearranjo Gênico/genética , Genes da Neurofibromatose 2 , Neoplasias Meníngeas/genética , Meningioma/genética , Neoplasias Induzidas por Radiação/genética , Adulto , Idoso , Sobreviventes de Câncer , Estudos de Casos e Controles , Neoplasias Cerebelares/radioterapia , Metilação de DNA , Feminino , Humanos , Leucemia/radioterapia , Masculino , Meduloblastoma/radioterapia , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Pessoa de Meia-Idade , Mutação , Neoplasias Induzidas por Radiação/etiologia , Análise de Sequência de DNA , Análise de Sequência de RNA , Adulto Jovem
15.
Pract Radiat Oncol ; 7(6): e401-e408, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28666906

RESUMO

PURPOSE/OBJECTIVE(S): Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT. METHODS AND MATERIALS: We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed. RESULTS: Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic leukemia (22%), chronic lymphocytic leukemia (3%), chronic myelocytic leukemia (14%), lymphoma (11%), and myeloma (3%). CSI was used for consolidation (30 patients, 81%) and gross disease treatment (7 patients, 19%). Median radiation dose (interquartile range) was 24 Gy (23.4-24) for photons and 21.8 Gy (21.3-23.6) for protons (P = .03). Proton CSI was associated with lower rates of Radiation Therapy Oncology Group grade 1-3 mucositis during CSI (7% vs 44%, P = .03): 1 grade 3 with protons versus 5 grade 1, 3 grade 2, and 2 grade 3 with photons. During CSI, other toxicities (infection, gastrointestinal symptoms) did not differ. Allogeneic stem cell transplant (SCT) was used in 95% of patients, with 53% of patients in remission before SCT. Myeloablative conditioning was used for 76%. During SCT admission and 100 days post-SCT, toxicities did not differ by CSI technique. Successful engraftment occurred in 95% of patients (P = .67). Progression or death occurred for 47% of patients, with only 1 CNS relapse. CONCLUSION: In our cohort, CSI offered excellent local control for CNS-involved hematologic malignancies in the pre-SCT setting. Acute mucositis occurred less frequently with proton CSI with comparable peritransplant/long-term toxicity profile, suggesting the need to further explore the benefit/toxicity profile of this technique.


Assuntos
Neoplasias do Sistema Nervoso Central/radioterapia , Radiação Cranioespinal/efeitos adversos , Radiação Cranioespinal/métodos , Leucemia/radioterapia , Linfoma/radioterapia , Adulto , Neoplasias do Sistema Nervoso Central/mortalidade , Feminino , Humanos , Leucemia/mortalidade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/radioterapia , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Fótons , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prótons , Estudos Retrospectivos , Transplante de Células-Tronco , Resultado do Tratamento
16.
Cancer Discov ; 7(7): OF2, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28559402

RESUMO

A new study in mice demonstrates that activating the RIG-I and STING signaling pathways, normally associated with antiviral immunity, can help protect the intestinal epithelium from damage caused by chemotherapy and radiation following stem cell transplantation. The findings may help in developing strategies to prevent graft-versus-host disease in patients with leukemia and other blood disorders.


Assuntos
Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas , Mucosa Intestinal/metabolismo , Leucemia/genética , Animais , Proteína DEAD-box 58/genética , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Leucemia/complicações , Leucemia/tratamento farmacológico , Leucemia/radioterapia , Proteínas de Membrana/genética , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/efeitos da radiação
17.
Rev. cuba. hematol. inmunol. hemoter ; 33(2): 1-14, abr.-jun. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-901083

RESUMO

Leukemia is a group of clonal diseases derived from a single cell with a genetic alteration in bone marrow or peripheral lymphoid tissue, and each type is determined by the specificity of the source cell. The objective of this research was to synthesize studies that characterize the clinical and epidemiological profile of patients with leukemia, the types of treatments used, duration and outcomes for the cases. This study is an integrative review of literature through databases Medical Literature Analysis and Retrieval System Online (MEDLINE), SCOPUS, Cumulative Index to Nursing & Allied Health Literature (CINAHL) and Science Direct. There were 4,274 articles rescued in the initial search, 188 were selected to compose the review sample after applying all the criteria for inclusion and exclusion adopted. Full articles were grouped into four categories, according to the variables of research: (a) more frequent subtypes of leukemia; (b) most widely used treatment; (c) duration of treatment; and (d) endpoint of the cases. It is concluded a prevalence of leukemia in pediatric patients, with a predominance of the subtype Acute Lymphoblastic Leukemia (ALL). In general, the male population is more affected by hematological malignancies. As the therapy is used, each leukemia subtype had its peculiarities regarding the treatment, especially the introduction of imatinib for chronic myeloid leukemia (CML) and prophylactic cranial irradiation for cases of ALL. Chronic leukemia showed higher treatment duration. There was a significant improvement in survival of Acute Myeloid Leukemia, Chronic Lymphoid leukemia, CML and ALL, the latter approximately with 90% cure rate in children.


La leucemia es un grupo de enfermedades clonales derivadas de una única célula con una alteración genética en la médula ósea o tejido linfoide periférico, y cada tipo se determina por la especificidad de la célula de origen. El objetivo de esta investigación fue sintetizar los estudios que caracterizan el perfil clínico y epidemiológico de los pacientes con leucemia, los tipos de tratamientos usados, la duración y los resultados para los casos. Este estudio es una revisión integradora de la literatura a través de bases de datos de análisis médicos, literatura y recuperación de sistema en línea (MEDLINE), SCOPUS, Cumulative Index de Enfermería y Salud Aliada Literatura (CINAHL) y Science Direct. Había 4 274 artículos rescatados en la búsqueda inicial, se seleccionaron 188 para componer la muestra de revisión después de aplicar todos los criterios de inclusión y exclusión adoptada. Los artículos completos se agruparon en cuatro categorías, según las variables de investigación: (a) los subtipos más frecuentes de leucemia; (b) el tratamiento más utilizado; (c) la duración del tratamiento; y (d) el punto final de los casos. Se concluye una prevalencia de leucemia en pacientes pediátricos, con predominio del subtipo de leucemia linfoblástica aguda (LLA). En general, la población masculina se ve más afectada por neoplasias hematológicas. Como se utiliza la terapia, cada subtipo de leucemia tenía sus peculiaridades con respecto al tratamiento, especialmente la introducción de imatinib para la leucemia mieloide crónica (CML) y la irradiación craneal profiláctica para los casos de ALL. La leucemia crónica mostró una mayor duración del tratamiento. Hubo una mejora significativa en la supervivencia de la leucemia mieloide aguda, leucemia linfoide crónica, LMC y LLA, aproximadamente, este último con la tasa de curación del 90% en los niños.


Assuntos
Humanos , Diagnóstico Clínico , Neoplasias Hematológicas/epidemiologia , Leucemia/epidemiologia , Leucemia/radioterapia
18.
Curr Neurol Neurosci Rep ; 17(2): 13, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28229399

RESUMO

PURPOSE OF REVIEW: Acute and chronic leukemias are heterogeneous diseases and can affect any part of the body upon initial discovery. Understanding the sequela of systemic involvement is key for proper diagnosis and treatment. RECENT FINDINGS: Over the decades, new research has emerged regarding neurological complications of the myeloid or lymphoid leukemias. Central nervous system involvement usually confers a poor prognosis and requires emergent treatment. Standard of care still involves systemic therapy, intrathecal administration of chemotherapeutic agents, and cranial radiation. Treatment-related side effects can occur and need to be recognized by any practitioner involved with patient care. It is imperative to understand neurologic complications from leukemia to prevent delays and initiate necessary treatment to maintain neurologic and cognitive function.


Assuntos
Leucemia/complicações , Doenças do Sistema Nervoso/complicações , Antineoplásicos/efeitos adversos , Tratamento Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Leucemia/diagnóstico , Leucemia/tratamento farmacológico , Leucemia/radioterapia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/radioterapia
19.
J Cancer Res Clin Oncol ; 143(5): 851-859, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28093639

RESUMO

BACKGROUND: Leukemia cutis (LC) is a rare clinical presentation of leukemia that is associated with poor prognosisabs. To date, the value of radiotherapy (RT) for the treatment of LC remains controversial. Therefore, the aim of this study was to analyse the effectiveness of various RT doses for LC. METHODS AND MATERIALS: Between January 2000 and January 2016, 13 patients underwent RT at our institution after exhibiting progressive disease following other treatment modalities. RESULTS: A total of 36 radiation courses were administered to 13 patients (8 females, 5 males) with a median age of 41 years (range 2-76). Radiation modalities included 32 focal treatments, while total skin electron beam therapy was applied to four patients. The median RT dose was 27 Gy (range 8-34). A complete response rate (CRR) to RT was achieved for 32/36 (89%) lesions (100% for AML lesions versus 33% for the other leukemias; P < 0.001). The median duration of local control (DOLC) for the entire cohort was 38 months (range 0-98), while the median survival (MS) from the time of LC presentation was 13 months (range 2.5-106). The CRR for the LC lesions treated with high-dose regimens (>26 Gy) versus low-dose regimens (≤26 Gy) was 95 versus 83%, respectively (P = 0.26), and the median DOLC was 44 months versus 10 months, respectively (P = 0.019). AML patients had a better long-term outcome than the other patients according to median DOLC (40 months versus 2 months, respectively; P < 0.001) and MS (24 versus 6 months, P = 0.004). RT was well tolerated without significant adverse events. CONCLUSION: A radiation dose ≤26 Gy confer a comparable CRR to high-dose regimens and appears to be an effective treatment for controlling LC progression. However, radiation doses >26 Gy were associated with a longer DOLC. LC patients with underlying AML are associated with better outcome compared with other types of leukemia.


Assuntos
Leucemia/radioterapia , Infiltração Leucêmica/radioterapia , Neoplasias Cutâneas/radioterapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Leucemia/diagnóstico por imagem , Leucemia/patologia , Infiltração Leucêmica/diagnóstico por imagem , Infiltração Leucêmica/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Adulto Jovem
20.
Cochrane Database Syst Rev ; 1: CD011305, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-28128441

RESUMO

BACKGROUND: Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies. OBJECTIVES: To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS: We searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status. SELECTION CRITERIA: We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow-up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L.Based on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all 'Risk of bias' domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno-occlusive disease (VOD). Evidence from RCTsA restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low-quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low-quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low-quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low-quality evidence).We are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal median 4.5 (IQR 3.6 to 5) (very low-quality evidence); or reduces the risk of developing any serious infection (one study, 89 participants, RR: 1.23, 95% CI 0.74 to 2.04, very low-quality evidence).A restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials; 95 participants; mean difference (MD) -3.58, 95% CI -5.66 to -1.49, low-quality evidence). Evidence from NRSWe are uncertain whether the restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-quality evidence); decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-quality evidence); or decreases the number of RBC transfusions (adjusted for age, sex and acute myeloid leukaemia type geometric mean 1.25; 95% CI 1.07 to 1.47 - data analysis performed by the study authors)No NRS were found that looked at: quality of life; number of participants with any bleeding; serious infection; or length of hospital stay.No studies were found that looked at: adverse transfusion reactions; arterial or venous thromboembolic events; length of intensive care admission; or readmission to hospital. AUTHORS' CONCLUSIONS: Findings from this review were based on four studies and 240 participants.There is low-quality evidence that a restrictive RBC transfusion policy reduces the number of RBC transfusions per participant. There is low-quality evidence that a restrictive RBC transfusion policy has little or no effect on: mortality at 30 to 100 days, bleeding, or hospital stay. This evidence is mainly based on adults with acute leukaemia who are having chemotherapy. Although, the two ongoing studies (530 participants) are due to be completed by January 2018 and will provide additional information for adults with haematological malignancies, we will not be able to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days we would need 1492 participants to have a 80% chance of detecting, as significant at the 5% level, an increase in all-cause mortality from 3% to 6%. Further RCTs are required in children.


Assuntos
Anemia/terapia , Transfusão de Eritrócitos/métodos , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/radioterapia , Doença Aguda , Adulto , Anemia/sangue , Anemia/etiologia , Criança , Transfusão de Eritrócitos/efeitos adversos , Neoplasias Hematológicas/sangue , Transplante de Células-Tronco Hematopoéticas , Hemoglobina A/análise , Humanos , Leucemia/sangue , Leucemia/tratamento farmacológico , Leucemia/radioterapia , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
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