Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis.@*METHODS@#The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed.@*RESULTS@#The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×109/L, including 15 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 7 cases >100×109/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×109/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×109/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 5 cases >100×109/L. In the 5 children with leukocyte count >100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×109/L and 100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×109/L and 50×109/L, 1 case between 50×109/L and 100×109/L, and 5 cases >100×109/L.@*CONCLUSION@#High-risk APL children with leukocyte count >100×109/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.

Cáncer de mama triple negativo: otra enfermedad y nuevo reto / Triple negative breast cancer: another disease and a new challenge

El cáncer de mama Triple Negativo es un subtipo molecular que se caracteriza por ausencia de expresión de receptores de estrógeno, progesterona y proteína HER2. Representa el 10 % a 15 % de todos los subtipos de cáncer de mama con impacto en el pronóstico y en las líneas de tratamiento; siendo negativo para receptores hormonales y HER2, la terapéutica hormonal y anti-HER2 no cuentan para su manejo. Aún no se dispone de productos dirigidos a blancos específicos para esta categoría.(AU)

The Triple Negative breast cancer is a molecular subtype characterized by no expression of the estrogen, the progesterone and the HER2 protein receptors. They represents 10 % to 15 % of all the breast cancer subtypes with an impact on the prognosis and in the treatment lines; is negative for the hormone receptors and for the HER2, hormonal and the anti-HER2 therapeutics do not count for the management of them. The products targeting specific to this category are not yet available(AU)

Disfunção diastólica precoce em pacientes com câncer de mama submetidas à quimioterapia / Early diastolic dysfunction in breast cancer patients undergoing chemotherapy

Fundamento: A quimioterapia para o câncer de mama está associada a complicações cardiovasculares graves, como a insuficiência cardíaca. A fração de ejeção do ventrículo esquerdo é o principal parâmetro para avaliar a função sistólica nessas pacientes. Todavia, a ocorrência de disfunção diastólica pode preceder à disfunção sistólica. Objetivos: Avaliar as funções diastólica e sistólica do ventrículo esquerdo de portadoras de câncer de mama em tratamento quimioterápico com antraciclinas. Métodos: Trata-se de estudo observacional, longitudinal, analítico e prospectivo. Estudaram-se 62 mulheres com câncer de mama, com idades de 21 a 75 anos, que realizaram ecocardiogramas basais e após 3 meses de tratamento. Avaliaram-se parâmetros de função diastólica, e as pacientes foram classificadas em disfunção diastólica tipos:1, 2 ou 3. Definiu-se a disfunção sistólica como fração de ejeção do ventrículo esquerdo ≤ 53%. Resultados: Decorridos 3 meses de tratamento, 35 pacientes (56,4%) apresentavam disfunção diastólica tipo 1, e apenas uma (1,6%) do tipo 2. A disfunção diastólica ocorreu em 26 pacientes já na etapa basal e surgiu em dez indivíduos no decurso do tratamento. Os parâmetros de função diastólica velocidade de onda E e relação E/A diminuíram significativamente (p < 0,05) com a quimioterapia, todavia, os demais não tiveram variação significativa. Apenas três pacientes apresentaram disfunção sistólica, porém verificou-se maior redução da fração de ejeção do ventrículo esquerdo no grupo que desenvolveu disfunção diastólica durante o tratamento comparativamente ao grupo que apresentava já disfunção diastólica no período basal (p = 0,04). Conclusão: A disfunção diastólica ocorre precocemente em portadoras de câncer de mama submetidas à quimioterapia. O surgimento de disfunção diastólica no decurso do tratamento se associa à redução significativa da fração de ejeção do ventrículo esquerdo. (AU)

Background: Chemotherapy for breast cancer is associated with serious cardiovascular complications such as heart failure. The left ventricular ejection fraction is the main parameter used to assess systolic function in these patients. However, the occurrence of diastolic dysfunction may precede that of systolic dysfunction. Objectives: To evaluate left ventricle diastolic and systolic functions in women with breast cancer undergoing chemotherapy using anthracyclines. Methods: This observational, longitudinal, analytical, and prospective study included 62 women with breast cancer aged 21­75 years old who underwent echocardiography at baseline and after three months of treatment. Diastolic function parameters were evaluated, and the patients were classified as diastolic dysfunction type 1, 2, or 3. Systolic dysfunction was defined as a left ventricular ejection fraction ≤ 53%. Results: After three months of treatment, 35 patients (56.4%) had type 1 diastolic dysfunction, while one (1.6%) had type 2. Diastolic dysfunction was identified in 26 patients at baseline and developed in 10 patients during treatment. Diastolic function parameters, E wave velocity, and E/A ratio decreased significantly (p < 0.05) with chemotherapy; however, the others showed no significant variations. Only three patients had systolic dysfunction, but there was a greater reduction in left ventricular ejection fraction in the group that developed diastolic dysfunction during treatment versus the group with diastolic dysfunction at baseline (p = 0.04). Conclusion: Diastolic dysfunction occurs early in women with breast cancer undergoing chemotherapy. Its onset during the course of treatment is associated with a significantly reduced left ventricular ejection fraction. (AU)

Current treatment preferences in acute myeloid leukemia: a survey in Brazil

ABSTRACT Introduction:: Most adults with acute myeloid leukemia (AML) will eventually relapse from their disease. The combination of 7-day cytarabine and an anthracycline on days 1-3 (the so called "7 + 3" regimen) can be considered standard of care of younger patients with AML. However, the treatment of the elderly ineligible for intensive chemotherapy remains a challenge. Low-dose of subcutaneous cytarabine or hypomethylating agents (HMA) have been studied this group. There are no studies investigating physician practice variation in treating AML in Brazil. Methods:: We developed a survey with ten questions in order to explore the approach to AML in Brazil. Results:: The sample size comprised 100 hematologists. Most reported regular (63%) or occasional (29%) treatment of AML patients. Karyotype analysis and polymerase chain reaction were available in 88% and 71% of institutions, respectively. Next generation sequencing analysis was used in 7% of instituitions. Younger patients receive the "7 + 3" protocol with continuous infusion of cytarabine and anthracycline in 98% of cases. The preferred anthracycline is daunorubicin (64%), followed by idarubicin (34%). The most prescribed daunorubicin dose was 60 mg/m2 (56%). Consolidation after CR with high cytarabine doses (HIDAC) was indicated by 84% of hematologists and 70% use 3 g/m2 twice a day for 3 days. Elderly and unfit patients received HMA (47%) as the preferred treatment. Conclusion:: We showed that the most prevalent AML treatments were according to current guidelines. There is room to improve on the availability of diagnostic tools and the capacity to perform bone marrow transplantation.

Supervivencia de pacientes adultos con leucemia mieloide aguda no promielocítica tratados con altas dosis de antraciclinas / Survival of adult patients with non-promyelocytic acute myeloid leukemia treated with high doses of anthracyclines

Introducción: La leucemia mieloide aguda es una enfermedad heterogénea caracterizada por la expansión clonal de precursores indiferenciados que provoca un fallo medular. Objetivo: Analizar la supervivencia de los pacientes adultos con leucemia mieloide aguda no promielocítica tratados con altas dosis de antraciclinas en la inducción. Métodos: Se realizó un estudio analítico, retrospectivo y longitudinal en 53 pacientes adultos menores de 60 años, tratados en el Instituto de Hematología e Inmunología, desde septiembre de 2013 hasta diciembre de 2018. Estos pacientes tenían diagnóstico de leucemia mieloide aguda no promielocítica y recibieron altas dosis de antraciclinas (daunorribicina) en el tratamiento de inducción. Resultados: Las probabilidades de supervivencia global a los 12 meses fue mayor para el grupo de 19 a 29 años con 59 por ciento y más baja para el de 40 a 49 años con 21 por ciento. En cuanto a la probabilidad de supervivencia libre de evento fue de 65 por ciento. Esta resultó mayor para los pacientes de los grupos de 19 a 29 años y de 30 a 39 años con 39 por ciento y 40 por ciento, respectivamente. En el grupo de 40-49 años disminuyó hasta 20 por ciento. En relación con la supervivencia global relacionada con los genes reordenados fue mayor para los pacientes que tenían los genes NPM1 y AML1-ETO y menor para los que tenían los genes FLT3 y BCR/ABL. Conclusiones: Los grupos de edades y las alteraciones genéticas no modifican la supervivencia de los pacientes con leucemias mieloide aguda no promielocítica tratados con dosis altas de antraciclinas(AU)

Introduction: Acute myeloid leukemia is a heterogeneous disease characterized by the clonal expansion of undifferentiated precursors that causes bone marrow failure. Objective: To analyze the survival of adult patients with non-promyelocytic acute myeloid leukemia treated with high doses of induced anthracyclines at induction. Methods: An analytical, retrospective and longitudinal study was carried out with 53 adult patients younger than 60 years, treated at the Institute of Hematology and Immunology, from September 2013 to December 2018. These patients had a diagnosis of non-promyelocytic acute myeloid leukemia and received high doses of anthracyclines (daunoribicin) under induction therapy. Results: The probabilities of overall survival at 12 months were higher for the group of 19- 29 years, accounting for 59%, and lower for the group of 40-49 years, accounting for 21 percent. In the age group of 19-29 years, the probability of event-free survival was 65 percent and the probability of disease-free survival was 44 percent. In the group of 40-49 years, it decreased to 27 percent; while in the group of 50-59 it increased, reaching 80 percent. Regarding overall survival associated with the rearranged genes, it was higher for the patients who had the NPM1 and AML1-ETO genes and lower for those who had the FLT3 and BCR/ABL genes. Conclusions: Age groups and genetic alterations do not modify the survival of patients with non-promyelocytic acute myeloid leukemias treated with high doses of anthracyclines(AU)

Cáncer de mama y su respuesta al tratamiento neoadyuvante según subtipo molecular / Breast cancer and its response to neoadjuvant treatment according to molecular subtipe

El cáncer de mama es una de las patologías más frecuentes a nivel mundial y en el Ecuador ocupa un sitio importante dentro de la mortalidad; en pacientes con tumores de estadios avanzados la quimioterapia neodyuvante es el procedimiento indicado para lograr una reducción tumoral satisfactoria. El objetivo fue determinar la respuesta clínica y patológica en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante según cada subtipo molecular, atendidos en el hospital "Teodoro Maldonado Carbo" en el período 2015 a 2017. Se hizo uso de un diseño no experimental, transversal de tipo correlacional. Pacientes con cáncer de mama que recibieron neoadyuvancia, en su mayoría con quimioterapia basada en antraciclinas y taxanos. Se clasificó a las pacientes por sus subtipos moleculares, los mismos se obtuvieron en base a las características inmunohistoquímicas de los reportes de patología que constan en el sistema AS-400. Se comprobó la respuesta clínica al tratamiento usando los Criterios RECIST 1.1. Como resultado los 171 pacientes fueron analizados. La edad promedio de las pacientes fue 55 13 años de edad; el 25% fueron luminal B (HER+), 24% luminal B (HER-), 22% triple negativo, 18% HER2+ y 12% luminal A; el 52% de las pacientes tuvieron estadio III de la enfermedad; el 75% (129) de las pacientes fue realizada una mastectomía radical modificada. Se pudo concluir que la respuesta patológica completa en pacientes con tratamiento neoadyuvante se relaciona con los subtipos moleculares y esto es estadísticamente significativo. Además, se evidenció las mayores tasas de respuesta patológica completa en los grupos moleculares de HER2+ y triple negativo.

Breast cancer is one of the most frequent pathologies worldwide and in Ecuador it occupies an important place in mortality. In patients with advanced stage tumors, the neo-adjuvant chemotherapy is the indicated procedure to achieve a satisfactory tumor reduction. The aim was to determine the clinical and pathological response in patients with breast cancer treated with neoadjuvant chemotherapy according to each molecular subtype, treated at the "Teodoro Maldonado Carbo" hospital in the period 2015 to 2017. We used a non-experimental, crosssectional type design. Patients with breast cancer who received neoadjuvant, mostly with chemotherapy based on anthracyclines and taxanes. The patients were classified by their molecular subtypes, they were obtained based on the immunohistochemical characteristics of the pathology reports that appear in the AS-400 system. The clinical response to treatment was checked using the RECIST 1.1 Criteria. As a result, a sum of 171 patients were analyzed. The average age of the patients was 55 + 13 years old; 25% were luminal B (Her +), 24% luminal B (Her-), 22% triple negative, 18% Her2 + and 12% luminal A; 52% of the patients had stage III of the disease; 75% (129) of the patients underwent a modified radical mastectomy. As a conclusion, the complete pathological response in patients with neoadjuvant treatment is related to molecular subtypes and this is statistically significant. Also, the highest rates of complete pathological response in the molecular groups of Her2 + and triple negative were evident.

Incorporación de las altas dosis de antraciclina en el tratamiento de la leucemia mieloide aguda del adulto / Incorporation of the high dose of anthracycline in the treatment of adult acute myeloid leukemia

Introducción: La leucemia mieloide aguda representa el 80 por ciento de las leucemias agudas entre los adultos; el tratamiento de inducción a la remisión, para los pacientes menores de 60 años, está basado en la combinación de antraciclinas y arabinósido de citosina. Objetivo: incorporar las altas dosis de antraciclinas al tratamiento de inducción de la leucemia mieloide aguda no promielocítica en pacientes adultos menores de 60 años. Método: Se realizó un estudio cuasiexperimental en 41 pacientes con este diagnóstico, atendidos en el servicio de Adultos del Instituto de Hematología e Inmunología, desde septiembre del 2013 hasta diciembre del 2016. A todos los pacientes se les realizó estudios morfológicos, inmunológicos, citogenéticos y moleculares al inicio de la enfermedad y ecocardiografía para determinar la fracción de eyección y de acortamiento del ventrículo izquierdo al año de finalizado el tratamiento, para determinar la cardiotoxicidad por el uso de las altas dosis de antraciclinas. Resultados: La distribución por edad fue mayor en el grupo de 46 a 52 años representado por el 26,8 por ciento de los casos y predominó el sexo masculino 60,9 por ciento. En el 85 por ciento de los casos la enfermedad apareció de novo. Según los criterios morfológicos de la clasificación Franco Británico Americana el 31,7 por ciento correspondió a la variante M1, en estrecha relación con las determinaciones por citometría de flujo, para esta variedad. Los genes más comúnmente involucrados fueron el NPM1 y el AML/ETO, para el 24 por ciento y 22 por ciento, respectivamente. El 56,1 por ciento de los pacientes alcanzó la remisión hematológica con un solo ciclo de tratamiento y el 14,6 por ciento, necesitó realizar un segundo esquema de inducción. No se reportaron eventos de cardiotoxocidad por antraciclina durante el tratamiento, ni al año de culminado este. Conclusiones: Con el uso de las altas dosis de antraciclina se lograron remisiones hematológicas, sin toxicidad cardiovascular demostrada(AU)

Introduction: Acute myeloid leukemia represents 80 percent of acute leukemias among adults; the induction treatment to obtain remission in patients under 60 years old is based on the combination of anthracyclines and cytosine arabinoside. Objective: to incorporate the high doses of anthracyclines to the treatment of induction of non-promyelocytic acute myeloid leukemia in adult patients under 60 years of age. Method: We conducted a quasi-experimental study in 41 patients with this diagnosis, at the adult clinic service of the Institute of Hematology and Immunology, from september 2013 to december 2016. Morphological, immunological, cytogenetic and molecular studies were carried out at the beginning of the disease and also echocardiography was performed to determine the ejection fraction and shortening of the left ventricle a year after the end of treatment, to determine cardiotoxicity due to the use of high doses of anthracyclines. Results: The distribution by age was higher in the group of 46 to 52 years represented by 26.8 percent of the cases and the male sex predominated 60.9 percent. In 85 percent of the cases the disease appeared de novo. According to the morphological criteria of the French American British classification, 31.7 percent corresponded to the M1 variant, in close relation with the determinations by flow cytometry, for this variety. The genes most commonly involved were NPM1 and AML / ETO, for 24 percent and 22 percent respectively. 56.1 percent of patients achieved hematological remission with a single treatment cycle and 14.6 percent of patients needed a second induction scheme. No anthracycline cardiotoxicity events were reported during the treatment, nor a year after the treatment, in the patients evaluated. Conclusions: With the use of high doses of anthracycline, have been hematological remissions, without demonstrated cardiovascular toxicity(AU)

Arterial Stiffness Use for Early Monitoring of Cardiovascular Adverse Events due to Anthracycline Chemotherapy in Breast Cancer Patients. A Pilot Study / Uso da Rigidez Arterial para Monitoramento Precoce de Eventos Adversos Cardiovasculares por Antracíclicos em Pacientes com Câncer de Mama. Um Estudo Piloto

Abstract Background: Chemotherapy with doxorubicin and cyclophosphamide, although efficient for treating breast cancer, is associated with cardiovascular complications. Recent studies seek to identify methods that can early detect cardiological and vascular changes as a strategy to decrease the incidence of cardiovascular comorbidities. Objective: To evaluate the role of arterial stiffness measurement in the monitoring of doxorubicin and cyclophosphamide-induced cardiotoxicity in breast cancer patients. Methods: Prospective longitudinal study in 24 breast cancer patients undergoing treatment with doxorubicin and cyclophosphamide. Patients underwent an indirect evaluation of arterial stiffness through non-invasive measurement of hemodynamic parameters such as pulse wave velocity with the Mobil-O-Graph® 24H PWA device at three different times of the chemotherapy treatment (pre-chemotherapy, after the first and the fourth cycle). The left ventricular ejection fraction was also evaluated by Doppler echocardiography (pre-chemotherapy and after the fourth chemotherapy cycle). Data were considered significant when p ≤ 0.05. Results: Patients had a mean age of 52.33 ± 8.85 years and body mass index of 31 ± 5.87 kg/m2. There was no significant difference between the hemodynamic parameters evaluated by the oscillometric method or in the left ventricular ejection fraction in the different evaluated periods. Conclusion: Evaluations of arterial stiffness by oscillometry and measurement of left ventricular ejection fraction by Doppler echocardiography showed equivalence in the values found, suggesting that the evaluation method of arterial stiffness studied could be used as a marker for cardiovascular adverse events associated with doxorrubicin-based chemotherapy drugs.

Resumo Fundamento: O tratamento quimioterápico com doxorrubicina e ciclofosfamida, apesar de eficiente no combate ao câncer de mama, está associado a complicações cardiovasculares. Trabalhos recentes identificam métodos que possam detectar alterações cardiológicas e vasculares precocemente, visando a uma estratégia para diminuição na incidência de comorbidades cardiovasculares. Objetivo: Avaliar o papel da medida da rigidez arterial no acompanhamento da ocorrência de eventos adversos cardiovasculares induzidos por doxorrubicina e ciclofosfamida em pacientes com câncer de mama. Métodos: Estudo longitudinal prospectivo realizado com 24 pacientes com câncer de mama em tratamento com doxorrubicina e ciclofosfamida. As pacientes foram submetidas à avaliação indireta da rigidez arterial, por mensuração não invasiva de parâmetros hemodinâmicos, como a velocidade de onda de pulso, pelo equipamento Mobil-O-Graph® 24H PWA em três diferentes momentos do tratamento quimioterápico (pré-quimioterapia, após o primeiro e após o quarto ciclos). Foi avaliada também a fração de ejeção do ventrículo esquerdo pelo ecoDopplercardiograma (pré-quimioterapia e após o quarto ciclo quimioterápico). Os valores de p ≤ 0,05 foram considerados significativos. Resultados: As pacientes apresentaram média de idade de 52,33 ± 8,85 anos e índice de massa corporal de 31 ± 5,87 kg/m2. Não houve diferença significativa entre os parâmetros hemodinâmicos avaliados pelo método oscilométrico ou na fração de ejeção do ventrículo esquerdo, nos diferentes períodos avaliados. Conclusão: As avaliações de rigidez arterial por oscilometria e medida da fração de ejeção do ventrículo esquerdo por ecoDopplercardiograma mostraram equivalência nos valores encontrados, sugerindo que o método de avaliação da rigidez arterial estudado possa ser utilizado como mais um marcador para eventos adversos cardiovasculares associados aos medicamentos quimioterápicos baseados em doxorrubicina.

Cardioproteção durante o tratamento oncológico / Cardioprotection during cancer treatment

O primeiro passo para a prevenção de cardiotoxicidade é avaliar o indivíduo quanto ao risco cardiovascular basal e identificar os pacientes de alto risco. É essencial a abordagem proativa, otimizando o tratamento das doenças cardiovasculares existentes e reduzindo os fatores que contribuem para o aumento do risco cardiovascular. Essa avaliação é um processo contínuo, que deve acontecer durante todo o tratamento. Nos pacientes candidatos a altas doses de antraciclina, algumas estratégias possíveis para mitigar a cardiotoxicidade são o uso de infusão contínua de antraciclina em vez de infusão em bolus, uso de doxorrubicina lipossomal em substituição a doxorrubicina tradicional e uso de dexrazoxano antes da infusão de antracíclico. As evidências atuais ainda não corroboram o uso rotineiro de bloqueadores neuro-hormonais ou estatinas como agentes cardioprotetores em todos os pacientes tratados com quimioterapia potencialmente cardiotóxica

he first step in preventing cardiotoxicity is to evaluate the baseline cardiovascular risk in the individual, and to identify high-risk patients. A proactive approach is essential, optimizing the treatment of existing cardiovascular patients and reducing the factors that contribute to the increase in cardiovascular risk. This evaluation is a continuous process that should occur throughout the treatment. In candidate patients for high-dose anthracycline, some possible strategies to mitigate cardiotoxicity are the use of continuous anthracycline infusion instead of as a bolus, the use of liposomal doxorubicin to replace traditional doxorubicin, and the use of dexrazoxane prior to anthracycline infusion. Current evidence does not support the routine use of neurohormonal blockers or statins as cardioprotective agents in all patients treated with potentially cardiotoxic chemotherapy

Manejo a longo prazo dos sobreviventes / Long-term management of survivors

A melhora dos resultados do tratamento oncológico com consequente aumento na sobrevida dos pacientes fez surgir um grupo chamado de sobreviventes. A incidência aumentada de doença cardiovascular nessa população é responsável por morbidade e mortalidade significativas a longo prazo. Este estudo é uma abordagem multidisciplinar, com foco em prevenção, diagnóstico e tratamento da doença cardiovascular anos após o final do tratamento, que reforça a importância da cardio-oncologia

The improvement in the results of cancer treatment, with a consequent increase in patient survival, has led to the emergence of a group known as survivors. The increased incidence of cardiovascular disease in this population is responsible for significant long-term morbidity and mortality. This study is a multidisciplinary approach, with focus on the prevention, diagnosis and treatment of cardiovascular disease years after the end of treatment, which reinforces the importance of cardio-oncology

Cardio-oncologia na população pediátrica / Cardio-oncology in the pediatric population

Nas últimas décadas, a oncologia pediátrica tem demonstrado expressivo sucesso no tratamento do câncer infantojuvenil, com significativo aumento das taxas de cura e sobrevida, principalmente devido ao diagnóstico precoce e à quimioterapia mais eficaz, além do auxílio da radioterapia em determinadas situações. Contudo, os medicamentos que curam o câncer também se comportam como adversários de vários sistemas orgânicos. Os sobreviventes do câncer infantojuvenil são, particularmente, mais vulneráveis às condições crônicas de morbidade relacionadas com os efeitos colaterais do tratamento, especialmente sobre o sistema cardiovascular ­ cardiotoxicidade. Quando não diagnosticados e tratados em tempo hábil, o dano cardiovascular relacionado ao tratamento do câncer poderá tornar-se progressivo e, frequentemente, irreversível. As complicações cardiovasculares lideram as causas de morbidade e mortalidade entre os pacientes oncológicos, depois das complicações relacionadas com o câncer propriamente dito. Estratégias de prevenção e monitoramento efetivo são a chave para um tratamento mais seguro. É incontestável a importância da parceria entre oncologistas pediátricos e cardiologistas pediátricos e o apoio da equipe multiprofissional para atender a crescente demanda dessa população de pacientes, com a finalidade maior da cura com qualidade de vida

In recent decades, pediatric oncology has shown good success in the treatment of children and adolescents with cancer, with a significant increase in the rates of cure and survival, mainly due to early diagnosis and more effective chemotherapy drugs, but also with the help of radiotherapy in certain situations. However, drugs that cure cancer also behave as opponents of several organ systems. Survivors of childhood cancer, in particular, are more vulnerable to chronic conditions of morbidity related to side effects of treatment, especially on the Cardiovascular System - Cardiotoxicity. If not diagnosed and treated in a timely manner, cardiovascular damage related to cancer treatment can become progressive and often, irreversible. Cardiovascular complications are the leading causes of morbidity and mortality among cancer patients, after complications related to cancer. Strategies for prevention and effective monitoring are the key to safer treatment. The importance of the partnership between Pediatric oncologists and cardiologists and the multiprofessional team is undeniable, to meet the growing demand of this patient population, with the main purpose of cure with quality of life

Quimioterapia e cardiotoxicidade / Chemotherapy and cardiotoxicity

A evolução do tratamento oncológico resultou no desenvolvimento de fármacos altamente eficazes. No entanto, os efeitos colaterais da terapia antitumoral ainda são frequentes e, muitas vezes, limitantes. Entre os efeitos adversos possíveis, a cardiotoxicidade representa um grupo importante de manifestações, com impacto negativo a curto e longo prazo na evolução desses pacientes. Esses eventos podem ocorrer na ausência de fatores de risco de doença cardiovascular e sua evolução ainda não está totalmente esclarecida. Curiosamente, podem ser desencadeadas tanto por terapias sistêmicas convencionais quanto por novas terapias relacionadas com alvos moleculares específicos. As definições de cardiotoxicidade ainda são diversas e não há um consenso universal. Em linhas gerais, pode ser entendida como qualquer alteração da homeostase do sistema cardiovascular induzida pelo tratamento do câncer. O dano cardíaco pode apresentar-se por vasta gama de condições clínicas, como por exemplo, alterações metabólicas, hipertensão arterial sistêmica, síndromes coronarianas agudas, tromboembolismo arterial e venoso, arritmias, entre outros. Muitos destes eventos têm prognóstico pior que muitas neoplasias. Assim, o conhecimento dos efeitos adversos cardíacos do tratamento antineoplásico é de suma importância, e a avaliação cardiovascular do paciente com câncer é fundamental. O intuito desta revisão é apresentar de forma prática as drogas oncológicas com maior potencial cardiotóxico e discutir de forma resumida seus principais efeitos cardiovasculares. Serão discutidas brevemente as definições, os mecanismos de agressão cardíaca e as manifestações clínicas principais, além da evolução e manejo inicial

The evolution of oncological treatment has resulted in the development of highly effective drugs. However, the side effects of antineoplastic therapy are still frequent, and often limiting. Among the possible adverse effects, cardiotoxicity represents an important group of manifestations, with negative impact on the clinical development of these patients in the short and long terms. These events can occur in the absence of risk factors for cardiovascular disease, and their clinical course is still not fully clarified. Interestingly, they can be triggered by both conventional systemic therapies and by new therapies with specific molecular targets. There are several definitions of cardiotoxicity, and there is no universal consensus. In general terms, it can be understood as any modification of cardiovascular system homeostasis induced by cancer treatment. Cardiac damage can present as a wide range of clinical conditions, such as metabolic changes, systemic arterial hypertension, acute coronary syndromes, arterial and venous thromboembolism, and arrhythmias, among others. Many of these events have a worse prognosis than many neoplasms. Thus, the knowledge of the adverse cardiac effects of antineoplastic treatment is of paramount importance, and the cardiovascular evaluation of the cancer patient is essential. The purpose of this review is to offer a practical presentation of oncological drugs with greater cardiotoxic potential, and to summarize its main cardiovascular effects. The definitions, mechanisms of cardiac aggression, and main clinical manifestations will be briefly discussed, as well as the clinical course and initial management

Monitorización de la ocurrencia de extrasístoles ventriculares relacionadas con la infusión de antraciclinas como herramienta para la Enfermería / Monitoring the occurrence of premature ventricular heartbeats related to the infusion of anthracyclines as a tool for nursing

El cáncer es responsable del 12 por ciento de todas las causas de muerte en el mundo, más de siete millones de personas mueren anualmente de esta enfermedad. Las formas de tratamiento incluyen cirugía, radioterapia y la quimioterapia combinada o no. Entre los quimioterápicos usados las antraciclinas, en especial la doxorrubicina están incluidas entre los agentes citotóxicos más utilizados en el tratamiento de leucemia aguda, linfomas Hodgkin y no Hodgkin, además del cáncer de mama. La mielodepresión grave y la toxicidad cardíaca son las dos reacciones adversas más frecuentes causas de extrasístoles ventriculares (ESV). El objetivo fue comparar la ocurrencia de ESV en el período pre-inmediato, inmediato y post inmediato durante el tratamiento con antraciclina y establecer una correlación entre el tiempo de tratamiento y la ocurrencia de ESV. Se trata de un ensayo clínico no controlado, tipo antes y después, con abordaje cuantitativo. La muestra de conveniencia fue de 30 pacientes sometidos al tratamiento con doxorrubicina en el servicio ambulatorio de quimioterapia de un hospital universitario. Se analizó el número de ESV, en los períodos pre, trans y post infusional de los pacientes sometidos a la infusión de antraciclina. En los períodos pre- trans y post infusional, no hubo diferencias estadísticamente significantes (p> 0,05), tanto por métodos paramétricos como por los no paramétricos. En la muestra analizada se puede efectuar la infusión de doxorrubicina con seguridad por el enfermero(AU)

The cancer is responsible for 12 percent of all causes of death in the world, more than 7 million people die annually of the disease. The forms of treatment include surgery, radiotherapy and chemotherapy combined or not. Among the chemotherapy used, the anthracyclines, in particular are included doxorubicin among the most cytotoxic agents used to treat acute leukemia, linfomas hodgkin e não hodgkin, than of breast cancer. The serious myelosuppression and the cardiac toxicity are the two major adverse reactions caused by antraciclinas. The occurrence of signs of cardiotoxicity in particular the extra-ventricular sistoles (EVS), is the object and reasons of this study, whose objectives were comparing the occurrence of extra-ventricular systole in the immediate pre and post per immediate during treatment with anthracycline and establish a correlation between time of treatment and the occurrence of ESV. This is an uncontrolled clinical trial, before, during and after a quantitative treatment. The sample of convenience consisted of 30 patients undergoing treatment with doxorubicin chemotherapy at the clinic of the university hospital (UH). It examined the number of EVS, in pre, and post per infusion of patients who underwent anthracycline infusion of the chemotherapy outpatient clinic of University Hospital. The results show that in pre-per pre-and post infusion, there were no statistically significant differences (p> 0,05), by parametric methods is not as parametric. It was concluded that the sample analysed the infusion of doxorubicin can be performed safely by nurse(AU)

Quimioterapia em câncer de mama / Chemotherapy for breast cancer

Em 2010, um milhão e meio de mulheres receberão o diagnóstico de câncer de mama no mundo, sendo 49.000 no Brasil. O câncer de mama e uma área em constante evolução, exigindo, tanto da parte de mastologistas quanto dos oncologistas, rápida adaptação aos novos conceitos. Sabe-se que o câncer de mama não e uma doença única e, portanto, seu tratamento deve ser individualizado. A quimioterapia é uma parte importante do tratamento desta doença e tem evoluído recentemente, juntamente com a cirurgia, hormonioterapia, radioterapia e outros tratamentos de suporte, fazendo com que a mortalidade por esta doença continue a diminuir. Baseado em dados dos estudos de perfil molecular, e possível que mais de 50% das pacientes recebam quimioterapia adjuvante desnecessariamente. Revisa-se aqui o papel dos novos testes de perfil molecular disponíveis e o estado atual do uso de quimioterapia no câncer de mama. Nesta revisão, e dado especial enfoque ao tratamento adjuvante e neoadjuvante, sendo descritas algumas particularidades como o tratamento das pacientes idosas, da doença HER-2 positiva e da doença metastática.

In 2010, one and a half million women will be diagnosed with breast cancer worldwide, and 49, 000 in Brazil. Breast cancer is a constantly evolving area requiring from Mastologists and Oncologists a fast adaptation to new concepts. Furthermore, breast cancer does not consist of a single entity, therefore, it requires individualized treatment approaches. Chemotherapy is an important treatment modality, and it has been a rapidly evolving area that has been contributing to the decreasing breast cancer mortality observed in recent years, along with surgery, hormone therapy, radiotherapy, and other supportive treatments. Based on data from molecular profiling studies, more than 50% of the patients may be receiving unnecessary adjuvant chemotherapy. We aim to review the role of new molecular profiling tests and the current state of art in chemotherapy treatment for breast cancer. We also address the important issue of chemotherapy treatment in elderly patients, and the management of HER -2 positive and metastatic disease.

Prevalence and risk factors for development of lymphedema following breast cancer treatment.

BACKGROUND: Early detection and multimodality therapy has resulted in an overall improvement of survival among breast cancer patients. Despite a significant shift in the treatment approach from radical mastectomy to breast conservation a significant number of patients develop lymphedema. This study was conducted to evaluate the prevalence and risk factors for development of lymphedema. SETTINGS AND DESIGN: Retrospective analysis for prevalence of lymphedema in a tertiary care regional cancer centre. MATERIAL AND METHODS: Three hundred treated breast cancer patients with a minimum follow up of one year were evaluated for the prevalence and risk factors for lymphedema. Lymphedema was assessed using a serial circumferential measurement method. More than 3 cm difference in circumference is considered as clinical significant lymphedema. Univariate and multivariate analysis were performed for evaluating the risk factors by using the Chi square test and Cox logistic regression analysis. RESULTS: The prevalence of clinically significant lymphedema was 33.5 % and 17.2 % had severe lymphedema. The prevalence of lymphedema was 13.4 % in patients treated with surgery only where as the prevalence was 42.4% in patients treated with surgery and radiotherapy. Stage of the disease, body surface area > 1. 5 m2, presence of co-morbid conditions, post operative radiotherapy and anthracycline based chemotherapy were significant risk factors in univariate analysis where as axillary irradiation and presence of co-morbid conditions have emerged as independent risk factors in multivariate analysis (P < 0.001). CONCLUSION: Post treatment lymphedema continues to be a significant problem following breast cancer therapy. Presence of co-morbid conditions and axillary radiation significantly increases the risk of lymphedema. A combination of axillary dissection and axillary radiation should be avoided whenever feasible to avoid lymphedema.

Capecitabine and Vinorelbine in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane

We have evaluated the efficacy and safety of the combination of capecitabine and vinorelbine in metastatic breast cancer (MBC) patients previously treated with anthracycline-and taxane-containing regimens. Between April 2000 and September 2002, 44 female MBC patients received oral capecitabine (1,250 mg/m(2) twice daily on days 114), and intravenous vinorelbine (25 mg/m2 on days 1 and 8) during each 3 weekchemotherapy cycle (median, 5 cycles/patient; total, 235 cycles). One patient achieved a complete response and 21 patients had partial responses, giving an overall response rate of 50% in the intention-to-treat analysis (95% CI, 35.0-65.0%). Median duration of response was 6.0 months (range 1.2-23.0 months). Patients were followed- up for a median of 16 months, with median progression-free survival being 5.3 months, and median overall survival being 17 months. Toxicities included grades III and IV neutropenia in 63 (26.8%) and 4 (1.7%) cycles, respectively, and grades II and III hand-foot syndrome in 12 (5.1%) and 4 (1.7%) cycles, respectively. Other nonhematologic toxicities were minimal and manageable. In conclusion, the combination of capecitabine and vinorelbine was effective and well tolerated in MBC patients even after treatment with anthracyclines and taxanes.

Novas drogas no tratamento do câncer de mama / Breast cancer treatment: new drugs

A resposta do câncer de mama à terapia hormonal já é conhecida há mais de um século pela ooforectomia cirúrgica. A eficácia comprovada do antiestrógeno tamoxifeno demonstrou diminuiçäo das recidivas no seu uso adjuvante e também resposta objetivas em pacientes com doença mestastática. Novas estratégias hormonioterápicas para a resposta a uma segunda e terceira linha de terapia têm sido buscadas pelos inibidores de aromatase. Antiestrógenos semelhantes ao tamoxifeno, com menos efeitos colaterais, têm sido estudados como os novos moduladores seletivos dos receptores estrogênicos. Novos quimioterápicos, estudados na última década, constituem um dos maiores avanços na quimioterapia do câancer de mama. Os taxanos associados às antraciclinas no tratamento de primeira linha dos casos de mau prognóstico e, isoladamente, no tratamento de doença metastática, os antimetabólicos, os alcalóides da vinca e as novas antraciclinas já estäo bem avaliados em estudos aleatorizados de fase III. E, por fim, o tratamento biológico com o desenvolvimento de anticorpos monoclonais contra a oncoproteína Her-2/neu reavivou as expectativas para que, em um futuro próximo, tenhamos, à disposiçäo, medicaçöes com menor toxicidade e racionalmente desenvolvidas, levando-se en conta as características biológicas do tumor