RESUMO

BACKGROUND: Cardiotoxicity is a recognized complication in breast cancer (BC) patients undergoing chemotherapy with anthracyclines with or without trastuzumab. However, the prognostic value of heart rate variability (HRV) indexes for early cardiotoxicity development remains unknown. METHODS: Fifty BC patients underwent TTE assessment before and three months after chemotherapy. HRV indexes were obtained from continuous electrocardiograms in supine position with spontaneous breathing, active standing, and supine position with controlled breathing. The magnitude of change (Δ) between supine-standing and supine-controlled breathing was calculated. Variables were compared using t-test or ANOVA. Cardiotoxicity predictive value was assessed by ROC curve analysis. A p value of < 0.05 was considered significant. RESULTS: TTE revealed reduced left atrial conduit strain in the cardiotoxicity group. Mean heart rate increased during all maneuvers at follow-up, with no differences in HRV indexes between patients with or without cardiotoxicity. However, a lower Δ in supine-controlled breathing of several HRV indexes predicted early cardiotoxicity identified by echocardiography (e.g. SDNN ≤ -8.44 ms: Sensitivity = 75%, Specificity = 69%). CONCLUSIONS: BC patients treated with chemotherapy maintain cardiac autonomic responses to physiological stimuli after 3 months of chemotherapy. However, a lower Δ during active standing and controlled breathing before chemotherapy may predict early cardiotoxicity.

RESUMO

INTRODUCTION: Several interventions have been tested for cardio-protection against anthracycline-induced cancer therapy-related cardiovascular dysfunction (CTRCD). The role of statins in this setting remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and Web of Science for randomized controlled trials (RCTs) comparing statins versus control (placebo or no intervention) for preventing anthracycline-induced CTRCD. We applied a random-effects model to pool risk ratios (RR) and mean differences (MD) with 95 % confidence intervals (CI). RESULTS: We included seven RCTs comprising 887 patients with planned chemotherapy with anthracycline-based regimens, of whom 49.8 % were randomized to statins. Relative to placebo, statins significantly reduced the incidence of cardiotoxicity/CTRCD (RR 0.46; 95 % CI 0.29 to 0.72; p < 0.001). The left ventricular end-systolic volume was also lower in patients treated with statin (MD -3.12 mL; 95 % CI -6.13 to -0.12 mL; p = 0.042). There was no significant difference between groups in post-anthracycline left ventricular ejection fraction (LVEF) overall. CONCLUSION: In this meta-analysis of RCTs, statins were significantly associated with a lower incidence of anthracycline-induced CTRCD and attenuated changes in the left ventricular end-systolic volume. Thus, our findings suggest that statins should be considered as a cardio-protection strategy for patients with planned anthracycline-based chemotherapy.

Assuntos

RESUMO

Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.

RESUMO

Evidences on the effects of chemotherapy treatment cycles on measures of muscle, mental state, social and cognitive performance are scarce. The objective of this study was to analyze the effects of chemotherapy cycles on muscle strength and activation, functional capacity, quality of life, fatigue and anxiety of women with breast cancer. Therefore, twenty-two women divided into a treatment group (n = 10; 46.6 ± 9.6 years) and control group (n = 12; 51.6 ± 7.0 years) participated in the study. Analysis of muscle performance, quality of life, fatigue and anxiety after the 2nd and 4th cycle of chemotherapy with anthracyclines were performed in women with breast cancer (TRA) and compared to healthy women (CTR). Two-way ANOVA was used to compare the variance of the means and the significance level was set as P≤0.05. The results showed Differences in the muscular activation of the vastus mediallis between the groups at post time (P = 0.038), as well as in the sit and stand test in the baseline (P<0.001) and post moment (P<0.001). Functional capacity performance was different between baseline (P<0.001) and post-time (P<0.001) groups. Additionally, the TRA group worsened the quality of life in the domains of functional capacity (P<0.001) and limitation of physical aspects (P = 0.002), besides presenting negative changes in fatigue. Thus, anthracycline chemotherapy cycles reduce muscular performance and affect biopsychosocial variables in women with breast cancer.

RESUMO

SUMMARY BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

RESUMO

Resumo Fundamento: A introdução das antraciclinas no tratamento do câncer infantojuvenil propiciou um aumento significativo na sobrevida, mas também nas taxas de morbimortalidade devido às complicações cardiovasculares (CVs). Objetivos: Conhecer o perfil cardiológico de pacientes pediátricos tratados com antraciclinas em um centro oncológico no Brasil e a incidência das complicações CVs. Métodos: Foram coletados, de prontuários de pacientes de ambos os sexos com idade até 19 anos - frequência e forma de apresentação clínica das complicações CVs Gerais (G1) e relacionadas à Disfunção Ventricular (G2) - e correlacionados com fatores de risco, faixa etária e estado vital, medicações cardiológicas e cardioprotetoras. Um valor de p < 0,05 foi considerado significativo. Resultados: Foram incluídos 326 pacientes, destes, 214 (65,6%) eram menores de 10 anos e 192 (58,89%) do sexo masculino. As complicações do G1 ocorreram em 141 (43,3%) pacientes e a mais frequente foi a hipertensão arterial sistêmica; as complicações do G2 ocorreram em 84 pacientes (25,76%). Uma Dose Cumulativa (DC) das antraciclinas > 250mg/m2 foi usada em 26,7% dos pacientes e a associação de complicações do G2 com essa DC não mostrou significância estatística (p=0,305; RC=1,330 e [95% IC= 0,770- 2,296]). As medicações cardiológicas mais usadas foram os diuréticos em 34,7% dos pacientes. Conclusões: O estudo mostrou, como na literatura, uma alta incidência de complicações CVs no tratamento do câncer infantojuvenil, sendo as do G1 as mais frequentes.

Abstract Background: The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and mortality rates due to cardiovascular (CV) complications. Objectives: To determine the cardiovascular profile of pediatric patients treated with anthracyclines at a cancer center in Brazil and the incidence of CV complications. Methods: The following data were collected from the medical records of patients of both sexes, aged younger than 19 years - frequency and form of clinical presentation of general CV complications (G1) and CV complications related to ventricular dysfunction (G2) - and correlated with risk factors, age range and vital status, cardiovascular and cardioprotective medications. A p<0.05 was considered statistically significant. Results: A total of 326 patients were included, 214 (65.6%) were younger than 10 years and 192 (58.9%) of male sex. G1 complications occurred in 141 (43.3%) patients, and the most frequent was systemic arterial hypertension; G2 complications occurred in 84 patients (25.8%). Cumulative dose (CD) of anthracyclines > 250mg/m2 was used in 26.7% of patients and the association of G2 complications with this CD was not statistically significant (p=0.305; OR=1.330 and [95% CI = 0.770- 2.296]). The most used cardiac medications were diuretics (34.7% of patients). Conclusions: In accordance with literature, the study showed a high incidence of CV complications in the treatment of children and adolescents with cancer, with general CV complications as the most prevalent.

RESUMO

ABSTRACT Introduction: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported Methods: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed Results: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% Conclusion: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

RESUMO

Despite advances in chemotherapy, the drugs used in cancer treatment remain rather harmful to the cardiovascular system, causing structural and functional cardiotoxic changes. Positron-emission tomography associated with computed tomography (PET/CT) has emerged like a promising technique in the early diagnosis of these adverse drug effects as the myocardial tissue uptake of fluorodeoxyglucose labeled with fluorine-18 (18F-FDG), a glucose analog, is increased after their use. Among these drugs, anthracyclines are the most frequently associated with cardiotoxicity because they promote heart damage through DNA breaks, and induction of an oxidative, proinflammatory, and toxic environment. This review aimed to present the scientific evidence available so far regarding the use of 18F-FDG PET/CT as an early biomarker of anthracycline-related cardiotoxicity. Thus, it discusses the physiological basis for its uptake, hypotheses to justify its increase in the myocardium affected by anthracyclines, importance of 18F-FDG PET/CT findings for cardio-oncology, and primary challenges of incorporating this technique in standard clinical oncology practice.

RESUMO

INTRODUCTION: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported METHODS: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed RESULTS: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% CONCLUSION: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

RESUMO

BACKGROUND AND AIM: Different studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA, DCK, GSTT1, and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML. METHODS: Fifty-one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA, DCK, GSTT1, and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi-square analysis. RESULTS: Patients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08-42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023-0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94-97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (-451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32-725, p = .007) and 3.8 OR (CI 95% 2.23-6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively. CONCLUSION: Our results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment.

Assuntos

RESUMO

Resumo Fundamento As evidências que embasam o uso de inibidores do sistema-renina-angiotensina aldosterona (SRAA) e betabloqueadores para prevenção de cardiomiopatia induzida por antraciclinas são controversas. Objetivo Realizamos uma metanálise para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. Métodos A metanálise incluiu estudos prospectivos e randomizados com adultos submetidos à quimioterapia com antraciclina e comparou o uso de terapias SRAA ou betabloqueadores versus placebo com seguimento de 6 a 18 meses. O desfecho primário foi alteração da fração de ejeção do ventrículo esquerdo (FEVE) durante a quimioterapia. Os desfechos secundários foram: a incidência de insuficiência cardíaca, mortalidade por todas as causas e alterações na medida do diâmetro diastólico final. A avaliação da heterogeneidade foi realizada por estratificação e meta-regressão. O nível de significância adotado foi p < 0,05. Resultados A busca resultou em 17 estudos, totalizando 1.530 pacientes. A variação (delta) da FEVE foi avaliada em 14 estudos. A terapia neuro-hormonal foi associada a um menor delta na FEVE pré-terapia versus pós-terapia (diferença média ponderada 4,42 [intervalo de confiança de 95% 2,3 a 6,6]) e maior FEVE final (p < 0,001). O tratamento resultou em menor incidência de insuficiência cardíaca (risk ratio 0,45 [intervalo de confiança de 95% 0,3 a 0,7]). Não houve efeito na mortalidade (p = 0,3). Para a análise da FEVE, foi documentada heterogeneidade substancial, não explicada pelas variáveis exploradas no estudo. Conclusão O uso de inibidores do SRAA e betabloqueadores para prevenção da cardiotoxicidade induzida por antraciclinas foi associado a redução menos pronunciada da FEVE, maior FEVE final e menor incidência de insuficiência cardíaca. Não foram observadas alterações na mortalidade. (CRD PROSPERO 42019133615)

Abstract Background The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. Objective We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. Methods The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. Results The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. Conclusion The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615)

RESUMO

Resumo Fundamento Agentes quimioterápicos (por exemplo, antraciclinas, trastuzumabe) comumente usados para o tratamento de tumores malignos demonstraram ter efeitos cardiotóxicos, que estão associados a um prognóstico ruim. A ecocardiografia tridimensional tem sido usada para prever a disfunção cardíaca induzida pela quimioterapia do câncer. Objetivos Avaliação do desempenho diagnóstico de parâmetros de strain, área global de strain (AGS), strain longitudinal (SLG), strain circunferencial (SCG) e strain radial (SRG) por metanálise. Métodos Estudos relevantes foram pesquisados nas bases de dados Embase, PubMed e Web of Science. A análise estatística foi realizada usando Stata 12. O resumo da curva característica operacional do receptor, sensibilidade, especificidade, razão de verossimilhança positiva (RVP), razão de verossimilhança negativa (RVN), e o correspondente intervalo de confiança de 95% para os quatro parâmetros de strain foram combinados. P<0,05 foi considerado estatisticamente significativo. Resultados Nove estudos envolvendo 650 participantes foram incluídos. AGS e SLG mostraram vantagens diagnósticas significativas sobre SCG e SRG. Para AGS, a sensibilidade foi de 0,85 (0,70, 0,93) e a especificidade foi de 0,82 (0,78, 0,86) com RVP de 4,76 (3,55, 6,39) e RVN de 0,18 (0,09, 0,39) e uma área sob a curva (AUC) de 0,85 (0,82, 0,88). Para SLG, a sensibilidade foi de 0,81 (0,74, 0,86) e a especificidade foi de 0,81 (0,68, 0,90) com RVP de 4,35 (2,42, 7,80) e RVN de 0,23 (0,17, 0,33) e uma AUC de 0,85 (0,82, 0,88).OGCS mostrou uma sensibilidade de 0,63 e uma especificidade de 0,79 com uma AUC de 0,77.O SRG mostrou uma sensibilidade de 0,74e uma especificidade de 0,66 com umAUC de 0,73. Conclusão Parâmetros 3D-STI de strain AGS e SLG mostraram bom desempenho na detecção precoce de disfunção cardíaca em pacientes com tumores recebendo quimioterapia.

Abstract Background Chemotherapeutic agents (e.g., anthracyclines, trastuzumab) commonly used for treating malignant tumors have been demonstrated to have cardiotoxic effects, which is associated with poor prognosis. Three-dimensional echocardiography has been used to predict cancer chemotherapy-induced cardiac dysfunction. Objectives Evaluation of the diagnostic performance of strain parameters, global area strain (GAS), longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) by meta-analysis. Methods Relevant studies were searched from the Embase, PubMed, and Web of Science databases. Statistical analysis was performed using Stata 12. The summary receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and corresponding 95% confidence interval for the four strain parameters were pooled. P<0.05 was considered statistically significant. Results Nine studies involving 650 participants were included. GAS and GLS showed significant diagnostic advantages over GCS and GRS. For GAS, the sensitivity was 0.85 (0.70, 0.93) and specificity was 0.82(0.78, 0.86) with PLR of 4.76 (3.55, 6.39) and NLR of 0.18 (0.09, 0.39) and an area under the curve (AUC) of 0.85 (0.82, 0.88). For GLS, the sensitivity was 0.81 (0.74, 0.86) and specificity was 0.81(0.68, 0.90) with PLR of 4.35(2.42, 7.80) and NLR of 0.23 (0.17, 0.33) and an AUC of 0.85 (0.82, 0.88). The GCS showed a sensitivity of 0.63 and a specificity of 0.79 with an AUC of 0.77. The GRS showed a sensitivity of 0.74 and a specificity of 0.66 with an AUC of 0.73. Conclusion 3D-STI strain parameters GAS and GLS showed good performance in detecting early cardiac dysfunction in patients with tumors receiving chemotherapy.

RESUMO

Abstract Background: The use of doxorubicin in chemotherapy has been associated with cardiotoxicity and heart failure. Physical exercise produces favorable morphofunctional adaptations in the cardiovascular system and may reverse cardiac dysfunction in patients undergoing chemotherapy. Objective: To assess the effects of physical training on myocardial structure, cardiac function, and exercise tolerance in Wistar rats initiated after the onset of cardiotoxicity-induced cardiotoxicity. Methods: This study investigated 30 adult male Wistar rats randomly divided into four groups: control (C), exercise (EX), doxorubicin (DX), and doxorubicin and exercise (DXEX). The DX and DXEX groups received six doses of doxorubincin from 1.25 mg/kg body weight up to a cumulative dose of 7.5 mg/kg. Injections were administered intraperitoneally three times a week for two weeks; after this stage, the EX and DXEX groups started physical training (swimming) sessions three times a week with a load of 5% of their body weight. Echocardiography and exercise tolerance tests were performed. Generalized linear models were used in statistical analysis, and a p<0.05 was set as statistically significant. Results: Left ventricular shortening fraction and ejection fraction were reduced in the DX group compared to C, EX, and DXEX. The DXEX group showed greater tolerance to effort when compared to the DX and C groups. Conclusion: Physical training, initiated after the onset of doxorubicin-induced cardiotoxicity, improved cardiac function and exercise tolerance in rats.

RESUMO

BACKGROUND: Cancer chemotherapy using anthracyclines is associated with cardiotoxicity (CTX), and left ventricular ejection fraction (LVEF) analysis is not sensitive to early cardiotoxic changes. Left ventricular global longitudinal strain (LV GLS) monitoring helps screen subclinical CTX; however, the intervals at which it should be performed remain unclear. We aimed to evaluate the incidence of CTX in women with breast cancer and the associated factors and compare two echocardiographic monitoring strategies using two cutoff points for LV GLS variation. METHODS: Patients with breast cancer prescribed doxorubicin underwent serial LVEF and LV GLS assessments using two-dimensional echocardiography every 3 weeks for 6 months. RESULTS: We included 43 women; none developed a clinical CTX. Considering a relative reduction of LV GLS > 15%, subclinical CTX was present in 12 (27.9%) and six (14%) patients at 3-week and 3-month intervals, respectively (P = 0.28). Additionally, considering a reduction of > 12%, subclinical CTX was present in 17 (39.5%) and 10 (23.3%) patients (P = 0.16), respectively. There were no significant differences in either reference value at 3-week (P = 0.19) and 3-month intervals (P = 0.41). Age ≥ 60 years (P = 0.018) and hypertension (HTN) (P = 0.022) were associated with subclinical CTX in the univariate analysis. CONCLUSIONS: There was no difference in the incidence of subclinical CTX between the two cutoff points and no benefit in performing echocardiography every 3 weeks compared with quarterly monitoring. Advanced age and HTN were associated with the development of subclinical CTX.

RESUMO

Anthracyclines are chemotherapeutic drugs widely used in the frontline of cancer treatment. The therapeutic mechanisms involve the stabilization of topoisomerase IIα, DNA, and the anthracycline molecule in a ternary complex that is recognized as DNA damage. Redox imbalance is another vital source of oxidative DNA damage. Together, these mechanisms lead to cytotoxic effects in neoplastic cells. However, anthracycline treatment can elicit cardiotoxicity and heart failure despite the therapeutic benefits. Topoisomerase IIß and oxidative damage in cardiac cells have been the most reported pathophysiological mechanisms. Alternatively, cardiac cells can undergo stress-induced senescence when exposed to anthracyclines, a state primarily characterized by cell cycle arrest, organelle dysfunction, and a shift to senescence-associated secretory phenotype (SASP). The SASP can propagate senescence to neighboring cells in an ongoing process that leads to the accumulation of senescent cells, promoting cellular dysfunction and extracellular matrix remodeling. Therefore, the accumulation of senescent cardiac cells is an emerging pathophysiological mechanism associated with anthracycline-induced cardiotoxicity. This paradigm also raises the potential for therapeutic approaches to clear senescent cells in treating anthracycline-induced cardiotoxicity (i,e, senolytic therapies).

Assuntos

RESUMO

RESUMO Pacientes oncológicos desenvolvem problemas cardíacos frequentes devido à toxidade dos quimioterápicos, com consequente impacto na capacidade funcional (CF) e na qualidade de vida (QV). O treinamento muscular inspiratório (TMI) pode ser um recurso terapêutico viável, já que estudos de causa-efeito demonstraram melhora da CF e da QV em outras populações. Contudo, seu efeito ainda não foi avaliado em pacientes cardio-oncológicos. Assim, o objetivo deste estudo foi descrever o efeito de um programa de TMI sobre a CF e a QV de uma paciente com cardiotoxicidade: LDM, com 41 anos, mulher e sedentária, que desenvolveu insuficiência cardíaca após tratamento quimioterápico. A QV foi avaliada pelo teste de Minnesota. Foram avaliados também a força muscular inspiratória dinâmica (S-Index) e o limiar glicêmico (LG) dos músculos inspiratórios. O LG foi determinado pela glicemia capilar por meio do glicosímetro digital (Accu-Chek - Roche) no menor valor da glicemia da carga correspondente ao teste muscular inspiratório incremental (TMII). A progressão da carga foi realizada a cada duas semanas. Ao final de dois meses, todos os testes foram reaplicados. No teste de Minnesota, os valores relacionados à CF, antes e após o TMI, foram de 36 vs. 8 (melhora de 78%); aos aspectos clínicos e psicológicos foram de 32 vs. 7 (melhora de 78%), a S-Index foram de 41 vs. 51cmH2O (melhora de 24%). O TMI melhorou a CF e a QV de uma paciente cardio-oncológica, configurando-se como um recurso terapêutico viável para essa população.

RESUMEN Los pacientes con cáncer desarrollan problemas cardíacos frecuentes debido a la cardiotoxicidad de la quimioterapia, con el consiguiente impacto en la capacidad funcional (FC) y la calidad de vida (CV). El entrenamiento muscular inspiratorio (IMT) puede ser un recurso terapéutico viable, ya que los estudios de causa-efecto han demostrado una mejora en la FC y la CV en otras poblaciones. Sin embargo, su efecto aún no se ha evaluado en pacientes cardio-oncológicos. Por lo tanto, el objetivo de este estudio fue describir el efecto de un programa de IMT sobre la FC y la CV de un paciente con cardiotoxicidad: LDM, 41 años, mujer y sedentaria, que desarrolló insuficiencia cardíaca después del tratamiento de quimioterapia. La CV se evaluó mediante la prueba de Minnesota. También se evaluaron la fuerza muscular inspiratoria dinámica (índice S) y el umbral glucémico (LG) de los músculos inspiratorios. El LG se determinó por glucemia capilar mediante el glucómetro digital (Accu-Chek - Roche) al valor más bajo de la carga glucélica correspondiente a la prueba muscular inspiratoria incremental (IMI). La progresión de la carga se realizó cada dos semanas. Después de dos meses, todas las pruebas se volvieron a aplicar. En la prueba de Minnesota, los valores relacionados con la FC, antes y después de THE, fueron 36 vs. 8 (78% de mejora); los aspectos clínicos y psicológicos fueron 32 vs. 7 (mejora del 78%), el índice S fue de 41 vs. 51cmH2O (mejora del 24%). El IMT mejoró la FC y la CV de un paciente cardio-oncológico, constituyendo un recurso terapéutico viable para esta población.

ABSTRACT Cancer patients develop frequent cardiac problems due to chemotherapy toxicity, which impacts functional capacity (FC) and quality of life (QoL). Inspiratory Muscle Training (IMT) may be a viable therapeutic resource since cause-effect studies have shown improvement in FC and QoL in other populations. However, its effect was not evaluated in cardio-oncology patients. The study aimed to describe the effect of an IMT program on the FC and QoL of a patient with cardiotoxicity, LDM, aged 41 years, female and, sedentary that developed heart failure after chemotherapy. The QoL was evaluated by the Minnesota test. Dynamic Inspiratory Muscle Strength (S-Index) and Glycemic Threshold (GT) of the inspiratory muscles were also evaluated. The GT was determined by capillary glycemia with a digital glucometer (Accu-Chek - Roche), at the lowest value of glycemia of the load corresponding to the Incremental Inspiratory Muscle Test (IIMT). The load progression was performed every two weeks. After two months, all tests were reapplied. In the Minnesota test, the values related to FC, pre and post IMT, were 36 v. 8 (78% improvement); the clinical and psychological aspects 32 v. 7 (78% improvement); S-Index was 41 v. 51cmH2O (24% improvement). IMT improved the FC and QoL of a cardio-oncology patient, configuring itself as a possible and viable therapeutic resource for this population.

RESUMO

BACKGROUND: Anthracycline (ANT) is often used for breast cancer treatment but its clinical use is limited by cardiotoxicity (CTX). CECCY trial demonstrated that the ß-blocker carvedilol (CVD) could attenuate myocardial injury secondary to ANT. Mieloperoxydase (MPO) is a biomarker of oxidative stress and galectin-3 (Gal-3) is a biomarker of fibrosis and cardiac remodeling. We evaluated the correlation between MPO and Gal-3 behavior with CTX. MATERIALS AND METHODS: A post hoc analysis was performed in the patients who were included in the CECCY trial. A total of 192 women had her blood samples stored during the study at -80°C until the time of assay in a single batch. Stored blood samples were obtained at baseline, 3 and 6 months after randomization. We excluded samples from 18 patients because of hemolysis. MPO and Gal-3 were measured using Luminex xMAP technology through MILLIPLEX MAP KIT (Merck Laboratories). RESULTS: 26 patients (14.9%) had a decrease of at least 10% in LVEF at 6 months after the initiation of chemotherapy. Among these, there was no significant difference in the MPO and Gal-3 when compared to the group without drop in LVEF (p = 0.85 for both MPO and Gal-3). Blood levels of MPO [baseline: 13.2 (7.9, 24.8), 3 months: 17.7 (11.1, 31.1), 6 months: 19.2 (11.1, 37.8) ng/mL] and Gal-3 [baseline: 6.3 (5.2, 9.6), 3 months: 12.3 (9.8, 16.0), 6 months: 10.3 (8.2, 13.1) ng/mL] increased after ANT chemotherapy, and the longitudinal changes were similar between the placebo and CVD groups (p for interaction: 0.28 and 0.32, respectively). In an exploratory analysis, as there is no normal cutoff value established for Gal-3 and MPO in the literature, the MPO and Gal-3 results were splited in two groups: above and below median. In the placebo group, women with high (above median) baseline MPO blood levels demonstrated a greater increase in TnI blood levels than those with low baseline MPO blood levels (p = 0.041). Compared with placebo, CVD significantly reduced TnI blood levels in women with high MPO blood levels (p < 0.001), but did not reduce the TnI levels in women with low baseline MPO blood levels (p = 0.97; p for interaction = 0.009). There was no significant interaction between CVD treatment and baseline Gal-3 blood levels (p for interaction = 0.99). CONCLUSIONS: In this subanalysis of the CECCY trial, MPO and Gal-3 biomarkers did not predict the development of CTX. However, MPO blood levels above median was associated with more severe myocardial injury and identified women who were most likely to benefit from carvedilol for primary prevention (NCT01724450).

Assuntos

RESUMO

PURPOSE: To evaluate the effectiveness of photobiomodulation (PBMT) in preventing dysgeusia in breast cancer patients treated with doxorubicin-cyclophosphamide (AC). METHODS: This is a phase II, randomized, triple-blind, placebo-controlled clinical trial involving 112 breast cancer patients treated with AC. The patients were divided equally into two groups: a test group treated with 2 J red laser and 3 J infrared laser on 21 points that were symmetrically distributed on the tongue on day 0 of four cycles of AC, and an equal placebo group treated with simulated PBMT to blind the patient, evaluator, and statistician. The clinicopathological and sociodemographic data, results of taste test, and subjective taste analysis, and the QoL, ECOG performance status, body mass index, and other side effects were recorded. The data were analyzed using ANOVA-RM/Bonferroni, Friedman/Dunn, and chi-square/Fisher's exact tests. RESULTS: PBMT patients showed less objective and subjective taste loss (p<0.05). On the other hand, the placebo group showed a higher ECOG status (p=0.037) and more significant weight loss (p<0.001) after four cycles of AC. The QoL was significantly higher in the PBMT group (p<0.05) at all assessment periods, and PBMT treatment also reduced the incidence of cachexia (p=0.020), anorexia (p<0.001), diarrhea (p=0.040), oral mucositis (p=0.020), and vomiting (p=0.008). CONCLUSION: PBMT reduced the taste loss and improved the overall health status and QoL of patients with breast cancer treated with AC. TRIAL REGISTRATION: Brazilian Clinical Trials Registry ( www.ensaiosclinicos.gov.br ) approval number RBR-9qnm34y, registered on 01/05/2021.

Assuntos