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1.
Medicina (Kaunas) ; 59(10)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37893506

RESUMO

Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD (p = 0.005). A similar pattern was observed in work status, sleep, and general health (p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue (p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant (p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.


Assuntos
Qualidade de Vida , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Qualidade de Vida/psicologia , Estudos Transversais , Diálise Renal , Insuficiência Renal Crônica/psicologia , Hospitais
2.
JCO Precis Oncol ; 7: e2300208, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37738545

RESUMO

PURPOSE: The main dose-limiting toxicity of anthracyclines is cardiotoxicity. Clonal hematopoiesis (CH), somatic mutations in hematopoietic stem or progenitor cells in patients without hematologic malignancy, is also associated with risk for adverse cardiovascular events and worse outcomes overall. We hypothesize that CH increases risk for doxorubicin-induced cardiotoxicity (DIC). METHODS: We conducted a retrospective cohort study in patients treated with doxorubicin for cancer (N = 100). Patients (n = 25) had incident symptomatic heart failure, decline in left ventricular ejection fraction, or arrhythmia. CH was identified using paired peripheral blood and tumor DNA. RESULTS: After adjusting for age at doxorubicin initiation, diabetes, dyslipidemia, and chest radiation, high cumulative dose of doxorubicin (>240 mg/m2; odds ratio [OR], 7.00; 95% CI, 1.77 to 27.74; P = .0056), CH (OR, 8.58; 95% CI, 2.05 to 35.99; P = .0033), and history of smoking (OR, 3.15; 95% CI, 1.00 to 9.93; P = .0495) were associated with DIC. CONCLUSION: This study provides preliminary evidence for CH as a predictive risk factor for DIC, which, with further investigation, could serve as an important precision medicine biomarker for the large number of patients with cancer who have CH.


Assuntos
Cardiotoxicidade , Hematopoiese Clonal , Humanos , Cardiotoxicidade/etiologia , Hematopoiese Clonal/genética , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Fatores de Risco , Doxorrubicina/efeitos adversos
3.
Transl Oncol ; 34: 101709, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37302348

RESUMO

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

5.
Front Oncol ; 12: 843741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847860

RESUMO

Background: Patients with inborn errors of immunity (IEI) have increased risk of developing cancers secondary to impaired anti-tumor immunity. Treatment of patients with IEI and cancer is challenging as chemotherapy can exacerbate infectious susceptibility. However, the literature on optimal cancer treatment in the setting of IEI is sparse. Objectives: We present a patient with specific antibody deficiency with normal immunoglobins (SADNI), immune dysregulation (ID), and stage III ovarian carcinoma as an example of the need to modify conventional treatment in the context of malignancy, IEI, and ongoing infections. Methods: This is a retrospective chart review of the patient's clinical manifestations, laboratory evaluation and treatment course. Results: Our patient is a female with SADNI and ID diagnosed with stage III ovarian carcinoma at 60 years of age. Her ID accounted for antinuclear antibody positive (ANA+) mixed connective tissue diseases, polyarthralgia, autoimmune neutropenia, asthma, autoimmune thyroiditis, and Celiac disease. Due to the lack of precedent in the literature, her treatment was modified with continuous input from infectious disease, allergy/immunology and oncology specialist using a multidisciplinary approach.The patient completed debulking surgery and 6 cycles of chemotherapy. The dosing for immunoglobulin replacement therapy was increased for prophylaxis. Chemotherapy doses were lowered for all cycles preemptively for IEI. The therapy included carboplatin, paclitaxel, bevacizumab, and pegfilgrastim. The patient completed six-months of maintenance medication involving bevacizumab.Her treatment course was complicated by Mycobacterium avium-complex (MAC) infection, elevated bilirubin and liver enzymes attributed to excessive immunoglobulin replacement therapy, and urinary tract infection (UTI) and incontinence.Cancer genetic analysis revealed no targetable markers and primary immunodeficiency gene panel of 407 genes by Invitae was unrevealing. Lab tests revealed no evidence of Epstein-Barr Virus (EBV) infection. Post-chemotherapy imaging revealed no evidence of cancer for 1 year and 4 months, but the disease relapsed subsequently. The patient's lung scarring requires vigilance. Conclusions: Our patient with ovarian cancer and IEI required modified treatment and prevention of complications. In cases of IEI, optimal chemotherapy should be titrated to minimize immunosuppression yet treat cancer aggressively while decreasing the risk of infection with prophylactic antibiotics and prolonged post-treatment surveillance, including pulmonary evaluation.

6.
Vaccines (Basel) ; 10(7)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35891212

RESUMO

The emergence of SARS-CoV-2 mutants, waning immunity, and breakthrough infections prompted the use of booster doses of the COVID-19 vaccine to fight against the pandemic. India started booster doses in January 2022 and it is critical to determine the intention of booster dose uptake and its correlates. Therefore, the current cross-sectional study aimed to investigate booster dose acceptability and associated predictors among the Indian population. A convenience sampling technique was utilized to recruit a sample of 687 Indian residents. A 55-item psychometric validated survey tool was used to assess booster dose acceptability, vaccine literacy and vaccine confidence. Univariate, bivariate, and multivariate statistical methods were used to analyze the data. Over 50% of participants reported their willingness to take the booster dose. Among the group not willing to take the booster dose (n = 303, 44.1%), a significantly larger proportion of respondents were unvaccinated with the primary series (12.2% vs. 5.2%, p < 0.001), had an annual income below 2.96 lacs/annum (52.8% vs. 33.1, p < 0.001), were residents of rural areas (38.0% vs. 23.2%, p < 0.001), were not living with vulnerable individuals (78.5% vs. 65.2%, p < 0.001) and did not have family/friends who had tested positive for COVID-19 (54.6% vs. 35.1%, p = 0.001). Demographic, vaccine variables and multi-theory model subscales to predict the initiation of booster dose among hesitant participants were statistically significant, R2 = 0.561, F (26, 244) = 11.978, p < 0.001; adjusted R2 = 0.514. Findings of this study highlight the need to develop evidence-based interventions to promote vaccine uptake, particularly among hard-to-reach communities living in developing countries.

7.
Biol Res Nurs ; 24(4): 433-447, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35499926

RESUMO

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Cardiopatias , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Cognição/fisiologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Feminino , Perfil Genético , Genômica , Cardiopatias/induzido quimicamente , Humanos , Proteínas Serina-Treonina Quinases , Sobreviventes/psicologia
8.
Breast Cancer Res Treat ; 192(2): 385-399, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997364

RESUMO

PURPOSE: Most studies of adherence to treatment for breast cancer have focused on early-stage patients. Findings from these studies may not generalize to patients with metastatic breast cancer (MBC). The objective of this study was to identify barriers and facilitators of adherence to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors among patients with MBC, guided by the social ecologic model (SEM). METHODS: Patients with MBC (N = 25), their caregivers (N = 9), and oncology providers (N = 13) completed semi-structured qualitative interviews exploring their experiences with CDK4/6 inhibitors. Interviews were audio-recorded, transcribed verbatim, and analyzed by three raters using a combined deductive and inductive approach. RESULTS: Qualitative analysis identified barriers and facilitators of adherence at each SEM level. Intrapersonal and interpersonal factors were most frequently discussed. Intrapersonal factors included knowledge/beliefs about CDK4/6 inhibitors, side effects, and establishing a routine. Interpersonal factors included effective communication with/coordination by the care team, support from family and friends, and information from other patients with MBC. Although less frequently discussed, policy factors (i.e., cost of CDK4/6 inhibitors) were of great concern to patients, caregivers, and providers. CONCLUSION: Barriers to adherence to CDK4/6 inhibitors exist at multiple levels. Our results underscore the potential value of a multilevel intervention (e.g., patient education, evidence-based strategies for symptom management, tips for open and assertive communication with providers, information about financial resources/support available, and so on) to support adherence in this population.


Assuntos
Neoplasias da Mama , Quinase 6 Dependente de Ciclina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Cuidadores , Quinase 4 Dependente de Ciclina , Feminino , Humanos , Pesquisa Qualitativa
9.
Clin Breast Cancer ; 22(2): 103-114, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34903452

RESUMO

PRECLINICAL STUDIES: have demonstrated a complex cross-talk between Notch and estrogen signaling in ERα-positive breast cancer. Gamma-secretase inhibitors (GSIs) are investigational agents that block the cleavage and activation of Notch receptors. In animal models of endocrine-resistant breast cancer, combinations of tamoxifen and GSIs produce additive or synergistic efficacy, while decreasing the intestinal toxicity of GSIs. However, results of a clinical trial of a GSI-endocrine therapy combination in the metastatic setting have not been published to date, nor had the safety of such combinations been investigated with longer term treatment. We conducted a phase 1b dose escalation trial (NCT01149356) of GSI RO4929097 with exemestane in patients with ERα+, metastatic breast cancer (MBC) STUDY OBJECTIVES: To determine the safety, tolerability and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of RO4929097 when administered in combination with exemestane in patients with estrogen receptor positive metastatic breast cancer RESULTS: We enrolled 15 patients with MBC. Of 14 evaluable patients, one had a partial response, 6 had stable disease and 7 progressive disease. Twenty % of patients had stable disease for ≥ 6 months. Common toxicities included nausea (73.3%), anorexia (60%), hyperglycemia (53.3%), hypophosphatemia (46.7%), fatigue (66.7%) and cough (33.0%). Grade 3 toxicities were uncommon, and included hypophosphatemia (13%) and rash (6.3%). Rash was the only DLT observed at 140 mg/d. Results suggest a possible recommended phase 2 dose of 90 mg/d. Ten patients with evaluable archival tissue showed expression of PKCα, which correlated with expression of Notch4. Mammospheres from a PKCα-expressing, endocrine-resistant T47D cell line were inhibited by a GSI-fulvestrant combination CONCLUSIONS: Our data indicate that combinations including endocrine therapy and Notch inhibitors deserve further investigation in endocrine-resistant ERα-positive breast cancer.


Assuntos
Androstadienos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzazepinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fluorocarbonos/uso terapêutico , Idoso , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor Notch3 , Receptores Notch/uso terapêutico
11.
Curr Oncol Rep ; 23(8): 99, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259950

RESUMO

PURPOSE OF REVIEW: To give an overview of the role of social media (SoMe) in cardio-oncology during the COVID-19 pandemic. RECENT FINDINGS: SoMe has been critical in fostering education, outreach, awareness, collaboration, dissemination of information, and advocacy in cardio-oncology. This has become increasingly evident during the COVID-19 pandemic, during which SoMe has helped share best practices, community, and research focused on the impact of COVID-19 in cardiology and hematology/oncology, with cardio-oncology at the interface of these two subspecialty fields. A strength of SoMe is the ability to amplify a message in real-time, globally, with minimal investment of resources. This has been particularly beneficial for the emerging field of cardio-hematology/cardio-oncology, a field focused on the interplay of cancer and cardiovascular disease. SoMe field especially during the COVID-19 pandemic. We illustrate how social media has supported innovation (including telemedicine), amplification of healthcare workers' voice, and illumination of pre-existing and continued health disparities within the field of cardio-oncology during the pandemic.


Assuntos
COVID-19/complicações , Doenças Cardiovasculares/terapia , Neoplasias/terapia , SARS-CoV-2/isolamento & purificação , Mídias Sociais/estatística & dados numéricos , Telemedicina , COVID-19/transmissão , COVID-19/virologia , Doenças Cardiovasculares/virologia , Humanos , Disseminação de Informação , Neoplasias/virologia
12.
Cardiooncology ; 7(1): 22, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059163

RESUMO

OBJECTIVE: Women with breast cancer (BCA) and cardiovascular disease (CVD) risk factors are at increased risk of developing cardiovascular complications when exposed to potentially cardiotoxic cancer therapy. The benefit of aggressive CVD risk factor modification to reduce adverse treatment-related psychologic and biologic effects is not well established. METHODS: Using a single group pre-test, post-test design, 33 women with BCA receiving anthracycline and/or trastuzumab therapy participated in a 6-month comprehensive CVD risk reduction program involving formal cardio-oncology evaluation along with regular motivational counseling for improved nutrition and physical activity. Study parameters were assessed at baseline and 6 months with paired t-tests used to evaluate changes after the intervention. RESULTS: The mental component summary score assessed by SF-36V2 improved significantly after program completion (45.0 to 48.8, effect size 0.37, p = 0.017), however the physical component summary score declined (46.2 to 40.9, effect size - 0.53, p = 0.004). Despite this decline in perceived physical health, markers of health-related fitness and nutritional status were maintained or improved. Systolic and diastolic blood pressure also improved after the intervention (136.7 to 124.1 mmHg, p = 0.001 and 84.0 to 78.7 mmHg, p = 0.031, respectively). No significant change in resting heart rate, body mass index, lipids, hemoglobin A1C, or left ventricular ejection fraction was observed. CONCLUSIONS: Patient-reported mental health improved significantly in women with BCA enrolled in a comprehensive CVD risk reduction program despite exposure to potentially cardiotoxic therapies. This study provides preliminary data for future randomized controlled trials evaluating the effects CVD risk reduction program in high-risk breast cancer cohorts.

13.
Curr Oncol Rep ; 23(6): 64, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33855620

RESUMO

PURPOSE OF REVIEW: This study aims to assess the current state of cardio-oncology in reference to advocacy efforts, access to care, and perspective of stakeholders in their ability to provide patient care as well as development of "across the aisle" synergy among cardiologists and oncologists and academic and non-academic centers in various worldwide locations. RECENT FINDINGS: During the last decade, there has been a significant and diverse growth in cardio-oncology. We reviewed the experience from cardiologists and oncologists across different healthcare systems, the global trends, the role of collaborative networks, and the importance of advocacy efforts. Cardio-oncology will continue to grow, but there is an unmet need to increase awareness, improve education, and expand access to care to larger segments of the cancer population in order to have a more significant impact on their health. The growing collaboration through professional societies and collaborative networks provides an opportunity to advance the cardiovascular care of cancer patients to meet the projected needs in a growing and more diverse population.


Assuntos
Cardiologia , Colaboração Intersetorial , Oncologia , Cardiologia/economia , Cardiologia/educação , Doenças Cardiovasculares/complicações , Acessibilidade aos Serviços de Saúde , Humanos , Oncologia/economia , Oncologia/educação , Neoplasias/complicações , Defesa do Paciente , Mídias Sociais
14.
Circ Genom Precis Med ; 14(3): e000082, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33896190

RESUMO

Cardiovascular disease and cancer are the leading causes of death in the United States, and hormone-dependent cancers (breast and prostate cancer) are the most common noncutaneous malignancies in women and men, respectively. The hormonal (endocrine-related) therapies that serve as a backbone for treatment of both cancers improve survival but also increase cardiovascular morbidity and mortality among survivors. This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence-based approach to prevent and detect adverse cardiovascular outcomes. Areas of uncertainty are highlighted, including the cardiovascular effects of different durations of hormonal therapy, the cardiovascular risks associated with combinations of newer generations of more intensive hormonal treatments, and the specific cardiovascular risks that affect individuals of various races/ethnicities. Finally, there is an emphasis on the use of a multidisciplinary approach to the implementation of lifestyle and pharmacological strategies for management and risk reduction both during and after active treatment.


Assuntos
Neoplasias da Mama/terapia , Doenças Cardiovasculares , Sistema Cardiovascular , Hormônios , Neoplasias da Próstata/terapia , American Heart Association , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/terapia , Feminino , Hormônios/efeitos adversos , Hormônios/uso terapêutico , Humanos , Masculino , Estados Unidos
15.
Cureus ; 13(2): e13096, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33728118

RESUMO

COVID-19 has become a pandemic. It affects multiple systems of the body including the nervous system. It invades the nervous systems through multiple routes - either olfactory tract, bloodstream (by binding to endothelial receptors) or via ACE-2 receptors in the brain. We report a case of Guillain-Barré syndrome (GBS) variant (acute motor axonal neuropathy (AMAN type)) associated with COVID-19 infection with positive polymerase chain reaction (PCR) test for COVID-19 and positive contact history with infected family member. GBS and its variants like AMAN can occur due to COVID-19 infection through its immune-mediated effects. Diagnosis of GBS should depend on the clinical and supportive criteria. The treatment should be started early to prevent progression and disease co-morbidities.

16.
JAMA Oncol ; 7(1): 61-69, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151286

RESUMO

IMPORTANCE: Indoleamine 2,3-dioxygenase 1 (IDO1) causes tumor immune suppression. The IDO1 pathway inhibitor indoximod combined with a taxane in patients with ERBB2-negative metastatic breast cancer was tested in a prospective clinical trial. OBJECTIVE: To assess clinical outcomes in patients with ERBB2-negative metastatic breast cancer treated with indoximod plus a taxane. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 double-blinded randomized 1:1 placebo-controlled clinical trial enrolled patients at multiple international centers from August 26, 2013, to January 25, 2016. Eligibility criteria included ERBB2-negative metastatic breast cancer, ability to receive taxane therapy, good performance status, normal organ function, no previous immunotherapy use, and no autoimmune disease. The study was discontinued in June 2017 because of lack of efficacy. Data analysis was performed from February 2019 to April 2020. INTERVENTIONS: A taxane (paclitaxel [80 mg/m2] weekly 3 weeks on, 1 week off, or docetaxel [75 mg/m2] every 3 weeks) plus placebo or indoximod (1200 mg) orally twice daily as first-line treatment. MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS); secondary end points were median overall survival, objective response rate, and toxic effects. A sample size of 154 patients would detect a hazard ratio of 0.64 with 1-sided α = .1 and ß = .2 after 95 events. Archival tumor tissue was stained with immunohistochemistry for IDO1 expression as an exploratory analysis. RESULTS: Of 209 patients enrolled, 169 were randomized and 164 were treated (85 in the indoximod arm; 79 in the placebo arm). The median (range) age was 58 (29-85) years; 166 (98.2%) were female, and 135 (79.9%) were White. The objective response rate was 40% and 37%, respectively (indoximod vs placebo) (P = .74). The median (range) follow-up time was 17.4 (0.1-39.4) months. The median PFS was 6.8 months (95% CI, 4.8-8.9) in the indoximod arm and 9.5 months (95% CI, 7.8-11.2) in the placebo arm (hazard ratio, 1.2; 95% CI, 0.8-1.8). Differences between the experimental and placebo arms in median PFS (6.8 vs 9.5 months) and overall survival (19.5 vs 20.6 months) were not statistically significant. Grade 3 or greater treatment-emergent adverse events occurred in 60% of patients in both arms. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that, among patients with ERBB2-negative metastatic breast cancer, addition of indoximod to a taxane did not improve PFS compared with a taxane alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01792050.


Assuntos
Neoplasias da Mama , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Taxoides/efeitos adversos , Triptofano/análogos & derivados
17.
J Natl Cancer Inst ; 113(5): 513-522, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33179744

RESUMO

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients-individuals with an active or prior cancer history and with or at risk of cardiovascular disease-are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.


Assuntos
COVID-19/complicações , Cardiotoxicidade/terapia , Doenças Cardiovasculares/terapia , Diagnóstico por Imagem/métodos , Neoplasias/terapia , SARS-CoV-2/isolamento & purificação , COVID-19/transmissão , COVID-19/virologia , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/virologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/virologia , Prova Pericial , Humanos , Neoplasias/diagnóstico , Neoplasias/virologia
18.
Cardiooncology ; 6(1): 28, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33292763

RESUMO

BACKGROUND: Re-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated. OBJECTIVES: To assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers' opinions on healthcare policies among oncology and cardiology practitioners. METHODS: An electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology, American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty. RESULTS: One thousand four hundred fifteen providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p = 0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p = < 0.001). Academic physicians (74.5%) felt better supplied with personal protective equipment (PPE) vs non-academic (74.5% vs 67.2%; p = 0.018). Telemedicine was less common in Europe 81% (74/91), and Latin America 64% (101/158), than the United States, 88% (950/1097) (p = < 0.001). 95% of all groups supported more active leadership from medical professional societies. CONCLUSIONS: These results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.

19.
J Clin Med ; 9(10)2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33081013

RESUMO

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized-natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33-68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

20.
Am Soc Clin Oncol Educ Book ; 40: 1-15, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32213102

RESUMO

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment-related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment-related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, ß-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.


Assuntos
Cardiotoxicidade/terapia , Doenças Cardiovasculares/terapia , Neoplasias/complicações , Idoso , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Medição de Risco
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