RESUMEN
BACKGROUND: Chemotherapy-induced left ventricular systolic dysfunction (LVSD) may limit survival in cancer patients and therefore should be treated timely with appropriate heart failure medication. This study aimed to evaluate quality of cardiac care in cancer patients with documented chemotherapy-induced LVSD in real-world clinical practice. METHODS: Using an institutional echo database, we screened 1,520 cancer patients for first documentation of chemotherapy-associated LVSD, defined as left ventricular ejection fraction (LVEF) ≤45%. Hospital charts of all 63 patients meeting inclusion criteria were reviewed regarding patient characteristics and frequency of heart failure medication prescription. RESULTS: Patients were 61 (interquartile range [IQR], 50-70) years old, mostly symptomatic, and had an average LVEF of 34 ± 8%. Most patients received anthracyclines (73%) and/or alkylating agents (73%) as part of their chemotherapeutic regimen. Median time from cancer diagnosis to first documentation of LVSD was 2.2 (0.7-5.2) years. Fewer than two-thirds of patients received guideline-recommended heart failure medication, and only one-half of patients received cardiology consult. Cardiology consultation was associated with a significantly higher frequency of heart failure medication prescription (100% vs. 52% for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (P < .0001); 94% vs. 41% for beta-blocker (P < .0001) and better survival (71% vs. 41%; P < .05). CONCLUSIONS: Chemotherapy-associated LVSD is insufficiently treated in cancer patients. Cardiology consultation improves rates of heart failure medication and therefore should be advocated in all patients with chemotherapy-induced LVSD.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/terapia , Anciano , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnósticoRESUMEN
Melanoma, despite its aggressive growth characteristics, is an antigenic tumor expressing several characterized neo- and differentiation antigens. Dendritic cells (DC) when pulsed with defined peptides have been shown to effectively induce melanoma-specific T cell responses in humans and mice. These protect animals from challenge with melanoma, but so far have failed to induce significant tumor regressions. To study the efficacy of DC-based anti-tumor vaccinations, we set up a therapeutic model using C57BL/6J mice with established pulmonary and subcutaneous metastases induced by the B16-melanoma cell line B78-D14. Mice were vaccinated twice with 20,000 antigen-presenting cells, either bone marrow-derived DC or epidermal Langerhans cells (LC), which were loaded with the tyrosinase-related protein 2 (TRP2) peptide. Generally, DC cultured with fetal calf serum (FCS) induced a dominant unspecific response. This was not seen using LC cultured without serum; however, vaccination with TRP2-loaded FCS-free LC alone failed to influence the growth of established B16 tumors. A reproducible reduction of tumor size and weight was only obtained if LC vaccinations with TRP2 were followed by a 5-day treatment of mice with 200,000 IU IL-2 intraperitoneally twice/daily. Omitting the TRP2 peptide abolished the efficacy of this combined treatment, demonstrating the crucial role of priming a melanoma-specific T cell response. Microcytotoxic assays performed with spleen-derived T cells and melanoma as well as congenic fibroblast lines as targets confirmed the TRP2-dependent specificity of LC-induced immune responses. Thus, despite the fact that tumor-specific T cells were primed, an additional IL-2-dependent stimulus was needed to translate this immune response into a therapeutic effect against established tumors.