RESUMO
OBJECTIVE: To determine the potential prognostic value of clinical and molecular biomarkers in the survival of patients with platinum-resistant ovarian cancer treated with olaparib and pegylated liposomal doxorubicin. METHODS: ROLANDO was a single-arm phase II trial that included patients with high-grade serous or endometrioid tumors and at least one previous platinum-resistant recurrence regardless of BRCA status. Patients received 6 cycles of pegylated liposomal doxorubicin every 28 days plus olaparib 300 mg twice daily. followed by olaparib 300 mg twice daily; monotherapy until progression or unacceptable toxicity. Prognostic factors including previous lines (and platinum-containing ones), BRCA mutation status, previous bevacizumab, CA-125 levels, and the neutrophil/lymphocyte ratio, lymphocyte/monocyte ratio, and platelet/lymphocyte ratio calculated at inclusion were analyzed through a multivariate logistic regression and factor analysis of mixed data. RESULTS: Thirty-one patients were included. Median age was 57 years (range 43-75), Eastern Cooperative Oncolgy Group performance status 0/1: 32.3%/67.7% and BRCA mutated: 16.1%. Prior treatment lines were >2 lines: 14 (45.2%) patients, ≥2 platinum lines: 21 patients (67.7%) and previous bevacizumab 19 (61.3%) patients. CA-125 was >2 upper limit normal in 24 (77.4%) patients. A high neutrophil/lymphocyte ratio was associated with worse overall survival by univariate/multivariate regression model (HR=11.18; 95% CI 1.1 to 114.5; p=0.042). No other factors were associated with overall survival in the multivariate model. A multifactorial signature based on clinical and molecular baseline characteristics was capable of defining six patient clusters. Three of these clusters had significantly better prognosis, with a median overall survival of 21.3 months (95% CI 12.2 to not reached). CONCLUSIONS: High neutrophil/lymphocyte ratio at platinum-resistant relapse indicated poor prognosis in patients treated with olaparib plus pegylated liposomal doxorubicin. A multifactorial clinical signature was more precise than single variables for implying the prognosis and may help in therapeutic assignment after further validation in large prospective cohorts.
Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Bevacizumab , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Doxorrubicina/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
There is no standard treatment for patients with gastric marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who are resistant to, or ineligible for, anti-Helicobacter pylori (anti-HP) therapy. In this study, we investigated the activity of the rituximab, cyclophosphamide, vincristine and prednisone (R-CVP) regimen in patients with gastric MALT lymphoma. Patients were included provided they had untreated gastric MALT lymphoma (except for anti-HP therapy) and were resistant to, or ineligible for, anti-HP therapy. Treatment plan consisted of six to eight 21-day cycles of the R-CVP chemotherapy regimen. Toxicity, response, relapse and survival were evaluated. Twenty patients (12 women and 8 men) were included in the analyses with median age of 59 years. Thirteen patients (65%) had stage I tumours, and seven patients (35%) had stages II-IV tumours. The overall response rate was 100%, with 19 (95%) complete responses and one (5%) partial response. Regimen toxicity was mild and mainly hematological, and no cases of gastric bleeding or perforation occurred. After a median follow-up of 56.3 months, three patients had relapsed, and 19 patients remained alive (specific lymphoma survival 100%), of whom 17 had no evidence of disease. In our experience, the R-CVP regimen is a well-tolerated and effective treatment for patients with gastric MALT lymphoma who are resistant to, or ineligible for, anti-HP therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
The prognosis of follicular lymphoma (FL) has significantly improved over the last decade, particularly following the introduction of the anti-CD20 monoclonal antibody rituximab, which has challenged the old concept of FL as an incurable disease. However, the decision whether to start treatment in a patient with advanced FL or adopt a watch-and-wait policy remains a subject of controversy. Furthermore, the optimal first-line treatment for FL remains a clinical challenge owing to the numerous different therapeutic options available. In this review, the authors focus on the initial management of patients with newly diagnosed FL, consider the different treatment options for every stage, paying special consideration to the therapeutic approaches for each clinical scenario, and discuss future directions.
Assuntos
Linfoma Folicular/terapia , Ensaios Clínicos como Assunto , HumanosRESUMO
PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.
Assuntos
Carboplatina , Esquema de Medicação , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Humanos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Estudos Retrospectivos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Pessoa de Meia-Idade , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversosRESUMO
Introducción: Para el desarrollo de cualquier sociedad es importante el recurso humano competente, lo que implica enrumbar los esfuerzos hacia el mejoramiento del desempeño profesional en aras de lograr que su impacto contribuya al progreso y desarrollo humanos. Objetivo: Caracterizar el desempeño profesional en Histología Humana de los especialistas en formación de Anatomía Patológica del Hospital Universitario "General Calixto García" durante el período 2015-2020. Métodos: Se realizó un estudio descriptivo-observacional con enfoque mixto. Coincidieron el universo y la muestra, compuestos por 13 especialistas en formación que se encontraban en el primer semestre del primer año de la especialidad y 8 profesores de la especialidad de Anatomía Patológica. El muestreo fue por conveniencia. Se utilizaron métodos teóricos y empíricos. Se empleó una Estadística descriptiva, en particular el análisis porcentual, y la frecuencia absoluta y relativa, a partir de los programas Microsoft Excel y el SPSS, los que permitieron el procesamiento cuantitativo de los instrumentos aplicados. Se empleó la tecnología para la determinación de problemas y potencialidades de la Educación Avanzada. Conclusiones: La aplicación de la tecnología antes mencionada permitió caracterizar el estado actual del desempeño profesional en Histología Humana del especialista en formación de Anatomía Patológica, lo cual reveló carencias y dificultades en las dimensiones: conocimiento teórico-práctico en Histología Humana, comportamiento humano, y comportamiento ético y bioético. La triangulación metodológica aplicada a los resultados de los instrumentos contribuyó a la identificación del inventario de problemas y potencialidades.
Introduction: Competent human resources are important for the development of any society, which implies directing efforts towards the improvement of professional performance in order to achieve their impact on and such contribution to human progress and development. Objective: To characterize the professional performance in Human Histology of specialists being trained in Pathological Anatomy at Hospital Universitario General Calixto García during the period 2015-2020. Methods: A descriptive-observational study with a mixed approach was conducted. The study universe and the sample coincided, composed of 13 specialists being trained in their first semester of the specialty's first academic year and 8 professors of the Pathological Anatomy specialty. The sampling was by convenience. Theoretical and empirical methods were used. Descriptive statistics were used, particularly the percentage analysis, as well as absolute and relative frequency, by using the programs Microsoft Excel and SPSS, which allowed the quantitative processing of the applied instruments. Technology was used for determining problems and potentialities of advanced education. Conclusions: The application of the aforementioned technology allowed characterizing the current state of professional performance in Human Histology of the specialist being trained in Pathological Anatomy, which revealed deficiencies and difficulties in the dimensions theoretical-practical knowledge in Human Histology, human behavior, as well as ethical and bioethical behavior. The methodological triangulation applied to the results of the instruments contributed to the identification of the inventory of problems and potentialities.
RESUMO
The differential diagnosis of new-onset pulmonary infiltrates during adjuvant therapy in a cancer patient is challenging. Opportunistic infections, pulmonary drug-induced toxicity and metastatic dissemination of the underlying cancer are the most common causes. However, although infrequent, the development of a second primary pulmonary neoplasia should be taken into account. We present the clinical case of a breast cancer patient who developed progressive pulmonary infiltrates during adjuvant therapy, who was finally diagnosed as having a second lung neoplasm of unexpected histology.
RESUMO
BACKGROUND: A high neutrophil to lymphocyte ratio (NLR) has been associated with adverse outcomes in non-small cell lung cancer (NSCLC). However, information on epidermal growth factor receptor (EGFR)-mutant advanced NSCLC is scarce, and most of the studies published have been conducted in Asian populations. We aimed to assess the influence of pretreatment NLR on progression-free survival (PFS) and overall survival (OS) in Western European patients treated with EGFR tyrosine kinase inhibitors (TKIs). METHODS: A retrospective evaluation of 41 patients with EGFR-mutant advanced NSCLC treated with EGFR TKIs between June 2010 and May 2016 was carried out. The association between several prognostic factors including pretreatment NLR and survival was analyzed. RESULTS: Median PFS and OS were 10.58 and 20.84 months, respectively. OS for patients with a high NLR was 7.4 months, compared to 24.6 months for patients with a low NLR (p = 0.0122). In multivariate analysis, poor performance status (ECOG PS ≥ 2) and presence of ≥ 3 metastatic locations were identified as significant independent prognostic factors for worse PFS. For OS, unfavorable prognostic factors were a high NLR and central nervous system metastasis at diagnosis. CONCLUSION: Pretreatment NLR is an independent prognostic factor for OS in Western European patients with EGFR-mutant NSCLC treated with EGFR TKIs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Linfócitos , Neutrófilos , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Feminino , Seguimentos , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Análise de SobrevidaAssuntos
Antineoplásicos Hormonais/efeitos adversos , Pneumonia em Organização Criptogênica/etiologia , Raios gama/efeitos adversos , Lesões por Radiação/etiologia , Tamoxifeno/efeitos adversos , Adulto , Anti-Inflamatórios/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Pneumonia em Organização Criptogênica/tratamento farmacológico , Pneumonia em Organização Criptogênica/patologia , Feminino , Humanos , Prednisona/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/patologiaRESUMO
Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL), both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life.
RESUMO
BACKGROUND: Late-onset neutropenia (LON) is a known adverse effect to rituximab therapy. Information about its real incidence and clinical implications comes from case reports and few retrospective studies specifically designed to study LON. However, large prospective studies of LON are lacking in the literature. We aimed to determine the incidence of LON in a group of non-Hodgkin lymphoma patients treated with rituximab and to analyze the clinical course, complications, and risk factors associated with LON. PATIENTS AND METHODS: We retrospectively reviewed 183 patients with a diagnosis of non-Hodgkin lymphoma consecutively treated with rituximab alone or in combination with chemotherapy. RESULTS: We identified 11 patients with grade 3/4 LON (13 episodes) out of 183 patients (6%). The median time to onset of LON was 75 days, and the median time to recovery from neutropenia was 100 days. The median neutrophil count nadir was 0.55 × 10(9)/L (range, 0.06-0.9 × 10(9)/L). Two patients presented infectious complications, one with fatal outcome. CONCLUSION: In our experience, the incidence of recognized LON is low (6%), although its real incidence may be greater because of the asymptomatic course and quick recovery in most cases. Infectious complications are unusual, but life-threatening complications can emerge. A careful evaluation of all cases of LON is warranted.