RESUMO
Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4-4.3) and 7.4 (95% CI: 6.4-8.9) in combination regimen and 2.0 (1.1-2.8) and 4.3 (95% CI: 1.9-7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.
Assuntos
Adenocarcinoma/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Espanha/epidemiologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , RamucirumabRESUMO
INTRODUCTION: Endoscopic resection is the common treatment in pT1 colorectal adenocarcinoma whenever possible. The presence of adverse histological factors requires subsequent lymph node evaluation. MATERIALS AND METHODS: We selected 29 colorectal pT1 adenocarcinoma including endoscopic polypectomies and the corresponding surgical specimens. All histologic parameters associated with N+ were evaluated by 2 pathologists, including: tumor differentiation grade, depth of invasion in the submucosa, angiolymphatic invasion (ALI), perineural invasion, chronic inflammation, tumor budding, poorly differentiated cluster, pre-existing adenoma, tumor border, and endoscopic resection margin. Univariate and multivariate logistic regression analysis were performed to assess the individual capacity of each variable to predict N+. RESULTS: In the univariate analysis, rectal tumor localization, ALI and poorly differentiated cluster was significantly associated with N+. Among the significant parameters, ALI had the highest area under the ROC curve (0.875). Multivariate analysis showed no independent variables associated with N+. CONCLUSIONS: We confirm that ALI and the presence of poorly differentiated cluster are frequently associated with N+ in early colorectal cancer. Consequently, these parameters should be routinely evaluated by pathologists.
Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Metástase Linfática/diagnóstico , Invasividade Neoplásica , Adenoma , Humanos , Linfonodos/patologia , Prognóstico , Fatores de RiscoRESUMO
Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child-Pugh class A.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Estadiamento de Neoplasias , Terapia Combinada , OncologiaAssuntos
Neoplasias da Mama/patologia , Carcinoma Ductal Pancreático , Carcinoma/secundário , Estrogênios , Metástase Linfática , Neoplasias Hormônio-Dependentes/secundário , Segunda Neoplasia Primária/patologia , Neoplasias Pancreáticas , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/terapia , Carcinoma/diagnóstico , Carcinoma de Células Acinares , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Feminino , Humanos , Neoplasias Pulmonares , Micrometástase de Neoplasia , Neoplasias Hormônio-Dependentes/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias Pancreáticas/cirurgia , PancreaticoduodenectomiaAssuntos
Carcinoma/secundário , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Retais/patologia , Neoplasias do Ânus/complicações , Neoplasias do Ânus/patologia , Carcinoma/complicações , Cistos/diagnóstico , Cistos/etiologia , Diagnóstico Diferencial , Humanos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/complicaçõesRESUMO
PURPOSE: To evaluate the safety profile and efficacy of whole brain radiotherapy (WBRT) concomitantly with temozolomide (TMZ) in patients with brain metastases (BM). METHODS AND MATERIALS: Patients with BM were randomly assigned to 30 Gy of WBRT with or without concomitant TMZ (75 mg/m(2)/d) plus two cycles of TMZ (200 mg/m(2)/d for 5 days). The primary outcome was analysis of neurologic toxicity. The primary efficacy measures were 90-day progression-free survival of BM and the radiologic response at Days 30 and 90. RESULTS: We enrolled 82 patients. No neurologic acute toxicity was observed. Grade 3 or worse hematologic toxicity was seen in 3 patients and Grade 3 or worse vomiting in 1 patient of the WBRT plus TMZ arm. The objective response rate at 30 and 90 days and overall survival were similar in both arms. The percentage of patients with progression-free survival of BM at 90 days was 54% for WBRT vs. 72% for WBRT and TMZ (p = 0.03). Death from BM was greater in the WBRT arm (69% vs. 41%, p = 0.03). CONCLUSION: The concomitant use of RT with TMZ was well tolerated and resulted in significantly better progression-free survival of BM at 90 days. Although caution should be used, these results suggest TMZ could improve local control of BM.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Terapia Combinada/métodos , Irradiação Craniana/efeitos adversos , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TemozolomidaRESUMO
Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group.
Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Metabolismo dos Lipídeos , 1-Acilglicerol-3-Fosfato O-Aciltransferase/genética , 1-Acilglicerol-3-Fosfato O-Aciltransferase/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células , Neoplasias Colorretais/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Análise de Regressão , Estudos Retrospectivos , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with colon cancer who are more likely to benefit from adjuvant chemotherapy. We investigated the effect of single-nucleotide polymorphisms (SNP) within genes involved in oxaliplatin and fluoropyrimidines metabolism, DNA repair mechanisms, drug transport, or angiogenesis pathways on outcome for patients with stage II and III colon cancer treated with adjuvant chemotherapy. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 202 patients with stage II and III colon cancer receiving oxaliplatin-based adjuvant chemotherapy from January 2004 to December 2009. Genotyping was performed for 67 SNPs in 32 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 patients treated with the same chemotherapy regimens. The combination of the selectin E (SELE) rs3917412 G>A G/G and the methylentetrahydrofolate reductase (MTHFR) rs1801133 T/T genotypes was associated with a significantly increased risk for recurrence in both the training [RR = 4.103; 95% confidence interval (CI), 1.803-9.334; P = 0.001] and the validation cohorts (RR = 3.567; 95% CI, 1.253-10.151; P = 0.017) in the multiple regression analysis considering the stage, lymphovascular invasion, and bowel perforation as covariates. The combined analysis of these polymorphisms was also significantly associated with overall survival in both cohorts (RR = 3.388; 95% CI, 0.988-11.623; P = 0.052, and RR = 3.929; 95% CI, 1.144-13.485; P = 0.020, respectively). Our findings suggest that the SELE rs3917412 and MTHFR rs1801133 SNPs could serve as pharmacogenetic predictors of tumor recurrence in patients with early-stage colon cancer treated with oxaliplatin-based adjuvant chemotherapy, thus allowing personalized selection of treatment to optimize clinical outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Compostos Organoplatínicos/administração & dosagem , Pirimidinas/administração & dosagem , Pirimidinas/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Reparo do DNA , Selectina E/genética , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Oxaliplatina , Farmacogenética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Recidiva , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCCIÓN: El tratamiento habitual del adenocarcinoma colorrectal pT1 consiste en la resección endoscópica siempre que sea posible. Se requiere la evaluación de los ganglios linfáticos locorregionales cuando se detectan factores histológicos adversos en las polipectomías endoscópicas. MATERIALES Y MÉTODOS: Se seleccionaron 29 adenocarcinomas colorrectales pT1 incluyendo las polipectomías endoscópicas y piezas quirúrgicas correspondientes. Se evaluaron por 2 patólogos todos los parámetros histológicos asociados a N+, incluyendo: grado de diferenciación tumoral, profundidad de invasión en submucosa, invasión angiolinfática (IAL), invasión perineural, inflamación crónica, gemaciones tumorales, grupos de tumor pobremente diferenciados, adenoma preexistente, borde tumoral y margen de resección endoscópico. Se realizó un análisis de regresión logística univariante y multivariante para evaluar la capacidad individual de cada variable para predecir N+. RESULTADOS: En el análisis univariante, la localización rectal, la presencia de IAL y la presencia de grupos de tumor pobremente diferenciados se asociaron significativamente con metástasis ganglionares. De todas estas variables, la presencia de IAL presentó la mayor área bajo la curva ROC (0,875). El análisis multivariante no encontró ninguna variable independiente asociada a N+. CONCLUSIONES: La IAL y la presencia de grupos de tumor pobremente diferenciados se asocia frecuentemente con N+ en cáncer colorrectal precoz, por lo que se debe implementar rutinariamente la evaluación de estos parámetros histológicos
INTRODUCTION: Endoscopic resection is the common treatment in pT1 colorectal adenocarcinoma whenever possible. The presence of adverse histological factors requires subsequent lymph node evaluation. MATERIALS AND METHODS: We selected 29 colorectal pT1 adenocarcinoma including endoscopic polypectomies and the corresponding surgical specimens. All histologic parameters associated with N+ were evaluated by 2 pathologists, including: tumor differentiation grade, depth of invasion in the submucosa, angiolymphatic invasion (ALI), perineural invasion, chronic inflammation, tumor budding, poorly differentiated cluster, pre-existing adenoma, tumor border, and endoscopic resection margin. Univariate and multivariate logistic regression analysis were performed to assess the individual capacity of each variable to predict N+. Results In the univariate analysis, rectal tumor localization, ALI and poorly differentiated cluster was significantly associated with N+. Among the significant parameters, ALI had the highest area under the ROC curve (0.875). Multivariate analysis showed no independent variables associated with N+. CONCLUSIONS: We confirm that ALI and the presence of poorly differentiated cluster are frequently associated with N+ in early colorectal cancer. Consequently, these parameters should be routinely evaluated by pathologists