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1.
Clin Transl Oncol ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38914756

ABSTRACT

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.

2.
Future Oncol ; 17(14): 1777-1791, 2021 May.
Article in English | MEDLINE | ID: mdl-33590772

ABSTRACT

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.


Subject(s)
Adenocarcinoma/therapy , Antibodies, Monoclonal, Humanized/administration & dosage , Paclitaxel/administration & dosage , Stomach Neoplasms/therapy , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Chemotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/statistics & numerical data , Esophagogastric Junction/pathology , Esophagogastric Junction/surgery , Female , Gastrectomy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/statistics & numerical data , Paclitaxel/adverse effects , Progression-Free Survival , Retrospective Studies , Spain/epidemiology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Ramucirumab
4.
Gastroenterol. hepatol. (Ed. impr.) ; 39(1): 1-8, ene. 2016. ilus, tab
Article in Spanish | IBECS | ID: ibc-149314

ABSTRACT

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


Subject(s)
Humans , Colorectal Neoplasms/pathology , Lymphatic Metastasis/pathology , Adenocarcinoma/pathology , Biomarkers, Tumor/analysis , Risk Factors , Histological Techniques/methods , Forecasting
6.
Gastroenterol Hepatol ; 39(1): 1-8, 2016 Jan.
Article in Spanish | MEDLINE | ID: mdl-26049903

ABSTRACT

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.


Subject(s)
Adenocarcinoma/pathology , Colorectal Neoplasms/pathology , Lymphatic Metastasis/diagnosis , Neoplasm Invasiveness , Adenoma , Humans , Lymph Nodes/pathology , Prognosis , Risk Factors
7.
Oncotarget ; 6(9): 7348-63, 2015 Mar 30.
Article in English | MEDLINE | ID: mdl-25749516

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Lipid Metabolism , 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics , 1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism , ATP Binding Cassette Transporter 1/genetics , ATP Binding Cassette Transporter 1/metabolism , Adult , Aged , Aged, 80 and over , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Proliferation , Colorectal Neoplasms/metabolism , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Recurrence , Regression Analysis , Retrospective Studies , Stearoyl-CoA Desaturase/genetics , Stearoyl-CoA Desaturase/metabolism , Time Factors , Treatment Outcome
8.
Mol Cancer Ther ; 13(9): 2226-37, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24980946

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Organoplatinum Compounds/administration & dosage , Pyrimidines/administration & dosage , Pyrimidines/chemistry , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , DNA Repair , E-Selectin/genetics , Genotype , Humans , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Oxaliplatin , Pharmacogenetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Recurrence , Regression Analysis , Retrospective Studies , Treatment Outcome , Young Adult
11.
Int J Radiat Oncol Biol Phys ; 61(1): 185-91, 2005 Jan 01.
Article in English | MEDLINE | ID: mdl-15629610

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Cranial Irradiation , Dacarbazine/analogs & derivatives , Dacarbazine/therapeutic use , Aged , Antineoplastic Agents, Alkylating/adverse effects , Combined Modality Therapy/methods , Cranial Irradiation/adverse effects , Dacarbazine/adverse effects , Disease-Free Survival , Female , Humans , Male , Middle Aged , Temozolomide
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