Paula Jiménez Fonseca

Level of HER2 Gene Amplification Predicts Response and Overall Survival in HER2-Positive Advanced Gastric Cancer Treated With Trastuzumab

PURPOSE Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. PATIENTS AND METHODS Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. RESULTS In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02). CONCLUSION The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.

Epithelial-mesenchymal transition markers in the differential diagnosis of gastroenteropancreatic neuroendocrine tumors.

OBJECTIVES To elucidate the role of epithelial-mesenchymal transition markers in gastroenteropancreatic neuroendocrine tumors (GEP NETs) and the potential usefulness in their clinical management. METHODS One hundred ten GEP NET paraffin-embedded samples were immunohistochemically analyzed for E-cadherin, N-cadherin, β-catenin, vimentin, Snail1, Snail2, Twist, and Foxc2 protein expression. RESULTS The 5-year survival rate was reduced for those patients showing high Snail1 protein levels, a cytoplasmic E-cadherin pattern, reduced N-cadherin expression, and loss of E-cadherin/β-catenin adhesion complex integrity at the cell membrane. Interestingly, high β-catenin expression was useful in identifying a grade 1 NET subgroup with a favorable clinical course. Importantly, it also helped to discriminate small-cell vs large-cell grade 3 neuroendocrine carcinomas. CONCLUSIONS β-Catenin and N-cadherin immunohistochemical detection might be a useful tool in the differential diagnosis of small-cell vs large-cell G3 neuroendocrine carcinomas. High Snail1 and Foxc2 expression is associated with the invasion and metastatic spread of GEP NETs.

Predictive factors for response to treatment in patients with advanced renal cell carcinoma

SummaryIntroduction The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments. Materials and methods The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well as 2 analytical variables in 135 patients with advanced RCC treated with cytokines (CK) and/or new targeted drugs (NTD). Results 67 patients were treated solely with NTD and 68 with CK (23 also received NTD). Univariate analysis: HIF1α did not correlate significantly with response to these drugs. Overexpression of CAIX was associated with more responses (%) to NTD (64.7 vs. 21.1; p = 0.004) and CK (22.6 vs. 0; p = 0.038). PTEN demonstrated predictive value of response to sunitinib (70.8 vs. 34.1; p = 0.005). p21 was associated with a lower response to sunitinib (35.9 vs. 65.4; p = 0.025). Thrombocytosis was not significantly associated with response to NTD, although it was with CK (0 vs. 20; p = 0.017). Neutrophilia correlated with a lower response to NTD (29.6 vs. 57.5; p = 0.045), although not with CK. Multivariate analysis: Overexpression of CAIX was an independent predictor of significantly higher response to NTD and CK; OR = 8.773 (p < 0.001). Conclusions Our findings highlight the usefulness of CAIX in selecting patients with advanced RCC as candidates for systemic treatment. PTEN and p21 may be important in predicting response to sunitinib. Thrombocytosis and neutrophilia correlate well with response to CK and NTD, respectively.

Prolonged Clinical Benefit of Everolimus Therapy in the Management of High-Grade Pancreatic Neuroendocrine Carcinoma

Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia

Background:We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN).Patients and methods:The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups.Results:The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm3, and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer–Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value.Conclusions:We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN.

Manejo de la infección y la neutropenia febril en el paciente con cáncer sólido

A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry

Background:The choice of chemotherapy in HER2-negative gastric cancer is based on centre’s preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).Methods:We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2–3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of ‘treatment-by-histology’ interaction, was used to estimate treatment effect.Results:Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525–0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054–1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49–0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50–0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46–0.88), P=0.046.Conclusions:As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Tapentadol for Cancer Pain Management: A Narrative Review

Pain is one of the most common symptoms in patients with cancer. The aim of this review is to summarize the most recent literature regarding tapentadol use in oncology patients and moderate or severe pain.

Soporte nutricional y nutrición parenteral en el paciente oncológico: informe de consenso de un grupo de expertos

Malnutrition is a common medical problem in cancer patients with a negative impact on quality of life. The aim of this study was to address different issues related to nutritional management of cancer patients in clinical practice. A multidisciplinary group of experts in Medical Oncology, Pharmacy, and Endocrinology and Nutrition prepared a list of topics related to the nutritional status of cancer patients and grouped them into three blocks: nutritional support, parenteral nutrition (PN), and home PN (HPN). A literature review was made of articles published in Spanish, English and French until April 2017. This consensus emphasizes several key elements that help physicians standardize management of the nutritional status of cancer patients in clinical practice, and establishes common guidelines for indication, monitoring, nutritional requirements, and access routes to PN.espanolIntroduccion: la malnutricion es un problema medico frecuente de los pacientes oncologicos que impacta de forma negativa en la calidad de vida. Objetivo: analizar y dar respuesta a diferentes cuestiones a la hora de afrontar el manejo nutricional de un paciente oncologico en la practica clinica. Metodos: un grupo multidisciplinar de expertos en Oncologia Medica, Farmacia y Nutricion elaboro una lista de temas relacionados con el estado nutricional del paciente oncologico que fueron agrupados en tres bloques: soporte nutricional; nutricion parenteral (NP); y nutricion parenteral domiciliaria (NPD) en el paciente oncologico. Se realizo una revision de la literatura que incluyo articulos publicados en espanol, ingles y frances hasta febrero de 2017. El documento se estructuro como un cuestionario con aquellas preguntas que, segun el criterio del panel, podrian generar mayor controversia o duda. Resultados: de las 18 cuestiones abordadas, 9 versaron sobre el soporte nutricional: 5 relacionadas con la NP y 4 trataron sobre la NPD. Dentro de las recomendaciones del panel destacar que, en el paciente oncologico, la NP esta indicada principalmente cuando no es posible el uso del tubo digestivo y/o la alimentacion oral y/o nutricion enteral no es suficiente o posible. Ademas, el objetivo de la NPD es mejorar o mantener, el estado de nutricion de un paciente en el ambito domiciliario. Conclusiones: esta revision constituye una herramienta para oncologos y especialistas responsables del manejo nutricional del paciente con cancer. EnglishBackground: Malnutrition is a frequent medical problem of cancer patients that negatively impacts their quality of life. Objective: To analyze and respond to different issues related to the nutritional management of cancer patients in the clinical setting. Methods: A multidisciplinary group of experts in Medical Oncology, Pharmacy, and Nutrition developed a list of topics related to the nutritional status of cancer patients, which were grouped into three blocks: Nutritional support; Parenteral nutrition (PN); and Home PN (HPN) in cancer patients. A literature search, which included articles published in Spanish, English, and French until February 2017, was carried out. The document was organized as a questionnaire with those questions that, according to the panel’s criteria, could generate greater controversy or doubt. Results: Of the 18 questions addressed, 9 focused on nutritional support: 5 were related to PN and 4 about HPN. Among the different recommendations, the panel emphasized that in the cancer patient, PN is indicated mainly when it is not possible to use the digestive tract and/or oral feeding and/or enteral nutrition is not sufficient or possible. Additionally, the objective of the HPN is to improve or maintain the nutritional status of a patient at home. Conclusions: This document seeks to lay down a set of recommendations and to identify key issues that may be useful for the nutritional management of cancer patients.

Living with Cancer: Through the Eyes of the Patient and the Physician

This article is co-authored by a patient with colon cancer and his treating oncologist, who interact at two different levels: the instrumental and the emotional and affective one. The patient relates in detail his personal experiences struggling with cancer, including his fears, expectations, purposes, and attitudes through the most important events in the evolution of his illness. The professional reflects how patient-based communication and shared decision-making impact on quality of life and coping with cancer.