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Background The purpose of this study was to evaluate the tolerability and efficacy of BMS-184476, an analog of paclitaxel, in patients with advanced non-small-cell lung cancer (NSCLC) progressing or relapsing following at least one prior chemotherapy regimen. Patients and methods Fifty-six previously treated advanced NSCLC patients received BMS-184476 at a dose of 60 mg/m2 administered intravenously over 1 h every 21 days. Results The median number of cycles delivered per patient was five (range one to 17). Dose reduction was required in only 3.8% of cycles. Grade 4 neutropenia occurred in 19.6% of patients, but no grade 4 thrombocytopenia or anemia was reported. Febrile neutropenia was observed in only two (3.6%) patients and there were no life-threatening events. Grade 3/4 peripheral sensory-motor neuropathy was reported in 9% of patients. Other non-hematological toxicities, such as nausea and vomiting, myalgia and arthralgia, diarrhea, and mucositis, were uncommon. Partial responses were observed in eight (14.3%) patients and stable disease in 33 (58.9%). Median progression-free survival was 3.7 months [95% confidence interval (CI) 2.7–5.4] and median overall survival was 10 months (95% CI 6–13.4). Conclusions BMS-184476 was well tolerated at the dose of 60 mg/m2 and showed evidence of antitumor activity in previously treated NSCLC.

En el presente trabajo se analiza la relacion de la estructura economico-financiera con la eficiencia de las mayores empresas del sector turistico espanol en el periodo 1995-1999. Para ello, en primer lugar se estudia, mediante analisis window con metodologia DEA, la eficiencia de estas empresas, con el objeto de observar su evolucion temporal y definir tres niveles distintos de eficiencia (robusta, variable e inestable). Finalmente, mediante modelos de regresion de datos de panel se determinan aquellas variables economico-financieras estadisticamente significativas en la eficiencia de las empresas, siendo esta informacion de utilidad en la toma de decisiones de los directivos que persiguen el comportamiento eficiente en las empresas del sector turistico.

Purpose To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. Patients and Methods We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. Results We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). Conclusion CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.

5 págs.; 2 figs.; 1 tab.; PACS numbers: 04.62.+v, 03.67.Hk, 98.80.-k, © 2015 American Physical Society. We analyze the implications of the violations of the strong Huygen's principle in the transmission of information from the early Universe to the current era via massless fields. We show that much more information reaches us through timelike channels (not mediated by real photons) than is carried by rays of light, which are usually regarded as the only carriers of information., L. J. G. and M. M-B. acknowledge financial support from the Spanish MICINN/MINECO Projects No. FIS2011- 30145-C03-02 and its continuation No. FIS2014-54800- C2-2-P. M. M-B. also acknowledges financial support from the Netherlands Organization for Scientific Research (Project No. 62001772). E. M-M. Acknowledges support form the NSERC Discovery programme.

Background: Lung cancer features like treatment resistance or tumor relapse have been linked to cancer stem cells (CSCs), a population of cells with self-renewal properties, and the ability to grow forming tumorspheres in non-adherent conditions. The aim of this study was to isolate and characterize tumorspheres from lung cancer cell lines and tumor tissue from resectable non-small cell lung cancer (NSCLC) patients and to use them as an in vitro platform for drug screening. Methods: This study was performed on cells from seven NSCLC tumor samples and five cell lines (H1650, H1993, H1395, A549 and PC9) grown in monolayer and as spheroids. The expression of 60 genes, including CSC-markers, pluripotency inducers, cell cycle regulators, invasion promoters and components of Notch, Wnt and Hedgehog pathways was analyzed by RTqPCR. Drugs commonly used in clinical guidelines (Cisplatin, Paclitaxel, Gefitinib, Erlotinib, Afatinib, Pemetrexed and Vinorelbine) and specific inhibitors of Wnt and Hedgehog pathways (Iwp2, Xav939, LDE225 and Vismodegib and Salynomicin) were tested in triplicates at 4 different concentrations. Cell viability was measured after 48h and 72h using MTS Assay, normalized to the respective mock-treated control cells and presented as percentage of control. Statistical analyses were considered significant at p Results: Lung tumorspheres had significant increased expression of CSC-related genes EPCAM1, CD44, CCND1, KLF4 and CDKN1A, compared to their paired-adherent cells. Likewise, epithelial to mesenquimal transition (EMT) inducer SNAI1 and integrin ITGA6 were overexpressed in spheroids too. Regarding stemness pathway, Notch pathway ligands JAG1 and DLL4 and receptors NOTCH1, NOTCH2 and NOTCH3 showed higher expression in lungspheres. In Wnt pathway, higher expression levels of WNT3, CTNNB1 and GSK3B were found in tumorspheres. No significant differences were found for the rest of genes. Drug screening showed classical anticancer drugs, such as Cisplatin, Vinorelbine or Pemetrexed, had mild cytotoxic effects on lungspheres, obtaining significant differences with the adherent-cultured cells. In contrast, the stemness pathways inhibitors IWP2, XAV939, Salinomycin and Vismodegib showed higher cytotoxic effects on spheroids than in cells grown in monolayers. Conclusions: Lung-tumorspheres derived from cancer cell lines and primary tumor tissues show increased levels of CSC markers and components of Notch and Wnt signaling pathways compared to the cells grown in adherence. Spheroids showed resistance to classical anticancer drugs, and a greater response to inhibitors from Notch, Wnt and Hedgehog pathways, strengthening its possible use as a short-term culture platform for a simple, and cost-effective screening to investigate novel therapeutic approaches. Supported by grants RD12/0036/0025 from RTICC-FEDER, PI12-02838/PI15-00753 from ISCIII and SEOM/2012. Citation Format: Alejandro Herreros-Pomares, Ester Munera-Maravilla, Silvia Calabuig-Fariñas, Rut Lucas, Rosa Farràs, Ana Blasco, Susana Torres, Jose Ferri, Ricardo Guijarro, Miguel Martorell, Eloísa Jantus-Lewintre, Camps Carlos. Gene characterization of lung-tumorspheres for their usage as an in vitro screening platform for testing new therapeutic strategies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1918. doi:10.1158/1538-7445.AM2017-1918

75 Background: Comprehensive and continuous care is esential for the correct management of cancer patients. To achieve this, specific programs for early diagnosis and long survivor care are needed. Since 2007, within the project “Oncology beyond the Hospital: Oncologic assistance at the Universitary General Hospital of Valencia”, the Oncologist Liaison was created. Methods: Two tracks were designed: High-resolution track for patients with suspicion of non-diagnosed cáncer; and Oncologist Liaison track, to organize the follow-up of cáncer long survivors. We present a descriptive and retrospective study by reviewing medical records of patients referred to the high-resolution diagnostic consultation; and long survivors followed up by the Oncologist Liaison from May 2007 to September 2015 (2016 data under review). Results: High-resolution track: 1,596 patients with suspected cancer were visited. The mean time between the primary care physician consultation and the oncologist visit was 4.32 days. Main reasons for consultation were: breast disease (25.4%), blood test disorders (16.4%), enlarged lymph nodes (11.1%) and radiological suspicion of tumor (12%). 424 cancers were diagnosed (26.5%) all having been studied in Oncologic Committee: 22.6% lung; 17% lung; 16.2% breast; 11.8% lymphomas; 12.5% superior dighestive tract; and19.8% miscelanea. Long-survivors track: 1406 patienst free from disease were referred for surveillance of recurrence and treatment sequelae: 44% breast; 20% gastrointestinal; 17% gynecological; 7% double neoplasia; 4% of lung cancer and other tumors, 8%. Conclusions: With the integration of the Oncologist Liaison in the continuum of care, we have achieved: Normalization of oncologic approach among patients and primary care physicians; implementation of a fast-track for patients with cancer suspicion: access to the oncologist in less tan a week; case study in the Oncologic Comittee in the following week; and consensus in diagnosis and treatment plan in each case. Ensure control over long-survivors.

Hydroelectrolytic disorders are one of the most common metabolic complications in cancer patients. Although often metabolic alterations affecting various ions are part of the manifestations of the oncological disease, even in the form of paraneoplastic syndrome, we must not forget that very often, these disorders could be caused by various drugs, including some of the antineoplastic agents most frequently used, such as platin derivatives or some biologics. These guidelines review major management of diagnosis, evaluation and treatment of the most common alterations of sodium, calcium, magnesium and potassium in cancer patients. Aside from life-sustaining treatments, we have reviewed the role of specific drug treatments aimed at correcting some of these disorders, such as intravenous bisphosphonates for hypercalcemia or V2 receptor antagonists in the management of syndrome of inappropriate antidiuretic hormone secretion-related hyponatremia.

[EN] Background. Angiogenesis and lymphangiogenesis are key mechanisms for tumor growth and dissemination. They are mainly regulated by the vascular endothelial growth factor (VEGF) family of ligands and receptors. The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve characterization of patients with worse clinical outcomes. Methods. RNA was obtained from tumor and normal lung specimens from 175 patients. Quantitative polymerase chain reaction was performed to analyze the relative expression of HIF1A, PlGF, VEGFA, VEGFA(165b), VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2. Results. Univariate analysis showed that tumor size and ECOG-PS are prognostic factors for time to progression (TTP) and overall survival (OS). This analysis in the case of angiogenic factors also revealed that PlGF, VEGFA, VEGFB and VEGFD distinguish patients with different outcomes. Taking into account the complex interplay between the different ligands of the VEGF family and to more precisely predict the outcome of the patients, we considered a new analysis combining several VEGF ligands. In order to find independent prognostic variables, we performed a multivariate Cox analysis, which showed that the subgroup of patients with higher relative expression of VEGFA plus lower VEGFB and VEGFD presented the poorest outcome for both TTP and OS. Conclusions. The relative expression of these three genes can be considered as an angiogenic gene signature whose applicability for the selection of candidates for targeted therapies needs to be further validated., This study was partially supported by a grant from the Instituto de Salud Carlos III (FIS PI06/1041 and PS09/1149), Red Tematica de Investigacion Cooperativa en Cancer (RD06/0020/1024), and FEDER.

7559 Background: MicroRNAs (miRNA) regulate gene expression, and are implicated in several processes like tumorogenesis. Here, we applied a multiplexed NGS approach to study differentially expressed miRNAs (tumor/ normal) in a cohort of resectable NSCLC patients and its correlation with clinical outcome. Methods: RNA was isolated from frozen lung specimens (tumor/ normal) from 33 patients. High-quality samples were analyzed and enriched in the miRNA fraction. Libraries were prepared according to manufactured instruction (SOLID), and miRNAs were sequenced. Data analysis was carried out using CLCbio software. First, raw data were annotated using miRBase and normalized by total reads followed by differential expression analysis. Results validation were performed by RTqPCR in an independent cohort (n= 195). Functional studies of differentially expressed miRNAS were done using in silico tools. Statistical significance was considered at p

Under the auspices of the Foundation for Excellence and Quality in Oncology (ECO), the Translational Research in Oncology Medical Services Study (INTRO) was conducted with the aim of describing the current state of, and future expectations for translational cancer research in Spanish medical centres. The first step in the investigation was intended to analyse the current condition of the national Medical Oncology Services network by examining different aspects of the oncology research field. A descriptive and observational multicentre study was performed at a statewide level; information was collected by surveying a cross-section of all those responsible for Medical Oncology Services in Spain. The survey was completed by key informants, who were selected independently by each service, between September 2010 and April 2011. We were able to gather comprehensive data from a total of 27 Spanish hospitals. These data enabled us to describe the allocation of human and material resources devoted to clinical and translational research across the Medical Oncology Services and to describe the organisational and functional components of these services and units. These data included information pertaining to the activities developed, their funding sources, and their functional dependence on other internal or external bodies. Finally, we explored the degree of dissemination and use of some specific techniques used for the genetic diagnosis of cancer, which have recently been introduced in Medical Oncology within the Spanish healthcare system. A wide range of variability exists between different oncology services in Spanish hospitals. Time should be spent reflecting on the need and opportunities for improvement in the development of translational research within the field of oncology.

7562 Background: Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. T...

Use of the radial artery for cardiac catheterization has significantly reduced the incidence and severity of complications at the access site. Nevertheless, occasionally unusual complications or atypical responses to treatment are observed. We describe two cases: a radial artery pseudoaneurysm that was unresponsive to compression treatment and a foreign-body inflammatory reaction at the radial artery access site. The characteristics, development and treatment of the 2 cases are described, and the pathogenic mechanisms are discussed.

El uso de la via transradial para el cateterismo cardiaco ha reducido drasticamente la incidencia y la gravedad de las complicaciones relacionadas con el acceso. No obstante, en ocasiones se producen complicaciones inusuales o cuya respuesta al tratamiento es atipica. Describimos 2 casos: un seudoaneurisma radial refractario al tratamiento compresivo y una reaccion inflamatoria a cuerpo extrano en el lugar de la puncion arterial. Se ilustran ambos casos, se detallan su evolucion y tratamiento y se discute su mecanismo patogenico.

e23276Background: Chemoresistance, tumor progression and metastasis have made of lung cancer the first cause of death cancer-related worldwide. Cancer stem cells (CSCs) are small subpopulations of ...

e23039Background: One of the most promising developments in translational cancer has been the emergence of liquid biopsy as a non-invasive biomarker. CTCs and cfDNA offer valuable prognostic and pr...

A B S T R A C T Introduction and objectives: The transradial approach is associated with a reduction in vascular access- related complications after primary percutaneous coronary interventions. The purpose of this study was to examine the feasibility of the routine use of transradial access in primary angioplasty and to evaluate how it affects subgroups with less favorable characteristics. Methods: We analyzed 1029 consecutive patients with an ST-segment elevation acute coronary syndrome treated with primary angioplasty. Results: Transradial access was the primary approach in 93.1% of the patients. The success rate of primary angioplasty was 95.9%, and 87.6% of the patients were event-free 30 days after the procedure. Crossover was required in 3.0% of the patients with primary transradial access, and this rate remained stable over the years. Predictors of the need for crossover were age older than 75 years (odds ratio=2.50, 95% confidence interval, 1.09-5.71; P=.03) and a history of ischemic heart disease (odds ratio=2.65; 95% confidence interval, 1.12-6.24; P=.02). Primary transfemoral access use was higher in women older than 75 years. Use of the transradial approach in this subgroup did not affect reperfusion time or the success of angioplasty, although there was a greater need for crossover (10.9% vs 2.6%; P=.006). Among patients in cardiogenic shock, the transradial approach was used in 51.5%; reperfusion times and angioplasty success rates were similar to those obtained with transfemoral access, but there was a greater need for crossover. Conclusions: Transradial access can be used safely and effectively in most primary angioplasty procedures. In older women and in patients in cardiogenic shock, there is a higher crossover requirement, with no detriment to reperfusion time.

■ PURPOSE: Efficient ways are needed to implement the secondary prevention (SP) of coronary heart disease. Because few studies have investigated Web-based SP programs, our aim was to determine the usefulness of a new Web-based telemonitoring system, connecting patients provided with self-measurement devices and care managers via mobile phone text messages, as a tool for SP. ■ METHODS: A single-blind, randomized controlled, clinical trial of 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. All patients received lifestyle counseling and usual-care treatment. Patients in the telemonitoring group (TMG) sent, through mobile phones, weight, heart rate, and blood pressure (BP) weekly, and capillary plasma lipid profile and glucose monthly. A cardiologist accessed these data through a Web interface and sent recommendations via short message service. Main outcome measures were BP, body mass index (BMI), smoking status, low-density lipoprotein-cholesterol (LDL-c), and glycated hemoglobin A 1c (HbA 1c ). ■ RESULTS: At 12-month followup, TMG patients were more likely (RR � 1.4; 95% CI � 1.1-1.7) to experience improvement in cardiovascular risk factors profile than control patients (69.6% vs 50.5%, P � .010). More TMG patients achieved treatment goals for BP (62.1% vs 42.9%, P � .012) and HbA1c (86.4% vs 54.2%, P � .018), with no differences in smoking cessation or LDL-c. Body mass index was significantly lower in TMG (� 0.77 kg/m 2 vs � 0.29 kg/m 2 , P � .005). ■ CONCLUSIONS: A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.

[EN] Background: Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer. A soluble fragment of the EGFR extracellular domain (sEGFR) can be detected in the blood of patients who have Non-small-cell lung cancer (NSCLC), but its clinical/ prognostic role must be further elucidated. Methods: sEGFR concentration was retrospectively determined by enzyme-linked immunosorbent assay in plasma samples from 308 advanced NSCLC patients (before treatment) and 109 healthy controls and correlated with clinico-pathological variables. Results: The concentration of sEGFR was lower in NSCLC patients than in controls (P, This work was sponsored in part by a grant from the Spanish Society of Medical Oncology (SEOM) and by a grant (RD06/0020/1024) from Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII), the Spanish Ministry of Science and Innovation and the European Regional Development Fund (ERDF) "Una manera de hacer Europa." The authors declare no conflicts of interest or any financial disclosure.

[EN] Background: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. Materials and methods: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m2 of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m2 of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m2 of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. Results: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. Conclusions: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival. © 2011 Feseo.

Background: Circulating DNA is observed at higher concentrations in patients with lung cancer than in controls. Qualitative and quantitative analysis of circulating DNA is a promising noninvasive tool. Our aim was to prospectively study the association between the catalytic subunit of telomerase (human telomerase reverse transcriptase [hTERT]) in plasma and clinical variables and survival in a large-scale non-small cell lung cancer (NSCLC) study. Methods: Four hundred forty-six patients with stages IIIB and IV NSCLC with a median follow-up of 9.7 months (range, 0.5-45) were analyzed. Blood samples were collected before therapy start (cisplatin/docetaxel). Quantification of baseline circulating DNA was determined as the amount of free hTERT in plasma, by using real-time quantitative polymerase chain reaction. Results: Patients with hTERT ¿49.8 ng/ml (median value) had a median time to progression (TTP) of 6.3 months compared with 4.9 for hTERT more than 49.8 ng/ml (p = 0.001). Overall survival (OS) was significantly higher (10.9 versus 9.3 months) at lower hTERT levels (p = 0.012). When calculations were done using hTERT as continuous variable, we did not observe independent significant differences. Thus, there is an apparent discrepancy in p values when hTERT is considered as a continuous versus dichotomized variable. There was a tendency to differentiate median hTERT levels with respect to response rates (complete response + partial response: 33.1 versus stable disease + progressive disease: 50.7 ng/ml, p = 0.12), but other clinical variables such as age, gender, performance status, stage, histology, and number of metastatic locations were not associated with hTERT. In multivariate analysis, hTERT was an independent prognostic variable for both TTP (hazard ratio: 1.44, p < 0.001) and OS (hazard ratio: 1.33, p = 0.007). Conclusions: In advanced NSCLC, high pretreatment circulating hTERT level is an independent poor prognostic marker for TTP and OS. Circulating DNA is a noninvasive marker, which may help to improve the prognostic profile of these patients. Copyright © 2011 by the International Association for the Study of Lung Cancer., Supported, in part, by the Spanish Society of Medical Oncology (SEOM).

[EN] In May 2007, the Consorcio Hospital General Universitario de Valencia created the position of "Liaison Oncologist". The holder of this position is responsible for coordinating specialised and primary hospital care in the geographic area of Valencia known as Health Care Department 9 to reduce the waiting time between cancer diagnosis and treatment. In this article we describe the implementation of the innovative proposal of the Liaison Oncologist's Consultation Clinic, which, apart from speeding up and directing diagnostic processes, facilitates access to treatment, prevents duplication of consultations and exploratory procedures by establishing therapeutic plans (preferential channels), gives continuity to diagnostic and therapeutic mechanisms, and permits active follow-up of patients who have finished treatment. An analysis of the results obtained shows that the clinic has allowed us to integrate the various aspects of medical oncology into one system and make it available to patients and primary and specialised care professionals. This system provides the patient with the highest quality of integrated health care, ensures the availability of continued health care to long-term survivors and establishes preferential channels between primary care and specialised cancer care to achieve a quick diagnosis.

Introduction: The vascular endothelial growth factor (VEGF) family of ligands and receptors (VEGFR) play an important role in tumor angiogenesis. Increased expression of angiogenic factors in tumors or in blood is associated with poor prognosis. The aim of this study was to investigate the role of VEGF-A and soluble VEGFR-2 (sVEGFR-2) as biomarkers in advanced non-small-cell lung cancer (NSCLC). Methods: We studied 432 patients with advanced NSCLC (stages IIIB-IV) treated with cisplatin and docetaxel and 89 healthy age-matched controls. Blood samples were collected before chemotherapy, and VEGF-A and sVEGFR-2 levels were determined by ELISA. Results: VEGF-A and sVEGFR-2 levels were higher in NSCLC patients than in the controls, but VEGF-A behaves as a better diagnostic biomarker. There were no significant associations between VEGF-A and sVEGFR-2 concentrations and clinical characteristics, such as ECOG-PS, gender, stage, histology, metastases, and treatment response. A patient subgroup characterized by a combination of high VEGF-A and low sVEGFR-2 levels exhibited the worst patient prognoses in terms of TTP and OS. Conclusions: VEGF-A and sVEGFR-2 levels were significantly higher in patients than in the controls. A combination of VEGF-A and sVEGFR-2 can be used as an independent prognostic biomarker in advanced NSCLC. © 2011 Elsevier Ireland Ltd., This work was supported in part, by a grant [PI06/104] from Instituto de Salud Carlos III and a grant [RD06/0020/1024] from Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation and European Regional Development Fund (ERDF) "Una manera de hacer Europa".

[EN] Background: Platinum doublets are standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether neutropenia is: (1) an indicator for treatment efficacy, or (2) associated with specific polymorphisms. Patients and Methods: Four hundred ninety-four patients, treated with cisplatin-docetaxel were retrospectively analyzed. Relative dose intensity (RDI) was assessed for both drugs. Neutrophil counts were assessed only on Day 21 of each cycle. Genotyping was performed for 4 different polymorphisms in ERCC1, XRCC3, XPD-23, and XPD-10. Results: The median overall survival was 9 months. The mean RDI was 0.94 for cisplatin and 0.93 for docetaxel. Four hundred three patients received ¿ 3 cycles of chemotherapy, and 239 received ¿ 6 cycles. Thirty-one percent developed neutropenia, and 19% had Grade (G)3-4 neutropenia. RDI was lower in patients with neutropenia (G1-4; 0.87-0.93) when compared with those without (G0; 0.94-0.95; P

Qualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients. Methods: We examined 308 stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. The KRAS mutational status was determined by an RT-PCR method that is based on allelic discrimination. Results: The median age of the patients was 60 years [31-80], 84% were male, 98% had a performance status of 0-1 and 84% of the patients were in stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated patients, 1% achieved a complete response (CR), 26% achieved a partial response (PR), 34% had stable disease (SD) and 39% had progressive disease (PD). Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p = 0.277). The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43-13.70] vs 10.03 months [8.80-11.26] in wt patients (p = 0.514). Conclusions: In advanced NSCLC patients, there were no significant differences between patients with or without KRAS mutations in plasma-free DNA with respect to the baseline characteristics, response rates, PFS or OS. © 2010 Elsevier Ireland Ltd., This work was sponsored in part by a grant from the Spanish Society of Medical Oncology (SEOM) and by a grant (RD06/0020/1024) from Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation & European Regional Development Fund (ERDF) "Una manera de hacer Europa". None of the funding agencies were involved in the design, data management, data analysis, manuscript preparation and review, or decision to submit.

A progressively ageing population and the high association between advanced age and cancer has resulted in an increased interest in the field of geriatric oncology with the objective being a more effective diagnosis and treatment of these patients. We performed an epidemiological analysis on an intent-to-treat of elderly population within our healthcare unit. This is a retrospective study of all patients attended in our Medical Oncology Department during the year 2002. A total 667 patients were assessed, 42% older than 70 years of age. The most frequent tumour sites were lung, colorectal and breast. The most frequent histology was adenocarcinoma. The diagnosis in advanced stages was significantly higher in older age group (76% vs. 59%). The use of symptom-control follow-up and palliative-care, compared with radio- and chemo-therapy, was higher in older age group. However, we observed no statistically significant differences with respect to inclusion in clinical trials. In conclusion, the elderly represents an important percentage of patients receiving cancer care. The distributions by sites and histology types are similar in both groups of age. Although the election of palliative treatment is more frequent in elderly population, the most frequently used treatments in both groups, were radiotherapy and chemotherapy. We didn't observe any significant differences about the inclusion in clinical trials.

[EN] The therapeutic options for patients with advanced non-small-cell lung cancer (NSCLC) are palliative. Therefore, the quality of life in oncology is considered as an endpoint in clinical trials, and several scales have been accepted for its measurement in parallel with other clinical determinations. However, its use in clinical practice is hindered by various obstacles that need to be overcome. In this article we examine the concept of the quality of life in patients with NSCLC, as well as giving an evaluation and interpretation of the results of various clinical trials. We describe the new technological methods used in daily clinical practice to measure the quality of life.

Cancer is a high incidence disease, forcing healthcare systems to assign a significant amount of resources to its treatment. New developments have arisen recently: development of new agents that act at specific steps of cellular differentiation and proliferation and identification of predictive genetic markers which allow sub-groups of patients that will benefit from these agents, alone or in combination with chemotherapy, to be targeted. The majority of new drugs coming to the market combine greater clinical benefit and higher costs. Constraints on healthcare budgets worldwide make it necessary to rationalise the expense by prioritising allocation of available resources to the most efficient interventions, so that the best possible clinical result can be obtained at a reasonable cost and with the best quality of life for the patient. Economic evaluation studies represent the only tool available to scientifically determine the cost-effectiveness of new treatments and the budgetary impact of their introduction to the therapeutic arsenal available for the treatment of cancer.

The communication doctor – patient plays a fundamental role in their relationship. Bad communication can imply a negative influence between patient and his family. The aim of this work is to obtain better insight in the process of the information that is contributed by the medical oncologist and to check whether the patients remembers this information after fifteen days. The information we present corresponds with the second phase of the “descriptive study on the process of communicating the diagnosis and the prognosis in oncology”. Cohort consisted in 71 cancer patients, who remembered the initial interview and performed a second one. The results obtained show that data collection is depending on the complexity of the transmitted information as well as of its emotional impact; which means that, the simpler and the more emotional impact, better to remember. Therefore this information supports the idea that communication is an evolutionary and continuing process, and is not limited to certain situations, being able to attend the needs both of the patient and his family, facilitating the patient a better adaptation to the oncological disease. La comunicación juega un papel fundamental en la relación médico-paciente. La mala comunicación así mismo, puede llegar a tener una influencia negativa en el paciente y sus familiares. El objetivo de este trabajo es profundizar en el proceso de información aportada por el médico oncólogo y el recuerdo que mantiene el paciente de dicha información transcurridos quince días. Los datos que presentamos se corresponden con la segunda fase del “estudio descriptivo sobre el proceso de comunicar el diagnóstico y el pronóstico en oncología”. La muestra esta formada por 71 pacientes, todos ellos realizaron una segunda entrevista y recordaban la entrevista inicial. Los resultados obtenidos muestran que el recuerdo está en función de la complejidad de la información transmitida así como del impacto emocional de la misma; es decir, a mayor simplicidad y mayor impacto emocional, mejor recuerdo. Por tanto estos datos apoyan la necesidad de que la comunicación sea un proceso evolutivo, y continuado, y no se reduzca a un momento puntual, atendiéndose a las necesidades tanto del paciente como de sus familiares, facilitándose así una mejor adaptación al proceso oncológico.

The purpose of this analysis was to study the association between the quantity of free circulating DNA and clinical variables in 99 advanced non-small cell lung cancer patients (NSCLC). The quantification in the serum of the gene of the catalytic fraction of telomerase (hTERT) by RT-PCR was used as a reference of the total amount of free DNA in blood. Patients were treated with cisplatin and docetaxel. The median hTERT level for patients in stage IIIB was 70.7 ng/ml vs. 53.1 ng/ml in patients in stage IV (p= 0.35). There was no association between hTERT values and therapy response, 53.9 ng/ml in the complete response (CR) + partial response (PR) group vs. 54.1 ng/ml in the stable disease (SD) + progressive disease (PD) group (p=0.23). In the multivariate analysis, hTERT was an independent predictive variable for time to progression (TTP) Hazard ratio (HR) 2.0, CI 95% 1.2-3.4, p=0.009) and overall survival (OS) (HR 2.4 CI 95% 1.3-4.3, p=0.004). The analysis of TTP and OS with a cut-off of hTERT at 40 ng/ml revealed that patients about this level had statistically poorer TTP (4 vs. 7 months, p= 0.009) and OS (5 vs. 15 months, p0.0001). In conclusion, in advanced NSCLC, high serum hTERT levels may be a poor prognostic indicator for TTP and OS.

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA BACKGROUND MicroRNAs (miRNA) are a class of small RNAs that regulate gene expression, and are implicated in several diseases including cancer. The aim of this study was to analyze the prognostic implications of deregulated miRNAs identified by NGS in a previous study performed on resectable-NSCLC tumor samples. MATERIAL AND METHODS Fresh-frozen tumor and normal adjacent lung tissue samples (N = 195) were obtained by surgical resection from NSCLC patients and storage in RNAlater® at -80°C until analysis. RNA was isolated biological specimens by Trizol based-methods. 22 deregulated miRNA were analyzed in paired tumor/normal samples by RTqPCR using TaqMan® microRNA assays. Statistical analyses were considered significant at p

7532 Background: Adenocarcinoma (ADC) is one of the most common types of non-small cell lung cancer (NSCLC). Deregulated microRNAs (miRNA) in tumor were associated with poor prognosis. In this stud...

11052 Background: The analysis of immune features of tumor microenvironment is leading to the development of new immunotherapies and the identification of new biomarkers. In this study, we have inv...

9617 Background: To develop and validate a prognostic score for serious neutropenic events based on characteristics available prior to starting chemotherapy Methods: FINITE is a prospective, multicenter study to assess prognostic factors and patterns of care in adult cancer patients with seemingly stable febrile neutropenia. For this analysis, we used only those clinical variables that are routinely available on Day 1 of chemotherapy in all solid tumor patients. The main outcome measure was occurrence of serious complications. A logistic regression with Penalized Maximum Likelihood Estimations (PMLE) was applied; to build an additive score, estimates were rounded as integers. To validate the model, the bootstrap bias-corrected c-index was calculated as a measure of prediction performance. A separate dataset with 216 patients was used for external validation. Results: We enrolled 1238 patients from 25 centers. The primary end point (serious complications) ensued in 161 patients (13%; 95% CI, 11.1%-14.9%) a...

The aim of the present study was to evaluate the efficacy and toxicity of weekly paclitaxel as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients.The outcome measured in 37 patients were: response rates, symptom relief (dyspnoea, asthenia and pain), toxicity, overall survival (OS) and time to progression (TTP).Objective response was seen in 8%, stable disease in 27% and disease progression in 62%. Three paclitaxel courses reduced the frequency of WHO grade 2-3 dyspnoea and asthenia from 38% and 43% to 13.5% and1%, respectively. Moderate to severe pain (VAS score 3-8) was reduced from 35.1% to 24.3%. Median OS was 38 weeks and TTP 12 weeks. Haematological toxicity included anaemia (30% grade 2-3) and neutropenia (8% grade 3). Nonhaematological toxicity included peripheral neuropathy (41% grade 1-2).In the routine outpatient setting, weekly paclitaxel is feasible, active and well-tolerated as second/third-line chemotherapy in patients with advanced NSCLC.

c-kit, a growth factor receptor with tyrosine kinase activity, plays an important role in the biology of cancer. Its expression has been documented in several malignancies. We performed a retrospective study in 85 patients diagnosed with small cell lung cancer (SCLC) to determine the prevalence and role of c-kit as a possible prognostic marker in this lung cancer malignancy. Demographic and clinical data were obtained from patient charts. c-kit, analyzed as immunohistochemical expression in paraffin-embedded tumour tissues, was observed in 60% of patients. All patients were former or present smokers. At diagnosis, 46% of the patients had limited disease (LD) and 54% extended disease (ED). c-kit expression was observed in 59% of LD and 61% of ED patients (p=0.4). Patients received a median of 4 cycles first-line combination chemotherapy (platinum and etoposide). In LD patients, time to progression (TTP) was 11.5 months in c-kit (+) versus 5.9 in c-kit (-) patients (p=0.14), and median survival 15.4 and 12.8 months, respectively (p=0.33). In the ED group, TTP was 5.5 months in c-kit (+) versus 3.8 in c-kit (-) patients (p=0.34), whereas median survival was 6.3 and 7.9 months, respectively (p=0.45). With the limited number of patients in mind, our findings tended towards an association between c-kit expression and survival in the LD group.

During the clinical evolution of patients with cancer there are many occasions, or phases of the disease, when there are no specific treatments and, as such, we need to provide maximum comfort following appropriate symptom control; in this stage it is fundamental to respect personal autonomy together with the option to reject futile treatment. With appropriate control of symptoms it is possible to reach the stage where the majority of the patients do not continue to suffer. Continuous-care providers for cancer patients are those who are responsible for providing help to resolve these situations. In palliative medicine there are highly-efficacious procedures to the help in these last hours. Sedation is applied when it is impossible to control symptoms by other means. With appropriate Carer cover, it is not necessary to introduce laws on assisted suicide and/or active voluntary euthanasia, neither because of the magnitude of demand, nor because of the difficulties in achieving appropriate control of symptoms.