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e18131 Background: Progression-free survival (PFS) in EGFR-mutant NSCLC p treated with erlotinib can range from a few months (m) to more than two years, but genetic influences on the duration of response remain unclear. The cytotoxic effect of erlotinib has been related to several proteins that regulate DNA damage response (eg, BRCA1, BRCA2). MCPH1 contains 3 BRCT domains which are conserved in important molecules involved in DNA damage signaling, including BRCA1, MDC1 and 53BP1. MCPH1 binds to BRCA2 and regulates the localization of BRCA2 and Rad51 at sites of DNA damage. MCPH1 also regulates the ATP-dependent SWI-SNF chromatin remodeling complex during DNA repair. Methods: We used the NanoString nCounter gene expression system, which captures and counts individual mRNA transcripts, to analyze the expression of 44 selected genes, many of which are involved in DNA damage response, in 55 erlotinib-treated NSCLC p. We identified MCPH1 and correlated expression levels with clinical outcomes. Results: p characteristics: 16 males, 39 females (70.9%); 39 never-smokers (70.9%), 12 former smokers, 4 current smokers; 34 with EGFR deletion in exon 19 (61.8%), 21 with L858R mutation (38.2%). PFS was not reached for patients with high MCPH1, while it was 19 m for those with intermediate levels and 9 m for those with low levels (P=0.01). Median survival was 31 m for p with high levels, not reached for p with intermediate levels and 17 m for p with low levels (P=0.004). Conclusions: The enhanced effect of erlotinib in the presence of elevated MCPH1 could be due to the fact that MCPH1 can interfere with the function of MDC1 and 53BP1. The role of MCPH1 merits validation as a predictive marker of erlotinib response.

7011 Background: Surgical resection is the standard treatment in early stages of NSCLC. Nonetheless, long-term survival rate even after surgical resection is disappointing. Several randomized trials and meta-analyses confirmed the survival benefit of adjuvant cisplatin-based CT for stage II and IIIA. BRCA1 is a component of multiple DNA repair pathways, functions as a molecular determinant of response to cytotoxic chemotherapeutics agents, and is an independent prognostic variable in resected p. Since BRCA1 mRNA expression has been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 expression may provide additional information for customizing adjuvant CT. Methods: Completely resected p with pathological lymph node involvement (N1, N2) received 4 cycles of customized adjuvant CT according BRCA1 l. Low l: gemcitabine-cisplatin, intermediate l: docetaxel-cisplatin, high l: docetaxel. Overall survival (OS) was the primary endpoint. Multivariate analysis for time to relapse (TTR) and survival was performed. Results: Eighty-three p were elegible. Most of the patients were male (83%). Type of surgery: 23% pneumonectomy, and 77% lobectomy or bilobectomy. Fifty-three per cent had low BRCA1 l, 33,7% intermediate l, and 13,3% expressed high l. Most of the tumors with adenocarcinoma histology had low l (71%). With a median follow-up of 41.6 months (m), median TTP for the whole group was 22.9 m (13.4-32.5): 20.3 m for low l, 56.5 m for intermediate l, and 51.9 m for high l (P=0.31). Median OS for the whole group was 63.6 m (33.3-93.9): 55 m for low l, and not reached for intermediate and high l (P=0.58). Forty-three p (51.8%) are still alive. Conclusions: Selection of customized CT based on BRCA1 expression l is feasible and could increase time to relapse and survival in resected N1-N2 p. No statistical differences for survival: 55 months for gemcitabine-cisplatin, and not reached for docetaxel-cisplatin and for docetaxel as single agent. Randomized phase III SCAT trial with the addition of a non-pharmacogenomic control arm is ongoing (372 patients included).

Eleven new C4d genomic primate sequences of the fourth complement factor (C4) have been obtained. Seven of them belong to five species not yet explored for this gene: Pan paniscus (pygmy chimpanzee), Cercopithecus aethiops (green monkey), Macaca mulatta (rhesus monkey), Macaca fascicularis (cynomolgus), and Saguinus oedipus (cotton top tamarin). The New World monkeys (tamarins, four individuals) sequenced for C4 have a single C4d sequence only, which shows a B isotypic specificity and a Rodgers 3 (Rg3), Chido 1 (Ch1) antigenicity. Rg3 and Ch1 could thus be the oldest Rg/Ch specificity (at least 50 million years old) and Rg1, Rg2, Ch3, and Ch6 could be more recent human-specific antigens. Mechanisms of C4d polymorphism generation were analyzed by compiling all the presently available sequences. Examples of both point mutations and crossing-over events among C4d primate sequences could be detected. The problem of a possible trans-species inheritance of C4d polymorphism was addressed and two apparently contradicting dendrograms were obtained. One of them, constructed by using both exon and intron sequences, does not support trans-species evolution, but supports the proposed theory of extensive homogenization of the C4 genes occurring within each species, because alleles from each primate species cluster together. Another completely different dendrogram, obtained by using exon sequences only, suggests the existence of trans-species evolution for C4d polymorphism, because alleles belonging to different species cluster together in a way similar to that found for HLA class I or II alleles. However, orangutan sequences group together in both kinds of C4d sequence dendrograms and seem to have arisen from an ancestor different from that of chimpanzee, gorilla and man C4d sequences. Finally, further data have been obtained that support trans-species conservation of A-ness and B-ness and the existence of trans-specifically conserved allelic motifs, both in intronic and exonic sequences.

Background: The CpG island methylator phenotype is associated with distinct clinicophatological characteristics as Estrogen Receptor (ESR1) positive and amplification of HER2 in breast cancer.Objetive: To evaluate epigenetics differences in tumor-related genes to ERS1 and HER2/neu status in primary breast cancer.Material and Methods: We quantified methylation levels of promoter of 5 genes (ERS1, RAR- β, 14-3-3 sigma, APC, E-Cadherin) which are to confer growth adventage to cells, in 107 women with breast cancer and 108 control subjects. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the hypermethylation. Tumours were classified as phenotype basal, luminal A, Luminal B and phenotype HER2+.Results: Ours analyses revealed low or absent methylation ESR1and 14-3-3σ in healthy controls and significant differences between breast cancer patients (pts) and healthy controls in relative serum levels of methylated gene promoters ESR1 (p=0.0112) and 14-3-3s (p=0.0047). Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179). Of the available cases, 60 pts (56%) were Luminal A, 10 pts (9.3%) Luminal B, 13 pts (12%) Basal like and 9 pts (8.4%) HER2+. We observed that methylated ERS1 was preferably associated with phenotype Basal Like and worse interval progression free and survival global though p>0.05 and the amplification HER2+ was correlation with significant more frequent methylation gene (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1151.

e19013 Background: phase II trial-efficacy & toxicity of sequential erlotinib in advanced NSCLC after platinum-based CT Methods: Pts with adv NSCLC, PS 0/1, adequate renal, hepatic and bone marrow function, no PD after CT. Treatment: erlotinib 150 mg/day starting 3–4 weeks after CT until progression. Safety was evaluated monthly and tumor evaluation bimonthly. Results: 47 pts enrrolled:42(89%)stageIV & 5(11%)wet IIIB, all valid for response & toxicity. Median age 62 y(r:39 -77): 39(83%) males and 8(17%) females. Histology: adenocarcinoma 8(61.7%), bronquioloalveolar 3(6.4%), large cell 3(6.4%), squamous12(25.5%). PS 0: 23(49%), PS 1:24(51%). 38(81.9%) completed 6 cycles of CT. Response: CR: 1(2.1%), PR: 2(51.1%), EE: 22 (46%). Sequential erlotinib improved RR in 6 (12.8%), 23 (48.9) prolonged stabilization, 18 (38.3%) had progression. Median TTP and OS were 9.4 m (95% CI, 4.96–13–84), and 19.23 m (95% CI, 8.82–29.64). No significant differences in TTP according to age, sex, PS, histology or previous response to CT, but yes depending on RR to erlotinib: PR: 31.5 m (95% CI 15.37–47.63), EE: 12.8 m (95% CI, 10.58–15.03), PD: 6.3 m (95% CI, 5.36–7.3), p < 0.001; and moreover depending on smoking status: Never: 21.67 m(95% CI, 5.39–37.94), previous smoker > 5 years: 14.03 m(95% CI, 10.77–17.30), previous smoker 1 year: 7.77 m(95% CI, 7.62–7.91), current smoker: 5.9 m(95% CI, 5.12–6.34), p 5 years previous smoker pts had a significant better survival. Toxicity: The most frequent was skin rash, grade (g) 1 in 11(23.4%), g 2: 16(34%) and g 3: 3(6.4%). Only 1 p had diarrea g 3, and no other side effects were observed. We found a significant benefit in p with g 2–3 skin toxicity respect g 0–1, in both TTP( p= 0.0003) and OS (p= 0.0014). Conclusions: Erlotinib-maintenance therapy after platinum-based CT had promising results. Pts with the best benefit were those with response to erlotinib, in never or past (> 5 years) smokers and with g 2–3 skin toxicity. No significant financial relationships to disclose.

ObjetivoEl propósito de este artículo es presentar los resultados del trasplante cardíaco (TC) desde que se inició esta modalidad terapéutica en España en mayo de 1984.Material y métodoSe ha realizado un análisis descriptivo de todos los TC realizados hasta el 31 de diciembre de 2008.ResultadosEl número total de trasplantes fue de 5.774. El perfil clínico medio del paciente que se trasplantó en España en 2008 fue el de un varón de 53 años, diagnosticado de cardiopatía isquémica no revascularizable con depresión grave de la función ventricular y situación funcional avanzada, a quien se implantó un corazón de 37 años procedente de un donante fallecido por hemorragia cerebral y con un tiempo de espera de 111 días. El tiempo medio de supervivencia ha ido increentándose con los años. Así, mientras en la serie global la probabilidad de supervivencia al 1.er, 5.°, 10.° y 15.” años es del 77, 66, 53 y 40%, respectivamente, en los últimos 5 años, la probabilidad de supervivencia al 1.er y 5.° años es del 80 y 70%, respectivamente. La causa más frecuente de fallecimiento es la infección (17%), seguida del combiado de enfermedad vascular del injerto y muerte súbita (15%), fallo agudo del injerto (13%), tumores (12%) y rechazo agudo (6%).ConclusionesLa supervivencia obtenida en España con el TC, sobre todo en los últimos años, sitúa al trasplante cardíaco como el tratamiento de elección para cardiopatías irreversibles en situación funcional avanzada y sin otras opciones médicas o quirúrgicas establecidas.ObjectiveThe purpose of this paper is to present the results obtained with heart transplantation (HT) since this therapeutic modality first began to be used in Spain in May 1984.Materials and methodsA descriptive analysis was performed of all HT performed until December 31, 2008.ResultsThe total number of transplants was 5,774. The average clinical profile of the spanish heart transplant patient in 2008 was that of a 53-year-old male who had been diagnosed with nonrevascularizable ischemic heart disease accompanied by severely depressed ventricular function and poor functional status. The implanted heart was typically from a 37-year-old donor who had died from brain hemorrhage. The average waiting time was 111 days. Mean survival time has progressively increased over the years. Whereas for the overall series, the probability of survival at 1, 5, 10 and 15 years was 77, 66, 53 and 40%, respectively, over the past 5 years, the probability of survival at 1 and 5 years was 80 and 70%, respectively. The most frequent cause of death was infection (17%), followed by the combination of graft vascular disease and sudden death (15%), acute graft failure (13%), tumors (12%) and acute rejection (6%).ConclusionsThe survival rates obtained in Spain with HT, especially in recent years, position heart transplant as the treatment of choice in irreversible heart failure patients without other established medical or surgical options.

ObjetivoEl propósito de este artículo es presentar los resultados del trasplante cardíaco (TC) desde que se inició esta modalidad terapéutica en España en mayo de 1984.Material y métodoSe ha realizado un análisis descriptivo de todos los TC realizados hasta el 31 de diciembre de 2010.ResultadosEl número total de TC es de 6.291. El perfil clínico medio del paciente que se trasplantó en España en 2010 fue el de un varón de 53 años, diagnosticado de cardiopatía isquémica no revascularizable con depresión grave de la función ventricular y situación funcional avanzada, al que se le implantó un corazón de 39 años procedente de un donante fallecido por hemorragia cerebral y con un tiempo en lista de espera de 99días.El tiempo medio de supervivencia se ha incrementado con los años. Así, mientras en la serie global la probabilidad de supervivencia al primer, quinto, décimo y décimo quinto años es del 78, 67, 54 y 40%, respectivamente, en los últimos 5 años, la probabilidad de supervivencia al primer y quinto años es del 85 y 73%, respectivamente.La causa más frecuente de fallecimiento es el fallo agudo del injerto (16,5%), seguido de infección (15,9%), combinado de enfermedad vascular del injerto y muerte súbita (13,7%), tumores (11,9%) y rechazo agudo (7,8%).ConclusionesLa supervivencia obtenida en España con el TC, sobre todo en los últimos años, lo sitúan como el tratamiento de elección para cardiopatías irreversibles en situación funcional avanzada y sin otras opciones médicas o quirúrgicas establecidas.ObjectiveThe purpose of this report is to present the results obtained with heart transplantation (HT) since this therapeutic modality first began to be used in Spain in May 1984.Materials and methodsA descriptive analysis was performed of all HT performed until December 31, 2010.ResultsThe total number of transplants is 6,291. The average clinical profile of the Spanish heart transplant patient in 2010 was that of a 53-year-old male who had been diagnosed with nonrevas-cularizable ischemic heart disease accompanied by severely depressed ventricular function and poor functional status. The implanted heart was typically from a 39-year-old donor who had died from brain hemorrhage. The average waiting list time was 99 days.Mean survival time has progressively increased over the years. Whereas for the overall series, the probability of survival at 1, 5, 10 and 15 years was 78, 67, 54 and 40%, respectively, over the past 5 years, the probability of survival at 1 and 5 years was 85 and 73%, respectively.The most frequent cause of death was acute graft failure (16.5%), followed by infection (15.9%), the combination of graft vascular disease and sudden death (13.7%), tumors (11.9%) and acute rejection (7.8%).ConclusionsThe survival rates obtained in Spain with HT, especially in recent years, position heart transplant as the treatment of choice in irreversible heart failure patients without other established medical or surgical options.

7540 Background: Different exon 19 deletion types have shown different in vitro sensitivity to erlotinib, with the lower IC50 for deletion E746_A750 (ELREA) (Yuza et al. Cancer Biol Ther 2007). This information prompted us to examine outcome according to type of exon 19 deletion in the EURTAC study. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Progression-free survival (PFS) was 9.7 months (m) vs 5.2 m, respectively (P

El profesional de la información (EPI) es una de las principales revistas científicas españolas sobre información, comunicación, bibliotecas y nuevas tecnologías de la información incluida en índices internacionales como los JCR, y SJR. EPI cuenta con una trayectoria de más de 20 años, lo que le ha convertido en una fuente de referencia y escaparate para el desarrollo de investigaciones en los ámbitos antes mencionados. En este sentido, resulta necesario entender cuáles son las principales líneas que se están desarrollando dentro del marco de la revista, sus principales autores y el impacto que tienen sus publicaciones en el desarrollo del estado del arte. En respuesta a esta necesidad, esta publicación analiza los últimos cinco años (2014-2018) de EPI utilizando SciMAT como herramienta bibliométrica para la creación de mapas de ciencia, identificando las áreas temáticas que han sido objeto de investigación durante el periodo de análisis, su composición, relación y peso en la evolución de la revista

Patients in cardiogenic shock benefit from mechanical reperfusion, but their mortality remains high even using intra-aortic balloon. It is not well known if a Mechanical Circulatory Support Program (MCSP) might improve the long term outcome of these patients. We have compared in-hospital and 1 year