Search

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort (C) 1), G1/2 gastrointestinal (C2), G1/2 pancreatic (C3) and G3 gastroenteropancreatic (GEP) (C4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month (m) disease control rate (DCR) for C1-3 and 9-m overall survival (OS) rate for C4. Median follow-up was 16.5 m; 9-m DCR was 25.9%/35.5%/25% for C1, 2, and 3 respectively. The 9-m OS rate for C4 was 36.1%. Benefit in C4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab was safe in NENs and showed modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Patients with resected colorectal cancer liver metastases display heterogeneous clinical behavior. The identification of new prognostic factors would help in making more accurate decisions. The aim of this study was to evaluate the survival impact of circulating tumor cells (CTCs) in this setting. We conducted a prospective study of patients with resected liver metastases of colorectal cancer. Patients were included in the study from February 2009 to January 2013. The CellSearch System™ was employed for the detection of pre- and postsurgery CTCs. A positive test was defined as two or more CTCs/7.5 mL of blood. Recurrence rate, disease-free survival, and overall survival were calculated, and univariate and multivariate analyses were performed. Forty-four patients were included in our study. After a median follow-up of 60 months (range 28–74), 32 patients experienced recurrence (72.7%). The CTCs number was determined and the test was positive in 8 patients (18.6%) before surgery and 13 patients (29.5%) after surgery. The postoperative detection of CTCs was not related to any clinical outcome; however, the preoperative detection of CTCs was significantly related to behavior. All patients in the preoperative CTC-positive group relapsed, versus 65% in the CTC-negative group (p = 0.051). Disease-free survival was 19 months in the preoperative CTC-negative group versus 7 months in the CTC-positive group (p = 0.01). Additionally, overall survival was 69 months in the preoperative CTC-negative group versus 17 months in the CTC-positive group (p = 0.004). Preoperative CTC count remained significant in multivariate analysis. In this cohort of colorectal cancer liver metastases patients, the presence of two or more preoperative CTCs was associated with disease progression and poor survival despite complete resection.

The Clouds and the Earth’s Radiant Energy System (CERES) Energy Balanced and Filled (EBAF) Edition 4.1 data product provides global surface irradiances. Uncertainties in the global and regional monthly and annual mean all-sky net shortwave, longwave, and shortwave plus longwave (total) irradiances are estimated using ground-based observations. Error covariance is derived from surface irradiance sensitivity to surface, atmospheric, cloud and aerosol property perturbations. Uncertainties in global annual mean net shortwave, longwave, and total irradiances at the surface are, respectively, 5.7 Wm−2, 6.7 Wm−2, and 9.7 Wm−2. In addition, the uncertainty in surface downward irradiance monthly anomalies and their trends are estimated based on the difference derived from EBAF surface irradiances and observations. The uncertainty in the decadal trend suggests that when differences of decadal global mean downward shortwave and longwave irradiances are, respectively, greater than 0.45 Wm−2 and 0.52 Wm−2, the difference is larger than 1σ uncertainties. However, surface irradiance observation sites are located predominately over tropical oceans and the northern hemisphere mid-latitude. As a consequence, the effect of a discontinuity introduced by using multiple geostationary satellites in deriving cloud properties is likely to be excluded from these trend and decadal change uncertainty estimates. Nevertheless, the monthly anomaly timeseries of radiative cooling in the atmosphere (multiplied by −1) agrees reasonably well with the anomaly time series of diabatic heating derived from global mean precipitation and sensible heat flux with a correlation coefficient of 0.46.

Multidisciplinari; Teràpia sistèmica; Càncer de tiroide Multidisciplinario; Terapia sistémica; Cáncer de tiroides Multidisciplinary; Systemic therapy; Thyroid cancer Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios make necessary a multidisciplinary approach that includes new diagnostic methods and surgical, radiopharmaceutical and systemic therapies. This guideline updates several aspects of management of thyroid cancer.

OBJECTIVE: Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC.MATERIALS AND METHODS: We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.

The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0–20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V 20, V 30, V 40, V 50, mean dose (D mean), minimum dose (D min), D 90 (dose received by 90% of the sphincter) and D 98. The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann–Whitney test. Mean Wexner score was 5.5 points higher in those patients with V 20 > 0 compared to those for which V 20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V 20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to

e16707 Background: Previously our group showed the potential use of a score based (SPI) on MGMT, NDRG-1 and PHLDA-3 immunohistochemistry (IHC) expression as predictor of outcome in operated PanNET (Viúdez et al. Oncotarget 2016). The present retrospective multicenter project is analyzing the predictive/prognosis role of MGMT, NDRG-1 and PHLDA-3 in patients treated with advanced PanNET treated CAPTEM or everolimus. Methods: IHC nuclear staining for MGMT and PHLDA-3 is being scored as 0, 1-5%, 6-50% and ≥ 51%. For NDRG-1, we are using a cytoplasmic score from 0 to 2 based on distribution pattern (null, patched or diffuse). Results: 60 of 105 pts have been fully analyzed., most of then women (53%) and median age of 63 (27-79). 30 pts were treated with CAPTEM and 30 pts with everolimus. Median previous lines were 1 (21,7% received chemotherapy previously), and 91,7% pf pts had ki67 < 20%. 65,5%, 10,2% and 29,1% were null for MGMT, NDRG-1 and PHLDA-3 IHC analysis. In the entire cohort K-M analysis showed significant differences for PFS or OS based on best response observed (p = 0,0001) and number previous lines received (p = 0,05), respectively. In pts treated with CAPTEM, log rank analysis showed significant differences for PFS (p = 0,047 HR:4,63 CI95%: 1,023-20,990) and OS (p = 0,040 HR:5,433 CI95%: 1,082-27,266) based on our SPI. Similar, although not significant, results were observed in everolimus-treated cohort for PFS (p = 0,529) and OS (p = 0,592) according to SPI. Conclusions: As it was described previously in operated PanNET, our SPI also seems to own predictive role in pts with advanced PanNET treated with CAPTEM or everolimus. More mature results of our work are needed and will be presented during 2020 ASCO Annual Meeting.

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8.74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88). Electronic supplementary material The online version of this article (10.1186/s40425-018-0405-z) contains supplementary material, which is available to authorized users.

Resumen Introduccion GIDEON es un estudio internacional prospectivo, no intervencionista, que evaluo la seguridad de sorafenib en pacientes con carcinoma hepatocelular (CHC) no resecable en la practica clinica diaria, incluidos pacientes Child-Pugh B. Objetivos Analisis de datos recogidos en Espana sobre seguridad y efectividad de sorafenib y los patrones de tratamiento. Metodos Se recogieron los datos demograficos y de la enfermedad, la dosis inicial usada, los acontecimientos adversos emergentes del tratamiento (AA) y las modificaciones de dosis a lo largo del seguimiento. Se valoraron la supervivencia global y el tiempo hasta la progresion de la enfermedad. La eficacia y la seguridad se analizaron en funcion de la clasificacion Child-Pugh y la dosis inicial. Resultados Se incluyo a 143 pacientes de 19 hospitales espanoles. El 24,5% eran pacientes Child-Pugh B. El 90,9% de los pacientes recibio una dosis inicial de 400 mg/12 h. En pacientes Child-Pugh A se modifico mas frecuentemente la dosis y la duracion del tratamiento fue mas larga. La incidencia de AA y de aquellos relacionados con el farmaco fue similar en los pacientes Child-Pugh A y B, aunque los AA graves fueron mas frecuentes en los pacientes Child-Pugh B. Los mas frecuentes fueron diarrea, fatiga y eritrodisestesia palmo-plantar. La mediana de supervivencia global fue de 384 dias, y superior en pacientes Child-Pugh A (593 vs. 211 dias en Child-Pugh B); la mediana hasta la progresion de la enfermedad fue de 177 dias, similar en ambos subgrupos. Conclusion El perfil de seguridad de sorafenib en pacientes espanoles con CHC no resecable es independiente de la funcion hepatica. El estado Child-Pugh no parece influir en el enfoque de dosificacion de sorafenib ni en el tiempo hasta la progresion, pero si parece ser un fuerte predictor de la supervivencia.

The behavior of the atmospheric downward longwave radiation at the surface under overcast conditions is studied. For optically thick clouds, longwave radiation depends greatly on the cloud base height (CBH), besides temperature and water vapor profiles. The CBH determines the cloud emission temperature and the air layers contributing to the longwave radiation that reaches the surface. Overcast situations observed at Girona (NE Iberian Peninsula) were studied by using a radiative transfer model. The data set includes different seasons, and a large range of CBH (0–5000 m). The atmosphere profiles were taken from the European Center for Medium-Range Weather Forecast analysis. The CBH was determined from ceilometer measurements and also estimated by using a suitable method applied to the vertical profile of relative humidity. The agreement between calculations and pyrgeometer measurements is remarkably good (1.6 ± 6.2 W m−2) if the observed CBH is used; poorer results are obtained with the estimated CBH (4.3 ± 7.0 W m−2). These results are better than those obtained from a simple parameterization based upon ground-level data (1.1 ± 11.6 W m−2), which can be corrected by adding a term that takes into account the CBH (−0.1 ± 7.3 W m−2). At this site, the cloud radiative effect (CRE) at the surface lies in the range 50–80 W m−2, has a clear seasonal behavior (higher CRE in winter), and depends upon the CBH. For the cold and the warm seasons, CRE decreases with CBH at a rate of −5 and −4 W m−2/km, respectively. Results obtained for other climates (subarctic and tropical) are also presented.

Aim To asses the moment of local recurrence and its influence on the appraisal of the results of neoadjuvant chemoradiotherapy (CRT). Methods We evaluated 317 patients with a preoperative diagnosis of stage II or III rectal cancer who underwent rectal resection. Gender, age, neoadjuvant treatment, circumferencial resection margin, adjuvant treatment, pretreatment carcinoembryonic antigen level, tumor location, TNM stage, lymph node retrieval, abdominoperineal resection, and lymphatic or vascular infiltration were registered prospectively. Follow-up was performed to detect local or systemic recurrences. Timing of local recurrence (LR) in regard to analyzed variables was performed by using analysis of variance. To evaluate the influence of late local recurrence (LLR) on the results of neoadjuvant CRT, we performed a log-rank test censoring all observations at 60 and at 120 months. Results After a mean follow-up of 73.6 months (range, 1–171), 68 patients developed a recurrence. Twenty-three patients developed LRs (6.9%), and 5 developed LLRs. The earliest relapse was diagnosed 4 months after rectal surgery, and the latest was diagnosed 120 months after surgery. Patients who underwent neoadjuvant CRT developed LR significantly later than patients without neoadjuvant CRT (51.8 vs 13.5 months; P = 0.002). LR rates in patients who underwent preoperative CRT and those who did not were 9.2% and 3.5% (difference, 5.7%), respectively, after censoring all observations at 60 months and 9.2% and 6.1% (difference, 3.1%) after censoring all observations at 120 months. Conclusion Local recurrence was diagnosed significantly later in patients treated with neoadjuvant CRT. Follow-up longer than 5 years is needed to evaluate definitive results in patients treated with neoadjuvant CRT.

Background: The main objective of this study was to find out if the application of adjuvant oxaliplatin (OXA) influences sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/ radiotherapy followed by lower anterior resection (LAR). Methods: Patients with LARC treated at our medical center with LAR and with absence of loco-regional relapse for at least two years were retrospectively analyzed independently of the type of adjuvant treatment that they received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, with score points inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Sphincter function as assessed by the Wexner test was compared between patients with and without OX treatment, using the non-parametrical Mann-Whitney test. Statistical analyses were conducted with IBM SPSS Statistics package, version 20. Results: 92 patients were included in our study since 2006. The mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group of patients without adjuvant OXA treatment was 6.0 (1.0-11.25), and of 5.0 (1.0-10.0) for the group that received adjuvant OXA. Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC according to the absence of deleterious effects over sphincter anal function. Due to the retrospective nature of our study, prospective studies should be warranted in similar scenarios.

3082 Background: Identification of “agnostic” genetic drivers in cancer is foreseen as a major step forward in precision medicine.Unfortunately, “off label” use of targeted therapies is not widely available and many oncogenic alteration do not present the same behaviour accross all tumor types.We aimed to analyze the real impact on patients management of the implementation of a systematic screening of genetic alterations in centers of the Spanish Group for Rare Cancer (GETHI). Methods: We designed an observational, prospective and multicenter study to molecularly characterize any adult patient with advanced cancer.Formalin fixed paraffin-embedded samples were studied by TrkA-C,ROS1 and ALK immunohistochemistry followed by RT-PCR when positive to confirm gene fusions. Additonally, the Next Generation Sequencing paltform ArcherFusion Plex (able to detect point mutations and rearrangements in 53 cancer related genes) was implemented.Clinical data regarding treatment administered and outcome, were collected from patients identified as harboring drugable alterations. Results: Up to 26 hospitals all over the country got involved in the study. 341 tumoral tissues, representing 41 different histologies were collected. Molecular studies could be performed in 292 samples that led to the identification of 33 patients as harboring somatic oncogenic mutations. 21 were considered druggable and 5 got targeted therapy directed against the alteration identified (three glioblastoma patients with EGFR mutations received erlotinib, one prostate cancer with a BRAF fusion received trametinib and one lung cancer with ALK translocation, previously deemed as negative by standard screening, received crizotinib). One of the glioblastoma patients achieved a long lasting stabilitation and both the prostate and lung tumors presented dramatic partial responses. Conclusions: Though only few cases harboring drugable alteratons got specif treatment, 50% achieved a meanignful benefit. A wide access to molecular screening and targeted drugs could improve the outcome of cancer patients.

Objective This study evaluates satisfaction with care (SC) in cancer patients treated at a Spanish day hospital to identify SC determinants and assess the relationship between SC and quality of life. Methods One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Cancer Outpatient Satisfaction with Care questionnaire for chemotherapy (OUT-PATSAT35 CT), the Oberst patients' perception of care quality and satisfaction scales, and an item on intention to recommend the hospital. Frequencies in the SC instruments, Spearman correlations between each scale of the OUT-PATSAT35 CT and overall satisfaction and between the subscales of OUT-PATSAT35 CT and of QLQ-C30 were calculated, and the determinants of patients' SC were calculated through multivariate regression models. Results Satisfaction with care was high: mean scores were >70 in all OUT-PATSAT35 CT areas except doctor availability and environment. These scores were in line with the other SC instruments. Correlation with overall satisfaction was high and statistically significant (p

Aim There is a lack of prognostic factors of preoperative chemoradiation for locally advanced rectal cancer. Thymidylate synthase (TS) is the most important target of 5-fluorouracil; three main genetic polymorphisms of TS have been described. We analysed the prognostic value of these in patients with locally advanced rectal cancer treated with fluoropyrimidine-based chemoradiation. Method Ninety-nine patients treated between November 2001 and March 2009 were included. All were treated by radiotherapy (5040 cGy) and concomitant fluoropyrimidine-based chemotherapy. Three polymorphisms were analysed: (i) a double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream of the ATG codon initiation site in the 5′-terminal regulatory region, (ii) a functional G > C single nucleotide polymorphism present in the second repeat of the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3′-untranslated region. DNA was extracted from paraffin-embedded core biopsies taken from the tumour and the genotype was analysed using polymerase chain reaction restriction fragment length polymorphism. Results The 6 bp polymorphism was significantly associated with disease-free survival (+ 6 bp/+ 6 bp vs−6 bp/−6 bp, P = 0.032 logistic regression). No differences were found in disease-free survival according to the other polymorphisms studied. No relationship was observed between the different TS genotypes and pathological regression. Conclusion The study suggests that the TS 6 bp polymorphism may be a predictor of disease-free survival in patients with locally advanced rectal cancer treated with fluoropyrimidine-based chemoradiation.

Purpose: This paper studies the Quality of Life (QL) of Spanish advanced non-small-cell lung cancer (NSCLC) patients receiving platinum-doublet chemotherapy, compares our results with those from studies from other cultural areas, and identifies factors associated with global QL and survival prognostic variables. Methods: EORTC QLQ-C30 and QLQ-LC13 questionnaires were completed three times by 39 patients along treatment and follow-up. Univariate and multivariate logistic regression analyses were performed to study global QL determinants (≤50 points considered low global-QL score). Analyses of prognostic variables for death were performed (Cox proportional hazards models). Results: QL mean scores in the whole sample were moderately high, with limitations (>30) in physical, role, social functioning, emotional areas, fatigue, pain, neuropathy and global QL. Differences with studies from other cultural areas were mainly found in the lower score for dyspnoea (≥15 points). There were no significant differences in QL scores between the first and second assessments. In six areas, the third assessment was lower than the first and second: fatigue, hair loss (>20 points); physical, social functioning, neuropathy (10–20 points); emotional functioning (5–10 points). The best model to explain the chances of low QL includes, as explanatory variables, high emotional functioning as protective factor and fatigue as risk factor (R2 = 0.70). Eight QL areas (four pain-related) and performance status showed a statistically significant association with survival. Conclusion: Patients adapted well to their disease and treatments. Platinum-doublet can be administered in advanced NSCLC patients. Our QL data are in line with those from other cultural areas. This study was supported by grants from the Instituto de Salud Carlos III and the Departamento de Salud del Gobierno de Navarra, Spain, to finance a research assistant to interview the patients.

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

Background Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)–tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition. Patients and methods Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated. Results Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3–9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12–26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2–12.4) compared with 5.5 mo (2.9–8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea. Conclusions The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.

Colorectal cancer remains a major public health concern in Europe and North America. It is responsible for one million new cases and half a million deaths per year worldwide. During the past few years new effective treatments have evolved improving the outcome of patients with this disease. Several alternatives are currently available for advanced colorectal cancer patients including different chemotherapeutic regimens (fluoropyrimidines, irinotecan and oxaliplatin) and targeted therapies such as bevacizumab and cetuximab. Different combinations achieve a median survival of over 2 years. Intense efforts focus on identifying agents targeting growth factor receptors, signal transduction pathways or angiogenesis mediators. One of the last available drugs for the management of advanced colorectal cancer is panitumumab, a well-tolerated and effective anti-EGFR monoclonal antibody approved as a single agent in chemotherapy refractory patients. We discuss the current evidence supporting panitumumab for metastatic colorectal cancer treatment, potential predictive biomarkers and ongoing clinical trials with different combinations including panitumumab.

A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome. METHODS: Eighty-seven chemotherapy-naive mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m(-2)) and CPT-11 (150 mg m(-2)), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m(-2) bid on days 1-7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS. RESULTS: The capecitabine RD was 1000 mg m(-2) bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6-13.4) and 27 months (95% CI; 17.2-36.8), respectively.The GSTP1-G genotype, the Kohne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P=0.004). CONCLUSION: First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A>G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy.

BACKGROUND To the authors' knowledge, liver damage after liver radioembolization with yttrium90-labeled microspheres has never been studied specifically. METHODS Using a complete set of data recorded prospectively among all patients without previous chronic liver disease treated by radioembolization at the authors' institution from September 2003 to July 2006, patterns of liver damage were identified and possible risk factors were analyzed. RESULTS In all, 20% of patients developed a distinct clinical picture that appeared 4 to 8 weeks after treatment and was characterized by jaundice and ascites. Veno-occlusive disease was the histologic hallmark observed in the most severe cases. This form of sinusoidal obstruction syndrome was not observed among patients who never received chemotherapy or in those in whom a single hepatic lobe was treated. Relevant to treatment planning, a possible risk factor was a higher treatment dose in relation to the targeted liver volume. A transjugular intrahepatic stent shunt improved liver function in 2 patients with impending liver failure, although 1 of them eventually died from it. CONCLUSIONS Radioembolization of liver tumors, particularly after antineoplastic chemotherapy, may result in an uncommon but potentially life-threatening form of hepatic sinusoidal obstruction syndrome that presents clinically with jaundice and ascites. Cancer 2008. © 2008 American Cancer Society.

The purpose of this trial was to define the maximum tolerated duration (MTD), dose-limiting toxicity (DLT), regimen-related toxicities (RRT), and pharmacokinetics of gemcitabine infused at a fixed dose rate (FDR) of 10 mg/m2/min, combined with docetaxel/melphalan/carboplatin, using autologous stem cell transplantation (ASCT). The duration of gemcitabine infusion was incrementally escalated as a single treatment on day −6 or as 4 daily infusions on days −5 to −2. Gemcitabine was followed by docetaxel (300 or 350 mg/m2) on day −5, and then melphalan (50 mg/m2/day) and carboplatin (333 mg/m2/day) on days −4 to −2. Fifty-two patients with refractory tumors were accrued with a median age of 40 (range: 6-66), a median of 3 (1-6) prior chemotherapy regimens, and 3 (1-7) organs involved. The gemcitabine MTD was defined at 20 hours (total dose 12,000 mg/m2) on both schedules. The DLT was enteritis. Three patients died from aspiration, catheter-related sepsis, and enteritis, respectively. The tumor response rate was 91%, with 50% complete responses. At current 2-year median follow-up, the event-free and overall survival (EFS, OS) rates are 54% (median 26 months) and 79% (median not reached), respectively. Gemcitabine area under the curve (AUC), but not clearance, increased linearly with infusion duration, and correlated with grade 3 RRT. Docetaxel showed a linear increase of its AUC and similar clearance compared with prior reports at lower doses. In conclusion, ASCT-supported infusions of gemcitabine at FDR could be prolonged up to 20 hours. The resulting gemcitabine/docetaxel/melphalan/carboplatin combination was highly active in refractory cancers and should be further tested in disease-specific trials.

Pancreatic neuroendocrine tumours (PanNETs) are considered a relatively unusual oncologic entity. Due to its relative good prognosis, surgery remains the goal standard therapy not only in localized disease but also in the setting of locally or metastatic disease. Most of the patients are diagnosed in metastatic scenario, where multidisciplinary approach based on surgery, chemotherapies, liver-directed and/or molecular targeted therapies are commonly used. Owing to a deeper molecular knowledge of this disease, these targeted therapies are nowadays widely implemented, being the likely discovery of predictive biomarkers that would allow its use in other settings. This review is focused on describing the different classifications, etiology, prognostic biomarkers and multidisciplinary approaches that are typically used in PanNET.

Pancreatic neuroendocrine tumor (PanNET) is a neoplastic entity in which few prognostic factors are well-known. Here, we aimed to evaluate the prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in 92 patients with resected PanNET and follow-up longer than 24 months. In multivariate analyses, ki-67 and our immunohistochemistry prognostic score (IPS-based on MGMT, NDRG-1 and PHLDA-3 IHC expression) were independent prognostic factors for disease-free-survival (DFS), while age and IPS were independent prognostic factors for overall survival (OS). Our IPS could be a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET.

Pancreatic neuroendocrine tumor (PanNET) is a neoplastic entity in which few prognostic factors are well-known. Here, we aimed to evaluate the prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in 92 patients with resected PanNET and follow-up longer than 24 months. In multivariate analyses, ki-67 and our immunohistochemistry prognostic score (IPS-based on MGMT, NDRG-1 and PHLDA-3 IHC expression) were independent prognostic factors for disease-free-survival (DFS), while age and IPS were independent prognostic factors for overall survival (OS). Our IPS could be a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET.

GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients.To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns.Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose.We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups.The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.

To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). We retrospectively reviewed the records of 72 consecutive patients (2007–2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

The application of nanotechnology in oncology has increased the efficacy and efficiency of some cytotoxic agents. The paradigm in this field is nab-paclitaxel, a soluble form of paclitaxel that is linked to albumin nanoparticles. The development of nanotechnology as a delivery system for paclitaxel has provided better pharmacokinetic and pharmacodynamic characteristics, neutralizing its hydrophobicity. This procedure significantly improves the treatment of metastatic breast cancer compared to conventional paclitaxel-based therapies, including other type of cancers such as metastatic pancreatic cancer, stage IIIB-IV non-small cell lung cancer (NSCLC) and metastatic melanoma. In these last cases, significant differences were found in primary end-points for patients treated with nab-paclitaxel-based chemotherapy compared to those treated with conventional treatments. The application of nanotechnology in cancer treatment may also improve the efficacy of other known drugs, as a result of improved pharmacokinetic and pharmacodynamic profiles, similarly to paclitaxel.

Pathological response has been shown to be a predictor for survival after preoperative chemotherapy and surgical resection of colorectal cancer liver metastases. This retrospective analysis evaluated the effect on pathological response of adding bevacizumab to standard neoadjuvant chemotherapy in patients with metastatic colorectal cancer (mCRC) and liver metastases.Patient records from two Spanish centres were retrospectively examined for this analysis. Patients were included if they had stage IV mCRC with liver metastases, were unresectable or marginally resectable tumour before chemotherapy, and had oxaliplatin- or irinotecan-based chemotherapy, with or without bevacizumab, before resection. Tumour response was evaluated using response evaluation criteria in solid tumours (RECIST). Pathological response was assessed by pathologists blinded to treatment.Ninety-five patients were included. Good pathological responses (PR0/PR1) were observed in 37 patients (39 %). The RECIST response rate was 51 %. Only 42 % of patients with a good pathological response had a complete or partial response according to RECIST, while 57 % of those with a poor pathological response had a complete or partial response according to RECIST. RECIST response rates were similar with and without bevacizumab, although 49 % of bevacizumab-treated patients had a good pathological response versus 27 % of those receiving chemotherapy alone (χ (2) P = 0.0302).Pathological response may be a better indicator of treatment efficacy than RECIST for patients with mCRC receiving bevacizumab in the neoadjuvant setting. Adding bevacizumab to chemotherapy has the potential to increase pathological response rates. Well-designed prospective clinical studies are required to establish the efficacy and tolerability of this approach.

Background: Quality of Life (QoL) is a key element in rectal cancer (RC) patients. Aims: this study assesses QoL in a sample of RC patients in their treatment follow-up period, and compares surgery modalities. Patients and methods: eighty four locally advanced RC patients who had received surgery and neoadjuvant chemoradiotherapy were included in the study. Of these, 70 had adjuvant chemotherapy. All patients completed the EORTC QLQ-C30 and the QLQ-CR29 once at least one year after completion of their treatment. Low anterior resection (LAR) patients also completed a Functional Evaluation questionnaire. Results: QoL scores in the EORTC questionnaires for the sample as a whole were high in most dimensions, in line with the general population's QoL values, although moderate limitations (> 30 points) were observed in urinary frequency, flatulence, impotence and sexual function. The scores for the Functional Evaluation were adequate (mean combined bowel function score of 18.2). LAR patients had a higher stool frequency than those with abdominoperineal resection (APR; p < 0.001). No differences in body image were found amongst LAR and APR patients. LAR patients with a lower anastomosis had higher faecal incontinence (p = 0.02), whereas those with a reservoir had better emotional functioning (p = 0.04) and higher faecal incontinence (p = 0.03). Conclusions: QoL scores and functional evaluation indicated patients had adapted to their disease and treatment. The few differences in QoL found between surgery modalities are in line with other recent studies and in contrast with earlier ones that suggested a lower QoL in APR patients.

241 Background: We aimed to evaluate the expression and prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in resected pancreatic neuroendocrine tumors (PanNET). Methods: Ninety-two patients with resected primary PanNET and follow-up > 24 months were included in this study. Nuclear staining for MGMT and PHLDA-3 were scored as 0, 1-5%, 6-50% and ≥ 51%; cytoplasmic NDRG-1 staining was scored based on intensity and pattern from 0 to 2. We then grouped IHC scores for MGMT (absent versus any expression); for NDRG-1 (0 versus 1 versus 2) and for PHLDA-3 ( < 50% versus ≥ 51%). Finally, we developed an immunohistochemistry prognostic score (IPS) based on MGMT, NDRG-1 and PHLDA-3 IHC expression to predict disease free survival (DFS) and overall survival (OS). The discriminatory ability of multivariate models combining the IPS and important clinical variables was assessed with Harrel’s c-index (HCI) and a modification of Harrell’s c-index (mHCI). Results: DFS was significantly worse in patients without any expression of MGMT compared with those with any grade of expression (HR: 2.21; 95%CI: 0.97-5.02; p = 0.013), in patients with moderate or high score for NDRG-1 (p = 0.005), and in those with high-expression for PHLDA-3 (HR: 1.94; 95%CI: 1.05,3.6; p = 0.036). A significant difference in OS was observed based on NDRG-1 score (p = 0.013). In multivariate analyses, ki-67 (HR: 2.45; 95% CI: 1.20-5.01; p = 0.01) and IPS (HR: 2.68; 95% CI: 1.60,4.49; p = 0.00018) were independent prognostic factors for DFS, while age (HR: 7.67; 95% CI: 2.14,27.45; p = 0.0017) and IPS (HR: 2.67; 95% CI: 1.11, 6.41; p = 0.03) were independent prognostic factors for OS. HCI for the multivariate DFS and OS models were 0.796 and 0.788, respectively. Conclusions: Our IPS is a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET. Prospective studies are warranted to validate our findings and determine its role for patients’ selection to neo/adjuvant treatments

This study evaluates satisfaction with care (SC) in cancer patients treated at a Spanish day hospital to identify SC determinants and assess the relationship between SC and quality of life.One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Cancer Outpatient Satisfaction with Care questionnaire for chemotherapy (OUT-PATSAT35 CT), the Oberst patients' perception of care quality and satisfaction scales, and an item on intention to recommend the hospital. Frequencies in the SC instruments, Spearman correlations between each scale of the OUT-PATSAT35 CT and overall satisfaction and between the subscales of OUT-PATSAT35 CT and of QLQ-C30 were calculated, and the determinants of patients' SC were calculated through multivariate regression models.Satisfaction with care was high: mean scores were70 in all OUT-PATSAT35 CT areas except doctor availability and environment. These scores were in line with the other SC instruments. Correlation with overall satisfaction was high and statistically significant (p0.01) for all subscales, especially for the nurses domain, which also had higher SC scores. Correlations between the EORTC QLQ-C30 and the OUT-PATSAT35 CT were low (≤ 0.35). Younger patients and those with breast cancer showed significantly lower satisfaction in most subscales. Unmarried patients and patients that had undergone surgery reported lower satisfaction only in specific subscales.Satisfaction with care among cancer patients treated at the day hospital is high. Nurses play a key and successful role. Age and tumour location revealed stronger relationships with SC. Correlations between SC and quality of life indicate that these concepts are complementary.

The OUT-PATSAT35 CT questionnaire evaluates satisfaction with care expressed by cancer outpatients receiving chemotherapy. This study assesses the psychometric properties of the OUT-PATSAT35 CT when applied to a sample of Spanish patients. One hundred seventy-six patients with different tumour sites and disease stages completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30, the OUT-PATSAT35 CT, the Oberst patients’ perception of care quality and satisfaction scales (OS) and the item on intention to recommend the hospital (IR). Psychometric evaluation of the structure, reliability and validity of the questionnaire was conducted. Multitrait scaling analysis showed that 32 of 34 item-scale correlation coefficients met the standards for convergent validity and that many of them met the standards for discriminant validity. Cronbach’s coefficients were good (0.78–0.97) for all scales except doctor availability and environment. Correlations between the QLQ-C30 and the OUT-PATSAT35 CT were low (≤0.40). Correlations between IR and the OUT-PATSAT35 CT were moderate, and correlations between this questionnaire and the OS were fairly low. Areas whose contents were more related had higher correlation coefficients (>0.50) and vice versa (

Sir, We have read with particular attention the recent article published in the BJC by Alvarez et al (2013). They, through endoscopic ultrasound elastography system and conventional immuno-histochemical assays, perform an intrinsic characterisation of tumour stroma's stiffness, fibroblast density and architecture focusing in type I collagen fibre arrangement, cancer-associated fibroblasts (CAFs) and activated CAF quantification. The analysis of post-treatment tissues from patients treated with nab-paclitaxel and gemcitabine combination showed a decrease in CAF number and changes in collagen architecture. These results reaffirm the potential ability of nab-paclitaxel to target the stroma and to change its phenotype, altering the ‘hard of the rock', as described by Garber (2010), intensifying its permeability to deliver cytotoxic agents such as gemcitabine by increasing tumour vascularisation or enzymatic inhibition (Frese et al, 2012) that would suppose a better pharmacokinetic profile (Von Hoff et al, 2011). Even though it is known the clinical benefit of nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer, the cellular or molecular mechanisms that are expressly addressing this stromal involution have not been appointed yet (Alvarez et al, 2013). In this sense, authors analysed the role of secreted protein, acidic and rich in cysteine (SPARC) although they could not find the correlation between the degree of SPARC expression and clinical or pathological responses due to its high affinity to albumin protein of nab-paclitaxel. SPARC strengthens the accumulation of nab-paclitaxel mediated by albumin in the ‘tumour's Achilles' heel' (Von Hoff, Annual meeting of the American Society of Clinical Oncology, 2009); however, the mere use of this endogenous transport system would not justify the clinical impact of this combined treatment. From our point of view the key may be in what Omary et al (2007) described as ‘a star on the rise' in pancreatic disease: the pancreatic stellate cells (PaSCs; α-SMA+ Nestin++ Vimentin++) because of their role as the main manufacturers of profibrotic extracellular matrix (ECM) components of the pancreatic tumour stroma, and which should match with the activated CAFs (SMA+ Vimentin+ fibroblasts) in Alvareźs paper. In pancreatic cancer, PaSCs show increased proliferation and migration properties, and so they could be a suitable target for nab-paclitaxel because of their ability to interfere with the mitotic activity (Gradishar, 2006). Alvarez et al (2013) demonstrate that although CAFs number decreases in patients treated with nab-paclitaxel plus gemcitabine in neoadjuvant setting, the average of activated CAFs remains unchanged. We would like to explain our hypothesis related to what is happening in the stroma: it could be a transient blockade of activated CAFs metabolism, a quiescent status forced for a pharmacologically active substance. Bachem et al (2005) show that cancer cells (CCs) induce a desmoplastic reaction in pancreatic adenocarcinoma by stimulating PaSCs in a paracrine way. So it could be an indirect elimination of principal fibrogenic mediators that stimulate proliferation (platelet-derived growth factor) and ECM synthesis (fibroblast growth factor -2 and transforming growth factor -s1) of activated PaSCs through the abrogation of CCs. In this sense, the hypothetical presence of surface cellular receptors for nab-paclitaxel in CCs could be an interesting pathway biomarker for the effectiveness of the drug as authors related. On the other hand, the ablation of physiological PaSCs functioning after nab-paclitaxel inclusion, in turn, would break the two-way communication between PaSCs and CCs (Apte et al, 2013). In this context, under normal conditions CCs recruit new PaSCs to their vicinity (Vonlaufen et al, 2008), whereas nab-paclitaxel would temporarily inhibit the main mechanism that rules the desmoplastic reaction. All these molecular mechanisms would allow to maintain and stabilise the activated CAF's number despite them being dysfunctional, and also would decline its CAF progeny. In this sense, Apte et al (2013) and Bachem et al (2005) propose that activated PaSCs can transform into a myofibroblast-like phenotype sub-population with the ability of secreting excess amounts of ECM. In conclusion, due to the dynamic nature of the stromal compartment, it is critically involved in the development and progresion of pancreatic tumours (Heinemann et al, 2013). Before using neadjuvant treatment it may be important to know the stroma's cellular activation grade with regard to PaSCs plus their number. In this sense, PaSCs or activated CAFs could give us ample information about tumoral potential of the stroma itself and so could have an important contribution for the patient's prognosis. Also, the fact that activated CAFs do not decrease after nab-paclitaxel treatment could not mean that these cells are not one of the main actors of stromal disruption but the primary target of nab-paclitaxel.

Background Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer. Methods Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3-4/N+) were treated with preoperative treatment: 1—patients receiving induction Ch or 2—neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor. Results There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high-body mass index (BMI > 25 kg/m2) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; χ2, P = 0.0024). Conclusions Preoperative treatment with Ch or ChRT for locally advanced gastric cancer can be performed safely with an acceptable operative morbidity and low operative mortality rate with careful consideration of the added risk associated with BMI and surgical resection of the pancreas and spleen. Ch and ChRT is feasible and effective in terms of pathological response and R0 resection. J. Surg. Oncol. 2011;104:124–129. © 2011 Wiley-Liss, Inc.

Downward atmospheric longwave radiation (DLR) is an important component of the terrestrial energy budget, strongly related with the greenhouse effect and therefore remarkably affecting the climate. In this study, DLR at the surface has been calculated using a one‐dimensional radiative transfer model, Santa Barbara DISORT Atmospheric Radiative Transfer (SBDART). A sensitivity study has been performed in order to assess the influence of several variables on DLR levels for cloudless conditions. Among these variables, the atmospheric profiles of temperature and water content have been confirmed as the most important. Calculations have been compared with measurements made with pyrgeometers. The study has been applied to data from two European stations, Payerne (Switzerland) and Girona (Spain). For the Payerne case, for which radio soundings were available, calculations show differences with measurements in the range −2.7 ± 3.4 W m−2. For Girona, where no in situ radio soundings are available, soundings taken about 90 km away and atmospheric profiles from a gridded analysis (European Centre for Medium‐Range Weather Forecasts (ECMWF)) were used along with the meteorological information at screen level. In the latter case, differences between modeling and measurements were about 0.3 ± 9.4 W m−2. From our results, it is found that radiative transfer modeling of DLR can produce results that agree with measurements reasonably well even if no in situ radio soundings are available; the use of profiles from the ECMWF analyses does not greatly increase the bias, while the dispersion of differences is only slightly larger than the uncertainty of the measurements. It has also been confirmed that radiative transfer modeling produces better results than previously published simple parameterizations based only on surface measurements This research was supported by the Spanish Ministry of Science and Innovation (MICINN) projects NUCLIER (CGL2004-02325/CLI) and NUCLIEREX (CGL2007-62664/CLI)

Primary or secondary liver cancer is a major cause of cancer-related mortality worldwide and local tumor growth within the liver determines survival in a great number of patients [1]. Although surgical resection is considered to be the only curative treatment for hepatocellular carcinoma (HCC) or metastases confined to the liver, only a small number of patients are candidates for this type of treatment. In most cases, hepatic resection is not a therapeutic option owing to the size, number, or location of the lesions. Therefore, a number of palliative local treatment modalities, including cryotherapy and radiofrequency or laser ablation, have gained importance in recent years. These methods, however, are only applicable to patients with a limited number of small lesions. Unfortunately, at the time of recognition, most patients already have extended liver disease. Liver metastases have been shown to depend heavily on the hepatic artery for most of their blood supply, whereas the normal liver parenchyma derives the majority of its blood supply from the portal vein [2].

Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefitinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response.

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

4566 Background: Emerging agents blocking the PD-1 pathway show activity and may transform the current treatment landscape of mccRCC. The aim of this study was to evaluate the efficacy and safety o...