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RESUMEN El tumor carcinoide de células caliciformes es una neoplasia mixta casi exclusiva del apéndice, con diferenciación neuroendocrina y mucinosa. La afección metastásica endometrial por carcinomas extragenitales, especialmente el tipo de células de anillo de sello, es rara. Se presenta un caso de tumor carcinoide de células caliciformes apendicular con metástasis endometrial. Se trató de paciente femenina de 70 años quien presentó sangrado genital. El examen ginecológico mostró sangrado genital en moderada cantidad de color rojo-marrón y cuello uterino endurecido. En la biopsia endometrial se halló nidos de células de anillo de sello. La impresión diagnóstica provisional fue carcinoma mal diferenciado de probable origen intestinal. Durante la intervención, el útero tenía consistencia pétrea, el apéndice cecal era fibrótico y engrosado y el epiplón engrosado con nódulos tumorales. Las secciones anatómicas del cuello y cuerpo uterino mostraron focos tumorales. En el apéndice cecal se encontró acúmulos de pequeño tamaño compuestos por células caliciformes. La inmunotinción fue positiva a sinaptofisina, CDX-2, EMA, CK20, CD56 focal. Estos hallazgos confirmaron el diagnóstico de tumor carcinoide de células caliciformes, un tumor caracterizado por infiltración de la pared apendicular por pequeños nidos o cordones de células caliciformes con mucina intracitoplasmática y expresión focal de marcadores neuroendocrinos. Estas neoplasias tienen un comportamiento más agresivo que los tumores neuroendocrinos. La metástasis endometrial es rara y puede ser confundida con un carcinoma primario de células de anillo de sello. Se debe considerar como diagnóstico diferencial después de excluir otros tumores primarios. ABSTRACT Goblet cell carcinoid tumor is an almost exclusive mixed neoplasm of the appendix with neuroendocrine and mucinous differentiation. Endometrial metastatic involvement by extragenital carcinomas, especially the signet ring cell type, is rare. A case of appendiceal goblet cell carcinoid tumor with endometrial metastasis is presented. This was a 70-year-old female patient who presented with genital bleeding. The gynecological examination showed moderate red-brown genital bleeding and hardened cervix. Endometrial biopsy reported nests of signet ring cells. The provisional diagnostic impression was poorly differentiated carcinoma of probable intestinal origin. During surgery, the uterus had a stony consistency, the cecal appendix was fibrotic and thickened, and the omentum was thickened with tumor nodules. Anatomical sections of the cervix and uterine body showed tumor foci. In the cecal appendix, small clusters composed of goblet cells were found. Immunostaining was positive for synaptophysin, CDX-2, EMA, CK20, focal CD56. These findings confirmed the diagnosis of goblet cell carcinoid tumor, a tumor characterized by infiltration of the appendiceal wall by small nests or cords of goblet cells with intracytoplasmic mucin and focal expression of neuroendocrine markers. These neoplasms have a more aggressive behavior than neuroendocrine tumors. Endometrial metastasis is rare and can be mistaken for a primary signet ring cell carcinoma. It should be considered as a differential diagnosis after other primary tumors have been excluded.

Spinal metastases are etiologically characterized by hematogenous, lymphatic, CSF or direct invasion by contiguity. Breast carcinoma is the one with the greatest predilection for bone tissue, presenting an osteolytic lesion in approximately 80% of patients. The aim of the study was to describe the case report of a patient affected by a neoplastic infiltration in the spine resulting from breast adenocarcinoma, with a still unknown primary site. This is an observational study of the descriptive type, carried out through the clinical data of a patient affected by breast carcinoma, initially diagnosed with fibromyalgia, being transferred to hospitalization and diagnostic clarification. Evolved with sudden paraplegia, generalized osteolytic lesions, metastatic in nature. It was observed that even after performing the anamnesis, physical examination, multidisciplinary assessments and imaging tests, they were unable to identify the neoplastic focus of the case in question and that only after the immunohistochemically examination was it possible to identification of the primary focus in the breast. Therefore, it is essential to search for investigative methods, more specific, that help in elucidating the diagnosis, thus allowing the establishment of adequate therapy and, consequently, a better prognosis for the affected. Las metástasis espinales se caracterizan etiológicamente por invasión hematógena, linfática, de LCR o directa por contigüidad. El carcinoma de mama es el que tiene mayor predilección por el tejido óseo, presentando una lesión osteolítica en aproximadamente el 80% de las pacientes. El objetivo del estudio fue describir el caso clínico de una paciente afectada por una infiltración neoplásica en la columna por adenocarcinoma de mama, con un sitio primario aún desconocido. Se trata de un estudio observacional de tipo descriptivo, realizado a través de los datos clínicos de una paciente afectada de carcinoma de mama, inicialmente diagnosticada de fibromialgia, siendo trasladada a hospitalización y aclaración diagnóstica. Evolucionó con paraplejía repentina, lesiones osteolíticas generalizadas, de carácter metastásico. Se observó que aun después de realizar la anamnesis, exploración física, valoraciones multidisciplinarias y pruebas de imagen, no se logró identificar el foco neoplásico del caso en cuestión y que solo después de la exploración inmunohistoquímica fue posible identificar el foco primario en el seno. Por tanto, es fundamental la búsqueda de métodos de investigación, más específicos, que ayuden a dilucidar el diagnóstico, permitiendo así el establecimiento de una terapia adecuada y, en consecuencia, un mejor pronóstico para el afectado. As metástases na coluna vertebral têm por caráter etiológico a disseminação hematogênica, linfática, liquórica ou invasão direta por contiguidade. O carcinoma de mama é o que apresenta maior predileção pelo tecido ósseo, apresentando lesão osteolítica em aproximadamente 80% dos pacientes. O objetivo do estudo foi descrever o relato de caso de uma paciente acometida por uma infiltração neoplásica em coluna vertebral decorrente de adenocarcinoma mamário, com sítio primário ainda desconhecido. Trata-se de um estudo observacional do tipo descritivo, realizado através dos dados clínicos de uma paciente acometida por carcinoma mamário, diagnosticada inicialmente com fibromialgia, sendo transferida para internação e elucidação diagnóstica. Evoluiu com paraplegia súbita, lesões osteolíticas generalizadas, de caráter metastático. Observou-se que mesmo após a realização da anamnese, exame físico, avaliações multidisciplinares e exames de imagem, estes foram incapazes de identificar o foco neoplásico do caso em questão e que somente após a realização do exame de imuno-histoquímica é que foi possível a identificação do foco primário em mama. Sendo assim, é essencial a busca por métodos investigativos, mais especificos, que auxiliem na elucidação do diagnóstico, permitindo assim o estabelecimento da terapéutica adequada e consequentemente um melhor prognóstico para os acometidos.

Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08-2.39, p = 0.018), but not PFS (HR = 1.04, 95% CI 0.74-1.46, p = 0.8) or PSA response (odds ratio = 1.14, 95% CI = 0.65-1.99, p = 0.7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naive, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR = 0.16, 95% CI = 0.06-0.46, p < 0.001) and PFS (HR = 0.31, 95% CI = 0.12-0.80, p = 0.02). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal patients (HR = 1.93, 95% CI = 1.19-3.12, p = 0.008) and a suggestion favoring docetaxel for AR-gained patients (HR = 0.53, 95% CI = 0.24-1.16, p = 0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained could benefit from docetaxel. This treatment selection merits prospective evaluation in a randomized trial. Patient summary: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker., V. Conteduca was funded by a European Society of Medical Oncology Translational Clinical Research Fellowship. A. Jayaram is supported by a grant from the Medical Research Council (MR/P002072/1). G. Attard is supported by a Cancer Research UK Advanced Clinician Scientist Grant (A22744). This work was funded in part by Prostate Cancer UK (PG12-49), the Instituto de Salud Carlos III (ISCII) PI16/01565 grant E. Gonzalez-Billalabeitia was funded by a grant from the Instituto de Salud Carlos III (ISCIII) PI15/01499. N. Romero-Laorden was funded by a grant from the Instituto de Salud Carlos III (CM14-00200). E. Castro is supported by a Prostate Cancer Foundation Young Investigator Award (2017). E. Castro and D. Olmos are supported by grants from the Ministerio de Economia, Industria y Competitividad (JCI-2014-19129 to E.C., RYC-2015-18625 to D.O.). B. Mellado and M. Marin-Aguilera work were supported by the Instituto de Salud Carlos III-Subdireccion General de Evaluacion y Fomento de la Investigacion (PI12/01226 and PI15/676) and co-funded by the European Regional Development Fund. Funding from CERCA Programme/Generalitat de Catalunya is gratefully acknowledged. During the conduct of the study, E. Castro was supported by a grant from the Ministerio de Educacion, Cultura y Deportes (CAS17/00182). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all data and had the final responsibility for the decision to submit for publication.

Background Lung adenocarcinoma (ADC) is the main cause of death related to lung cancer. The aim of this study was to identify poor prognostic factors for overall survival (OS) in patients with stage IV lung ADC in real‐world clinical practice. Methods Patients were selected from the Surveillance Epidemiology and End Results (SEER) database. Chi‐square bivariate analysis was used for the association of binary qualitative variables. A multivariate Cox regression analysis was performed to determine the impact of these prognostic factors on OS. Results A total of 46 030 patients were included (51.3% men, mean age 67.03 ± 11.6), of whom 41.3% presented with metastases in bone, 28.9% in brain, 17.1% in liver and 31.8% in lung. Patients with liver metastases presented with two or more metastatic sites more frequently than patients without liver metastases (P, In this study we identified male sex, age = 65 years, lack of family support and liver and brain metastases as poor prognostic factors for overall survival (OS) in patients with stage IV lung ADC. The presence of liver metastases emerged as the worst prognostic factor. Consequently, it should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy.

We would like to extend our gratitude to the all the patients and the healthy volunteers who participated in the study, as well as the University of Granada, Biomedicine PhD program. This work was supported by Roche Spain, the PhD grant from the University of Granada (DdMP) (2014) and the PhD grant from the Spanish Government (ARM) (FPU) 2014, REF FPU14/05461., Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC., Roche Spain, University of Granada (DdMP), Spanish Government REF FPU14/05461

Trabajo de fin de grado. Grado en Medicina. Curso académico 20xx-20xx, OBJETIVOS: Analizar la eficacia de Nivolumab en términos de respuesta y supervivencia en los pacientes con Carcinoma de Células Renales metastásico (CCRm) que han progresado a una o varias líneas de tratamiento previo. MATERIAL Y MÉTODOS: Hemos realizado un estudio retrospectivo, descriptivo de los pacientes con CCRm que han recibido tratamiento con Nivolumab tras la progresión a líneas previas en el Hospital Universitario de Salamanca. Los datos se analizaron mediante el programa estadístico IBM SPSS Statistics, versión 25.0. En el estudio comparativo de las variables cuantitativas, se utilizó la U de Mann-Whitney y el test de Kruskal Wallis. Para las variables cualitativas se utilizó el test de Fisher. Se ha realizado un análisis de supervivencia con Kaplan-Meier utilizando el test de Log-rank. RESULTADOS: Han recibido Nivolumab un total de 36 pacientes. El tipo histológico más frecuente fue el Carcinoma Renal de Células Claras (CRCC) en el 75% y tan solo un 17,14% presentaban enfermedad de Buen Pronóstico del International Metastatic Database Consortium (IMDC). Obtuvieron respuesta objetiva (RO) el 27,8% y la Supervivencia Global (SG) a los 12 y 24 meses ha sido del 63,1% y del 54,69%, respectivamente. Presentaron toxicidades el 33,3% de los pacientes. Tanto la Supervivencia Libre de Progresión (SLP) como la SG fueron superiores en los pacientes con toxicidades, hallándose significación estadística. También se obtuvo mayor supervivencia en los pacientes con ≤ 2 localizaciones metastásicas y en aquellos con RO. CONCLUSIONES: A pesar de ser una serie con elevado número de factores de mal pronóstico, tanto las RO como la supervivencia no difieren de las obtenidas en el contexto de ensayos clínicos ni en la práctica clínica habitual con Nivolumab. Al igual que lo comunicado recientemente en diversos estudios retrospectivos, la presencia de toxicidades se relaciona de manera significativa con una mayor supervivencia.

Background: Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy. Patients and methods: A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue. Results: ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 - 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 - 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%. Conclusions: Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection., This work was supported by Merck, S.L., Madrid, Spain, an affiliate of Merck KGaA, Darmstadt, Germany and partially by the Instituto de Salud Carlos III (Ministerio de Economia y Competitividad) and 'Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa' grants [FIS PI12-01589 to RS] and RETICC Cancer: Grupo Cancer Digestivo - Instituto de Salud Carlos III. TTD ULTRA study (EC11-050) was supported by the Ministerio de Sanidad y Politica Social [SPI/2885/2011]. To CM grants [PI15/00457 and DTS15/00048].

BackgroundTreatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.MethodsFrail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. Main objective: to assess progression-free survival (PFS) rate at 6months. Treatment consisted of 28-daycycles of orally administered regorafenib 160mg/day (3 weeks followed by 1 week rest).ResultsForty-seven patients were included in the study. Median age was 81years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6months (95%CI 2.7-8.4). Median overall survival (OS) was 16months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%).ConclusionsThe study did not meet the pre-specified boundary of 55% PFS rate at 6months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach.Trial registrationThis trial was prospectively registered at EudraCT (2013-000236-94). Date of trial registration: April 9th, 2013., Financial support for this research was provided by Bayer Hispania, which has no role in the design of the study; collection, analysis, and interpretation of data; and in writing the manuscript.

The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular-targeted agents). The prospective, multi-site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to describe real-world treatment prior to approval of the immune checkpoint inhibitor ipilimumab. This retrospective cohort of patients, who started second-line/subsequent treatment (index therapy) for advanced melanoma within 3 years before ipilimumab approval, was selected randomly by chart review. Collected data included treatment history, patient outcomes, and healthcare resource utilization. All patients had >= 1 year of follow-up data. This analysis included 177 patients from Europe (69%) and North America (31%). The most common index therapies (used alone or in combination) were fotemustine (23%), dacarbazine (21%), temozolomide (14%), and platinum-based chemotherapy (14%). Most patients (89%) discontinued index treatment during the study period; the most common reason was disease progression (59%). Among patients with tumor assessment (153/177; 86%), 2% had complete response, 5% had partial response, and 12% had stable disease on last tumor assessment. At 1-year study follow-up, median progression-free survival was 2.6 months (95% confidence interval [CI], 2.1-2.9) and median overall survival was 8.8 months (95% CI, 6.5-9.7). During follow-up, 95% of the patients had healthcare visits for advanced melanoma, 74% of whom were hospitalized or admitted to a hospice facility. These results provide insights into patient care with advanced melanoma in the era before ipilimumab and may serve as a benchmark for new agents in future real-world studies., This study was funded by Bristol-Myers Squibb.

El objetivo del presente informe es evaluar la eficacia/efectividad y la seguridad de la ablación mediante microondas frente a la radiofrecuencia en el tratamiento de tumores hepáticos primarios y secundarios. O obxectivo do presente informe é avaliar a eficacia/efectividade e a seguridade da ablación mediante microondas frente á radiofrecuencia no tratamento de tumores hepáticos primarios e secundarios

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT) is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed. The aim of this study was to prospectively validate a gene expression panel (composed of GAPDH, VIL1, CLU, TIMP1, TLN1, LOXL3 and ZEB2) for detecting circulating tumor cells (CTCs) as prognostic and predictive tool in blood samples from 94 metastatic CRC (mCRC) patients. Patients with higher gene panel expression before treatment had a reduced progression-free survival (PFS) and overall-survival (OS) rates compared with patients with low expression (p = 0.003 and p ≤ 0.001, respectively). Patients with increased expression of CTCs markers during treatment presented PFS and OS times of 8.95 and 11.74 months, respectively, compared with 14.41 and 24.7 for patients presenting decreased expression (PFS; p = 0.020; OS; p ≤ 0.001). Patients classified as non-responders by CTCs with treatment, but classified as responders by CT scan, showed significantly shorter survival times (PFS: 8.53 vs. 11.70; OS: 10.37 vs. 24.13; months). In conclusion, our CTCs detection panel demonstrated efficacy for early treatment response assessment in mCRC patients, and with increased reliability compared to CT scan. ACIS (Axencia de Coñecemento en Saude); SERGAS. Cofinanced ERDF Funds 2007–2013

Background: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. Methods: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. Results: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7 % out of 966 post-implementation cycles compared with 23.1 % out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33 % pre-implementation vs. 44.5 % post-implementation cycles; p < 0.0001), diarrhea (74.0 % vs. 80.5 %; p = 0.011) and dyslipemia (25.0 % vs. 44.6 %; p < 0.001). Conclusions: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction., This study was funded by Pfizer, S.L.U. Medical writing assistance was provided by Esther Tapia, PhD and was founded by Pfizer. The authors gratefully say thanks to Ma Luz Samaniego for his help with the statistical analyses.

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain., Novartis have provided funding for this observational study.

Metastatic lesions to the mandible may be originated from primary tumors elsewhere in the body. However, metastatic colonic carcinomas to this bone have been described infrequently. We report the case of a 71-year-old man with an adenocarcinoma in the sigmoid colon with liver metastasis. The patient underwent chemotherapy with indication of sigmoidectomy and retroperitoneal lymphadenectomy. One year and four months after the first metastatic diagnosis, the patient presented a tumor mass in the body and branch of the right mandible. Histopathological and immunohistochemical analysis with monoclonal antibodies specific for CEA, CK20, CDX-2, and vilin were compatible with the diagnosis of moderately differentiated metastatic adenocarcinoma with colonic origin. However, due to the wide spread of the disease, the patient died four months later. Tumor markers have been applied in clinical practice to assist in the diagnosis and to help guide prognosis, staging and treatment of cancer. The management of metastatic lesions remains a controversial issue and the development of new and more specific markers of gastrointestinal differentiation that may promote early diagnosis, are of continuous interest.

Metastatic lesions to the mandible may be originated from primary tumors elsewhere in the body. However, metastatic colonic carcinomas to this bone have been described infrequently. We report the case of a 71-year-old man with an adenocarcinoma in the sigmoid colon with liver metastasis. The patient underwent chemotherapy with indication of sigmoidectomy and retroperitoneal lymphadenectomy. One year and four months after the first metastatic diagnosis, the patient presented a tumor mass in the body and branch of the right mandible. Histopathological and immunohistochemical analysis with monoclonal antibodies specific for CEA, CK20, CDX-2, and vilin were compatible with the diagnosis of moderately differentiated metastatic adenocarcinoma with colonic origin. However, due to the wide spread of the disease, the patient died four months later. Tumor markers have been applied in clinical practice to assist in the diagnosis and to help guide prognosis, staging and treatment of cancer. The management of metastatic lesions remains a controversial issue and the development of new and more specific markers of gastrointestinal differentiation that may promote early diagnosis, are of continuous interest.

Background: Patients with transitional cell carcinoma of the urothelial tract (TCCU) who fail initial platinum-based chemotherapy for advanced disease represent a challenge in daily clinical practice. Vinflunine is approved by the European Medicine Agency (EMA) but, up to now, limited experience has been reported outside clinical trials. Methods: We assessed the efficacy and safety of vinflunine in an unselected group of 102 consecutive patients with metastatic TCCU. Results: The median age was 67 years (range 45-83). Among the most common comorbidities that patients presented at baseline were hypertension (50.5%) and diabetes (20.7%). Distant metastases were present in retroperitoneal nodes (58%), lung (29.3%), and bone (20.2%). The ECOG 0, 1 and 2 performance status at the start of vinflunine were 31.3%, 60.6% and 8.1%, respectively. The most commonly reported adverse events of any grade were constipation 70.6% (5.9% grade 3-4), vomiting 49.1% (2% grade 3-4), neutropenia 48.1% (12.8% grade 3-4) and abdominal pain 34.3% (4.9% grade 3-4). A median of 4 cycles of vinflunine was administered per patient (range 1-18). Median progression free and overall survival for all patients (N = 102) were 3.9 months (2.3-5.5) and 10 months (7.3-12.8), respectively. Time to tumor progression was 4.3 months (2.6-5.9). Two patients (2%) achieved CR, 23 (22.5%) patients had PR, and 42 (41.2%) presented SD as best response. The clinical benefit rate with vinflunine was 65.7%. Conclusions: Our results show that the behavior of vinflunine in routine clinical practice resembles that of the pivotal phase III randomized study.

OBJECTIVE: To evaluate the impact of surgical treatment of metastatic epidural spinal lesions on the quality of life of patients, pain relief and survival. METHODS: Patients with single or double spinal lesions, in good clinical conditions to undergo surgery, were included. Staging and prognostic evaluation were performed, based on imaging studies, according to the criteria of Enneking and Tokuhashi, and neurological status (Frankel), pain (visual analogue scale, VAS) and quality of life index (Oswestry) were also assessed. Survival was calculated. RESULTS: The study included 67 patients, 34 men and 33 women, aged 13-88 years (mean: 53). Most had the breast (23 cases) as the primary site of the tumor and metastasis in the lumbar region, especially in L2 and L3. Pathologic fractures were diagnosed in 45 patients. The mean VAS score was initially 9 (5-10) reducing in the second day after surgery to 2 (1-7) and to 1 (0-6) in the first and sixth months. Following 6 months, 18 deaths were observed (one intraoperatively, five in the first month and 12 at 6 months). The neurological status was correlated with survival: patients who were Frankel E before surgery showed increased survival. CONCLUSION: The surgery does not influence patient survival, except for patients with neurological deficits, who have a worse prognosis. Treatment of metastatic lesions is often palliative, but patients present improved neurological and pain relief and few complications after surgery, justifying surgical intervention. OBJETIVO: Avaliar o impacto do tratamento cirúrgico de lesões metastáticas epidurais na coluna vertebral sobre a qualidade de vida dos pacientes, a melhora da dor e a sobrevida. MÉTODOS: Pacientes com lesão única ou dupla na coluna vertebral, em condições de serem submetidos à cirurgia, foram incluídos. Foram realizados estadiamento e avaliação prognóstica a partir de exames de imagem, pelos critérios de Enneking e Tokuhashi, avaliação neurológica (Frankel), da dor (escala visual analógica, EVA) e da qualidade de vida (índice de Oswestry). Foi calculada a sobrevida. RESULTADOS: Foram incluídos no estudo 67 pacientes, 34 homens e 33 mulheres, com idade de 13 a 88 anos (média: 53). A maioria tinha a mama (23 casos) como sítio primário do tumor e metástase na região lombar, principalmente em L2 e L3. Fratura patológica foi diagnosticada em 45 pacientes. O escore médio na escala EVA foi inicialmente 9 (5-10), reduzindo-se, no segundo dia após a cirurgia, para 2 (1-7) e para 1 (0-6) no primeiro e sexto meses. No seguimento aos 6 meses, foram observados 18 óbitos (um intraoperatório, cinco no primeiro mês e 12 aos 6 meses). A situação neurológica correlacionou-se com a sobrevida: os pacientes que no momento da cirurgia estavam em Frankel E apresentaram sobrevida maior. CONCLUSÃO: A cirurgia não influencia na sobrevida do paciente, exceto nos pacientes com déficit neurológico, que apresentam pior prognóstico. O tratamento da lesão metastática é muitas vezes paliativo, mas os pacientes apresentam melhora neurológica e alívio da dor e poucas complicações, justificando a intervenção cirúrgica. OBJETIVO: Evaluar el impacto del tratamiento quirúrgico de lesiones metastásicas epidurales en la columna vertebral sobre la calidad de vida de los pacientes, la mejoría del dolor y la sobrevida. MÉTODOS: Se incluyeron pacientes con lesión única o doble en la columna vertebral, en condiciones de ser sometidos a cirugía. Se realizaron estadiamiento y evaluación pronóstica, a partir de exámenes de imagen, según los criterios de Enneking y Tokuhashi, evaluación neurológica (Frankel) y del dolor (escala visual analógica, EVA), y de la calidad de vida (índice de Oswestry). Se calculó la sobrevida. RESULTADOS: Se incluyeron en el estudio 67 pacientes, 34 hombres y 33 mujeres, de edades de 13 a 88 años (promedio: 53). La mayoría tenía la mama (23 casos) como sitio primario del tumor y metástasis en la región lumbar, principalmente en L2 y L3. Fractura patológica fue diagnosticada en 45 pacientes. La puntuación promedio en la escala EVA fue, inicialmente, 9 (5-10), reduciéndose, en el segundo día después de la cirugía, para 2 (1-7) y para 1 (0-6) en el primero y sexto meses. En el seguimiento, a los 6 meses, se observaron 18 óbitos (uno intraoperatorio, cinco en el primer mes y 12 a los 6 meses). La situación neurológica se correlacionó con la sobrevida: los pacientes, quienes a la fecha de la cirugía estaban en Frankel E, presentaron sobrevida más prolongada. CONCLUSIÓN: La cirugía no tiene influencia en la sobrevida del paciente, excepto para los pacientes con déficit neurológico, que presentan pronóstico peor. Muchas veces, el tratamiento de la lesión metastásica es un paliativo, pero los pacientes presentan mejoría neurológica y alivio del dolor, y pocas complicaciones, justificando la intervención quirúrgica.

PURPOSE: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance. METHODS: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance. RESULTS: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance. CONCLUSIONS: We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies.

Background: In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings: KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI: 1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18-2.64). Conclusions/Significance: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses., This work was supported by Roche (www.roche.es) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: Controversy exists with regard to the impact that the different components of diagnosis delay may have on the degree of invasion and prognosis in patients with colorectal cancer. The follow-up strategies after treatment also vary considerably. The aims of this study are: a) to determine if the symptoms-to-diagnosis interval and the treatment delay modify the survival of patients with colorectal cancer, and b) to determine if different follow-up strategies are associated with a higher survival rate. Methods/Design: Multi-centre study with prospective follow-up in five regions in Spain (Galicia, Balearic Islands, Catalonia, Aragon and Valencia) during the period 2010-2012. Incident cases are included with anatomopathological confirmation of colorectal cancer (International Classification of Diseases 9th revision codes 153-154) that formed a part of a previous study (n = 953). At the time of diagnosis, each patient was given a structured interview. Their clinical records will be reviewed during the follow-up period in order to obtain information on the explorations and tests carried out after treatment, and the progress of these patients. Symptoms-to-diagnosis interval is defined as the time calculated from the diagnosis of cancer and the first symptoms attributed to cancer. Treatment delay is defined as the time elapsed between diagnosis and treatment. In non-metastatic patients treated with curative intention, information will be obtained during the follow-up period on consultations performed in the digestive, surgery and oncology departments, as well as the endoscopies, tumour markers and imaging procedures carried out. Local recurrence, development of metastases in the follow-up, appearance of a new tumour and mortality will be included as outcome variables. Actuarial survival analysis with Kaplan-Meier curves, Cox regression and competitive risk survival analysis will be performed., This study has received a grant for each participating group from the Ministry of Science and Innovation, Carlos III Institute, Healthcare Research Fund; PS09/00663, PI09/01800, PS09/00954, PS09/01614 and PS09/01375. In addition, the study has received the support of the Health Promotion and Preventive Activities - Primary Healthcare Network, which is supported by other grants from the Ministry of Health ISCIII-RETCI G03/170 and RD06/0018.; The study is also partially supported by a XUGA grant (08CSA073916PR) and the Galician Network for Colorectal Cancer Research.