The management of paediatric acute pain in Spain in 2021: Results of a national survey among paediatric anaesthesiologists.

OBJECTIVE: To improve knowledge about routine clinical practice in the management of paediatric acute pain in Spain. METHODS: A telematic survey was conducted via the Internet on a representative sample of healthcare professionals involved in the management of paediatric acute pain (specifically anaesthesiologists) in Spain. The survey included 28 questions about their usual clinical practice in the assessment and treatment of acute pain, and also training and organisational aspects in paediatric acute pain. RESULTS: The survey was completed during March 2021 by 150 specialists in anaesthesiology. The respondents widely experienced in the management of acute paediatric pain (mean years of experience: 14.3: SD: 7.8), essentially in acute postoperative pain (97% of cases). Although 80% routinely used validated paediatric acute pain assessment scales, only 2.6% used specific scales adapted for patients with cognitive impairment. Most of the respondents routinely used analgesic drugs such as paracetamol (99%) or metamizole (92%), but only 84% complemented these drugs with a loco-regional blocking technique or other non-steroidal anti-inflammatory drugs (62%). Furthermore, only 62.7% acknowledged having received specific training in paediatric acute pain, only 45% followed hospital institutional protocols, and a scant 28% did so through paediatric pain units. CONCLUSIONS: The survey identified important points for improvement in the training and organisation of acute pain management in Spanish paediatric patients.

Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

Clinical, molecular, and immune correlates of the Immunotherapy Response Score in patients with advanced urothelial carcinoma under atezolizumab monotherapy: analysis of the phase II IMvigor210 trial.

BACKGROUND: In the advanced urothelial carcinoma (aUC) scenario there are no consistent immune checkpoint blockade predictive biomarkers. Recently a novel pan-tumor molecular tissue-based biomarker, the Immunotherapy Response Score (IRS), has been proposed. We conducted a retrospective study to validate the prognostic/predictive utility of the IRS in patients with aUC under atezolizumab monotherapy and to characterize its underlying molecular/immune features in the context of the IMvigor210 phase II trial. PATIENTS AND METHODS: This is a post hoc pooled analysis of 261 patients with available clinical, molecular, and immune tumor data treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial. Efficacy endpoints were overall survival (OS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using chi-square or Fisher's exact tests. All P values were two-sided, and those <0.05 were considered statistically significant. RESULTS: High IRS was significantly associated with a better OS in univariable [hazard ratio (HR) = 0.49, P < 0.001] and multivariable (HR = 0.60, P = 0.018) analyses. DCR and ORR were significantly higher among high IRS patients (DCR for high IRS versus low IRS patients: 57% versus 32%, P < 0.001; ORR: 42% versus 10%, P < 0.001). High IRS patients presented a higher probability of DC and response in univariable [DC: odds ratio (OR) = 2.72, P < 0.001; response: OR = 3.92, P < 0.001] and multivariable (DC: OR = 2.72, P < 0.001; response: OR = 3.92, P < 0.001) analyses. CONCLUSIONS: This study validates IRS as a strong independent prognostic and predictive biomarker for OS and DC/response in patients with aUC treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial.

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

Oral microbiome and systemic antineoplastics in cancer treatment: A systematic review.

BACKGROUND: Oral mucositis is one of the most common side effects in cancer patients receiving systemic antineoplastics. However, the underlying biological mechanisms leading to this condition are still unclear. For this reason, it has been hypothesised that systemic antineoplastics may cause an imbalance on the oral microbiota that subsequently triggers oral mucosa damage. MATERIAL AND METHODS: A systematic review was performed following the PRISMA protocol and the PICO question established was: patients diagnosed with cancer, who are candidates for receiving systemic antineoplastics (P=Patients), that undergo oral microbiome determinations (I=Intervention), before and after systemic antineoplastics administration (C=Comparison), to analyse changes in the oral microbiome composition (O=Outcome). The bibliographic search was carried out in PubMed and other scientific repositories. RESULTS: Out of 166 obtained articles, only 5 met eligibility criteria. Acute myeloid leukaemia (AML) was the most frequent type of cancer (40 %) among the participants. Only one of the studies included a control group of healthy subjects. Heterogeneity in the protocols and approaches of the included studies hindered a detailed comparison of the outcomes. However, it was stated that a decrease in bacteria α diversity is often associated with oral mucositis. On the other hand, fungal diversity was not associated with oral mucositis although α diversity was lower at baseline on patients developing oral candidiasis. CONCLUSIONS: There is insufficient scientific evidence of oral microbiological changes in patients undergoing systemic antineoplastics. Further investigations ought to be carried out to identify microorganisms that might play a key role in the pathogenesis of oral mucosa damage in patients undergoing systemic antineoplastics.

Rethinking prognostic factors in locally advanced or metastatic urothelial carcinoma in the immune checkpoint blockade era: a multicenter retrospective study.

BACKGROUND: Few studies have investigated the safety and efficacy of anti-PD-(L)1 antibodies in metastatic urothelial carcinoma (mUC) in daily clinical practice. Knowledge about the influence of baseline clinical and analytical factors on therapy outcomes is scarce. PATIENTS AND METHODS: We conducted a multicenter retrospective study involving 119 previously treated or untreated mUC patients under anti-PD-(L)1 therapy in a real-world scenario. The objectives of this study were to confirm the safety and efficacy of anti-PD-(L)1 monotherapy and to identify pretreatment factors influencing therapy outcomes. In addition, an independent prognostic model for overall survival (OS) was developed and internally validated. RESULTS: Median OS was 7.8 months [95% confidence interval (CI), 5.4-10.4], median progression-free survival (PFS) was 2.80 months (95% CI, 2.4-3.4), disease control rate (DCR) was 40% (95% CI, 31-49), and overall response rate (ORR) was 24% (95% CI, 15-31). Presence of peritoneal metastases was associated with poor OS [hazard ratio (HR) = 2.40, 95% CI, 1.08-5.33; P = 0.03]. Use of proton-pump inhibitors (PPI) was associated with poor OS (HR = 1.83, 95% CI, 1.11-3.02; P = 0.02) and PFS (HR = 1.94, 95% CI, 1.22-3.09; P = 0.005), and lower DCR (OR = 0.38, 95% CI, 0.17-0.89; P = 0.03) and ORR (OR = 0.18, 95% CI, 0.02-1.60; P = 0.002). The three risk category prognostic model developed included Eastern Cooperative Oncology Group performance status, PPI use, albumin level, presence of liver metastases, and presence of peritoneal metastases variables and was associated with higher risk of death (HR = 3.00, 95% CI, 1.97-4.56; P = 0.0001). CONCLUSIONS: This study confirms anti-PD-(L)1 monotherapy as a safe and effective treatment option in daily clinical practice for mUC patients. It also describes the presence of peritoneal metastases as an independent prognostic factor for OS and underlines the association between PPI use and worse therapeutic outcomes. Finally, it proposes a new easy-to-use risk-assessment model for OS prediction.

[Virtual reality as a tool for the prevention, diagnosis and treatment of cognitive impairment in the elderly: a systematic review]. / Realidad virtual como herramienta de prevención, diagnóstico y tratamiento del deterioro cognitivo en personas mayores: revisión sistemática.

INTRODUCTION: In recent decades, research into the effects of virtual reality on different neurological disorders has increased exponentially. Yet, the literature focused on the beneficial effects of virtual reality on cognitive impairment in elderly people is limited. AIM: To explore the application of virtual reality as a preventive, diagnostic or therapeutic tool for cognitive impairment in elderly people. PATIENTS AND METHODS: A literature search was conducted in the Medline and Web of Science databases, including all the literature published from their inception up until December 2019. RESULTS: Of the 270 publications found, 15 met the inclusion criteria: two examined the effect of virtual reality as a tool for the prevention of cognitive impairment, six looked at its possible applications in diagnosis, and seven explored its effectiveness as a form of treatment. CONCLUSIONS: There is evidence of the potential effect of virtual reality as a preventive strategy against the development of cognitive impairment in elderly people. There is also evidence of its applicability as a diagnostic tool for detecting the development of mild cognitive impairment or dementia, and of its effectiveness as a treatment, since it improves the cognitive functioning of elderly people with cognitive impairment. Further studies are needed that are more methodologically robust and have long follow-up times in order to examine the real impact of virtual reality and to be able to generalise its application in different areas of the management of cognitive impairment.

TITLE: Realidad virtual como herramienta de prevención, diagnóstico y tratamiento del deterioro cognitivo en personas mayores: revisión sistemática.Introducción. En las últimas décadas, se ha incrementado exponencialmente la investigación sobre los efectos de la realidad virtual en diferentes trastornos neurológicos. Sin embargo, la bibliografía centrada en los beneficios de la realidad virtual sobre el deterioro cognitivo en personas mayores es limitada. Objetivo. Explorar la aplicación de la realidad virtual como herramienta preventiva, diagnóstica o de tratamiento del deterioro cognitivo en personas mayores. Pacientes y métodos. Se llevó a cabo una búsqueda bibliográfica en las bases de datos Medline y Web of Science, incluyendo toda la bibliografía publicada desde sus inicios hasta diciembre de 2019. Resultados. De las 270 publicaciones encontradas, 15 cumplieron los criterios de inclusión: dos examinaron el efecto de la realidad virtual como herramienta de prevención del deterioro cognitivo; seis, su aplicabilidad diagnóstica; y siete, su efectividad como tratamiento. Conclusiones. Existe evidencia del potencial efecto de la realidad virtual como estrategia preventiva frente al desarrollo de deterioro cognitivo en personas mayores. Existe también evidencia de su aplicabilidad como herramienta diagnóstica de detección de desarrollo de deterioro cognitivo leve o demencia, y de su efectividad como tratamiento, ya que mejora el funcionamiento cognitivo de personas mayores con deterioro cognitivo. Son necesarios futuros estudios metodológicamente más robustos y con amplios tiempos de seguimiento para examinar el impacto real de la realidad virtual y poder generalizar su aplicación en los diferentes ámbitos de manejo del deterioro cognitivo.

miRNAs in liquid biopsy for oral squamous cell carcinoma diagnosis: Systematic review and meta-analysis.

Oral squamous cell carcinoma (OSCC) is often diagnosed at advanced stages and is associated with poor survival rates. Increasing evidence suggests that microRNAs (miRNAs) present in liquid biopsies could be potential biomarkers for non-invasive OSCC diagnosis. Here, we performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of blood and salivary miRNAs in detecting OSCC. A literature search using PubMed EMBASE, Web of Science, LILACS, Scopus, and the Cochrane Library was undertaken up to February 2019. Study quality was assessed with the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess the heterogeneity. Twenty-five study units from 16 articles with 2562 subjects were included in this meta-analysis. The pooled sensitivity and specificity of blood and salivary miRNAs in the diagnosis of OSCC were 0.78 (95% CI: 0.76-0.80) and 0.82 (95% CI: 0.79-0.84), respectively, and the pooled positive and negative likelihood ratios were 4.31 (95% CI: 3.38-5.51) and 0.25 (95% CI: 0.20-0.32), respectively. The overall area under the curve was 0.91 (95% CI: 0.88-0.93), with a diagnostic odds ratio of 21.46 (95% CI: 13.37-34.45). These findings provide evidence regarding the potential clinical application of blood and salivary miRNAs as a novel, non-invasive, and accurate diagnostic tool for OSCC.

EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer.

INTRODUCTION: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. METHODS: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. RESULTS: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. CONCLUSIONS: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

Author Correction: Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer.

Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08-4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.

Active study: undetected prevalence and clinical inertia in the treatment of breakthrough cancer pain (BTcP).

AIMS: To prove if there is clinical inertia in the identification and treatment of episodes of breakthrough cancer pain (BTcP), comparing actual results from clinical practice with clinical oncologists' prior perception. DESIGN: Observational and descriptive study, using information collected by practising medical oncologists, at three moments: (a) questionnaire regarding their professional judgement of the handling of patients with BTcP in their practice, (b) cross-sectional clinical screening, to detect possible existing cases of BTcP in a representative sample of their patients, (c) retrospective self-audit of clinical case histories of patients diagnosed with BTcP to find out about how it has been handled. PARTICIPANTS AND STUDY PERIOD: A random sample on a state level of 108 specialists in medical oncology. 540 patients who suffer some type of cancer pain on the designated study date for each specialist (July-December 2016). RESULTS: The global prevalence of BTcP in the study sample covered 91.3% of the patients who were suffering some type of cancer pain. Barely 2% of the doctors surveyed suspected figures around this mark. 40.9% of the cases had not been previously detected as BTcP by their doctors. Although 90% of the patients who had previously been diagnosed with BTcP received a specific analgesic treatment for the symptoms, 42% of those patients with known BTcP were not able to control their episodes of pain. CONCLUSIONS: Clinical inertia is a serious problem in the handling of BTcP in medical oncology services, where it is the subject of a significantly low level of detection and treatment, despite the contrasting perception of specialists.

[Childhood ischemic cerebrovascular disease in a paediatric emergency service: a descriptive study]. / Enfermedad cerebrovascular de tipo isquemico posnatal en urgencias pediatricas: estudio descriptivo.

AIM: To describe the clinical presentation, risk factors and complementary tests in patients of our paediatric emergency service with a final diagnosis of ischemic stroke. PATIENTS AND METHODS: Retrospective, analytical and observational study, performed in a Paediatric Emergency Service of a tertiary-level hospital. We included patients aged 1 month to 14 years during a 12-years period with a final diagnosis of ischemic cerebrovascular disease (CVD). We analyzed personal history, symptomatology and initial complementary tests. RESULTS: Twelve patients were included, 66% males, with a median age of 77 months. 42% had remarkable history. The most frequent clinical manifestation was motor disorder (75%). 42% were diagnosed in the first 24 hours, noticing an earlier diagnosis after the introduction of a multidisciplinary protocol about CVD. CT was performed in all patients, except in two cases in whom MRI was performed. 50% of the CTs were initially normal. In the etiological study developed lately, only 42% of the patients had risk factors. 91% had some kind of sequel. CONCLUSIONS: CVD is uncommon in pediatrics, but with a high morbimortality, so it is important to make an early diagnosis. Clinical and personal history are fundamental, nevertheless, we mainly deal with a previously healthy child without known risk factors at the time of the first evaluation. In case of clinical suspicion of stroke, a normal initial CT does not rule out a CVD, so other additional tests, such as MRI, are necessary.

TITLE: Enfermedad cerebrovascular de tipo isquemico posnatal en urgencias pediatricas: estudio descriptivo.Objetivo. Describir la presentacion clinica, los factores de riesgo y las pruebas complementarias realizadas en pacientes atendidos en urgencias con diagnostico de ictus isquemico. Pacientes y metodos. Estudio retrospectivo, analitico observacional, realizado en urgencias pediatricas de un hospital de tercer nivel. Se incluyeron pacientes entre 1 mes y 14 años durante 12 años, con diagnostico de enfermedad cerebrovascular (ECV) de tipo isquemico. Se analizaron los antecedentes personales, la sintomatologia y las pruebas complementarias iniciales. Resultados. Se recogieron 12 pacientes (66% varones), con una mediana de edad de 77 meses. El 42% presento algun antecedente reseñable. La manifestacion clinica mas frecuente fue la alteracion motora (75%). El 42% fueron diagnosticados en las primeras 24 horas, y se objetivo un diagnostico mas temprano tras la introduccion de un programa multidisciplinar sobre manejo de la ECV. En todos se realizo inicialmente una tomografia axial computarizada (TAC) craneal, salvo en dos casos en los que se hizo una resonancia magnetica. La mitad de las TAC fueron normales al inicio. En el estudio etiologico posterior se encontraron factores de riesgo solo en cinco pacientes (42%). El 91% presento algun tipo de secuela. Conclusiones. La ECV es poco frecuente en pediatria, con elevada morbimortalidad, y es importante realizar un adecuado diagnostico precoz. Son fundamentales la historia clinica y los antecedentes personales, aunque en la valoracion inicial es frecuente encontrarse ante niños sanos sin factores de riesgo conocidos en ese momento. Ante la sospecha clinica de ictus, una TAC craneal inicial normal no descarta una ECV y son necesarias otras pruebas, como la resonancia magnetica.

PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PURPOSE: Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. METHODS: PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. RESULTS: This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. CONCLUSION: The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Oncologist's knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study.

PURPOSE: Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for oncologic patients, which remain under diagnosed and undertreated. In 2012, the Spanish Society of Medical Oncology (SEOM) published a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP. METHODS: Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline. RESULTS: A total of 83 oncologists with a mean experience of 13 years responded. Overall, 82% were aware of different guidelines to manage BTcP. Notably, attitudes toward guidelines were highly positive and there was nearly unanimous agreement that CPG provided the best scientific evidence available (99%), on the minimum information to be gathered for the medical history (100%), on the need for a specific treatment for BTcP (100%), and fentanyl as the first-choice drug (99%). Interestingly, there were discrepancies between what oncologists agreed with and what they do in clinical practice. In fact, 87.6% declare full compliance with SEOM guideline, although adherence to registration of BTcP data in medical records ranged from 30.1 to 91.6% (mean 64.5%); therapeutic management compliance was higher ranging from 75.9 to 91.6%. Main barriers identified were time pressure together with vague statements and limited dissemination of the guidelines. CONCLUSION: Despite oncologist's clinical practice is increasingly guided by GPC, it suffers from limited compliance, at least in part due to suboptimal statements. Improved dissemination and education are needed to enhance guideline implementation.

Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review.

The importance of mutation identification for advanced colorectal cancer treatment with anti-epidermal growth factor receptor agents is well established. However, due to delays in turnaround time, low-quality tissue samples, and/or lack of standardization of testing methods a significant proportion of patients are being treated without the information that Kirsten rat sarcoma and neuroblastoma rat sarcoma (RAS) testing can provide. The detection of mutated circulating tumor DNA by BEAMing technology addresses this gap in care and allows these patients to receive international guideline-recommended expanded RAS testing with rapid turnaround times. Furthermore, the overall concordance between OncoBEAM RAS colorectal cancer testing and standard of care tissue testing is very high (93.3%). This article presents an overview of the clinical utility and potential applications of this minimally invasive method, such as early detection of emergent resistance to anti-epidermal growth factor receptor therapy. If appropriately implemented, BEAMing technology holds considerable promise to enhance the quality of patient care and improve clinical outcomes.

SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2016).

Chemotherapy-induced nausea and vomiting is one of the most worrisome adverse effects of chemotherapy for cancer patients. It can cause severe discomfort and affect the quality of life. In recent years, the incorporation of new drugs has increased the efficacy of antiemetic treatments in the control of emesis associated with chemotherapy. This guideline, in which we give some treatment recommendations with level of evidence and grade of recommendation, provides an update of the previously published guideline of the Spanish Society of Medical Oncology and represents our continued commitment to improving supportive care in cancer patients.

Development and characterization of a three-dimensional co-culture model of tumor T cell infiltration.

Tumor growth and metastasis entangle the alteration and recruitment of non-malignant cells to the primary tumor, among them immune cells, constituting the tumor microenvironment (TME). Communication between tumor cells and their stroma has been shown as a fundamental driving force of the tumoral process. A great deal of effort has been focused on depicting their specific interactions and crosstalk. However, most research has been carried out in 2D conventional cultures that alter cell morphology and intracellular signaling processes. Considering these premises, we have developed a 3D cell co-culture model to mimic T cell infiltration into the tumor mass and explore tumor-immune cells interactions in the TME. Expression of specific cell markers and assessment of cell proliferation were carried out to characterize the proposed 3D co-culture model. Additionally, the study and profiling of the secretome revealed a subset of particular cancer-related inflammation proteins prompted upon 3D cultivation of tumor cells in presence of lymphocytes, pointing out an intercellular communication. Altogether, these results suggest that our 3D cell co-culture model can be a useful tool to identify and study critical factors mediating the crosstalk between tumor and immune cells in the TME. Finally, the potential of this model as a drug-screening platform has been explored using docetaxel as a model antitumoral compound.

Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study.

BACKGROUND: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. PATIENTS AND METHODS: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. RESULTS: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2-34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). CONCLUSION: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. CLINICAL TRIAL NUMBER: NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.

Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes.

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.