Efficacy of nintedanib and docetaxel in patients with advanced lung adenocarcinoma treated with first-line chemotherapy and second-line immunotherapy in the nintedanib NPU program.

PURPOSE: Both nintedanib/docetaxel and anti-PD-1/PD-L1 immunotherapies have demonstrated efficacy as second-line treatment of patients with advanced lung adenocarcinoma. This is the first report on the efficacy of the nintedanib/docetaxel combination following first-line platinum-based chemotherapy and subsequent immunotherapy in a real-world setting. METHODS/PATIENTS: From May 2014 to December 2015, 390 patients in 108 Spanish centres enrolled in the nintedanib named patient use program. Inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. The objective was to evaluate the efficacy of the nintedanib/docetaxel combination in patients who also received immunotherapy. RESULTS: Eleven patients met the inclusion criteria; with a median age of 67 years. PD-L1 expression was positive in six patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (95% CI 1.9-4.6). Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) or nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (95% CI 0-6.1). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. Median PFS of nintedanib/docetaxel was 3.2 months (95% CI 1.9-4.5). Best response was partial response in four patients (36%), stable disease in five patients (46%), and progressive disease in two patients (18%), for an ORR of 36% and a DCR of 82%. CONCLUSION: Our experience suggests an encouraging efficacy of nintedanib/docetaxel in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy, reinforcing the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma.

Improvement of appropriate pharmacological prophylaxis in hospitalised cancer patients with a multiscreen e-alert system: a single-centre experience.

PURPOSE: Thromboprophylaxis use among medical inpatients, including cancer patients, is suboptimal. We aimed to evaluate the impact of a novel multiscreen version (v2.0) of an e-alert system for VTE prevention in hospitalised cancer medical patients compared to the original software. METHODS: Prospective study including 989 consecutive adult cancer patients with high-risk of VTE. Patients were followed-up 30 days post-discharge. Two periods were defined, according to the operative software. RESULTS: E-alert v2.0 was associated with an increase in the use of LMWH prophylaxis (65.5% vs. 72.0%); risk difference (95% CI) 0.064 (0.0043-0.12). Only 16% of patients in whom LMWH prophylaxis was not prescribed lacked a contraindication. No significant differences in the rates of VTE (2.9% vs. 3.2%) and major bleeding (2.7% vs. 4.0%) were observed. CONCLUSIONS: E-alert v2.0 further increased the use of appropriate thromboprophylaxis in hospitalised cancer patients, although was not associated with a reduction in VTE incidence.

Targeted DNA sequencing for assessing clonality in multiple lung tumors: A new approach to an old dilemma.

BACKGROUND: The differential diagnosis between multiple primary lung cancer (MPLC) and advanced lung cancer has traditionally relied on conventional radiology and pathology. However, the outcomes of traditional diagnostic workup are often limited, and staging is uncertain. Increasing evidence suggests that next-generation sequencing (NGS) techniques offer the possibility of comparing multiple tumors on a genomic level. OBJECTIVES: The objective of this study is to assess the clinical impact utility of targeted sequencing in patients presenting with multiple synchronous or metachronous lung tumors. MATERIALS AND METHODS: We describe the diagnostic workup conducted in a patient with three lung tumors, where we used a targeted 50-gene DNA sequencing panel (Ion AmpliSeq TM Cancer Hotspot Panel v2) to assess clonality and establish an accurate lung adenocarcinoma stage. Positive results were confirmed by pyrosequencing or Sanger sequencing. RESULTS: Three surgically resected lung tumors were submitted for targeted sequencing. The tumor from the upper right lobe was positive for a TP53 c.659A > G mutation and native for KRAS. The tumor from the upper left lobe was positive for TP53 c.725G > T and KRAS c.35G > T mutations. The tumor from the lower left lobe was positive for TP53 c.1024C > T and KRAS C.34G > T mutations. Results and reviewed literature in the field support the diagnosis of MPLC instead of a single advanced lung cancer. CONCLUSION: Targeted DNA sequencing significantly increases diagnostic accuracy in patients with multiple lung tumors. NGS panels should be available for patients presenting with multiple lung tumors.

Perceived quality in a dementia unit: patients' caregivers as information providers. / Calidad percibida en una unidad de demencias: el portavoz del paciente como proveedor de información.

INTRODUCTION: Dementia units (DU) provide comprehensive and specialised care to patients with dementia. However, assessment in these units normally focuses on patient management. The aim of this study was to determine satisfaction of the caregivers of patients managed in a DU and how they rated DU care. METHODS: We created a self-administered questionnaire which was completed by 236 caregivers visiting the DU in 2015. The questionnaire included 6 dimensions (accessibility, organisation, professionalism, relationship with staff, information, and facilities); data were analysed using problem rates. RESULTS: A total of 53.4% caregivers completed the questionnaire; most were women, patients' spouses, or first-degree relatives. The overall problem rates was 15.0% (95% CI, 13.9-16.1), with sizeable differences between dimensions: from 0.1% (95% CI, 0.0-0.4) for 'relationship with staff' and 'professionalism' to 49.3% (95% CI, 45.4-53.2) for 'information'. Waiting times over 30minutes were perceived as excessive. Information problems were not directly related to patient management. Satisfaction was scored 8.29/10 (median 8; SD 1.45); 77.3% (95% CI, 69.8-74.8) of respondents were highly satisfied. Ninety-nine percent of the caregivers stated that they would recommend the DU. CONCLUSIONS: This questionnaire provides interesting data on care quality as perceived by patients' caregivers. Our results have allowed us to identify problems and implement corrective actions. Our questionnaire has proved to be a useful tool for evaluating and improving care quality in DUs.

[Effectiveness of an intervention to improve safety culture. Less is more?] / Efectividad de una intervención para mejorar la cultura de seguridad. ¿Menos es más?

OBJECTIVE: To assess the impact of a long-term initiative to improve safety culture among professionals working in a Health Area, and to know their perceived usefulness. MATERIAL AND METHODS: An uncontrolled intervention study was designed in a public health care organization including a 3rd level hospital and 5,000 professionals. To measure the impact, the AHRQ Survey was conducted by telephone. A total of 7 dimensions of culture were measured, before starting the project (2012, n=100) and 3 years later (2015, n=207). Variations between 2012 and the respondents aware of the project in 2015 (RAP) were compared, as also between this last group and the rest of respondents (RNAP). The utility was assessed using a 5-item Likert scale, defining higher utility by medians 4 or higher. RESULTS: The response rates were above 80%. In 2015, the 41.5% of respondents were RAP (95%CI: 34.8-48.3), which was perceived as of high utility. Negative variations were detected in "sense of security" (-9.9%, P<.01, vs. 2012, and -4.2% between 2015 groups) and "feedback and communication errors" (-10.0% vs. 2012, and -8.9% between 2015 groups, P<.05). There was a not-significant positive variation in "openness in communication" (1.3% vs. 2012, and 6.9% between 2015 groups). The "management support" showed a not-significant improve in 2015 (37.0%, 95%CI: 30.9-43.1, in RAP; and 38.3%, 95%CI: 33.1-43.4, in RANP) in comparison to 2012 (31.4%, 95%CI: 28.4-39.7). CONCLUSIONS: A paradoxical worsening is detected in several dimensions, this probably due to immaturity of the organization and the instrument used. Thus, tools explicitly considering the degree of maturity may be more appropriate to measure cultural changes, although more studies are needed.

Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value.

Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations.

[Can anybody understand the informed consent documents? A proposal to make it easier]. / ¿Pero alguien entiende los consentimientos informados? Una propuesta para facilitar su comprensión.

OBJECTIVE: To assess the readability of informed consent documents as written by doctors, by analysing the results and the differences between the sections of the document and services, with the aim of helping to improve them. MATERIAL AND METHODS: Descriptive study of the texts from 359 documents sent for accreditation in the Arrixaca Hospital (Murcia, Spain). Both length and readability are assessed. Length is measured in words (adequate up to 470, excessive over 940), and readability in INFLESZ points (suitable if over 55). RESULTS: Length ranged from 73 to 1018 words (mean 360, standard error 8.8, adequate length OR 3.66±0.81). The larger sections were "risks" and "nature of the procedure", and the shorter ones, "alternatives" and "contraindications", P<.0001. The INFLESZ value ranged from 18.1 to 86.4 points (mean 45.8, standard error 0.45), and was better in non-surgical services. Only 12.5% of the documents achieved an INFLESZ value over 55 (OR 0.12±0.03), with 70% in non-surgical procedures, P<.0001. The better readability sections were the "nature" and the "risks", and the worst ones, were "contraindications" and "alternatives", P<.0001. CONCLUSIONS: The length of proposed documents is adequate, but they are not sufficiently readable, especially if they come from surgical services. The section length is unbalanced, with "contraindications" and "alternatives" being shorter and more difficult to understand. It is essential to check the readability before using an informed consent document. For this purpose, tools like that proposed could be useful.

[Introduction of an accreditation system for hospital informed consent forms]. / Introducción de un sistema de acreditación para los documentos de consentimiento informado hospitalario.

OBJECTIVE: To describe an accreditation system for informed consent forms (ICF) in a tertiary hospital, as an intervention to improve their quality, and to check the improvements achieved. MATERIAL AND METHODS: Following an external evaluation of the ICF quality in a public hospital in Murcia (Spain), an accreditation committee set the ICF requirements and associated procedures. Effectiveness is assessed by comparing two external evaluations carried out by the EMCA Program (2011 and 2013) and based on 19 criteria and a sample of 60 ICF for every public hospital in Murcia Region. RESULTS: To be accredited, every ICF must meet the 19 external criteria plus 5 based on legibility, readability and scientific and technical validity. A form to fill in the contents of every ICF was agreed, which would be reviewed, approved and validated for five years. Before the implementation, 8.2 defects/ICF were detected. The accreditation system obtained an 89% improvement (0.9 defects/ICF) and achieved significant improvements in 18 criteria, 16 of which are benchmarked. DISCUSSION: The accreditation system achieved a substantial improvement in the ICF (obtaining a better result in external evaluations) and guarantees their contents, legibility and readability. This system needs to be extended to other hospitals, since it is not clear whether common ICFs would be suitable. However, this improvement is structural and does not guarantee that the overall information/consent procedure is done properly, thus complementary strategies for measurement and improvement are required.

Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Platinum/5-fluorouracil plus cetuximab is a standard systemic treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Pemetrexed has shown activity in SCCHN. This phase II study evaluated pemetrexed with cisplatin and cetuximab in recurrent/metastatic SCCHN. METHODS: Patients received cetuximab 250 mg/m(2) (loading dose: 400mg/m(2))days 1, 8 and 15; pemetrexed 500 mg/m(2)+cisplatin 75 mg/m(2) on day 1, q3w up to six cycles and folic acid, vitamin B12 and prophylactic medications. After a minimum of four cycles, responding patients were eligible for maintenance with pemetrexed and cetuximab, or either as monotherapy, until progression or toxicity. Efficacy (primary end-point: progression-free survival [PFS]) and toxicity were evaluated. RESULTS: Sixty-six patients received ≥1 cycle of the triplet. Most patients were male (80.3%), with a median age of 62 years and Eastern Cooperative Oncology Group (ECOG) performance status of 1 (71.2%). Diagnoses included oropharynx (45.5%) and larynx (24.2%) cancers, with locoregional disease (51.5%) alone, or combined with distant metastases (48.5%). Median (m) PFS was 4.4 months (95% confidence interval [CI]: 3.6, 5.4); median overall survival was 9.7 months (95% CI: 6.5, 13.1). Objective response rate was 29.3%; 23 patients had stable disease (39.7%). Drug-related grade 3/4 toxicities included neutropaenia (33.3%), fatigue (24.2%), anorexia (12.1%) and infection (10.6%). Five treatment-related deaths (7.6%) occurred. CONCLUSIONS: Efficacy results were consistent with current standard treatment for this patient population, but the pre-specified mPFS of 5.5 months was not achieved. Grade 3/4 toxicities were also consistent with standard treatment, although treatment-related deaths were higher than expected.

Percepción de los médicos de familia acerca de un programa de ayuda a la prescripción para reducir las interacciones medicamentosas / No disponible

Objetivo: Conocer la opinión de los médicos de familia sobre la utilidad y formato de presentación de un programa de ayuda a la prescripción dirigido a reducir la aparición de interacciones medicamentosas. Material y métodos: Estudio descriptivo transversal. Realización de una encuesta y evaluación de resultados. Emplazamiento: Atención primaria, región de Murcia. Participantes: 189 médicos de familia integrados en el programa PRISMAp, que recibieron información periódica acerca de las interacciones medicamentosas detectadas en sus pacientes a través de la historia clínica electrónica. Mediciones principales: mediante escala de Likert de 5 ítems, se formulan preguntas sobre utilidad (6), posibles mejoras (5) y formato del informe recibido (3). Se construyeron indicadores de acuerdo (puntuaciones de valor "4" o "5") y desacuerdo (valores "1" o "2") para cada una de ellas. Resultados: Respondieron 83 médicos (tasa de respuesta 43,9%). El 77,5% opinaron que PRISMAp fue adecuado para avisarle de interacciones, para el 52,0% le informó frecuentemente de interacciones que no conoce, y le hizo cambiar la prescripción inicial al 41,3%. Las oportunidades de mejora más valoradas fueron la incorporación al módulo de prescripción electrónica (93,3%) y que adviertiera de la posible interacción en el momento de realizar la prescripción (94,7%).Conclusiones: Este estudio aporta una aproximación a las percepciones y un mejor entendimiento de las actitudes de los médicos de familia acerca de los programas de ayuda a la prescripción, y en especial de los dirigidos a reducir interacciones medicamentosas, que son considerados útiles y capaces de mejorar la seguridad de sus prescripciones (AU)

Objective: To assess GP views on the usefulness and the kind of issue of a programme aimed to reduce the occurrence of drug interactions (DI) in primary care. Material and methods: Cross-sectional study. Questionnaire survey of GPs participating in the PRISMAp programme. Setting: Primary care, Murcia Region of Spain. Participants: 189 GPs participating in the PRISMAp programme who received periodic information about the DI detected in the electronic medical records of their patients. Measurements: questions about the usefulness (6), opportunities to improve (5) and the kind of issue of the report received (3) where asked using a 5-items Likert scale. The agreement/disagreement were obtained considering the percentage of Likert scores greater and smaller than 3, respectively. Results: The response rate was 43.9% (83 of 189). Of these, 77.5% think that PRISMAp is suitable to warn them about DI, 41.3% have changed their prescriptions, and 52.0% have frequently been informed about DI that they did not know. The best valued opportunities to improve were the incorporation of recommendations to the electronic prescription module (93.3%) and the warning of potential DI when prescribing (94.7%).Conclusions: This study provides an approach to the perceptions and a better understanding of the GPs attitudes toward the programmes aimed to assist their prescriptions and, specially, toward those aimed to reduce the DI. They are considered useful and able to improve the safety or their prescription (AU)

Uso de tecnologías de la información para mejorar la seguridad de la prescripción en Atención Primaria / Using information technology to improve drug safety in primary care

ObjetivoAyudar a los médicos de familia a detectar y a prevenir problemas relacionados con interacciones medicamentosas para lograr una prescripción de más calidad y mejorar la seguridad de los pacientes.Material y métodosEstudio de intervención no controlado basado en metodología de evaluación y mejora de calidad. Emplazamiento: 2 áreas de salud de la Región de Murcia. Participantes: pacientes de 139 médicos de familia que utilizan habitualmente la historia clínica electrónica (más de 100 prescripciones electrónicas por semana: 188.353 individuos y 334.088 prescripciones al inicio del estudio y 202.988 individuos y 335.198 prescripciones al final del estudio). Intervención: 1) diseño de un programa informático detector de pacientes con interacciones clínicamente importantes que deberían evitarse (tipos 1 y 2 de la base de datos del Colegio Oficial de Farmacéuticos); 2) elaboración automatizada de un informe sobre éstas para cada médico, que incluye identificación del paciente, medicamentos, evidencias disponibles y recomendaciones de actuación, y 3) realización de sesiones clínicas por farmacéutico entrenado en el centro de salud coincidentes a su entrega.ResultadosInteracciones preintervención: prevalencia del 1,29%; por paciente en riesgo el 6,57% y por médico de familia el 20,2%. Postintervención: prevalencia del 1,06% (mejora del 17,6%; p<0,000001); por paciente en riesgo el 5,17% (mejora del 21,4%; p<0,000001) y por médico de familia el 17,7 (mejora del 12,1%; p<0,001).ConclusionesImplantar este tipo de tecnología puede ser útil para la seguridad del paciente, por lo que debería extenderse a todos nuestros médicos. Deben valorarse otras tecnologías, como sistemas de alerta electrónica concurrentes con la prescripción para las interacciones de especial frecuencia o trascendencia(AU)

PurposeTo help family doctors to detect and prevent problems related to drug-drug interactions in order to attain a higher quality prescription and an improvement in patient safety.MethodsUncontrolled study of an intervention based on quality evaluation and improvement methods.SettingTwo health areas in Murcia Region (Spain).PatientsSubjects appointed to 139 family doctors regularly using electronic clinical records (including doctors who were producing over 100 electronic prescriptions per week: 188,953 subjects and 334.088 prescriptions at the start, and 202,988 subjects and 335.198 prescriptions at the end of study). Intervention: (1) A software able to collect patients who had clinically important drug-drug interactions those that should be avoided (BOT I+II) was designed. (2) A report on these interactions was drawn up and delivered periodically to every single doctor, including patient identification and information on the drugs involved, possible consequences, and recommendations about what to do. (3) Clinical and educative sessions given by a trained pharmacist were carried out in doctors’ health centre coinciding with their delivery.ResultsDrug-drug interactions pre-intervention: prevalence 1.29%; by patient at risk 6.57%; by doctor 20.2. Post-intervention: prevalence 1.06% (improvement 17.6%, P<.000001), by patient at risk 5.17% (improvement 21.4%, P<.000001), by doctor 17.7 (improvement 12.1, P<.001).ConclusionsDeveloping this technology leads to progress in patient safety, therefore it should be extended to all our family doctors. Other technologies such as an electronic alert when prescribing should be considered, particularly for either higher frequency or important consequences interactions(AU)

[Using information technology to improve drug safety in primary care]. / Uso de tecnologías de la información para mejorar la seguridad de la prescripción en Atención Primaria.

PURPOSE: To help family doctors to detect and prevent problems related to drug-drug interactions in order to attain a higher quality prescription and an improvement in patient safety. METHODS: Uncontrolled study of an intervention based on quality evaluation and improvement methods. SETTING: Two health areas in Murcia Region (Spain). PATIENTS: Subjects appointed to 139 family doctors regularly using electronic clinical records (including doctors who were producing over 100 electronic prescriptions per week: 188,953 subjects and 334.088 prescriptions at the start, and 202,988 subjects and 335.198 prescriptions at the end of study). INTERVENTION: (1) A software able to collect patients who had clinically important drug-drug interactions those that should be avoided (BOT I+II) was designed. (2) A report on these interactions was drawn up and delivered periodically to every single doctor, including patient identification and information on the drugs involved, possible consequences, and recommendations about what to do. (3) Clinical and educative sessions given by a trained pharmacist were carried out in doctors' health centre coinciding with their delivery. RESULTS: Drug-drug interactions pre-intervention: prevalence 1.29%; by patient at risk 6.57%; by doctor 20.2. Post-intervention: prevalence 1.06% (improvement 17.6%, P<.000001), by patient at risk 5.17% (improvement 21.4%, P<.000001), by doctor 17.7 (improvement 12.1, P<.001). CONCLUSIONS: Developing this technology leads to progress in patient safety, therefore it should be extended to all our family doctors. Other technologies such as an electronic alert when prescribing should be considered, particularly for either higher frequency or important consequences interactions.

Role of surgery in a multidisciplinary approach to superior sulcus tumors (SST): morbidity and prognostic factors for long-term success after resection.

BACKGROUND: Optimal management of SST is still controversial several years after the proposal of a multidisciplinary approach including neoadjuvant chemotherapy and external radiation. Our objective is to report our experience of this multidisciplinary approach from the surgical point of view. PATIENTS AND METHODS: From January 1997 to January 2008, 24 patients were treated surgically (18 with induction chemotherapy and 15 with radiotherapy). The surgical approach was thoracic (14 cases, 1 with a spinal approach) or cervical (10 patients, 2 thoracotomies). Pulmonary surgery performed consisted of 11 wedge resections, 10 lobectomies, 1 pneumonectomy and 2 cases without lung resection (1 exploratory thoracotomy and 1 local progression after a previously resected tumor). Intraoperative radiotherapy (IORT) was given in 7 cases. Partial vertebral body resection was performed in 5 cases. A pathologically complete response (pT0) was found in 7 cases (29 %). RESULTS: Surgery-related morbidity was mainly due to respiratory distress (5 patients). Two patients died in the first month after surgery (mortality: 8 %). The surgical approach (cervical vs. thoracic) did not influence postoperative morbidity ( p = NS). Overall 5-year survival was 56.6 % according to the Kaplan-Meier method. No influence on survival was observed with regard to the approach (cervical vs. thoracic), the use of IORT, or the performance of spinal surgery. Patients with a complete pathological response had a better 5-year survival, but this did not reach statistical significance. CONCLUSION: Surgery has a role in the multidisciplinary approach, especially when we consider long-term survival. A multidisciplinary approach using neoadjuvant chemo and radiotherapy has a high rate of complete pathological response. It is also associated with a high incidence of postoperative distress syndrome. The 5-year survival is acceptable.

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes.

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators.

Arritmia fatal secundaria a hiperpotasemia asintomática y sin alteración inicial electrocardiográfica / No disponible

La hiperpotasemia es una alteración hidroelectrolítica frecuente en lospacientes hospitalizados. Presentamos a continuación el caso de unapaciente oncológica con hiperpotasemia asintomática y sin alteracioneselectrocardiográfi cas que presentó a las pocas horas una parada cardíaca.Se revisa el manejo diagnóstico y terapéutico actualmente recomendadopara controlar este desequilibrio potencialmente mortal. Debería realizarseun control frecuente de las cifras de potasemia aunque el pacienteesté asintomático y sin alteraciones electrocardiográfi cas(AU)

Hyperpotassemia is a common hydroelectrolytic disturbance in hospitalizedpatients. We report herein the case of an asymptomatic oncologicalpatient with no electrocardiographic alterations who suffered cardiacarrest. We review the diagnosis of this life-threatening complication andtherapeutic approaches. Blood potassium levels should be measuredfrequently, even if patients are asymptomatic or show no electrocardiographicdisorders(AU)

Arritmia fatal secundaria a hiperpotasemia asintomática y sin alteración inicial electrocardiográfi ca / Fatal arrhythmia caused by asymptomatic hypeerkalemia with normal basal electrocardiogram

La hiperpotasemia es una alteración hidroelectrolítica frecuente en los pacientes hospitalizados. Presentamos a continuación el caso de una paciente oncológica con hiperpotasemia asintomática y sin alteracioneselectrocardiográficas que presentó a las pocas horas una parada cardíaca. Se revisa el manejo diagnóstico y terapéutico actualmente recomendado para controlar este desequilibrio potencialmente mortal. Debería realizarseun control frecuente de las cifras de potasemia aunque el paciente esté asintomático y sin alteraciones electrocardiográficas

Hyperpotassemia is a common hydroelectrolytic disturbance in hospitalized patients. We report herein the case of an asymptomatic oncological patient with no electrocardiographic alterations who suffered cardiacarrest. We review the diagnosis of this life-threatening complication and therapeutic approaches. Blood potassium levels should be measured frequently, even if patients are asymptomatic or show no electrocardiographicdisorders

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.

[Small-cell lung cancer]. / Carcinoma microcítico de pulmón.

Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches.

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP (AU)