Search

In this paper, we review the current state of breakthrough cancer pain (BTcP) management. BTcP is a heterogeneous condition and a global problem for cancer patients. It is often managed suboptimally, which results in a negative outcome for patients, healthcare providers, and healthcare systems. Several barriers to the appropriate management of BTcP have been identified. These include, among others, an incomplete definition of BTcP, poor training of healthcare providers and patients alike, a lack of a multidisciplinary approach and the absence of specific protocols and tools. We provide some actions to help physicians and patients improve their approach to BTcP, including specific training, the design of easy-to-use tools for BTcP identification and assessment (such as checklists and pocket-sized cards), individualized treatment, and the use of multidisciplinary teams.

Management of malunion of the distal radius remains difficult. Planning of the correction of the articular displacement requires a comprehensive analysis by CT arthrography to analyze bone, cartilage and ligaments. Arthroscopy is a valuable tool in the context of joint trauma. In the absence of osteoarthritis, the correction can be carried out as early as possible in the weeks or months following the initial fracture. The use of locking plates allows early mobilization after surgery. This correction aims to prevent the development of secondary osteoarthritis.

The wrist's function is at stake in young active adults with partial intra-articular fractures of the distal radius. The high energy nature of these injuries, displaced fractures with risk of malunion in case of insufficient treatment, and associated ligament or cartilage damage all hinder the prognosis of these fractures. Many classification systems exist to help us analyze and in some cases, select a treatment. Optimal management requires a high-quality preoperative assessment and a precise surgical technique coupled with the use of arthroscopy to deal with joint and ligament injuries in the same operation. Devices that address the fragmented nature of these fractures provide the best fixation. The primary treatment goal is reduction with less 1mm intra-articular step-off in order to reduce the risk of secondary osteoarthritis and to treat associated ligament damage, which is very common and often under-estimated. Treating the fracture and any associated lesions during the same operation is the best way to ensure a good functional outcome.

Background Exosomes are small membranous vesicles (around 40-130 nm), that have been detected in different biological samples, that play a key role in NSCLC and being relevant in stem cell differentiation as well. The main objective of this study was to analyze the exosomes cargo from NSCLC cell cultures growth in monolayer (2D) and suspension conditions (3D, lung tumorespheres). Methods Cultures were established from NSCLC resected patients and cell lines. Exosomes isolation was performed by ultracentrifugation. Characterization was carried out by NTA, electron microscopy, immunoblot and flow cytometry. Mutational status of EGFR and RAS genes was analyzed by BEAMing dPCR. Transcriptomic analysis has been carried out from exosomal RNA with microarrays, (p ≤ 0.01). Consequently, XAGE1B (significantly expressed gene in exosomes) was analyzed by RTqPCR in 189 paired fresh-frozen tumor and normal tissue samples of resected NSCLC. Prognostic value was assessed by Kaplan‐Meier curves (log rank‐test), considering significant p Results Exosomal characterization through NTA and electron microscopy showed an exosomes size from 108-125 nm. Specific markers were detected by IB and FC. Mutational analysis of EGFR and RAS genes in exosomes shown the same pattern displayed by the origin cells. Transcriptomic analysis showed that the expression of mRNAs, miRNAs and precursors were significantly different between 3D and 2D-derived exosomes. A pathway enrichment was carried out to know in which processes (cancer-related) are involved. Significant differential expression was also found between ADC vs SCC–derived exosomes. Concretely, XAGE1B is overexpressed in ADC-derived exosomes (p = 0.00003). This overexpression in ADC was validated in NSCLC cohort (p = 0.002). Furthermore, it has revealed a significant association with patient prognosis for overall survival in the ADC group (n = 74)(OS 49.8 vs. NR months, p = 0.043). Conclusions Differences in exosomal cargo have been observed between: i) 3D vs. 2D cultures and ii) ADC vs. SCC. In addition, the same mutational pattern was detected in exosomes as compared with parental cells. Therefore, exosomes can be a useful source of biomarkers in NSCLC analysis. Supported by grant GV/2018/026, PI18/00266, & AECC Valencia. Legal entity responsible for the study Fundacion de Investigacion del Hospital General Universitario de Valencia. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

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. pre-print 339 KB

Background Target therapy guide by biomarkers have become the standard of care for patients with lung cancer (LC). So, identify those molecular alterations is one of the most important care needs nowdays. Our objective was to know the implementation degree of these tests in a large cohort of patients in Spain using the Thoracic Tumor Registry (TTR) of the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group). Methods The TTR is an observational cohort multicenter study of LC in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating institute. The registry was approved by the Spanish Drug Agency as a non-post-authorization, non-interventional study. We analyzed the molecular biomarkers considering all stages of LC. Results A total of 7,872 patients from 58 Spanish centers were enrolled between August 2016 to December 2018. The most frequent screened molecular test was the EGFR mutations, it was performed in 4,456 patients (67.5%). The proportion of biomarker evaluation has varied over time, ranging from 57.9% prior to 2012 up to 73.7% in 2017. The molecular assessment of some biomarkers reached 81.4% of these patients, with some differences between Regional Communities, regarding the molecular tests performed. Three thousand four hundred forty-six (3,446) patients (52.2%) had a stage IV at diagnosis. There was performed some biomarker test in 92% of the 2570 patients with stage IV and non-squamous histology. In those stage IV non-squamous patients, the EGFR and ALK test were performed in 92% and 79% respectively but 2 years ago ALK test was done only in 40% of the patients. ROS1 was studied in 20% of the cases. Conclusions Although no national plan exists for molecular biomarker analysis in Spain, the implementation of biomarkers tests in all the hospitals that contribute to the TTR is high. The increase in the ALK analysis in the last period is relevant. As we have some regional differences, it is important to understand the causes to improve them. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, Merck Sharp and Dohme, Lilly. Disclosure All authors have declared no conflicts of interest.

Background In 2017, the ECO Foundation (Excellence and Quality in Oncology) completed the EIO-50 project to learn about the diagnostic and treatment criteria of opioid-induced constipation (OIC) in cancer patients. The EIO-Praxis project was designed as a continuation of EIO-50, to learn about the current clinical practice of oncology professionals for the management of patients with OIC (process, follow-up and results). Methods 77 health care professionals (HCP) from oncology units participated in the study. Each investigator collected information from 10 medical records of cancer patients who received OIC treatment, with a total of 770 records. In each center, 6 indicators of its structure were collected and the completion of a questionnaire with 15 questions regarding patient’s follow-up and treatment process was conducted. Results According to healthcare professionals (HCP), an average proportion of 47.5% of cancer patients received treatment with opioids. From these, an average of 44.9% developed OIC. 51.9% of the investigators didn’t follow any guidelines for the management of patients with OIC. The mean age of the patients of the study was 61.6 years old. The mean duration of opioid treatment was 4.9 months, with an average time of 16.5 days from the start of opioid treatment to the appearance of the first symptoms of OIC. Only in 55.1% of the patients, the presence of functional constipation before starting opioid treatment was assessed. Patients of the study presented the following Rome IV criteria symptoms: 82.6% reduced bowel frequency, 52.9% fewer than three spontaneous bowel movements per week, 54.4% development or worsening of straining and stool consistency (54.2%). The majority of the patients were treated with laxatives (76.0%). Oral Peripherally Active µ-Opioid Receptor Antagonist (PAMORA) was also used in 54.8% of the patients. Conclusions Despite new guidelines for the management of constipation in cancer patients were published in 2018, the management of OIC is still insufficient. After laxative failures, the use of PAMORA drugs should be taken into consideration for the management of OIC. Legal entity responsible for the study ECO Foundation. Funding Kyowa Kirin. Disclosure E. Aranda Aguilar: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi. J. Garcia Foncillas: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Research grant / Funding (institution): Merck. E. Diaz Rubio: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Genomica; Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Speaker Bureau / Expert testimony: MSD; Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Sysmex. R. Lopez: Shareholder / Stockholder / Stock options, Licensing / Royalties: Nasasbiotech; Shareholder / Stockholder / Stock options: Mtrap Inc; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Janssen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Pierre Fabre. All other authors have declared no conflicts of interest.

Background Tobacco use, mainly as cigarette smoking, is the leading cause of lung cancer. Eighty-five percent of LC occur in smokers. Understanding the Spanish smoking habits allows the government to design health care policies against this consumption. To do so, the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group) made this analysis within the context of the Thoracic Tumor Registry (TTR). Methods The TTR is an observational cohort multicenter study in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating site. The registry was approved by the Spanish Drug Agency, as a non-post-authorization, non-interventional study. Results Data have been collected from 6,600 LC from 58 different hospital sites across Spain. 12% (866 p) were non-smokers, 46% (3,039 p) were former smokers and 39% (2,611 p) were smokers. There were significant differences by gender, more women were non-smokers (37 % vs. 45% in males), meanwhile more former smokers were male (53.4% vs. 27.9% in women) (p-valor Conclusions Tobacco use is the leading cause of LC in Spain accounting 85% of the cases. Consumption has increased in both genders, but specially in women, in our country among lung cancer patients. Tobacco cessation campaigns, especially in women, should be a priority in western countries, like Spain, and it has to be adapted to regional differences in tobacco use. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, MSD, Lilly. Disclosure M. Provencio: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Purpose To evaluate the outcome of a silicone implant used after failure of primary trapeziometacarpal (TMC) surgery. Methods We retrospectively reviewed 22 Tie-in silicone implants performed between January 2005 and December 2015. All silicone implants were used for revision after failure of TMC surgery. We determined the time between implantation and the date of diagnosis of the failed revision procedure (rupture, major wear, dislocation, or poor clinical tolerance). Results Median survival was 2.15 years. Only 3 patients did not show wear, but one was lost after 1 year of follow-up. We found 10 cases with rupture of the implant, 5 with implant instability (subluxation or dislocation), 3 implants with abnormal wear, and 1 patient who reported residual pain. A total of 42% of failures were associated with silicone synovitis Conclusions Survival of the Tie-in silicone implant in TMC revision surgery is poor; nearly half of implants failed at 2 years. The rate of silicone synovitis is also important because future revision might be more complex owing to bone loss. Type of study/level of evidence Therapeutic IV.

OBJECTIVES: Caregivers of terminal patients often report a higher prevalence of unmet needs than cancer survivors. However, very few interventions have been carried out to support caregivers of patients in advanced stages, and, in most cases, they have not been rigorously designed and evaluated. The ultimate aim of this research was to obtain specific information about the sociodemographic characteristics, the different types of care provided, the symptoms due to burdens, the impact of caring on the quality of life, and the unmet needs of informal caregivers of dependent patients with cancer. This is to design effective intervention programs that can be implemented from the hospital setting itself and therefore, to improve their quality of life and prevent the deterioration of their health. STUDY DESIGN: A cross-sectional design and survey methodology were used for descriptive purposes. METHODS: The sample was composed of 132 informal caregivers of dependent patients with cancer, from a public hospital in Valencia, Spain, who were identified through the patient database of the oncology service, over the 4-month data collection period. Self-administered questionnaires were combined with personal interviews: Interview Protocol for the main caregiver, Questionnaire ICUB97, and survey of hospital quality. RESULTS: The most frequently provided types of care included the following: keeping the patient company, acting as an intermediary between them and healthcare workers, and helping them to do basic daily life activities. The main negative consequences caregivers reported were the following: feeling more tired, having less free time, changing their daily routines, and having fewer social relationships/interactions and various emotional and physical symptoms. Many of the needs of informal caregivers were not being met: resolution of doubts about illness, training in the care they should provide to the patient, and psychological help. CONCLUSIONS: Recommendations for the development of effective intervention programs are offered: increasing the psychological services provided in oncology units, training medical staff in communication skills, facilitating access to information about the disease through different means, training for informal caregivers in care techniques, coping and communication skills, self-care, and organization of time. On the one hand, implementing effective intervention programs for informal caregivers will reduce the amount withdrawing from their care duties and on the other hand, the proliferation of what are known as secondary patients.

[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., This study was funded by Kyowa Kirin Farmacéutica S. L.U. through Fundación ECO.

PurposeAfter surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice.Methods/patientsWe classified 105 patients with resected CRC (stage I-III) into five molecular subtypes using BRAF(V600E) and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated.Results and conclusionsRAS and BRAF(V600E) mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26months; p value=0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAF(V600E) mutated (6.7%) and RAS/BRAF(V600E) wt (35.2%); and two were dMMR: BRAF(V600E) mutated (4.8%) and BRAF(V600E) wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAF(V600E) wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAF(v600E) or RAS oncogenes (median of DFS=45.5 vs 40.98months in RAS mutated group; p=0.084 and vs 34.13 in BRAF(v600E) mutated group; p=0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.

Purpose To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab. Methods Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0–1) vs. group 2 with high expression (2–3). Results Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy. Conclusions Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.

The economic situation showed that the resources devoted to health spending are limited, making rationalisation of their consumption necessary. The relevance of pharmacoeconomic analyses is becoming crucial. The ECO Foundation, promoting the quality of oncology care, set out to analyse the consensus on the new therapeutic targets inclusion and the integration of pharmacoeconomics when evaluating their effectiveness. Study about pharmacoeconomic estimations was performed during the first ECO-Seminar (2010). It was developed using a modified Delphi method, in four stages: (1) committee coordinator establishment, (2) expert-panel selection, (3) preparation and submission of survey (1 question) by email, and (4) analysis of the degree of consensus reached. Results were obtained from surveys completed by 35 experts. Regarding the tolerable annual cost for the approval of new drugs, 68.8 % of the respondents considered a cost per quality-adjusted life year (QALY) gained between €30,000 and 100,000 acceptable (34.4 % €30,000–60,000; 34.4 % €60,000–100,000), 21.9 % of the respondents found costs between €100,000–150,000/QALY and 9.3 % of the respondents found costs above €150,000/QALY acceptable. The costs of new drugs are higher than traditional treatments, making it a priority to identify subgroups of patients with specific molecular profiles as candidates for higher-efficiency-targeted therapies. The allocation of the available resources to the most effective interventions, to achieve the best clinical outcomes with lower costs and best subjective profile possible, allows expenditure to be rationalised. Pharmacoeconomic studies are a basic tool for obtaining better health outcomes according to the available resources, while also considering the other needs of the population.

Malignant insulinoma is an infrequent functional endocrine tumor of the pancreas. Adequate therapy is a demanding challenge for oncologists and endocrinologists. To evaluate the results of multidisciplinary management of malignant insulinoma. Retrospective review of patients with malignant insulinoma treated from 1995 to 2011. Seven patients with malignant insulinoma were included: four males and three females; median age was 61.8 years (range 37-78). Six tumors were sporadic and one was diagnosed in a patient with a type 1 multiple endocrine neoplasia (MEN-1). Surgery was performed in six cases and one patient was considered unresectable. Hypoglycemias persisted in all cases and somatostatin analogs, glucocorticoids and diazoxide were used. Two patients received everolimus. Other techniques were chemoembolization and internal radiation therapy with yttrium-90. Successful liver transplant was done in the patient with MEN-1. Hypoglycemia management is complex and requires multiple therapies. Further evaluations will be necessary to determine the best treatment.

Objective: To evaluate the impact and type of side-effects in patients treated with cetuximab and provide a description of the general measures and treatment. Methods: Retrospective safety study. We included all patients that received cetuximab from January to December 2009. All information was obtained from the Pharmacy and Oncology Department’s Access databases and reviewed the patient’s medical history. All data was registered in an Excel workbook. Skin toxicity was graded by the current National Cancer Institute-Common Toxicity Criteria (NCI-CTC). Results: During the study period 43 patients received treatment with cetuximab. Acneiform eruption was present in 30 of the cases (69.8%): 14 patients with grade 1 (48.3%), 13 with grade 2 (44.8%) and 3 with grade 3 (10.3%). These adverse effects appeared in a median of seven (4---28) days. In a median of 40 (20---56) days, ten patients (23.3%) presented xerosis, and three (7%) suffered painful fissures in hands and feet after a median of 28 (21---35) days. Paronychia was present in two patients after a median of 42 (35---49) days. Finally, an alteration in hair growth was observed in two patients with overgrowth of facial hair and one patient with overgrowth of the eyelashes. Five patients presented important conjunctivitis. Three infusion reactions occurred.

OBJECTIVE: To evaluate the impact and type of side-effects in patients treated with cetuximab and provide a description of the general measures and treatment. METHODS: Retrospective safety study. We included all patients that received cetuximab from January to December 2009. All information was obtained from the Pharmacy and Oncology Department's Access databases and reviewed the patient's medical history. All data was registered in an Excel workbook. Skin toxicity was graded by the current National Cancer Institute-Common Toxicity Criteria (NCI-CTC). RESULTS: During the study period 43 patients received treatment with cetuximab. Acneiform eruption was present in 30 of the cases (69.8%): 14 patients with grade 1 (48.3%), 13 with grade 2 (44.8%) and 3 with grade 3 (10.3%). These adverse effects appeared in a median of seven (4-28) days. In a median of 40 (20-56) days, ten patients (23.3%) presented xerosis, and three (7%) suffered painful fissures in hands and feet after a median of 28 (21-35) days. Paronychia was present in two patients after a median of 42 (35-49) days. Finally, an alteration in hair growth was observed in two patients with overgrowth of facial hair and one patient with overgrowth of the eyelashes. Five patients presented important conjunctivitis. Three infusion reactions occurred. A grade-based treatment algorithm was used for all patients that presented cutaneous toxicity. CONCLUSIONS: A considerable number of patients treated with cetuximab develop dermatological side-effects which left untreated could represent a threat to the efficacy of the therapy. Therefore effective management is mandatory, patient education and immediate treatment based on a grade-based algorithm to alleviate symptoms is necessary, so that patient compliance is guaranteed.

Objective: To study the effectiveness and safety of pemetrexed in non-small cell lung cancer. Method: Retrospective study (March 2006-May 2008) of pemetrexed use. Information was obtained from the Access database belonging to the Pharmacy and Oncology Departments, the registry of external consultations and clinical histories. Data were analysed using SPSS software version 12.0. Quantitative variables are expressed as the median (minimummaximum). Results: The study included 44 patients (61.7 [39-77] years old), mostly male (86%), smokers or former smokers (80%) with predominantly epidermoid/squamous disease (46%) or adenocarcinoma, in a good functional state (86%) and in stage >III upon beginning pemetrexed treatment (93%). Prior treatment with taxanes and taxane treatment along with a prior history of neutropoenia were the criteria for changing to pemetrexed in 34.4% and 22.7% of the patients, respectively. None of the patients presented a complete or partial response: 18.2% showed disease stability and 81.8% showed disease progression. The main reasons for discontinuing pemetrexed were progression of the disease (54.5%) and worsening of symptoms (15.9%). Median survival after beginning chemotherapy was 22.2 months (ranging from 16-28.4) and 7.8 months (4.4-11.2) after beginning pemetrexed treatment. These last figures were significantly higher in women and those with an ECOG of 0 to 1. The most common adverse effects were weakness and neurotoxicity. Conclusion: In each of the cases, pemetrexed was used as a second-line treatment or higher with a good safety profile. A complete or partial response was not reached in any of the cases, but survival after beginning pemetrexed was equal to or longer than that achieved in other studies.

Cancer is a disease of high incidence, which determines that the health systems will be forced to allocation a significant amount of resources. In an era of evidence-based medicine and increasing cost pressures, it is important to understand the relative clinical and economic impact of the many drug treatment strategies available for cancer patients. Currently, resources that may be spent in pharmacoeconomics expenditure are limited so it is necessary to rationalize their consumption and priorize in the allocation of these resources to the options with higher economic advantages. Pharmacoeconomic studies will permit us to know what is the efficiency of different therapeutic alternatives so they will help to determine the therapeutic options that we should use in routine medical practice.

Objective To study the effectiveness and safety of pemetrexed in non-small cell lung cancer. Method Retrospective study (March 2006-May 2008) of pemetrexed use. Information was obtained from the Access database belonging to the Pharmacy and Oncology Departments, the registry of external consultations and clinical histories. Data were analysed using SPSS software version 12.0. Quantitative variables are expressed as the median (minimum-maximum). Results The study included 44 patients (61.7 [39–77] years old), mostly male (86%), smokers or former smokers (80%) with predominantly epidermoid/squamous disease (46%) or adenocarcinoma, in a good functional state (86%) and in stage ≥III upon beginning pemetrexed treatment (93%). Prior treatment with taxanes and taxane treatment along with a prior history of neutropoenia were the criteria for changing to pemetrexed in 34.4% and 22.7% of the patients, respectively. None of the patients presented a complete or partial response: 18.2% showed disease stability and 81.8% showed disease progression. The main reasons for discontinuing pemetrexed were progression of the disease (54.5%) and worsening of symptoms (15.9%). Median survival after beginning chemotherapy was 22.2 months (ranging from 16–28.4) and 7.8 months (4.4–11.2) after beginning pemetrexed treatment. These last figures were significantly higher in women and those with an ECOG of 0 to 1. The most common adverse effects were weakness and neurotoxicity. Conclusion In each of the cases, pemetrexed was used as a second-line treatment or higher with a good safety profile. A complete or partial response was not reached in any of the cases, but survival after beginning pemetrexed was equal to or longer than that achieved in other studies.

The performance of a readout system for the Synchrotron Radiation Detector (SRD) is studied. The detector is proposed as part of the Alpha Magnetic Spectrometer experiment, an experiment to fly on the International Space Station (ISS) beginning of 2005. The SRD is designed to detect the synchrotron radiation from electrons and positrons (TeV energy range) produced in the earth's magnetic field. For the planned array of scintillators and photomultipliers a readout system is chosen, which is compact, space qualified and has a low-power consumption. The low-power chip APV, originally designed for the CMS experiment at LHC (CERN), is foreseen for the readout. To overcome the diffuse background from photons and charged particles the SRD readout must have a time resolution better than 10 ns. The intrinsic time resolution (sigma from Gauss fit) of the APV25-S0 was found to be 0.46±0.01 and 0.68±0.02 ns for the APVM, whereas the time resolution of the photomultiplier-APV readout system was measured to be 2.73±0.10 ns for the APV25-S0 and 2.90±0.21 ns for the APVM. The investigated timing capabilities of the photomultiplier-APV readout system show that the APV chip is suitable for the SRD readout.

The Prototype Synchrotron Radiation Detector (PSRD) is a small-scale experiment designed to measure the rate of low-energy charged particles and photons in near the Earth's orbit. It is a precursor to the Synchrotron Radiation Detector (SRD), a proposed addition to the upgraded version of the Alpha Magnetic Spectrometer (AMS-02). The SRD will use the Earth's magnetic field to identify the charge sign of electrons and positrons with energies above 1 TeV by detecting the synchrotron radiation they emit in this field. The differential energy spectrum of these particles is astrophysically interesting and not well covered by the remaining components of AMS-02. Precise measurements of this spectrum offer the possibility to gain information on the acceleration mechanism and characteristics of all cosmic rays in our galactic neighbourhood. The SRD will discriminate against protons as they radiate only weakly. Both the number and energy of the synchrotron photons that the SRD needs to detect are small. The identification is complicated by the presence of a large particle and photon background. Existing measurements of these backgrounds are insufficient for the construction of the large-scale SRD, so a measurement in space was indispensable. The PSRD was designed to fly as a Space Shuttle secondary payload, within the Shuttle Small Payloads Project. The flight on board the Space Shuttle Endeavour took place from 5 to 17 December 2001. The scientific goal, hardware and the flight of the PSRD are described in this report.

The innermost region of the CMS detector will consist of silicon pixel and silicon microstrip detectors. One microstrip detector module is essentially composed of three elements: a set of silicon sensors, a mechanical support structure and the Front End Electronics (FE hybrid). During the production phase of the CMS tracking device, various quality and functionality tests of each detector component have to be performed to assure a stable tracker performance for a time scale of about 10 years of LHC running. This demands a chain of testing procedures beginning at the Hybrid component level and ending at the assembled module level. Each production and assembly step needs a specific testing environment and procedure (e.g. long- or short-term tests and temperature cyclings). A compact, cost efficient test and diagnostic tool which is suited for the operation and characterization of hybrids and silicon detector modules will be presented. The test setup is mainly composed of two printed circuit boards, one interface to the PC and the graphical user interface.

Resume Objectif : Expliquer le caractere inconstant de la paresie hemidiaphragmatique apres bloc inter-sterno-cleido-mastoidien (inter-SCM). Type d'etude : Etude prospective, comparative, en simple aveugle. Patients : 16 patients de classe ASA 1–2. Methodes : Evaluation de la paresie diaphragmatique apres bloc inter-SCM par un radiologue ignorant la technique et le cote opere. Determination de la course diaphragmatique (CD) sur des cliches thoraciques pris en double exposition, en phases pre- et postoperatoires (CD pre, CD post) du cote homolateral et controlateral. Tous les patients ont recu un melange adrenaline de 20 mL de bupivacaine a 0,5 % et de 20 mL de lidocaine a 2 %, injecte par l'aiguille de stimulation, ou par le catheter, apres controle radiologique de sa position. Ils ont ete repartis en deux groupes equilibre. Groupe 1 : injection via l'aiguille apres obtention d'une flexion digitale a la stimulation, ou via le catheter en position infraclaviculaire ; groupe 2 : injection via l'aiguille apres contraction du deltoide ou du biceps, ou via le catheter en position susclaviculaire. Resultats : Tous les patients ont eu un bloc satisfaisant. Du cote opere, la course diaphragmatique etait diminuee apres realisation du bloc dans le groupe 2 ( P Conclusion : La paresie diaphragmatique est evitable si l'anesthesique local est injecte par l'aiguille apres obtention d'une flexion des doigts, ou par un catheter en position infraclaviculaire.

Purpose : This pilot study was designed to evaluate the efficacy and toxicity of the gemcitabine/vinorelbine combination in non-small-cell lung cancer (NSCLC) patients who had failed cisplatin-based first-line chemotherapy. Patients and methods : Eligible patients had refractory or resistant NSCLC, WHO performance status 0–2, adequate hematologic parameters and normal hepatic, renal and cardiac function. Gemcitabine (1200 mg/m 2 ) was administered on days 1, 8 and 15; vinorelbine (25 mg/m 2 ) was administered on days 1 and 8, every 4 weeks until patients experienced disease progression. Results : From September 1997 to March 1998, 16 patients were enrolled (six: stage IIIB; ten: stage IV). All 16 patients were assessable for toxicity and evaluated for response. One complete (6.25%) response and no partial responses were observed. Median survival was 25 weeks (95% CI, 19–30). A median of 3.31 courses per patient was administered, and the median interval between courses was 28 days. The median delivered dose was 664.85 mg/m 2 per week of gemcitabine and 10.71 mg/m 2 per week of vinorelbine, corresponding to a relative dose intensity of 0.73 and 0.85, respectively. Grade 2/3 thrombocytopenia occurred in 13 (24.52%) of 53 courses administered. Neutropenia Grade 2/3 occurred in 14 courses (26.41%). There were seven (13.20%) episodes of fever related to the drug administration. Mild asthenia was observed in six (37.5%) patients. Other toxicities were mild to moderate. Conclusion : These results suggest that this gemcitabine/vinorelbine combination is not an active salvage regimen in patients with refractory NSCLC. The combination merits further evaluation with modified regimens.

In order to check the system aspects of the forward-backward MSGC tracker designed for the future CMS experiment at LHC: 38 trapezoidal MSGC counters assembled in six multi-substrates detector modules were built and exposed to a muon beam at the CERN SPS. Results on the gain uniformity along the wedge-shaped strip pattern and across the detector modules are shown together with measurements of the detection efficiency and the spatial resolution. (C) 1999 Elsevier Science B.V. All rights reserved.

We describe the construction, test and installation procedures, and the experience gained with the operation of a small but complete system of high-rate Micro-Strip Gas Chambers, made on thin borosilicate glass with a diamond-like coating with chromium or gold strips. A set of detectors, fully equipped with read-out electronics and each with an active area of 100 × 100 mm 2 , was exposed during six months to a high-intensity muon beam at CERN with a peak intensity of ∼ 10 4 mm −2 s −1 . Continuous monitoring of the performance of the chambers during the beam runs allowed the evaluation of detection efficiency and the monitoring of accidental rates, as well as the study of ambient induced variations and aging in realistic beam conditions. No significant difference has been found in the operation of under-and over-coated plates. Efficiencies could reach ∼ 98% in best operating conditions, although local lower values were often observed due to missing channels (open strips, broken bonds and dead electronic channels). The long-term operation of the chambers has been more difficult than expected, with the appearance of break-downs and loss of efficiency in some detectors, possibly induced by the presence of small gas leaks, to water permeation or to residual reactivity of the quencher gas (dimethylether).

In 1993 the L3 detector at LEP has been equipped with a Silicon Microstrip Detector (SMD). In this paper we give a full description of the various components of the SMD readout and DAQ system.

The L3 central tracking detector has been in operation since the start-up of LEP (Large Electron Positron collider) in 1989. This detector consists of a Time Expansion Chamber (TEC), a layer of Plastic Scintillating Fibers and a Z-chamber. The TEC gives a high spatial resolution and an excellent multi-track reconstruction capability. The fibers are designed to calibrate the drift velocity with high precision. The Z-Chamber provides TEC with accurate information about the z-coordinates of the tracks. A description of the design and the infrastructure of these three detectors, including the readout and data acquisition system, is given. The performance of the detectors during the 1990 and 1991 LEP running periods is presented.