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Oral anticoagulation should be discontinued after 3 months for a first episode of pulmonary embolism secondary to a major transient/reversible risk factor, nevertheless some caution is needed in patients presenting with high-risk pulmonary embolismhttp://bit.ly/2NIdmQl

Introduction: Patients with advanced lung cancer expierence high physical symptom burden with substantial psychological distress. Early palliative care (EPC) addresses the complex suportive care needs improving QOL and mood. The mechanisms are uncertain. We examined wether coping strategy influences QOL in patients with depressive or anxiety symptoms. Materials and Methods: We conducted a multi-centre cross-sectional study o f patients with advanced lung cancer. 125 patients completed assessments of AOL (QLQ-C15-PAL), depressive and anxiety symptoms (HADS) and coming (brief COPE questionnaire). The data were analyzed by descreptive statistics. To determine whether coping strategy has a moderating effect on the relationship between mood and QOL, the interaction term between mood and coping strategy was added in a multiple regression model. Results: Positive reframing correlates with global QOL (r=.25, p Conclusion: Patients with advanced lung cancer using positive reframing as coping strategy experience higher QOL. Self-blame leads to more insomnia and worse emotional wellbeing. Anxious patients using emotional coping have higher QOL, those using denial have lower QOL. Patients with depressive symptoms using positive refraiming as coping strategy experience higer QOL. Providing skills to cope effectively could impact QOL in these patients.

Bronchopleural fistulas can occur as a rare but severe complication after pulmonary resection. Established guidelines for the proper treatment of patients with bronchopleural fistulas do not exist. Apart from attempts to close the fistula, emphasis is placed on preventive measures, early treatment with antibiotics, drainage of the empyema and aggressive nutritional and rehabilitative support. For inoperable patients, endoscopic procedures are the only therapeutic option. Unfortunately, large (>8 mm) or central bronchopleural fistulas are usually not suitable for such endoscopic management. Recently, some groups have published a few case reports about a novel technique for the endobronchial closure of bronchopleural fistulas, using an Amplatzer device, originally designed for transcatheter closure of cardiac septal defects. We applied the same technique as a life-saving treatment in a ventilated patient who was considered inoperable due to a high oxygen need. The operation was successful. The patient could be weaned from ventilation and was eventually discharged from the hospital to a rehabilitation facility several weeks after the insertion of the device. Until now, endoscopic techniques have only been useful for the treatment of small, peripheral, bronchopleural fistulas and even then only as a bridge to surgery in high-risk surgical patients. In this case report, we demonstrate that the use of an Amplatzer device can expand the importance of endoscopic techniques in the treatment of bronchopleural fistulas. An Amplatzer device, for endobronchial closure, can indeed be administered for large and central bronchopleural fistulas. Moreover, it can be considered as a definite alternative to surgery in inoperable patients.

Erlotinib has been shown to prolong progression-free (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). We report here on effectiveness data on the subsample of 261 patients from 40 centres in Belgium involved in the TRUST study. Median age was 63 years. Most (69.0%) were male and current/former smokers (84.7%); with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (74.3%), stage IV disease (75.1%) and adenocarcinoma by histology (54.0%). Erlotinib was administered mainly as second- (47.1%) or third-line treatment (48.3%). Response rate was 6.5%; disease control rate 58.3%. Median PFS was 2.2 months. Better PS (P = 0.0384), stage IIIB disease (P = 0.0018) and presence of rash (P

This prospective observational study examined the adherence to published European guidelines on erythropoiesis-stimulating agents (ESAs) and the pattern of use and effect of darbepoetin alfa (DA) 500 microg once every 3 weeks (Q3W) for the treatment of chemotherapy-induced anaemia (CIA).A total of 293 patients were included (263 solid tumour, 30 haematologic malignancy). Their mean age was 63 years, 51% were male, 57% had platinum-based chemotherapy. DA was started at a haemoglobin (Hb) level between 9 and 11 g/dL in 82% of patients.In an analysis correcting for transfusions, 55% of patients achievedor =2 g/dL increase in Hb, and a Hb level of11 g/dL was reached in 81%. Transfusion rate was 27%. Most patients (70%) were treated in a Q3W chemotherapy, and planned synchronisation of chemotherapy and Q3W DA could be maintained in 76%.Adherence to European guidelines for DA treatment was good, and Q3W DA treatment was in synchronisation with Q3W chemotherapy in the majority of the patients, thereby reproducing the findings of a recent phase III study.

INTRODUCTION: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor., SCOPUS: ar.j, info:eu-repo/semantics/published

Protected specimen brushing (PSB), combined with quantitative culture, is now recognized as one of the reference methods for diagnosis of nosocomial pneumonia. However, no criteria exist with which to assess the quality of the PSB sample. We studied numbers of inflammatory cells and bronchial cells per microscopic field (magnification: x500, objective x50) in cytospin preparations of PSB samples. Results of cell count and quantitative culture in a first study period were compared with those in a second study period, following adaptation of the PSB technique and collection of samples from more peripheral sites. The cellular content of samples from patients and controls was investigated. We examined 86 samples from patients with suspected nosocomial pneumonia and 15 samples from uninfected controls. The number of samples with a high cellular content was considerably greater in the second study period. No positive cultures were obtained from samples containing10 cells per field. The numbers of cells in samples from uninfected controls were comparable to the numbers in samples from patients. Our results indicate that absence of cells probably represents inadequate sampling. Negative PSB cultures with cytospin preparations containing10 cells per microscopic field should therefore be considered with caution, and resampling considered.

SummaryA patient with malaise, uveitis and a nodular infiltrate in the left lower lobe of the lung is described.An open lung biopsy established the diagnosis of necrotizing sarcoid granulomatosis.The differential diagnosis of necrotizing sarcoid granulomatosis with sarcoidosis and angiocentric granulomatosis (Wegener’s disease) is extensively discussed.Ourcase illustrates that NSG and sarcoidosis could be pathogenetically related.

Erlotinib has been shown to prolong progression-free (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). We report here on effectiveness data on the subsample of 261 patients from 40 centres in Belgium involved in the TRUST study. Median age was 63 years. Most (69.0%) were male and current/former smokers (84.7%); with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (74.3%), stage IV disease (75.1%) and adenocarcinoma by histology (54.0%). Erlotinib was administered mainly as second- (47.1%) or third-line treatment (48.3%). Response rate was 6.5%; disease control rate 58.3%. Median PFS was 2.2 months. Better PS (P = 0.0384), stage IIIB disease (P = 0.0018) and presence of rash (P0.0001) were associated with longer PFS. OS rates at 1, 2 and 3 years were 26.4%, 10.9% and 6.4% respectively. Median OS was 5.9 months. Female gender (P = 0.007), better PS (P0.0001), stage IIIB disease (P = 0.0355) and presence of rash (P0.0001) were associated with longer OS. The findings confirm the therapeutic benefit of erlotinib in a broad range of patients in a sample from a country with a historically high lung cancer morbidity and mortality burden. Several determinants of PFS and OS are identified.

Purpose The objective is to explore changes over time in the information and participation preferences of newly diagnosed stage IIIb/IV non-small-cell lung cancer patients. Methods Patients were recruited by physicians in 13 hospitals and interviewed every 2 months until the fourth and every 4 months until the sixth interview. Results Sixty-seven patients were interviewed three times. Over a period of 4 months from diagnosis, half of patients changed their information preferences for palliative care and end-of-life decisions with a possible or certain life-shortening effect (ELDs, e.g., non-treatment decisions) in both directions, from not wanting to wanting the information, but alsoand as muchfrom wanting to no longer wanting it. The latter were more likely to be in a better physical condition. Preferences for participation in medical decision making also changed: 50% to 78%, depending on the type of decision (general, treatment, transfer or ELD), changed their preference towards wanting more or less participation. Pain seemed to be a trigger for patients wanting more involvement, which contrasts with studies suggesting that patients who are more ill tend to give up more control. Conclusions Doctors should regularly ask their advanced lung cancer patients how much information and participation they want because preferences do change in unexpected ways.

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.

The aim of this study was to investigate the anti-tumour activity of temozolomide in patients with malignant pleural mesothelioma. 27 chemotherapy-naive patients with histologically-proven malignant mesothelioma were treated with temozolomide 200 mg/m(2)/day, given orally on days 1 5 of each 28-day cycle. Therapy continued up to 10 cycles unless disease progression or excessive toxicity mandated discontinuation. Toxicity, symptom improvement and pain intensity were regularly assessed. With a median relative dose intensity of 97%, toxicity was moderate with grade 3 or more nausea, vomiting, thrombocytopenia, leucocytopenia, neutropenia, febrile leucocytopenia, arthralgia, infection and fever with infection occurring in 13, 13, 10, 3, 7 and 3% of patients for the remaining events, respectively. Overall, I objective response was observed (response rate 4%, 95% Confidence Interval (Cl): 0.1-19), Median Survival was 8.2 months. Symptom assessment showed no improvement and an increase of pain was observed during the study. Thus, oral temozolomide is an inactive agent in malignant mesothelioma. (C) 2002 Elsevier Science Ltd. All rights reserved.

Lymphomatoid granulomatosis is a unique form of pulmonary angiitis and granulomatosis characterized histologically by a necrotizing angiocentric and angiodestructive lymphoid infiltrate, which in most cases represents a proliferation of Epstein-Barr virus infected B-cells, with a prominent T-cell reaction. The most common radiographic findings in lymphoma-toid granulomatosis are multiple rounded mass densities, often suggestive of metastatic tumour. We report a case of spontaneous pneumothorax with bronchopleural fistula in a patient suffering from lymphomatoid granulomatosis.

The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m(-2), as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and antihistamines. This regimen was well tolerated, with

Cancer patients receiving chemotherapy are at increased risk of venous thromboembolism (VTE). The presence of cancer and anticoagulant use are risk factors for bleeding, yet data on bleeding risk are limited in these patients. This analysis evaluated the risk of major bleeding in cancer patients receiving chemotherapy using a US claims database. This retrospective cohort study used the MarketScan® databases, a nationwide database containing data from about 100 payers and covering > 30 million patients annually. Adult cancer patients receiving chemotherapy within 6 months of cancer diagnosis between January 2004 and December 2010 were included. Cancers of interest were: lung, colon/rectum, pancreas, bladder, stomach, and ovary. The index date was the first date of chemotherapy. Patients were followed until the earliest of: 1) first diagnosis of major bleeding; 2) termination of enrolment in the health plan; 3) end of study. The primary outcome was the first occurrence of major bleeding, based on selected ICD-9-CM/CPT codes, following chemotherapy initiation. Of 74,575 patients identified, exclusion of those with prior history of bleeding at baseline (∼5%) resulted in 70,822 patients included in the analysis. Mean age was 62 years, 37% were ≥ 65 years, and 52% were male. Average time of follow up and chemotherapy were 14.3 and 8.6 months, respectively; 6% had a history of VTE within 6 months prior to the index date. Major bleeding occurred in 5.8% of patients and the incidence rate for all cancers combined was 4.9 per 100 person-year (PY) and 10.5, 9.3, 6.2, 4.3, 3.6, and 3.3/100 PY for pancreatic, stomach, lung, bladder, colon/rectum, and ovarian cancer, respectively. Approximately 14% of patients (N = 10,456) developed VTE after chemotherapy initiation (> half in the first 3 months of chemotherapy treatment). Of these, 7.8% experienced major bleeding with incidence rates ranging from 5.9-17.7/100 PY after VTE. Major bleeding incidence in cancer patients receiving chemotherapy varies by cancer type with the highest rates in patients with upper gastrointestinal cancer. Compared to the overall cohort, major bleeding risk was higher in cancer patients who developed VTE. Disclosure J.H. Zong: Employee of Sanofi. L. Eckert: Employee of Sanofi. L. Zhang: Employee of Sanofi. W.S. Dai: Employee of Sanofi. A.T. Cohen: Consult: Astellas, AZ, Bayer, BI, BMS, Daiichi, GSK, JJ ResFund: AZ, Bayer, BI, BMS, Daiichi, GSK, JJ BoardSpeakerAdvis comm: Bayer, BI, BMS, Daiichi, GSK, J&J, Mitsubishi, Pfizer, Sanofi. All other authors have declared no conflicts of interest.

Background There is a need for tools to effectively select elderly cancer patients for therapies with significant potential toxicity such as chemotherapy. The Comprehensive Geriatric Assessment (CGA) is recommended by several guidelines to guide the oncologist in treatment decision making. However, because CGA is time and man-power consuming a two-step approach with screening has been recommended. This pilot study was undertaken to evaluate the predictive value of 2 frailty screening tools in relation to the tolerability of chemotherapy in ‘fit’ older cancer patients. Methods Patients over 65 years with various types and stages of cancer were screened for CGA before start of treatment with the Groningen Frailty Indicator (GFI) and the G8 screening tool. ‘Fit’ patients were defined as having a normal screening test. A G8 score of ≤14 corresponds with an abnormal screening test. For the GFI we evaluated 2 cut-off values. Serious adverse events (SAE) were recorded during the first cycle of treatment. Results From October 2009 to December 2011, 85 patients (44 women) were included in the study. The median age was 76 years old (range: 66-88 years). The treatment intent was curative in 39 patients (46%) and palliative in 46 patients (54%). In total, 15 patients (18%) had a SAE of which 3 resulted in death. According to the GFI, 60% were ‘fit’ while the G8 identified 30% as ‘fit’ prior to treatment. The probability to complete the 1e cycle of chemotherapy without a SAE for ‘fit’ patients was according to the G8 and the GFI (cut-off ≥4) respectively 77% (95%CI: 63-89%) and 78% (95%CI: 73-86%). The alternative cut-off ≥3 for the GFI resulted in probability of 85% (95%CI: 73-94%) to tolerate treatment. Conclusion Patients with a normal screening test for CGA are considered to be able to tolerate proposed treatments comparable to younger patients. However, no data exist concerning this assumption. In this study, we attempted to address this in a heterogenic sample of older cancer patients for 2 screening tools. Further research is needed to compare standard of care with this CGA-based approach with screening. Disclosure All authors have declared no conflicts of interest.

Background: Pertuzumab (P), a monoclonal antibody, targets the HER2 receptor and prevents dimerization of HER2 and HER2, HER2 and HER1 or HER2 and HER3. P is active against HER2 overexpressing breast cancer (Baselga et al, ASCO 2007) but has no meaningful single agent activity against non-small-cell lung cancer (NSCLC). Erlotinib (E) inhibits HER1 tyrosine kinase signalling, is active against a number of tumour types and is widely registered for the treatment of relapsed NSCLC. By combining E and P signaling via HER1, HER2 and HER3 are inhibited. Inhibition of multiple HER signaling pathways could prove to be clinically useful. Methods: This is a phase I, dose escalating study. Consenting NSCLC patients (pts) with ECOG performance status of 0 or 1, progression after previous chemotherapy and adequate cardiac reserve (baseline LVEF >55%) were recruited in 2 cohorts. All pts had tumour specimen for evaluating biomarkers potentially associated with response. The 1st cohort received P at the full dose of 840mg iv loading dose with 420mg iv maintenance every 3 weeks plus E at a dose of 100mg orally daily. If the maximum tolerated dose (MTD) was not reached, a 2nd cohort was to be recruited (these pts were to receive the full dose of P plus E at the full dose of 150mg orally daily). Dose limiting toxicity (DLT) was initially defined as any adverse event (AE) > grade 3; an incidence of DLT in 2 out of 6 pts was defined as MTD. Based on experience with the 1st cohort, the protocol was modified to exclude rash as a DLT (rashes encountered were manageable and responded to interruption or reduction of E). Subsequently a 2nd cohort (9 pts) has been recruited. Results: In the 1st cohort tolerability was good, the common AEs being diarrhea in 3 pts (50%) which was generally mild and self-limiting and rash which was reported by all 6 pts (100%). Rash was severe (grade 3) in 3 pts, but responded to either dose reduction of E to 50 mg orally daily or to withdrawal of treatment. In the 2nd cohort, the combination has been well tolerated with no DLTs reported to date. Conclusions: For Phase II evaluation, a full dose of E (150mg orally daily) with full dose of P appears to be suitable.

Broncholithiasis, although recognized in antiquity by Aristotle, was first reported by Petersen in 1885 (1) but has been rarely mentioned in recent medical literature. Advances in technology in recent years, especially the chest CT-scan and fiberoptic bronchoscopy (FOB), have enabled the diagnosis of broncholithiasis to be established before lithoptysis or surgical resection. We will illustrate this with a review of our experience in four recent cases.

A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVC3). They were seen between 1986–1993, at the department of Radiotherapy in Middelheim General Hospital Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). All patients with a small cell carcinoma received chemotherapy as initial treatment, but they didn’t respond, relapsed or became evolutive during treatment. Each treatment was started with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in case of a less good response or with the conventional fractionation of 200 cGy daily in patients with a good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventysix percent of the patients with non-small cell lung carcinoma showed a good relief of their symptoms. It was very unexpected but the major part of NSCLC responded more quickly than SCLC, within 3 days after initiating treatment. In SCLC, 94% of the patients responded and this until death. The palliation index which is defined as the ratio of the symptom free period on the total survival and should be I in ideal circumstances, was 0.60 in case of NSCLC and 0.95 in case of SCLC. In this last group death was mainly due to disease progression in distant sites.

A patient is presented with progressive respiratory failure, caused by pulmonary fat embolism as proved by an open lung biopsy. Four and a half yrs earlier, she underwent a right hip operation. We surmise that a loosening hip prosthesis caused the marrow embolisation.

We report on two patients. The first patient is a 62-year-old female patient who had cholecystectomy in 1970, and in whom two small bile duct stones were removed after endoscopic sphincterotomy in 1987. Within two months of this procedure, she developed three episodes of documented acute pancreatitis. The other patient, a 58-year-old female, developed acute pancreatitis three months after an endoscopic sphincterotomy for stones in the common bile duct. In both patients, ERCP revealed a cicatricial stenosis of the common bile duct and the pancreatic duct. The condition was resolved by repeat sphincterotomy. The first patient needed repeated endoscopic insertion of bilioduodenal endoprostheses and an endoprosthesis in the pancreatic duct. It is interesting to note that, in contrast to surgical reports, very few postpapillotomy stenoses are reported by endoscopists.

7597 Background: Compared to chemotherapy, 1st line treatment with EGFR-TK inhibitors results in superior progression-free survival (PFS) in Asian patients with advanced NSCLC with activating EGFR TK domain mutations. We conducted a prospective study with 1st line erlotinib in Caucasian pts with EGFR TK domain mutations. Methods: Multicentre phase II study. EGFR mutation status was determined in a central lab on macro-dissected biopsies obtained from pts with advanced adenocarcinoma with a non- or past smoking history. Pts were given erlotinib, 150 mg daily till disease progression or prohibitive toxicity. The primary end point of the study was a 70% PFS at 3 months. Results: An EGFR mutation was found in 64 (28%) of 247 pts screened. Eighteen pts did not enter the study because of deterioration, withholding of consent after mutation analysis, or failing other clinical selection criteria. Forty six pts (8 male, 38 female) with median age of 72 years (35-83), median performance status of 1 (1-3) stage dist...

Human epidermal growth factor receptor (HER)2/neu kinase domain mutations are found in approximately 1–4% of lung adenocarcinomas with a similar phenotype to tumors with epidermal growth factor receptor (EGFR) mutations. Afatinib is a potent irreversible ErbB family blocker. We determined the tumor genomic status of the EGFR and HER2 genes in non- or light smokers with lung adenocarcinoma in patients who were entered into an exploratory Phase II study with afatinib. Five patients with a non-smoking history and metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were identified, three of which were evaluable for response. Objective response was observed in all three patients, even after failure of other EGFR- and/or HER2-targeted treatments; the case histories of these patients are described in this report. These findings suggest that afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting treatments have failed.