Nivolumab and ipilimumab in the real-world setting in patients with mesothelioma.

OBJECTIVES: Nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4) is a new first-line treatment combination for patients with pleural mesothelioma. Nivolumab-ipilimumab improved the survival, however, 30.3% of the patients suffered from grade 3-4 treatment related adverse events (TRAE's) and TRAE's led to discontinuation in 23.0% of all patients. Here, we present the first real-world data of nivolumab plus ipilimumab in patients with malignant mesothelioma treated in two mesothelioma expert centers. METHODS: Clinical data of patients with mesothelioma treated with nivolumab and ipilimumab were prospectively collected. Clinical parameters were obtained every visit, CT scans were evaluated every 12 weeks and adverse events were assessed continuously during the treatment. Data on grade 2-5 TRAE's and activity (overall response rate (ORR), duration of response (DOR), disease control rate (DCR), median progression-free survival (mPFS) and median overall survival (mOS) were reported. RESULTS: Between January 2021 and August 2022, 184 patients were treated with nivolumab plus ipilimumab. The median follow-up was 12.1 months (95 %CI 11.1 - 13.1). Grade 3-4 TRAEs were seen in 27.7 % of the patients and 25.0 % discontinued immunotherapy treatment early because of TRAE's. ORR was 21.7 % (95 % CI 15.7-27.7), median DOR was 5.7 months (IQR 3.2-8.7) and DCR at 12 weeks 56.0 % (95 % CI 48.8-63.2). The mPFS was 5.5 months (95 %CI 4.1-6.9), mOS was 14.1 months (95 % CI 11.1-18.2). CONCLUSIONS: Nivolumab plus ipilimumab had an equal efficacy in a real-world comparable population but also a high risk of TRAE's, leading to discontinuation of treatment in 25% of the patients.

Pilot Study to Predict Pharmacokinetics of a Therapeutic Gemcitabine Dose From a Microdose.

Microdose studies are exploratory trials to determine early drug pharmacokinetics in humans. In this trial we examined whether the pharmacokinetics of gemcitabine at a therapeutic dose could be predicted from the pharmacokinetics of a microdose. In this prospective, open-label microdosing study, a gemcitabine microdose (100 µg) was given intravenously to participants on day 1, followed by a therapeutic dose (1250 mg/m2 ) on day 2. Gemcitabine and its metabolite 2',2'-difluorodeoxyuracil (dFdU) were quantified in plasma and intracellularly by using liquid chromatography-mass spectrometry). Noncompartmental pharmacokinetic analysis was performed. Ten patients participated in this study. The mean area under the plasma concentration-time curve (AUC0-8 ) of gemcitabine after microdosing was 0.00074 h·mg/L and after therapeutic dosing was 16 h·mg/L. The mean AUC0-8 of dFdU following the microdose and therapeutic dose were 0.022 h·mg/L and 169 h·mg/L, respectively. Exposure to gemcitabine after the therapeutic dose was within 2-fold of the exposure following a microdose, when linearly extrapolated to 1250 mg/m2 . However, the shape of the concentration-time curve was different, as reflected by poor scalability in volume of distribution (939 L versus 222 L). Furthermore, intracellularly phosphorylated gemcitabine and phosphorylated dFdU levels could not be predicted from the microdose. The AUC0-8 of gemcitabine at therapeutic dose was accurately predicted by the pharmacokinetics of a microdose, when linearly extrapolated to 1250 mg/m2 . Volume of distribution, elimination rate constant, and intracellular pharmacokinetics of the therapeutic dose could not be predicted from the microdose, which demonstrates limitations of the microdose approach in this case.

Ultra-sensitive LC-MS/MS method for the quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma for a microdose clinical trial.

In microdose clinical trials a maximum of 100 µg of drug substance is administered to participants, in order to determine the pharmacokinetic properties of the agents. Measuring low plasma concentrations after administration of a microdose is challenging and requires the use of ulta-sensitive equipment. Novel liquid chromatography-mass spectrometry (LC-MS/MS) platforms can be used for quantification of low drug plasma levels. Here we describe the development and validation of an LC-MS/MS method for quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in the low picogram per milliliter range to support a microdose trial. The validated assay ranges from 2.5-500 pg/mL for gemcitabine and 250-50,000 pg/mL for dFdU were linear, with a correlation coefficient (r2) of 0.996 or better. Sample preparation with solid phase extraction provided a good and reproducible recovery. All results were within the acceptance criteria of the latest US FDA guidance and EMA guidelines. In addition, the method was successfully applied to measure plasma concentrations of gemcitabine in a patient after administration of a microdose of gemcitabine.

A randomized controlled trial comparing indwelling pleural catheters with talc pleurodesis (NVALT-14).

BACKGROUND: Symptomatic malignant pleural effusion (MPE) occurs frequently in patients with metastatic cancer. The associated prognosis is poor and the success rate of talc pleurodesis (TP) is low. Indwelling pleural catheters (IPCs) are commonly inserted when TP has been unsuccessful. METHODS: We compared talc pleurodesis with the use of an indwelling pleural catheter in patients with recurrent MPE in a multicenter randomized controlled trial (superiority design). The primary endpoint was improvement from baseline in Modified Borg Score (MBS) 6weeks after randomized treatment. Secondary endpoints were hospitalization days, re-interventions, and adverse events. RESULTS: Dyspnea improved significantly (p<0.01) after either treatment, but the magnitude of this improvement did not differ significantly between arms (median 3 and 1 for TP:IPC respectively in rest, p=0.16, (TP 13:IPC 16) and 3 and 1 during exercise, p=0.72 (TP 13:IPC 17)). There was no difference in dyspnea during exercise between TP and IPC at week 6 following treatment, while at rest TP patients (n=13) reported less dyspnea than IPC patients (n=18) (median 0 vs 1, p=0.002). Compared to TP, patients with an IPC had significantly less hospital days during randomized treatment (median: 0 vs 5, p<0.0001), and total hospitalizations for all causes (median: 1.6 vs 1.0, p=0.0035). Fewer IPC patients underwent more than one re-intervention (7/45 vs 15/43, p=0.09). The mean number of re-interventions was lower following IPC (0.21 vs 0.53, p=0.05). Equal number of adverse events occurred. CONCLUSIONS: IPC was not superior in the primary endpoint, improvement of the modified Borg scale (MBS). However, IPC patients had lower hospital stay, fewer admissions and fewer re-interventions. The IPC is an effective treatment modality in patients with symptomatic malignant pleural effusion.

[Financial compensation for asbestosis patients]. / Financiële compensatie voor patiënten met asbestose.

Asbestosis in the Netherlands is a rare work-related form of pulmonary fibrosis caused by long-term, intensive exposure to asbestos. It can have a great impact on patients' quality of life and life expectancy even 20-30 years after initial exposure. The Dutch Institute of Asbestos Victims (IAS) mediates between the victims and their employers or former employers about payment of compensation. Liability procedures against a previous employer are long and stressful. Since 1 April 2014 it has, therefore, been possible to receive financial aid from the state. The IAS and the Netherlands Asbestosis Panel determine who is eligible for this. In this article we look in detail at the conditions for, and the process of, application for this financial aid. Since the introduction of this arrangement, more than 250 asbestosis victims have applied for aid; so far, 65 applicants have met the required conditions.

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†.

BACKGROUND: Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. PATIENTS AND METHODS: In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. RESULTS: Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). CONCLUSION: Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC.

Treatment patterns and survival analysis in 9014 patients with malignant pleural mesothelioma from Belgium, the Netherlands and England.

INTRODUCTION: Pleural mesothelioma has a dismal prognosis and is refractory to local treatment. Combination chemotherapy can increase median survival by several months and was gradually introduced in the period 2003-2006. Elderly patients may be unfit for chemotherapy but little is known about age-related treatment practice. To determine treatment patterns and current survival outcome, three large population-based registries were queried in a uniform manner. METHODS: Data from the Belgian Cancer Registry, the Netherlands Cancer Registry and the UK National Lung Cancer Audit were analyzed for patients diagnosed with pleural mesothelioma since 2007. Treatment patterns and survival rates were compared between countries and age-groups. RESULTS: The study included 900, 2306 and 5808 patients from Belgium, the Netherlands and England, respectively. Fifty-nine percent of patients were 70 years or older and 84% were men. Chemotherapy use decreased with advancing age and was used more often in Belgium (60%) than in the Netherlands (41%) and England (37%). For patients aged 70-79 years, chemotherapy use was 55%, 36% and 34% in the respective countries. Median survival was 10.7 months in Belgium versus 9.2 months for the Netherlands and 9.5 months for England. Survival rates decreased with advancing age. On average, median survival was 5.6 months longer for patients treated with chemotherapy, irrespective of age. CONCLUSIONS: Combined analysis of data from three countries with high mesothelioma rates demonstrates that chemotherapy has become standard treatment for younger patients. Elderly patients currently account for more than half of all cases and less toxic treatment options will be required to improve their prospects.

[Is one single exposure to asbestos life-threatening?]. / Eén keer asbest: levensgevaarlijk?

The media occasionally reports on possible asbestos exposure during demolition of houses in an urban setting. The risk for the development of any asbestos-related cancer in these settings is considered to be lower than for that in occupational exposure. Offermans et al. examined a Dutch cohort of 58,279 workers in the period from 1986 to 2007. They concluded that the risk of lung cancer, laryngeal cancer and mesothelioma increased with exposure to asbestos. The risk of development of lung cancer was higher for anyone with increased years of exposure to asbestos fibre combined with a smoking habit. The study was well conducted, but exact data on fibre concentration and type of asbestos are lacking. We suggest that occasional exposure to asbestos poses hardly any risk for the general population. However, rules and regulations for the removal of asbestos-containing material remain important as asbestos exposure remains a serious health risk, especially in smokers.

Quantitative determination of erlotinib and O-desmethyl erlotinib in human EDTA plasma and lung tumor tissue.

BACKGROUND: To increase knowledge about lung tumor tissue levels of erlotinib and its primary active metabolite, and about erlotinib plasma levels in intercalated dosing schedules, a sensitive and accurate method for determination of erlotinib and O-desmethyl erlotinib (OSI-420) in human plasma and lung tumor tissue has been developed. RESULTS: A method with HPLC-MS/MS was validated over a linear range from 5 to 2500 ng/ml in plasma and from 5.0 to 500 ng/ml for lung tumor tissue homogenate (50-5000 ng/g for lung tumor). Calibration curves in plasma were used to quantify analytes in lung tumor tissue homogenate. Lung tumor tissue of 15 patients has been collected and analyzed with the presented method. CONCLUSION: This method has been successfully validated and applied to determine plasma and lung tumor tissue concentrations of erlotinib and O-desmethyl erlotinib in patients with non-small-cell lung cancer.

Prognosis and prognostic factors of patients with mesothelioma: a population-based study.

BACKGROUND: It is important to regularly update survival estimates of patients with malignant mesothelioma as prognosis may vary according to epidemiologic factors and diagnostic and therapeutic management. METHODS: We assessed overall (baseline) survival as well as related prognostic variables in a large cohort of 1353 patients with a confirmed diagnosis of malignant mesothelioma between 2005 and 2008. RESULTS: About 50% of the patients were 70 years or older at diagnosis and the median latency time since start of asbestos exposure was 49 years. One year after diagnosis, 47% of the patients were alive, 20% after 2 years and 15% after 3 years. Prognostic variables independently associated with worse survival were: older age (HR=1.04 per year 95% CI (1.03-1.06)), sarcomatoid subtype (HR=2.45 95% CI (2.06-2.90)) and non-pleural localisation (HR=1.67 95% CI (1.26-2.22)). CONCLUSION: Survival of patients with malignant mesothelioma is still limited and depends highly on patient age, mesothelioma subtype and localisation. In addition, a substantial part of the patients had a long latency time between asbestos exposure and diagnosis.

Mapping use of radiotherapy for patients with non-small cell lung cancer in the Netherlands between 1997 and 2008.

AIM: After the publication of several reports that the utilisation rate of radiotherapy for patients with non-small cell lung cancer (NSCLC) varies for both medical and non-medical reasons, the utilisation of radiotherapy was studied in four regions in the Netherlands. MATERIALS AND METHODS: Data from 1997-2008 were collected from the population-based cancer registries of four comprehensive cancer centres ('regions'), which represent about half of the Dutch population, resulting in 24 185 non-metastatic patients with NSCLC. Treatment had to be started or planned within 6 months of diagnosis. We evaluated the utilisation of radiotherapy according to age, gender and period for each region. RESULTS: The utilisation of radiotherapy alone decreased over time (from 35 to 19%), whereas the utilisation of radiotherapy in combination with chemotherapy increased (from 5 to 19%). The total utilisation rate remained rather stable at about 40%. The differences between the four regions remained in general no more than 15%. Elderly patients with stage I and II disease had increased odds of receiving radiotherapy (≥75 versus <50 years: odds ratio 2.6, 95% confidence interval 2.0-3.3, whereas this was the opposite for patients with stage III disease: odds ratio 0.5, 95% confidence interval 0.4-0.6). For 17-24% of all patients, especially the elderly, best supportive care was applied. CONCLUSIONS: In the Netherlands, with good accessibility to medical care and well-implemented national guidelines, variation between the four regions is limited for the treatment of non-metastatic NSCLC with radiotherapy.

Gene polymorphisms, pharmacokinetics, and hematological toxicity in advanced non-small-cell lung cancer patients receiving cisplatin/gemcitabine.

BACKGROUND: This study quantified the impact of drug pathway-associated genetic variants on the pharmacokinetics (PK) of gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Thirty-seven patients with advanced NSCLC were sampled for plasma concentrations of gemcitabine, difluoro-deoxy uridine (dFdU), intracellular gemcitabine triphosphates (dFdCTP), and unbound platinum concentrations after gemcitabine 1,250 mg/m(2) i.v. followed by cisplatin 75 mg/m(2). We analyzed 13 germline single nucleotide polymorphisms and one deletion-glutathione S-transferase (GST) M1-within six drug pathway-associated genes (GSTM1, GSTP1, cytidine deaminase (CDA), solute carrier (SLC) 28A1, SLC28A2, and deoxycytidine kinase). PK models were fitted to the data using nonlinear mixed-effects modeling, and genetic data were tested on drug PK and hematological toxicity. RESULTS: Patients carrying the nonsynonymous CDA SNP 79A >C (CDA*2) had a 21% lower gemcitabine clearance as compared to wild-type patients (outcomes and complications.0.0009), but the risk for chemotherapy-associated neutropenia (61% vs. 32%, P = 0.07) and severe neutropenia (17% vs. 5%, P = 0.26) was not significantly higher. Other gene polymorphisms were not associated with drug PK parameters or hematological toxicity. The known functional mutant variant CDA*3 was not found in any of the patients. CONCLUSIONS: Although the mutant CDA*2 allele results in an increased exposure to gemcitabine in Caucasian patients, this study gives no definite conclusion on the clinical relevance of this finding. Further studies should look into the relationship between CDA genotypes, plasmatic CDA activity, and clinical outcome in patients receiving gemcitabine-based chemotherapy.

Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy.

BACKGROUND: The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy. METHODS: Quantitative PCR or immunohistochemistry were used to analyze the expression of ß-tubuline IIA (TUBB2A), ß-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC. RESULTS: Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R=-0.45, p<0.01 for ERCC1; R=-0.40, p=0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R=-0.36, p=0.015) and ABRX (R=-0.46, p=0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR=0.26, log-rank p=0.02). CONCLUSIONS: The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR.

Markers for the non-invasive diagnosis of mesothelioma: a systematic review.

BACKGROUND: Numerous markers have been evaluated to facilitate the non-invasive diagnostic work-up of mesothelioma. The purpose of this study was to conduct a structured review of the diagnostic performance of non-invasive marker tests for the detection of mesothelioma in patients with suspected mesothelioma. METHODS: Studies on the diagnostic accuracy of serum and cytological markers published till 31 December 2009, available in either PUBMED or Embase, to detect or exclude the presence of mesothelioma were extracted. Study quality was assessed with use of the Quadas criteria. RESULTS: In total, 82 articles were included in this systemic review. Overall, quality of the incorporated studies to address our objective was poor. The most frequently studied immunohistochemical markers for cytological analysis were EMA, Ber-Ep4, CEA, and calretinin. The most frequently investigated serum marker was soluble mesothelin-related protein (SMRP). The markers CEA, Ber-EP4, and calretinin were most valuable in discriminating mesothelioma from other malignant diseases. Markers EMA and SMRP were most valuable in discriminating mesothelioma from non-malignant diseases. No marker performed well in discriminating between mesothelioma and all other diseases. CONCLUSION: Currently, there is only limited evidence to properly assess the value of non-invasive marker tests in the diagnosis of mesothelioma. Studies were of limited value to address our objective and results showed considerable unexplained study heterogeneity.

Pleural drainage and pleurodesis: implementation of guidelines in four hospitals.

The aim of the present study was to evaluate the implementation of the 2003 Dutch guideline on the diagnosis and treatment of malignant pleural effusions, and the potential effect of the implementation on the clinical outcome of pleurodesis. All patients with malignant pleural effusion who had a pleural drain placed with the intention of performing pleurodesis were registered prospectively in four centres. Details of the procedure and fluid recurrence and survival data were noted. Patients with a proven malignancy (n = 100) were entered into the registration database. Diagnostic guideline recommendations were followed in 60-70% of the patients. Surprisingly, pleurodesis was performed in only 75% of the patients, mainly due to the presence of a trapped lung. All pleurodeses were performed using talc, according to the guideline. Follow-up revealed fluid recurrence in 27 (36%) patients after a mean follow-up of 17 days (range 2-285 days); 14 patients with successful pleurodesis died with a median survival of 61 days (range 13-174 days). Systemic treatment following pleurodesis and good apposition of the pleural surfaces during drainage were good prognostic factors. Despite reasonable-to-good adherence to the guideline, the number of successful pleurodeses was low. Better predictors of a good pleurodesis outcome are needed.

Non-small cell lung carcinoma of the superior sulcus: favourable outcomes of combined modality treatment in carefully selected patients.

The combination of radiotherapy and concurrent chemotherapy followed by surgery (trimodality treatment) is currently regarded as optimal treatment for non-small cell lung cancer of the superior sulcus (SST) or Pancoast tumour. The possibility to administer intensive combined modality treatment is influenced by tumour stage, comorbidity and performance status of these patients, and therefore a strict patient selection is necessary. This study focuses on patient selection and its results. We retrospectively evaluated choices of treatment and outcome of all patients with SST treated in the Netherlands Cancer Institute from 1994 to 2004. After identification of patients with SST in registration databases, the following characteristics were analyzed: symptoms, comorbidity, tumour stage, treatment characteristics, toxicity, local control, disease-free and overall survival. Fifty-two patients, 37 men and 15 women, were identified. They were diagnosed with stage IIB (27%), stage IIIA (8%), stage IIIB (42%) and stage IV (23%). Twelve patients after induction (chemo)radiotherapy underwent surgical resection. In eight patients a pathologic complete response was found. The 2- and 5-year survival after induction treatment and surgery was 75 and 39%, respectively. Other patients did not receive surgical treatment because of stage IV disease (n=12), comorbidity (n=8), irresectability (extensive tumour growth and/or persisting N2-3 status; n=14) or insufficient response to induction treatment (n=6). Eleven patients were treated with concurrent chemoradiotherapy (5-year survival 20%) and 17 patients with (sequential) radiotherapy and/or chemotherapy (5-year survival 6%). Local recurrence rates were 0% after induction treatment and surgical resection, 32% after concurrent chemoradiotherapy and 72% after (sequential) radiotherapy and/or chemotherapy. In conclusion, only 30% of M0 patients with SST were eligible for combined modality treatment followed by surgery. In this subgroup, concurrent chemoradiotherapy followed by surgery was associated with excellent local control and acceptable survival.

[Chronic indwelling pleural catheter for malignant pleural effusion in 25 patients]. / Ervaringen met een verblijfsdrain in de thorax bij 25 patiënten met pleuritis carcinomatosa.

OBJECTIVE: To describe the experience with an indwelling pleural catheter in patients with pleuritis carcinomatosa. DESIGN: Prospective follow-up study. METHOD: The placement of an indwelling pleural catheter was considered as a treatment possibility for patients who presented with symptomatic accumulation of pleural fluid that returned following previous drainage or pleurodesis or when the fluid had not been drained off previously but there were strong radiological indications for a 'trapped lung'. The intervention was considered to be contraindicated by the following: dyspnoea that had not been reduced by previous pleural punctures performed for relief, dyspnoea caused by many different factors, a tendency for haemorrhaging that could not be corrected. The drain used was a Pleurx indwelling catheter, a thorax drain that is tunnelled subcutaneously, can remain in situ for a long time and offers the patient the opportunity to drain off fluid himself at any desired moment. RESULTS: In the period September 2003-May 2005, the treatment was considered in 40 patients. Ultimately, the catheter was inserted in 25 patients; the clinical deterioration of most of the other patients was too quick. Of the group, 33 patients (82%) died with a median survival of 70 days. All catheters functioned until they were removed or until the patient died. In 3 patients, the drainage procedure was complicated by empyema and in 1 patient by haemoptysis. From the total number of catheters, 9 were removed while the patient was still alive and in 6 patients, spontaneous pleurodesis occurred following 3, 4, 4, 5, 6, and 8 months respectively. In general, the patients were able to handle the catheter without problems and the symptoms were brought and kept adequately under control. CONCLUSION: The Pleurx indwelling pleural catheter was an efficacious treatment supplement for patients with malignant pleural effusion, in whom the standard pleurodesis was not effective.

Occupational asbestos exposure: how to deal with suspected mesothelioma cases--the Dutch approach.

INTRODUCTION: Patients with asbestos-related diseases, such as malignant mesothelioma (MM), are not uniformly treated in Europe when they apply for compensation. In The Netherlands, the Institute of Asbestos Victims (IAV) acts on behalf of patients with a malignant mesothelioma. In the majority of cases, the diagnosis is clear but in some, uncertainty remains. In these cases a specialist opinion of the Mesothelioma Group of the Dutch Thoracic Society (DTS) is required. The process of data handling and final outcome for these patients is discussed and compared with the situation in other European countries. MATERIALS AND METHODS: Dutch patients with a possible malignant mesothelioma and occupational exposure to asbestos presented their cases to the IAV. In 10% of the cases, pathological confirmation of a malignant mesothelioma could not be obtained. These cases were presented to the Mesothelioma Group to obtain a clinical diagnosis based on clinical reports, occupational history, X-ray examination and other factors. Each case was reviewed by three independent pulmonologists experienced in MM. The majority view was binding for acceptance or rejection of the diagnosis. RESULTS: In the period January 2000 until May 2005, the IAV received 1747 cases for compensation. In 161 cases no definitive diagnosis could be made on pathology and were presented to the Mesothelioma Group. Of these cases, 117 (73%) were considered to be compatible with the clinical diagnosis malignant pleural mesothelioma. Forty-four cases (27%) were rejected. In 75% of the cases (112 of 150), the conclusion of the three independent specialists was unanimous; in 11 cases one specialist refrained from a diagnosis. The median time from request to submission of the report was 34 days (range 1-185 days). CONCLUSIONS: Compared with other European countries, this approach, as determined by the IAV and Mesothelioma Group of the DTS, is an effective and rapid way to investigate claims of patients with a possible occupationally related malignant mesothelioma.