Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor.

BACKGROUND: Initial response of small-cell lung cancer (SCLC) to chemotherapy is high, and recurrences occur frequently, leading to early death. This study investigated the prognostic value of circulating tumor cells (CTCs) in patients with SCLC and whether changes in CTCs can predict response to chemotherapy. Patients and methods In this multicenter prospective study, blood samples for CTC analysis were obtained from 59 patients with SCLC before, after one cycle, and at the end of chemotherapy. CTCs were measured using CellSearch systems. RESULTS: At baseline, lower numbers of CTCs were observed for 21 patients with limited SCLC (median = 6, range 0-220) compared with 38 patients with extensive stage (median = 63, range 0-14,040). Lack of measurable CTCs (27% of patients) was associated with prolonged survival (HR 3.4; P ≤ 0.001). CTCs decreased after one cycle of chemotherapy; this decrease was not associated with tumor response after four cycles of chemotherapy. CTC count after the first cycle of chemotherapy was the strongest predictor for overall survival (HR 5.7; 95% CI 1.7-18.9; P = 0.004). CONCLUSION: Absolute CTCs after one cycle of chemotherapy in patients with SCLC is the strongest predictor for response on chemotherapy and survival. Patients with low initial CTC numbers lived longer than those with higher CTCs.

Prevention of anaemia by early intervention with once weekly epoetin alfa during chemotherapy.

This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb

Multi-centre prospective study on diagnosing subtypes of lung cancer by exhaled-breath analysis.

OBJECTIVES: Lung cancer is a leading cause of mortality. Exhaled-breath analysis of volatile organic compounds (VOC's) might detect lung cancer early in the course of the disease, which may improve outcomes. Subtyping lung cancers could be helpful in further clinical decisions. MATERIALS AND METHODS: In a prospective, multi-centre study, using 10 electronic nose devices, 144 subjects diagnosed with NSCLC and 146 healthy subjects, including subjects considered negative for NSCLC after investigation, breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Also, analyses into subtypes of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), and analyses of patients with small cell lung cancer (SCLC) were performed. RESULTS: Choosing a cut-off point to predominantly rule out cancer resulted for NSCLC in a sensitivity of 94.4%, a specificity of 32.9%, a positive predictive value of 58.1%, a negative predictive value (NPV) of 85.7%, and an area under the curve (AUC) of 0.76. For AC sensitivity, PPV, NPV, and AUC were 81.5%, 56.4%, 79.5%, and 0.74, respectively, while for SCC these numbers were 80.8%, 45.7%, 93.0%, and 0.77, respectively. SCLC could be ruled out with a sensitivity of 88.9% and an NPV of 96.8% with an AUC of 0.86. CONCLUSION: Electronic nose technology with the Aeonose™ can play an important role in rapidly excluding lung cancer due to the high negative predictive value for various, but not all types of lung cancer. Patients showing positive breath tests should still be subjected to further diagnostic testing.

[Problematic cases of mesothelioma reported to the Dutch Institute for Asbestos Victims: evaluation by the Mesothelioma Working Group of the Netherlands Association of Pulmonologists and Specialists in Tuberculosis]. / Problematische mesothelioomcasussen aangemeld bij het Instituut Asbestslachtoffers: beoordeling door de werkgroep Mesotheliomen van de Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose.

OBJECTIVE: To analyse the assessments of problematic cases reported to the Dutch Institute for Asbestos Victims (IAS) by the Mesothelioma Working Party of the Netherlands Association of Pulmonologists and Specialists in Tuberculosis (NVALT). DESIGN: Descriptive. METHOD: The pathological confirmation of a malignant pleural mesothelioma of occupational origin is difficult in about 10% of the cases. The IAS has requested the Mesothelioma Working Party of the NVALT to review these cases. When no definitive diagnosis can be made on histological or cytological grounds, three pulmonologists reach a conclusion on the basis of correspondence, X-ray examination and other information. RESULTS: In the period January 2000--March 2004 the Working Party evaluated 132 cases, two-thirds of whom (n = 89) were assessed to be compatible with 'malignant pleural mesothelioma' and one-third of whom (n = 43) were felt to be non-compatible. In 69% of the cases (91/132) the conclusions of the three independent specialists were unanimous. The median time from request to report was 25 days (range: 1-185). CONCLUSION: This approach was effective and rapid.

Cyfra 21-1 and TPA as markers in malignant mesothelioma.

BACKGROUND: Serum concentrations of CEA and Cyfra were compared in patients with mesothelioma. MATERIALS AND METHODS: Serum levels of patients were analysed for prognosis of survival and follow up of disease. RESULTS: Cyfra 21-1 and TPA have significant prognostic value for survival. CONCLUSION: Assays measuring CK19 fragments seem to be good markers in the management of patients with malignant mesothelioma.

Wedge-shaped applicator for additional light delivery and dosimetry in the diaphragmal sinus during photodynamic therapy for malignant pleural mesothelioma.

In situ light dosimetry during photodynamic therapy (PDT) of malignant pleural mesothelioma (MPM) after tumour resection facilitates the delivery of a controlled light distribution to the inner thoracic surface. Illumination of the diaphragm-induced sinus, however, remains difficult. Our aim was to develop a wedge-shaped light applicator with incorporated light dosimetry to deliver an additional fluence limited to the sinus. The wedge-shaped applicator contains a cylindrical diffuser for light delivery and two isotropic detectors for simultaneous light dosimetry. These detectors were placed at strategic positions where the fluence rate is maximal or minimal (middle and edge). Prior to its clinical use, the performance of the sinus light applicator was tested in several optical tissue phantoms with different optical properties. The fluence rate distribution over the surface of the applicator showed little change when the wedge was submerged in four different optical phantoms. During clinical PDT of MPM the applicator had to be re-located manually four times in order to give an additional fluence of approximately 2 J cm(-2) to the entire sinus. The light applicator enables dosimetry-controlled light delivery for additional illumination of the sinus region that is often under-illuminated during thoracic integral illumination of MPM.

Cervical mediastinoscopy in The Netherlands: past or present? A retrospective analysis of 218 procedures.

BACKGROUND: Cervical mediastinoscopy (CM) has been considered the gold standard for the evaluation of mediastinal lymph nodes in the staging of non-small cell lung cancer (NSCLC) for many years. Recent publications on the value of PET scanning might reduce the use of CM in the near future. The aim of this study was to analyse the data of our CM procedures for their reliability and contribution in the assessment of mediastinal lymph nodes. METHODS: In the period 1995-1999, 219 patients underwent CM. Data were available on 218 procedures and were analysed retrospectively. CM was performed in 162 men and 56 women with a median age of 56 years [range 29 to 80 years]. RESULTS: Median hospitalisation time was three days. There was no mortality and morbidity was 6%. In 96% of procedures representative lymphoid tissue was obtained. In 24%, biopsies contained malignancy. CONCLUSIONS: CM is a relatively safe procedure with a high diagnostic yield. As long as PET scanning remains available at a limited level, CM remains the gold standard in The Netherlands for patients with apparently operable NSCLC.

[Diagnostic examination for causes of exudative pleurisy]. / Diagnostiek naar de oorzaak van exsudatieve pleuritis.

In two patients, men aged 65 and 57 years with complaints of exertional dyspnoea, dry cough, diminished appetite and weight loss, the cause of pleural fluid formation was not discovered despite several diagnostic procedures. In the first patient a diffuse mesothelioma was found at autopsy. The second patient had pleurisy secondary to an adenocarcinoma in the upper lobe of the right lung; he died from lung embolism after the second, diagnostic, thoracoscopy. It can be difficult to establish the diagnosis in patients with a pleural effusion. Specific reasons for this are abundant formation of connective tissue in cases of malignant pleural disease and subsequent risks of sampling errors.

Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma.

UNLABELLED: Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. METHOD: Gemcitabine 1250 mg m(-2) was administered on day 1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5-7 months) with a median survival from registration of 9.6 months (95% CI 8-12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule.