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  • Article: The role of conventional bronchoscopy in the workup of suspicious CT scan screen-detected pulmonary nodules.
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    ABSTRACT: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the cost-effectiveness of a screening program could be enhanced and the potential harms of bronchoscopy avoided. All consecutive participants with a positive result on a CT scan lung cancer screening between April 2004 and December 2008 were enrolled. The diagnostic sensitivity and negative predictive value were calculated at the level of the suspicious nodules. In 95% of the nodules, the gold standard for the outcome of the bronchoscopy was based on surgical resection specimens. A total of 318 suspicious lesions were evaluated by bronchoscopy in 308 participants. The mean ± SD diameter of the nodules was 14.6 ± 8.7 mm, whereas only 2.8% of nodules were > 30 mm in diameter. The sensitivity of bronchoscopy was 13.5% (95% CI, 9.0%-19.6%); the specificity, 100%; the positive predictive value, 100%; and the negative predictive value, 47.6% (95% CI, 41.8%-53.5%). Of all cancers detected, 1% were detected by bronchoscopy only and were retrospectively invisible on both low-dose CT scan and CT scan with IV contrast. Conventional white-light bronchoscopy should not be routinely recommended for patients with positive test results in a lung cancer screening program.
    Chest 02/2012; 142(2):377-84. · 5.25 Impact Factor
  • Article: The role of the ¹⁸f-fluorodeoxyglucose-positron emission tomography scan in the Nederlands Leuvens Longkanker screenings Onderzoek lung cancer screening trial.
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    ABSTRACT: In computed tomography lung cancer screening programs, up to 30% of all resections are futile. To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program. ¹⁸F-Fluorodeoxyglucose-PET scans were made in 220 test positives. Nodules were classified as positive, indeterminate, or negative based on visual comparison with background activity. Gold standard for a positive PET was the presence of cancer in the resection specimen or the detection of cancer during more than 2 years follow-up. Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were calculated at participant level and 95% confidence intervals (CIs) constructed. The sensitivity of PET to detect cancer was 84.2% (95% CI: 77.6-90.7%), the specificity 75.2% (95% CI: 67.1-83.3), the positive predictive value 78.9% (95% CI: 71.8-86.0), and the NPV 81.2% (95% CI: 73.6-88.8). The resection rate for benign disease was 23%, but 26% of them had a diagnosis with clinical consequences. A preoperative PET after an inconclusive nonsurgical workup reduced the resection rate for benign lesions by 11 to 15%, at the expense of missing 12 to 18% lung cancer cases. A preoperative PET after a conclusive nonsurgical workup reduced the resection rate by 78% at the expense of missing 3% lung cancer cases. A preoperative PET scan in participants with an inconclusive nonsurgical workup is not recommended because of the very low NPV, but after a conclusive nonsurgical workup, the resection rate for benign disease can be decreased by 72%.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2011; 6(10):1704-12. · 4.55 Impact Factor
  • Article: A multicenter phase II study of erlotinib and sorafenib in chemotherapy-naive patients with advanced non-small cell lung cancer.
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    ABSTRACT: This multicenter, phase II study evaluates the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, plus sorafenib, a multityrosine kinase inhibitor against vascular endothelial growth factor receptors, in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients with stage IIIB/IV NSCLC received erlotinib (150 mg once a day) and sorafenib (400 mg twice a day) until disease progression or unacceptable toxicity. The primary end point was the rate of nonprogression at 6 weeks. Secondary end points included objective response rate (ORR), time to progression, overall survival, and adverse events. Exploratory end points included pretreatment EGFR and KRAS mutation status, pharmacokinetics, and cytochrome P450 polymorphisms. Fifty patients initiated therapy. The nonprogression rate at 6 weeks was 74%: 12 (24%) partial response and 25 (50%) stable disease. Ultimately, the ORR was 28%. Median time to progression was 5.0 months [95% confidence interval (95% CI), 3.2-6.8 months]. Median overall survival was 10.9 months (95% CI, 3.8-18.1 months). Grade 3/4 adverse events included fatigue (16%), hand-foot skin reaction (16%), rash (16%), diarrhea (14%), and hypophosphatemia (42%). There was one treatment-related fatal pulmonary hemorrhage. Patients with wild-type EGFR had a higher ORR (19%) than previously reported for single-agent erlotinib/sorafenib. Erlotinib levels were lowered. This was associated with CYP3A4 polymorphism and was possibly due to sorafenib. Despite a possible drug interaction, sorafenib plus erlotinib has promising clinical activity in patients with stage IIIB/IV NSCLC and has an acceptable safety profile. Further evaluation of this combination as potential salvage therapy in EGFR mutation-negative patients and the possible drug interaction is warranted.
    Clinical Cancer Research 06/2010; 16(11):3078-87. · 7.74 Impact Factor
  • Article: Sorafenib in patients with advanced non-small cell lung cancer that harbor K-ras mutations: a brief report.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2010; 5(5):719-20. · 4.55 Impact Factor
  • Article: Re: Sarcoid-like reaction to malignancy on whole-body integrated 18F-FDG PET/CT: prevalence and disease pattern.
    Clinical radiology 01/2010; 65(1):94-6; author reply 96-7. · 1.65 Impact Factor

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