A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion.

Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on quality of life. We conducted a randomized phase II trial to assess the palliative value of cediranib, an oral vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). After a baseline paracentesis or thoracentesis (on day 0), patients with symptomatic malignant ascites and/or pleural effusion were randomized between immediate treatment with cediranib (Immediate Cediranib) or delayed treatment with cediranib (Delayed Cediranib) on day 29, or after a new puncture was needed. The primary objective of the study was the puncture-free survival, defined as the time from study start (day 1) to the first need for paracentesis or thoracentesis, or time to death, whichever event occurred first. Twelve patients were enrolled. The median puncture-free survival was 45 days (range 10-368) in the Immediate Cediranib patients and 7 days (range 4-13) in the Delayed Cediranib patients (P = 0.011). The change in puncture-free interval (the puncture-free survival after study start minus the puncture-free interval before study start) increased with a median of 31 days in the Immediate Cediranib patients and shortened with a median of 3 days in the Delayed Cediranib patients (P = 0.015). The most common adverse events were fatigue and anorexia. In conclusion, cediranib increased the puncture-free survival and puncture-free interval with an acceptable toxicity profile. This is the first study in which an oral VEGFR TKI showed beneficial palliative effects in patients with malignant effusions.

Comparison of two region of interest definition methods for metabolic response evaluation with [18F]FDG-PET.

AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (DMRglu). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROIfixed thresholds was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROIfixed volumes was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROIfixed volumes is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. RESULTS: In CRC, only ROIfixed volumes based DMRglu showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROIfixed volumes determined DMRglu was an independent predictor for both overall and progression free survival in NSCLC whereas ROIfixed thresholds determined MRglu was not. After dichotomization at the median DMRglu, median survival ratio was higher in ROIfixed volumes than ROIfixed thresholds for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13). CONCLUSION: ROIfixed volumes based DMRglu shows better correlation with survival than DMRglu determined from a ROIfixed thresholds.

Comparison of two region of interest definition methods for metabolic response evaluation with [¹8F]FDG-PET.

AIM: In therapy response monitoring by [¹8F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (ΔMR(glu)). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROI(fixed thresholds) was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROI(fixed volumes) was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROI(fixed volumes) is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. RESULTS: In CRC, only ROI(fixed volumes) based ΔMR(glu) showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROI(fixed volumes) determined ΔMR(glu) was an independent predictor for both overall and progression free survival in NSCLC whereas ROI(fixed thresholds) determined MRglu was not. After dichotomization at the median ΔMR(glu), median survival ratio was higher in ROI(fixed volumes) than ROI(fixed thresholds) for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13). CONCLUSION: ROI(fixed volumes) based ΔMR(glu) shows better correlation with survival than ΔMR(glu) determined from a ROI(fixed thresholds).

Transesophageal endoscopic ultrasound-guided fine-needle aspiration for the mediastinal staging of extrathoracic tumors: a new perspective.

BACKGROUND: Several extrathoracic tumors metastasize to the mediastinum. Mediastinoscopy is the standard method to obtain tissue proof of mediastinal spread, but drawbacks are its invasiveness, requirement for general anesthesia and costs. Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is indicated in lung cancer staging guidelines as a minimally invasive alternative for surgical staging. The diagnostic values in patients with suspected mediastinal metastases and various (previous) extrathoracic malignancies were assessed. PATIENTS AND METHODS: Consecutive patients with suspected mediastinal metastases (on computed tomography or positron emission tomography) and an (previous) extrathoracic malignancy underwent EUS-FNA. RESULTS: Seventy-five patients with current (n = 14) or previously diagnosed (n = 61) extrathoracic malignancies were evaluated. EUS-FNA detected mediastinal malignancies in 43 patients (57%) [metastases of extrathoracic tumors, n = 36 (48%); second malignancy (lung cancer), n = 7 (9%)]. Mediastinal metastases were found at subsequent surgical staging in seven patients or during follow-up (one patient). In seven patients, an alternative diagnosis was established. Sensitivity, specificity, accuracy and negative predictive value of EUS-FNA for mediastinal staging were 86%, 100%, 91% and 72%, respectively. CONCLUSION: EUS-FNA is a minimally invasive mediastinal staging method for patients with extrathoracic malignancies to confirm nodal metastatic spread and therefore may qualify as an alternative for surgical staging.

A rare cause of chylothorax and lymph edema.

Chylothorax is a form of pleural effusion rarely caused by metastasis of solid tumors. Because chylothorax causes complaints by local compression of the lung, as well as weight loss resulting from loss of triglycerides, it needs thorough investigation. We present the case of gastric carcinoma presenting with a chylothorax and unilateral lymph edema. Although rare, the differential diagnosis of chylothorax should include gastric cancer even in the absence of upper abdominal complaints.

Pulmonary hypertension: its diagnosis and management, a multidisciplinary approach.

Pulmonary hypertension is a devastating complication of various, but rare diseases and can also occur as an isolated entity. It causes morbidity and mortality in all patients. Ongoing research has provided some insight into the pathophysiology and clinical manifestations, and new therapeutic options have recently become available for some types of pulmonary hypertension. In order to provide optimal care for an individual patient it is mandatory to establish the type and severity of the pulmonary hypertension in each patient. The diagnostic protocol used in our hospital is presented along with a description of two case histories. An algorithm of the different therapeutic strategies now available is given as well as recommendations for follow-up.

Pleural small cell carcinoma in pre-existent asbestos related pleural disease.

Extrapulmonary small cell carcinoma (SCC) is a very rare disease, and a primary pleural manifestation is extremely rare. A case of SCC of the pleura in a 66-year-old man with pre-existent asbestos-related pleural plaques is presented. This is the first case of pleural SCC in a patient with asbestos-induced pleural disease and the third reported case of a pleural SCC. The SCC developed in an area with pre-existent pleural thickening, underlining the need for careful analysis of alterations in the manifestation of pleural disease in patients with asbestos exposition.