Noncontrast perfusion single-photon emission CT/CT scanning: a new test for the expedited, high-accuracy diagnosis of acute pulmonary embolism.

BACKGROUND: Standard ventilation and perfusion (V˙/Q˙) scintigraphy uses planar images for the diagnosis of pulmonary embolism (PE). To evaluate whether tomographic imaging improves the diagnostic accuracy of the procedure, we compared noncontrast perfusion single-photon emission CT (Q˙-SPECT)/CT scans with planar V˙/Q˙scans in patients at high risk for PE. METHODS: Between 2006 and 2010, most patients referred for diagnosis of PE underwent both Q˙-SPECT/CT scan and planar V˙/Q˙scintigraphy. All scans were reviewed retrospectively by four observers; planar scans were read with modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II and Prospective Investigative Study of Pulmonary Embolism Diagnosis (PISA-PED) criteria. On Q˙-SPECT/CT scan, any wedge-shaped peripheral perfusion defect occupying > 50% of a segment without corresponding pulmonary parenchymal or pleural disease was considered to show PE. The final diagnosis was established with a composite reference standard that included ECG, ultrasound of lower-extremity veins, D-dimer levels, CT pulmonary angiography (when available), and clinical follow-up for at least 3 months. RESULTS: One hundred six patients with cancer and mean Wells score of 4.4 had sufficient follow-up; 22 patients were given a final diagnosis of PE, and 84 patients were given a final diagnosis of no PE. According to PIOPED II, 13 studies were graded as intermediate probability. Sensitivity and specificity for PE were 50% and 98%, respectively, based on PIOPED II criteria; 86% and 93%, respectively, based on PISA-PED criteria; and 91% and 94%, respectively, based on Q˙-SPECT/CT scan. Seventy-six patients had additional relevant findings on the CT image of the Q˙-SPECT/CT scan. CONCLUSIONS: Noncontrast Q˙-SPECT/CT imaging has a higher accuracy than planar V˙/Q˙imaging based on PIOPED II criteria in patients with cancer and a high risk for PE.

Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer: a phase I study.

PURPOSE: Folate receptor α expression is highly restricted in normal adult tissues but upregulated in a wide range of human cancer types, including epithelial ovarian cancer. Farletuzumab, a humanized monoclonal antibody against folate receptor α, has shown antitumor activity and favorable toxicity in preclinical evaluation. This phase I, dose-escalation study was conducted to determine the safety of weekly i.v. farletuzumab and establish the maximum tolerated dose (MTD). EXPERIMENTAL DESIGN: Patients with platinum-refractory or platinum-resistant epithelial ovarian cancer received farletuzumab (12.5-400 mg/m(2)) on days 1, 8, 15, and 22 of a 5-week cycle. Intrapatient dose escalation was not permitted. Dose-limiting toxicity (DLT) was defined by treatment-related adverse event of grade 3 or higher, and the MTD was the highest dose at which one or none of six patients experienced a DLT. Disease progression was recorded using Response Evaluation Criteria in Solid Tumors criteria and serum CA-125. RESULTS: Twenty-five heavily pretreated patients were included in the safety, efficacy, and pharmacokinetic analyses. No DLTs or MTDs were encountered, and dose escalation was continued to farletuzumab 400 mg/m(2). C(max) and AUC(0-24) (area under the serum concentration-time curve) increased in an approximately dose-proportional manner, and a nuclear imaging substudy confirmed tumor targeting. There were no objective responses. Stable disease by Response Evaluation Criteria in Solid Tumors was observed in nine (36%) patients and CA-125 reduction in four. Three patients received continued therapy and completed a total of up to three cycles. CONCLUSIONS: In this phase I study, farletuzumab administered as an i.v. infusion at doses of 12.5 to 400 mg/m(2) was generally safe and well tolerated in the management of heavily pretreated patients with epithelial ovarian cancer.

Arterial desaturation syndrome following pleurodesis with talc slurry: incidence, clinical features, and outcome.

The objectives were to define the incidence, risk factors, clinical features and outcome of arterial desaturation syndrome following talc pleurodesis in patients with malignant pleural effusions. This retrospective, observational study took place at a tertiary care cancer center in New York. All patients were those with malignancy who underwent pleurodesis with talc in 1998 at Memorial Sloan Kettering Cancer Center. Characteristics of patients are described by using summary statistics. Differences between groups were assessed with the Fisher's exact statistic for categorical variables and Student's t-test for continuous variables. Among patients who were considered to have arterial desaturation syndrome, we evaluated the relation of SaO2/FIO2 pre- and post-talc installation using a paired Student's t-test. During 1998, 120 patients underwent pleurodesis with talc, and 8 (7%) developed arterial desaturation following the procedure. Symptoms included chest pain, dyspnea, fever, and increased need for oxygen supplementation developed typically within 1 day. Three of the eight patients in this series required mechanical ventilation, but all recovered uneventfully after treatment, which included high-dose corticosteroids. Patients with breast and ovarian cancer appeared to be at increased risk for this complication compared to those patients with other types of cancer (p = 0.01). Approximately 7% of patients who have undergone sclerosis with talc for a malignant pleural effusion will develop arterial desaturation with clinically significant hypoxia requiring supplemental oxygen following the procedure. It appears that most patients recover from this complication and that those with breast and ovarian cancer may be at higher risk.

Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine.

Chemotherapy that targets microtubular trafficking induces responses in most patients with prostate cancer. One regimen under investigation is the combination of docetaxel and estramustine. We report on 2 patients with androgen-independent disease who received continuous weekly docetaxel and estramustine and who died of irreversible respiratory failure. The clinical, pathologic, and radiographic data support drug toxicity as the likely etiology. Inclusive of these patients, only 17 cases (10 fatal) of acute pulmonary toxicity using docetaxel have been reported, despite its wide use. We recommend that patients receiving weekly docetaxel, with or without estramustine, have frequent treatment breaks and be evaluated with computed tomography of the chest every 8 weeks.