Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine followed by weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC. METHODS: Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m(2). RESULTS: In total, 46 patients were included. Median age was 59.6 years (range 41.3-74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin-gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin-gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin-gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin-gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity. CONCLUSION: Sequential chemotherapy with carboplatin-gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.

Favorable outcome of chronic disseminated candidiasis in four pediatric patients with hematological malignancies.

Four children were diagnosed with chronic disseminated candidiasis (CDC) during treatment for hematological malignancies. All presented with persistent fever, not responsive to broad-spectrum antibiotics, abdominal distension and hepatosplenomegaly. Two children needed artificial ventilation because of respiratory insufficiency. The time between onset of neutropenic fever and diagnosis of CDC ranged from 20-49 days. Ultrasound and computed tomography failed to demonstrate CDC during the neutropenic phase. All children needed a liver or spleen biopsy to establish the diagnosis of CDC. Three of four patients continued chemotherapy during treatment for the fungal infection. All patients had a favorable outcome, both in terms of the invasive Candida infections, as well as their underlying malignancies.

Extravascular lung water index measurement in critically ill children does not correlate with a chest x-ray score of pulmonary edema.

INTRODUCTION: Extravascular lung water index (EVLWI) can be measured at the bedside using the transpulmonary thermodilution technique (TPTD). The goal of this study was to compare EVLWI values with a chest x-ray score of pulmonary edema and markers of oxygenation in critically ill children. METHODS: This was a prospective observational study in a pediatric intensive care unit of a university hospital. We included 27 critically ill children with an indication for advanced invasive hemodynamic monitoring. No specific interventions for the purpose of the study were carried out. Measurements included EVLWI and other relevant hemodynamic variables. Blood gas analysis, ventilator parameters, chest x-ray and TPTD measurements were obtained within a three-hour time frame. Two radiologists assessed the chest x-ray and determined a score for pulmonary edema. RESULTS: A total of 103 measurements from 24 patients were eligible for final analysis. Mean age was two years (range: two months to eight years). Median cardiac index was 4.00 (range: 1.65 to 10.85) l/min/m2. Median EVLWI was 16 (range: 6 to 31) ml/kg. The weighted kappa between the chest x-ray scores of the two radiologists was 0.53. There was no significant correlation between EVLWI or chest x-ray score and the number of ventilator days, severity of illness or markers of oxygenation. There was no correlation between EVLWI and the chest x-ray score. EVLWI was significantly correlated with age and length (r2 of 0.47 and 0.67 respectively). CONCLUSIONS: The extravascular lung water index in critically ill children does not correlate with a chest x-ray score of pulmonary edema, nor with markers of oxygenation.

Undertreatment of tracheal carcinoma: multidisciplinary audit of epidemiologic data.

National epidemiologic data were examined to determine the eligibility for curative therapy in tracheal carcinoma. An expert audit of primary tracheal carcinomas registered from 2000 to 2005 with the Netherlands Cancer Registry (NCR) included blinded patient data and radiographic review to assess diagnosis and resectability. Actual treatment was compared with the opinions of a multidisciplinary panel (Radboud panel) and a second reviewer. Of 101 NCR-registered primary tracheal carcinomas, the Radboud panel diagnosis was metastatic disease or local extension of adjacent tumors in 34. Seventeen cases were excluded for missing data. In 50 cases confirmed by panel and a second reviewer, actual treatment consisted of surgery in 12 (24%), radiotherapy in 29 (58%), endobronchial treatment in 6 (12%), and observation in 3 (6%). Both panel and second reviewer identified 16 additional surgical candidates, a total of 28 (56%) of 50. Treatment recommendations of panel and second reviewer disagreed in four cases (8%). One-third of NCR-registered primary tracheal carcinomas were misclassified nontracheal primary tumors involving the trachea. A majority of cases meeting audit criteria for diagnosis and surgical resection was treated with other modalities. Interreviewer disagreement was small. The audit of a national cancer registry suggests that incorrect diagnosis and undertreatment are common in rare airway tumors.

Disseminated aspergillosis in an adolescent with acute lymphoblastic leukemia.

Disseminated aspergillosis in immunocompromised patients has a mortality rate of almost 100%. Despite the development of new antifungal agents, the outcome of disseminated aspergillosis has only improved slightly, particular in patients with central nervous system (CNS) involvement. The use of combination antifungal therapy might improve the dismal outcome of disseminated aspergillosis. We describe a critically ill adolescent with acute lymphoblastic leukemia who was successfully treated with voriconazole and caspofungin for disseminated aspergillosis with involvement of the lung, brain and thyroid gland.

Variability in the description of morphologic and contrast enhancement characteristics of breast lesions on magnetic resonance imaging.

RATIONALE AND OBJECTIVE: The objective of this study was to evaluate the interobserver variability in reporting descriptive kinetic and morphologic enhancement features at breast magnetic resonance imaging. MATERIALS AND METHODS: Four observers evaluated 103 lesions, 49 malignant and 54 benign, proven by histopathology. They used standardized terminology with the following characteristics: "early enhancement kinetics" and "late enhancement kinetics" in curves from both reader-determined and preset regions of interest (ROIs), "enhancement pattern," "shape," "margin," "internal enhancement," and a final assessment score. Agreement was calculated using the kappa statistic. Differences in agreement were calculated using Fisher exact test. RESULTS: kappa was 0.27 for both early and late enhancement; preset ROIs improved kappa to 0.47 and 0.67, respectively (odds ratios, 1.7 and 4.5). kappa was 0.45 for pattern, 0.42 for shape, 0.26 for margin, 0.25 for internal enhancement, and 0.28 for final assessment. CONCLUSIONS: There was considerable variability in the use of most generally accepted terms. The preparation of ROIs was a major source of variability in the interpretation of enhancement curves.

The role of MRI in invasive lobular carcinoma.

PURPOSE: To determine the value of MR imaging in the detection and measurement of tumor size in patients with invasive lobular carcinoma (ILC) compared to mammography and ultrasound. MATERIALS AND METHODS: From 36 cases of ILC in 34 patients who were surgically treated, the pre-operative imaging measurements, being mammography, ultrasound and contrast enhanced MR, were retrospectively re-evaluated for tumor detection and size. Findings were compared with pathology. Two radiologists were used for evaluation of the mammograms, the other imaging modalities were only evaluated by one radiologist. The Pearsons correlation test was used to determine the correlation between histopathological and imaging measurements for each imaging modality. RESULTS: For mammography, ultrasound and MRI the false negative scores were respectively 14%, 3% and 0%. The percentage for underestimated, correctly estimated and overestimated measurements on imaging were 56%, 33% and 11% for radiologist 1 and 50%, 33% and 17% for radiologist 2 on mammography. For ultrasound and MRI these percentages were respectively 53%, 47%, 0% and 14%, 75%, 11%. The correlation coefficients for mammography were respectively r = 0.34 (p < 0.05) and r = 0.27 (p > 0.05) for both radiologists, for Ultrasound r = 0.24 (p > 0.05) and for MRI r = 0.81 (p < 0.01). CONCLUSION: Of the three imaging modalities contrast enhanced MR has the lowest false negative rate in detecting ILC and has the highest accuracy in measuring the size of the ILC. MR could play a key role in the pre-operative work-up for accurate tumor size determination.