A phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in advanced colorectal cancer.

BACKGROUND: This phase 1 clinical trial was conducted to determine the safety, maximum-tolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC). METHODS: Patients with refractory stage IV CRC were treated with bevacizumab 5 mg kg(-1) i.v. every 2 weeks (fixed dose) plus oral cyclophosphamide q.d. and imatinib q.d. or b.i.d. in 28-day cycles with 3+3 dose escalation. Response was assessed every two cycles. Pharmacokinetics of imatinib and cyclophosphamide and circulating tumour, endothelial, and immune cell subsets were measured. RESULTS: Thirty-five patients were enrolled. Maximum-tolerated doses were cyclophosphamide 50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(-1) i.v. every 2 weeks. Dose-limiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities. Imatinib exposure increased insignificantly after adding cyclophosphamide. Seven patients (20%) experienced stable disease for >6 months. Circulating tumour, endothelial, or immune cells were not associated with progression-free survival. CONCLUSION: The combination of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable without significant drug interactions. A subset of patients experienced prolonged stable disease independent of dose level.

Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dose-finding trial with pharmacokinetic and biomarker correlates.

BACKGROUND: Based upon preclinical evidence for improved antitumor activity in combination, this phase I study investigated the maximum-tolerated dose (MTD), safety, activity, pharmacokinetics (PK), and biomarkers of the mammalian target of rapamycin inhibitor, temsirolimus, combined with sorafenib in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with incurable HCC and Child Pugh score ≤B7 were treated with sorafenib plus temsirolimus by 3 + 3 design. The dose-limiting toxicity (DLT) interval was 28 days. The response was assessed every two cycles. PK of temsirolimus was measured in a cohort at MTD. RESULTS: Twenty-five patients were enrolled. The MTD was temsirolimus 10 mg weekly plus sorafenib 200 mg twice daily. Among 18 patients at MTD, DLT included grade 3 hand-foot skin reaction (HFSR) and grade 3 thrombocytopenia. Grade 3 or 4 related adverse events at MTD included hypophosphatemia (33%), infection (22%), thrombocytopenia (17%), HFSR (11%), and fatigue (11%). With sorafenib, temsirolimus clearance was more rapid (P < 0.05). Two patients (8%) had a confirmed partial response (PR); 15 (60%) had stable disease (SD). Alpha-fetoprotein (AFP) declined ≥50% in 60% assessable patients. CONCLUSION: The MTD of sorafenib plus temsirolimus in HCC was lower than in other tumor types. HCC-specific phase I studies are necessary. The observed efficacy warrants further study.

Imaging malignant and apparent malignant transformation of benign gynaecological disease.

Common benign gynaecological diseases, such as leiomyoma, adenomyosis, endometriosis, and mature teratoma, rarely undergo malignant transformation. Benign transformations that may mimic malignancy include benign metastasizing leiomyoma, massive ovarian oedema, decidualization of endometrioma, and rupture of mature teratoma. The aim of this review is to provide a contemporary overview of imaging findings in malignant and apparent malignant transformation of benign gynaecological disease.

Investigating the CT localizer radiograph: acquisition parameters, patient centring and their combined influence on radiation dose.

OBJECTIVE: To systematically investigate the effect of CT localizer radiograph acquisition on the tube current modulation and thus radiation dose of the subsequent diagnostic scan. METHODS: Localizer radiographs of an abdominal section CT phantom were taken, and the resulting volume CT dose index (CTDIvol) for the diagnostic scan was recorded. Variables included tube potential, the phantom's alignment within the CT scanner gantry in both the vertical and horizontal directions and the X-ray source angle at which the localizer was acquired. RESULTS: Diagnostic scan CTDIvol decreased with increasing tube potential. Vertical (table height) movement was found to affect radiation dose more than horizontal movement, with ±50 mm table movement resulting in a standard deviation in the diagnostic scan CTDIvol of 4.4 mGy, compared with 2.5 mGy with ±50 mm horizontal movement. Correspondingly, localizer angles of 90° or 270° (3 o'clock and 9 o'clock X-ray source positions) were less sensitive overall to alignment errors, with a standard deviation of 2.5 mGy, compared with a 0° or 180° angle, which had a standard deviation of 3.8 mGy. CONCLUSION: To achieve a consistently optimized radiation dose, the localizer protocol should be paired with the diagnostic acquisition protocol. A final acquisition angle of 90° should be used when possible to minimize dose variation resulting from alignment errors. ADVANCES IN KNOWLEDGE: Localizer parameters that affect radiation output were identified for this scanner system. The importance of tube potential and acquisition angle was highlighted.

Acute and subacute dual energy CT findings of pulmonary embolism in rabbits: correlation with histopathology.

OBJECTIVE: The purpose of this study was to describe quantitative dual energy CT (DECT) findings and their accuracy in the detection of acute and subacute pulmonary embolism (PE) in rabbits. METHODS: Pulmonary emboli were created in 24 rabbits by gelatin sponge femoral vein injection. Conventional CT pulmonary angiography (CTPA) and DECT were obtained at either 2 h, 1 day, 3 days or 7 days after embolisation (n=6 rabbits for each time point). The location and number of PEs in the different stages were recorded at CTPA and iodine maps from DECT on a per-lobe basis. With histopathology as the reference standard, sensitivity and specificity of CTPA and DECT were calculated. CT and iodine map overlay values of the embolic and non-embolic areas were measured for each scan. RESULTS: With histopathology as the reference standard, the overall sensitivity and specificity of CTPA were 98% and 100% and those of iodine maps were 100% and 95%, respectively. Conventional CT and iodine map values of the embolised and non-embolised areas were significantly different between 2 h and 1 day (p<0.001), but not between 3 days and 7 days (p>0.05). A statistical difference was found for overlay values measured in the embolic and non-embolic regions for four groups. CONCLUSION: Iodine maps derived from DECT show alterations in lung perfusion for acute and subacute PE in an experimental rabbit model and show comparable sensitivity for PE detection and conventional CTPA.

Dual-energy computed tomography in pulmonary embolism.

The introduction of modern dual-energy CT (DECT) scanners has enabled contrast material to be distinguished at imaging without the need for a separate unenhanced scan. Images of pulmonary parenchymal contrast enhancement obtained using DECT improve the detection of defects, augmenting our ability to detect pulmonary emboli; however, with these advances new pitfalls are also introduced. In this pictorial review, we present the technique, clinical applications and causes and remedies of false results of dual-energy pulmonary parenchymal enhancement defects in pulmonary embolism.

Diagnostic evaluation of cystic pancreatic lesions.

BACKGROUND: Cystic pancreatic neoplasms (CPNs) present a unique challenge in preoperative diagnosis. We investigated the accuracy of diagnostic methods for CPN. MATERIAL AND METHODS: This retrospective cases series includes 70 patients who underwent surgery at a university hospital for presumed CPNs between 1997 and 2003, and for whom a definitive diagnosis was established. Variables examined included symptoms, preoperative work-up (including endoscopic retrograde cholangiopancreatography (ERCP) in 22 cases and endoscopic ultrasound (EUS) in 12), and operative and pathological findings. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) scans (n=50 patients; CT=48; MRI=13) were independently reviewed by two blinded GI radiologists. RESULTS: The final histopathologic diagnoses were mucinous cystic neoplasm (n=13), mucinous cystadenocarcinoma (10), serous cystadenoma (11), IPMN (14), simple cyst (3), cystic neuroendocrine tumor (5), pseudocyst (4), and other (10). Overall, 25 of 70 were malignant (37%), 21 premalignant (30%), and 24 benign (34%). The attending surgeon's preoperative diagnosis was correct in 31% of cases, incorrect in 29%, non-specific "cystic tumor" in 27%, and "pseudocyst vs. neoplasm" in 11%. Eight had been previously managed as pseudocysts, and 3 pseudocysts were excised as presumed CPN. In review of the CT and MRI, a multivariate analysis of the morphologic features did not identify predictors of specific pathologic diagnoses. Both radiologists were accurate with their preferred (no. 1) diagnosis in <50% of cases. MRI demonstrated no additional utility beyond CT. CONCLUSIONS: The diagnosis of CPN remains challenging. Cross-sectional imaging methods do not reliably give an accurate preoperative diagnosis. Surgeons should continue to err on the side of resection.

Pyelonephritis mimicking colitis on CT: case report.

We report a patient with acute pyelonephritis in whom the dominant computed tomographic findings were ascending colon and cecal wall thickening and pericolonic fat stranding, likely related to contiguous inflammation from the right kidney. To our knowledge, this is the first report of acute pyelonephritis affecting the right colon mimicking colitis on computed tomography.

Peritoneal coccidioidomycosis: a potential CT mimic of peritoneal malignancy.

Peritoneal involvement is a rare extrapulmonary manifestation of coccidioidomycosis. We report a patient with meningeal coccidioidomycosis who was found to have multiple, globular, peripherally enhancing deposits in the peritoneal cavity at abdominal computed tomography, raising the consideration of peritoneal malignancy. Aspiration biopsy demonstrated peritoneal coccidioidomycosis. The particular computed tomographic findings of peritoneal coccidioidomycosis seen in this patient have not been previously described.