Extracranial Venous abnormalities: A true pathological finding in patients with multiple sclerosis or an anatomical variant?

OBJECTIVE: To evaluate the extracranial venous anatomy with contrast-enhanced MR venogram (CE-MRV) in patients without multiple sclerosis (MS), and assess the prevalence of various venous anomalies such as asymmetry and stenosis in this population. MATERIALS AND METHODS: We prospectively recruited 100 patients without MS, aged 18-60 years, referred for contrast-enhanced MRI. They underwent additional CE-MRV from skull base to mediastinum on a 3T scanner. Exclusion criteria included prior neck radiation, neck surgery, neck/mediastinal masses or significant cardiac or pulmonary disease. Two neuroradiologists independently evaluated the studies to document asymmetry and stenosis in the jugular veins and prominence of collateral veins. RESULTS: Asymmetry of internal jugular veins (IJVs) was found in 75 % of subjects. Both observers found stenosis in the IJVs with fair agreement. Most stenoses were located in the upper IJV segments. Asymmetrical vertebral veins and prominence of extracranial collateral veins, in particular the external jugular veins, was not uncommon. CONCLUSION: It is common to have stenoses and asymmetry of the IJVs as well as prominence of the collateral veins of the neck in patients without MS. These findings are in contrast to prior reports suggesting collateral venous drainage is rare except in MS patients. KEY POINTS: • The venous anatomy of the neck in patients without MS demonstrates multiple variants • Asymmetry and stenoses of the internal jugular veins are common • Collateral neck veins are not uncommon in patients without MS • These findings do not support the theory of chronic cerebrospinal venous insufficiency • MR venography is a useful imaging modality for assessing venous anatomy.

Phase 1 Evaluation of [(64)Cu]DOTA-Patritumab to Assess Dosimetry, Apparent Receptor Occupancy, and Safety in Subjects with Advanced Solid Tumors.

PURPOSE: The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [(64)Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors. PROCEDURES: Dosimetry subjects (n = 5) received [(64)Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n = 3 out of 6) received [(64)Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy. RESULTS: The tumor SUVmax (± SD) was 5.6 ± 4.5, 3.3 ± 1.7, and 3.0 ± 1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044 ± 0.008 mSv/MBq and 0.46 ± 0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00 ± 0.32 at baseline to 0.57 ± 0.17 after stable patritumab, corresponding to a RO of 42.1 ± 3. CONCLUSIONS: [(64)Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

A phase I study of pegylated liposomal doxorubicin and temsirolimus in patients with refractory solid malignancies.

This study aimed to determine the maximum-tolerated dose and dose-limiting toxicities of pegylated liposomal doxorubicin (PLD) in combination with temsirolimus (T) in patients with refractory solid tumors. Using a standard "3+3" dose escalation design, 23 patients were enrolled in three dosing cohorts in this phase I study. The starting dose level was PLD at 30 mg/m(2) every 4 weeks and T at 20 mg weekly. Pharmacokinetics (PK) of doxorubicin were evaluated for patients in the expansion cohort. The most common treatment-related adverse events of all grades were mucositis/stomatitis (69.6%), anorexia (52.2%), thrombocytopenia (52.2%), and fatigue (47.8%). The recommended doses of this combination for phase II studies are 25 mg/m(2) PLD and 25 mg T. PK analyses suggested increased exposure of doxorubicin in this combination regimen compared to doxorubicin administered as a single agent, possibly due to PK drug interactions. Out of 18 patients evaluable for a treatment response, two had partial responses (PR) (breast cancer and hepatocellular carcinoma) and six had stable disease (SD). Two patients remained on treatment for more than 1 year. The combination of PLD and T is tolerable, and the treatment resulted in clinical benefit. The combination regimen should be further explored in appropriate tumor types.