Management of hepatic malignancies is a ubiquitous medical problem. Surgical resection of primary or metastatic liver cancer, with or without adjuvant chemotherapy, is the most effective method for enhancing survival; however, hepatic malignancies in the vast majority of patients are unresectable both at initial manifestation and at recurrence. In these patients, palliative cytoreductive therapies may help to retard tumor progression and therefore favorably alter the course of the disease. Since hepatic neoplasms are principally supplied by the hepatic artery, various arterially delivered cytotoxic agents have been developed to achieve these objectives. Recently, the Food and Drug Administration approved the transarterial administration of yttrium-90 microspheres for liver-directed therapy. Effective use of these devices requires knowledge of the accumulated clinical experience and a dedicated multidisciplinary effort to ensure optimal outcomes and avoid therapy-specific life-threatening complications.

Purpose Trastuzumab resistance has been linked to activation of the phosphoinositol 3-kinase (PI3K) pathway. Phosphatase and tensin homolog (PTEN) is a dual phosphatase that counteracts the PI3K function; PTEN loss leads to activation of the Akt cascade and the downstream mammalian target of rapamycin (mTOR). Preclinical studies demonstrated that mTOR inhibition sensitized the response to trastuzumab in mice with HER2 overexpressing and PTEN-deficient breast xenografts. Our trial evaluated the safety and efficacy of the combination of everolimus and trastuzumab in women with HER2-overexpressing metastatic breast cancer (MBC) that progressed on trastuzumab-based therapy. Patients and Methods This represents a pooled analysis (n = 47), stemming from two trials that occurred concurrently in The University of Texas MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, and Dana-Farber Cancer Institute. Patients with HER2-overexpressing MBC who had progressed on trastuzumab-based therapy received trastuzumab every 3 weeks in combination with daily everolimus. Results Among 47 patients, the combination of everolimus and trastuzumab provided partial responses in seven patients (15%) and persistent stable disease (lasting 6 months or longer) in nine patients (19%), resulting in a clinical benefit rate of 34%. The median progression-free survival (PFS) was 4.1 month. Fatigue, infection, and mucositis were the predominant nonhematologic toxicities. Trastuzumab did not have significant influence on the pharmacokinetic profile of everolimus. Patients with PTEN loss demonstrated decreased overall survival (P = .048). However, PFS was not affected by PTEN loss. Conclusion Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing MBC.

In speech production research using real‐time magnetic resonance imaging (MRI), the analysis of articulatory dynamics is performed retrospectively. A flexible selection of temporal resolution is highly desirable because of natural variations in speech rate and variations in the speed of different articulators. The purpose of the study is to demonstrate a first application of golden‐ratio spiral temporal view order to real‐time speech MRI and investigate its performance by comparison with conventional bit‐reversed temporal view order. Golden‐ratio view order proved to be more effective at capturing the dynamics of rapid tongue tip motion. A method for automated blockwise selection of temporal resolution is presented that enables the synthesis of a single video from multiple temporal resolution videos and potentially facilitates subsequent vocal tract shape analysis. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.

No abstract

No abstract

This study provides evidence that targeting tyrosine kinase receptors such as the vascular endothelial growth factor pathway and the platelet-derived growth factor-beta receptor may have value in the treatment of VHL-related tumors including pheochromocytoma.

No abstract

Peptide receptor radiotherapy (PRRT) with somatostatin analogs has been successfully utilized as a treatment for somatostatin overexpressing tumors for years. Treatment of neuroendocrine tumors (NETs) with the beta particle emitter 177 Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs (GEP-NETs). Despite the success of 177 Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted alpha-emitter therapy with isotopes such as lead-212 ( 212 Pb) has the potential to improve both. Herein, we present the preliminary results of the phase 1 first-in-human dose-escalation trial evaluating 212 Pb-DOTAMTATE in patients with somatostatin receptor positive NETs.Methods: A total of 20 subjects with histologically confirmed NETs, prior positive somatostatin analogue scans, and no prior history of 177 Lu/ 90 Y/ 111 In PRRT, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of 212 Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose (RP2D) regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 µCi/kg) of 212 Pb-DOTAMTATE administrated at 8-week intervals, intravenously.Results: Ten subjects received the highest dose of 2.50 MBq/kg/cycle (67.6 µCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events (TEAEs) being nausea, fatigue, and alopecia.No serious TEAEs were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiological response (ORR) of 80% was observed for the first 10 subjects treated at the RP2D. Conclusion:Targeted alpha therapy with 212 Pb-DOTAMTATE has been shown to be well-tolerated.Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, it would provide a substantial benefit over currently FDA approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.