BACKGROUND.: There are limited effective treatment options available and a poor 5‐year survival for patients with inoperable neuroendocrine liver metastases (NETLMs). In this study, the authors prospectively assessed the safety and efficacy of treatment with yttrium 90 (⁹⁰Y) radioactive microspheres for patients with unresectable NETLMs.METHODS.: Radioactive ⁹⁰Y resin microspheres (selective internal radiation [SIR‐Spheres]) were administered through a temporarily placed percutaneous hepatic artery catheter concomitantly with a 7‐day systemic infusion of 5‐fluorouracil to patients with progressive, unresectable NETLMs. Patients were monitored prospectively, and the response to treatment was measured by using cancer markers and tumor size on computed tomography imaging studies.RESULTS.: Thirty‐four patients (22 men) with a mean age 61 years (range, 32‐79 years) who had unresectable NETLMs were treated between December 2003 and December 2005. The mean (±standard error) follow‐up was 35.2 ± 3.2 months. The site of the primary neuroendocrine tumor was the bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in 15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor), glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of unknown origin (2 tumors). Complications after ⁹⁰Y radioembolization included abdominal pain, which was mild to severe; nausea and fever; and lethargy that lasted from 1 week to 1 month. Two patients developed biopsy‐proven radiation gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from liver dysfunction and pneumonia. Subjective changes from recorded baseline hormone symptoms were reported every 3 months. Symptomatic responses were observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at 6 months. Radiologic liver responses were observed in 50% of patients and included 6 (18%) complete responses and 11 (32%) partial responses, and the mean overall survival was 29.4 ± 3.4 months). In patients who had evaluable chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after ⁹⁰Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at 3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in 8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months.CONCLUSIONS.: In this open study of 34 patients, the results demonstrated that radioembolization with ⁹⁰Y resin microspheres can achieve relatively long‐term responses in some patients with nonresectable NETLMs. Cancer 2008. © 2008 American Cancer Society.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination.