© Oxford University Press 2006.
IN THIS ISSUE
PSA Velocity and Life-Threatening Prostate CancerProstate-specific antigen (PSA) levels are currently used to screen men for prostate cancer, but a substantial number of men are overdiagnosed—they are treated for cancers that would not have become life-threatening. To determine whether the rate at which PSA levels change over time, or PSA velocity, is useful for screening men for life-threatening prostate cancer, Carter et al. (p. 1521) calculated the PSA velocities of 980 men enrolled in the Baltimore Longitudinal Study of Aging. The authors found that men with a high PSA velocity 10–15 years before their prostate cancer diagnosis had a greater risk of death from prostate cancer 25 years later than men with a low PSA velocity during that period (1,240 vs. 140 per 100,000 person-years). The authors conclude that it may be possible to identify men with life-threatening prostate cancer at a time when it is possible to prevent death from the disease.
In an editorial, Church (p. 1509) suggests that ongoing clinical trials will help to resolve the issues surrounding PSA screening for prostate cancer. He suggests using applied mathematics to develop more accurate tools for prostate cancer screening.
Risk of New CNS Cancers in Childhood Cancer Survivors
Although subsequent primary tumors of the central nervous system (CNS) are known to occur among survivors of childhood leukemia and brain tumors, the risks over time and in relation to patient factors and treatment have not been thoroughly investigated. Neglia et al. (p. 1528) analyzed the occurrence of subsequent primary CNS tumors in a cohort of more than 14,000 5-year survivors of childhood cancer. The authors used data from the Surveillance, Epidemiology, and End Results program to estimate the excess risk of subsequent primary CNS tumors and matched each patient to four cancer-survivor control subjects to investigate the effects of prior radiation and chemotherapy treatment. Children who were treated with radiation had excess risks of glioma and meningioma, and the risks increased with treatment intensity. The excess risk of glioma was highest for children who were treated before age 5. The authors conclude that the developing brain may be especially susceptible to radiation.
In an editorial, Ron (p. 1510) notes that, although improvements in cancer treatment during the past 30 years have increased survival, long-term survivors of childhood cancer have excess risks of developing subsequent cancers. She suggests that the number of secondary cancers may be reduced by identifying patients likely to have long-term treatment effects of treatment and individualizing their care.
Statins, Fibrates, and Risk of Melanoma
Several randomized trials of statins and fibrates for heart disease prevention have reported lower melanoma incidence in persons receiving these medications. In vitro animal models and human case–control studies have suggested that statins and fibrates may reduce the risk of melanoma. To evaluate the relationship between these drugs and melanoma, Freeman et al. (p. 1538) reviewed published and unpublished melanoma incidence data from 36 trials that had randomly assigned participants to receive statins or fibrates versus an alternative therapy for a minimum of 6 months. They found no overall association between the use of statins or fibrates and melanoma incidence. The authors conclude that the most effective way to prevent melanoma remains limiting one's exposure to ultraviolet radiation.
Vesicular Stomatitis Virus and Treatment of Glioma
The multifocal and invasive nature of glioma is a major clinical challenge in treatment of this disease. Vesicular stomatitis virus (VSV) has been shown to have anti-cancer activity in several cancer models, including preclinical models of brain tumors. Lun et al. (p. 1546) investigated the efficacy and safety of a mutant form of VSV with a single–amino acid deletion that enhances the antiviral response of normal cells but not tumor cells. The virus was able to infect and kill all 14 glioma cell lines tested, even lines resistant to a different oncolytic virus, reovirus. Primary human gliomas cultured from surgical specimens were also infected and killed by the virus. When administered intravenously to mice bearing human gliomas, the virus prolonged survival and infected both multifocal gliomas and invasive glioma cells and did not appear to have toxic effects. The ability to infect invasive glioma cells via an intravenous route would be an important advance, although the authors note that clinical trials will be necessary to evaluate efficacy in humans.
EphA2 Agonist, Paclitaxel, and Ovarian Tumor Growth
The EphA2 oncoprotein, a tyrosine kinase receptor, is overexpressed in many cancers, including ovarian cancer, and previous studies have indicated that reducing EphA2 expression may inhibit ovarian tumor growth. To investigate EphA2's role, especially its impact on angiogenesis, Landen et al. (p. 1558) used an EphA2 agonistic antibody, EA5, in several mouse orthotopic ovarian cancer models. Tumor growth was somewhat reduced in mice injected with EA5 antibody, but it was more dramatically reduced by the combination of EA5 and paclitaxel. The combination treatment also increased the survival of the tumor-bearing mice. EA5 treatment of tumors led to decreased vascular endothelial growth factor expression and decreased microvessel density and to increased apoptosis in tumor-associated endothelial cells.
Hormone Receptor Assays and Breast Cancer Prediction
The levels of steroid hormone receptors in breast cancer are currently determined by immunohistochemical assays, but the original research that established the ability of hormone receptor levels to predict patient outcomes used extraction assays. Regan et al. (p. 1571) investigated whether using immunohistochemical assays instead of extraction assays on the same patient tumor specimens would change the conclusions of two clinical trials. The trials, which had compared adjuvant chemoendocrine therapy with endocrine therapy alone among pre- and postmenopausal patients with lymph node–negative breast cancer, had shown that combination therapy was of benefit to pre- and postmenopausal patients with estrogen receptor (ER)–negative tumors but not those with ER-positive tumors. The two assays produced similar estimates of the association between patient outcome and ER status among all patients and between outcome and progesterone receptor (PgR) status among postmenopausal patients. However, among premenopausal patients, PgR status from an immunohistochemical assay could better predict patient outcome than that from extraction assays.
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