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Provider Volume, Specialty, and Patient OutcomesProvider (i.e., hospital or surgeon) procedure volume for many types of cancer operation is strongly associated with patient outcomes. For many diseases, care rendered by a specialist has been associated with better outcomes. In companion papers, Schrag et al. (p. 163) and Earle et al. (p. 172) used SEER–Medicare data to examine these associations among a population-based cohort of women aged 65 years or older who had surgery for a primary ovarian cancer diagnosed from 1992 through 1999. Schrag et al. found that neither hospital- nor surgeon-specific procedure volume was associated with 60-day mortality following primary ovarian cancer resection but that hospital procedure volume was inversely associated with 2-year mortality. There was no association between 2-year mortality and surgeon procedure volume; neither hospital volume nor surgeon volume was strongly associated with overall survival. The authors conclude that hospital- and surgeon-specific procedure volumes are not strong predictors of survival outcomes among elderly women following surgery for ovarian cancer.
Earle et al. found that patients with stage I or II disease were more likely to undergo lymph node dissection if treated by a gynecologic oncologist than by a general gynecologist or a general surgeon. Patients with stage III or IV disease were more likely to undergo a debulking procedure if the initial surgery was performed by a gynecologic oncologist than by a general gynecologist or a general surgeon and were more likely to receive postoperative chemotherapy when operated on by a gynecologic oncologist or a general gynecologist than by a general surgeon. Patients operated on by gynecologic oncologists or general gynecologists had better survival than patients operated on by general surgeons. The authors conclude that ovarian cancer patients who were treated by gynecologic oncologists had marginally better outcomes than those treated by general gynecologists and clearly superior outcomes compared with patients treated by general surgeons.
In an accompanying editorial, Lipscomb (p. 151) urges that future studies of the volume–outcome relationship build on Schrag et al. and Earle et al. to pursue a more comprehensive understanding of the roles that provider specialty, provider experience level, patient disease status, and other factors play in the choice of treatment strategy—and, ultimately, on outcomes. He also notes the empirical and methodologic challenges posed by such analyses of the determinants of cancer care quality in diverse real-world settings.
STAT1 Promoter Methylation and Squamous Cell Cancer
To determine whether loss of STAT1 expression is associated with squamous cell carcinoma growth, Xi et al. (p. 181) analyzed STAT1 expression in squamous cell carcinoma of the head and neck (SCCHN) tumors and in normal oropharyngeal mucosa, and they assessed STAT1 promoter methylation in SCCHN tumors and paired peripheral blood lymphocytes. They also compared cell death in SCCHN cell lines that were treated with the demethylating agent azacytidine alone and in combination with cisplatin, growth of SCCHN cells that do and do not express STAT1, and growth of xenograft tumors derived from these cells. STAT1 expression was frequently lost in SCCHN tumors with STAT1 promoter methylation. Overexpression of STAT1 reduced the growth of xenograft tumors. Azacytidine-treated SCCHN cells had higher STAT1 expression and were more sensitive to cisplatin than untreated cells. The authors conclude that STAT1 can function as a tumor suppressor in SCCHN.
In an accompanying editorial, Lee and Yu (p. 154) discuss previous studies of the STAT proteins and their different roles in cancer. They note that STAT1 promoter demethylation, as observed by Xi et al., may be important in restoring its tumor suppressor activity.
Akt Activity and Interleukin-12 Efficacy in Neuroblastoma
The antiapoptotic protein Akt may mediate the resistance of human neuroblastoma cells to apoptosis; phosphorylated/activated Akt inhibits the proapoptotic protein Bid. Neuroblastoma has responded to immunotherapeutic approaches in preclinical studies. Khan et al. (p. 190) examined the antitumor efficacy and mechanisms of action of the central immunoregulatory cytokine interleukin-12 (IL-12) in mice bearing neuroblastoma tumors. They found that IL-12 induced complete tumor regression and long-term survival of tumor-bearing mice and profound tumor cell apoptosis in vivo. IL-12 increased the expression of proapoptotic genes and decreased Akt phosphorylation within established TBJ tumors in conjunction with activation and subcellular translocation of Bid. The authors conclude that IL-12 may possess unique therapeutic activity against tumors that express high levels of activated Akt.
Dynamic Monitoring of Oncolytic Adenovirus In Vivo
To develop a noninvasive dynamic monitoring system to detect oncolytic adenovirus replication for application in human chemotherapy, Le et al. (p. 203) designed red fluorescent protein–labeled adenoviruses and used a noninvasive imaging system to detect the labeled virus particles in athymic mice carrying xenograft tumors that were derived from cancer cell lines carrying the labeled virus. Detection of the labeled virus correlated with oncolytic adenovirus replication, and the label had little effect on the replication, encapsidation, cytopathic effect, thermostability, and adenovirus receptor binding of the labeled virus. The authors found that replication efficiency of the adenovirus was variable and that viral replication, spreading, and persistence in the mouse model were similar to observations from preclinical studies and from clinical trials with DNA viruses. They conclude that the labeling is a promising approach for the dynamic assessment of oncolytic function in vivo.
Acute Myeloid Leukemia Following Hodgkin Lymphoma
To determine whether the increased risk of acute myeloid leukemia (AML) after treatment for Hodgkin lymphoma differs with time after and age at Hodgkin lymphoma diagnosis, Schonfeld et al. (p. 215) estimated the excess absolute risk of AML per 10,000 person-years of 1-year Hodgkin lymphoma survivors. Of the 35,511 survivors who were identified from 1970 to 2001 in 14 population-based cancer registries in Nordic countries and in North America, 217 were diagnosed with AML. Excess absolute risk was highest during the first 10 years after Hodgkin lymphoma diagnosis and higher in patients who were diagnosed before age 35 than those diagnosed at 35 years or older. Excess absolute risk declined after 1984; the authors conclude that this reduction may be associated with changes in chemotherapy.
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