Using the Radiosensitivity Index (RSI) to Predict Pelvic Failure in Endometrial Cancer Treated With Adjuvant Radiation Therapy.

PURPOSE: Variability exists in the adjuvant treatment for endometrial cancer (EC) based on surgical pathology and institutional preference. The radiosensitivity index (RSI) is a previously validated multigene expression index that estimates tumor radiosensitivity. We evaluate RSI as a genomic predictor for pelvic failure (PF) in EC patients treated with adjuvant radiation therapy (RT). METHODS AND MATERIALS: Using our institutional tissue biorepository, we identified EC patients treated between January 1999 and April 2011 with primarily endometrioid histology (n = 176; 86%) who received various adjuvant therapies. The RSI 10-gene signature was calculated for each sample using the previously published algorithm. Radiophenotype was determined using the previously identified cutpoint where RSI ≥ 0.375 denotes radioresistance (RR) and RSI < 0.375 describes radiosensitivity. RESULTS: A total of 204 patients were identified, of which 83 (41%) were treated with adjuvant RT. Median follow-up was 38.5 months. All patients underwent hysterectomy with bilateral salpingo-oophorectomy with the majority undergoing lymph node dissection (n = 181; 88%). In patients treated with radiation, RR tumors were more likely to experience PF (3-year pelvic control 84% vs 100%; P = .02) with worse PF-free survival (PFFS) (3-year PFFS 65% vs 89%; P = .04). Furthermore, in the patients who did not receive RT, there was no difference in PF (P = .87) or PFFS (P = .57) between the RR/radiosensitive tumors. On multivariable analysis, factors that continued to predict for PF included the RR phenotype (hazard ratio [HR], 12.2; P = .003), lymph node involvement (HR, 4.4; P = .02), and serosal or adnexal involvement (HR, 5.3; P = .01). CONCLUSIONS: On multivariable analysis, RSI was found to be a significant predictor of PF in patients treated with adjuvant RT. We propose using RSI to predict which patients are at higher risk for failing in the pelvis and may be candidates for treatment escalation in the adjuvant setting.

The seroprevalence of Helicobacter pylori in a referral population of children in the United States.

OBJECTIVES: The purpose of this study was to determine the prevalence of serum antibodies directed against Helicobacter pylori (H. pylori) in children referred to children's hospitals or medical centers throughout the United States. METHODS: This multisite cross-sectional prospective study involved 992 children from 12 states using a validated anti-H. pylori IgG enzyme immunoassay. The children were recruited into two groups: those without any GI complaints (non-GI referral, n = 619) and those who were referred for endoscopy because of abdominal pain (GI referral, n = 373). RESULTS: GI referral children had a higher rate of seropositivity (22.5%) than non-GI referral children (14.1%) from the same geographic regions. In both groups, older children were more likely to be seropositive for H. pylori, as were nonwhite children and those with lower socioeconomic status. H. pylori seropositivity rates were higher in GI referral children with four or more household members (relative risk [RR] = 1.47; CI 1.01-2.14). Multivariate analysis controlling for age, ethnicity, and household income, showed that presence of GI symptoms were associated with a nearly 2-fold risk for H. pylori seropositivity (odds ratio = 1.77, CI 1.27-2.47). Epigastric pain (RR = 2.21; CI = 1.33-3.66) and having three or more episodes of abdominal pain in the last 3 months (RR = 0.59, CI = 0.35-0.99) were the only specific symptoms significantly associated with H. pylori seropositivity. CONCLUSIONS: The H. pylori seropositivity rate of GI referral children with symptoms of abdominal pain was significantly higher. H. pylori infection in early childhood was found to be associated primarily with the child's household size and socioeconomic status.

Evaluation of the effects of strain-specific antigen variation on the accuracy of serologic diagnosis of Helicobacter pylori infection.

It has been suggested that enzyme immunoassay (EIA) kits validated in one region may yield variable diagnostic performance results in different regions, possibly due to strain-specific differences in antibody responses in different populations. We tested (13)C-urea breath test-characterized serum samples from 109 U.S. patients and 288 Japanese patients using enzyme immunoassay with different preparations of high-molecular-weight cell-associated (HM-CAP) antigens that are conserved across Helicobacter pylori strains. Replicate antigens were prepared from five H. pylori clinical isolates. Eight antigen preparations were evaluated: two of U.S. origin and six of Japanese origin. The accuracies achieved with the eight antigen preparations ranged from 94.4 to 96.3% with the U.S. samples. With the Japanese samples the accuracies achieved ranged from 92.3 to 97.2%. Use of a pool of HM-CAP antigens prepared from isolates from Japan resulted in a higher median enzyme immunoassay value and slightly fewer samples with indeterminate results compared to the results obtained by use of the U.S. standard HM-CAP antigen for H. pylori-positive patients (accuracies, 97.2 and 92.3%, respectively), suggesting that variations in performance between both antigen source and patient population might be reduced by using antigens pooled from several strains.