The aim of this study is to investigate p16INK4a expression by immunocytochemistry for ascites in advanced ovarian cancer and explore the possibility to predict chemotherapeutic response and prognosis. The immunocytochemical study was performed on cytology of ascites obtained from 37 Stage III or Stage IV ovarian cancer patients with measurable disease before platinum/taxane‐based first‐line chemotherapy following primary cytoreductive surgery or as neoadjuvant chemotherapy. Twenty‐one of 21 (100%) responders and 6 of 16 (44%) nonresponders showed p16INK4a immunopositivity (p < 0.001). Immunopositivity was frequently observed in serous adenocarciomas (17 of 18, 94%). Overall survival was significantly better in immunopositive cases compared with immunonegative cases (p = 0.0006). For subcellular localization, cytoplasm was diffusely positive in immunopositive cases (n = 27), 12 of which showed stronger nuclear immunostaining and demonstrated superior overall survival. In vitro expression of p16INK4a protein was also examined for both parent chemosensitive and acquired chemoresistant ovarian cancer cell lines. Chemosensitive KF28 parent cells showed stronger nuclear staining compared with chemoresistant KFr13Tx cells showing stronger cytoplasmic staining by immunocytochemistry, which were also confirmed by western blotting. Our data suggest that p16INK4a expression in cytology of ascites is a candidate marker in prediction of the primary response to chemotherapy and prognosis. © 2009 UICC
BACKGROUND.Adequate representation of women in research has been deemed essential.METHODS.Cancer research published in 8 journals in 2006 was reviewed. The percentage of women among study participants was compared with the proportion expected from population‐based estimates of sex‐specific cancer incidence, using binomial tests. Differences were assessed in sex distribution of participants by funding source, author sex, and focus of research with the Student t test, and in a linear regression model controlling for cancer type.RESULTS.A total of 1534 cancer research articles were identified, of which 661 (representing 1,096,098 participants) were prospective clinical studies and were analyzed further. For all 7 non‐sex–specific cancer types assessed, the majority of studies analyzed included a lower proportion of women than the proportion of women among patients having cancer of that type in the general population. Among studies focusing on cancer treatment, women constituted a significantly lower overall proportion of the participants in the analyzed studies than expected for 6 of 7 non‐sex–specific cancer types (P < .001). Among non‐sex–specific studies, the mean percentage of participants who were women was 38.8%. Non‐sex–specific studies reporting government funding had a higher percentage of female participants (mean 41.3% vs 36.9%; P = .005). In a regression model controlling for cancer type, lack of government funding (P = .03) and focus on cancer treatment (P = .03) were found to be independent significant predictors of a lower percentage of female participants.CONCLUSIONS.Women were under‐represented as participants in recently published, high‐impact studies of non‐sex–specific cancers. Studies that received government funding included a higher proportion of female subjects. Cancer 2009. © 2009 American Cancer Society.
Purpose Radiation-induced gastric bleeding has been poorly understood. In this study, we describe dosimetric predictors for gastric bleeding after fractionated radiotherapy and compare several predictive models. Materials & Methods The records of 139 sequential patients treated with 3-dimensional conformal radiotherapy (3D-CRT) for intrahepatic malignancies between January 1999 and April 2002 were reviewed. Median follow-up was 7.4 months. Logistic regression and Lyman normal tissue complication probability (NTCP) models for the occurrence of ≥ grade 3 gastric bleed were fit to the data. The principle of maximum likelihood was used to estimate parameters for all models. Results Sixteen of 116 evaluable patients (14%) developed gastric bleeds, at a median time of 4.0 months (mean 6.5 months, range 2.1–28.3 months) following completion of RT. The median and mean of the maximum doses to the stomach were 61 and 63 Gy (range 46 Gy–86 Gy), respectively, after bio-correction to equivalent 2 Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis was most predictive of gastric bleed (AUROC=0.92). Best fit Lyman NTCP model parameters were n =0.10, and m =0.21, with TD50(normal) =56 Gy and TD50(cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD50 value for the cirrhosis patients points out their greater sensitivity. Conclusion This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding, and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.
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