International journal of cancer. Journal international du cancer
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Comparative Study
Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing.
Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1-related families. ⋯ We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial.
Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). ⋯ A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.
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Antibody-directed enzyme prodrug therapy (ADEPT) has displayed antitumor activity in animal models and clinical trials. We examined whether antitumor immunity is generated during ADEPT by employing an immunoenzyme composed of the monoclonal antibody (MAb) RH1 conjugated to beta-glucuronidase to target rat AS-30D hepatocellular carcinoma tumors. A glucuronide prodrug of p-hydroxyaniline mustard was used to treat malignant ascites after immunoenzyme localization at the cancer cells. ⋯ Depletion of CD8(+) but not CD4(+) T cells or natural killer (NK) cells reduced the cytolytic activity of peritoneal lymphocytes. ADEPT did not cure tumor-bearing rats depleted of CD4(+) and CD8(+) T cells even though it was curative when given 7 days after tumor transplantation in rats with an intact immune system, indicating that ADEPT can synergize with host immunity to increase therapeutic efficacy. These results have important implications for the clinical application of ADEPT.
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Randomized Controlled Trial Clinical Trial
Short-term sexual function after prostate brachytherapy.
Sexual function was evaluated in 34 patients with low-risk prostate cancer (PSA < or = 10, Gleason score < or = 6, clinical stage T1/T2) undergoing brachytherapy in a phase III prospective randomized trial comparing iodine-125 ((125)I) to palladium-103 ((103)Pd). The mean and median International Index of Erectile Function (IIEF) scores for the entire group were 14.2 and 16.5, respectively, and there was no difference between these scores when stratified by isotope. IIEF scores < 6, 6 to 11, and > or = 12 were recorded in 35% (12/34), 6% (2/34), and 59% (20/34) of patients, respectively. ⋯ All four impotent patients who used sildenafil responded favorably. With a median follow-up of 13 months, 65% of patients undergoing prostate brachytherapy maintained sexual function without pharmacologic support. Including sildenafil responses, 76.5% of patients sustained erections sufficient for sexual intercourse.
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In 1986, the European Organization for Research and Treatment (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. The questionnaire was designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of 5 multiitem scales (physical, role, social, emotional and cognitive functioning) and 9 single items (pain, fatigue, financial impact, appetite loss, nausea/vomiting, diarrhea, constipation, sleep disturbance and quality of life). ⋯ Moreover, the factor analysis results in a 6-factor solution that satisfies the criteria of reproducibility, interpretability and confirmatory setting. Performance status showed an improvement (p < 0.0025) during the studied period. These results support that the QLQ-C30 (version 3.0) has proven to be a reliable and valid measure of the quality of life in Greek cancer patients receiving palliative care treatment.