Phase III randomised chemoprevention study of Selenium on the recurrence of non-invasive bladder cancer. The SELEnium and BLAdder cancer Trial (SELEBLAT)
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SUBMITTER: Goossens M
PROVIDER: S-EPMC4582342 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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Project description:In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 ?g/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.This is the first report on a selenium randomized trial in bladder cancer patients.ClinicalTrials.gov identifier: NCT00729287.
| S-EPMC3352119 | biostudies-literature
Project description:Although non muscle-invasive bladder cancer can be treated successfully by surgical resection, there is a high rate of recurrence, which frequently develops into an invasive form of cancer. Due to the lack of marker molecules to predict recurrence, it is currently recommended that after resection each patient is screened via cystoscopy at least twice a year. This results in a psychic burden to the patient and substantial economic costs to the health care system. Using antibody microarrays targeting 724 different cancer-related proteins, we studied protein profiles of patients with and without recurrence. The analysis revealed 255 proteins of differential abundance. Most are involved in the regulation and execution of apoptosis and cell proliferation. For prognosis, a signature of 20 proteins was determined that predicts bladder cancer recurrence with 100% sensitivity and 80% specificity. As a measure of overall accuracy, the area under the curve (AUC) value was found to be 90%. This is well within a clinically relevant window of quality and should support decision making about the stringency of surveillance or even different treatment options.
2014-04-07 | E-MEXP-3625 | biostudies-arrayexpress
Project description:ImportanceSelenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.ObjectiveTo determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.Design, setting, and participantsThis multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required.InterventionsOral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo.Main outcome and measuresRecurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022).ResultsThe study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment.Conclusions and relevanceIn this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required.Trial registrationisrctn.org Identifier: ISRCTN13889738.
| S-EPMC10582794 | biostudies-literature
Project description:PurposeSelenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation.Patients and methodsPatients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence.ResultsThe first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected.ConclusionSelenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.
| S-EPMC3821010 | biostudies-literature
Project description:Bladder cancer (BC) is the 10th most common cancer globally and has a high mortality rate if not detected early and treated promptly. Non-muscle-invasive BC (NMIBC) is a subclassification of BC associated with high rates of recurrence and progression. Current tools for predicting recurrence and progression on NMIBC use scoring systems based on clinical and histopathological markers. These exclude other potentially useful biomarkers which could provide a more accurate personalized risk assessment. Future trends are likely to use artificial intelligence (AI) to enhance the prediction of recurrence in patients with NMIBC and decrease the use of standard clinical protocols such as cystoscopy and cytology. Here, we provide a comprehensive survey of the most recent studies from the last decade (N = 70 studies), focused on the prediction of patient outcomes in NMIBC, particularly recurrence, using biomarkers such as radiomics, histopathology, clinical, and genomics. The value of individual and combined biomarkers is discussed in detail with the goal of identifying future trends that will lead to the personalized management of NMIBC.
| S-EPMC9599984 | biostudies-literature
Project description:Next-generation sequencing (NGS) is widely used in muscle-invasive bladder cancer but has limited use in non-muscle-invasive bladder cancer (NMIBC) due to significant heterogeneity and high cancer-specific survival. Therefore, we evaluated the genomic information of NMIBC and identified molecular alterations associated with tumour recurrence. A total of 43 patients with NMIBC who underwent transurethral resection of the bladder were enrolled. We performed NGS using an Oncomine panel of tumour specimens and blood samples corresponding to each specimen. The somatic mutation results were analysed by pairwise comparison and logistic regression according to the recurrence of bladder tumours within 1 year. The median incidence of genetic variations in 43 tumour samples was 56 variations per sample, and a high tumour mutation burden (TMB) was associated with tumour recurrence (median variation 33 vs. 64, p = 0.023). The most mutated gene was adipose tissue macrophages (ATM) (79%), followed by neurofibromatosis-1 (NF1) (79%), and neurogenic locus notch homolog protein 1 (NOTCH1) (79%). In multivariable analysis, mutation of epidermal growth factor receptor (EGFR) (odds ratio [OR], 9.95; 95% confidence interval [CI], 1.40-70.96; p = 0.022) and telomerase reverse transcriptase (TERT) (OR, 7.92; 95% CI, 1.22-51.51; p = 0.030) were significant factors associated with the recurrence of bladder tumour within 1 year. Our results revealed that high TMB, EGFR mutation, and TERT mutation had a significant association with tumour recurrence in NMIBC. In addition, somatic mutations in EGFR and TERT could be useful prognostic biomarkers in NMIBC.
| S-EPMC10606398 | biostudies-literature
Project description:Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.
| S-EPMC8114939 | biostudies-literature
Project description:IntroductionDistant recurrence of non-muscle invasive bladder cancer is a rare condition that is poorly understood and difficult to detect in follow-up protocols.Case presentationA 73-year-old female with a history of T1N0M0 bladder cancer 8 years ago suffered from a left axillary tumor, a left lung tumor, left mediastinal lymph node swelling, and bilateral adrenal gland tumors. Initially, she was diagnosed with metastatic left breast cancer of the left accessory mamma by needle biopsy of an axillary tumor. Subsequent bronchoscopic biopsy of the mediastinal lymph node revealed metastatic urothelial carcinoma, although no recurrence was detected in the urinary tract. She underwent systemic therapy, and all regions shrank without reprogression.ConclusionNon-muscle invasive bladder cancer should be managed considering distant metastasis. If the origin of the metastatic lesions is unknown, this disease should be considered as a possible origin, even in the absence of urinary tract recurrence.
| S-EPMC11531879 | biostudies-literature
Project description:We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.
| S-EPMC11327297 | biostudies-literature
Project description:PurposeDespite positive responses in phase II clinical trials, the bioreductive prodrug apaziquone failed to achieve statistically significant activity in non-muscle invasive bladder cancer in phase III trials. Apaziquone was administered shortly after transurethral resection and here we test the hypothesis that haematuria inactivates apaziquone.MethodsHPLC analysis was used to determine the ability of human whole blood to metabolise apaziquone ex vivo. An in vitro model of haematuria was developed and the response of RT112 and EJ138 cells following a 1-h exposure to apaziquone was determined in the presence of urine plus or minus whole blood or lysed whole blood.ResultsHPLC analysis demonstrated that apaziquone is metabolised by human whole blood with a half-life of 78.6 ± 23.0 min. As a model for haematuria, incubation of cells in media containing up to 75% buffered (pH 7.4) urine and 25% whole blood was not toxic to cells for a 1-h exposure period. Whole blood (5% v/v) significantly (p < 0.01) reduced the potency of apaziquone in this experimental model. Lysed whole blood also significantly (p < 0.05) reduced cell growth, although higher concentrations were required to achieve an effect (15% v/v).ConclusionsThe results of this study demonstrate that haematuria can reduce the potency of apaziquone in this experimental model. These findings impact upon the design of further phase III clinical trials and strongly suggest that apaziquone should not be administered immediately after transurethral resection of non-muscle invasive bladder cancer when haematuria is common.
| S-EPMC6499894 | biostudies-literature