Bias in Reporting of Randomized Clinical Trials in Oncology

Background:Bias in reporting efficacy and toxicity in clinical trials can influence treatment decisions. We evaluated the quality of reporting the primary endpoint and of toxicity in Randomized Clinical Trials in medical oncology.Methods:Three independent studies were undertaken. The first and second studies, identify use of spin in the reporting of the primary endpoint in the conclusion statement of the abstract and underreporting of toxicity. The third study assessed the prevalence of honorary and ghost authorship.Results:All studies met their objectives showing that the prevalence of spin in the reporting of primary endpoints, underreporting of toxicity and the incidence of ghost and honorary authors are highly prevalent in oncology literature. Conclusion:Use of spin in reporting of outcomes is common for studies with a negative primary endpoint. Reporting of toxicity is limited, especially for studies with positive primary endpoints. Ghost and honorary authorship are prevalent.M.Sc

Adjuvant Radiotherapy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis

Purpose: Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy (RNU) with bladder cuff excision. Neoadjuvant or adjuvant chemotherapy is often used in locally advanced disease. The role of adjuvant radiotherapy (RT), however, remains controversial. To further explore the potential role of adjuvant RT, we performed a systematic review and meta-analysis of the literature from 1990 to present. Methods and Materials: We identified 810 candidate articles from database searches, of which 67 studies underwent full-text review, with final inclusion of 20 eligible studies. Among the included studies, there were no randomized controlled trials and a single prospective trial, with the remainder being retrospective series. We performed quantitative synthesis of the results by calculating the pooled odds ratios (OR) for the primary outcome of locoregional recurrence (LRR) and secondary outcomes of overall survival (OS), cancer-specific survival (CSS) and distant recurrence (DR). Results: Adjuvant RT, which was mostly prescribed for locally advanced or margin-positive disease following RNU, significantly reduced locoregional recurrence risk OR 0.43 (95% CI: 0.23–0.70), and the effect remained significant even following subgroup analysis to account for adjuvant systemic therapy. The effect of adjuvant RT on 3-year OS, 5-year CSS and DR was non-significant. However, 5-year OS was unfavourable in the adjuvant RT arm, but study heterogeneity was high, and analysis of small-study effects and subgroups suggested bias in reporting of outcomes. Conclusions: Adjuvant RT in the setting of locally advanced UTUC improves locoregional control following definitive surgery, but does not appear to improve OS. Higher-quality studies, ideally randomized controlled trials, are needed to further quantify its benefit in this setting, and to explore multi-modal treatments that include systemic agents given concomitantly or sequentially with RT, which may offer an OS benefit in addition to the locoregional control benefit of RT

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials†.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy. PATIENTS AND METHODS: Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT. RESULTS: In the training set, both dNLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11-1.50, P < 0.001 and HR 1.41; 95% CI 1.21-1.64, P < 0.001, respectively] after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline. In the validation set, dNLR remained an independent prognostic factor for OS (HR 1.43; 95% CI 1.20-1.70, P < 0.001), whereas duration of initial ADT was not (HR 1.16; 95% CI 0.97-1.37, P = 0.10). In subgroup analyses of the TAX327 study, docetaxel improved OS irrespective of dNLR and duration of initial ADT. CONCLUSION: The dNLR was prognostic for OS in men with mCRPC receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials and could be incorporated into prognostic nomograms