A DREAM Challenge to Build Prediction Models for Short-Term Discontinuation of Docetaxel in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Docetaxel has a demonstrated survival benefit for patients with metastatic castration-resistant prostate cancer (mCRPC); however, 10% to 20% of patients discontinue docetaxel prematurely because of toxicity-induced adverse events, and the management of risk factors for toxicity remains a challenge. PATIENTS AND METHODS: The comparator arms of four phase III clinical trials in first-line mCRPC were collected, annotated, and compiled, with a total of 2,070 patients. Early discontinuation was defined as treatment stoppage within 3 months as a result of adverse treatment effects; 10% of patients discontinued treatment. We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to predict early discontinuation of docetaxel treatment. Clinical features for all four trials and outcomes for three of the four trials were made publicly available, with the outcomes of the fourth trial held back for unbiased model evaluation. Challenge participants from around the world trained models and submitted their predictions. Area under the precision-recall curve was the primary metric used for performance assessment. RESULTS: In total, 34 separate teams submitted predictions. Seven models with statistically similar area under precision-recall curves (Bayes factor ≤ 3) outperformed all other models. A postchallenge analysis of risk prediction using these seven models revealed three patient subgroups: high risk, low risk, or discordant risk. Early discontinuation events were two times higher in the high-risk subgroup compared with the low-risk subgroup. Simulation studies demonstrated that use of patient discontinuation prediction models could reduce patient enrollment in clinical trials without the loss of statistical power. CONCLUSION: This work represents a successful collaboration between 34 international teams that leveraged open clinical trial data. Our results demonstrate that routinely collected clinical features can be used to identify patients with mCRPC who are likely to discontinue treatment because of adverse events and establishes a robust benchmark with implications for clinical trial design.

Factors affecting visual acuity after accelerated crosslinking in patients with progressive keratoconus / Fatores que afetam a acuidade visual após crosslinking acelerado entre pacientes com ceratocone progressivo

ABSTRACT Purpose: The present study aimed to report the outcomes of patients with progressive keratoconus who were treated via accelerated crosslinking (CXL) 6 months earlier and to determine the factors that promoted improved visual acuity after treatment. Methods: This retrospective study included 35 eyes of 34 patients with progressive keratoconus who underwent CXL. Topographical measurements were obtained preoperatively and in the first, third, and sixth months postoperatively using a rotating Scheimpflug camera. The uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), flat keratometry (K) value (K1), steep K value (K2), average K value (avgK), topographic cylindrical value (Cyl), apical keratoscopy front (AKf), apical keratoscopy back (AKb), symmetry index front (SIf), symmetry index back (SIb), and thinnest point of the cornea (ThkMin) were recorded. Results: At the 6-month follow-up, the mean UCVA and BCVA values were improved, and the K values remained stable. Statistically significant decreases in AKf (p=0.04) and the thinnest point of the cornea (p=0.001) and a statistically significant increase in AKb (p=0.01) were observed. A correlation analysis revealed that the preoperative BCVA, UCVA, K1, K2, avgK, AKf, and AKb values significantly affected visual acuity at the 6-month follow-up. Conclusions: Accelerated CXL is an effective treatment for the prevention or even reversal of keratoconus progression. The preoperative K values and apexes of the anterior and posterior cornea were found to affect visual acuity at 6 months after accelerated CXL. Both AKb steepening and AKf flattening appear to be important factors in the stabilization of keratometric values and improvement of visual outcomes.

RESUMO Objetivo: O objetivo do estudo é relatar os resultados do sexto mês após o tratamento de crosslinking acelerado (CXL) em pacientes com ceratocone progressivo e determinar os fatores que afetam a melhora da acuidade após o tratamento. Métodos: Neste estudo retrospectivo, foram incluídos 35 olhos de 34 pacientes com ceratocone progressivo que se submeteram CXL. Acuidade visual não corrigida (UCVA) e melhor acuidade visual corrigida (BCVA) foram registradas. Medidas topográficas foram obtidas utilizando uma câmara Scheimpflug rotativa no pré-operatório e no 1º, 3º e 6º meses após a cirurgia. Os valores de ceratometria (K) mais plana (K1), K mais curva (K2), médio de K (avgK), astigmatismo topográfico (Cyl), ápice anterior da ceratoscopia (AKf), ápice posterior da ceratoscopia (AKb), índice anterior de simetria (SIf), índice posterior de simetria (SIb) e ponto mais fino da córnea (ThkMin) foram avaliados. Resultados: A média UCVA e BCVA melhoraram, enquanto valores de K ficaram estáveis 6º mês. Houve uma diminuição estatisticamente significativa na AKf e um aumento estatisticamente significativo na AKb (p=0,04, p=0,01, respectivamente). O ponto mais fino da córnea diminuiu significativamente (p=0,001). Na análise de correlações, além da UCVA e BCVA pré-operatórias; valores K1, K2, avgK, AKf e AKb pré-operatórios influenciaram significativamente a acuidade visual no 6º mês de acompanhamento. Conclusões: CXL acelerado é uma forma eficaz de tratamento na prevenção ou no mesmo inversão da progressão do ceratocone. A acuidade visual no 6º mês após CXL acelerado foi afetada a partir dos valores de K e dos ápice anterior e posterior da córnea. Encurvamento do AKb e aplanamento do AKf parecem ser fatores importantes na estabilização dos valores ceratométricos e na melhora da acuidade visual.