Summary Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest—namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial—ENTHUSE M1—in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39–4·62, p<0·0001; reference model: 2·56, 1·85–3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified...

Patients with cerebellar metastases have more distinct clinical presentations and outcomes than patients with non-cerebellar lesions. The findings of this study may help risk stratify and guide treatment regimens aimed at maximizing outcomes for patients with cerebellar metastases.

Objectives Patients with a variety of different primary cancers can develop intracranial metastases. Patients who develop intracranial metastases are often grouped into the same study population, and therefore an understanding of outcomes for patients with different primary cancers remain unclear. Methods Adults who underwent intracranial metastatic tumor surgery from 1997–2011 at a single institution were retrospectively reviewed. Primary pathologies were compared using Fisher’s exact and Student’s t-test, and Cox regression analysis was used to identify factors associated with survival. Results About 708 patients underwent surgery during the reviewed period, where 269 (38%) had non-small cell lung cancer (NSCLC), 106 (15%) breast cancer (BC), 72 (10%) gastrointestinal (GI) cancers, 88 (12%) renal cell cancer (RCC), and 88 (12%) melanoma. The most notable differences were that NSCLC patients were older, BC younger, BC had more primary tumor control, and NSCLC less extracranial spread. BC had longer survival, RCC had longer local progression free survival (PFS), and NSCLC had longer distal PFS. The factors independently associated with survival for NSCLC (female, recursive partitioning analysis (RPA) class, primary tumor control, solitary metastasis, tumor size, adenocarcinoma, radiation, discharge to home), BC (age, no skull base involvement, radiation), GI cancer (age, RPA class, Karnofsky performance scale (KPS), lack of preoperative motor deficit, non-esophageal tumors, non-hemorrhagic tumors, avoidance of new deficits), melanoma (preoperative seizures, solitary metastasis, smaller tumor size, discharge to home, chemotherapy), and RCC (KPS, chemotherapy) were distinctly different. Discussion These differences between patients with different primary cancers support the fact that patients with intracranial disease are not all the same and should be studied by their primary pathology.

The nomogram described is currently being used at each return visit to assess the need for a surveillance biopsy, and could increase retention in AS.

BackgroundMultiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups—including the costs of screening and subsequent diagnosis, treatment, and adverse events—remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios.MethodsWe determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate).ResultsUnder the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively.ConclusionsWith constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with screening men 70 and older.Electronic supplementary materialThe online version of this article (10.1186/s12894-018-0344-5) contains supplementary material, which is available to authorized users.