The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal.

During cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient 1-3. Prior case reports and small Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

In the SEER-Medicare database, differences in breast cancer survival between black and white women did not substantially change among women diagnosed between 1991 and 2005. These differences in survival appear primarily related to presentation characteristics at diagnosis rather than treatment differences.

Doses of CA4P on a daily times five schedule of 52 to 65 mg/m2 were reasonably well-tolerated. The 52 mg/m2 dose is recommended for further study based on cumulative phase I experience with CA4P. Antitumor efficacy was observed, and the use of DCE-MRI provided a valuable noninvasive measure of the vascular effects of CA4P treatment.

Statement of Translational RelevanceDetection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery to identify patients with minimal residual disease (MRD) who will ultimately recur has emerged as a potentially transformative approach in oncology. Early identification of patients with MRD through ctDNA detection could identify patients in whom additional therapy might salvage the chance of cure. To date, ctDNA MRD assays have employed a tumor-informed approach, requiring initial sequencing of tumor tissue to guide ctDNA detection, and thus cannot be used when a patient has insufficient tumor tissue for analysis. Here, we evaluate the first tumoruninformed, plasma-only ctDNA assay integrating genomic and epigenomic signatures to detect MRD in post-operative colorectal cancer (CRC) patients, without requiring parallel tumor sequencing, which produced favorable sensitivity and specificity, comparable to tumor-informed approaches. These data highlight the feasibility and potential clinical utility of plasma-only ctDNA-guided MRD detection.

Background and aims Approximately 50% of all patients with pancreatic ductal adenocarcinoma (PDA) develop diabetes mellitus before their cancer diagnosis. Screening individuals with new-onset diabetes might therefore allow earlier diagnosis of PDA. We sought to develop and validate a PDA risk prediction model to identify high-risk individuals among those with new-onset diabetes. Methods We conducted a retrospective cohort study in a population representative database from the UK. Individuals with incident diabetes after the age of 35 and 3 or more years of follow up after diagnosis of diabetes were eligible for inclusion. Candidate predictors consisted of epidemiologic and clinical characteristics available at the time of diabetes diagnosis. Variables with P values below .25 in the univariable analyses were further evaluated using backward stepwise approach. Model discrimination was assessed using receiver operating characteristic curve analysis. Calibration was evaluated using the Hosmer–Lemeshow test. Results were internally validated using a bootstrapping procedure. Results We analyzed data from 109,385 patients with new-onset diabetes. Among them, 390 (0.4%) were diagnosed with PDA within 3 years. The final model (area under the curve, 0.82; 95% CI, 0.75–0.89) included age, body mass index, change in body mass index, smoking, use of proton pump inhibitors and anti-diabetic medications, as well as levels of HbA1C, cholesterol, hemoglobin, creatinine, and alkaline phosphatase. Bootstrapping validation showed negligible optimism. If the predicted risk threshold for definitive PDA screening was set at 1% over 3 years, only 6.19% of the new-onset diabetes population would undergo definitive screening, which would identify patients with PDA with 44.7% sensitivity, 94.0% specificity, and a positive predictive value of 2.6%. Conclusion We developed a risk model based on widely available clinical parameters to help identify patients with new-onset diabetes who might benefit from PDA screening.

Purpose. This analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses were based on the intent-to-treat population. To assess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results. The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant increases in overall survival (OS; HR, 0.80; 95% CI, 0.71-0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46 -0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecanbased), extent of disease (liver metastases only, extensive disease), age (Ͻ65, Ն65 years), Eastern Cooperative Oncology Group performance status (0, Ն1), and KRAS status (wildtype, mutant) were consistent with the overall analysis. Incidence rates of grade Ն3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment. Conclusion. The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials. The Oncologist 2013;18:1004 -1012 Implications for Practice: Several randomized trials of bevacizumab have been conducted to address specific questions regarding its use for patients with metastatic colorectal cancer (mCRC); however, because of their sample size limitations, subgroup analyses are frequently of limited power. By pooling individual patient data from seven randomized trials, more comprehensive analyses of the efficacy and safety of bevacizumab were made possible because of the large number of included patients. In addition, outcomes in clinically relevant subgroups were examined, and the data from these subgroups were consistent with those reported in the overall analyses. The results of this pooled analysis help further the clinician's understanding of the overall risks and benefits associated with adding bevacizumab to chemotherapy for patients with mCRC.

The combination of EMP and 96-hour paclitaxel is an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms.