Citations

Purpose Symptoms and complications of metastatic colorectal cancer (mCRC) differ by metastatic sites. There is a paucity of prospective survival data for patients with peritoneal carcinomatosis colorectal cancer (pcCRC). We characterized outcomes of patients with pcCRC enrolled onto two prospective randomized trials of chemotherapy and contrasted that with other manifestations of mCRC (non-pcCRC). Methods A total of 2,095 patients enrolled onto two prospective randomized trials were evaluated for overall survival (OS) and progression-free survival (PFS). A Cox proportional hazard model was used to assess the adjusted associations. Results The characteristics of the pcCRC group (n = 364) were similar to those of the non-pcCRC patients in median age (63 v 61 years, P = .23), sex (57% males v 61%, P = .23), and performance status (Eastern Cooperative Oncology Group performance status 0 or 1 94% v 96%, P = .06), but differed in frequency of liver (63% v 82%, P < .001) and lung metastases (27% v 34%, P = .01). Median OS (12.7 v 17.6 months, hazard ratio [HR] = 1.3; 95% CI, 1.2 to 1.5; P < .001) and PFS (5.8 v 7.2 months, HR = 1.2; 95% CI, 1.1 to 1.3; P = .001) were shorter for pcCRC versus non-pcCRC. The unfavorable prognostic influence of pcCRC remained after adjusting for age, PS, liver metastases, and other factors (OS: HR = 1.3, P < .001; PFS: HR = 1.1, P = .02). Infusional fluorouracil, leucovorin, and oxaliplatin was superior to irinotecan, leucovorin, and fluorouracil as a first-line treatment among pcCRC (HR for OS = 0.62, P = .005) and non-pcCRC patients (HR = 0.66, P < .001). Conclusion pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC. Future trials for mCRC should consider stratifying on the basis of pcCRC status.

Mesenchymal stem cells (MSCs) represent a heterogeneous population of stromal cells with pluripotent mesenchymal differentiation potential. They have been found to have immunosuppressive properties and the ability to modulate angiogenesis and endogenous tissue repair byin vitroand animal studies. Clinical trials have examined the utility of these cells in autoimmune and inflammatory conditions. In particular, in allogeneic hematopoietic stem cell transplant (HSCT), multiple studies have been conducted to explore the use of MSC to treat acute and chronic graft-versus-host disease (GVHD) and for cotransplantation with HSCT to promote HSC engraftment and prevent GVHD. We review here the results of these studies and discuss some challenges of this treatment modality in this disease setting.

A two‐stage model for evaluating both trial‐level and patient‐level surrogacy of correlated time‐to‐event endpoints has been introduced, using patient‐level data when multiple clinical trials are available. However, the associated maximum likelihood approach often suffers from numerical problems when different baseline hazards among trials and imperfect estimation of treatment effects are assumed. To address this issue, we propose performing the second‐stage, trial‐level evaluation of potential surrogates within a Bayesian framework, where we may naturally borrow information across trials while maintaining these realistic assumptions. Posterior distributions on surrogacy measures of interest may then be used to compare measures or make decisions regarding the candidacy of a specific endpoint. We perform a simulation study to investigate differences in estimation performance between traditional maximum likelihood and new Bayesian representations of common meta‐analytic surrogacy measures, while assessing sensitivity to data characteristics such as number of trials, trial size, and amount of censoring. Furthermore, we present both frequentist and Bayesian trial‐level surrogacy evaluations of time to recurrence for overall survival in two meta‐analyses of adjuvant therapy trials in colon cancer. With these results, we recommend Bayesian evaluation as an attractive and numerically stable alternative in the multitrial assessment of potential surrogate endpoints. Copyright © 2011 John Wiley & Sons, Ltd.

Background and Purpose— Helicopter transportation of patients with acute stroke who have received recombinant tissue-type plasminogen activator is commonly considered the best option. We evaluated if transportation by helicopter can reduce complications and improve clinical outcomes in patients with acute stroke. Methods— We conducted a review of consecutive patients with acute ischemic stroke transferred to our hospital after intravenous thrombolysis initiated at a referral center. Results— A total of 122 patient transportations were analyzed, 94 by air and 28 by ground. Time from activation of the transport system to arrival at our hospital was significantly shorter with air transportation (53 versus 68 minutes, P =0.04). Two complications were noted in the air group and no complications were noted in the ground group ( P =1.0). All other outcome measures were not significantly different between groups. Conclusions— Air transfer of patients with acute ischemic stroke treated with thrombolysis does not seem to impart any benefit to patient outcomes when compared with ground transport. Therefore, ground transport should be considered for these patients unless they are being considered for emergency endovascular rescue therapy.