Purpose: To develop a prognostic model and nomogram using baseline clinical variables to predict death among men with metastatic hormone-refractory prostate cancer (HRPC). Experimental Design: TAX327 was a clinical trial that randomized 1,006 men with metastatic HRPC to receive every three week or weekly docetaxel or mitoxantrone, each with prednisone. We developed a multivariate Cox model and nomogram to predict survival at 1, 2, and 5 years. Results: Ten independent prognostic factors other than treatment group were identified in multivariate analysis: (a) presence of liver metastases [hazard ratio (HR), 1.66; P = 0.019], (b) number of metastatic sites (HR, 1.63 if z2 sites; P = 0.001), (c) clinically significant pain (HR, 1.48; P < 0.0001), (d) Karnofsky performance status (HR, 1.39 if V70; P = 0.016), (e) type of progression (HR, 1.37 for measurable disease progression and 1.29 for bone scan progression; P = 0.005 and 0.01, respectively), (f) pretreatment prostate-specific antigen (PSA) doubling time (HR, 1.19 if <55 days; P = 0.066), (g) PSA (HR, 1.17 per log rise; P < 0.0001), (h) tumor grade (HR, 1.18 for high grade; P = 0.069), (i) alkaline phosphatase (HR, 1.27 per log rise; P < 0.0001), and (j) hemoglobin (HR, 1.11 per unit decline; P = 0.004). Despite the recent demonstration of palliative and survival benefits with docetaxel-based regimens, men with metastatic hormone-refractory prostate cancer (HRPC) have a poor prognosis, with a median survival of 16 to 20 months (1, 2). The biology of prostate cancer is heterogeneous, with expected survival depending on performance status, presence of visceral metastases, baseline prostate-specific antigen (PSA), advanced primary Gleason sum, baseline hemoglobin, lactate dehydrogenase, albumin, and alkaline phosphatase (3, 4). Nomograms have been developed as stratification tools for phase III clinical trials evaluating cytotoxic chemotherapy based on data from multiple studies that assessed prognostic factors (3 -5).Baseline PSA kinetics [PSA doubling time (PSADT) or PSA velocity] have not been shown conclusively to be an independent prognostic factor in HRPC, with most analyses based on retrospective reviews of relatively small numbers of patients (6 -9). These analyses were limited by the number of controllable covariates, the duration of follow-up, potential confounders, and measurement bias. Furthermore, past prognostic analyses are limited by the inclusion of various types of noncytotoxic therapy and did not include patients treated with docetaxel-based therapy (3, 4).In 2004, docetaxel was approved for the treatment of men with metastatic HRPC based on large multicenter randomized clinical trials (1, 2). The TAX327 study randomized 1,006 patients to receive one of two schedules of docetaxel or mitoxantrone, each given with low-dose prednisone, and showed an extension of overall survival, improvement in quality of life, pain control, PSA decline, and objective tumor response (2). A second phase III study using estramustine phosphate in combination w...

Purpose: Recent studies sought to refine lung cancer classification using gene expression microarrays. We evaluate the extent to which these studies agree and whether results can be integrated.Experimental Design: We developed a practical analysis plan for cross-study comparison, validation, and integration of cancer molecular classification studies using public data. We evaluated genes for cross-platform consistency of expression patterns, using integrative correlations, which quantify cross-study reproducibility without relying on direct assimilation of expression measurements across platforms. We then compared associations of gene expression levels to differential diagnosis of squamous cell carcinoma versus adenocarcinoma via reproducibility of the gene-specific t statistics and to survival via reproducibility of Cox coefficients.Results: Integrative correlation analysis revealed a large proportion of genes in which the patterns agreed across studies more than would be expected by chance. Correlation of t statistics for diagnosis of squamous cell carcinoma versus adenocarcinoma is high (0.85) and increases (0.925) when using only the most consistent genes identified by integrative correlation. Correlations of Cox coefficients ranged from 0.13 to 0.31 (0.33-0.49 with genes selected for consistency). Although we find genes that are significant in multiple studies but show discordant effects, their number is approximately that expected by chance. We report genes that are reproducible by integrative analysis, significant in all studies, and concordant in effect.Conclusions: Cross-study comparison revealed significant, albeit incomplete, agreement of gene expression patterns related to lung cancer biology and identified genes that reproducibly predict outcomes. This analysis approach is broadly applicable to cross-study comparisons of gene expression profiling projects.

Objectives. We surveyed Ugandan parents who enrolled their children in a randomized pediatric malaria treatment trial to evaluate the parents’ levels of understanding about the treatment trial and the quality of the parents’ consents to allow their children to participate in the study. Methods. We conducted 347 interviews immediately following enrollment at 4 Ugandan sites. Results. A majority (78%) of the parents, most of whom where mothers (86%) had at most a primary school education. Of the participating mothers, a substantial percentage reported that they remembered being told about the study’s purpose (77%), the required number of visits (88%), the risks involved (61%), treatment allocation (84%), and their ability to discontinue their children’s participation (64%). In addition, most reported knowing the trial’s purpose (80%) and the required number of visits (78%); however, only 18% could name possible side effects from the drugs being administered, and only 19% knew that children would not all be administered identical treatments. Ninety-four percent reported that they made the enrollment decision themselves, but 58% said they felt pressure to participate because of their child’s illness, and 15% said they felt some type of pressure to participate from others; 41% reported knowing that they did not have to participate. Conclusions. The consent Ugandan parents provided to allow their children to participate in the malaria study was of mixed quality. Parents understood many of the study details, but they were not very aware of the risks involved or of randomization. Many parents felt that they could not have refused to participate because their child was sick and they either did not know or did not believe that their child would receive treatment outside of the study. Our results indicate that further debate is needed about informed consent in treatment studies of emergent illnesses in children.

The ultrasonographic characteristics of hepatic metastases within patients were more similar than between patients. Such information is important because it suggests that, in patients with more than 1 metastasis, the echogenic appearance of an index lesion may predict the echogenic appearance of additional occult disease.

Because of the inaccuracy in automated volume estimation, the confidence a clinician should have in estimating VDT should be highly dependent on the degree of observed growth and on the CT scan slice thickness. The performance of CT scanners with slice thicknesses of > or = 2.5 mm for assessing growth in pulmonary nodules is essentially inadequate for 1-mm changes in nodule diameter.