Imprecision in automated volume measurements of pulmonary nodules and its effect on the level of uncertainty in volume doubling time estimation.

BACKGROUND: Detection of small indeterminate pulmonary nodules (4 to 10 mm in diameter) in clinical practice is increasing, largely because of increased utilization and improved imaging technology. Although there currently exists software for CT scan machines that automate nodule volume estimation, the imprecision associated with volume estimates is particularly poor for nodules < or = 6 mm in diameter, with greater imprecision associated with increasing CT scan slice thickness. This study examined the effects of the volume estimation error associated with four CT scan slice thicknesses (0.625, 1.25, 2.50, and 5.00 mm) on estimates of volume doubling time (VDT) for solid nodules of various sizes. METHODS: Data reflecting the accuracy of 1,624 automated volume estimations were obtained from experiments incorporating volume estimation software, performed on a commercially available lung phantom. These data informed mathematical simulations that were used to estimate imprecision around VDT estimates for hypothetical pairs of volume estimates for a given solid pulmonary nodule observed at different time points. RESULTS: The confidence intervals around the VDT estimates were extremely wide for 2.50- and 5.00-mm slice thicknesses, often encompassing values traditionally associated with both benignity and malignity for simulated 1- and 2-mm growths in diameter. CONCLUSIONS: 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.

Patient variability in intraoperative ultrasonographic characteristics of colorectal liver metastases.

OBJECTIVE: To determine the distribution of echogenicity (hypoechoic, isoechoic, or hyperechoic) and predominant intraoperative ultrasonography (IOUS) echogenic appearance of colorectal liver metastasis. The interpatient and intrapatient variability of tumor IOUS echogenicity was assessed. DESIGN: Retrospective review of prospectively collected database. SETTING: Tertiary cancer center. PATIENTS: Between January 1998 and July 2001, 99 patients (194 tumors) underwent hepatic resection for colorectal metastases. MAIN OUTCOME MEASURES: During surgery, IOUS of the liver was performed and the images were digitally recorded. Images were randomly coded, blindly reviewed, and scored for echogenicity and ultrasonographic appearance pattern. RESULTS: The ultrasonographic appearance of the colorectal liver metastasis was hypoechoic in 52.0%, isoechoic in 35.7%, and hyperechoic in 12.3% of cases. Most colorectal liver metastases appeared homogeneous (50.8%). Less commonly, identified lesions were characterized by a target or "bull's-eye" appearance (20%) or contained calcifications (19%). Clinicopathologic characteristics, including patient age and sex, as well as tumor size, number, and location and presence of hepatic steatosis, did not correlate with tumor echogenicity or ultrasonographic appearance pattern (all P > .05). Lesions within patients were more similar in echogenicity than lesions between patients (P < .001). Similarly, intrapatient variability in appearance pattern was significantly less than the variability between patients (P = .002). CONCLUSIONS: 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.

A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis.

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 > or =2 sites; P = 0.001), (c) clinically significant pain (HR, 1.48; P < 0.0001), (d) Karnofsky performance status (HR, 1.39 if < or =70; 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). A nomogram was developed based on this multivariate model and validated internally using bootstrap methods, with a concordance index of 0.69. CONCLUSIONS: This multivariate model identified several new independent prognostic factors in men with metastatic HRPC, including PSA doubling time, and led to the successful development of a clinically applicable nomogram. External prospective validation may support the wider use of this prognostic baseline model for men with HRPC treated with chemotherapy.

Quality of parental consent in a Ugandan malaria study.

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.

A cross-study comparison of gene expression studies for the molecular classification of lung cancer.

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.