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Limited-sampling models for estimation of the carboplatin area under the curve.

BACKGROUND: The area under the curve (AUC) of free carboplatin, is a major determinant of toxicity and response. A conventional pharmacokinetic study to determine AUC requires frequent blood sampling. One strategy for overcoming this problem is to apply a limited sampling model (LSM). MATERIALS AND METHODS: We developed LSMs by stepwise forward multiple regression analysis using 27 data series from 24 patients with lung cancer (training data set) who received carboplatin in combination with oral etoposide. The models were then validated using 24 data series from 18 patients (test data set). RESULTS: In the test data set, the single-sample model was confirmed to give excellent estimation of the AUC: AUC (mg/ml x min) = 0.93 x C3h + 0.47 (MPE% = 4.4%, RMSE% = 8.9%). Furthermore, the two-sample model was shown to improve both the bias and precision of AUC estimation: AUC = 0.16 x C1h + 2.26 x C8h + 0.75 (MPE% = 0.9%, RMSE% = 5.3%). CONCLUSIONS: Our models are useful for future trials to define the accurate relationships between the dose-intensity and effect of carboplatin.

Adenocarcinoma↗

The effect of random measurement error on receiver operating characteristic (ROC) curves.

In this paper confidence intervals for the area under the ROC curve are adjusted for the presence of measurement error. A parametric normal model is assumed. The ratio of intra-individual to inter-individual variance provides a relative measure of the amount of measurement error. An exact adjusted confidence interval is developed for the equal variance case and an approximation is derived for the unequal variance case. We illustrate, using an example, the effect of ignoring the measurement error on the confidence interval for the area and show that the effect can be substantial on the decision as to the diagnostic effectiveness of the marker. We also examine, by means of a simulation study, the coverage probability of the unadjusted confidence interval and show that it can be far from its nominal value when measurement error is present.

Breast↗

Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database.

Despite recent advances in the diagnosis and treatment of head and neck cancer, there has been little evidence of improvement in 5-year survival rates over the last few decades. To determine more accurate trends in site-specific outcomes as opposed to a more general overview of head and neck cancer patients, we analyzed the site-specific data collected in the Surveillance, Epidemiology, and End Results-SEER Public-Use Database 1973-1999. Based on the selection criteria, 96,232 cases were evaluated for trend analysis in incidence, clinical stage, treatment and 5-year survival. During the period 1973-1999, site-specific incidence rates for head and neck cancer changed significantly. Site-specific analysis of survival from 1974-1997 showed significant improvements in 5-year survival rates for cancers of the nasopharynx, oropharynx and hypopharynx (38.1% to 56.7% for nasopharynx, p < 0.001; 36.3% to 49.1% for oropharynx, p = 0.001 and 28.3% to 33.3% for hypopharynx, p = 0.015). The prognosis for early-stage salivary gland cancer during 1983-1997 and late-stage larynx cancer during 1974-1997 also demonstrated improvement (82.7% to 88.5%, p = 0.012 and 22.2% to 38.3%, p = 0.013, respectively). On the other hand, the prognosis for regional stage oral cavity cancer as well as early-stage larynx cancer patients declined during 1983-1997 (49.2% to 43.8%, p = 0.032 and 82.3% to 74.3%, p = 0.002, respectively). Site-specific changes in treatment and staging were also noted. Site-specific analysis allows for a more accurate description of incidence, staging, treatment, and prognostic trends for head and neck cancer.

Adult↗