CUSUM analysis of the SCC antigen in patients with head and neck cancer.

PURPOSE: Serial postoperative serum squamous cell carcinoma antigen (SCCAg) levels in a group of head and neck cancer patients were evaluated using a cumulative sum (CUSUM) technique to determine the prognostic value of serial SCCAg levels in predicting tumor recurrence. MATERIALS AND METHODS: A retrospective analysis of serial postoperative SCCAg measurements in 75 patients with squamous cell carcinoma of the head and neck (SCCHN) from two previous studies of SCCAg was performed. Serum SCCAg levels were determined by radioimmunoassay. A V-mask was used to detect significant deviations of greater than 1 SD of the CUSUM from the reference value. SETTING: Oncologic head and neck practice at a tertiary referral hospital. PATIENTS OR OTHER PARTICIPANTS: Seventy-five consecutive patients with a minimum of three postoperative SCCAg determinations were reviewed to provide equal numbers with and without recurrent disease. All patients who remained disease-free were followed for a minimum of 2 years. All patients were previously untreated and underwent surgical therapy. MAIN OUTCOME MEASURES: CUSUM curve of postoperative SCCAg levels and 2-year disease-free survival. RESULTS: In a group of 38 patients with 2-year disease-free survival, the CUSUM analysis did not detect any significant deviation in postoperative SCCAg levels for up to 23 months after surgery. In a group of 37 patients who subsequently died of disease, a deviation of greater than 1 SD was noted as early as 5 months postoperatively and persisted throughout the course of their monitoring for up to 36 months. CONCLUSIONS: The CUSUM technique is more sensitive for detecting postoperative changes in serial measurements of the SCCAg and may be applicable to the monitoring of individual patients for recurrent disease.

The impact of lag time on the estimation of pharmacokinetic parameters. I. One-compartment open model.

Lag time in pharmacokinetics corresponds to the finite time taken for a drug to appear in systemic circulation following extravascular administration. Lag time is a reflection of the processes associated with the absorption phase such as drug dissolution and/or release from the delivery system and drug migration to the absorbing surface. Failure to specify the lag time can lead to inappropriate or erroneous estimates of pharmacokinetic parameters. This has been demonstrated in the case of a one-compartment open model by the pharmacokinetic analysis of bioequivalence data from a study involving the administration of propoxyphene napsylate to human volunteers. Subsequently, pharmacokinetic and statistical analyses of data obtained from a series of 49 simulations involving a wide range of absorption and elimination rate constants (0.05 to 5.00 and 0.01 to 0.95 hr-1, respectively) showed that lag time has a substantial effect on several primary and secondary pharmacokinetic parameters.