Faculty Bibliography

PURPOSE/OBJECTIVE:To validate radiation safety instructions to patients and to evaluate the potential radiation doses to members of the public after (125)I or (103)Pd prostate implantation. METHODS AND MATERIALS/METHODS:Radiation dose rate measurements were made in the immediate postoperative period on 636 consecutive patients with stage T1-T2 prostate cancer who underwent transperineal (125)I or (103)Pd implantation at Memorial Sloan-Kettering Cancer Center during the period from August 1995 through January 2003. RESULTS:The mean radiation dose rate at the anterior skin surface following a prostate implant was 37 microSv/hr for (125)I and 8 microSv/hr for (103)Pd. At 30 cm from the anterior skin surface, these dose rates were reduced to 6 microSv/hr for (125)I and 3 microSv/hr for (103)Pd. At 1 m from the anterior skin surface the dose rates from both types of implants were reduced to less than 1 microSv/hr. The effect of body weight on dose rates from (125)I sources was examined for a select sub-group of patients and the measured dose rate was found to decrease with increasing body weight. In another group of patients, dose rate measurements were made on both lateral skin surfaces and were less than 16.8 microSv/hr in all cases. Assuming a 33% occupancy factor and utilizing the mean measured dose rate for (125)I, the time required to reach an effective dose equivalent limit of 5 mSv for caregivers was estimated to be 19 days on contact with the skin surface. Using a similar calculation, the lifetime doses for (125)I at a distance of 30 cm from the anterior skin surface, as well as the lifetime doses for (103)Pd on contact with the skin surface and at 30 cm from the anterior skin surface can be shown to be less than 5 mSv. CONCLUSIONS:The large number of cases available for this study permits a validation of radiation safety recommendations and provides concrete information from which the permitted exposure times following implantation can be estimated. The data support the conclusion that patients treated with these implants do not represent a radiation risk to members of the public.

PURPOSE/OBJECTIVE:There are several nomograms for the patient considering radiation therapy for clinically localized prostate cancer. Because of the questionable clinical implications of prostate-specific antigen (PSA) recurrence, its use as an end point has been criticized in several of these nomograms. The goal of this study was to create and to externally validate a nomogram for predicting the probability that a patient will develop metastasis within 5 years after three-dimensional conformal radiation therapy (CRT). PATIENTS AND METHODS/METHODS:We conducted a retrospective, nonrandomized analysis of 1,677 patients treated with three-dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to 2000. Clinical parameters examined were pretreatment PSA level, clinical stage, and biopsy Gleason sum. Patients were followed until their deaths, and the time at which they developed metastasis was noted. A nomogram for predicting the 5-year probability of developing metastasis was constructed from the MSKCC cohort and validated using the Cleveland Clinic series of 1,626 patients. RESULTS:After three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to 13%). A nomogram constructed from the data gathered from these men showed an excellent ability to discriminate among patients in an external validation data set, as shown by a concordance index of 0.81. CONCLUSION/CONCLUSIONS:A nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT.

PURPOSE/OBJECTIVE:To assess the merit of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after external beam radiotherapy for prostate cancer by testing alternative prostate-specific antigen (PSA) failure definitions against the "gold standard" of clinical failure and to study the effect of backdating the time of failure. METHODS AND MATERIALS/METHODS:Nine participating institutions agreed to submit follow-up results for all patients with clinically localized prostatic cancer (Stage T1b, T1c, T2, N0M0) treated between 1986 and 1995 by external beam radiotherapy only, to doses of >or=60 Gy, with no androgen deprivation before treatment. A total of 4839 men met the study criteria, with a median follow-up time of 6.3 years. The prediction of clinical failure by 102 definitions of biochemical failure was assessed using various quantitative measures. RESULTS:Four definitions were superior as measured by the sensitivity, specificity, positive and negative predictive values, and hazard of clinical failure after biochemical failure: two rises of at least 0.5 ng/mL backdated, PSA level at or greater than the absolute nadir plus 2 ng/mL at the call date, and PSA level at or greater than the current nadir plus 2 or 3 ng/mL at the call date. The absolute nadir was the lowest measured PSA level during all of follow-up, and the current nadir was the lowest PSA measured previous to a particular PSA measurement during follow-up. With the possible exception of patients in the low-risk group, the likelihood of ultimate clinical failure decreased as the time of biochemical failure increased. Failure definitions based on PSA levels >0.2 or 0.5 ng/mL were inferior to other definitions. Backdating the failure time introduced bias into the estimate of freedom from biochemical failure, which was increasingly overestimated at shorter median follow-up times. This bias can be circumvented either by using a failure definition based on the call date or by backdating the censoring times of patients with one or two rises who could potentially have failure at a future (unobserved) time. A short follow-up time as such does not result in bias unless the failures are backdated; in the absence of backdating, it is the precision of failure-free survival that is increasingly compromised as the follow-up time is reduced. CONCLUSION/CONCLUSIONS:The ASTRO failure definition ended the confusion resulting from different failure definitions that had been in use, and it did so accurately enough that it is probably not necessary to recalculate previously published results. Nevertheless, for the current pooled analysis of outcome in 4839 men with a 6.3-year median follow-up, other definitions of biochemical failure were superior as assessed by various quantitative measures of concordance of biochemical and ultimate clinical failure. An additional disadvantage of the ASTRO definition is the bias introduced by backdating failures, as well as the necessarily retrospective nature of its application. Some "current" definitions, but not those based on the PSA level rising above a fixed threshold, have significantly higher sensitivity and specificity, do not lead to biased estimations of biochemical disease-free survival, and are directly applicable during patient counseling. These are all issues that would play a role in replacing the ASTRO consensus definition.