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Purpose: We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to determine the impact of patient age on outcome., Patients and Methods: From 1980 to 1993, 146 patients were treated with BCT for DCIS. All patients underwent excisional biopsy, and 64% underwent re-excision. All patients received whole-breast irradiation to a median dose of 45 Gy. Ninety-four percent of patients received a boost to the tumor bed, for a median total dose of 60.4 Gy. All slides on every patient were reviewed by one pathologist. The median follow-up period was 7.2 years., Results: Seventeen patients developed an ipsilateral local recurrence, for 5- and 10-year actuarial rates of 10.2% and 12.4%, respectively. The 10-year rate of ipsilateral failure was 26.1% in patients younger than 45 years of age versus 8.6% in older patients (P =.03). On multivariate analysis, young age was independently associated with recurrence of the index lesion (true recurrence/marginal miss ¿TR/MM failures), regardless of how it was analyzed (eg, < 45 years of age or as a continuous variable). In addition, young patients had a dramatically higher 10-year rate of invasive TR/MM failures (19.9% v 3.2%). In a separate multivariate analysis for the development of invasive TR/MM failures, only patient age and predominant nuclear grade were independently associated with recurrence. The relationship between excision volume and outcome was analyzed in the 95 patients who underwent re-excision. The 5-year actuarial rate of TR/MM failure was significantly worse only in young patients with smaller (< 40 mL) re-excision volumes (33.3% v 9.1%; P =.02). In a separate multivariate analysis of only these 95 patients (25 of whom were < 45 years of age), the volume of re-excision had the strongest association with outcome (P =.05). Patient age was no longer associated with local recurrence., Conclusion: These findings suggest that young patients with DCIS have a significantly greater risk of local recurrence after BCT that is independent of other previously defined risk factors. Our data also suggest that the extent of resection may in part be related to the less optimal results that are observed in these patients.

Background: The authors retrospectively reviewed their institution's long term experience with conventional external beam radiation therapy (RT) for localized prostate carcinoma to identify criteria associated with long term biochemical cure., Methods: Between January 1987 and December 1994, 871 patients were treated with external beam RT alone for clinically localized prostate carcinoma at William Beaumont Hospital, Royal Oak, Michigan. All patients received only external beam RT to a median total dose of 66.6 grays (Gy) (range, 59.4-70.4 Gy). No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 5.0 years (range, 0. 2-11.8 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition., Results: In the entire study group, 380 patients experienced biochemical failure at a median interval of 1.5 years after the completion of RT. The 5-year and 7-year actuarial rates of biochemical control were 50% and 48%, respectively. On multivariate analysis, a higher pretreatment prostate specific antigen (PSA) level, higher Gleason score, higher clinical T classification, higher nadir level, and shorter time interval to nadir all were associated significantly with biochemical failure (P < 0.001). The median intervals to biochemical failure for patients with pretreatment PSA levels /= 20.0 ng/mL were 2.2 years, 1.5 years, and 1.2 years, respectively (P < 0. 001). The median intervals to biochemical failure for patients with Gleason scores of 2-4, 5-7, and 8-10 were 1.8 years, 1.5 years, and 1.1 years, respectively (P < 0.001). Only 6 patients failed beyond 5 years after treatment even though 136 patients were at risk for failure beyond this point. When restricting analysis to 643 patients (74%) with >/= 3 years of PSA follow-up, the median nadir level for biochemically controlled patients was 0.6 ng/mL and occurred at a median interval of 1.9 years after RT versus a median nadir level of 1.3 ng/mL (P = 0.002) occurring at a median interval of 1.0 years (P < 0.001) in those patients who experienced biochemical failure. Patients were divided into subgroups based on their PSA nadir level and time to nadir. The 5-year actuarial biochemical control rates for patients with nadir values of /= 4.0 ng/mL were 78%, 60%, 50%, 20%, and 9%, respectively (P < 0.001). The 5-year actuarial biochemical control rates for patients who reached their nadir at < 1.0 years, 1.0-1.9 years, 2.0-2.9 years, and >/= 3.0 years were 30%, 52%, 64%, and 92%, respectively (P < 0.001). All 52 patients who achieved a nadir of /= 2.0 years to reach this nadir had biochemically controlled disease., Conclusions: These results suggest that a patient has a high likelihood of biochemical cure after treatment for prostate carcinoma with conventional doses of external beam RT if he has not demonstrated biochemical failure within 5 years of treatment. Patients with lower pretreatment PSA levels and lower Gleason scores may require longer follow-up than those with less favorable characteristics to achieve the same certainty of cure. Patients who achieve a PSA nadir /= 2.0 years to reach this nadir have the highest probability of cure., (Copyright 1999 American Cancer Society.)

Purpose/objective: The use of brachytherapy in the management of breast cancer has increased significantly over the past several years. Unfortunately, few techniques have been developed to compare dosimetric quality and target volume coverage concurrently. We present a new method of implant evaluation that incorporates computed tomography-based three-dimensional (3D) dose-volume analysis with traditional measures of brachytherapy quality. Analyses performed in this fashion will be needed to ultimately assist in determining the efficacy of breast implants., Methods and Materials: Since March of 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. Eight patients treated with high-dose-rate (HDR) brachytherapy who had surgical clips outlining the lumpectomy cavity and underwent computed tomography (CT) scanning after implant placement were selected for this study. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system. The lumpectomy cavity, target volume (lumpectomy cavity plus a 1-cm margin), and entire breast were outlined on each axial slice. Once all volumes were entered, the programmed HDR brachytherapy source positions and dwell times were imported into the 3D planning system. Using the tools provided by the 3D planning system, the implant dataset was then registered to the visible implant template in the CT dataset. The distribution of the implant dose was analyzed with respect to defined volumes via dose-volume histograms (DVH). Isodose surfaces, the dose homogeneity index, and dosimetric coverage of the defined volumes were calculated and contrasted. All patients received 32 Gy to the entire implanted volume in 8 fractions of 4 Gy over 4 days., Results: Three-plane implants were used for 7 patients and a two-plane implant for 1 patient. The median number of needles per implant was 16.5 (range 11-18). Despite visual verification by the treating physician that surgical clips (with an appropriate margin) were within the boundaries of the implant needles, the median proportion of the lumpectomy cavity that received the prescribed dose was only 87% (range 73-98%). With respect to the target volume, a median of only 68% (range 56-81%) of this volume received 100% of the prescribed dose. On average, the minimum dose received by at least 90% of the target volume was 22 Gy (range 17.3-26.9), which corresponds to 69% of the prescribed dose., Conclusion: Preliminary results using our new technique to evaluate implant quality with CT-based 3D dose-volume analysis appear promising. Dosimetric quality and target volume coverage can be concurrently analyzed, allowing the possibility of evaluating implants prospectively. Considering that target volume coverage may be suboptimal even after radiographically verifying accurate implant placement, techniques similar to this need to be developed to ultimately determine the true efficacy of brachytherapy in the management of breast cancer.

Purpose: We reviewed our institution's experience treating patients with localized prostate cancer with external beam radiation therapy (RT) to determine how differences in the length of follow-up affect the determination of treatment outcome using the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Panel Definition of biochemical failure (BF)., Methods and Materials: From January 1987 through December 1997, 1109 patients with localized prostate cancer were treated with definitive external beam RT at William Beaumont Hospital, Royal Oak, Michigan. All patients received external beam RT to a median total prostate dose of 66.6 Gy (range: 59.4-70.4 Gy). A total of 1096 patients (99%) had sufficient prostate-specific antigen (PSA) follow-up to determine their biochemical status. To test the impact of differences in follow-up on the calculation of BF, 389 patients with at least 5 years of PSA follow-up were selected as the reference group for the initial analysis. BF was then retrospectively determined using the Consensus Panel definition at yearly intervals, ignoring the remainder of each patient's follow-up. The median follow-up for this group of patients was 6.6 years (range: 5.0-11.6 years). In a second analysis, patient cohorts were randomly selected with varying median PSA follow-up intervals in order to more accurately represent a population whose follow-up is distributed continuously over a defined range. Seven cohorts were randomly selected with 200 patients in each cohort. Cohorts were individually identified such that half of the patients (100) had 2 years or less follow-up than the stated time point for analysis and half (100) had up to 2 years more follow-up than the time point chosen for analysis. For example, in the cohort with a median follow-up of 3 years, 100 patients with a PSA follow-up from 1 to 3 years were randomly selected, and 100 patients with a follow-up from 3 to 5 years were randomly selected, thus generating a median follow-up of 3 years for this cohort (range: 1 to 5 years). This process was repeated five times for five random samples of seven cohorts each. Biochemical failure was calculated according to the Consensus Panel definition., Results: In the first analysis, significantly different rates of biochemical control (varying by 6-21%) were calculated for the same actuarial year chosen for analysis depending only upon the length of follow-up used. For example, the 3-year actuarial rate of biochemical control (BC) varied from 71% when calculated with 3 years of follow-up versus 50.4% with 7 years (p < 0.01). These differences in actuarial rates of BC were observed in all subsets of patients analyzed (e.g., PSA < 10, Gleason < or = 6, n = 132,p < 0.001; PSA < 10, Gleason > or = 7, n = 33, p = 0.03; PSA > or = 10, Gleason < or = 6, n = 109, p < 0.001; and PSA > or = 10, Gleason > or = 7, n = 72, p = 0.002). The absolute magnitude of the difference in actuarial rates of BC was greatest during years 2 (range 18-30%), 3 (range 16-25%), and 4 (range 15-24%) after treatment. In the second analysis using median PSA follow-ups (as defined above), statistically significant differences in actuarial rates of BC were again observed. For example, the 3-year actuarial rate of BC varied from 74.8% with a median follow-up of 2 years versus 49.2% with a median follow-up of 6 years. These dramatic differences in BC were still observed beyond 5 years., Conclusion: When the ASTRO Consensus Panel definition of BF is used to calculate treatment success with external beam RT for prostate cancer, adequate follow-up is critical. Depending upon the length of time after treatment, significantly different rates of BC (varying by 15% to 30%) can be calculated for the same time interval chosen for analysis. These results suggest that data should only be reported if the length of follow-up extends at least beyond the time point at which actuarial results are examined for the majority of patients.

Background: Lumpectomy and radiation therapy is considered a standard treatment option for ductal carcinoma in situ (DCIS) of the breast. The incidence of locally recurrent carcinoma using this therapeutic approach ranges from 6%-19%. Multiple studies have attempted to identify factors associated with the development of local recurrences in these patients. Despite extensive reports examining this issue, no factor(s) has consistently been correlated with outcome., Methods: This review examines the criteria that various authors have proposed as being associated with recurrence, including DCIS grade, size, histologic subtype, status of surgical margins, and technical factors to help clarify their roles in optimizing treatment outcome. The issue of the definition of the type of recurrence is also addressed., Results: Though multiple studies have examined the impact of grade, histologic subtype, necrosis, and DCIS size on outcome, no consistent results have been observed to suggest that these factors can be routinely used to guide therapy. The adequacy of excision appears to correlate with local control but is imprecisely defined by margin status alone. Based upon recent data, it appears that atypical ductal hyperplasia and cancerization of lobules in the context of coexistent DCIS, may need to be considered as part of the DCIS lesion that should be excised. This issue may account for some of the disparate results of different studies of DCIS. For statistical purposes, recent studies also suggest that only recurrences developing within or adjacent to the bed of the initial DCIS lesion should be considered when analyzing factors associated with outcome. Recurrences developing elsewhere in the breast may include new DCIS and invasive lesions that bear no biologic relationship with the initial DCIS lesion. Finally, since it is impossible to insure that all DCIS has been removed, it may be more appropriate to consider DCIS lesions as adequately or inadequately excised instead of completely or incompletely excised. Since DCIS is essentially a microscopic disease, pathologists should have a primary role in helping to define the adequacy of excision., Conclusions: Additional studies with complete pathology review and longer follow-up are needed to reach a consensus on which prognostic factors are consistently associated with recurrence for patients with DCIS treated with lumpectomy and radiation therapy. At the present time, adequacy of excision appears to correlate with outcome. However, more precise and consistent methods need to be developed to assist in the determination of adequate DCIS extirpation.

Objectives: To determine the factors associated with outcome by reviewing our institution's experience treating patients with external beam radiation therapy (RT) after radical prostatectomy., Methods: Sixty-one patients received RT to the prostatic fossa after radical prostatectomy for prostate cancer (median dose 59.4 Gy). Thirty-eight patients received adjuvant RT within 6 months of surgery for adverse pathologic findings only. Therapeutic RT was administered to 23 patients either for a persistently elevated postoperative prostate-specific antigen (PSA) level (n = 2), a rising PSA level more than 6 months after surgery (n = 9), or a biopsy-proven local recurrence (n = 12). Preoperative and preradiation PSA values, Gleason score, pathologic findings, patient age, total RT dose, and indication for RT were analyzed for their impact on biochemical control. The median follow-up was 48 months., Results: Patients treated with adjuvant RT achieved 3 and 5-year biochemical control rates of 84% and 67%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. No variable was associated with 5-year outcome. The 5-year actuarial rate of biochemical control for patients treated with therapeutic RT was 16%. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical control. Only a pre-RT PSA level of 2 ng/mL or less was associated with an improved rate of biochemical control at 3 years (80% versus 27%, P = 0.001). However, at 5 years, this difference was not statistically significant. A separate analysis was performed to determine the prognostic factors associated with outcome for the entire group of patients. Only the indication for RT (adjuvant versus therapeutic) was associated with 5-year outcome. Patients treated with adjuvant RT had a statistically significant improvement in 5-year actuarial rates of biochemical control (67% versus 16%, P <0.001) and disease-free survival (66% versus 46%, P = 0.037) but not in overall survival. There were no statistically significant differences between patient groups with respect to age, preoperative PSA, Gleason score, pathologic T stage, median follow-up, and total RT dose., Conclusions: At our institution, patients treated with adjuvant RT after prostatectomy for adverse pathologic findings achieved excellent rates of biochemical control that were significantly better than that of similar patients treated therapeutically for persistent or rising PSA or clinical local recurrence.

Brachytherapy boosts in combination with external-beam radiation therapy allow a highly conformal dose of radiation to be delivered to the prostate in a safe, efficient manner. Several types of brachytherapy boost techniques are used currently. Techniques based on transrectal ultrasound (TRUS) guidance clearly provide the most accurate method of radioactive source placement with reduced toxicity. Temporary implants employing remote afterloading systems with high-dose-rate (HDR) brachytherapy offer the added advantage of further optimizing dose distribution after needle placement. Novel brachytherapy programs using intraoperative real-time dosimetric analyses provide additional options for performing truly conformal dose escalation. Results with these newer boost techniques appear to be as good as or better than other forms of therapy in comparably staged patients. Until standardized methods of reporting treatment data are uniformly applied and longer follow-up is obtained with other treatment modalities, brachytherapy boosts combined with external-beam radiation should be considered an acceptable treatment option for patients with locally advanced prostate cancer. The challenge for the future will be to determine which treatment approach is optimal given certain critical pretreatment prognostic factors. In addition, the role of adjuvant androgen deprivation in controlling this malignancy will be critical and awaits the results of several recently initiated or completed randomized trials.