C. Mitchell

Accelerated Treatment of Breast Cancer

PURPOSE Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P =.31 and 2% v 1%, P =.63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P =.24), disease-free survival (87% v 91%, P =.55), overall survival (90% v 93%, P =.66), or cause-specific survival (97% v 99%, P =.28). CONCLUSION Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

PURPOSE To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. METHODS AND MATERIALS Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. RESULTS The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. CONCLUSION Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Long-term patterns of in-breast failure in patients with early stage breast cancer treated with breast-conserving therapy: a molecular based clonality evaluation.

Background:The clonality of ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy (BCT) was established using a polymerase chain reaction-based allelic imbalance assay of microsatellite loci to compare tumor suppressor gene alteration patterns. Methods:The clonality of IBTRs relative to the initial invasive carcinomas were analyzed using a polymerase chain reaction-based allelic imbalance assay in 57 patients treated with BCT, including both whole breast irradiation and accelerated partial breast irradiation. Results:Thirty-four IBTRs (60%) were clonally related to the initial carcinoma and 23 (40%) were clonally different. Clonally related IBTRs were more frequently higher grade (70% vs. 32%, P = 0.019) and developed sooner after initial treatment (mean time interval to IBTR was 5.1 years in clonally related versus 9.3 years in clonally different cases [P = 0.002]). Twelve patients subsequently developed distant metastases, of which 9 (75%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 44% of all cases. The proportion of IBTRs that were clonally related at 5, 10, and 15 years after BCT were 82%, 48%, and 33%, respectively. Conclusions:This analysis demonstrates the inaccuracy of clinically establishing the clonality of most IBTRs. Clonally related IBTRs occurred sooner than clonally different IBTRs, were more frequently associated with the development of distant metastases and had a worse prognosis. Molecular clonality assays provide a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and provide an accurate assessment of the efficacy of various forms of local therapy.

Differences in disease presentation, management techniques, treatment outcome, and toxicities in African-American women with early stage breast cancer treated with breast-conserving therapy.

Data on patients who received breast‐conserving therapy (BCT) for early stage breast cancer were examined to detect differences in disease presentation, management techniques, long‐term treatment outcomes, and toxicities based on race.

A randomized assessment of three quality of life (QOL) questionnaires for prostate cancer patients undergoing different radiation treatment modalities

Abstract Purpose: The goal of this prospective, randomized study was to assess and compare compliance of patients diagnosed with prostate cancer to completing three different validated QOL instruments pre-treatment and six months later. Materials and Methods: Between April 2000 and April 2001, 124 patients were asked to fill out only one of three randomly selected QOL questionnaires (version A, B, C). Each addressed urinary and sexual function. One also addressed patients’ physical, social, family, emotional, and functional well being. Study patients received External Beam Radiation Therapy (EBRT) or Brachytherapy (BRACHY), according to departmental policy. Exclusion criteria included current/previous hormone therapy and prostatectomy. Patients were asked to return the questionnaire at their first treatment visit. The three tools were: A The Functional Assessment of Cancer Therapy for Prostate Patients (FACT-P), The Sexual Adjustments Questionnaire (SAQ), and The American Urological Association (AUA) Questionnaire. The Fact-P questionnaire elicits information about physical, social, family, emotional, and functional well being as they relate to prostate cancer. SAQ focuses on sexual function; the AUA on urinary symptoms. B SAQ and AUA only; identical to Version A, but does not address physical, social, family, emotional, and functional well-being. C The International Prostate Symptom Score (I-PSS) Questionnaire, which addresses urinary symptoms and Patient Sexual Function Questionnaire, which focuses on erectile function. Additionally, patients were asked to respond yes/no to four variables designed to evaluate these questionnaires: 1) ease of understanding, 2) too personal, 3)addresses concerns regarding urinary function and sexual potency and 4) willingness to complete questionnaire in six months. These variables were examined for any trends that may exist between the different questionnaires. Results: Fifteen (12%) of the 124 patients returned incomplete questionnaires due to the personal nature. When the 109 completed questionnaires were analyzed,the favorable responses of the four variables were compared. Favorable responses were received less frequently with version A when compared to version B (p=0.07) or Version C (p=0.08). Specifically, patients felt that version C addressed their concerns more effectively then version A (p= 0.03). Also, patients more frequently felt that version B was less personal when compared to versions A and C (p=0.01). When the patient responses were analyzed by treatment type, the group receiving EBRT appeared to trend toward version B. The group receiving BRACHY appeared to trend toward version C. Conclusion: Table I demonstrates that version B or C would provide a more effective QOL assessment. Patient accrual will continue to assess possible differences between B and C questionnaires. Evaluation Question Version A (n=35) Version B (n=35) Version C (n=39) 1. Easy to understand 86% yes 83% yes 95% yes 2.Too Personal 29% yes 14% yes 28% yes 3. Addresses Concerns 66% yes 77% yes 79% yes 4. Fill Out Again 80% yes 83% yes 85% yes Overall Favorable Responses 76% 82% 83%