Local control, toxicity, and cosmesis in women younger than 50 enrolled onto the American Society of Breast Surgeons MammoSite Radiation Therapy System registry trial.

BACKGROUND: The American Society of Breast Surgeons enrolled women onto a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System (RTS) breast brachytherapy device. This report examines local recurrence (LR), toxicity, and cosmesis as a function of age in women enrolled onto the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated in 1440 women. Of these, 130 occurred in women younger than 50 years of age. Fisher's exact test was performed to correlate age (<50 vs. > or = 50 years) with toxicity and with cosmesis. The association of age with LR failure times was investigated by fitting a parametric model. RESULTS: Women younger than 50 were more likely to develop fat necrosis: 4.6% (6 of 130) vs. 1.8% (24 of 1319) (P = .0456). Other toxicities were comparable. At 2 years, cosmesis was excellent or good in 87% of assessable women aged <50 years (n = 74) and in 94% of assessable older women (n = 751) (P = .0197). At 3 years, this difference disappeared: excellent or good in 90% (56 of 62) of younger women vs. 93% (573 of 614) of older women (P = .2902). The crude LR rate for the group was 1.7% (25 of 1449). There was no statistically significant difference in LR as a function of age. In women <50, 3.1% (4 of 130) developed a LR; in the older patients, 1.6% (21 of 1319) developed LR (3-year actuarial LR rates, 2.9% vs. 1.7%, respectively; P = .2284). CONCLUSIONS: Accelerated partial breast irradiation with the MammoSite RTS results in low toxicity and produces similar cosmesis and local control at 3 years in women younger than 50 when compared with older women.

Phase I trial of concomitant chemoradiotherapy for cervical cancer and other advanced pelvic malignancies.

Purpose. The aim of this study was to determine the feasibility and toxicity of concomitant hydroxyurea (HU) and escalating doses of 5-fluorouracil (5-FU) in locally advanced cervical cancer and other pelvic malignancies undergoing radiation therapy (RT). Methods. Treatment consisted of 5-FU, HU, and pelvic RT delivered in an alternate-week fashion. 5-FU was administered as a continuous intravenous infusion at a starting dose of 600 mg/m2/day and was escalated to 1000 mg/m2/day in cohorts of three patients. The HU dose was 500 mg twice daily. Chemoradiotherapy was administered on a 5-day cycle. Following a 9-day rest, the cycle was repeated until the completion of the pelvic RT. Results. Twenty-one patients (18 cervix, 1 bladder, 1 vagina, 1 ovary) were enrolled. 5-FU escalation to 1000 mg/m2/day was well tolerated. No patients developed grade 3-4 hematologic toxicity. Grade 2 leukopenia was noted in 3 patients (14.3%). Grade 3 mucositis, diarrhea, and dermatitis occurred in 10, 10, and 5% of patients, respectively. None of the 99 treatment cycles were delayed secondary to acute toxicity. The overall response rate in the 18 cervical cancer patients was 89% (78% complete, 11% partial). Conclusions. Concomitant continuous infusion 5-FU, twice daily HU, and pelvic RT delivered in an alternate-week fashion is well tolerated. Further study is necessary to evaluate the therapeutic efficacy of this regimen in patients with advanced cervical and other pelvic malignancies.

Natural history of node-positive breast cancer: the curability of small cancers with a limited number of positive nodes.

PURPOSE: The long-term outcome of node-positive breast cancer was analyzed to determine the risk of metastatic disease as a function of tumor size and number of positive nodes. METHODS: From 1927 to 1987, 501 women with node-positive breast cancer were treated at the University of Chicago Medical Center. Patients were treated with radical, extended radical, or modified radical mastectomy. Forty-eight patients received multiagent chemotherapy, and 118 were treated with hormonal therapy. The mean survival duration is 120 months, with a maximal follow-up time of 485 months (40 years). RESULTS: The number of nodes that contained metastatic disease and the pathologic size of the primary tumor were significant determinants of disease-free-survival (DFS) by multivariate analysis (P < .001). In patients with fewer than four positive nodes, tumor size was of prognostic importance, with small tumors more likely to be cured by local-regional therapy. The 20-year DFS rate for patients with one positive node was 69%; however, if the primary tumor was < or = 2 cm, the 20-year DFS rate was 81%, compared with 59% if the tumor was larger than 2 cm. Patients with two or three positive nodes had a 73% 20-year DFS rate if the tumor size was < or = 2 cm, compared with 53% 20-year DFS in patients with tumors larger than 2 cm. CONCLUSION: In patients with T1 lesions with less than four nodes positive, the long-term DFS rate is comparable to that for node-negative breast cancer of the same size. Four or more nodes positive is an indicator of likely systemic disease.

Natural history of node-negative breast cancer: a study of 826 patients with long-term follow-up.

PURPOSE: We were interested in examining the long-term outcome of patients with node-negative breast cancer to address the following questions: (1) Is node-negative breast cancer a disease that is curable by local modalities? (2) Are there predictors of disseminated disease in node-negative breast cancer? (3) Are there subgroups of tumors that have different times to recurrence? METHODS: From 1927 to 1984, 826 women with node-negative breast cancer were treated at the University of Chicago. Patients underwent either a radical or extended radical mastectomy (83%) or a modified radical mastectomy (13%). RESULTS: Follow-up evaluation ranged from 9 to 523 months (43.6 years); the mean follow-up period of survivors is 162 months (13.5 years). On multivariate analysis, the strongest predictor of outcome and time to relapse was pathologic tumor size. Patients with tumors less than 2 cm had a 20-year disease-free survival (DFS) rate of 79% and a median time to recurrence of 48 months as compared with patients with tumors greater than 2 cm, who had a survival rate of 64% (P < .001) and a median time to recurrence of 37 months (P = .01). CONCLUSION: With extended follow-up evaluation, node-negative breast cancer is a curable disease. Size is the strongest predictor of dissemination and rate of relapse. These data suggest that given the natural history of node-negative breast cancer, analysis of clinical trials with short follow-up periods can be misleading, since it may identify those patients whose tumors have a greater virulence but not necessarily a greater likelihood to metastasize.

Ultrasound guidance for placement of difficult intracavitary implants.

Placement of a radiation implant in patients with cervical cancer may be difficult because of distortion of the canal by tumor or fibrosis from previous radiation. The objective of this study was to determine whether ultrasound may be useful in recognizing or preventing complications associated with placement of an intracavitary implant. Transabdominal ultrasound was used during and after 20 intracavitary implants in patients with cervical cancers. In placing 20 implants, there were 9 placed in less than satisfactory relation to the anatomy of the uterus. In 6 patients, occult perforations occurred, with two-thirds not detected by the operator. Increased difficulty was seen at the time of placement of a second implant after external radiation. By using ultrasound, correction of the misplaced tandem could be made immediately without resorting to more invasive surgical approaches.

Variation in radiation sensitivity during the cell cycle of two human squamous cell carcinomas.

Changes in the radiation age response are described in two cell lines derived from human squamous cell carcinomas. A radioresistant tumor cell line, JSQ-3, has a DO of 240 cGy and is polyploid with a DNA content of 2.68. A relatively radiosensitive tumor cell line, SCC-61, has a DO of 126 cGy and has a DNA index of 1.16. Tumor cells were separated and synchronized by centrifugal elutriation; flow cytometry was used to determine cell-cycle parameters and relative synchrony. The radioresistant cell line, JSQ-3B, was found to have twice the number of cells in S-phase than the more sensitive cell line (28% and 13% for JSQ-3B and SCC-61B, respectively). Both cell lines, despite differences in intrinsic radiosensitivity, were most resistant during S-phase (DOs of 258 and 157 cGy for JSQ-3B and SCC-61B, respectively) and were maximally sensitive during G1 (DOs of 193 and 95 cGy for JSQ-3B and SCC-61B, respectively). Clinical implications of our findings are discussed.

Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a preliminary report).

Twenty-five patients with invasive transitional cell carcinoma of the bladder (Stage T2, T3, T4) received combined modality therapy using four cycles of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease are currently alive, 7 with normal bladder function. The two with T4 disease are dead of disease. Three patients required salvage cystectomy for local recurrence and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50 months with a median of 31 months. No late chemo-radiotherapy treatment-related complications to the intestines or in bladder function (other than one bladder stone formation) occurred. These preliminary results are encouraging and warrant further evaluation of this innovative approach in treating invasive carcinoma of the bladder. T2 and T3 patients with a complete or partial response to MVAC may be excellent candidates for a bladder-sparing treatment.