Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.

PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.

Carcinoma of the cervix and the use of hyperbaric oxygen with radiotherapy: a report of a randomised controlled trial.

BACKGROUND AND PURPOSE: A randomised controlled trial of hyperbaric oxygen in the radiotherapy of Stage IIb and III carcinoma of cervix was performed between 1971 and 1980. Apart from an abstract giving an interim report in 1977, results have not been published. MATERIAL AND METHODS: In a four arm study, 335 patients were randomised to treatment in 10 or 28 fractions, in hyperbaric oxygen or in air. Data is available concerning 327 cases and this has been analysed. RESULTS: There was no advantage in tumour control shown with the use of hyperbaric oxygen. There was evidence for an increase in late radiation morbidity when treatment was given in hyperbaric oxygen rather than in air and when, using 10 fractions, a total dose of 45 rather than 40 Gy was achieved. For late intestinal morbidity, the fractionation sensitivity (alpha/beta ratio) was calculated to be 4.3 Gy and the steepness of the dose response curve (gamma50) to be 2.6. CONCLUSIONS: Hyperbaric oxygen gave no benefit in the treatment of patients with stage IIb and III carcinoma of the cervix treated with radiotherapy using two fractionation regimes. Important data regarding late radiation morbidity has been revealed.

A randomized, placebo-controlled, double-blind phase 2 study of docetaxel compared to docetaxel plus zosuquidar (LY335979) in women with metastatic or locally recurrent breast cancer who have received one prior chemotherapy regimen.

PURPOSE: To determine if concomitant administration of docetaxel plus zosuquidar.3HC1 can prolong progression-free survival in patients with metastatic breast cancer. METHODS: A randomized, double-blind, multicenter, placebo-controlled clinical trial comparing docetaxel plus 500 mg zosuquidar.3HCl (DZ) with docetaxel plus placebo (DP). RESULTS: A total of 170 patients were enrolled and randomly assigned to treatment. The median age was 53 years (range, 31-74 years). 81.7% of patients had prior chemotherapy in the adjuvant setting and 18.3% in the neoadjuvant setting. The median progression-free survival time was statistically different between groups [7.2 months (DZ) vs. 8.3 months (DP)]. Once the stratification factor relative to progression following prior chemotherapy was considered, no significant treatment difference existed. CONCLUSION: The combination of zosuquidar.3HCl plus docetaxel is safe. The analysis of efficacy data is complex, but it can be concluded that there is no difference in progression-free survival, overall survival, or response rate in the study as a whole.

Pregnancy and abortion in breast cancer patients. Two case reports and a literature review.

Breast cancer in pregnancy is by itself not an indication for abortion. We document the case histories of 2 patients with breast cancer (recurrent or advanced) who elected to carry pregnancies to term. Pregnancy concurrent with or subsequent to breast cancer is not associated with a worse prognosis than would be observed in non-pregnant women. Treatment for breast cancer may be an indication for abortion, but chemotherapy may be administered to pregnant patients, although it should be avoided in the first trimester if possible. Treatment such as radiotherapy may not be aimed at improving survival and this knowledge may affect a patient's decision regarding abortion. Breast cancer patients undergoing abortion must be aware of the exact indications for the procedure and the difference between medical and social indications.

A re-evaluation of isotope screening for skeletal metastases in node-negative breast cancer.

OBJECTIVE: To determine the accuracy and cost-effectiveness of skeletal scintigraphy in women with early, node-negative (T1-2N0M0) breast cancer. DESIGN: Retrospective, where scintigraphic prediction of metastases was compared with the criterion standard of radiological confirmation during a follow-up of 5 - 10 years. SETTING: Tertiary referral breast clinic at Groote Schuur Hospital. PATIENTS: Six hundred and seventy-three women with clinical T1-2N0M0 breast cancer who had skeletal scintigraphy between 1974 and 1987, and who had been followed up for more than 5 years. INTERVENTIONS: Initial skeletal scintigraphy, annual follow-up with radiological examination of symptomatic areas. MAIN OUTCOME MEASURES: Correlation of the sites indicated by scintigraphy with the initial presence or later development of metastases at 1 - 10 years, and the cost. RESULTS: Five hundred and sixty-one (83.4%) scans were normal, 35 (5.2%) indicated benign processes, and 77 (11.4%) were suggestive or diagnostic of metastatic disease, with radiological confirmation in 3 (initial detection rate 3/673, 0.44%; accuracy rate 3/77, 3.9%). Of the remaining 74 abnormal scans without radiological confirmation of metastases, 62 has a focus at a single site, and 45 were of low intensity and equivocal, with no apparent explanation. The cumulative sensitivity for predicting site of metastases at 1 year was 33% (3/9) and the positive predictive value 4.0% (3/75). At 10 years the sensitivity was 5.0% (3/60) and the positive predictive value 5.0% (3/65). The total cost of screening was calculated to be R323 460.00, suggesting that the cost for each patient in whom metastases were detected was R64 629.00. CONCLUSION: While scintigraphy may be of value in symptomatic or more advanced disease, screening of node-negative women had a minimal detection rate, was expensive and cannot be supported.

Prospective randomized trial of combined oncological therapy for gastric carcinoma.

One hundred forty-two patients with all stages of gastric carcinoma were prospectively stratified into two divisions according to T.N.M. stage following, but irrespective of the type of surgical procedure. Division I (T1-3, N1-2, M0) was randomized into a control group, and a treatment group who received 2000 rad in 8 fractions over 10 days with intravenous 5 Fluorouracil (5 F.U.) at a dose of 500 mg daily x 4 days preirradiation and then 12.5 mg/kg daily for 5 days every 28 days for six courses. Division II (T4 or M1) was randomized into three groups; a control group, a group who received radiotherapy and 5 F.U. in the same schedule as division one and a group who received Thiotepa 45 mg intravenously daily for three days and then every 28 days for 6 months. Four and one-half years after commencement of the trial 86% of the patients had died. There was no difference in survival rate between the treatment and control groups, (p greater than 0.5) in Division I or II. Survival appeared to correlate with the T.N.M. stage of disease and not therapy. Blind assessment of the quality of life showed no difference between the treatment groups and the controls. In the dose schedules used, this form of oncological therapy had no effect on survival or quality of life in patients with gastric carcinoma.

Giant condyloma (Buschke--Loewenstein tumor) of the anorectum.

A case of giant condyloma of Buschke and Loewenstein is presented. The clinical course and pathology of these tumors are reviewed. This case illustrates the delay in establishing the diagnosis in spite of numerous biopsies. It is emphasized that the only effective treatment is wide local excision.

Carcinoma of the thoraco-abdominal oesophagus.

A new approach in the management of carcinoma of the thoraco-abdominal oesophagus, by means of pre-operative chemotherapy, in the form of Methotrexate and irradiation, followed by a one-stage resection, using a thoracic/abdominal approach, is described. This resulted in a marked tumour regression without leading to difficulty with operative management.

Randomised trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma.

Lipiodol injected into the hepatic artery is selectively retained in hepatomas so has been used as a vehicle for cytotoxic drugs. This study compared treatment with 5-epidoxorubicin emulsified in lipiodol and infused into the hepatic artery with symptomatic treatment alone in a randomised trial. Of 136 patients with hepatoma 78 (57%) were not eligible, eight (6%) refused to take part, and 50 entered the trial (chemotherapy: n = 25, symptomatic treatment: n = 25). The two groups had similar prognostic indices. Seven of 25 patients allocated to chemotherapy were unable to receive it. The slight survival disadvantage associated with chemotherapy was not significant (median survival 48 days compared with 51 days, log rank chi 2 = 0.07, p > 0.05). Patients given chemotherapy spent significantly longer in hospital, however (median three days compared with one, p = 0.0008). Changes in symptoms and indices of tumour growth did not differ significantly between the two groups. It is concluded that infusion of 5-epidoxorubicin emulsified in lipiodol for hepatoma increased morbidity but did not affect survival. In addition, most patients were unsuitable for this treatment because of advanced disease. The patients in the trial had a short median survival time so the conclusions may not be valid for other patients with hepatoma.

Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer?

BACKGROUND: The prognosis of breast cancer in very young women is generally considered to be unfavourable. Therefore, the outcome of adjuvant therapy was analysed in a population of young (<35 years) premenopausal patients treated in four randomised controlled trials. METHODS: Between 1978 and 1993 the International Breast Cancer Study Group (IBCSG) treated 3700 premenopausal and perimenopausal patients with various timing and duration of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF with or without low-dose prednisone and oophorectomy). 314 of these women were less than 35 years old at randomisation. FINDINGS: Relapse and death occurred earlier and more often in younger (<35 years) than in older (> or = 35) patients with a 10 year disease-free survival of 35% (SE 3) versus 47% (1) (hazard ratio 1.41 [95% CI 1.22-1.62], p<0.001) and overall survival of 49% (3) versus 62% (1) (1.50 [1.28-1.77], p<0.001). Younger patients with oestrogen-receptor positive tumours had a significantly worse disease-free survival than younger patients with oestrogen-receptor negative tumours. By contrast, among older patients the disease-free survival was similar irrespective of oestrogen-receptor status. INTERPRETATION: Young premenopausal breast cancer patients treated with adjuvant CMF chemotherapy had higher risk of relapse and death than older premenopausal patients, especially if their tumours expressed oestrogen receptors. The endocrine effects of chemotherapy alone are insufficient for the younger age group and these patients should strongly consider additional endocrine therapies (tamoxifen or ovarian ablation) if their tumours express oestrogen receptors.

The neutron therapy clinical programme at the National Accelerator Centre (NAC).

A total of 721 patients were treated in the neutron therapy programme at NAC from February 1989-March 1995 with a p(66)/Be isocentric unit. The preliminary results showed: 3-year local control and survival probabilities of 57 and 79% respectively for advanced salivary gland tumours; increased local control for twice-daily neutron therapy for advanced head and neck cancer compared with photon therapy; local control rates of 68 and 83% for locally advanced breast cancer treated with 17 and 19 Gy respectively; complete response rates of 67% for macroscopic residual soft tissue sarcomas and those with irresectable disease of less than 10 cm; complete response rate of 56% for macroscopic residual uterine sarcoma with a median follow up of 38 months; 2-year local control rate and survival of 44 and 38% respectively for advanced squamous carcinoma of the maxillary antrum; complete response rate of 38% for advanced osteosarcomas and chondrosarcomas.