Reduced thoracic vertebrae metastases following post mastectomy parasternal irradiation.

A retrospective study of 118 women with breast cancer metastatic to bone is presented. All had originally received post mastectomy adjuvant radiation therapy for Stage II (T2 N0, T2 N1, T1 N1) infiltrating duct carcinoma of breast. Sixty-two women (group A) received a parasternal portal and 56 women (group B) did not. There was significantly less metastatic involvement of the mid-dorsal vertebrae D5-6-7-8, 13% in group A compared to 60% in group B. The mean time to diagnosis of metastatic disease was 33 months (group A) and 36 months (group B). The dose of radiation to the vertebrae through which the parasternal beam exited was estimated at between 1000-1600 rad over three to four weeks. This observation may have significant implications for the management of high risk operable breast cancer.

Adjuvant therapy for Dukes C adenocarcinoma of colon.

Forty-two patients with adenocarcinoma of the colon, who received surgery between 1975 and 1978 and were to found to have pericolonic fat infiltration and lymph node metastases, were analyzed for disease free period and overall survival. Twenty-one patients had received post-operative X ray therapy, and post-X ray therapy intravenous 5-Fluorouracil adjuvant therapy. Twenty-one patients, matched by age, sex, ethnic origin and site of disease were untreated. The 5 year survival rate for the treated group was 65% compared with 36% for the control group (P greater than 0.2). At 5 years 55% of the treated group were disease free but only 12% of the control group remained disease free (P = 0.04). The significance of this work needs to be established by a randomized and prospectively controlled clinical trial.

Modification of the response of mouse skin to x-irradiation by a polar solvent, N,N-dimethylformamide.

The modification of the response of mouse skin to either single or split (24 hrs) graded doses of X rays by topically applied N,N-dimethylformamide (DMF) was investigated. DMF was applied daily for 5 days prior to irradiation. At a radiation dose level producing dry desquamation, DMF enhanced the X ray response by a factor of 1.3. Also, at the same level of response, the fraction of X ray dose repaired in 24 hours was 0.57, whereas for the DMF-treated and irradiated skin, this factor was 0.41, indicating a reduction of about 28% in subeffective damage repair. The times of maximal involvement of the skin reactions were not different in the X ray plus DMF treated mice versus mice receiving x-irradiation only. The data indicate that DMF is able to modify intrinsic radiation sensitivity of mouse skin epithelial cells, possibly through a reduction in the magnitude of the shoulder region of the survival curve.

Adjuvant treatment of high-risk stage II breast cancer with doxorubicin followed by high-dose chemotherapy and autologous stem-cell transplantation: a single-institution experience with 132 consecutive patients.

Several studies have shown conflicting results with the use of intensive consolidation chemotherapy for breast cancer. The aim of the present study was to investigate the efficacy, feasibility and toxicity of high-dose chemotherapy with stem cell support in patients with high-risk stage II breast cancer. From February 1994 to November 1998, 132 consecutive patients with multinode positive breast cancer were entered to the study. In total, 86 patients had >or=10 positive axillary lymph nodes, and 46 had 4-9 positive axillary lymph nodes with at least two additional predetermined risk factors at diagnosis. All patients were offered adjuvant chemotherapy (doxorubicin, 75 mg/m(2) x 4) followed by high-dose chemotherapy (cyclophosphamide 6000 mg/m(2), carboplatin 800 mg/m(2) and thio-tepa 500 mg/m(2)) and autologous stem cell support with growth factor. In all, 131 patients also received local radiation therapy and tamoxifen based on receptor status. After a median follow-up of 51 months (range 27-87), the disease-free and overall survival rates were 72 and 81%, respectively. There was no difference in the outcome for high-risk patients with > or < than 10 positive axillary lymph nodes. On Cox regression analysis only progesterone receptor status was predictive of disease-free, but not overall survival. There were no treatment-related deaths; grades III-IV toxicity was relatively low. This combined approach of doxorubicin followed by high-dose chemotherapy and stem-cell support, followed by locoregional radiotherapy, was safe and seems to be effective in patients with multinode positive stage II breast cancer. In previous trials of adjuvant high-dose therapy in this patient population, treatment-related morbidity and mortality markedly influenced the outcome. For this high-risk patient population, further testing of intensive chemotherapy regimens with a lower toxicity profile is warranted.

CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus cnf (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: a phase III randomized multicenter study.

A multicenter phase III randomized study compared the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer. The standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), was administered to 77 women. The experimental protocol, CNF (cyclophosphamide, mitoxantrone, 5-FU), in which mitoxantrone (Novantrone) replaced methotrexate, was given to 68 patients. Follow-up of the 145 patients by six participating hospitals showed no statistically significant difference (p = 0.6) between the two treatment regimens during a median follow-up of 4.5 years in terms of overall survival. There was, however, a significant advantage (p = 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF). Toxic side effects associated with CNF (particularly alopecia and myelotoxicity) were relatively more frequent but acceptable and did not lead to dose reduction. In light of its association with improved disease-free survival in this study, larger studies should be undertaken on the role of mitoxantrone as adjuvant treatment in stage II breast cancer.

Prophylactic low-dose post-operative orthovoltage radiotherapy in stage II breast cancer.

Between the years 1974 and the beginning of 1977, 199 patients with stage II infiltrating duct carcinoma of the breast were treated with post-operative radiation, using a 250 kVp X-ray machine. Three treatment schedules were used consisting of 22, 26.2 and 29.6 Gy (2200, 2620 and 2960 rad) total tumour dose, calculated at 2 cm depth, with 5, 3 and 3 fractions a week respectively. The frequency of local recurrences, mainly in the chest wall, were 20.3%, 8.3% and 8.1% respectively. The latter two frequencies were not different from those reported for the commonly used high dose treatments of 45-60 Gy (4500-6000 rad) delivered either as given doses or tumour doses. An approximate 70% five year survival rate was similar in the three groups and does not differ from results observed with high doses. Low dose treatment is advantageous, because it has fewer complications and it can be delivered in a smaller number of sessions, making it more convenient to the patient, without loss of efficacy. The results presented of the low dose treatment may reflect the existence of an optimal dose level of radiation.

[Extraskeletal Ewing's sarcoma].

5 patients diagnosed as having extraskeletal Ewing's sarcoma have been referred to our adult oncology unit since 1980. All were men, ranging in age from 18-57 (mean 32 years). The primary tumor was located on the trunk in 4 and in an extremity in 1. Wide tumor excision was feasible in only 2. 3 died within 27 months and 2 are alive, 13 and 67 months, respectively, following diagnosis. This study demonstrates the highly aggressive nature of extraskeletal Ewing's sarcoma and the need for early diagnosis and efficient chemotherapy.

Combined local hyperthermia and x-irradiation in the treatment of metastatic tumours.

Six patients, all with evidence of metastatic or locally recurrent tumours, were selected for inclusion in a trial study of simultaneous hyperthermia and ionizing radiation therapy. Heat was applied by hot air, or microwaves, or a combination of both. When examined after treatment, 3 patients were found to be free of the lesions treated. One patient had a partial response, followed by regression of the tumour; one patient died with metastases in the lungs and one patient responded to the treatment but died from a massive pulmonary embolus. The simultaneous application of hyperthermia and ionizing radiation therapy was well tolerated. It induced disappearance of tumours in cases where conventional methods had failed, and with far greater efficiency than conventional therapeutic methods.

Hodgkin's disease of the lung.

The clinical and radiological findings in 16 patients with Hodgkin's disease involving the lung are reviewed. Lung involvement was evident at initial presentation in 11 patients and appeared during the course of the disease in five patients. All the patients had hilar as well as mediastinal lymphadenopathy; most of them--14 of 16--had the nodular sclerosis type of the disease. Patients with these combined findings are apparently more likely to develop lung lesions. Seven of the 11 patients with lung involvement at presentation were symptomatic and received combined chemotherapy in addition to radiotherapy. The lung lesions responded completely in 10 of the 11 patients, and in one they cleared slowly after more than a year of treatment. The question remains open as to whether an asymptomatic patient in the high-risk group, as described above, should receive either adjuvant chemotherapy or radiation therapy to the lung on the prophylactic basis. Our own policy is to add chemotherapy as an adjuvant to female patients and to males who have children.