Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B.

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.

With modern imaging techniques, is staging laparotomy necessary in pediatric Hodgkin's disease? A Pediatric Oncology Group study.

PURPOSE: To determine whether the information gained from staging laparotomy can be predicted by imaging and/or clinical factors in children with Hodgkin's disease. PATIENTS AND METHODS: Between 1986 and 1991, 216 consecutive pediatric patients with Hodgkin's disease underwent laparotomy and were treated on two concurrent protocols in a multiinstitutional cooperative group. All patients had computed tomography (CT) of the chest, abdomen, and pelvis. Clinical factors studied included sedimentation rate, B symptoms, histology, number and location of involved sites, sex, mediastinal involvement, and age. Pretreatment CTs were centrally reviewed in 88 cases for the presence and size of both supradiaphragmatic and infradiaphragmatic lymph nodes, intrinsic spleen lesions, and splenic size. Models were generated that were predictive of any abdominal disease, splenic involvement, extensive splenic involvement, and upstaging at the laparotomy. False-positive and false-negative rates were calculated. RESULTS: For the end point of any abdominal disease, a model based on B symptoms, histology, sedimentation rate, and number and location of involved sites was highly significant (P < .0001). However, the success in predicting abdominal disease in an individual patient was limited: false-negative rate, 26%; false-positive rate, 32%. Highly significant models based on clinical factors and/or radiographic findings were also generated to predict splenic involvement, extensive splenic involvement, and upstaging with laparotomy, but they also had high false-positive and false-negative rates. CONCLUSION: Laparotomy findings cannot be predicted accurately in the majority of patients based on knowledge of CT findings and clinical factors.

Chronic vermal herniation in a case of osteosarcoma of the occipital bone.

Upward projection of the cerebellar vermis through the tentorial hiatus is called upward vermal herniation (UVH). UVH is less common in clinical practice than uncal herniation. Even more uncommon is chronic vermal herniation and impaction in the tentorial hiatus. To illustrate this phenomenon, we present the clinical, radiological, and morphological features of vermal impaction in a patient with a postradiation osteosarcoma of the occipital bone. In spite of nearly total excision of the tumor pushing the cerebellum upward, his postoperative course was complicated by respiratory problems and an altered level of consciousness, finally resulting in death. His clinical status paralleled the computed tomographic (CT) demonstration of persistent obliteration of the supramesencephalic cistern. CT makes more reliable the detection and management of UVH, but a high index of suspicion is necessary for prevention of this complication.

Proton NMR relaxation times in the peripheral blood of cancer patients.

The proton spin lattice relaxation time (T1) of serum and leucocytes of cancer patients and normal volunteers was measured using pulsed NMR techniques. There was no statistically significant difference in the serum T1 values of cancer patients relative to normal. An increase in T1 relative to normal values was detected in the white blood cells of patients with active leukaemia. In these patients T1 fell to normal levels after the initiation of treatment. The variation of leucocyte T1 with the course of the disease for five patients having leukaemia is presented.

Hematologic depression following therapy with strontium-89 chloride.

Initial clinical trials using strontium-89 (Sr-89) chloride for the treatment of painful skeletal metastases have observed minimal or no hematological depression secondary to the radiostrontium. A patient with marked bone marrow depression temporally related to the administration of the Sr-89 is reported, and the need for close hematological monitoring is emphasized. Bone marrow tumor replacement may predispose patients to marrow depression from radiostrontium, and such patients should be treated with caution.

Medulloblastoma: treatment results with radiation therapy.

The treatment results in 18 patients with medulloblastoma were reviewed retrospectively. All patients were treated postoperatively with simultaneous craniospinal irradiation. Forty-four percent of the total group were alive without evidence of disease. Six of the 12 patients eligible for analysis at three years after completion of treatment had continuous disease-free survival. Six patients with intracranial recurrence received a second course of whole-brain irradiation, and two of these are alive.

Results of radiotherapy for stage I and II Hodgkin's disease.

Fifty-six patients with pathologically staged I and II (A and B) Hodgkin's disease were treated with radiation therapy. Three-year relapse-free survival, total survival, and complications were analyzed. Chemotherapy was valuable as rescue treatment and as part of the initial treatment in patients with stage IIB disease. Complications were minimal.

Definitive irradiation in the treatment of Hodgkin's disease. Analysis of outcome, prognostic factors, and long-term complications.

BACKGROUND: In the curative treatment of Hodgkin's disease, many institutions give doses above 40 Gray (Gy). To assess the effectiveness of treating patients with 35 Gy, data from a single institution regarding survival, prognostic factors, patterns of failure, and secondary complications were reviewed. METHODS: Data for a total of 172 patients with Hodgkin's disease were reviewed. All patients received definitive irradiation between 1971 and 1994. Median follow-up was 110 months. Kaplan-Meier methods were used to estimate survival, relapse-free survival, and complication rates. RESULTS: Relapse-free survival was 83% at 5 years and 76% at 10 years. The only two prognostic factors related to relapse-free survival were the stage of disease and the number of sites. The involved infield control rate was 96%. The 10-year estimates of hypothyroidism and second malignancies were 14% and 10%, respectively. CONCLUSIONS: Doses of 35 Gy are adequate for treating Hodgkin's disease. The stage of disease and the number of sites are predictive of relapse-free survival. The incidence of late complications necessitates long term surveillance of these patients.

The inverse compensating filter.

When a single-field technique is used in megavoltage x-ray therapy, a uniform entrance dose is often required. If there is a large variation in source-to-surface distance over the field, an inverse type of compensating filter is necessary to achieve entrance dose uniformity. The production and utilization of these filters is discussed.

Relationship of lesion size to survival in patients with stage IB squamous cell carcinoma of the cervix uteri treated by radiation therapy.

Forty-five patients with Stage IB squamous cell carcinoma of the cervix uteri were treated with radiation therapy alone. The five year actuarial survival rate of the 22 patients in group 1 in whom the tumor was less than 4 centimeters in diameter was 95 per cent, which was significantly higher than the 67 per cent survival rate in the 23 patients in group 2 with bulky lesions greater than or equal to 4 centimeters in diameter, p less than 0.05. These results of radiation therapy are consistent with surgical results recently reported and indicate that patients with bulky lesions, especially those tumors greater than or equal to 4 centimeters in size, comprise a high risk subset within the Stage IB classification. A new classification is proposed in which bulky lesions are designated Stage IC, advanced overt, so that such high risk patients might be identified and more efficacious treatment regimens might be developed.

Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma.

BACKGROUND: Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity. METHODS: The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the first. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group. RESULTS: After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P < 0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity. CONCLUSIONS: The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved.