From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.
A consecutive 10-year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis-free survival were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent) were high grade. High-grade tumours were divided into two groups; 80 (29 per cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2. Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading was found to be the prognostic factor associated with the strongest predictive value. Five-year survival in low-grade and intermediate tumours (95 and 86 percent, respectively) differed significantly (P less than 0.0001) from high grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high-grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).
Two hundred ninety patients with Hodgkin's disease pathologic stage (PS) I or II were treated in the prospective randomized trial of the Danish National Hodgkin Study (see Appendix) with radiotherapy +/- adjuvant combination chemotherapy. The initial tumor burden of each patient was assessed, combining tumor size of each involved region and number of regions involved. Multivariate analyses of prognostic factors including treatment, tumor burden, histologic subtype, pathologic stage, number of involved regions, mediastinal size, systemic symptoms, erythrocyte sedimentation rate (ESR), sex, and age were carried out. With regard to disease-free survival tumor burden was by far the most important prognostic factor for patients treated with adjuvant chemotherapy as well as for patients treated with radiotherapy alone. With regard to survival from Hodgkin's disease only tumor burden and age were independently significant. A combination of tumor burden, histologic subtype, and sex singled out patients with a high relapse rate both after radiotherapy only, and after radiotherapy plus chemotherapy. This combination also singled out patients destined to die from Hodgkin's disease more accurately than other prognostic factors.
Serial serum samples from 37 patients with Hodgkin's disease (HD) and 39 healthy controls were studied for antibodies to human herpes virus-6 (HHV-6) using ELISA and indirect immunofluorescent antibody (IFA) tests and to the Epstein-Barr virus (EBV) using a radio-complement fixation assay. Antibodies to HHV-6 in the pre-treatment sera from the HD patients were not significantly different from those of controls, but significant changes in titers related to clinical course were noted among the HD patients. HHV-6 IFA titers increased significantly in the course of follow-up in patients who relapsed and decreased significantly over time in patients who did not. These serologic studies support tissue-based investigations indicating that EBV plays a greater etiologic role in HD than HHV-6, although HHV-6 serology may be of prognostic value or may assist in identifying individuals with immunologic abnormalities. The identification of diverse HHV-6 antibody patterns using different assays may reflect the presence of a number of antibodies with varying implications, similar to those identified for EBV.
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