Monitoring referral and treatment in soft tissue sarcoma: study based on 1,851 patients from the Scandinavian Sarcoma Group Register.

This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 198688 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.

Local recurrence of deep-seated, high-grade, soft tissue sarcoma: 459 patients from the Scandinavian Sarcoma Group Register.

This study was based on 459 adult patients with deep, high-grade, soft tissue sarcoma of extremities or trunk wall reported to the Scandinavian Sarcoma Group Register (1986-1993). All patients had their definitive surgery for primary tumor at a sarcoma center. The median follow-up was 7.5 (3-12) years. 204 patients are still alive. 68 patients had amputations and 391 underwent limb-sparing surgery. Among 183 patients with intralesional or marginal margins after limb-sparing surgery, 65% had postoperative radiotherapy and 9% of the 198 patients with wide margins. The local recurrence rate after limb-sparing surgery was 26%. The rate with an intralesional or marginal margin was 39% without postoperative radiotherapy versus 24% when radiotherapy was given. It was 25% after a wide margin, and no recurrences were noted among the 10 patients with a compartmental surgical margin. Among patients with a wide margin, a subset fulfilling criteria for a myectomy was defined. The local recurrence rate was 26% among these 62 and there was no advantage of myectomy over other wide margins. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved in center-operated patients without increasing the amputation rate. Instead, increased use of radiotherapy in all patients with inadequate margins, and to a larger extent in those with wide margins will improve local control.

Consequences of local recurrence of soft tissue sarcoma: 205 patients from the Scandinavian Sarcoma Group Register.

From the Scandinavian Sarcoma Group Register, information on 1,224 surgically-treated patients with soft tissue sarcoma (STS) of the extremity or trunk wall, diagnosed between 1987 and 1995, was collected. 205 patients, one third of whom were referred to a center with a local recurrence, had a total of 284 local recurrences. This analysis describes the treatment for these local recurrences, complications and risk of further recurrences. 169 patients were surgically treated for their first local recurrence. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence had been treated with only surgery with a marginal margin, compared to 0.28 if treated with surgery with a marginal margin and radiotherapy or with a wide margin (p = 0.0008). In extremity STS, the crude amputation rate for local recurrences was 0.22 (31 of 142)-i.e., higher than for primary tumors 0.09 (96 of 1065) (p < 0.0001). A high local recurrence rate after treatment outside of sarcoma centers has earlier been shown. We conclude that the consequences of local recurrence in terms of morbidity and costs justifies referral of STS patients for multidisciplinary evaluation and multimodality treatment.

Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study.

PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.

Clinical course in synovial sarcoma: a Scandinavian sarcoma group study of 104 patients.

We analyzed treatment and outcome in 104 Scandinavian patients with synovial sarcoma in the extremities or trunk wall, diagnosed between 1986 and 1994. Only surgically treated patients without metastases at diagnosis were included. Median follow-up of survivors was 6 (3-11) years. 34 patients developed metastases. The overall 5- and 7-year survival rates were 0.76 (95% CI 0.66-0.83) and 0.69 (0.58-0.78), respectively. Large tumor size and amputation were significantly associated with impaired metastasis-free survival. Patients with local recurrence had a higher risk of metastases following the local event. Local excision with inadequate margin was associated with a higher risk of local recurrence.

Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study.

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.

Megestrol acetate versus aminoglutethimide for metastatic breast cancer.

In this prospective, randomized study the clinical response and toxicity of megestrol acetate (MA) and aminoglutethimide (AG) as second-line treatment in patients with metastatic breast cancer was compared. 176 patients were included, and 150 received treatment greater than 8 weeks and are evaluable for treatment response. The two groups did not differ with regard to prognostic factors. Response rate for the AG and MA groups were 34% and 31% respectively, with duration of response of 13.1 and 13.0 months. Stable disease was obtained in 33% and 35% respectively. No difference was observed in survival. Side effects occurred more frequently in the AG group (42%) than in the MA group (18%).

Treatment with secretin and a cholecystokinin-like peptide in patients with pancreatic cancer. A pilot study.

Secretin and cholecystokinin (CCK) have trophic effects on the pancreas and may therefore have a place in the treatment of pancreatic cancer. The present study was performed to examine whether these hormones may cause harm in patients with pancreatic cancer receiving cytostatics. The cytostatics were 5-fluorouracil, adriamycin, and mitomycin C(FAM). Secretin plus Thr28Nle31CCK25-33, in doses stimulating pancreatic secretion to about 60% of maximal, were given as a continuous 6-day intravenous infusion just before (four patients) or immediately after (five patients) starting treatment with FAM. Five patients received FAM only. When considering symptoms, laboratory findings, abdominal CT scans, and survival, no evidence was found that secretin and CCK may cause serious or unpleasant side effects in patients with pancreatic cancer receiving cytostatics.

Combination chemotherapy of germ cell tumors of the testis with vincristine, adriamycin, cyclophosphamide, actinomycin D and medroxyprogesterone acetate.

Forty-three patients with disseminated germ cell cancer were treated with a combination of vincristine, Adriamycin, cyclophosphamide, actinomycin-D, and medroxyprogesterone acetate. All the 43 patients were considered evaluable for response. Thirty-one patients (72%) achieved a complete or partial remission and 14 (32.5%) achieved a complete remission. The patients who attained an objective response obtained a significant prolongation of life compared with the nonresponders (median survival 55 vs. 23 weeks). Responses were seen in all histologic categories and most frequently in patients with metastases confined to the lungs. The major side effects were leukopenia and stomatitis. There were no deaths related to toxicity of the chemotherapy.

Blood B and T lymphocytes and in vitro cellular immune reactivity in untreated human malignant lymphomas and other malignant tumors.

Peripheral blood lymphocytes and their in vitro reactivity have been recorded prior to treatment in 18 patients with Hodgkins disease, 11 with lymposarcoma, 13 with reticulosarcoma, 20 with various solid tumors and 37 normal control persons. The mean total numbers of lymphocytes, those of T lymphocytes,and the mean reactivity to PHA and ConA were reduced in all groups except lymphosarcoma, although with varying degrees of statistical significance. The percentages of T and B lymphocytes appeared to be normal in all groups, but the ranges of values were somewhat greater than among the normal controls. The mean total numbers of B lymphocytes were normal in all patient groups. All reductions seemed to be more pronounced in patients with disseminated than in those with localized disease, but none of these differences was statistically significant. All patient groups appeared to have reduced reactivity in MLC, while the ability to stimulate control lymphocytes was nearly normal. The results fail to indicate an in vitro immunological abberation specific to Hodgkin's disease. It seems that human malignant, neoplastic diseases are associated with a relatively selective reduction of the total numbers and reactivity of blood T lymphocytes. Various explanations of the reactivity impairment are proposed. The pathogenesis of the reduction of the total number of blood T lymphocytes remains obscure.