Five-year results in Ewing's sarcoma. The Scandinavian Sarcoma Group experience with the SSG IX protocol.

The first Scandinavian protocol for Ewing's sarcoma, SSG IV, resulted in a local control rate of 74% and 5-year metastasis-free survival (MFS) of 43%. The second protocol, SSG IX, was started in order to improve upon these results. It featured four chemotherapy cycles, each consisting of two courses of VAI (vincristine, doxorubicin, ifosfamide) alternating with one course of PAI (cisplatin, doxorubicin, ifosfamide) at 3-weekly intervals. Total treatment time was 35 weeks. Local therapy was given at week 9. Inoperable or non-radically operated patients received hyperfractionated accelerated radiotherapy 1.5 Gy twice daily between chemotherapy courses to a total dose of 42-60 Gy, depending on surgical radicality and tumour localisation. 88 patients were included (58 male, 30 female, mean age 20 years; range 5-65 years). The tumour (73 M0 and 15 M1) was located centrally in 31 patients (35%), in the extremities in 34 (39%) and other sites in 23 (26%) of cases. The median size of tumour was 10 cm (range 2-23), soft tissue was invaded in 87%. Surgery was the local therapy for 60 (68%) patients: amputation in 8 and local excision in 52. The surgical margins were wide in 35 patients, marginal in 14 and intralesional in 3. Radiotherapy was given to 17 non-radically operated patients postoperatively and to 28 patients with inoperable tumours primarily. Histological responses were evaluated in 52 patients. 9 local recurrences were observed (10%). Distant metastases developed in 24 M0 patients (33%). The estimated 5-year MFS was 58% and overall survival (OS) 70% for M0 and 27% and 28% for M1 patients, respectively. Survival was favourable in patients with non-metastatic extremity tumours (90%) and tumours operated with wide margins (90%). Patients with a total necrosis after chemotherapy had a better OS than those with a partial or poor response (P=0.003). The toxicity (World Health Organisation) was acceptable (gastrointestinal G1-2; haematological G3-4). The SSG IX protocol gave better local control and survival rates than the SSG IV. Whether this is due to a higher therapeutic efficacy of the present protocol cannot be ascertained in this comparison with a historical control.

Diagnosis and tumor response in osteosarcoma and Ewing's sarcoma, according to treatment protocols SSG II, SSG VIII, ISG/SSG I, SSG IV and SSG IX.

114 patients with osteosarcoma in the extremities had been reported to the SSG II trial, 132 to the SSG VIII trial and, until October 1998, 99 to the ISG/SSG I trial. The SSG IV trial included 53 patients and the SSG IX trial 104 patients until October 1998. In the SSG II trial, 19% were good responders (grades III and IV) as compared to 51% in the SSG VIII trial. On reevaluation was the response changed in one forth of the cases in both the SSG II and SSG VIII trials. In 9 and 10 cases (8%), respectively, the reevaluation resulted in a change from "good responder" to "bad responder". In the ISG/SSG I trial, the preliminary results showed a good response in 22% of the cases. In the SSG IV trial, 44% were good responders (grades III and IV), as compared to 54% in the SSG IX trial.

Survival of patients with viable malignant non-seminomatous germ cell tumour persistent after cisplatin-based induction chemotherapy.

OBJECTIVES: Review of the outcome in patients with viable residual postchemotherapy malignant germ cell tumour treated at the Norwegian Radium Hospital from 1980 to 1993 and to establish prognostic factors. METHODS: During the years 1980-1993, about 270 patients with malignant non-seminomatous germ cell tumours underwent postchemotherapy surgery at the Norwegian Radium Hospital. In 27 of these patients, residual viable malignant germ cell tumour was found in the operation specimen. These patients were scheduled to receive 3 adjuvant cisplatin-based chemotherapy cycles after surgery, if possible, containing cytostatic agents not given during induction chemotherapy. All patients were followed up until death or January 1st, 1995 (median observation time in surviving patients: 51 months; range: 9-166 months). RESULTS: Sixteen patients developed a relapse after surgery after a median time of 4 weeks (range 1-19 weeks), 12 of them before any adjuvant chemotherapy could be started. Only 2 of these relapsing patients could be salvaged. At the last follow-up, 13 patients were alive, and a 43% 5-year survival was obtained. All deaths occurred within 3 years after surgery. The 9 patients with elevated alpha-fetoprotein and/or human chorionic gonadotropin before surgery have a particularly low survival rate (11%), as compared to the 18 patients with normal markers (62%). The most important prognostic parameter for the postoperative survival was, however, the initial tumour burden: the 14 patients with initially large or very large tumour volume (MRC criteria) had a 9% 5-year survival, whereas the percentage was 84% for the 13 patients with small volume disease. CONCLUSION: Prognosis is poor in patients in whom residual malignant germ cell tumour persists in spite of conventional cisplatin-based induction chemotherapy, especially in patients who initially present with large or very large volume disease and/or pre-operatively elevated tumour markers. More effective treatment modalities have to be developed for these patients. The role of high-dose chemotherapy with stem cell support should be investigated in future trials, especially in the subgroup of patients with poor prognosis.