Primary metastatic Ewing's family tumors: results of the Italian Sarcoma Group and Scandinavian Sarcoma Group ISG/SSG IV Study including myeloablative chemotherapy and total-lung irradiation.

BACKGROUND: The Italian Sarcoma Group and the Scandinavian Sarcoma Group designed a joint study to improve the prognosis for patients with Ewing's family tumors and synchronous metastatic disease limited to the lungs, or the pleura, or a single bone. PATIENTS AND METHODS: The study was opened in 1999 and closed to the enrollment in 2008. The program consisted of intensive five-drug combination chemotherapy, surgery and/or radiotherapy as local treatment, and consolidation treatment with high-dose busulfan/melphalan plus autologous stem cell rescue and total-lung irradiation. RESULTS: During the study period, 102 consecutive patients were enrolled. The median follow-up was 62 months (range 24-124). The 5-year event-free survival probability was 0.43 [standard deviation (SD) = 0.05] and the 5-year overall survival probability was 0.52 (SD = 0.052). Unfavorable prognostic factors emerging on multivariate analysis were a poor histological/radiological response at the site of the primary tumor [relative risk (RR) = 3.4], and incomplete radiological remission of lung metastases after primary chemotherapy (RR = 2.6). One toxic death and one secondary leukemia were recorded. CONCLUSIONS: This intensive approach is feasible and long-term survival is achievable in ∼50% of patients. New treatment approaches are warranted for patients responding poorly to primary chemotherapy.

Health status at long-term follow-up in patients treated for extremity localized Ewing Sarcoma or osteosarcoma: a Scandinavian sarcoma group study.

BACKGROUND: The purpose of this study was to evaluate late effects and symptom complaints in long-term survivors (>5 years) of Extremity Bone Sarcoma (EBS survivors). The results were compared with findings in age- and gender-matched individuals from the general population (NORMs). PATIENTS AND METHODS: Among 155 EBS survivors approached, 133 (86%) were included, and 110 of them (83%) attended an outpatient examination. Health status was evaluated by a mailed questionnaire concerning demographic and current health issues, and physical examinations at the outpatient clinic. Age- and gender-adjusted normative controls were drawn from participants of the Health Study of Nord-Trøndelag County (HUNT 2). RESULTS: Median age at follow-up was 29 (15-57) years. Median follow-up was 12 (6-22) years. Of EBS survivors 42% had > or =1 somatic disease, 33% had ototoxicity and 13% had reduced renal function. EBS survivors were more likely to have heart disease (odds ratio [OR], 7.9; 95% confidence interval [95% CI], 2.5-25.3; P = 0.001), hypertension (OR, 3.4; 95% CI, 1.1-10.1; P = 0.03) and thyroid disease (OR, 3.0; 95% CI, 1.1-8.3; P = 0.04) compared to NORMs. EBS survivors reported more diarrhoea (29% vs. 19%, P = 0.02), palpitations (23% vs. 13%, P = 0.01) and shortness of breath (11% vs. 5%, P = 0.01) than NORMs. CONCLUSIONS: EBS survivors have poorer health status compared to age- and gender-matched controls. Long-term follow-up of these patients is therefore mandatory.

Chemotherapy in soft tissue sarcoma. The Scandinavian Sarcoma Group experience.

The Scandinavian Sarcoma Group (SSG) started its first chemotherapy study in soft tissue sarcoma (STS) in 1981 (SSG I). This study evaluated single agent doxorubicin given adjuvant in a prospective randomized trial in patients with high-grade STS. Neither overall survival nor disease-free survival was improved. Combination chemotherapy was hereafter studied in a phase II study (1991-1994) combining ifosfamide and continuous infusion etoposide with growth factor support (SSG X). The response rate in previously untreated patients was high (42%), but complete remissions were few. Analysis made on patients operated after chemotherapy indicated improved survival in this subgroup. Meta-analyses of adjuvant chemotherapy for localised resectable STS in adults, including the SSG I trial, has indicated improved disease-free survival and a trend towards improved overall survival. Presently, SSG is testing whether such a benefit can be found for adjuvant ifosfamide and doxorubicin treatment given after primary surgery in selected patients with high-grade STS and other well defined unfavourable prognostic factors (SSG XIII).