a scandinavian sarcoma group protocol for patients with high-risk soft tissue sarcoma of the extremities and trunk wall

Conditions: Soft Tissue Sarcoma; Non Metastatic Disease

Summary: ssg xx is a phase ii trial for high-risk soft tissue sarcomas (sts) of the extremities and trunk wall. prognostic factors (histopathological markers) are used to identify high-risk tumors. ssg xx will evaluate chemo- and radiotherapy given adjuvantly to these patients. in a specified group of patients also preoperatively given therapy will be studied.

ssg xx, the third adjuvant sts protocol by ssg, is a phase ii non-randomized trial in patients with high risk to develop metastases. ssg xx is based on a previous ssg trial (ssg xiii) regarding use of prognostic markers to identify high-risk tumors and include very similar chemo- and radiotherapy treatment schedules compared to ssg xiii, but the new protocol also includes a treatment arm with preoperative chemo- and radiotherapy for patients with an obvious risk for intralesional surgery initially. patients: in this new adjuvant protocol ssg adopts an inclusion decision algorithm based on the following criteria: 1.vascular invasion or 2. presence of at least two of the risk factors: tumor size =\>8 cm, necrosis or infiltrative growth(all defined microscopically by the pathologist. the system was developed retrospectively by evaluation of 434 primary histologically high grade (iii-iv) sts from the ssg registry, and was later validated in a series of 175 patients in which patients with a high risk for metastases (\>40 %) and low risk (\<15 %) were separated (engellau j et al.eur j ca 2007 43: 1927-34). inclusion criteria: age ≥ 18 y and \<75 y. primary end point is metastasis-free survival. local recurrence and toxicity will also be studied. treatment: six cycles of doxorubicin 60mg/m2 and ifosfamide 6g/m2 will be given adjuvantly (to patients ≥ 70y: 50mg/m2 and 5g/m2 ). dependent on surgical resection margins, 36gy or 45gy (1,8gy per fraction, two fractions daily) will be given interpolated with chemotherapy. conclusion: ssg xx will evaluate chemo-and radiotherapy given adjuvantly to patients with sts and high risk for metastases (arm a). in a specified group of patients also preoperatively given therapy will be studied(arm b). other sarcoma centers are invited to participate in the study.

Eligibility criteria:
inclusion criteria: group a: histological high-grade malignancy soft tissue sarcomas of the extremity and trunk wall. patients fulfilling the high-risk criteria defined above (see detailed description) group b: patients with histological high-grade malignancy soft tissue sarcomas of the extremity and trunk wall for whom surgery carries an obvious risk of intralesional margin other inclusion criteria for therapy group a and group b * age ≥ 18 y and ≤ 75 y * who grade 0-1 * adequate cardiac function (lvef ≥ 50%) * normal gfr (clearance) * adequate haematologic and liver function * all histotypes except those listed below exclusion criteria: the following histological types: * extraskeletal osteosarcoma and - chondrosarcoma, ewing/pnet, rhabdomyosarcoma, kaposi´s sarcoma, malignant mesenchymoma, clear cell sarcoma, alveolar soft part sarcoma, epithelioid sarcoma * radiation induced sarcoma * no previous anthracycline treatment * less than 5 years free of another primary malignancy * more than 12 weeks have elapsed since primary surgery (group a) * more than 4 weeks from diagnostic biopsy to start of chemotherapy (group b)

Keywords: soft-tissue sarcomas prognostic factors adjuvant chemotherapy radiotherapy metastases-free survival toxicity high malignancy grade high-risk for metastases adult