Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy
1. Soft tissue sarcoma of adults, primary or locally recurrent, with spindle-cell or
pleomorphic histology, belonging to one of the following for the randomization
myxoid-Round Cell liposarcoma (cellular component >5 %), leiomyosarcoma, synovial
sarcoma, malignant peripheral nerve sheat tumor, undifferentiated pleomorphic sarcoma
(ex Malignant fibrous histiocytoma)
Or belonging to one of the following for the registration (Group 2):
myxofibrosarcoma, unclassified Spindle Cell, pleomorphic liposarcoma, pleomorphic
rabdomiosarcoma Or belonging to either group but not being evaluable for response
(re-excision after previous inadequate resection or primary definitive surgery)
The histological diagnosis must be made according to the WHO criteria and will have
to be centrally reviewed before randomization.
2. High malignancy grade: grade 3 of 3, according to Coindre, or grade 2 at biopsy with
a radiological evidence of more than 50% of necrosis in the tumor mass.
3. Deep seated extremities, girdles and/or superficial trunk (thoracic or abdominal
4. Size of primary tumor (visible or previously inadequately resected) >5 cm at
instrumental staging (CT, MRI), or locally recurrent of any size.
5. Age > 18 years.
6. ECOG performance status <1.
7. Adequate bone marrow function:
WBC >3.500/mm3 neutrophil >1.500/mm3 platelets >150.000/mm3 hemoglobin >11 g%.
8. Adequate renal (creatinine <1.3 mg%), and hepatic function (bilirubin <1.5 mg% and
transaminases <2 x n.v. If ALP > 2.5 x ULN, ALP LF and/or GGT < ULN).
9. Adequate cardiac function (FE >50%).
10. Signed informed consent.
11. Complete compliance of the participating center with the protocol requirements.
1. Pregnancy or lactation.
2. Distant metastasis.
3. Other malignancies within past 5 years, with the exception of carcinoma in situ of
cervix and basocellular skin cancers treated with eradicating intent.
4. Sarcoma histotypes other than those mentioned in the inclusion criteria.
5. Prior CT and/or RT.
6. Serious psychiatric disease that precludes informed consent or limits compliance.
7. Medical disease limiting survival to less than two years, limiting compliance or
which in the physician's opinion might interfere significantly with the toxicity of
8. Cardiovascular diseases resulting in a New York Heart Association Functional Status >
9. Uncontrolled bacterial, viral or fungal infection.
10. Impossibility of ensuring adequate follow-up.
11. Failure to comply with the requirements of the present protocol leading to exclusion
of the participating center.