Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall (UN-RESARC)

Maria Sklodowska-Curie National Research Institute of Oncology

Status and phase

Unknown

Phase 2

Conditions

Fibrosarcoma

Malignant Peripheral Nerve Sheath Tumors

Myxoid Liposarcoma

Lymphangiosarcoma

Pleomorphic Rhabdomyosarcoma

Dedifferentiated Liposarcoma

Histiocytic Sarcoma

Pleomorphic Liposarcoma

Liposarcoma

Myxofibrosarcoma

Myosarcoma

Undifferentiated Sarcoma

Sarcoma

Leiomyosarcoma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Triton Tumor

Treatments

Radiation: Hypofractionated radiotherapy

Drug: Sequential chemotherapy - 3 courses of AI

Study type

Interventional

Funder types

Other

Identifiers

NCT03651375

URESARC1

Details and patient eligibility

About

After a screening, which consists of biopsy, physical examination, initial diffusion-weighted magnetic resonance imaging (DWI-MRI), body computed tomography (CT) scan, blood tests and case analysis on Multidisciplinary Team (MDT) meeting, a patient will receive the first course of chemotherapy - doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm (AI regimen) with prophylactic mesna. Then a patient will be irradiated 5x5 Gy and after radiotherapy he or she will receive two courses of AI within 4-6 weeks, depending on the tolerance. Then the response analysis in DWI-MRI and toxicity assessment and will be performed. On the second MDT meeting, a final decision about resectability of the tumor will be made. In case of resectability, a patient will be referred to surgery.

Full description

There is lack of standard treatment of marginally resectable sarcomas. Results of commonly used approaches are unsatisfactory. The addition of neoadjuvant/induction chemotherapy before the irradiation and in the prolonged gap between the end of hypofractionated 5x5 Gy radiotherapy and surgery may allow to obtain the R0 resection rate, high pathological response rate and/or a higher rate of limb-sparing/conservative surgery as well as to increase patients' survival.

Hypofractionation represents a variation of radiotherapy fractionation in which the total dose is divided into fewer fractions with an increased fraction dose. Such treatment may lead to additional biological effects when compared to conventionally fractionated radiotherapy (eg. vascular damage, increased immunogenicity, and antigenicity). The main advantages of hypofractionation are those related to the decreased overall treatment time what is more convenient for both patients and physicians, increased compliance and makes the treatment more cost-effective. Intriguing, such an approach may provide an additional benefit when treating non-radiosensitive tumors with a low alpha/beta ratio (eg. sarcomas).

The basis of the study was a trial conducted by Kosela et al. in our center, which showed that preoperative short 5x5 Gy radiotherapy with immediate surgery is an effective and well-tolerated treatment of resectable sarcomas of extremities or trunk wall.

The rationale of chemotherapy comes from the interim analysis of a multicenter, international EORTC study comparing neoadjuvant systemic approaches in high-risk sarcomas. It was proven that AI regimen, which consists of ifosfamide and anthracyclines allowed to obtain 20% benefit in relapse-free survival and overall survival as compared to pathologically-tailored chemotherapy.

Enrollment

46 patients

Sex

All

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Able to provide informed consent
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
Age ≥18 years old
Histologic diagnosis of soft tissue sarcoma
Primary or recurrent tumor localized on extremities or trunk
Grade 2 or grade 3 tumor
Marginally resectable tumor as assessed by a multidisciplinary team
Adequate renal function (serum creatinine ≤ 1.5 ULN)
Adequate liver function (total bilirubin, AST, ALT 3x < ULN)

Exclusion criteria

Radiation-induced sarcoma
Second active malignancy, not including localized basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with a history of other malignancies are eligible if they have been continuously disease-free for > 10 years prior to the time of registration.
History of radiation to the affected volume
Histologic diagnosis of rhabdomyosarcoma (except pleomorphic subtype), angiosarcoma, epithelioid sarcoma, clear cell sarcoma, extraskeletal chondrosarcoma, alveolar soft part sarcoma, osteogenic sarcoma, Ewing's sarcoma/PPNET, aggressive fibromatosis, dermatofibrosarcoma protuberans
Contraindications to radiotherapy, chemotherapy or surgery
Metastatic disease except primary resectable isolated lung metastases