Neoplasms

All Conditions

Rare Diseases

Sarcoma

Liposarcoma

Liposarcoma, Myxoid

Neoplasms, Adipose Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Myxoid Liposarcoma

5x5 Gy radiotherapy and delayed surgery (after 6-8 weeks)

Preoperative hypofractionated 5x5 Gy radiotherapy (5 consecutive days) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with daily image guidance.

Hypofractionated radiotherapy

After a screening, which consists of pathology confirmation, physical examination, magnetic resonance imaging (MRI), body computed tomography (CT) scan, blood tests, and case analysis on Multidisciplinary Team (MDT) meeting, patient will be irradiated 5x5 Gy and after radiotherapy and then referred for surgery 6-8 weeks after the radiotherapy completion.

Myxoid liposarcoma has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). Response to preoperative treatment involves in decrease in tumor size, a large percentage in tumor necrosis (which according to some reports has a beneficial effect on the reduction of local recurrence rates) and also among other in a change in vasculature of the tissue.

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 use of preoperative hypofractionated radiotherapy 5x5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced soft tissue sarcomas showed in a published study a good local control rate, with a favorable amount of late toxicities. In this patient population, there were 22 patients with primary myxoid liposarcoma and the local control rate in this group was 86%.

In the proposed study we plan to increase the gap between the end of radiotherapy and surgery to commonly applied five weeks to better assess the changes occurring in the tumor after treatment and to evaluate the impact of longer treatment interval on reducing the proportion of early complications of treatment.

Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall (LIPO-MYX Trial)

Hypofractionated 5x5 Gy Radiotherapy With Prolonged Gap Before Surgery in Preoperative Treatment of Patients With Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall

Maria Sklodowska-Curie National Research Institute of Oncology

Nervous System Diseases

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Histiocytoma, Malignant Fibrous

Fibrosarcoma

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Histiocytic Sarcoma

Lymphangiosarcoma

Myosarcoma

Histiocytoma

Neoplasms, Connective Tissue

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neoplasms, Fibrous Tissue

Neurofibromatoses

Neurofibroma

Histiocytic Disorders, Malignant

Histiocytosis

Lymphatic Diseases

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Embryonal Sarcoma

Neurofibromatosis

Antineoplastic Agents

All Drugs and Chemicals

Doxorubicin

Liposomal doxorubicin

Ifosfamide

Isophosphamide mustard

Mesna

1xAI (doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm) + 5x5 Gy radiotherapy + 2xAI + surgery

Three courses of doxorubicin and ifosfamide (AI, doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm with prophylactic mesna), one before radiotherapy and two within the gap between radiotherapy and surgery.

Sequential chemotherapy - 3 courses of AI

Preoperative hypofractionated 5x5 Gy radiotherapy (5 consecutive days) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with a daily image guidance with cone beam-CT-based position verification.

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.

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.

Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall

Hypofractionated 5x5 Gy Radiotherapy With Sequential Doxorubicin and Ifosfamide-based Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall

HIF-1 (hypoxia-inducible factor 1) - marker of hypoxia, predicting tumor response on radiotherapy; CD105/CD31/VEGF-A - tumor microvessel density; CD14, CD163, CD68KP i CD68 PG-M1 - tumor associated macrophages.

Radiological assessment of tumor change, especially diffusion parameters in DWI-MRI 6 weeks after the end of irradiation, according to the EORTC criteria.

The study will be stopped prematurely if the rate of non-hematological toxicity grade 3 \>30%

Bai Yun, Master

Gao Xianshu, Master

This study will follow-up different immune cell populations in the blood before, during and after high dose radiation therapy which should give new information of the efficacy of Local Hypofractionated Radiotherapy and a rationale for adjuvant immunotherapy.

* Patient information and collection of a signed informed consent form
* Clinical data collection
* Blood samples of 5 mL:

  1. after registration, prior to the first fraction of radiotherapy
  2. during radiotherapy sessions
  3. one month, 3 months after the last radiotherapy session
* Storage of the blood samples at ambient temperature
* Transportation of the samples to the Institute of Biology of Lille (IBL) - CNRS UMR8161 for analysis
* Destruction of the samples at the end of the analysis

Tumor Response in Hypofractionated Radiotherapy

Biomarkers of Tumor Response in Hypofractionated Radiotherapy

The primary endpoint is the change of the percentage of immune cells before, during and after radiotherapy

Local control of radiotherapy will be assessed based on Response Evaluation Criteria in Solid Tumors(RECIST)1.1

Acute and late toxicities will be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAEv4.0).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall (LIPO-MYX Trial)	NCT03816475	Myxoid Liposarc...	Hypofractionate...	18 Years -	Maria Sklodowska-Curie National Research Institute of Oncology
Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall	NCT03651375	Sarcoma Fibrosarcoma Leiomyosarcoma Liposarcoma Myosarcoma Histiocytic Sar... Synovial Sarcom... Lymphangiosarco... Malignant Perip... Myxofibrosarcom... Myxoid Liposarc... Undifferentiate... Pleomorphic Lip... Undifferentiate... Dedifferentiate... Pleomorphic Rha... Malignant Trito...	Sequential chem... Hypofractionate...	18 Years - 100 Years	Maria Sklodowska-Curie National Research Institute of Oncology
Tumor Response in Hypofractionated Radiotherapy	NCT02854449	Neoplasms		18 Years -	Peking University First Hospital
Tumor Response in Hypofractionated Radiotherapy	NCT02854449	Neoplasms		18 Years -	Peking University First Hospital
Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall (LIPO-MYX Trial)	NCT03816475	Myxoid Liposarc...	Hypofractionate...	18 Years -	Maria Sklodowska-Curie National Research Institute of Oncology
Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall	NCT03651375	Sarcoma Fibrosarcoma Leiomyosarcoma Liposarcoma Myosarcoma Histiocytic Sar... Synovial Sarcom... Lymphangiosarco... Malignant Perip... Myxofibrosarcom... Myxoid Liposarc... Undifferentiate... Pleomorphic Lip... Undifferentiate... Dedifferentiate... Pleomorphic Rha... Malignant Trito...	Sequential chem... Hypofractionate...	18 Years - 100 Years	Maria Sklodowska-Curie National Research Institute of Oncology

Spots Global Cancer Trial Database for dose hypofractionation