Neoadjuvant Chemotherapy Combined With Targeted Treatment in High-risk Retroperitoneal Sarcoma

The goal of this clinical trial is to explore the potential survival benefits of neoadjuvant chemotherapy combined with target treatments followed by radical surgery in patients with primary high-risk/grade retroperitoneal sarcoma.

The main questions it aims to answer are:

* Whether the 1,3-year progression-free survival time(PFS) is prolonged in the neoadjuvant therapy group, compared with the surgery-only group.
* The Overall survival time in the two groups.
* The safety and tolerance in the neoadjuvant therapy group.

Participants will be allocated into two groups once they meet the inclusion criteria.

* Surgery-only Group: Patients will directly undergo surgeries after the confirmation of diagnosis through pre-operative biopsy.
* Neoadjuvant therapy group: Patients will receive the neoadjuvant chemotherapy combined with target treatment for three circles before the following sarcoma resectional surgeries.


Eligibility Criteria:
Inclusion Criteria:

* Histologically proven primary high-risk Retroperitoneal sarcoma(RPS) (Including Dedifferentiated liposarcoma (DDLPS), leiomyosarcoma(LMS), Undifferentiated pleomorphic sarcoma(UPS), Solitary fibrous tumor(SFT)).
* Primary localized RPS without histories of surgical resection, chemo- or radio-therapy, targeted therapy. Patients who underwent laparotomy with biopsy only will also be considered as primary cases.
* Without histories of second malignant tumors.
* In DDLPS

  * Diagnosis should be confirmed based on MDM2(Mouse double minute 2 homolog) and CDK4(Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while MDM2 amplification in the Fish test is highly recommended.
  * All grade 2-3 DDLPS can be included.
* In LMS

  * All grades of LMS can be included.
  * Tumor size ≥10cm
* In UPS or SFT

  * All grades of UPS can be included.
  * High-risk SFT with a score ≥6 in 'Risk stratification of SFT for development of metastasis' introduced in The 5th edition of the WHO(World Health Organization) Soft tissue sarcoma classification.
* Sarcoma without protruding across the diaphragm
* Possibility of R0/R1 resection evaluated through preoperative MDT(multi-disciplinary team) discussion
* No multi-organ or system dysfunction/failure or patients with slight dysfunction of organ/system could be easily recovered
* Tolerable of chemotherapy and surgery through MDT evaluation and tests.
* American Society of Anesthesiologist (ASA) ≤3
* Fully understand the informs and consent to participate in the study.

Exclusion Criteria:

* Sarcoma confirmed originating from the GI tract, uterus, or urinal tract.
* Patients included in the study through preoperative biopsy or MDT discussion, with WDLPS, grade 1 LPS, or other types of tumors not mentioned in the Inclusion criteria evaluating through final pathological findings.
* Sarcoma protruded into the chest cavity evaluated through preoperative imaging or surgical reports.
* Metastasis confirmed pathologically or highly suspicious metastatic lesions through radiological findings, PET-CT(Positron emission tomography) is highly recommended, MDT discussion and evaluation are needed.
* Histories of administration of Anthracyclines, Ifosfamide, and targeted agents.
* Severe contradiction to surgery and chemotherapies, including persistent myelosuppression, myocardial/cerebral/pulmonary infarction, uncontrolled cardiac arrhythmia, etc within the last 6 months
* Indication of severe infection or undergoing surgeries with high-risk hemorrhages in one month.
* Persistent one or more organ or system dysfunctions, could not be recovered prior to the study.
* Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control methods.
* Patients with psychological conditions