Phase III Study of The Role of Barrier Resection in Local Control in Treatment of Extremity Soft Tissue Sarcomas

1. Background Soft tissue sarcoma (STS) is a category of malignancy with mesenchymal origin, its incidence is 10-20 cases/million and accounts for 1% of all human malignant neoplasms. The most common STSs include undifferentiated polymorphic sarcoma/malignant fibrohistiocytoma (UPS/MFH), synovial sarcoma, fibrosarcoma and liposarcoma.

The rarity of the tumor, the various subtypes and heterogeneous behavior make the diagnosis and treatment of sarcoma a challenge. Many patients, especially those from developing countries were diagnosed with a late stage disease or recurrent sarcoma being treated with many unplanned resections, which would impact limb function or even survival. Except those with unresectable diseases, surgical resection remains the mainstay of treatment for soft tissue sarcoma, the defined aim of surgery is R0 resection with a good functional outcome. With development of modern strategy and technique, limb sparing surgery has been implied in more than 80% of cases and was proven to have similar local control as amputation without sacrifice of survival. The most common limb sparing surgeries include compartment resection and wide resection. Compartment resection has been gradually replaced by functional compartment resection, aiming at more function preservation, while so far there has been no evidence-based and clinically comprehensible definition of the term "wide resection". Many textbooks still advocate the need to obtain a 2- to 3cm surgical margin width in all directions when resecting a soft tissue sarcoma, but some other orthopaedic and surgical oncologists recommended 1cm or 5cm margin width for STS.

Local recurrence-free interval is the major end-point in evaluating the quality of surgery, functional outcomes and treatment morbidities are equally important end-points. Five-year local recurrence-free estimations for limb and trunk wall sarcoma should be below 20%, and approaching 10%. Margin status is reported to be a key prognostic factor for local recurrence. Surgical margin width is determined mainly by the distance from the tumor edge to the periphery of the specimen, and should be co-assessed by surgical oncologist and pathologist. Different margin width of 1-5cm has been recommended for obtaining a safe margin, as stated above, but in a limb sparing surgery, margins exceeding 1 cm were obtained in only 47% of patients and it's nearly impossible to obtain 2 cm margins in all directions for an extremity STS. With adjuvant therapies, a close dissection can be adequate in order to preserve important functional structures， but the following questions are unanswered:1. How close is safe for STS resection? 2. Is a margin close to periosteum has the same oncologic result as a margin close to muscular membrane or subcutaneous fat? As we all know that local anatomy influences sarcoma growth by setting natural barriers to extension, and sarcoma might infiltrate or compress surrounding structures, thus, a rational resection should be designed mainly based on the understanding of these characteristics. Scientists investigated different barriers and converted them into different margin width in order to facilitate a safe resection. Among these efforts, a barrier resection was reported to be an option for recurrent extremity STSs and obtained satisfactory local control.

Barrier resection was defined as "en bloc" removal of tumor with surrounding barriers. The barriers include muscular fascia, vascular adventitia, epineurium and periosteum, in some cases where there is no barrier, 3-5cm of healthy tissue is considered equivalent. Barrier resection was developed according to the above characteristics of STSs, which featured with the fact that sarcomas take the path of least resistance and initially grow within the anatomical compartment in which they arose, and the phenomenon that skip metastases are limited within the same anatomic compartment in which the primary lesion is located. Furthermore, a barrier resection can be designed preoperatively based on imaging studies and is easy to perform intraoperatively based on understanding of local anatomy, and also, it's easy for pathologists to obtain materials for margin evaluation.

Another content of barrier resection is repair and reconstruction, which includes vessel replacement, dynamic restoration, supporting and wound coverage. With the assistance of repair and reconstruction, sacrifice of margin safety would be no longer needed and in some selected cases, adjuvant radiotherapy would be spared.