Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02120768 |
| Other study ID # |
1310128-1-1312 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 3
|
| First received |
April 1, 2014 |
| Last updated |
April 22, 2014 |
| Start date |
March 2014 |
| Est. completion date |
December 2018 |
Study information
| Verified date |
April 2014 |
| Source |
Fudan University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
China: Food and Drug Administration |
| Study type |
Interventional
|
Clinical Trial Summary
The randomized, controlled trial is aiming at comparing local control rate between two
surgical resections, barrier resection and local wide resection with 1cm or equivalent
normal tissues. This is based on the fact that the goal of local surgical treatment is to
remove the tumor with negative margin and best functional outcome, but there is a lack of
standard principle of surgery. Some surgical oncologists recommended enlarging surgical
field in which case the associated muscle was removed from origin to insertion, the previous
surgical scar and radiation field were also grossly remove, though there would be extra
trauma and unacceptable function impairment, they believe that patients would benefit from
"big operations". Most other surgeons would perform a sarcoma resection through normal
tissues, and reported a fair local control as long as a negative margin was obtained. As
reported by various authors, recurrent STSs are associated with higher risk to develop
further recurrence as compared to primary STSs, thus, efforts should focus on this category
of STSs to improve outcome.
Description:
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.
Well defined "R" classification is widely implied to determine the margin status in
STSs, in brief, R0 is microscopically negative, R1 is microscopically positive but
macroscopically negative, R2 is macroscopically positive. The goal of resection is R0
resection with a good functional outcome, but it's impossible to confirm margin status
for all cut edges intraoperatively, while postoperative examination can't guide
intraoperative manipulation. So far there has been no evidence-based and clinically
comprehensible definition of the term "wide resection", though many guidelines
recommended a 1cm normal tissue around tumor. Thus, our study aims at investigating the
difference between barrier resection and 1cm margin resection, with local recurrence as
main end-point, disease specific survival and functional outcome as secondary
end-points.
2. Aims First end-point: Compare the local recurrence between barrier resection and 1cm
margin resection.
Secondary end-point:
Disease specific survival (DSS) Functional outcome (MSTS) Surgical complications (Grade)
The first end-point is to compare the local recurrence between barrier resection and 1cm
margin resection, it's designed based on the following facts:
1. In compartment theory of Enneking, muscle is independent compartment and most recurrent
STSs develop in the same compartment as its original site.
2. The "R" classification of UICC categorized resection margin with margin status, but not
margin width, most guidelines recommended 1cm margin resection and a muscle resection
from origin to insertion was not required any more. As a result, local control for
recurrent STSs was reported to have higher recurrent rate as compared to primary STSs.
3. Some authors in China reported that barrier resection was effective in local control
with acceptable extremity functional outcome.
3. Schedule:
From Jan. 2014 to Dec. 2018, as following:
2014.01-2014.03: Methodology and infrastructure construction. 2014.04-2015.09: Sample
collection, Surveillance, data gathering. 2015.10-2018.12: Followup, data analysis.
Patients with recurrent extremity STSs are candidates of the study, preoperative CT or MRI
should be taken for orientation. As reported previously, barrier resection was associated
with comparable local recurrent rate as primary STSs, closing to 15% and 5% of amputation
rate, while Eilber reported a recurrent rate and amputation rate for recurrent STSs of 18%
and 38%, respectively.
Muscles in trunk don't have independent compartment, thus a barrier resection is not
feasible for patients with trunk recurrent STSs. Retroperitoneal STSs have distinctive
anatomy and biological behavior, thus are also excluded.
4. Randomization: Patients would be randomized as 1:1 to two groups. Randomization should be
taken after radiological evaluation and inclusion. Patients would be stratified according to
histologic subtypes and adjuvant therapies.
Patients would be followed up for at least 24 months for disease status and the survival
information will be followed up to postoperative 60 months.
