Summary of recommendations

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Summary of recommendations

For explanation of levels of evidence and grades for recommendations, see Levels of evidence and grades for recommendations below. You may also like to refer to the Appendix - Guideline Development Process

Recommendations

Diagnosis

What are the most appropriate imaging modalities for diagnosis and staging of BSTTs?

Recommendation Grade
Magnetic resonance imaging is the imaging modality of choice for extremity tumours. B
Practice point(s)
CT is usually adequate for abdomino-pelvic masses.
Further imaging and biopsy only performed after review by a surgeon or other member of a sarcoma team.
CT chest be performed at diagnosis to assess for metastatic disease.
PET-CT may be used prior to radical surgery of soft tissue sarcomas.

What is the impact of delay in referral to a specialist centre in BSTTs?

Recommendation Grade
Immediate referral to a specialist sarcoma unit to be sought when a tumour of bone or soft tissue (other than simple lipoma) is suspected. D
Practice point(s)
In practice, any mass lesion greater than 5cm in size, and lesions deep to or attached to deep fascia, should be considered a sarcoma until proven otherwise.
Refer to a specialist sarcoma unit.

Multidisciplinary Treatment

What is the role of prognostic factors in management of BSTTs?

Recommendation Grade
Statistical models assessing the influence of prognostic factors can be used to counsel patients and to stratify their need for adjuvant therapies or entry into clinical trials. D
Practice point(s)
Accurate data collection will facilitate further study in this area. Tissue banking will allow further assessment of tumours as new diagnostic and therapeutic modalities emerge.

What is the outcome of a second opinion in BSTT pathology?

Recommendation Grade
Whenever a primary diagnosis of bone or soft tissue sarcoma is made outside the context of a specialist sarcoma unit, wherever possible, referral to an expert pathologist (within a specialist sarcoma unit) for review of the diagnosis and grade should be undertaken before definitive management is instituted. D

Does referral to a specialist centre improve outcomes?

Recommendation Grade
Patients with suspected sarcoma to be referred to a specialist sarcoma unit prior to diagnosis in order to reduce the rates of incomplete excision, reoperation, local recurrence and to improve survival. C

Chemotherapy (systemic therapies)

What is the role for adjuvant systemic therapy for adults with BSTT?

Recommendation Grade
The use of post-operative chemotherapy in adult type soft tissue sarcomas is not the current standard of care. D
Curative treatment of high-grade osteosarcoma comprises chemotherapy and surgery. B
The use of pre-operative chemotherapy in adult type soft tissue sarcomas is not the standard of care. D
Pre-operative chemotherapy for high-grade osteosarcoma including cisplatin, doxorubicin and in selected patients high-dose methotrexate, improves outcomes compared to regimens omitting high-dose methotrexate. C
As for osteosarcoma, doxorubicin and cisplatin are indicated for malignant fibrous histiocytoma of bone. D
As for osteosarcoma, doxorubicin and cisplatin are indicated for high-grade spindle cell sarcomas of bone and malignant fibrous histiocytoma. D
Curative treatment of Ewings sarcoma comprises of a combination of chemotherapy and surgery and/or radiotherapy. B
Practice point(s)
Patients considered for chemotherapy should be referred for clinical trial participation.

What is the role for systemic therapy in advanced soft-tissue sarcoma?

Recommendation Grade
There is no evidence to support combination chemotherapy regimens over sequential single agent regimens in the first-line treatment of advanced soft-tissue sarcomas. B
Single agent ifosfamide can be considered as second-line treatment for patients who have not received ifosfamide as first-line. B
Dacarbazine with or without gemcitabine is reasonable third-line therapy after exposure to doxorubicin and ifosfamide in advanced soft tissue sarcoma. B
Systemic therapy with paclitaxel is reasonable in all patients with angiosarcoma, given the palliation that can be offered by these agents. D
Practice point(s)
Clinical trial participation should be considered for patients with soft tissue sarcomas.

Radiotherapy

What is the evidence for radiotherapy in limb and extremity soft tissue sarcoma in terms of local recurrence, survival and limb salvage?

Recommendation Grade
All patients with large, localised, high-grade extremity soft tissue tumours should be offered radiotherapy. B
Omission of radiotherapy may be considered in select patients with small, superficial, extremity soft tissue tumours. D
Practice point(s)
Radiotherapy does not compensate for inadequate surgery.

What is the evidence that pre-operative radiotherapy is superior to post-operative radiotherapy in limb and extremity soft tissue sarcoma in terms of local recurrence, survival and limb salvage and morbidity?

Recommendation Grade
The timing of radiotherapy needs to be individualised dependent upon resection and reconstructive considerations. B
Practice point(s)
Pre-operative radiotherapy may be the preferred approach in certain situations such as:
A tumour of borderline resectability, and pre-operative radiotherapy may render it resectable.
Radiosensitive histology (eg., myxoid liposarcoma), where tumour downstaging may be advantageous.
Where adjacent critical structures (eg., brachial plexus) may limit the total dose of post-operative radiotherapy.

What is the evidence that radiotherapy, either pre-operative or post-operative, decreases local recurrence or improves survival in truncal sarcomas?

Recommendation Grade
In patients with non-metastatic truncal sarcomas, adding radiotherapy to surgery is appropriate to further improve local control. When offered, pre-operative radiotherapy is preferable to post-operative radiotherapy. C

What is the evidence that radiotherapy, either pre-operative or post-operative, decreases local recurrence or improves survival in retroperitoneal sarcomas?

Recommendation Grade
In patients with non-metastatic retroperitoneal sarcomas, adding radiotherapy to surgery is appropriate to further improve local control. When offered, pre-operative radiotherapy is preferable to post-operative radiotherapy. C

What are the indications for IMRT, brachytherapy, intraoperative radiotherapy (IORT), extra-corporeal radiotherapy and particle therapy in the management of BSTTs?

Recommendation Grade
Brachytherapy (as an alternate or as a boost to external beam radiation) improves local control over surgery alone for high grade sarcomas for the limb and trunk. B
IORT boost to external radiation could be considered in combination with surgery for management of retroperitoneal sarcomas. B
It maybe reasonable to consider IMRT for patients with retroperitoneal and extremity/truncal sarcomas as adjuvant to surgery, if resource permits, for potential advantages in reduction of radiation dose to normal tissues. D
Reconstruction using the patients own resected bone (previously bearing the sarcoma) fragment after a large extra-corporeal dose of radiation is a possible option reported to have satisfactory to good functional outcomes. D
Particle beam therapy appears to offer good local control with acceptable toxicity. D

Surgery

What are the factors influencing the extent of surgery in BSTTs?

Recommendation Grade
Pre-operative radiation therapy may allow preservation of vital structures without compromising local control. C
It is important that wide surgical margin is achieved to prevent local recurrence and poor survival outcomes. B
Pre or post-operative radiation therapy should be considered in the management of soft tissue sarcoma. Decision should be made in the setting of a multidisciplinary team. A
Musculoskeletal tumours are best managed in a specialist sarcoma unit by a multidisciplinary team. C
Isolated limb perfusion should be considered in patients with extensive soft tissue sarcoma where there is doubt whether limb salvage surgery can be achieved. Decision should be made in the setting of a multidisciplinary team. C
Soft tissue sarcomas initially excised with residual disease and/or positive margins will require re-excision, preferably in a specialist sarcoma unit. These tumours should be re-excised with wide margins and usually require adjuvant radiotherapy. C
Grade 1 Chondrosarcoma can be safely managed with intralesional excision with cementation. Distinction between this and other grades requires correlation of clinical and radiological features. C
Retroperitoneal sarcomas are best managed in a specialised tumour centre by a multidisciplinary unit. C
Limb salvage surgery is an acceptable treatment in the management of osteosarcoma. C
Practice point(s)
Any lump greater than 5 cm or deep to the deep fascia should be considered a sarcoma until proven otherwise.
Persistent and unremitting pain, not responsive to oral analgesics and nocturnal in occurrence should stimulate investigation for a bone tumour.
Complete imaging (anatomic and functional including XR, CT, MRI, nuclear scan) should be undertaken of a bone and soft tissue tumour prior to surgical manipulation.
Biopsy should be performed under image guidance to determine the track of the biopsy, and the target of the biopsy to confirm representativeness. Computed tomographic guidance is recommended. Biopsy should be performed after all imaging modalities have been completed to minimise the impact of biopsy induced image artifact.
Sarcomas are best managed at a specialist sarcoma unit.
Local recurrence is related to the adequacy of surgical margins. Wide surgical margins should be employed for bone and soft tissue sarcomas except when close margins are planned and adjuvant radiotherapy/chemotherapy is employed.
Tissues of different resistance to tumour invasion that surround a tumour may be used to calculate the quality of surgical margins. In this way, more careful planning of surgical margins may be undertaken when contemplating limb-sparing surgery.
Combination therapy is required to adequately manage bone and soft tissue sarcomas. Radiotherapy and wide margin surgery are used for soft tissue sarcomas. Chemotherapy and wide margin surgery are used for bone sarcomas.
Radiotherapy is recommended for low grade soft tissue sarcomas particularly if these tumours are large and excised with marginal margins.
Adequacy of surgical margins achieved should be assessed by a expert musculoskeletal pathologist. Refer to the Royal College of Pathologists of Australasia Soft Tumour Resection Structured Reporting Protocol 1st Edition 2011

What are the factors that impact on the choice of reconstructive options in BSTTs?

Recommendation Grade
Consider vascularised flap coverage (including free tissue transfer) in reconstruction of sarcoma defects when post-operative radiotherapy is anticipated. D
Provision of education and psychological support is an important component in holistic care of the sarcoma patient. C
The decisions for reconstruction of skeletal elements are ideally made at a specialist sarcoma unit. D
When restoration of vascularity to a limb is required following sarcoma resection, prioritise arterial reconstruction and consider the need for venous reconstruction. D
Sarcomas are better managed in a specialist sarcoma unit with planning of primary resection, reconstruction and timing of radiotherapy (where required) for optimal outcome. D
Consider vascularised tissue in reconstruction of bone and soft tissue in lower extremity sarcoma. D
Consider vascularised tissue coverage in management of soft tissue sarcomas, particularly when large resections or radiotherapy expected, and in children. C
Consider vascularised tissue in reconstruction of bone and soft tissue in upper extremity sarcoma. D
Recognise that pre-operative radiotherapy leads to a higher wound complication profile than (i) no radiotherapy, and (ii) post-operative radiotherapy. B
Referral to specialist hand and upper limb surgical team to be sought when surgical resection and reconstruction is required for sarcoma in the hand and forearm area. D
Consider vascularised flap coverage (including free tissue transfer) in reconstruction of sarcoma defects following pre-operative radiotherapy. B
Consider incorporation of thoracoplastic techniques with mesh and vascularised flap coverage in management of chest wall defects following sarcoma resection. C
Practice point(s)
The nature of reconstruction of defects following sarcoma resection is often complex due to the required size of resection, likelihood of need for perioperative radiotherapy with associated surgical challenges, and variation in involved tissue types. Specialist Multidisciplinary Team management is advised for all cases for optimal outcome.
Optimisation of general patient factors, both physical (including diabetic control, nutrition, minimising smoking and avoiding preventable perioperative morbidity) and psychological, will provide benefits to patient outcome. Patient education regarding the disease process and treatment options is also important in achieving the best holistic outcome.
Radiotherapy (in any form) reduces vascularity and impairs wound healing. Reconstructive options are affected by choice and timing of radiotherapy. A treatment plan for each case should be discussed at commencement of treatment to determine best timing and choice of surgical resection, surgical reconstruction and radiotherapy. This will allow best outcome with minimisation of surgical-related and radiotherapy-related morbidity.
When limb-preserving surgery is undertaken, care should be taken to reconstruct all resected tissues. This includes skeletal stability in bony reconstruction, reconstruction of neurovascular structures and functional muscle groups, and overlying soft tissue coverage.
In all resection defects requiring soft tissue coverage, vascularised tissue is the preferred reconstruction. This may be in the form of locoregional flap transfer, or free flap tissue transfer with reconstruction of the tissue vascularity using micro-surgical anastamoses of blood vessels. This enables best healing of underlying structures, reduces infection and other complication risks relating to skeletal implants, and provides greatest resilience to radiotherapy.
Restoration of function is the priority in reconstruction of the bony skeleton. Many options are available for reconstruction in metadiaphyseal areas, with preference for biological reconstruction where possible. Endoprosthetic reconstruction is commonly used in periarticular reconstruction.
Limb salvage procedures result in better functional outcomes, but do not necessarily result in greater quality of life.

What preoperative optimisation strategies improve outcomes in BSTTs?

Recommendation Grade
Pre-operative embolisation may be considered in selected cases. D
Pre-operative imatinib mesylate may be considered in selected patients with DFSP when surgery is difficult or potentially mutilating. D
Practice point(s)
It is advisable to consider the suitability and applicability of pre-operative optimisation strategies, such as embolisation, prior to surgery for large or complex BSSTs.

What is the role of regional chemotherapy in BSTTs?

Recommendation Grade
Isolated limb perfusion (ILP) may be considered as a palliative alternative to amputation in patients with extremity soft tissue sarcoma. D
Practice point(s)
The toxicity of isolated limb perfusion (ILP) with melphalan is increased when combined with TNFα.
ILP may be considered to downstage extremity soft tissue sarcoma when primary amputation would otherwise be considered.

Follow-up

What are the measures to assess treatment response in BSST's?

Recommendation Grade
Functional imaging may assist standard methods of evaluating response to pre-operative chemotherapy or radiation therapy. D

What is the ideal duration, frequency and modality of follow-up for BSTTs?

Recommendation Grade
Regular clinical examination is part of routine surveillance for local recurrence. D
High risk patients in whom pulmonary metastasectomy would be considered, are advised to undergo three to six month CT chest until five years. D
Practice point(s)
Where the primary site is difficult to examine, for example the retroperitoneum or following complex/flap reconstructions routine imaging may be appropriate.
Follow-up intervals recommended in current multinational guidelines are each three to four months in years one and two after diagnosis, six monthly in years three to four and annual thereafter.

Late metastases may occur >10 years after diagnosis and there is no universally accepted stopping point for tumour surveillance. By contrast, the incidence of late effects of treatment increases with time.

For patients enrolled in clinical trials, the above recommendations may vary in accordance with the follow-up protocols of these trials.

For patients considered suitable for pulmonary metastasectomy, low dose protocol non- contrast CT chest is the modality of choice for pulmonary surveillance.

Levels of evidence and grades for recommendations

The following table provides a list of the evidence-based recommendations detailed in the content of each topic question. The table below provides details on the highest level of evidence identified to support each recommendation (I-IV). The Summary of Recommendations table includes the grade for each recommendation (A-D). The key references that underpin the recommendation are provided in the last column. Individual levels of evidence can be found in the Evidence Summaries for each recommendation in each question.

Each recommendation was assigned a grade by the expert working group taking into account the volume, consistency, generalisability, applicability and clinical impact of the body of evidence supporting each recommendation. When no Level I or II evidence was available and in some areas, in particular where there was insufficient evidence in the literature to make a specific evidence-based recommendation, but also strong and unanimous expert opinion amongst the working group members about both the advisability of making a clinically relevant statement and its content, recommended best practice points were generated. Thus, the practice points relate to the evidence in each question, but are more expert opinion-based than evidence-based. These can be identified throughout the guidelines with the following: Practice point (PP).

Grade of recommendation Description
A Body of evidence can be trusted to guide practice
B Body of evidence can be trusted to guide practice in most situations
C Body of evidence provides some support for recommendation(s) but care should be taken in its application
D Body of evidence is weak and recommendation must be applied with caution
PP

(practice point)

Where no good-quality evidence is available but there is consensus among Guideline committee members, consensus-based guidance points are given, these are called "Practice points"

Adapted from: National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC; 2009.[1] (https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf)

Level of evidence was assigned according to the following criteria from the NHMRC Evidence Hierarchy[1]:

Level Intervention Diagnosis Prognosis Aetiology Screening
I A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies A systematic review of level II studies
II A randomised controlled trial A study of test accuracy with: an independent, blinded comparison with a valid reference standard, among consecutive patients with a defined clinical presentation A prospective cohort study A prospective cohort study A randomised controlled trial
III-1 A pseudo-randomised controlled trial (i.e. alternate allocation or some other method) A study of test accuracy with: an independent, blinded comparison with a valid reference standard, among non-consecutive patients with a defined clinical presentation All or none All or none A pseudo-randomised controlled trial (i.e. alternate allocation or some other method)
III-2 A comparative study with concurrent controls:
  • Non-randomised, experimental trial
  • Cohort study
  • Case-control study
  • Interrupted time series with a control group
A comparison with reference standard that does not meet the criteria required for Level II and III-1 evidence Analysis of prognostic factors amongst untreated control patients in a randomised controlled trial A retrospective cohort study A comparative study with concurrent controls:
  • Non-randomised, experimental trial
  • Cohort study
  • Case-control study
III-3 A comparative study without concurrent controls:
  • Historical control study
  • Two or more single arm study
  • Interrupted time series without a parallel control group
Diagnostic case-control study A retrospective cohort study A case-control study A comparative study without concurrent controls:
  • Historical control study
  • Two or more single arm study
IV Case series with either post-test or pre-test/post-test outcomes Study of diagnostic yield (no reference standard) Case series, or cohort study of patients at different stages of disease A cross-sectional study Case series

Source: National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC; 2009. (https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf)

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References

  1. 1.0 1.1 National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for guideline developers. Canberra: National Health and Medical Research Council; 2009 Available from: https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf.

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