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

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

Introduction

Truncal sarcomas are rare, accounting for about 6% of all soft tissue sarcomas (STS) and about half of all malignant tumours arising on the chest wall. The clinical behaviour of chest wall sarcomas is similar to extremity sarcomas. Thus, they should be treated similarly to extremity sarcomas.[1] [2]

Because of the rarity of this type of sarcoma, data concerning treatment and results are sparse. In the largest single institution study by Memorial Sloan-Kettering Cancer Center (MSKCC) spanning over a period of forty years looking at 189 patients, the authors reported overall five year survival was 66%, with low grade sarcomas showing 90% survival as compared to 49% with high grade sarcomas. Local recurrence was more common in high grade tumours even after resection, and adjuvant treatment was recommended. However with low grade tumours, resection alone provided good survival at 90%. The most common tumours seen were desmoids, liposarcoma, rhabdomyosarcoma and Fibrosarcoma. Survival was similar to that of patients with sarcomas of the extremities.

Rationale for Radiotherapy

Given the similarity to extremity sarcomas in terms of local recurrence and metastases, most reports suggest treating them as for extremity sarcomas.

Radiation therapy is a well-established modality in Sarcoma of the extremities along with surgery to achieve good local control of up to 90%, especially in high grade sarcomas. There are many institutional reports of high local control by adding radiation therapy to surgery.

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Evidence for Local control benefit with radiotherapy in addition to surgery

A systematic review in 2003 by the Swedish group concluded that, “there is strong evidence that adjuvant radiotherapy improved local control in combination with surgery in the treatment of STS of extremities and trunk in patients with negative, marginal or minimal microscopic positive surgical margins. A local control rate of 90% has been achieved”[3]

A more recent study looked at twenty year data of 1093 sarcoma patients, 151 of whom were truncal sarcomas and concluded that “adjuvant radiotherapy (RT) effectively prevents local recurrence in soft tissue sarcoma and the effect was most pronounced in deep seated high grade tumours, even when removed with a wide surgical margins”[4]

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Pre-operative versus post-operative radiotherapy

As with extremity sarcomas, there are potential benefits with pre-operative RT compared with post-operative RT such as:

  • The main advantage of pre-operative RT is that the gross tumour volume can be precisely defined for radiation treatment planning, allowing accurate targeting of the radiation volume around the tumour.
  • The tumour itself can act to displace small bowel from the high-dose radiation treatment volume, resulting in safer and less toxic treatment.
  • Higher RT doses can be delivered to the actual tumor field, since bowel adhesions to tumour are less likely compared to the post-operative setting.
  • The risk of intraperitoneal tumour dissemination at the time of the operation may be reduced by pre-operative RT.
  • Radiation is considered to be biologically more effective in the pre-operative setting.
  • It is possible that an initially unresectable tumour may be converted to one that is potentially resectable for cure.

Potential downsides of pre-operative radiation therapy include delay in wound healing and requirement of surgery to treat this complication.

Post-operative radiation therapy on the other hand allows detailed evaluation of pathology (grade, margins, etc) but disadvantages include higher doses or radiation therapy, larger volumes of radiation therapy, maybe technically difficult trying to cover larger volumes and finally potential late adverse events including fibrosis and bone fractures which may impact on quality of life.

With lack of randomised controlled trials to guide us when dealing with this cohort (truncal sarcomas) individualised multidisciplinary discussion of the benefits of the choice and order of surgery or radiotherapy may be appropriate.

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Newer radiotherapy techniques

There is some evidence that newer RT techniques such as intraoperative electron beam therapy (IORT) may be beneficial, but this is usually confined to few centres worldwide and not available in Australia. There is some promise with the use of intensity modulated radiation therapy (IMRT) in truncal sarcomas but still in early stages and may take some time for results to come.

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Evidence summary and recommendations

Evidence summary Level References
In patients presenting with non-metastatic truncal sarcomas, improved local control is seen with adding radiation therapy to surgery. Pre-operative radiotherapy is preferable. Post-operative radiotherapy (in the absence of spacing devices) is associated with significant toxicity.

Evidence regarding radiotherapy benefit in improving overall survival is not clear.

III-2, IV [3], [4]
Evidence-based recommendationQuestion mark transparent.png 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


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Issues requiring more clinical research study

A number of gaps in the evidence have been identified. These include:

• Clear definition of truncal sarcomas - sarcomas of the body (external) excluding limbs and head, with regular audit of outcomes.

• Nationally run randomised controlled trial looking into pre-operative versus post-operative RT in truncal sarcomas will answer questions more definitively regarding concerns related to toxicity.

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References

  1. Tsukushi S, Nishida Y, Sugiura H, Nakashima H, Ishiguro N. Soft tissue sarcomas of the chest wall. J Thorac Oncol 2009 Jul;4(7):834-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19487966.
  2. Gross JL, Younes RN, Haddad FJ, Deheinzelin D, Pinto CA, Costa ML. Soft-tissue sarcomas of the chest wall: prognostic factors. Chest 2005 Mar;127(3):902-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15764774.
  3. 3.0 3.1 Strander H, Turesson I, Cavallin-Ståhl E. A systematic overview of radiation therapy effects in soft tissue sarcomas. Acta Oncol 2003;42(5-6):516-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14596510.
  4. 4.0 4.1 Jebsen NL, Trovik CS, Bauer HC, Rydholm A, Monge OR, Hall KS, et al. Radiotherapy to improve local control regardless of surgical margin and malignancy grade in extremity and trunk wall soft tissue sarcoma: a Scandinavian sarcoma group study. Int J Radiat Oncol Biol Phys 2008 Jul 15;71(4):1196-203 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18207661.

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Appendices

Further resources