The role of radiotherapy in the treatment of soft tissue sarcoma

Radiation oncologist, Dr Nirasha Chiranjan, educates us on how radiotherapy is used in the treatment of soft tissue sarcoma.

What are soft tissue sarcomas (STS)?

STS are rare malignant tumours that arise from mesenchymal tissue (soft tissue) at any body site. They represent less than 1% of all newly diagnosed malignant tumours¹. The most common sites are the extremities (limbs), trunk and retroperitoneum (abdominal cavity, usually internal)².

Therapeutic goals

Before the introduction of radiotherapy for extremity STS, amputation was the standard of care which resulted in significant physical and psychological morbidity. In treating extremity STS, the major therapeutic goals are survival, avoidance of a local recurrence, maximising function, and minimising morbidity³. 

Due to the rarity of this disease, patients with soft tissue sarcoma should be managed by a multi-disciplinary team, made up of a radiation oncologist, medical  oncologist, surgeon, pathologist, radiologist and allied health workers, to ensure best care and rehabilitation. 

Each patient needs to be individualised, based on their age, functional status, tumour type and grade, tumour location and presence of distant metastases.

Treatment

Limb-sparing surgical resection and radiation therapy are recommended for most patients with STS of the extremities or chest wall. The addition of radiation therapy minimises the risk of a local recurrence and maximises function and long-term survival.

Surgery alone is usually reserved for small tumours less than 5cm that are low grade. Radiotherapy is recommended in addition to surgery  for most other patients with sarcomas. 

Two randomised clinical trials both showed that the combination of limb-sparing surgery and radiotherapy reduced the risk of local recurrence by 25% when compared to limb-sparing surgery alone^5,6.

Radiotherapy is used to effectively eradicate microscopic disease and is used in doses ranging from 50 to 70Gy⁴. Higher radiation doses are usually reserved for patients with positive margins. 

Timing of radiotherapy

Radiotherapy can be administered preoperatively or postoperatively. There is no difference in local control between either two.

Preoperative radiotherapy allows for a reduction in the tumour size and more conservative surgery. A lower radiation dose is administered to a smaller target volume. 

Postoperative radiotherapy, however, is associated with more wound healing problems. 

Radiation for STS is generally well-tolerated with most side effects related to the site of delivery. Long-term side effects are uncommon and are mainly due to scarring of the soft tissues, leading to hardening contractures, joint stiffness and swelling¹².

Radiotherapy techniques

A variety of radiotherapy techniques can be employed to improve disease control and functional outcomes. Modern radiotherapy machines  and advanced treatment planning techniques, like intensity-modulated radiation therapy (IMRT) and stereotactic radiotherapy have been shown to reduce side effects in the preoperative and postoperative radiotherapy setting^7,8. 

Stereotactic radiotherapy may be used in the metastatic setting, to control disease that has spread to other sites, most commonly the lungs⁹.

Brachytherapy is a specialised radiotherapy technique that can be   used in the management of soft tissue sarcomas. Catheters are implanted at the time of surgery and radiation is delivered via these catheters to the tumour bed thereby reducing radiation exposure to normal surrounding tissues and resulting in a shorter radiation treatment time¹¹. 

Trials have demonstrated that brachytherapy is effective in high grade tumour and not in low grade tumours. Definitive radiotherapy has been used in patients who are unable to tolerate surgery or who would not accept amputation as a treatment option. Radiotherapy using higher doses is required to maintain good local control and with this, more late side effects may be experienced¹⁰. 

Final thought

Therefore, radiotherapy plays an important role in the multimodality treatment of STS. Future directions in radiotherapy will aim for more conformal techniques, like proton therapy and IMRT, to improve disease outcomes and minimise toxicity.

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68:7.
• Pisters PWT, Weiss M, Maki R. Soft-tissue sarcomas. In: Haller DG, Wagman LD, Camphausen C, Hoskins WJ, eds. Cancer management: a multidisciplinary approach. 14th ed. Norwalk, Conn: UBM Medica, 2011
• Schray MF, Gunderson LL, Sim FH, Pritchard DJ, Shives TC, Yeakel PD. Soft tissue sarcoma: integration of brachytherapy, resection, and external irradiation. Cancer1990;66(3):451–456
• Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982; 196:305.
• Pisters PW, Harrison LB, Leung DH, et al. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996; 14:859.
• Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998; 16:197.
• O’Sullivan B, Griffin AM, Dickie CI, et al. Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma. Cancer 2013; 119:1878.
• Wang D, Zhang Q, Eisenberg BL, et al. Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial. J Clin Oncol 2015; 33:2231.
• Stragliotto CL, Karlsson K, Lax I et al. A retrospective study of SBRT of metastases in patients with primary sarcoma. Med Oncol2012;29(5):3431–3439
• Tepper JE, Suit HD. Radiation therapy alone for sarcoma of soft tissue. Cancer 1985; 56:475.
• Pearlstone DB, Janjan NA, Feig BW et al. Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field. Cancer J Sci Am1999;5(1):26–33
• Baldini EH, Lapidus MR, Wang Q et al. Predictors for major wound complications following preoperative radiotherapy and surgery for soft-tissue sarcoma of the extremities and trunk: importance of tumor proximity to skin surface