ASTRO Guideline Provides Clarity on Radiation Use in Soft Tissue Sarcoma

Kilian E. Salerno, MD

The American Society for Radiation Oncology (ASTRO) released a new clinical guideline, which was also published in Practical Radiation Oncology, outlined recommendations and patient selection for optimal radiation dosing, sequencing, and treatment planning for patients with soft tissue sarcoma.^1,2

The guidelines, which are specific to patients with extremity and superficial truncal soft tissue sarcoma and retroperitoneal sarcomas, also focus on the need for multidisciplinary care in the treatment of this patient population.

"Management of soft tissue sarcoma can be complicated, with the potential for poor outcomes and significant morbidity if treated suboptimally. The addition of radiation therapy to surgery reduces the chance of local recurrence," said Kilian E. Salerno, MD, vice chair of the guideline task force and a radiation oncologist at the National Cancer Institute. "This guideline stresses the importance of multidisciplinary input prior to initiation of treatment and provides detailed recommendations on indications for radiation therapy, dose and planning techniques. ASTRO developed this guideline to provide clear guidance on the role of radiation therapy in patient-centered, multidisciplinary oncologic care."

Through a multidisciplinary task force, ASTRO issued the following evidence-based recommendations for patients with soft tissue sarcoma:

• Radiation treatment is recommended for patients with primary, localized extremity, and truncal soft tissue sarcomas who are at a higher risk of local recurrence; final or expected surgical margins; and other factors that are detailed in the guideline;
• Generally, radiation treatment is not suggested for those who are at low risk of local recurrence;
• In patients for whom surgery and radiation are indicated, preoperative radiation is recommended. Postoperative radiation is recommended for specific situations, such as the identification of unanticipated adverse pathologic features after resection or unplanned excision—for example, uncontrolled pain or bleeding—or when the risk of wound healing complications outweighs the risk of long-term, permanent adverse effects (AEs);
• The routine use of radiation treatment, in addition to surgical resection, is conditionally not recommended in patients with primary localized retroperitoneal sarcomas. Selective use of radiation therapy can be an option for those with retroperitoneal sarcomas who are at a high risk of local recurrence, and is preferably preoperative radiation for select cases. Postoperative radiation is not recommended for patients with primary, localized retroperitoneal sarcomas.
• Optimal dosing, fractionation, target delineation and delivery techniques for preoperative and postoperative radiation therapy are also mentioned, including suggestions for image guidance and patient positioning, with a callout to patients' long-term functional outcomes.

With regards to dosing, the task force issued a strong recommendation that if preoperative radiation is planned for patients with primary, localized retroperitoneal sarcoma, the recommend dosage is 5000 cGy in 25-once daily fractions or 5040 cGy in 28 once-daily fractions. Furthermore, four-dimensional CT and delineation of an internal gross tumor volume are recommended for primary localized retroperitoneal sarcomas above the iliac brim in patients for whom preoperative radiation is planned.

Anatomically constrained clinical tumor volume or internal tumor volume, volumetric contouring of organ at risk (OAR), and use of appropriate dose constraints are recommended for treatment planning when preoperative radiation is planned for those with primary, localized retroperitoneal sarcomas. However, the authors noted that physicians should discuss radiation plans with a surgeon on whether ipsilateral kidney and/or partial liver resection is planned because this will have an impact OAR constraints.

Additionally, for patients with primary, localized retroperitoneal sarcomas with planned preoperative radiation, intensity-modulated radiation—including volume-modulated arc therapy—is suggested to minimize dose to OARS and therefore reduce AEs. Three-dimensional conformal radiation can be used instead in select situations.

Finally, daily use of image-guided radiation with weekly, at minimum, volumetric image guidance is recommended if preoperative radiation is planned for patients with primary localized retroperitoneal sarcomas.

The guideline also features treatment procedures for initial local management and local management following an unplanned excision.

Soft tissue sarcomas account for an estimated 1% of all adult cancers with more than 50 subtypes. Treatment for this type of malignancy requires a multidisciplinary approach of orthopedic, surgical, radiation, and medical oncologists, plus specialized radiologists and pathologists. Surgical resection is the mainstay of treatment, followed by radiation for those at a high risk of recurrence. However, sarcoma clinical practice has evolved to include preoperative radiation approaches, which is suggested to decrease the risk of long-term AEs.

"When radiation is indicated, it generally should be given before surgery because the long-term side effects are less severe," said B. Ashleigh Guadagnolo, MD, MPH, chair of the guideline task force and a professor of radiation oncology at The University of Texas MD Anderson Cancer Center. "The side effects of preoperative radiation therapy can be serious, but they are reversible. Postoperative radiation therapy side effects, however, are, in many cases, permanent because more radiation dose is required when given after surgery, and it often needs to be given to a larger area of the body."

ASTRO noted that because not all patients can be treated at high-volume centers to receive treatment for these rare cancers, comprehensive guidelines are necessary to disseminating therapeutic decisions.

The guideline was based on a systematic literature review of articles published from January 1980 through September 2020. Data comprised patients aged at least 18 years who were diagnosed with primary, localized soft tissue sarcoma involving the extremity, superficial trunk, or retroperitoneum, and underwent resection and radiation.

The task force involved in putting together the guideline comprised radiation, medical, orthopedic, and surgical oncologists; a radiation oncology resident; a pathologist; a medical physicist; and a patient representative.

In addition to ASTRO, ASCO, Musculoskeletal Tumor Society (MSTS), and the Society of Surgical Oncology (SUO) also collaborated on the guideline, which was endorsed by the Canadian Association of Radiation Oncology, European Society for Radiotherapy and Oncology, MSTS, the Royal Australian and New Zealand College of Radiologists, and SUO.

In the publication of the guideline, the authors noted that future studies will determine whether dosing and/or sequencing alterations may optimize outcomes and quality of life. Additional areas within soft tissue sarcoma treatment could be included in future guidelines, such as initial evaluation and imaging; biopsy techniques; use of brachytherapy; options for resection and reconstruction; how to treat sarcoma subsites beyond extremity, trunk, and retroperitoneum; therapies for patients with unresectable, recurrent, or metastatic disease; and the role of systemic therapy.

“Although surgical resection with wide margins remains the mainstay of local management for primary, localized [soft tissue sarcoma, radiation] plays an important role in achieving optimal oncologic outcomes with respect to tumor control as well as function preservation for many patients,” the authors concluded.

References

1. Salerno KE, Alektiar KM, Baldini EH, et al. Radiation therapy for treatment of soft tissue sarcoma in adults: executive summary of an ASTRO Clinical Practice Guideline. Pract Rad Oncol. Published online July 25, 2021. doi:10.1016/j.prro.2021.04.005
2. ASTRO issues clinical guideline on radiation therapy for soft tissue sarcoma in adults. News release. American Society for Radiation Oncology (ASTRO). July 27, 2021. Accessed August 17, 2021. https://bit.ly/3AV8eQ1