Five versus Twenty-Five: Should soft tissue sarcomas be treated with hypofractionated regimens?

The February #radonc #JC focuses on pre-operative hypofractionated radiation regimen to treat Soft Tissue Sarcomas (STS).

The discussion will begin Saturday, February 19^th at 8 AM CST and go through Sunday, February 20^th, culminating in the live hour from 1-2 pm CST, Sunday February 20^th.

Soft tissue sarcomas (STS) are treated using a multidisciplinary approach. Both pre-operative and post-operative radiation treatments have been utilized. Despite pre-operative radiation having a higher risk of wound complications compared to post-operative radiation, the benefits of smaller field size, decreased radiation dose and improved long-term toxicities have resulted in popularity of the pre-operative approach (1).

Considering the lower α/β ratio of sarcomas, hypofractionation might result in a better response. It can also be more convenient for patients and reduce the time to surgical resection. However, there is still some concern about the possibility of toxicity.

There have been studies looking at pre-operative hypofractionated radiation for STS (2-9). These studies use different radiation regimens ranging from 25-40 Gy in 5-10 fractions. R0 resection rates range from 62% to 100% with a 5-year local control of 89% to 97%. The rate of wound complication is 10-38%.

In this month’s #RadOnc #JC, we will focus on a phase II trial looking at using 35 Gy in 5 fractions in the pre-operative setting for STS:

Bedi M et al. Could Five Be the New Twenty-Five? Long-term Oncologic Outcomes from a Phase II, Prospective, 5-Fraction Pre-operative Radiation Therapy Trial in Patients with Localized Soft Tissue Sarcoma

We are thrilled to be joined by Dr. Meena Bedi (@DrMeenaBedi), Dr. Shauna Campbell (@ShaunaRadonc) and Dr. Matthew Spraker (@SprakerMdPhD) for this month’s #RadOnc #JC

Our guiding topics this month are as follows:

T1. Background: What data supports the use of a hypofractionated regimen in STS? What is unique about this study compared to other available trials?

T2. Methods: What were the eligibility criteria? How were patients simulated and contoured? What was the chemotherapy regimen? What were the endpoints?

T3. Results/Discussion: What were the important findings of this trial? was toxicity different compared to standard fractionated regimens? What were the limitations of this study? How does this compare to current local practices?

T4. #PatientsIncluded: What is important for patients who have been diagnosed with STS?  What is important when speaking with their radiation oncologists on options including hypofractionated regimens?

T5. Next steps: How can this trial change treatment options in STS? What else can improve outcomes for STS?

References:

1. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359(9325):2235-41.

2. Kosela-Paterczyk H, Szacht M, Morysinski T, Lugowska I, Dziewirski W, Falkowski S, et al. Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas. Eur J Surg Oncol. 2014;40(12):1641-7.

3. Kubicek GJ, LaCouture T, Kaden M, Kim TW, Lerman N, Khrizman P, et al. Preoperative Radiosurgery for Soft Tissue Sarcoma. Am J Clin Oncol. 2018;41(1):86-9.

4. Kalbasi A, Kamrava M, Chu FI, Telesca D, Van Dams R, Yang Y, et al. A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma. Clin Cancer Res. 2020;26(8):1829-36.

5. Temple WJ, Temple CL, Arthur K, Schachar NS, Paterson AH, Crabtree TS. Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas. Ann Surg Oncol. 1997;4(7):586-90.

6. MacDermed DM, Miller LL, Peabody TD, Simon MA, Luu HH, Haydon RC, et al. Primary tumor necrosis predicts distant control in locally advanced soft-tissue sarcomas after preoperative concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2010;76(4):1147-53.

7. Meyer JM, Perlewitz KS, Hayden JB, Doung YC, Hung AY, Vetto JT, et al. Phase I trial of preoperative chemoradiation plus sorafenib for high-risk extremity soft tissue sarcomas with dynamic contrast-enhanced MRI correlates. Clin Cancer Res. 2013;19(24):6902-11.

8. Ryan CW, Montag AG, Hosenpud JR, Samuels B, Hayden JB, Hung AY, et al. Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas. Cancer. 2008;112(11):2432-9.

9. Pennington JD, Eilber FC, Eilber FR, Singh AS, Reed JP, Chmielowski B, et al. Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas. Am J Clin Oncol. 2018;41(12):1154-61.