Combined Radiotherapy and Surgery Effective for Extremity STS

New research provides insights on treatment of extremity soft tissue sarcomas (STS) that incorporates radiotherapy (RT) and surgery, with data published in Cancers (Basel) showing patients are highly likely to tolerate this therapy combination, with clinicians in turn having more choices to optimize treatment modalities and enhance patient care.¹

STS is rare, in that it accounts for a scant 1% of all adult solid malignancies, the study authors noted; within this group, however, are more than 80 histologic subtypes.²

Still, data are scarce on the relationship between surgery and radiation therapy, specifically timing of the latter. “This dearth of data has posed challenges in comparing series, particularly those employing modern radiotherapy techniques such as intensity-modulated radiation therapy (IMRT) or hypofractionated schedules,” they wrote, adding that their goal with the present investigation was to assess potential relationships between these 2 treatment modalities and compare those findings with the current literature.¹

The adult patient population in this monocentric study (N = 169) was treated between 2007 and 2020, all with surgery and radiation therapy. Tumor characteristics helped determine radiation regimen. Patients could have received radiation either before or after surgery, and normofractionated, hypofractionated, or hyperfractionated regimens were utilized. The investigators made sure to note, “Irradiation of the entire circumference of the limb was avoided with the incorporation of a dosimetry-defined volume of normal tissue called the ‘skin corridor.’”

In this study, the most common adverse events from surgery and radiotherapy to treat soft tissue sarcoma were radiodermatitis and acute edema | Image Credit: Dr_Microbe-stock.adobe.com

At first, patients were evaluated weekly during RT, and then for up to 5 years, every 4 to 6 months they were evaluated as needed by a radiation oncologist, surgeon, and medical oncologist. Annual evaluations came after the 5-year mark.

Overall, 50.9% of patients were female, but there were more male patients (51.6%) in the postoperative RT group (n = 155) and more female patients (78.6%) in the preoperative RT group (n = 14). Their median overall age was 64 (range, 21-94) years (P = .264), and more patients in the postop RT group were older than 60 years vs the preop RT group (60.6% vs 42.9%).

Tumors were primarily located on the body’s proximal, or right, side (74.6%, overall; 73.5%, postop RT group; 85.7%, preop RT group); were grade 3 (41.4%, overall; 43.2%, postop RT group) or grade 1 (50.0%, preop group); had a margin status of R0 (62.7%, 63.5%. and 57.4%, respectively); were classified as TNM T2b (69.2%, 68.4%, and 78.6%), meaning they were 4 cm to 5 cm³; and were a liposarcoma (33.1%, 31.0%, and 57.1%);

The median intervals between receipt of RT and surgery were 82 days in the postop RT group and 83 days in the preop RT group, and median duration of RT, 37 days. IMRT was the most common type of RT received (79.3%, overall; 77.4%, postop group; 100%, preop group).

“To facilitate comparisons among the various schedules due to the different fractionation schemes, doses were converted to BEDGy₄ or BEDGy₁₀,” the authors noted, referring to the biologically effective dose (BED) measured in Gy of radiation.

The median dose of BEDGy₄ was 75, overall and in both RT groups, and the most common BED₄ dose was 75 Gy or greater, in 96.4% of the overall study population, 96.8% of those who received postop RT, and 92.9% of those who received preop RT. The median dose of BEDG_y10 was 60, overall and in both RT groups, and the most common BED₁₀ dose was 60 Gy or greater, in 94.0%, 95.5%, and 92.9%, respectively. Also, most patients received a normofractionated (1.8-2 Gy/d) RT regimen (91.2%, 91.0%, and 92.9%).

There were wound complications (WCs) in 22.5% of the postop RT group (n = 32)—and among these, 84.2% developed at least 1 WC—vs 42.9% (n = 6) of the preop RT group (OR, 2.88; 95% CI, 0.93-8.9; P = .088). However, WCs were less common in patients with upper-limb extremity STS vs lower-limb extremity STS (7.9% vs 92.1%; OR, 0.14; 95% CI, 0.042-0.49; P = .001). Tumors that were 5 cm or smaller had a significant association with a lower WC rate (13.2% vs 86.8%; OR, 0.29; 95% CI, 0.11-0.79; P = .02), and upper limb localization and distality were favorable prognostic factors for WCs (ORs, 0.2 and 0.188, respectively).

The most common adverse event overall was radiodermatitis, in 78% of the overall study population, followed by acute edema in 34.1%. Most common chronic complications related to RT were telangiectasias in 21.7% and fibrosis in 38.7%.

Speaking to the strength of their findings, the authors note their “meticulous examination” and comprehensive analysis, while limitations include that their study was retrospective and may have contained limited documentation of adverse events, and they did not identify significant risk factors for fractures.

“This comprehensive analysis sheds light on various factors influencing treatment outcomes and provides valuable insights for clinical practice,” they concluded.

References

1. Lebas A, Le Fevre C, Waissi W, Chambrelant I, Brinkert D, Noel G. Complications and risk factors in patients with soft tissue sarcoma of the extremities treated with radiotherapy. Cancers (Basel). 2024;16(11):1977. doi:10.3390/cancers16111977

2. Jo VY, Fletcher CDM. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014;46(2):95-104. doi:10.1097/PAT.0000000000000050

3. Cancer staging. National Cancer Institute. Accessed June 25, 2024. https://www.cancer.gov/about-cancer/diagnosis-staging/staging