The role of neoadjuvant radiochemotherapy in the management of localized high-grade soft tissue sarcoma

Abstract

Background Standard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT). Methods Overall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied. Results UVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies. Conclusions The results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings.

Neoadjuvant Radiotherapy Is Associated with Fewer Acute Adverse Skin Reactions Without Increased Risk of Postoperative Wound Complications in High-Grade Extremity Soft Tissue Sarcoma - A Retrospective Comparative Study with A Mean Follow-Up of 7 Years

“…A 10-year retrospective study revealed neoadjuvant chemoradiotherapy and surgery resulted in high rates of survival with tolerable short-and long-term toxicity for patients with high grade extremity and truncal STS [12]. The retrospective study conducted by Kobus et al also revealed similar findings [13].…”

A novel nomogram and prognostic factor for metastatic soft tissue sarcoma survival

“…Chemotherapy plays a crucial role in STS treatment, employing pharmaceutical intervention to disrupt cancer cell growth and division. For highly malignant mSTS, chemotherapy is frequently utilized as part of a comprehensive treatment plan, either before or after surgery ( 39 ). Sensitivity to chemotherapy varies based on the subtype and molecular characteristics of STS, necessitating personalized treatment approaches.…”

Soft Tissue Sarcomas in Adolescents and Young Adults

“…[75][76][77][78] Neoadjuvant or adjuvant chemotherapy is considered for localized disease in the settings of high-grade and large tumors in adults but is less widely adopted and, similar to radiation, the sequencing of therapy has not been established. 48,49,79,80 A histology-tailored approach to therapy has not been demonstrated to be superior to standard chemotherapy. 34 However, there have been some histologyspecific therapy identified that could be alternatives to standard chemotherapy in adults such as NY-ESO-1-directed therapy in synovial sarcoma and myxoid/round cell LPS and trabectedin in myxoid LPS.…”