Abstract

Simple SummaryNeoadjuvant radiotherapy has gained popularity as a treatment strategy for locally advanced soft tissue sarcoma of the extremities. However, little is yet known about the benefits and risks of adding preoperative chemotherapy. High-risk patients with soft tissue sarcomas of the extremities are treated with a combined preoperative radiochemotherapy at our institution. This study reports an analysis of patients treated either with primary surgery or with preoperative radiochemotherapy, followed by surgery. This kind of multimodal therapy leads to excellent oncological outcomes and is associated with low rates of severe postoperative complications in highly specialized centers.Background: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy. Methods: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m2/d, d1–5, q28) and doxorubicine (50 mg/m2/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6–202). Results: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21–93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis (p = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications (p = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group. Conclusions: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.

Highlights

  • Neoadjuvant treatment modalities of soft tissue sarcoma (STS) of the extremities have become more and more popular over the last decade [1,2], little is known about the advantages of a combined radiochemotherapeutic approach

  • A recent analysis of advanced STS at our institution confirmed that neoadjuvant radiochemotherapy is associated with good feasibility and high local efficacy

  • At time of diagnosis more than half of the patients (53%) had stage I or II according to AJCC [28] and were classified as being low-risk, while 47% had stage III or IV

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Summary

Introduction

Neoadjuvant treatment modalities of STS of the extremities have become more and more popular over the last decade [1,2], little is known about the advantages of a combined radiochemotherapeutic approach. NRCT was applied to patients with unfavorable conditions for a complete resection of STS already in 1992 as a phase-II-study [16] These conditions included: unresectable or borderline resectable STS, unfavorable tumor location (retroperitoneum or head and neck region, infiltration of vessels and bones), high-risk tumor (tumor size ≥ 5 cm, grade II-III, deep/extracompartmental location) and recurrent sarcoma. This approach was proved to be a safe and effective treatment providing good 3-year survival rates (OS, MFS and DFS: 83%, 68% and 64%, respectively) [16].

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