Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications

Abstract

Soft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments.

Keywords: chemotherapy; neoadjuvant; radiotherapy; soft tissue sarcoma; trial.

Figure 1.

A 38-year-old man was diagnosed with a 8 × 6 × 21 cm mass in his right posterior thigh (a, b) [contrast-enhanced magnetic resonance imaging (MRI), TW1 weighted sequences]. Percutaneous core needle biopsy revealed a high-grade round-cell myxoid liposarcoma (round cells component > 60%). This patient was treated with three cycles of epirubicin (120 mg/m²) and ifosfamide (9000 mg/m²) and concomitant radiotherapy (50 Gy in 25 fractions). After neoadjuvant chemoradiation, contrast-enhanced MRI showed dimensional changes (8 × 2 × 16 cm) and modification in pattern of contrast enhancement, suggesting a tissue response (c, d). Surgery involved a wide excision of the posterior thigh with the sciatic nerve dissected off the tumour (e–g). The pathology report showed two small areas with hypercellularity (0.5 and 1.5 cm, respectively) and negative surgical margins.

Figure 2.

A 58-year-old man was diagnosed with a 6 × 20 cm mass in his left volar forearm. Percutaneous core needle biopsy revealed a high-grade myxofibrosarcoma (a, b) [contrast-enhanced magnetic resonance imaging (MRI), TW1 weighted sequences]. This patient was treated with three cycles of epirubicin (120 mg/m²) and ifosfamide (9000 mg/m²) and concomitant radiotherapy (50 Gy in 25 fractions). MRI showed an increase in tumour dimension and a strong reduction of tissue contrast enhancement, suggesting a tissue response (c, d). Surgery involved a wide excision of the posterior forearm (e). The tumour was resected together with the median nerve which was completely surrounded by the tumour (f, g). The pathology report showed significant presence of necrosis (70% of the tumour mass) and limited residual tumour (30%).