BNCT for primary synovial sarcoma

Highlights

• The first evaluation of BNCT for treating primary synovial sarcoma.

• The first patient with synovial sarcoma receiving two courses of BNCT.

• The first instance of partial control of tumor by BNCT as adjuvant therapy.

Abstract

Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic nerve, declining surgery because of potential dysfunction of the affected limbs, received two courses of BNCT. The tumor thus reduced was completely resected with no subsequent recurrence. The patient is now able to walk unassisted, and no local recurrence has been observed, demonstrating the applicability of BNCT as adjuvant therapy for synovial sarcoma. Further study and analysis with more experience accumulation are needed to confirm the real impact of BNCT efficacy for its application to synovial sarcoma.

Introduction

Sarcoma is a very rare malignant neoplasm originating from nonepithelial cells, different from cancer, and representing only 1% of adult malignant tumors (NCCN Guidelines Version 2, 2018). Synovial sarcoma, one of such malignant tumors, comprising approximately 5–10% of all soft tissue sarcomas (Desar et al., 2018) usually presents in the extremities (Sultan et al., 2009), typically with a predilection for adolescents and young adults (Herzog, 2005). Although synovial sarcoma is named after its common periarticular location and its pathological similarity to the synovium, its origin differs from that of synovial tissue (Thway and Fisher, 2014). Histologically, it displays epithelial differentiation and is classified mainly into biphasic and monophasic subtypes. The former has both distinct epithelial and sarcomatous components while the latter only has a sarcomatous component. In the epithelial component, tumor cells are arranged in glands, papillary structures, and cellular nests. On the other hand, spindle-shaped cells proliferate diffusely in the sarcomatous component. An infrequent, poorly differentiated subtype has also been identified (Thway and Fisher, 2014). Currently, synovial sarcoma is also characterized by a reciprocal chromosomal translocation t(X;18)(p11.2;q11.2) that creates a unique chimeric fusion SS18/SSX gene transcript (Clark et al., 1994; Ladanyi, 2001).

The standard treatment for primary localized synovial sarcoma, presently, is wide surgical resection of the tumor and subsequent radiation therapy, and although the role of chemotherapy is still under investigation, synovial sarcoma is sensitive to cytotoxic chemotherapy with drugs such as doxorubicin, ifosfamide, trabectedin and pazopanib (Stacchiotti and Van Tine, 2018). Nevertheless, the prognosis of the disease is poor: the 5-year overall survival rate is only around 60% (Wang et al., 2017); furthermore, metastases occur in almost 50% of cases (Krieg et al., 2011), necessitating search for new therapeutic strategies. Recent studies have demonstrated that boron neutron capture therapy (BNCT), with the use of biologically neutral p-borono-l-phenylalanine (BPA), has some limited success in the treatment of head and neck cancers (Wang et al., 2018; Koivunoro et al., 2019) but loco-regional occurrence almost invariably occurs. The selective uptake of BPA by the tumor depends on its transport into cells by the L-type amino acid transporter 1 (LAT1) system expressed mainly on tumor cell membranes (Detta and Cruickshank, 2009; Wongthai et al., 2015). The efficacy of BNCT has been demonstrated in the treatment of malignant melanoma of the vulva and extramammary Paget's disease (Hiratsuka et al., 2018). However, no reports on its use to treat synovial sarcoma suggested that this was worthy of investigation. With that in mind, BNCT was for the first time applied to primary synovial sarcoma arising from the peripheral nerve of the left thigh. The purpose of this study is to clarify the outcome of BNCT and to discuss its application to primary synovial sarcoma.