bims-myxlip 2022-03-13 papers

Issue of 2022–03–13
six papers selected by
Laura Mannarino, Humanitas Research

Am J Transl Res. 2022 ;14(2): 1268-1278

NY-ESO-1 as a diagnostic and prognostic marker for myxoid liposarcoma.

Uiree Jo, Jin Roh, Min Jeong Song, Kyung-Ja Cho, Wanlim Kim, Joon Seon Song.

INTRODUCTION: Myxoid liposarcoma (MLS) is a common lipogenic sarcoma, which is difficult to diagnose in small specimens. New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) is a cancer-testis antigen expressed in neoplastic tissue. In this study, NY-ESO-1 expression was assessed in various soft tissue tumors (STTs), and we also evaluated its diagnostic utility.
METHODS: We included 434 cases of STTs for collection of clinicopathological data. Tissue microarrays were designed, and immunostaining for NY-ESO-1 was examined. We investigated the correlation between NY-ESO-1 expression and various clinicopathological parameters. We also evaluated the role of NY-ESO-1 as a diagnostic marker for MLS and its possible use in prognostication.
RESULTS: Sixty-four of the 434 STTs (14.75%) were immunoreactive for NY-ESO-1, and the most frequent type of tumor in the NY-ESO-1 positive group was MLS (70.3%, 45/64), followed by synovial sarcoma (17.2%, 11/64). MLS showed 72.6% (45/62) immunopositivity for NY-ESO-1. The sensitivity and specificity of NY-ESO-1 expression for the diagnosis of MLS were 84.4% and 100%, respectively, compared to DDIT3 fluorescence in situ hybridization. When restricting analysis to the MLS (n=62), the NY-ESO-1 positive group had a poor overall survival (OS) rate (P=0.039).
CONCLUSION: NY-ESO-1 was substantially and widely expressed in the majority of MLS cases. NY-ESO-1 positivity by IHC staining was also a predictor of a poor OS in patients with MLS. It is possible to use NY-ESO-1 for diagnosis and for predicting a prognosis in patients with MLS, and it may be used as a therapeutic target.

Keywords: DDIT3; Myxoid liposarcoma; NY-ESO-1; immunohistochemistry; soft tissue tumors

Ther Adv Med Oncol. 2022 ;14 17588359221081073

Overview of systemic therapy options in liposarcoma, with a focus on the activity of selinexor, a selective inhibitor of nuclear export in dedifferentiated liposarcoma.

Prapassorn Thirasastr, Neeta Somaiah.

Liposarcoma (LPS) is a common soft tissue sarcoma that encompasses diverse subtypes of well-differentiated/dedifferentiated, myxoid/round cell, and pleomorphic LPS. There is heterogeneity among the various LPS types with regard to prognosis, molecular pathogenesis, and response to treatment. Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) are most common types, which share common genetic alteration of chromosome 12q13-15 amplification resulting in amplification of oncogenes, including MDM2 (Mouse double minute 2), CDK4 (cyclin-dependent kinase 4), and HMGA2 (High mobility group protein AT-hook 2). Despite sharing the same molecular alteration, DDLPS has a worse prognosis, with a higher recurrence rate and higher propensity for metastases compared to WDLPS. Here we provide an overview of the LPS treatment landscape focusing on recent developments in the treatment of DDLPS with a focus on selinexor. Selinexor, a selective inhibitor of XPO1, was recently evaluated in a phase 3 trial, the first prospective randomized trial in DDLPS, and we discuss its efficacy in context of other available agents for DDLPS.

Keywords: dedifferentiated liposarcoma; liposarcoma; selinexor; soft tissue sarcoma; systemic treatment in liposarcoma

DOI: https://doi.org/10.1177/17588359221081073

J Int Med Res. 2022 Mar;50(3): 3000605221082852

Descriptive epidemiology of soft tissue and bone sarcomas in Lebanon.

Maroun Bou Zerdan, Paul Meouchy, Nour Abdul Halim, Said Saghieh, Eman Sbaity, Rachid Haidar, Jaber Abbas, Amir Ibrahim, Mohamad Khalifeh, Hazem I Assi.

OBJECTIVES: Most epidemiologic studies on soft tissue sarcomas (STS) and bone sarcomas (BS) are performed in western countries, with few in the Middle East and North Africa region. We describe the epidemiology of sarcomas in Lebanon using the medical records database at the American University of Beirut Medical Center (AUBMC).
METHODS: This single-center retrospective cohort study included patients with sarcomas registered in the database between 2015 and 2019. Their charts were reviewed for baseline characteristics, tumor biology and location, treatment modalities, recurrence, metastasis, and death.
RESULTS: The cohort included 234 patients with STS and 99 patients with BS. Most tumors were <10 cm in size. The most common subtypes were liposarcoma for STS and osteosarcoma for BS. The most common location of STS was the thigh. The most frequent sites of STS metastasis were the lungs. Histological subtype, smoking status, and tumor size and grade were significant for progression-free survival (PFS) in patients with STS. By multivariable analysis, smoking was significantly associated with poorer PFS in STS. For BS, only tumor grade was significant for PFS.
CONCLUSION: The epidemiology of sarcomas at AUBMC is similar to that previously reported. Smoking history was associated with poorer survival in patients with STS.

Keywords: Soft tissue sarcoma; angiosarcoma; dermatofibrosarcoma; leiomyosarcoma; liposarcoma; malignant fibrous histiocytoma; rhabdomyosarcoma

DOI: https://doi.org/10.1177/03000605221082852

Curr Treat Options Oncol. 2022 Mar 09.

Immunotherapy and Biomarkers in Sarcoma.

Thanate Dajsakdipon, Teerada Siripoon, Nuttapong Ngamphaiboon, Touch Ativitavas, Thitiya Dejthevaporn.

OPINION STATEMENT: Sarcoma describes a rare and heterogeneous group of diseases. Current treatment options for metastatic sarcoma are quite limited. Conventional treatments with chemotherapy or anti-angiogenic agents result in a non-durable response and a survival rate of approximately 12 to 18 months. In addition, the benefits of such treatments remain limited in some sarcoma subtypes only. Immunotherapy is an emerging treatment for several cancer types with promising outcomes. Studies at the cellular level have shown a relatively high immunogenicity in some subtypes of sarcoma. It is therefore hypothesized that sarcoma may respond to immunotherapy. However, sarcoma is a heterogeneous disease and differences in terms of immunogenicity exist. A multitude of immune-based treatment approaches for sarcoma have been explored. This includes immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapy. Single-agent immunotherapy has exhibited efficacy against some sarcoma subtypes, including alveolar soft-part sarcoma, angiosarcoma, and undifferentiated pleomorphic sarcoma. Combination immunotherapy appears superior to single-agent immunotherapy in terms of response, and several ongoing studies of immunotherapy using single/combination immune checkpoint inhibitors and combination with anti-angiogenesis have begun to report beneficial results. Predictive and prognostic biomarkers are also under active investigations, with particular interest in tumor-infiltrating lymphocytes or high tumor mutational burden levels. However, the information is still limited and further studies are needed.

Keywords: Adoptive cell therapy; Biomarkers; Bone sarcoma; Immunotherapy; Soft tissue sarcoma; Therapeutic vaccines

DOI: https://doi.org/10.1007/s11864-022-00944-6

Curr Treat Options Oncol. 2022 Mar 08.

Role of Virus-Directed Therapy in Soft Tissue Sarcoma.

Hira Chaudhary, Sandra D'Angelo.

OPINION STATEMENT: Bone and soft tissue sarcoma are rare cancers of mesenchymal origin with the characteristics of heterogeneity and diversity that account for less than 1% of solid malignant cancers. Conventional chemotherapy remains standard of care with response rates of 10-15% that are usually dependent on histologic subtype as some subtypes are chemotherapy resistant. There remains a large unmet clinical need for new and novel options promoting the development of promising therapeutic options such as immunotherapy. With more than 80 different subtypes, the heterogeneity of sarcoma requires thoughtful clinical trial design. In the sarcoma field, recent breakthroughs have occurred in the context of histology-specific approach based on underlying tumor biology. To that end, immunotherapy approaches will need to take a similar approach. Oncolytic viruses (OVs) have emerged as a promising treatment for many solid tumors and shown encouraging results in sarcoma. This review mainly focuses on collective clinical data highlighting the role of OVs as immunotherapy being used in soft tissue sarcoma (STS) and bone sarcomas. Combining OVs with T cell-activating checkpoint inhibition, adoptive cell therapy or targeted therapies may yield increased potency, improve antitumor efficacy of oncolytic virotherapy, and offer a new prospect for the treatment of sarcoma.

Keywords: Adenovirus; Biomarker; Immunotherapy; Oncolytic viral therapy; Sarcoma; T-VEC; Tumor-infiltrating lymphocyte

DOI: https://doi.org/10.1007/s11864-022-00956-2

Cancers (Basel). 2022 Mar 02. pii: 1290. [Epub ahead of print]14(5):

Immunologic Gene Signature Analysis Correlates Myeloid Cells and M2 Macrophages with Time to Trabectedin Failure in Sarcoma Patients.

Brett A Schroeder, Yuzheng Zhang, Kimberly S Smythe, Parth Desai, Anish Thomas, Pedro Viveiros, Borislav A Alexiev, Farres Obeidin, Eleanor Y Chen, Lee D Cranmer, Michael J Wagner, Robin L Jones, Jean S Campbell, Robert H Pierce, Qianchuan He, Seth M Pollack.

Patients with metastatic soft tissue sarcoma (STS) have a poor prognosis and few available systemic treatment options. Trabectedin is currently being investigated as a potential adjunct to immunotherapy as it has been previously shown to kill tumor-associated macrophages. In this retrospective study, we sought to identify biomarkers that would be relevant to trials combining trabectedin with immunotherapy. We performed a single-center retrospective study of sarcoma patients treated with trabectedin with long-term follow-up. Multiplex gene expression analysis using the NanoString platform was assessed, and an exploratory analysis using the lasso-penalized Cox regression and kernel association test for survival (MiRKAT-S) methods investigated tumor-associated immune cells and correlated their gene signatures to patient survival. In total, 147 sarcoma patients treated with trabectedin were analyzed, with a mean follow-up time of 5 years. Patients with fewer prior chemotherapy regimens were more likely to stay on trabectedin longer (pairwise correlation = -0.17, p = 0.04). At 5 years, increased PD-L1 expression corresponded to worse outcomes (HR = 1.87, p = 0.04, q = 0.199). Additionally, six immunologic gene signatures were associated with up to 7-year survival by MiRKAT-S, notably myeloid-derived suppressor cells (p = 0.023, q = 0.058) and M2 macrophages (p = 0.03, q = 0.058). We found that the number of chemotherapy regimens prior to trabectedin negatively correlated with the number of trabectedin cycles received, suggesting that patients may benefit from receiving trabectedin earlier in their therapy course. The correlation of trabectedin outcomes with immune cell infiltrates supports the hypothesis that trabectedin may function as an immune modulator and supports ongoing efforts to study trabectedin in combination with immunotherapy. Furthermore, tumors with an immunosuppressive microenvironment characterized by macrophage infiltration and high PD-L1 expression were less likely to benefit from trabectedin, which could guide clinicians in future treatment decisions.

Keywords: M2 macrophage; PD-L1; myeloid cells; sarcoma; trabectedin

DOI: https://doi.org/10.3390/cancers14051290