Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

Background: Ewing sarcoma (ES) is a malignant type of bone and soft tissue tumor with EWSR1–ETS gene fusions as the primary driver alteration. Incidence is higher in White populations compared to Black and Asian populations. Researchers use next-generation sequencing to identify alterations as potential therapeutic targets. We compared the data from the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets in the USA with the data from Center for Cancer Genomics and Advanced Therapeutics in Japan. Methods: We sequenced tumor DNA from 81 ES samples using the FoundationOne® CDx for multigene panel testing. Genetic alterations were interpreted via the Cancer Knowledge Database (CKDB) and potentially actionable alterations were classified into levels A–F. Results: Analysis of 81 ES samples revealed 556 mutations in 197 genes and 126 copy-number alterations in 58 genes. Potentially actionable alterations were detected in 10 patients (12.3%) at CKDB levels A or C. STAG2 mutations accounted for 3.7%, TP53 mutations for 17.3%, and CDKN2A deletions for 13.6%. There was no significant difference in overall survival after genomic profiling test enrollment for STAG2 and TP53 mutations (P = .663 and P = .767), but those with CDKN2A and CDKN2B deletions had poor prognosis (P = .024 and P = .012). Conclusion: Compared to previous reports, Japanese ES cases showed lower STAG2 and higher TP53 mutation frequencies. CDKN2A and CDKN2B deletions may serve as prognostic biomarkers indicating unfavorable outcomes.

Introduction: We aimed to identify a new biomarker using ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG) positron emission tomography (PET)/computed tomography (CT) parameters to identify osteosarcoma patients with standard response after neoadjuvant chemotherapy (NAC). Patients and Materials: Fifty-four patients with conventional osteosarcoma (age ≤39 years) were included in this study. All patients underwent ¹⁸ F-FDG PET/CT before (PET1) and after NAC (PET2). We measured PET parameters, including maximum, average, and peak standardized uptake value (SUVmax, SUVave, and SUVpeak); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). Their changes (ΔPET = PET2/PET1) were also examined. The patients were classified into 4 groups based on the histological tumor necrosis rate (TNR): G0 (<50%), G1 (50 to < 90%), G2 (90 to < 100%), and G3 (100%). G0 and G1 patients were enrolled in the standard responder (SR) group (n = 35), while G2 and G3 patients were enrolled in the good responder (GR) group (n = 19). We examined the correlation between changes in each ¹⁸ F-FDG PET/CT parameter and TNR as well as overall survival (OS) and progression-free survival (PFS) among the 4 groups. In the SR group, the median value of ΔSUVmax was calculated and correlated with prognostic stratification. Results: The changes in each PET parameter were correlated with TNR, with SUVpeak showing the strongest correlation. Moreover, in the SR group, there were no differences in OS or PFS between G0 and G1. Patients in the SR group were stratified into 2 groups according to the median ΔSUVmax value (0.62). Patients with ΔSUVmax < 0.62 had significantly better OS (P < 0.01) and PFS (P = 0.02) in comparison with patients with ΔSUVmax ≥ 0.62. In multivariate analyses, ΔSUVmax showed a correlation with OS in the SR group. Discussion: This study revealed that ΔSUVmax may confirm the preoperative stratification of the prognosis be a predictive biomarker for patients in the SR group. Moreover, the preoperative identification of patients with a worse prognosis in the SR group has a significant impact on improving the clinical outcomes of patients with osteosarcoma. Level of Evidence: Prognostic studies, Level III . See Instructions for Authors for a complete description of levels of evidence.