Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non–UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15⁺), macrophages (CD68⁺), cytotoxic T cells (CD8⁺), Tregs (FOXP3⁺), and PD-L1⁺ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.

Pathologic complete response to checkpoint inhibition in MSI-high leiomyosarcoma.

To study the applicability of 2 common nomograms in retroperitoneal sarcoma patients treated in an Asian tertiary hospital, and to study relapse patterns. Patients from 1st January 2000 to 31st December 2017 were retrospectively analysed. R2 resection from an external institution were ineligible. Harrel's C concordance index and calibration plots were used to assess nomograms' accuracy. 109 patients were eligible, with a median age of 56, median tumour size of 16 cm and median follow up of 44.1 months. Most common subtypes were DDLPS (46.8%), LMS (19.3%) and WDLPS (13.8%). Overall, 81.1% had passed away from sarcoma. Recurrence patterns differed with subtypes; 6.7% of WDLPS and 66.7% of LMS had distant relapses. WDLPS patients had a median sarcoma specific survival of 139 months (122-NA), while the rest had a median SSS of 72.3 months (59.7-NA). The 5-years and 7-year OS were 63.0% (95% CI: 53.6%-74.0%) and 51.6% (41.1%-64.8%) respectively. The 5-years and 7-year DFS were 22.4% (15.5%-32.3%) and 17.5% (11%-27.8%) respectively. The 4-years, 8-years and 12-year SSS were 71.3% (62.7%-81.0%), 51.8% (40.8%-65.8%) and 32.2% (19.7%-52.6%) respectively. The concordance indices for 7-year DFS and OS (Sarculator) were 0.63 and 0.73. The concordance indices for 4-, 8- and 12-year SSS (MSKCC) were 0.64, 0.72 and 0.72. Both nomograms were effective in our cohort. Both nomograms can be further improved by specifying the type of relapse and including a longer-term endpoint for the Sarculator.