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.

Background The literature reports a wide variety of reconstructive methods for pharyngolaryngoesophageal (PLO) defects, the most widely used being anterolateral thigh (ALT), radial forearm (RFF), and jejunal free flaps (JFF). However, there is a lack of uniform agreement among head and neck surgeons as to which technique offers the best results. With an increasing number of salvage PLO extirpations, determining the role of radiotherapy in influencing postoperative complication rates is becoming ever more important. Hence, this study aims to provide an up-to-date comparison of surgical and functional outcomes of the fasciocutaneous ALT and RFF versus the intestinal JFF for circumferential and partial PLO defects and determine whether radiotherapy, both preoperative and postoperative, influences the postoperative fistula and stricture rates in circumferential defects. Methods A systematic review and meta-analysis were performed using PubMed for reports published in the most recent 10 years between 2007 and 2017. Results A total of 33 articles comprising 1213 patients were reviewed. For circumferential defects, fistula and stricture rates were significantly lower in JFF than ALT and RFF. Of note, there was no statistical difference in tracheoesophageal speech and oral alimentation rates between JFF and the FC flaps. For near-circumferential and partial defects, ALT has a significantly lower fistula rate than RFF. There was no statistical Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation difference in stricture and oral alimentation rates between ALT and RFF. Fistula rates were significantly higher in patients who had preoperative radiotherapy than those without. However, there was no significant difference in fistula and stricture rates for postoperative radiotherapy. Conclusions Jejunal free flaps still remain an excellent first choice for PLO reconstruction of circumferential defects. For near-circumferential and partial defects, ALT seems to have a better performance than RFF. Preoperative radiotherapy was associated with an increased risk of fistula formation in circumferential PLO defects but not postoperative radiotherapy.

Jejunal flap has a significantly lower rate of stricture for reconstruction of circumferential pharyngeal defects when compared with RFF or ALT flaps.