ABSTRACT
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.
Subject(s)
Hemangiosarcoma , Neoplasm Proteins , Cell Line, Tumor , Female , Hemangiosarcoma/classification , Hemangiosarcoma/genetics , Hemangiosarcoma/immunology , Humans , Inflammation/classification , Inflammation/genetics , Inflammation/immunology , Male , Neoplasm Proteins/genetics , Neoplasm Proteins/immunologySubject(s)
Exome Sequencing , Eye Proteins/genetics , Germ-Line Mutation , Lymphoma, Extranodal NK-T-Cell/diagnosis , Lymphoma, Extranodal NK-T-Cell/genetics , Adult , Biopsy , Eye Proteins/metabolism , Gene Expression , Gene Expression Profiling , Humans , Immunohistochemistry , Lymphoma, Extranodal NK-T-Cell/metabolism , Male , Pedigree , SiblingsABSTRACT
AIM: A nomogram for prediction of 12-year sarcoma-specific survival has been developed based on patients with soft tissue sarcomas treated in Memorial Sloan Kettering Cancer Centre (MSKCC). We aim to evaluate the predictive accuracy of the MSKCC sarcoma nomogram in a cohort of patients treated at an Asian institution. This has not been validated in an Asian population and thus its universal applicability remains unproven. MATERIALS AND METHODS: Between 1990 and 2013, 840 adult patients underwent treatment for primary soft tissue sarcoma (STS) at the National Cancer Centre Singapore. Patients who presented with locally recurrent or metastatic disease were excluded from the analysis. The variables included in the MSKCC nomogram included age at diagnosis, tumor size, histologic grade, histologic subtype, depth and site. A total of 399 patients were left for analysis. The nomogram was validated by assessing its extent of discrimination and level of calibration. RESULTS: All patients had deep tumors. Disease occurred most commonly in the lower extremity (n = 149 [37.3%]), the most common histologic subtype was "Others" (angiosarcoma, ewing's sarcoma, endometrial stromal sarcoma, sarcoma NOS [not otherwise specified] and rhabdomyosarcoma). Sixty-four percent of all patients had high-grade tumors while 36% had low-grade tumors. The median patient age at diagnosis was 54 years (range: 17-88 years). The median follow up time for all patients and surviving patients were 29 (range: 1-174) and 33 (range: 1-157) months, respectively. The observed 5- and 10-year sarcoma-specific survival were 55% and 33%, respectively. The concordance index was 0.71. For level of calibration, the observed correspondence between predicted and actual outcomes suggest that the MSKCC nomogram generally predicts well for patients with higher survival probability, but consistently overpredicts survival for the other groups, in our cohort of patients. CONCLUSION: The MSKCC sarcoma nomogram was found to be accurate in terms of extent of discrimination. In terms of level of calibration, it generally predicts well for patients with higher survival probability, but consistently overpredicts survival for the other groups in our population.
Subject(s)
Nomograms , Sarcoma/classification , Adolescent , Adult , Aged , Aged, 80 and over , Asian People , Cohort Studies , Female , Humans , Middle Aged , Oncology Service, Hospital , Sarcoma/pathology , United States , Young AdultABSTRACT
This study aimed to describe the epidemiology and risk factors for cytomegalovirus (CMV) infection and end-organ disease in patients with lymphoma undergoing potentially curative or salvage therapy. We retrospectively reviewed 534 patients with lymphoma treated at an Asian tertiary cancer center between January 2007 and December 2010. Overall, 48 patients (9.0%) experienced CMV infection, with 12 patients (25.0%) being further diagnosed with CMV end-organ disease. Many patients with CMV infection were male, with poor performance status, non-Hodgkin lymphoma and advanced disease, and received rituximab use. Moreover, patients receiving rituximab and HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) regimens had a high rate of CMV end-organ disease. In Asian patients with lymphoma receiving curative or salvage therapy, CMV infection was relatively common (9.0%). Most of these were likely to be reactivation in nature. A small group, especially those on rituximab or HyperCVAD, developed CMV end-organ disease (12/534). Such patients should be monitored closely for CMV end-organ disease. Alternatively, prophylaxis should be studied.
