Alveolar soft-part sarcoma (ASPS) is a morphologically distinctive mesenchymal tumor characterized by a canonical ASPL-TFE3 fusion product. In the metastatic setting, standard cytotoxic chemotherapies are typically ineffective. Studies have suggested modest clinical response to multitargeted receptor tyrosine kinase inhibitors. Here, we report sustained partial responses in two patients with immune checkpoint inhibition treated with either durvalumab (anti-PD-L1) alone or in combination with tremelimumab (anti-CTLA-4), which appeared unrelated to tumor immune infiltrates or mutational burden. Genomic analysis of these patients, and other cases of ASPS, demonstrated molecular mismatch-repair deficiency signatures. These findings suggest that immune checkpoint blockade may be a useful therapeutic strategy for ASPS. .

There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological reevaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons). In total, 95 patients initially classified with UPS were identified. Following pathology re-review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N 5 44); UPS(N 5 18); and Others (N 5 27; including undifferentiated spindle cell sarcoma (N 5 15) and dedifferentiated liposarcoma (N 5 6)). Seven cases were excluded from further analysis for other reasons. Baseline demographics of the finalized cohort (N 5 88) showed a median age of 66 years (32-95), primarily with stage I-III disease (92%) and high-grade (86%) lesions. Somatic mutations were identified in 31 cases (35%)(Total mutations 5 36: solitary mutation(n 5 27); two mutations( 5n 5 3); three mutations(n 5 1)). The most commonly identified mutations were in TP53 (n 5 24), ATM (n 5 3) and PIK3CA (n 5 2). Three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations, mainly related to biomarkers of prediction of response; however few had targetable driver mutations. Somatic mutation status did not influence disease free or overall survival. Based on the small number of clinically relevant mutations, these data do not support the routine use of targeted NGS panels outside of research protocols in UPS.Soft tissue sarcomas (STS) are a heterogeneous group of tumors of mesenchymal origin and represent approximately 1% of adult cancers. 1 Advances in molecular testing have provided significant insights into the biological drivers of these rare cancers which has prompted the incorporation of molecular data into the current classification of these tumors. 2,3 One of the most common subtypes of STS is undifferentiated pleomorphic sarcoma (UPS), previously known as malignant fibrous histiocytoma (MFH). 4 These tumors are characterized by a lack of an overt line of differentiation and classically represent a diagnosis of exclusion once potential histologic mimics have been excluded (e.g.

Immune checkpoint proteins, such as PD-L1 and PD-1, are important in several cancers; however, their role in osteosarcoma (OSA) and soft tissue sarcoma (STS) remains unclear. Our aims were to determine whether subsets of OSA/STS harbor tumor-infiltrating lymphocytes (TILs) and express PD-L1, and how PD-L1 expression is related to clinical outcome. Tissue sections of 25 cases each of untreated undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), liposarcoma (LPS) and 24 of leiomyosarcoma (LMS) were subjected to immunohistochemistry (IHC) for immune cells, PD-L1 and PD-1. RT-qPCR was utilized to quantify levels of PD-L1 mRNA from 33 UPS, 57 MFS and 79 OSA primary-untreated specimens. PD-L1 mRNA levels were tested for their correlation with overall survival in patients presenting without metastases. Transcriptome analysis evaluated biological pathway differences between high and low PD-L1 expressers. A subset of UPS and MFS contained TILs and expressed PD-L1 and PD-1; LMS and LPS did not. PD-L1 levels by IHC and RT-qPCR were positively correlated. PD-L1 over-expression was associated with better survival for UPS and OSA, but not MFS. The Th1 pathway was significantly activated in UPS with high levels of PD-L1 and improved survival. Some sarcoma subtypes harbor TILs and express PD-L1. Patients with UPS and OSA with high levels of PD-L1 had better overall survival than those with low expression levels. Important biological pathways distinguish PD-L1 high and low groups. The stratification of patients with OSA/STS with respect to potential immune therapies may be improved through investigation of the expression of immune cells and checkpoint proteins.

Methods to optimize healing through dietary strategies present an attractive option for patients, such that healing from delicate oral surgeries occurs as optimally as possible with minimal patient-meditated complications through improper food choices. This review discusses findings from studies that have investigated the role of diet, either whole foods or individual dietary components, on periodontal health and their potential role in wound healing after periodontal surgery. To date, research in this area has largely focused on foods or individual dietary components that may attenuate inflammation or oxidant stress, or foster de novo bone formation. These studies suggest that a wide variety of dietary components, including macronutrients and micronutrients, are integral for optimal periodontal health and have the potential to accelerate oral wound healing after periodontal procedures. Moreover, this review provides guidance regarding dietary considerations that may help a patient achieve the best possible outcome after a periodontal procedure.

11059 Background: Alveolar Soft Part Sarcoma (ASPS) is a distinctive tumor characterized by a canonical ASPL-TFE3 fusion. Treatment options are limited. We assessed tumor immune cell infiltrates, and correlated this with patients receiving PD-1 blockade. Methods: A retrospective institutional review was performed for 18 cases of ASPS. Immunohistochemistry was performed on paraffin-embedded tissue (PET) for T-lymphocyte markers (CD3/CD4/CD8), and PD-1/PD-L1 (Ventana). Expression was quantified by standard methods: (total cells per high power field: score; 0:0; 1-10:1; 11-50:2; 50-99:3; 100:4). Select cases underwent DNA sequencing analysis using whole exome (WES, > 80X, n = 4) and genome (WGS, > 30X, n = 1) sequencing. Indel analysis was conducted via mutect2 ( > 5% variant allele frequency) and mutational signature was performed using deconstructSigs. Results: The median age was 27 (15-54). Disease status at diagnosis was: 44% localized; 56% metastatic. The median overall survival was 17 yrs (2.9-31). Four patients (pts) received immunotherapy with PD-1 blockade with 1 complete response (CR), 2 durable partial responses (PR) and 1 stable disease (SD). PET was available in 12 cases. PD-1/PD-L1 expression (≥1) was seen in 50% and 17%, respectively. Composite CD3, CD4 and CD8 infiltration were 2, 1, and 1, respectively. Patients with CR/PR to PD-1 blockade (n = 3) had no clear correlation with PD-1, PD-L1 or lymphocyte markers. Exomic characterization (n = 4) demonstrated no clear excess mutation burden compared to Ewing sarcoma (5.7 vs 6.4 mut/MB). Mutational signatures via COSMIC were identified in the mismatch repair (MMR) pathway in 2 of 4 cases (Pt A: Signature (S) 26; pt B: S6 and S15). Pt B also underwent WGS which confirmed a COSMIC signature in the MMR pathway. Indel analysis did not confirm aberrations in standard MMR or polymerase genes. Conclusions: Preliminary findings suggest activity with PD-1 blockade in ASPS; however, this does not appear to correlate with tumour-infiltrating T lymphocytes. Genomic analysis suggests an MMR signature may account for these responses, but standard MMR aberrations were not identified. Further validation is underway.