Soft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50–50.4 Gy in 25–28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio – 0.16, 95% confidence interval: 0.034–0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.
Background
Differentiating large lipomas from atypical lipomatous tumors (ALT) is challenging and preoperative management guidelines are not well-defined. The diagnostic ambiguity leads many surgeons to refer all patients with large lipomatous masses to an oncologic specialist, perhaps unneccessarily.
Study Design
In this retrospective cohort study of patients with nonretroperitoneal lipomatous tumors, preoperative characteristics discernible without invasive diagnostic procedures were evaluated for diagnostic predictive value.
Results
319 patients (256 with lipomas, 63 with ALTs) treated between 1994 and 2012 were identified. Patients with ALTs were older (60.5 vs. 53.5 years, p<0.0001), had larger tumors (16.0 vs 8.3 cm, p<0.0001), had tumors more often located on an extremity (88.9% vs. 60.5% torso, p<0.0001), and more frequently had a history of prior operations at the same site, exclusive of excision leading to diagnosis and referral (20.6% vs. 5.9%, p=0.001). Local recurrence was observed in 2 patients with lipomas (0.8%) vs. 14 with ALTs (22.6%, p<0.0001). No patients with ALTs developed distant metastases or disease-specific mortality with a median follow-up of 27.4 months (range 0–164.6 months). On multivariate analysis age ≥55 years, tumor size ≥10 cm, extremity location, and history of prior operations were predictors for diagnosis of ALT (p<0.05).
Conclusions
Characteristics of lipomatous masses that are associated with a diagnosis of ALT include patient age ≥55 years, tumor size ≥10 cm, previous resection, and extremity location (vs torso). These easily identifiable traits may guide surgical management or referral to a specialist.
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