2182 - A Prospective Trial Evaluating the Impact of Sarcoma SBRT on the Patient's Immune System: Baseline Results
Presenter(s)
E. S. Murphy1, C. M. Diaz-Montero2, P. Rayman2, C. A. Reddy1, P. Baucco3, P. Anderson4, M. Trucco5, S. Zahler5, S. Thomas5, D. Shepard4, G. T. Budd4, G. Schwartz4, Z. D. Burke6, L. Nystrom6, N. Mesko6, A. Magnelli1, K. Fritchie7, J. G. Scott8,9, S. Kilpatrick7, B. Rubin7, J. Dermawan7, and S. R. Campbell10; 1Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH, 2Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH, 3Cancer Center Research, Cleveland Clinic, Cleveland, OH, 4Department of Hematology Oncology, Cleveland Clinic, Cleveland, OH, 5Department of Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic, Cleveland, OH, 6Department of Orthopaedic Surgery, Cleveland Clinic, Cleveland, OH, 7Cleveland Clinic, Cleveland, OH, 8Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 9Department of Translational Hematology and Oncology Research, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 10Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH
Purpose/Objective(s): We found that the neutrophil to lymphocyte ratio (NTLR) at the time of stereotactic body radiotherapy (SBRT) was prognostic for survival and that changes over time predicted for local relapse for patients undergoing SBRT for metastatic sarcoma. We sought to prospectively evaluate the baseline immune profile of patients receiving SBRT for metastatic sarcoma and hypothesize that there will be a correlation with survival.
Materials/Methods: Patients receive 5 fraction SBRT with a biologic equivalent dose of =95 Gy for metastatic sarcoma. Labs are collected prior to SBRT, after last fraction of SBRT, at 3 to 6 months, and at 1 year or time of progression. Labs consist of CBC, albumin, LDH, CRP, MDSCs and immune and inflammatory panels. High parameter flow analysis was performed. Data was analyzed using flow cytometry analysis software to visualize clusters of cells at baseline by Uniform Manifold Approximation and Projection (UMAP), FlowSOM, and Marker Enrichment Modeling (MEM). Patients were assessed for SBRT response by RECIST control, and survival.
Results: Nine patients with a median age of 23 enrolled on our IRB approved protocol. Median follow up is 4.8 months. 4 patients have died at a median of 3.25 months post SBRT. Sarcoma diagnoses include Ewing’s (5), osteosarcoma (2), MPNST (1) and pleomorphic liposarcoma (1). Five patients had 1 target treated with SBRT and 4 patients had 2. Targets included lung (6), soft tissue (3), bone (2), and kidney (1). Number of metastases at time of SBRT included 1 (n=2 patients), =5 (4), >5-10 (1), >10 (2). 5 patients received concurrent therapy, 1 of which was considered lymphocytic and 1 patient received steroids at time of SBRT. At time of this analysis, only 1 patient experienced local recurrence, 3 had regional recurrence and 7 had distant failure. Five patients had a complete response to SBRT and 3 had a partial response. Patients that survived <6 months had higher frequencies of monocytic MDSC (CD33+HLADR-CD14+) and large granular lymphocytes (CD56+CD16+) at baseline than those that survived >6 months. Patients that survived >6 months had higher frequencies of memory CD4+ T cells and CD57+ T cells at baseline than those that survived < 6 months. There was no significant difference in baseline NTLR, albumin, CRP, or LDH for these small patient groups.
Conclusion: On this trial, patients with metastatic sarcoma had early good responses to SBRT. Patients receiving SBRT for metastatic sarcoma may have different baseline MDSCs, large granular lymphocytes, and memory T cells that relate to survival post SBRT. We will continue to enroll patients on this trial and additional analyses will be performed to assess impact of SBRT on patients’ immune system, control and survival outcomes.