(P 539) SARCOMA STEREOTACTIC BODY RADIOTHERAPY AND IMMUNE SYSTEM TRIAL

Objective: The role of radiotherapy has been limited for patients with sarcoma; however, patients with limited metastases may be curable with aggressive local treatment. Stereotactic body radiotherapy (SBRT) delivers focused high dose radiotherapy in a few treatments, creating a non-invasive locally ablative tool. Early data demonstrate a potential role for SBRT for metastatic sarcoma, but the optimal dose and strategy to incorporate with systemic/immunotherapy is not yet known. Our preliminary studies show that local control is significantly improved when a biologic effective dose (BED) of ≥ 95 Gy SBRT is used for patients with radiosensitive sarcoma and ≥ 120 Gy for radioresistant sarcoma. We also found that baseline neutrophil to lymphocyte ratio (NTLR) prior to SBRT predicted for overall survival and that change over time correlated with local failure. We hypothesize that utilizing optimal BED of SBRT will result in durable 1-year local control and that NTLR and immune and inflammatory markers over time will predict for local control and survival.
Primary

Objective: To evaluate the impact of SBRT on the immune system by measuring the neutrophil to lymphocyte ratio for patients with metastatic or unresectable sarcoma.

Secondary Objectives
To evaluate local control with SBRT for metastatic or unresectable sarcoma using the biologically effective dose (BED) of > 95 Gy of SBRT identified from our previously treated patient population.
To estimate rates of acute ≥ grade 3 CTCAE, v. 5.0 adverse events related to SBRT using the biologically effective dose (BED) of > 95 Gy of SBRT.
To evaluate the impact of SBRT on the immune system by collecting laboratory data for patients with metastatic or unresectable sarcoma including Immune and inflammatory markers via Olink, Myeloid-derived suppressor cells (MDSC), complete blood count (CBC) with differential, Albumin, Lactate Dehydrogenase (LDH), and C-reactive protein (CRP)

Methods: Patients will receive SBRT to one or more sites using an optimal BED regimen. Systemic therapy will be held for the week of SBRT and the type (more or less lymphocytic) will be documented. Patients will be followed clinically for symptom improvement, control, toxicity, impact on quality of life (via Peds QOL instruments), and survival.

Progression will be determined by follow up imaging and/or tumor board consensus. Both local and distant progression will be documented. Local failure will designate as in-field or marginal. In-field recurrences are defined as >80% of the volume of the recurrent lesion was within the 95% isodose line, whereas marginal recurrences are defined as 20% to 80% of the volume of the recurrent lesion within the 95% isodose line. Out of field recurrences are defined as < 20% of the volume of the recurrent lesion within the 95% isodose line.

Blood samples will be collected pre- and post-SBRT (within 2 weeks), at follow-up (3 to 6 months), and at 1 year from SBRT. Blood samples include: Immune and inflammatory markers via Olink Panel, Myeloid-derived suppressor cells (MDSC), Complete blood count (CBC) with differential, Albumin, Lactate Dehydrogenase (LDH), and C-reactive protein (CRP). Analytical Methods include
phenotypic and functional characterization of immune and non-immune components will involve but not be limited to analysis including flow cytometry, genomics, transcriptomics, metabolomics, spatial phenoptics, and/or assay and/or quantification of soluble components.

Results: NA. Trials in progress submission

Conclusion: NA Trials in progress submission