(P 328) DETERMINING BIOMARKERS FOR GEMCITABINE RESPONSE IN SOFT TISSUE SARCOMAS: LESSONS LEARNED FROM PANCREATIC CANCER

Objective: Despite multiple new anticancer therapeutics, long-term survival of patients with Soft Tissue Sarcomas (STS) remains poor due to rapid disease progression. STS can become resistant to systemic therapy resulting in short periods of disease control. Gemcitabine is one systemic therapy that is commonly used as therapy for STS. Studies have identified Deoxycitidine Kinase (DCK) and Solute Carrier Family 28 Member 3 (HCNT3) as genes that regulate gemcitabine metabolism in Pancreatic Ductal Adenocarcinomas (PDAC). Here we investigate whether DCK and HCNT3 expression can serve as genetic biomarkers and predict response to Gemcitabine therapy in STS.

Methods: Participants enrolled in the prospective Electronic Health Record (EHR)-Based Comprehensive Bone and Soft Tumor Registry (NCT02677961) at The Ohio State James Cancer Center who had received gemcitabine-based chemotherapy for the treatment of bone and soft tissue sarcoma were eligible for this study. A total of 179 patients were identified who had received at least one cycle of gemcitabine-based chemotherapy, between January 1st, 2014, to December 31st, 2022. Whole exome RNASeq expression data was available for 36 of these patients who had received gemcitabine-based chemotherapy in the setting of active disease

Results: Of the 36 patients included in this study, 22 were female and 14 were male. Nine different main disease types were identified in the patient subset. These include angiosarcoma (8), chondrosarcoma (1), leiomyosarcoma (16), liposarcoma (3), malignant peripheral nerve sheath tumor (1), myxofibrosarcoma (2), osteosarcoma (2), undifferentiated pleomorphic sarcoma (3), and undifferentiated spindle cell sarcoma (1). The mean time to treatment discontinuation (TTD) among all patients was 178 days. Among DCK low-expressors (n = 16), the median TTD was 86 days; among high-expressors (n = 16), the median TTD was 147 days. Differences between groups did not reach statistical significance (HR = 3.63, p = 0.132).
Among HCNT3 low-expressors (n = 16), the median TTD was 83 days; among high expressors (n = 16), the median TTD was 98 days. Differences between groups did not reach statistical significance (HR = 1.29, p = 0.5105). Among combination of HCNT3-low and DCK-low expression (n = 10), the median TTD was 87 days; among HCNT3-high and DCK-high expression (n = 10), the median TTD was 147 days. Differences between the groups reached statistical significance (HR = 2.55, p = 0.0459)

Conclusion: The combination of DCK and HCNT3 expression by clinical RNASeq is a potential biomarker of gemcitabine-response in sarcoma, but larger studies are necessary to evaluate the potential clinical significance and possible role of DCK and HCNT3 expression in identifying patients most likely to benefit from gemcitabine-based chemotherapy.