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Volitionrx — Volition — ACVIM Forum 2022
25 slides from Volitionrx's conference presentation, Jun 24, 2022
Slide 1: Evaluation of Plasma Nucleosome Concentrations in Healthy Dogs and Dogs with Various Common Cancers
Evaluation of Plasma Nucleosome Concentrations in Healthy Dogs and Dogs with Various Common Cancers. Heather Wilson-Robles, DVM, DACVIM (Oncology) Friday, June 24, 2022 | 9:45-10:15 AM
Slide 2: Speaker Disclosure
Speaker Disclosure Evaluation of Plasma Nucleosome Concentrations in Healthy Dogs and Dogs with Various Common Cancers Heather Wilson-Robles, DVM, DACVIM (Oncology) FINAL DISCLOSURE: Grant/Research Support- Volition Veterinary Diagnostic Development Grant/Research Support- Fred and Vola Palmer Chair
Slide 3: The Basic Concept
The Basic Concept • Cancer & cell death results in chromatin fragmentation and release of nucleosomes into the blood. • Nucleosomes contain >200 possible modifications that regulate every fundamental cellular process. • Measuring nucleosome levels and modifications in circulation have the potential
Slide 4: Circulating Nucleosomes in Cancer
Circulating Nucleosomes in Cancer
Slide 5: H3.1 ELISA Assay
H3.1 ELISA Assay HRP Reporter Detection Antibody Nucleosome Capture Antibody
Slide 6: Materials and Methods
Materials and Methods . -~-_“— Pas
Slide 7: Sample Collection and Case Recruitment
Sample Collection and Case Recruitment • Samples were either collected at the Texas A&M Small Animal Teaching Hospital (AUPs CA 2019-0211 and 2017-0350) or from the NCI Division of Cancer Treatment and Diagnosis Biorepository. • A total of 134 healthy animals were recruited for this study. • A total
Slide 8: Results
ng/mL — 2022 ACVIMexazEy Results a H3.1 Nucleosome Levels Across Multiple Cancer Types 4a aa 4, ak a4 ’ a a 4 aft 4 a a a Diagnosis * Healthy 4 Cancer
Slide 9: AUC 68.74%
80% - > 60% - = <7) Cc oO QD 40%- 20% - AUC 68.74%
Slide 10: Additional Cases
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Slide 11: Circulating Nucleosomes in Dogs with Lymphoma
Circulating Nucleosomes in Dogs with Lymphoma Dolan, C, Wilson-Robles, H et al. Characterizing Circulating Nucleosomes in the plasma of dogs with lymphoma BMC Vet Res 17, 276 (2021)
Slide 12: Lymphoma
Lymphoma Dolan, C, Wilson-Robles, H et al. Characterizing Circulating Nucleosomes in the plasma of dogs with lymphoma BMC Vet Res 17, 276 (2021)
Slide 13: Diagnosis by Lymphoma Stage
Diagnosis by Lymphoma Stage Stage I: Stage II: Stage III: Stage IV: Stage V: 7 of 11 cases detected 1 of 7 cases detected 28 of 37 cases detected 31 of 39 cases 27of 33 cases detected detected 63.6% 14.3% 75.7% 81.6% 81.8% B cell lymphoma: T cell lymphoma: 10/18 cases detected 41/43 cases detected 9
Slide 14: Circulating Nucleosomes in Dogs with Hemangiosarcoma
Circulating Nucleosomes in Dogs with Hemangiosarcoma Hemangiosarcoma vs Healthy AUC 92.9% Wilson-Robles, H., Miller, T., Jarvis, J. et al. Characterizing circulating nucleosomes in the plasma of dogs with hemangiosarcoma. BMC Vet Res 17, 231 (2021)
Slide 15: Diagnosis by Stage in HSA
Diagnosis by Stage in HSA Stage I: Stage II: Stage III: 6 of 9 cases detected 19 of 25 cases detected 27 of 30 cases detected 66.7% 76% 90% Wilson-Robles, H., Miller, T., Jarvis, J. et al. Characterizing circulating nucleosomes in the plasma of dogs with hemangiosarcoma. BMC Vet Res 17, 231 (2021)
Slide 16: Histiocytic Sarcoma
Histiocytic Sarcoma • 26 cases total • H3.1 Concentration • Median 69.6 ng/mL • Mean 261.22 ng/mL • Range 21.8-1800 • Location • Visceral (n=21) • Bone (n=5) • Versus healthy • p< 0.0001
Slide 17: Oral Melanoma
Oral Melanoma • 49 cases in total • 7 haired skin • 42 oral tumors • H3.1 Concentration • Median for cutaneous tumors – 24.8 ng/mL • Median for oral tumors – 60.0 ng/mL • Tumor Size • Median for cutaneous tumors- 3 cm • Median for oral tumors- 4 cm • Versus Healthy • p= 0.000025
Slide 18: Mast Cell Tumors
Mast Cell Tumors • 126 cases in total • Tumor grade • 9 grade 1 • 87 grade 2 • 26 grade 3 • H3.1 concentrations • Low grade median 21.68 ng/mL; mean 41.9 ng/mL • High grade median 38.2 ng/mL; mean 149.7 ng/mL • p= 0.005 • When compared to healthy dogs • p >0.99 (low grade) • p= 0.005 (high grade)
Slide 19: Osteosarcoma
Osteosarcoma • 49 total cases • 17 elevated • Sensitivity 60.7% at 97% specificity • H3.1 Concentration • Median 43.2 ng/mL; mean 72.7 ng/mL • Range 0.1-446 ng/mL • Versus healthy • p= 0.035
Slide 20: Soft Tissue Sarcoma
Soft Tissue Sarcoma • 51 total cases • 15 elevated • Sensitivity 48.19% with a specificity of 97% • H3.1 Concentration • Median 25.09 ng/mL; mean 200.07 ng/mL • Range 0.1-2500 ng/mL • Versus Healthy • p = 0.704
Slide 21: Discussion
Discussion In this case series, plasma nucleosome concentrations were able to identify 174 of 229 (76%) systemic cancers (lymphoma, hemangiosarcoma and Histiocytic sarcoma). Overall, in 7 of the most common cancers, plasma nucleosome concentrations were able to identify 49.8% of all cancers tested.
Slide 22: Discussion
• Similar findings to the PATHFINDER study (Galleri test by GRAIL) Discussion • Positive Predictive Value 49% in their study of over 50 different cancers in humans.
Slide 23: Discussion
Discussion • Also similar to the OncoK9 test • Able to identify 54.7% of cancers they tested. • 85.4% of lymphoma, hemangiosarcoma and osteosarcoma cases.
Slide 24: Summary
Summary Elevated plasma nucleosome concentrations may be a useful tool for the early detection of cancer in geriatric pet dogs. This test should not be used in lieu of traditional diagnostics but as a companion test. The ELISA platform lends itself to being a low-cost test that requires a small samp
Slide 25: Questions?
Questions? Heather Wilson-Robles, DVM DACVIM (Oncology) hwilson@cvm.tamu.edu