Intralesional liquid brachytherapy in dogs with appendicular osteosarcoma

1. Intralesional liquid brachytherapy in dogs with appendicular osteosarcoma Henry CJ1, 2, Lattimer JC1, Selting KA1, Loy M3, Ketring A4, Axiak S1, Souza CHM1, Tate D1, Frank RK5, Simon J5, Dodson S6, Stearns S3 1Department of Veterinary Medicine and Surgery, and 2Department of Internal Medicine, Hematology/Oncology Division, School of Medicine, University of Missouri, Columbia, MO; 3Valco Instruments Company, Inc., Houston, TX; 4University of Missouri Reseach Reactor Center, University of Missouri, Columbia, MO; 5IsoTherapeutics Group, LLC, Angleton, TX; 6Angleton Veterinary Clinic, Angleton, TX

2. Canine osteosarcoma Local disease Limits quality and quantity of life Some not amenable to amputation Background

3. Background • Local therapies • Surgical limb salvage • Palliative care (pain management ± chemo) • Radiation therapy • Palliative vs. definitive • Radioisotope: 153Sm-EDTMP • Local (intraarterial) vs. systemic therapy

4. Background • Holmium (166Ho) / Samarium (153Sm) • 1.8 MeV beta/0.7 MeV beta and 103 keV gamma • t ½= 26.8 h (Ho) and 46.3 h (Sm) • $$$$$$$$ • Yttrium (90Y) • 2.2 MeV beta • t ½= 64 h • $

5. Hypothesis • Intralesional liquid brachytherapy will effectively palliate bone pain associated with osteosarcoma, allowing dogs to retain their affected limbs longer.

6. Materials and methods • Dogs • Appendicular OSA limited to one site • Evaluation: • Bloodwork • nuclear scintigraphy • thoracic and affected limb radiography • CT or PET/CT imaging of the tumor

8. Materials and methods • Day -14: Doxorubicin 30 mg/m2 • Day 0: Radioisotope in a colloid-like suspension- Target 50 Gy • improved dosimetry • decrease systemic myelosuppression • 4 cycles of chemotherapy • Combination doxorubicin 20 mg/m2 followed 3 hours later by carboplatin 200 mg/m2 q 3 weeks • Beginning 2 weeks after the intralesional therapy

11. Materials and methods • Hand held, battery operated drill unit • Cutting tip formed on the end of a wire • 21 gauge guide needle • .017 diameter hole through cortical bone • Adapters facilitate multiple injection sites • Injection of radioisotope using a precision, glass HPLC syringe encapsulated within a shield

15. Results • 14 dogs treated • MU (n=10) and Angleton (n=4) • 2 dogs (1/site) had multiple bone lesions at presentation • Holmium/samarium (n=3) • Yttrium (n=11)

16. 2 month interval

17. 4 month interval

18. Results • Response • CR (n=1) negative PET scan • Difficult to evaluate with standard criteria due to bony remodeling • PET scans may further define remission • No pathologic fractures post procedure

19. Results • Amputation in 5 dogs • Time to amputation= 52 days (17-87 days) • 4 dogs still “leg-on” and still on study • Follow up time= 6 mo, 4 mo, 4 mo, 1.5 mo • 7 dogs still alive • 4 dogs dead due to disease • One dog died of DCM

20. Conclusions • Treatments were well tolerated • Minimal pain • Normal healing • Palliation of pain (subjective)

21. Future directions • Other tumor applications of liquid brachytherapy • Combining radiation modalities such as brachytherapy and external beam • Assessment of response by PET scan • Dose escalation

22. University of Missouri Jimmy Lattimer Carolyn Henry Alan Ketring Carlos Souza Angleton Veterinary Clinic Funding The Gabriel Foundation Isotherapeutics Valco Instruments Co., Inc. Max Loy Stan Stearns Acknowledgements

23. Questions?