1. Intralesional liquid brachytherapy in dogs with appendicular osteosarcoma Henry CJ 1, 2, Lattimer JC 1, Selting KA 1, Loy M 3, Ketring A 4, Axiak S 1, Souza CHM 1, Tate D 1, Frank RK 5, Simon J 5, Dodson S 6, Stearns S 3 1 Department of Veterinary Medicine and Surgery, and 2 Department of Internal Medicine, Hematology/Oncology Division, School of Medicine, University of Missouri, Columbia, MO; 3 Valco Instruments Company, Inc., Houston, TX; 4 University of Missouri Reseach Reactor Center, University of Missouri, Columbia, MO; 5 IsoTherapeutics Group, LLC, Angleton, TX; 6 Angleton Veterinary Clinic, Angleton, TX

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

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

4. Background Holmium ( 166 Ho) / Samarium ( 153 Sm) –1.8 MeV beta/0.7 MeV beta and 103 keV gamma –t ½= 26.8 h (Ho) and 46.3 h (Sm) –$$$$$$$$ Yttrium ( 90 Y) –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/m 2 Day 0: Radioisotope in a colloid-like suspension- Target 50 Gy –improved dosimetry –decrease systemic myelosuppression 4 cycles of chemotherapy –Combination doxorubicin 20 mg/m 2 followed 3 hours later by carboplatin 200 mg/m 2 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. Acknowledgements 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

23. Questions?