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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
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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,

Mar 31, 2015

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Page 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,

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

Page 2: 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,

Background

• Canine osteosarcoma• Local disease

– Limits quality and quantity of life– Some not amenable to amputation

Page 3: 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,

Background

• Local therapies– Surgical limb salvage– Palliative care (pain management ±

chemo)– Radiation therapy

• Palliative vs. definitive

– Radioisotope: 153Sm-EDTMP– Local (intraarterial) vs. systemic therapy

Page 4: 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,

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– $

Page 5: 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,

Hypothesis

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

Page 6: 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,

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

Page 7: 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,
Page 8: 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,

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

Page 9: 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,
Page 10: 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,
Page 11: 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,

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

Page 12: 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,
Page 13: 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,
Page 14: 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,
Page 15: 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,

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)

Page 16: 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,

2 month

interval

Page 17: 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,

4 month

interval

Page 18: 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,

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

Page 19: 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,

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

Page 20: 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,

Conclusions

• Treatments were well tolerated– Minimal pain– Normal healing– Palliation of pain (subjective)

Page 21: 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,

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

Page 22: 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,

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

Page 23: 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,

Questions?