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Use of an Artificial Lymphatic System During Carboplatin Infusion to Improve Canine Osteosarcoma Blood Flow and Clinical Response

¹ Orthopaedic Surgical Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021-6007
² The Animal Medical Center, 510 E 62nd Street, New York, New York 10021
³ College of Veterinary Medicine and Biomedical Science, Colorado State University, Ft. Collins, Colorado 80523

Correspondence: Address correspondence and reprint requests to: Gene R. DiResta, PhD; E-mail: direstag{at}mskcc.org

Background: The artificial lymphatic system (ALS), a mechanical system designed to reduce increased interstitial fluid pressure in solid tumors and enhance the delivery of chemotherapy, was evaluated within a randomized clinical trial treating spontaneously occurring canine appendicular osteosarcoma (OS), a tumor similar to its human OS counterpart.

Methods: An ALS was investigated for its ability to increase OS blood flow and increase uptake of intravenously administered carboplatin.

Results: Blood flow increased by 314% in tumors with active ALS drains versus 126% in control tumors (P < .03). Tumor carboplatin uptake increased by 51% after drain activation (P = .07). Microvascular density (MVD) was measured in tumors after surgical amputation and in corresponding bone regions in a cohort of normal dogs. The OS tumors had equivalent MVD as normal bone, and MVD was higher in the humerus than the femur (P < .03) in both tumor and normal bone. Median survival between the ALS-treated and control cohorts was not different despite increased drug uptake or ALS manipulation. Compared with historic controls, ALS drain insertion into tumors to reduce interstitial fluid pressure did not worsen the prognosis.

Conclusions: The findings in canine spontaneously occurring OS indicate that an ALS may be of value as a chemotherapy adjunct for enhancing the delivery of chemotherapy to tumor interstitium.

Key Words: Osteosarcoma • Carboplatin • Blood flow • Interstitial fluid pressure • Microvessel density • Canine • Artificial lymphatic system