Palliative limb spare for osteosarcoma

Transtumoral Plating as a Novel Method for Palliative Limb Spare in Canine Patients with Distal Radial Osteosarcoma: a Pilot Study

Primary Investigator: Sarah Boston

Co-investigators: Paul Woods, Tom Gibson, Tony Mutsaers

Introduction

Standard treatment for osteosarcoma involves amputation followed by chemotherapy. There is a population of dogs that will not tolerate amputation due to their size and/or to concurrent orthopedic and neurological problems. For these dogs, a limb spare procedure can be performed. For some owners, this procedure is cost prohibitive. As well, it has a high complication rate.

Surgical stabilization of bone cancer for impending fracture or pathological fracture has now become standard practice in human surgical oncology. These procedures are primarily performed for tumors that have metastasized to bone. A significant reduction in pain and improvement in function have been observed when impending or pathologic fractures are treated in this manner and it is recommended for pathologic fracture treatment in human oncology patients, almost regardless of their anticipated survival time. Current strategies in bone cancer pain management in humans include surgical stabilization of lytic and/or fractured bone, decreasing the tumor-induced bone loss, elimination of tumor proliferation and pain medication.

Pain medications commonly used for the treatment of bone cancer pain include NSAIDs, opioids and gabapentin. NSAIDs are usually the first line of medication used in veterinary and human medicine for bone cancer pain. Opioids are also frequently used in humans. However, the dose required to manage moderate to severe bone cancer pain in people is usually high enough that undesirable side effects that interfere with the patient’s quality of life are also present. In a mouse model of bone tumor pain, gabapentin was shown to attenuate bone cancer pain when used acutely or chronically. Pamidronate has also been shown to attenuate bone cancer pain due to its osteoclast inhibiting effect.

Standard therapy for osteosarcoma includes removal of the primary tumor and treatment of micrometastatic disease. There is some evidence that removal of the primary tumor may allow angiogenesis that induces the progression of pulmonary metastatic disease. The angiogenesis was previously suppressed by substances released by the primary tumor. If the primary tumor can remain in place without causing pain to the patient, it may continue to suppress metastatic spread in certain cases. This may allow for prolonged success of treatment, even with a palliative protocol.

An optimal palliative approach to bone cancer in dogs would treat the bone cancer pain by multiple modalities, while still aiming to suppress metastatic disease. Surgical stabilization of bone tumors is not routinely performed in dogs. Surgical stabilization may reduce pain by preventing forces from going through the weakened bone and prevent pathological fracture. Additional treatment with pamidronate will reduce bone osteolysis to decrease pain. Chemotherapy can also be added to this regimen to treat the primary tumor pain as well as metastases. Ongoing treatment with NSAIDs and gabapentin should help to control ongoing pain associated with bone cancer.

Objective

The objective of this study is to develop a novel surgical method for palliative treatment of canine osteosarcoma of the distal radius. The procedure involves placing a bone plate across the tumor to prevent fracture and decrease pain associated with weight bearing and movement. Other palliative treatments will be used after surgery to improve pain control and, hopefully, survival. If this procedure is successful, it will offer another treatment option for dogs with osteosarcoma that will be accessible to an increased number of patients.

Hypothesis:

The use of palliative limb spare in dogs with an osteosarcoma of the distal radius will provide patients with good to excellent limb use and a good quality of life for a period of time that is comparable to or exceeds that of palliative radiation.

Materials and Methods

This study will involve 6 client dogs with naturally occurring osteosarcoma of the distal radius. Clients will be offered all options for the treatment of distal radial osteosarcoma, including amputation, limb spare, palliative radiation or short-term palliation with analgesics. This novel therapy and study will also be discussed. For inclusion in the study, dogs must have stage IIa osteosarcoma. This will be determined by three-view thoracic radiography and bone scan. If bone scan is not available, long-bone survey radiography will be performed. Dogs will also have a CBC,serum biochemistry and urinalysis prior to anesthesia and surgery.

Surgical Procedure: The limb will be clipped and prepared for surgery. A dorsal midline approach will be made to the entire radius and the metacarpal bones. An 18-22 hole 3.5 DCP plate or 3.5/2.7 DCP limb spare plate will be placed on the dorsal surface of the radius and 3rd or 4th metacarpal bone. The plate will extend from the proximal radius to distal metacarpal bone. The bone plate will be affixed in place in a buttress fashion. The most proximal and distal screws will be placed first and the rest of the screws will be filled in. There will be no screws placed in tumor bone. A bone biopsy will be taken from tumor bone with a Jamshidi needle to confirm the diagnosis of osteosarcoma. Postoperative radiographs will be obtained and a soft-padded bandage will be placed on the limb. Patients will recover in the ICU for a minimum of 24 hours postoperatively for supportive care and analgesia. Patients will be discharged once they are ambulatory and do not require parental pain medication. This will likely be 48 hours postoperatively.

Dogs will be treated with an NSAID (unless contraindicated),tramadol and gabapentin for postoperative pain control. They will be placed on cephalexin for 7 days postoperatively. The owners will have the option to use an NSAID long term or intermittently for their dog, depending on the dog’s need for analgesia. All dogs will be treated with gabapentin long term for pain control. At the time of discharge, dogs will be treated with intravenous pamidronate at a dose of 1mg/kg given as an intravenous infusion in 250cc of saline. Pamidronate will be given monthly for the duration of the study. Dogs will return to OVC 10-14 days postoperatively for a recheck, suture removal and to initiate chemotherapy. The chemotherapy protocol used will be alternating carboplatin/adriamycin at standard doses, given once every 3 weeks for a total of 6 doses of chemotherapy. A pretreatment CBC and serum biochemistry will be performed every visit. Three-view thoracic radiographs will be performed every 6 weeks. Once chemotherapy is finished, dogs will return every 10 weeks for reassessment and thoracic radiographs. Limb-use will be evaluated by one observer (TG) at each visit and graded as excellent, good, fair and poor. Complications or health concerns will be evaluated if and when they occur. Owners will fill out a questionnaire at each visit to evaluate pain control and function at home. If complications arise with the limb, an amputation is the most likely course of action that will be recommended. Dogs will be restaged with three-view thoracic radiographs and a bone scan prior to amputation. If the patient is too painful to withstand bone scan, long-bone survey radiography will be performed instead.

The study will evaluate: patient comfort and limb use, time to metastasis, median survival time and complications associated with this procedure.

Anticipated Results and Significance

Patients are expected to have a significant improvement in comfort and limb-use post operatively. The overall outcome with this procedure as far as length of time for palliation of bone tumor pain, time to metastasis, or survival time is unknown.

This is a novel surgical procedure for distal radial osteosarcoma in dogs. My hope is that this study will provide an alternative to current limb spare procedures that will involve decreased cost, decreased surgery time, decreased complications, increased availability, good quality of life and a survival time that is comparable to or exceeds that of other palliative options. This study will allow us to investigate the concept of concomitant tumor resistance in canine patients. Until now, concomitant resistance has only been evaluated in murine models. If there is proof of concept shown with this study, there may be further applications of this treatment principle in human patients with osteosarcoma.

Thank you for your interest in this study. For more information or to refer a case to OVC for study enrollment, please contact me or our oncology service at 519-823-8830.

Sincerely,

Sarah Boston, DVM, DVSc, Diplomate ACVS
Assistant Professor of Small Animal Surgery
Ontario Veterinary College, University of Guelph