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Hemangiosarcoma in a Dog

Ruthanne Chun, DVM, DACVIM (Oncology), University of Wisconsin–Madison

Oncology

|
October 2013
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Peer Reviewed

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A 10-year-old, spayed Labrador retriever crossbreed with acute-onset weakness and lethargy was presented on emergency to a referral institution.

History
The dog had no history of travel or trauma and was current on vaccinations and appropriate parasite control. At presentation, it was recumbent but conscious and responsive.

Related Article: What Type of Anemia?

Physical Examination
Examination findings included muffled heart sounds, poor peripheral pulses, pale mucous membranes with a CRT of 2 seconds, rectal temperature of 98.7°F, and distal extremities cool to the touch. ECG suggested ventricular premature contractions. Echocardiography revealed pericardial effusion and a right atrial mass (Figure 1).

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Figure 1. Echocardiography revealed pericardial effusion (asterisk) and a right atrial (RA) mass (arrow). (LA = left atrium, LV = left ventricle, RV = right ventricle)

Imaging & Laboratory Results
A peripheral catheter was placed and shock fluid therapy initiated, followed by ultrasound-guided pericardiocentesis; this resulted in immediate clinical improvement. Following stabilization, staging tests for suspected hemangiosarcoma were performed. No visible metastatic disease was identified on thoracic radiographs and abdominal ultrasound (Figure 2).

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CBC results were suggestive of anemia (hematocrit 35%; range, 39%–57%) and RBC morphology changes (2+

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poikilocytes and acanthocytes per HPF, 1+ crenation RBCs per HPF) but no other abnormalities. Significant abnormalities on serum biochemistry profile included elevated alanine aminotransferase levels (117 U/L; range, 3–69 U/L) and aspartate aminotransferase (95 U/L; range, 21–53 U/L). Pericardial fluid analysis showed hemorrhagic effusion with no evidence of neoplasia. 


Figures 2A, 2B & 2C. Thoracic radiographs (A, B) and abdominal ultrasound (C) failed to identify any visible metastatic disease.

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Initial Treatment
The clients opted to have the dog undergo pericardiectomy to prevent further episodes of tamponade and, if possible, resect the tumor. Before surgery, crossmatch was performed and prothrombin time (8.8 sec; control, 8.6 sec) and partial thromboplastin time (17 sec; control, 14.5 sec) were noted. The right atrial mass was surgically removed. Histopathology confirmed hemangiosarcoma.

The patient was released the day after surgery and had a seemingly uncomplicated recovery; however, 7 days later, the patient was again presented with acute-onset weakness and lethargy. Physical examination revealed a palpable fluid wave consistent with abdominal effusion, and ultrasonography suggested a large cavitary splenic mass and peritoneal effusion.

Abdominocentesis and centrifugation of the fluid sample were compatible with hemorrhage based on comparison of PCV/TS of the abdominal fluid with that of peripheral blood. Shock therapy with isotonic crystalloids was initiated, and hematology results were compatible with anemia (hematocrit 24%), thrombocytopenia (90,000/µL; range, 175,000–500,000), and leukocytosis characterized by mature neutrophilia (18,000/µL; range, 2,600–10,000). RBC morphology changes continued (2+ anisocytes and polychromasia per HPF, 1+ schistocytes and target/leptocytes per HPF).

The dog’s clinical condition continued to deteriorate despite resuscitative efforts, and the client elected emergency splenectomy. A packed RBC transfusion was initiated preoperatively, and the dog received a second unit of RBCs during surgery. Surgery and anesthesia proceeded without complication; the dog recovered well and was released 2 days after surgery.

Related Article: Commonly Used Chemotherapy Drugs: Part 1

Ask Yourself: Which is the best recommendation for ongoing management of this patient?

A. Tyrosine kinase inhibitor monotherapy

B. Piroxicam therapy

C. Doxorubicin chemotherapy

D. CHOP chemotherapy

E. Metronomic chemotherapy

Correct Answer
C. Doxorubicin chemotherapy

Doxorubicin chemotherapy remains the standard of care for dogs with hemangiosarcoma. Dogs with minimal residual disease postoperatively have a better prognosis than dogs with measurable disease. Veterinary oncologists continue to investigate therapies to better control this common, biologically aggressive disease.

Related Article: Cytotoxic Chemo­therapeutic Agents

Postsurgical Treatment
About 2 weeks after surgery, doxorubicin chemotherapy was initiated at 30 mg/m2 IV q3wk for 5 doses1,2 (see Treatment at a Glance). This therapy was well tolerated and followed by treatment with toceranib (2.75 mg/kg PO q2d), which has potential antiangiogenic activity through both antivascular endothelial growth factor and anti–platelet-derived growth factor activity.3,4

As part of the minimum database before toceranib is started, a CBC, serum biochemistry profile, urinalysis, urine protein: creatinine ratio, and blood pressure measurements were conducted, with no significant findings.3 Weekly CBC tests after starting toceranib were normal, but a serum biochemistry profile at week 4 showed elevated BUN (48 mg/dL; range, 7–32 mg/dL) and creatinine (1.9 mg/dL; range, 0.5–1.5 mg/dL) levels. Urine-specific gravity was 1.023 with rare, finely granular casts identified on sediment analysis. Blood pressure was normal. The toceranib was discontinued, and follow-up renal profile 2 weeks later showed mildly progressive azotemia (BUN, 57 mg/dL; creatinine, 2.4 mg/dL); however, the urine protein:creatinine ratio was normal at 0.10.

At diagnosis of renal failure, the dog was 5 months post-hemangio-sarcoma–diagnosis and clinically normal. The client requested other treatment options for hemangiosarcoma; metronomic chemotherapy with cyclophosphamide and piroxicam or with single-agent chlorambucil was offered.2,5,6 Because of client concern about hemorrhagic cystitis with cyclophosphamide, metronomic chlorambucil was initiated at 4 mg/m2/day PO. Aside from a Veterinary Cooperative Oncology Group (VCOG) score of grade 1 diarrhea, the drug was well tolerated.7

Treatment at a Glance

  • Surgery to eliminate gross disease and bring the patient to a microscopic disease setting and delay further hemorrhage
  • Doxorubicin chemotherapy (30 mg/m2 IV q3wk for 5 doses)1,2
  • Metronomic options to consider following chemotherapy:
    • Cyclophosphamide (15 mg/m2/day PO) and piroxicam (0.3 mg/kg/day PO)
    • Chlorambucil (4 mg/m2/day PO)
  • Potentially more direct antiangiogenic options to consider following chemotherapy:
    • Toceranib (2.75 mg/kg PO q2day)3,4
    • Masitinib (12.5 mg/kg/day PO)

Outcome
Approximately 10 months after the initial diagnosis, the dog was euthanized because of signs compatible with intracavitary hemorrhage. Necropsy was not performed.

The Take-Home

  • Right atrial hemangiosarcoma may be associated with splenic disease or disease at other distant sites.
  • No studies correlate echocardiographic appearance with tumor amenability to resection.
  • Ultrasonography may miss small metastatic lesions.
  • Surgery and chemotherapy remain the standard of care for hemangiosarcoma.
  • New therapeutic options for this disease are continually being evaluated.

RUTHANNE CHUN, DVM, DACVIM (Oncology), is past president of the Veterinary Cancer Society and associate dean of clinical affairs at her alma mater, University of Wisconsin–Madison. Her clinical research interests include hemangiosarcoma, osteosarcoma, lymphoma, and bladder cancer. Dr. Chun lectures nationally and internationally on communication skills and oncology. She completed her comparative oncology residency at Purdue University.


HEMANGIOSARCOMA IN A DOG • Ruthanne Chun

References

1. A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxo-rubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma. Teske E, Rutteman GR, Kirpenstein J, Hirschberger J. Vet Comp Oncol 9:283-289, 2011.
2. Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs. Lana S, U’ren L, Plaza S, et al. JVIM 21:764-769, 2007.
3. Receptor tyrosine kinase inhibitors: Molecularly targeted drugs for veterinary cancer therapy. Bavcar S, Argyle DJ. Vet Comp Oncol 10:163-173, 2012.
4. In vitro effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell lines. Lyles SE, Milner RJ, Kow K, Salute ME. Vet Comp Oncol 10:223-235, 2012.
5. Metronomic therapy with cyclophosphamide and piroxicam effectively delays tumor recurrence in dogs with incompletely resected soft tissue sarcomas. Elmslie RE, Glawe P, Dow SW. JVIM 22:1373-1379, 2008.
6. Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer. Leach TN, Childress MO, Greene SN, et al. Vet Comp Oncol 10:102-112, 2012.
7. Veterinary cooperative oncology group––Common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.1. Vet Comp Oncol 2:1-30, 2011.

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