58 LEARNING CURVE / Cancer Treatment
The common primary sites for hemangiosarcoma are the spleen, the right atrium of the heart, the liver and the subcutis.
metastasis almost certainly is present in most dogs at the time of diagnosis, and the eventual outcome for dogs with this disease often follows the rupture of a large or rapidly growing tumor, which results in acute, severe hemorrhage, col- lapse, shock and death. The response to treatment is unre-
warding. Commonly cited median sur- vival for dogs with splenic hemangiosar- coma (the most common form) treated with the standard of care ranges from 3 to 5 months (Clifford et al. 2000), with slightly better survival in dogs that had no gross metastasis at diagnosis, and up to approximately 15% to 20% surviving more than 12 months. This is consistent with data from 112 cases seen at our hospital over approximately a 30-month period between 2009 and 2011. Few sar- comas show the metastatic potential seen in hemangiosarcoma. It also is not rare for sarcomas to be
chemoresistant. Combined, the high rate of metastasis and chemoresistance places hemangiosarcoma alongside osteosar- coma as two prototypical canine sarco- mas that are essentially incurable using conventional therapies. This has led to numerous controlled studies and anec- dotal instances of experimental therapy for this disease. Most studies using combinations of cytotoxic drugs, metronomic dose
Trends magazine, April 2013
schedules, autologous vaccines, and sun- dry immune-based and antiangiogenic therapies have not shown consistent improvement over the accepted standard of care. Perhaps the resistance is due to the
peculiar origin and the insidious natural history of this tumor. Hemangiosarcoma can occur in virtually any organ, albeit it tends to be associated with organs or regions that have complex vascular net- works (spleen, heart, liver, lungs, brain, kidney, muscle, bone marrow and skin). Visceral tumors show similar biological behavior, while cutaneous tumors are relatively indolent and can be curable. Unfortunately, these clinicopatho-
logical observations provide no answers to our questions as to whether the tumors show site or substrate specific- ity and whether they originate from a single cell type. An apparent breed-spe- cific predilection for different topologi- cal forms of the disease also has been noted (Anderson et al. 2011), suggest- ing that tumors at different sites could have different etiologies. On the other hand, these differences
may be driven by other microenviron- mental factors that are independent of the cell of origin. Over the past decade, we have developed a resource of hemangio- sarcoma-derived cell lines with represen- tation of anatomical and breed diversity,
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68