By Beth Overley-Adamson | DVM, DACVIM (Oncology)
Hemangiosarcoma (HSA) is a highly aggressive tumor that arises from the cells that make up the blood vessels. These cells undergo a genomic alteration from normal to malignant that allows them to escape the body’s normal surveillance system and allows them to proliferate and grow. HSA can occur most anywhere in the body, but it most commonly develops in the spleen, liver, heart, and skin.
HSA is highly aggressive and locally invasive. It invades and destroys the organs in which it arises. It also avidly metastasizes or spreads to sites elsewhere in the body. Metastasis is a process in which tumor cells leave the primary tumor site through the blood or lymph systems. These cells then travel to other sites in the body, where the malignant cells can take root and grow into new nodules or masses. HSA most commonly spreads to the liver, mesentery, and lungs.
The causes of canine HSA are not well understood. In humans, the tumor is called angiosarcoma, and certain environmental toxins are known to play a role. These include arsenicals, thorium dioxide, and vinyl chloride. In dogs, genetics are thought to play a role, as certain breeds have increased risk. These breeds include the Golden Retriever, Labrador Retriever, and German Shepherd dogs. Sun exposure plays a role in one of the more benign presentations of this cancer, called cutaneous HSA, in which discrete, superficial lesions arise in the sparsely haired skin of dogs.
The spleen is the most common location for HSA, and these splenic tumors can grow very large, rupture, and bleed into the abdomen. Because of this, one of the most common presentations seen is a dog with acute lethargy, pale gums, and a distended abdomen. Though other disease states can cause splenic rupture and abdominal bleeding (hemoabdomen), about two-thirds of patients who present this way will be diagnosed with HSA.
Unfortunately, it is hard to distinguish between benign and malignant causes of splenic rupture without a surgical biopsy. Thus, stabilization of the patient followed by surgical removal and biopsy is recommended unless definitive evidence of metastatic spread exists. Without evidence of metastatic spread, it is important to know that benign lesions (hemangioma, hematoma, ruptured hyperplastic nodules) and less aggressive tumor types (such as marginal zone lymphoma) can present the same way.
Because rupture of this tumor can cause acute and significant bleeding, many dogs present first through the emergency service, where stabilization of the patient can occur. Diagnostics will be recommended, and these include blood work (CBC, serum chemistry analysis, coagulation testing), chest radiographs, physical exam, and abdominal ultrasound. Diagnostics often show a bleeding splenic or bleeding, right atrial (heart) mass, low red blood cell counts (called anemia) that may be regenerative, and elevated white blood cells. A sample of the fluid from the abdomen from the or the sac around the heart usually looks like blood. Other findings can include nodular lesions in the lungs, newly arising pigmented lesions in the skin, or masses in the liver or mesentery noted during abdominal sonography.
If there is a solitary bleeding mass, surgery and biopsy are recommended. Surgery can be both diagnostic and therapeutic as it can help stop the bleeding and provide tumor tissue for diagnosis.In the short term, surgery can greatly improve quality of life for a patient. However, overall survival expectations with surgery alone are low. In oncology, we use median survival times to evaluate treatments for the cancers we treat. A median is the middle value of a set, which means that 50% of patients did better and 50% did worse than median survival time. For HSA, reported median survival times with surgery alone range from 9-86 days. In one study, dogs with more advanced stage disease (stage III) had a median survival time of 40 days.
Because survival times are poor, additional treatment with systemic therapy (usually chemotherapy) is recommended. The median survival times reported with surgery plus standard chemotherapy range 4-7 months with about 10-15% alive at one year. While some dogs will have much longer term survival, most dogs develop metastatic nodules in the abdomen or lungs and eventually succumb to bleeding from these lesions. Without surgery, the average survival time can be hours to weeks depending on the presentation. Anti-bleeding therapies can be tried to staunch bleeding and improve quality of life for a short time, but there is no guarantee a bleeding mass will stop on its own, and if a bleed is successfully stopped, it will usually start to bleed again in the near future. .
Standard medical therapy usually includes the use of an intravenous chemotherapy called Doxorubicin (Adriamycin). However, depending on a specific patient’s health and circumstances, other treatments may be recommended instead. Because HSA is such an aggressive cancer, other therapies are often recommended for use in combination with IV chemotherapy. These are usually given orally at home by the pet parent. The chemotherapy treatments are given in the hospital on an outpatient basis every 2-3 weeks for a total of 4-5 treatments. After completion of the primary protocol, oral maintenance therapies may be recommended and discussed.
During treatment, blood work is assessed regularly to ensure patient safety and to monitor red blood cell counts, which can show early evidence of potential bleeds. Prior to the third or fourth treatment, we also recommend restaging diagnostics that may include chest radiographs and/or abdominal ultrasound. These test results provide objective evidence that the treatment used is being effective.
For patients that cannot undergo IV chemotherapy, lower dose or metronomic therapies have an indication of efficacy for this cancer based on small studies. Metronomic protocols use one or more oral medications in combination. Side effect risks are usually quite low, but periodic monitoring, blood work, and exams are still required during such treatment. While this treatment most likely will not be shown to be equivalent to IV treatment in terms of tumor response and efficacy, it is a reasonable treatment consideration for certain patients.
It is important to note that there is no cure for HSA at this time. The goal of treatment is to slow down tumor progression and allow patients both improved and prolonged quality of life, particularly when compared with those who do not have similar therapy. Because we know this is not curative, we do all that is possible to provide a good quality of life during treatment. Side effects of IV chemotherapy might include vomiting and diarrhea, deceased white blood cell counts, and hair loss (in certain breeds like poodles). We provide pre-emptive anti-nausea medications and antidiarrheals as needed. Because IV treatment can temporarily but significantly decrease white blood cells (neutrophils) around 5-9 days after treatment, patients can become vulnerable to secondary infections for about 2-4 days during a treatment cycle. Therefore, antibiotics are sometimes prescribed as well.
What we most expect from treatment are temporary, mild, and self-limiting effects that might include 1-2 days of mild lethargy, soft stool, or a picky appetite. Only about 5% will have side effects serious enough to warrant hospitalization or supportive care. And if a patient suffers intolerable side effects after one treatment, we will modify the dose on the next treatment visit, as our number one priority will also be the patient’s quality of life.
In addition to drugs used to directly treat the tumor, we often recommend other drugs to palliate or improve patient health and life quality. One treatment that is frequently used is a Chinese nutraceutical, called Yunnan Baiyao. While some studies have looked at its potential as an anti-tumor drug, it is mainly used to slow down or prevent bleeding from nodules or tumors. Tranexamic acid is another medication used for bleeding as well.
In terms of other treatments, there is ongoing evaluation of the benefit of certain, repurposed drugs, such as propranolol. These treatments are sometimes also recommended. Other treatments considered can include Losartan, targeted therapies, non-steroidal anti-inflammatories, and low-dose chemotherapy agents,
Various experimental strategies are under evaluation for HSA. These include the creation and use of autologous tumor vaccines and also the use of alternative targeted therapies as determined by genomic evaluation. Such therapies have been proven safe and may be of benefit for some patients, but studies to determine their true benefit are still underway. As such, these additional therapies are considered as treatments to use in addition to standard treatment and not as a replacement or alternative at this time. The benefits and risks of these additional treatment strategies would be best discussed with a veterinary oncologist.
Finally, in the past we have used a mushroom extract (Turkey Tail), marketed as a nutraceutical that is called I’m-yunity. An early, dose-finding study showed potential promise for this treatment in a small cohort of dogs. However, a more recent, 2022 study showed no improvement in survival with the use of this nutraceutical in combination with standard therapy. That said, it is still often used and may benefit some patients. It does not seem to hurt. There are currently no reported side effects, but the clinical trials have been small and side effects have not been studied in depth.