Palliative care is defined as treatment of symptoms of a condition, rather than treatment of the underlying condition itself. The World Health Organization defines palliative care as “the active total care of patients whose disease is not responsive to curative treatment”. The goal of palliative care is to improve or at least maintain the quality of life without necessarily slowing the progression of cancer or improving the lifespan.
Although for the clinician, our goal is often to attempt to cure, for many owners the primary goal of the treatment of any condition is quality and not the quantity of life. The goal of this lecture is to provide several examples of Palliative care in the form of surgical intervention, use of chemotherapy, radiation therapy, pain management, and nutrition.
Pain is a primary concern of most owners upon hearing the diagnosis of cancer and their feeling of not wanting their pet to be considered ”in pain”. Pain is a normal physiologic response that typically serves a protective function; however, pathologic pain, results from overt damage to nerves or tissues. Tumors are generally poorly innervated structures but may induce pain via by the pressure on normal tissue and their subsequent destruction. Primary treatment of the tumor may result in some degree of pain control even if the tumor does not respond by a reduction in volume. The analgesic effectiveness of radiation therapy is well documented in the treatment of bone pain, metastases, and cancer of the central nervous system. The effect of chemotherapy on cancer pain is generally associated with a reduction in tumor size. Surgery can relieve pain and discomfort via removal or an ulcerated superficial mass, large oral tumors preventing adequate nutrition, gastrointestinal obstruction, abscessed tumor, compression of nervous tissue by a tumor etc. The benefits of this type of therapy needs to be adequately weighed against the risks such as the associated hospitalization time, recovery time, and the overall expected duration of benefit.
- Anti-inflammatory and analgesic agents:
- Glucocorticosteroids are certainly associated with increased urination, drinking, appetite, as well as an overall improvement in the perceived of quality of life. There may be some benefit in patients with cancer in which the tumor has resulted in: include intracranial pressure, acute spinal cord compression, bone pain (metastatic disease), neuropathic pain secondary to tumor infiltration, lymphedema, and hepatic/splenic capsular distention.
- Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesic drugs in human and veterinary medicine. NSAIDs act both centrally to produce analgesia and peripherally to decrease inflammation primarily by decreasing prostaglandin production through inhibition of the cyclooxygenase (COX) enzyme. NSAIDs are effective at controlling mild to moderate pain and when combined with other analgesics such as opioids medications, a synergistic effect may occur.
- Opioid analgesics are added if insufficient analgesia is achieved with non-opioids. An example includes the use of Tylenol (Tylenol 4 with 60 mg codeine dosed at 1-2 mg/kg PO TID-QID, based on the codeine component). In cats, oral butorphanol (0.2-1.0 mg/cat PO BID- QID) is used quite often. Morphine tablets or morphine suppositories may also be used but the administration can be problematic. Transdermal fentanyl administration has been very useful for both pre-emptive pain relief and ongoing pain relief from chronic pain.
- False inhibitory neurotransmitters (i.e., Gabapentin, trade name Neurontin) are to treat chronic pain including neuropathic pain and chemotherapy-induced peripheral neuropathy. The exact mechanism by which gabapentin induces analgesia is unclear, however, Gabapentin has become the drug of choice for treatment of neuropathic pain, allodynia, and hyperalgesia in animals. The dose range is wide for gabapentin (5-20 mg/kg every 8-12 hours).
- Bisphosphonates: Bisphosphonates are used to decrease bone resorption by inhibiting the production of new osteoclasts, inhibiting the ability of mature osteoclasts to resorb bone, and inducing osteoclast apoptosis. By inhibiting tumor-associated osteolysis, bisphosphonates may reduce the pain associated secondary to primary and metastatic bone tumors. Pamidronate and Zoledronate in veterinary medicine. A dosage of 1.0-2.0 mg/kg every 4 weeks has been reported. In an effort to lower the risk of renal toxicity, the pamidronate dose is diluted in 250 mL 0.9% NaCl and administered over 2 hours. Zoledronate is administered at a dosage of 0.25mg/kg IV over 15 minutes q 4 weeks and is considered more potent than pamidronate.
Alternative therapies: Although data is limited, acupuncture, chiropractic management, and physical therapy may be incorporated into the pharmacologic management of pain to enhance overall well-being.
Although surgical intervention is generally associated with curative intent and long-term local control, there are several instances when surgical intervention may be employed in a palliative setting.
- Improved patient comfort: In cases where a surgical cure is not possible or is not the goal of the client, surgical cytoreduction may be employed. The most common instance is a large sarcoma in an older patient. In some cases, these sarcomas will grow large enough that they outgrow their own blood supply and they become necrotic, infected, or they interfere with nutrition, urination or defecation, respiration or ambulation. In these cases, the mass can be removed as a marginal or intralesional excision. A wide excision is not recommended and a radical excision, such as amputation, is only recommended when necessary. In the case of a marginally excised soft tissue sarcoma, mass recurrence is very likely. In the author’s experience, a second cytoreductive surgery will not be as successful in the face of recurrence and with generally result in a second recurrence of the mass within half of the time of the first recurrence. Amputation of the limb in cases of bone cancer and/or pathological fracture are considered palliative and will not afford a long-term survival in cases of metastatic osteosarcoma or osteosarcoma when the owner has no intention of treating with chemotherapy. However, amputation is the most effective method available for the treatment of bone cancer pain and should be considered, even in cases where the expected survival time is short. Other cases where palliative surgery may be employed include uncontrolled hemorrhage, abscessed or obstructive lymph nodes or oral tumors that are painful and/or infected. Each case must be considered in light of patient comfort and overall prognosis. However, in many cases, a surgical procedure may give the patient a better quality of life, even in the short term and this approach should not be discouraged because it is “too much to put a patient through”.
- Removal of fluid from the thorax or abdomen: Surgical placement of a pleural port catheter in the thorax or abdomen is a method that will allow for removal of malignant effusion from the affected cavity. This can be useful for mesothelioma or carcinomatosis. The port is sutured subcutaneously, with fenestrated tubing going into the body cavity. A non-coring needle, called a Huber needle, is used to evacuate fluid from the cavity intermittently. This can often be done without sedation. The port can also be used to administer intracavitary chemotherapy, which can be useful for malignant effusions.
- Vascular access ports: Vascular access ports are similar in design to the pleuralport catheter and they provide longstanding vascular access with a subcutaneous port. This can be useful in cases of long-term chemotherapy or for cases that are having daily radiation therapy.
- Feeding tube placement: Feeding tube placement is controversial in cases where cancer is being palliative. The need for enteral feeding is a stopping point for many clients, especially if this is a life-long requirement. However, adequate nutrition is important and feeding via an esophageal or gastrostomy tube is much more effective than attempts at syringe feeding by the client, which carry an inherent risk of inadequate nutrition and/or hydration and aspiration pneumonia.
We often break radiation therapy into one of two categories based on the total radiation dose and fractionation scheme:
- Definitive (curative intent) radiation protocols typically entail the delivery of 2.25 to 3.20 Gy/fraction on a M-F schedule for a total of 16 to 25 treatments resulting in a total dose of 48 to 63Gy. Generally, this is reserved for the microscopic setting.
- Palliative (hypofractionated) radiation protocols typically involve the administration of a larger dose per fraction, with fewer total fractions and lower total radiation dose. On the positive side, in regard to quality of life, palliative protocols typically are associated with little to no acute adverse effects seen with definitive protocols such as moist desquamation of the skin or oral mucositis. The larger dose/fraction, however, is associated with an increased risk of late adverse effects, but ideally, most animals receiving palliative radiation therapy typically will not live long enough to develop late effects. Palliative radiation therapy is used commonly in the treatment of canine appendicular osteosarcoma. The literature suggests 50% of patients experience pain relief by the second treatment and overall 75% experience pain relief by the completion of the 4th treatment. The median duration of pain relief is ~ 2-5 months. Palliative radiation protocols have been assessed in a variety of cancers including oral tumors, nasal tumors, hemangiosarcoma, thyroid carcinoma, mast cell tumor, injection site sarcoma and soft tissue sarcomas.
- Stereotactic radiation therapy is also considered hypofractionated delivery extremely high doses/fraction in 1-3 treatments. It is sometimes called radiosurgery, and an example is CyberKnife. This is a non-invasive way to deliver radiation therapy with similar precision as a surgical procedure, but with fewer treatments (and hence fewer hospital visits and time) than other palliative radiation protocols.
Oncologists generally do not see an ethical dilemma with the use of radiation therapy in a palliative setting since there are little acute side effects with these “palliative” protocols and most of the anticipated late side effects will occur well beyond the assumed lifespan of that patient. The bigger issue is a result of the financial impact of radiation therapy. In the USA, a palliative (4-6 fraction protocol) will cost $3000-3800 and stereotactic radiation therapy for a single fraction (as in OSA) is $8,000 and for a three-fraction protocol ($12,000).
Chemotherapy, when used in a palliative setting, is administered to attempt reduction or stabilization of the tumor to improve quality of life. One could say treatment of any bulky tumor would be described as “palliative”, however, for the purposes of this lecture, we reserve this for patients whose cancer has adversely affected their quality of life. Responses to chemotherapy in such a setting have been noted with transitional cell carcinoma, hemangiosarcoma, soft tissue sarcoma, mast cell tumor, histiocytic sarcoma, thyroid carcinoma, etc.
The dilemma more so when utilizing chemotherapy in a palliative setting is working to ensure the quality of life is not substantially impacted. Generally, we will provide supportive medications such as appetite stimulants, antinausea medication, antidiarrheals medications in an attempt to mitigate chemotherapy-related side effects. The use of palliative chemotherapy also requires frank and honest discussions with owners regarding outcome and potential side effects, to help weight the pros and cons of such therapy.
The use of expandable stents for relieving luminal obstruction secondary to cancer can be performed under fluoroscopic guidance, and have been evaluated in patients with urethral, esophageal, and colonic neoplasia. In many cases, this may actually be a life-saving procedure.
Malnutrition can occur as a result of cancer and it has been shown that while 4% of dogs with cancer were emaciated (defined as body conditioning score < 3 out of 9) at the time of initial diagnosis, 68% had documented evidence of weight loss and 15% had moderate to severe muscle wasting. Cancer cachexia is defined as a metabolic alteration and weight loss despite adequate nutrition. This is not to be confused with cancer anorexia which is weight loss and metabolic alterations associated with inadequate nutrition. Cancer cachexia is a real entity and likely underestimated in veterinary medicine. The incidence is likely higher in cats than dogs. The cause is unknown, however, metabolic alterations in carbohydrate, protein, and lipid metabolism occur as a result of cancer. Cancer cells prefer anaerobic glycolysis which results in hyperlactatemia. The conversion of lactate to glucose (Cori cycle) yields a net energy loss. A negative nitrogen balance can also lead to immunosuppression.
There are three associated phases of cachexia:
- Silent phase: No clinical signs of the disease are present, however, biochemical changes such as hyperlactatemia, hyperinsulinemia, and alterations in amino acid and lipid profiles are noted.
- Clinical Phase: At this point, patients will demonstrate signs such as anorexia, lethargy, and weight loss.
- Severe Phase: This phase is associated with weakness, severe debilitation, and significant weight loss.
A nutritional assessment is based on both a thorough history (type of food, number of meals, how voracious a patient is in eating) and physical examination (assess body weight, body condition score, and overall muscle mass). The extent of nutritional support is based upon the results of the history and exam. Mild interventions are often indicated, such as introducing higher caloric diets or medications such as appetite stimulants (megesterol acetate, prednisone, cyproheptadine, and mirtazapine), antiemetics (metoclopramide, dolasetron, ondansetron, and maropitant), or gastrooproteectants (famotidine, sucralfate, and omeprazole).
For some, there is an ethical dilemma in the placement of feedings whether nasogastric, gastric or intestinal for palliation. In rare cases, in which a bulky mass prevented the ability to ingest adequate nutrition, I have used more aggressive means to ensure adequate nutritional intake but this represents a minority of cases.
Medical oncologists are all too frequently asked by the client the following question….”what diet should I use?” Owners are also always concerned that their pet is getting enough to eat and is there is a “cancer diet”. So what do I recommend? I try to recommend a diet relatively low in simple carbohydrates, with moderate amounts of bioavailable proteins as well as soluble and insoluble fiber, and moderate amounts of polyunsaturated fatty acids (high in omega-3). Often times I may supplement the current diet with additional protein and fish oil. I have found the additional protein content often encourages a more vigorous appetite in dogs. In regards to fish oil supplementation, there is recent data regarding a veterinary based product which I often recommend for my patients.
*This text is from ACVC Proceedings 2017 Clifford and Liptak
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