Supportive Care: Treating the Patient, Not Just the Tumor
ACVIM 2008
Dennis Bailey, DVM, DACVIM (Oncology)
Ithaca, NY, USA

Introduction

The single most important goal when caring for a cancer patient is to provide and sustain excellent quality of life for as long as possible. Several different factors can impact quality of life. Cancer can directly impair the function of the organ(s) in which it resides. It also can induce a variety of paraneoplastic syndromes, metabolic disturbances affecting organs other than those directly infiltrated by the cancer cells. The treatment modalities used to treat cancer--surgery, radiation therapy, and chemotherapy--usually are well-tolerated but on occasion can induce adverse effects that interfere with quality of life. Lastly, many cancer patients have concurrent illnesses that are unrelated to their cancers. All of these different factors must be taken in consideration when developing a comprehensive cancer treatment plan.

Supportive care treatment plans need to be tailored to the individual. General treatment guidelines are outlined below. During this presentation, several clinical examples will be used to illustrate how to apply these guidelines to clinical patients.

Clinical Staging

Once a patient has been definitively diagnosed with cancer, the next step is to stage the patient's cancer. Clinical staging refers to determining the distribution and extent of dissemination of the cancer. In a broader context, it also includes assessing overall health and quality of life. Clinical staging always begins with a thorough history. Among the questions that the owner should be asked: When did you first notice the tumor? Has it changed in size or appearance since then? Have you noticed any changes in appetite? Have you observed any vomiting? Are stools normal in color and consistency? Have you noticed any changes in drinking or urination? Have you noticed any change in body weight or conditioning? Have you noticed any changes in energy level? Have you noticed any behavior changes? Does your pet have any other health concerns? Is your pet receiving any medications? Do you have any specific questions or concerns? It is important to leave questions open-ended to ensure that the responses are as unbiased as possible. For example, it is preferable to ask "Have you noticed any changes in appetite?" rather than "Have you noticed a decrease in appetite?" Also, it is important to continue to ask owners these questions at each recheck examination to make sure that any changes in quality of life are identified and addressed quickly. At our hospital, we have incorporated many of these questions into a short questionnaire that we ask owners to complete before each visit.

The next step in clinical staging is a thorough physical examination. As part of the exam, the pet's attitude, attentiveness, and playfulness should be evaluated. An accurate body weight should be obtained, and body condition should be assessed. Any visible tumors should be measured with calipers and recorded on a topography map. All of these things should be done at every visit so that any changes over time are recognized. Additionally, if possible, the same people should evaluate the pet at every visit for continuity.

The diagnostic tests recommended as part clinical staging will depend on the results of history and physical examination as well as the biologic behavior of the tumor in question. A complete blood count, chemistry panel, and urinalysis are always recommended as part of a general health screen and to assess general organ function. For tumors involving the head or trunk, cross-sectional imaging using CT or MRI might help better delineate the local extent of the tumor and its proximity to adjacent vital organs. This is very helpful when planning surgery or radiation therapy. Thoracic radiographs are used most commonly to assess for pulmonary (lung) metastasis, although CT is gaining popularity because it provides better resolution. Ultrasonography is used to assess intra-abdominal structures. Bone marrow aspirates are indicted for patients with hematopoietic cancers such as lymphoma or leukemias. Assessment of regional lymph nodes is best accomplished with lymph node biopsy, but fine needle aspiration and cytology is used routinely as well.

The definitive tissue diagnosis obviously is very important when developing a treatment plan. Knowing the type of cancer, its biologic behavior, and its potential responsiveness to surgery, radiation therapy, and/or chemotherapy helps the oncologist determine which treatment modalities potentially would effective. Equally important, though, are the clinical staging results. These results help the oncologist determine which of these treatment modalities, if any, are reasonable for this individual patient. For example, while the combination of surgery and radiation therapy can be very effective for some dogs with cutaneous mast cell tumors, aggressive local therapy is not indicated in a dog where clinical staging identified distant metastatic disease. Chemotherapy would be indicated instead. Additionally, clinical staging helps put the cancer treatment in the context of the entire patient. Many patients have metabolic derangements, nutritional imbalances, and/or pain that should be addressed before initiating aggressive cancer treatment. Clinical staging can also be used to help predict any possible adverse effects that the patient might encounter during treatment, allowing supportive care measures to be implemented prophylactically. Lastly, if it is decided that the patient is not a good candidate for definitive cancer treatment, then supportive care can be implemented as a palliative measure. Specific supportive care considerations are discussed below.

Intravenous Fluid Support

Intravenous fluids might be indicated for a variety of reasons, one of the most important being to maintain adequate hydration. Adequate intravascular fluid (plasma) volume is needed to ensure tissue perfusion and the efficient delivery of oxygen and nutrients as well the removal of waste products. Many cancer patients are clinically or subclinically dehydrated. This can result from decreased water intake (inadequate drinking and/or eating moist foods) or increased water loss (such as from vomiting or having diarrhea). Also, some cancers can cause effusions, the accumulation of fluid in body cavities such as the pleural or peritoneal cavities. Here, total body water remains the same, but it is redistributed from places where it is needed (such as the plasma) to places where it is not needed (such as the pleural or peritoneal cavity). Additionally, cancer can cause systemic inflammation, where blood vessels become "leaky" and loose fluid. All of these things ultimately can result in poor tissue perfusion. If a cancer patient is not eating adequately, impaired delivery of what few nutrients are ingested will only exacerbate the negative energy balance. Additionally, poor perfusion of intestines can worsen any adverse gastrointestinal effects associated with chemotherapy treatment. In a patient that already is dehydrated, additional fluid loss through severe vomiting and/or diarrhea can lead to a downward spiral with catastrophic consequences, including shock and death.

By changing the fluid type and rate, intravenous fluids also can be used to correct specific metabolic disorders. For example, hypokalemia (low blood potassium level) is commonly seen in cats secondary to anorexia, vomiting, and kidney disease. This can be corrected by supplementing the intravenous fluids with additional potassium (usually in the form of potassium chloride, KCl). As another example, lymphoma sometimes can cause hypercalcemia (an increase in blood calcium level--see sessions T6 and T7 on paraneoplastic syndromes). Here, diuresing the patient with a fluid that is high in sodium and void of calcium (such as 0.9% NaCl) can help flush the excess calcium from the patient's body.

Nutritional Support

Malnutrition is a common complication of cancer. A recent veterinary study indicated that while only 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.1 Cancer cachexia is a complex metabolic syndrome characterized by weight loss, anorexia, and wasting of lean body mass secondary to the growing malignancy. The factors contributing to cancer cachexia can be divided into two broad categories. The first category includes mechanical and functional abnormalities that lead to decreased nutrient intake. Oral tumors can cause dysphagia and considerable pain. Gastrointestinal tumors can cause pain, early satiety, mechanical obstruction, nausea, vomiting, diarrhea, and malabsorption of nutrients. Advanced-stage neoplasia, regardless of its anatomic location, often is associated with partial or complete anorexia. Chemotherapy can cause nausea, anorexia, vomiting, and diarrhea. Radiation therapy can cause painful mucositis when the mouth is included within the treatment field. The second group of factors contributing to cancer cachexia includes numerous metabolic derangements that prevent the body from efficiently using the nutrients it has. Abnormalities in the way the body uses carbohydrates, proteins, and lipids have all been identified. The result is that a cancer patient can lose weight and lean muscle mass even in the face of adequate food intake. The underlying mechanisms for these metabolic derangements are not completely understood, but substances released by the tumor itself and by the patient's body in response to the tumor are both thought to play important roles.2

A patient's nutritional assessment is based on both a thorough history and physical examination. It is important to ask an owner about his or her pet's usual dietary habits, including the type of food fed, the amount fed at each meal, the number of meals per day, the types and amounts of treats given, and the voraciousness of the pet's appetite. The owner should then be asked about any recent changes in dietary habits as well as any changes in body weight or body conditioning. Physical examination should then be used to objectively assess weight, body condition, and muscle mass. If available in the medical record, previous assessments should be used as a baseline for comparison. Early changes associated with cancer cachexia may be as subtle as the pet not finishing its food as quickly as usual or requiring some coaxing. As cancer cachexia progresses, the pet's nutritional intake will become inadequate despite coaxing and offering palatable foods, and eventually weight loss and muscle wasting will become evident.

How aggressively to provide nutritional support depends on the severity of the patient's nutritional deficiencies. Minimal deficiencies can be overcome by offering palatable foods such as Hills a/d or boiled chicken and rice. (The latter is not nutritionally balanced, and additional supplements are needed if this diet is going to be used long-term.) For moderate anorexia, appetite stimulants such as prednisone, cyproheptadine, and mirtazapine can be used. If food intake is thought to be reduced because of nausea, gastroprotectants such as famotidine and sucralfate should be considered. Anti-emetics such as metoclopramide, dolasetron, ondansetron, and maropitant are indicated to help control nausea and vomiting. Whenever possible, it is preferable to prevent gastrointestinal problems than to wait and have to reverse them. For example, consider a patient that experiences mild anorexia and vomiting a few days after its first chemotherapy treatment. The next time the patient receives that same chemotherapy drug, appetite stimulants and anti-emetics should be initiated right away as a prophylactic measure to prevent the adverse gastrointestinal effects before they ever begin.

If voluntary food intake cannot be restored or maintained at adequate levels, then supplemental feeding is needed. Whenever possible, it is preferable to use the GI tract (i.e., use a feeding tube). This way, the nutrients provided are digested and metabolized through their normal pathways. In addition, food within the intestine plays a critical role in maintaining gut health and function. The most commonly used feeding tubes are esophagostomy tubes and gastrostomy tubes. Both tubes can be left in place indefinitely. The main advantage of an esophagostomy tube is the ease of placement--they can be placed quickly and easily under light general anesthesia without any specialized equipment. In contrast, gastrostomy tube placement usually is done surgically or with endoscopic guidance. The main advantage of a gastrostomy tube is that it is wider in diameter and can accommodate a wider variety of foods. Additionally, low-profile gastrostomy tubes can be used to eliminate the need for cumbersome and potentially uncomfortable bandages. Parenteral (intravenous) nutrition should be used only when the gastrointestinal tract is not functioning properly (e.g., if a patient has intractable vomiting).

There is a lot of discussion about so-called "cancer diets". The general features of these diets include low quantities of simple carbohydrates, moderate quantities of highly digestible proteins rich in arginine and glutamine, and relatively high quantities of lipids and omega-3-fatty acids.3 However, the use of such diets has been evaluated only in dogs with lymphoma, and the clinical benefit was questionable.4 The author believes it is more important for a patient's diet to be palatable and nutritionally balanced. Changing a pet's diet to a cancer diet should be considered only if caloric and general nutritional requirements are being maintained without any difficulty. Remember, get the patient to eat first; worry about what it is eating second.

Pain Management

Cancer pain is one of the most important factors affecting overall quality of life. In human oncology, it is estimated that cancer pain is experienced by 30-50% of people undergoing active cancer treatment and 70-90% of people with advanced disease.5 It is difficult to accurately assess the prevalence of pain in veterinary cancer patients, but it is reasonable to assume that it is comparable to that reported in people. Cancer pain likely is underappreciated in veterinary cancer patients because it is relatively difficult to assess objectively. Physiologic variables such as heart rate, respiratory rate, and pupil size are not reliable indicators of pain. Instead, pain assessment is based primarily on behavior. Subtle changes in activity level, attitude, appetite, or grooming can be early signs of pain. As pain becomes more severe, aversion to petting/palpation may be noticed. Vocalization usually is seen only when pain is severe. Because the owner sees the pet every day in its own environment, he or she is best able to assess behavior changes. Therefore, it is crucial to educate the owner about what signs to look for, to ask the owner for feedback on a regular basis, and to trust the information provided by the owner.

It is very important to always be aware of the potential for cancer pain and to take a proactive approach with respect to its diagnosis and treatment. Pain can be prevented far more easily than it can be reversed. Chronic pain induces physical changes in the spinal cord that alter the way pain signals are processed, resulting in heightened sensitivity to painful stimuli (hyperalgesia) and perception of pain in response to stimuli that normally would not be considered painful (allodynia). These changes also decrease the efficacy of analgesic medications, making it much more difficult to alleviate a patient's pain. Additionally, even if the pain eventually is controlled, the physical changes in the spinal cord often are not fully reversible.

Pain management typically is most effective when multiple treatment modalities are used in combination. The World Health Organization has outlined a three-step hierarchy for the management of cancer pain.6 For patients with mild pain, non-opioid analgesics such as nonsteroidal anti-inflammatory drugs (carprofen, deracoxib, meloxicam) are attempted first. For moderate pain, a weak opioid such as codeine, buprenorphine, or tramadol can be added on. For severe pain, strong opioids such as morphine or fentanyl are indicated. While veterinary analgesia centers around the use of nonsteroidal anti-inflammatory drugs and opioids, the adjunct use of additional drugs such as gabapentin and amantadine is gaining popularity.

In addition to using analgesics, several other treatment modalities should be considered and used whenever appropriate. Local anesthetic nerve blocks are very useful for orofacial tumors and for phantom pain associated with amputation. Depending on the anesthetic agent(s) used, the blockade can last for hours, days, or even weeks. Bisphosphonates are drugs that inhibit bone resorption, and they are an effective treatment for pain caused by cancer-associated bone destruction. Pamidronate is a bisphosphonate that has been used to treat canine osteosarcoma with good success.7 Palliative radiation therapy is another extremely effective treatment option for controlling pain. The exact mechanism for pain relief remains uncertain, but it likely involves a combination of reducing local inflammation and killing some of the tumor cells. In veterinary oncology, palliative radiation therapy is used commonly to control pain associated with primary bone tumors such as osteosarcoma. This is one of the most effective treatments for relieving bone pain, with up to 90% of dogs enjoying a significant improvement in comfort for around 2-4 months.8

Conclusion

Few words evoke the emotional response that cancer does. Many owners have fears and misconceptions that lead them to believe that cancer treatment is hopeless and only leads to unnecessary suffering. Because of this, it is important to emphasize that our focus is on quality of life. One of the best ways to illustrate this commitment is to discuss and incorporate supportive treatments when outlining a cancer treatment plan. This alone will help dispel many of the fears associated with cancer treatment. In addition, because owners often play an active role with many of these supportive measures, they often feel more involved and even empowered. By treating the patient as whole rather than just the tumor, patient care improves, quality of life is restored and sustained, and the human-animal bond is further strengthened.

References

1.  Michel KE, et al. J Vet Intern Med 2004;18:692.

2.  Lelbach A, et al. Med Sci Monit 2007;13:RA168-RA173.

3.  Roudebush P, et al. Vet Clin North Am Small Anim Pract 2004;34:249.

4.  Ogilvie GK, et al. Cancer 2000;88:1916.

5.  Portenoy RK, et al. Lancet 1999;353:1695.

6.  World Health Organization. Cancer Pain Relief, 2nd ed 1996.

7.  Fan TM, et al. J Vet Intern Med 2007;21:431.

8.  Green EM, et al. J Am Anim Hosp Assoc 2002;38:445.

Speaker Information
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Dennis Bailey, Jr., DVM, DACVIM (Oncology)
Ithaca, NY


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