Kathryn E. Michel, DVM, MS, DACVN
Weight loss is a common finding in human cancer patients and one which has been shown to have associations with clinical outcome.1 Weight loss in association with neoplasia can occur for a number of reasons including effects of the tumor and the cancer therapy. However, the weight loss seen in many human cancer patients does not appear to be attributable to decreased food intake alone. In simple starvation individuals lose principally adipose tissue, whereas patients with neoplasia can experience loss of both lean and adipose tissues.2 Furthermore, the magnitude of the weight lost often does not correspond to the amount of food consumed, and this weight loss cannot be reversed by a concomitant increase in caloric intake.3 This paraneoplastic syndrome of cancer cachexia is hypothesized to result from metabolic alterations that exist as a consequence of the underlying tumor. Derangements in carbohydrate, lipid, and protein metabolism have been found in both human and canine cancer patients that may contribute to weight loss.4-14 There is also evidence that cytokines, including TNFα, IL-1, and IL-6, could play a role in these metabolic alterations.15,16
Cancer cachexia syndrome has been implicated as a negative prognostic factor for survival, surgical risk, response to chemotherapy, and tolerance of treatment in human cancer medicine.17-19 There have been some preliminary studies in companion animal cancer patients looking at body condition and weight loss. When body condition was evaluated in dogs seen at the oncology service at the University of Pennsylvania only 5% of the dogs were considered significantly underweight with a BCS <4/9 (1= cachectic, 4-5=optimal for dogs 5=optimal for cats, 9=obese) while 29% were classified as significantly overweight (>7/9).20 Conversely, an investigation of feline cancer patients at the same institution documented that up to 44% of cats with cancer treated through the oncology service had a BCS <5/9.21 This study also found that both a low BCS as well as a low body weight had a negative impact on prognosis with both cats with solid tumors and cats with lymphoma having significantly shorter survival times if their BCS or their body weight were low. Furthermore, a positive correlation between remission status and BCS was found; cats in remission were more likely to weigh more and have a higher BCS, thus the presence of weight loss or cachexia was not found to be an independent negative prognostic indicator as it has been in similar studies in human oncology.22 Nevertheless, the results suggest that weight loss and deterioration of body condition are significant problems in feline cancer medicine and may have consequences for response to treatment, remission duration and quality of life. These findings were supported by a study presented at the 2007 Veterinary Cancer Society meeting which reported that cats diagnosed with lymphoma that gained weight during treatment had a significantly longer median survival time than cats whose weight decreased or was unchanged.23 They concluded that weight changes during treatment of feline lymphoma are prognostic for outcome and that their findings suggested that, in addition to chemotherapy, nutritional support and weight loss prevention are essential components of treatment for feline lymphoma.
It remains unknown is to what extent the weight loss seen in feline cancer patients is attributable to decreased appetite or the direct effects of the tumor or therapy on nutrient assimilation or metabolism and to what extent cancer cachexia syndrome may be responsible. However, it would seem prudent to pay careful attention to the nutritional status and feeding management of our feline cancer patients in hopes that such intervention would be able to avert or ameliorate loss of weight and body condition and improve response to therapy and overall prognosis.
Nutritional Assessment of Cancer Patients
The process of nutritional assessment involves evaluation of not only the patient's nutritional status buts also the diet it is receiving and how that diet is being fed. Furthermore, this process should not be an initial one time exercise but an on-going practice throughout the patient's course of treatment so that adjustments can be made in diet and feeding recommendations based on the patient's response to therapy.
The medical history of a cancer patient should be assessed in five areas: 1) pre-existing or ongoing weight loss; 2) extent of voluntary dietary intake; 3) the presence of persistent gastrointestinal signs either from the primary disease or treatment the patient is receiving; 4) the patient's functional capacity (e.g., weakness, presence of exercise intolerance); and 5) the impact of the patient's underlying disease state. When dealing with cancer patients one must consider the ways in which the tumor could directly or indirectly affect food intake, the impact that cancer therapy may have on food intake and metabolism, and the recognition that the tumor itself may exert effects on metabolism that negatively influence nutritional status.
It is often difficult to document a history of weight lost since most animals are only weighed when they come in to a veterinary clinic and not always then. It is critical that cats being treated for cancer are weighed consistently on the same scale and that the scale is sensitive and accurate for animals in the feline weight range. It is also important to know the time course over which the weight loss has occurred. Rapid weight loss is generally of greater concern because it is more likely to involve a greater percentage of lean tissue catabolism than a more gradual weight loss. Having said that, cancer cachexia syndrome, as documented in human cancer patients is characterized by loss of both lean body mass and adipose tissue and can take a chronic course.
The physical exam focuses on changes in body composition, specifically wasting of fat stores and muscle mass, presence of edema or ascites, presence of mucosal or cutaneous lesions, and appearance of the patient's hair coat. Several excellent body condition scoring systems (BCS) have been developed for cats.24,25 However, these systems do not apply well to cats with cancer because they depict patients that deviate from optimal based on under-or overconsumption of protein and calories. It has been reported in a study from the University of Pennsylvania that over 90% of cats diagnosed with cancer have evidence of muscle wasting even in cases where the patient had adequate or even excessive fat stores.21 Without a careful examination, which involves palpation of skeletal muscle mass over bony prominences (such as the scapulae or vertebral column) some these patients might be misclassified as overweight or even obese. Thus muscle mass should be subjectively evaluated in addition to using one of the standard body condition scoring systems available.
The findings of the historical and physical assessment are used to categorize the patient as: A: well nourished; B: borderline or at risk of becoming malnourished; and C: significantly malnourished. Coupling this assessment with the patient's cancer diagnosis, stage, treatment protocol, and prognosis will aid in making decisions about nutritional therapy.
Assessment of Voluntary Food Intake
In order to be able to assess whether that patient's food intake is adequate, you must have a caloric goal, select an appropriate food, and formulate a feeding recommendation for the patient. By doing so, you will have an accurate accounting of how much food is offered to the patient, and will be able to evaluate the patient's intake based on how much of the food is consumed.
For hospitalized patients, we recommend using an estimate of resting energy requirement (RER) as your initial caloric goal as most hospitalized patients are not expending much more energy than RER while they are caged. Under such conditions most patients eating at least RER will lose little if any weight. Clearly if a patient is willing to consume calories in excess of RER it should be permitted to do so. However, starting out with this amount of food will provide a goal to aim for with patients who have a decreased appetite. It is critical to monitor both the patient's food intake and body weight to establish whether the patient is in energy balance or not and to permit timely adjustment of the dietary plan if the patient is not responding as anticipated.
The majority of cancer patients are treated as out-patients and therefore will require additional caloric intake to compensate for energy expended on voluntary physical activity. Under these circumstances, the daily energy requirement (DER) should be estimated and used to calculate your initial caloric goal. This information should be converted into clear feeding directions for the cat's caregiver using specific portions of whichever foods are being offered to the patient. There should be a plan for reporting back to the clinician about daily food intake and for accurately monitoring body weight on a regular basis to assess the patient's response and allow for modification of the feeding plan as appropriate.
Determining the Need for Assisted Feeding
Patients who are unable to eat or whose voluntary food intake is insufficient to maintain energy balance will require some form of intervention whether it as simple as coax feeding or more a more aggressive approach using some form of assisted feeding. Clearly the feeding management of those patients who are already significantly malnourished at the time of presentation should receive immediate attention. However, it is often the case that reduced food intake as a consequence of the cancer therapy can be anticipated. Therefore a plan should be in place for nutritional intervention should the need arise particularly, in the case of patients whose nutritional status is considered borderline at the commencement of therapy.
When a cat exhibits a decreased appetite it is natural to try to tempt it to eat by offering a variety of palatable foods. Very often the caregiver will further attempt to coax the patient to eat by putting the food close to the cat's face or actually placing food in its mouth. Sometimes these techniques can be successful and lead to adequate food intake by the patient. However, such efforts are labor intensive and time consuming. A feeding plan with specific caloric goals should be worked out in advance so the caregiver can assess the adequacy of the patient's food intake. Furthermore, it is very important to recognize that cats sometimes associate nausea, general indisposition, or pain with the act of eating or even the sight or scent of food. This is called learned food aversion and can further complicate achieving adequate food intake in a patient.
Much of the information gleaned in your nutritional assessment will aid in making the choice of the best route for assisted feeding access. Other information to evaluate in the decision making process should include: 1) assessment of gastrointestinal tract function; 2) assessment of other organ systems that may have an impact on the patient's ability to tolerate specific nutrients; 3) assessment of the patient's ability to tolerate a feeding tube and tube placement; and 4) assessment of the patient's risk for pulmonary aspiration. If parenteral nutrition is being contemplated, it is also necessary to include assessment of the ability to obtain vascular access and the patient's fluid tolerance.
There are some additional considerations to take into account when assessing cancer patients for assisted feeding. Certain chemotherapeutic agents can impair wound healing with the consequence of greater risk of septic complications with tubes that are placed into the peritoneal cavity (e.g., gastrostomy and enterostomy tubes). This risk can be magnified if the patient is receiving immunosuppressive drugs. Radiation therapy can have similar consequences if the tube placement is within the field of treatment. The esophagostomy tube has many of the advantages of a gastrostomy tube but carries a lower risk of serious septic complications. These tubes are simple and inexpensive to place and usually well-tolerated by feline patients.
One final consideration is the fact that assisted feeding is a form of life-support. Used properly it could have the benefit of both prolonging life and ensuring a better quality of life for the patient. However, there may be circumstances, in terminal patients, where humane euthanasia is in the better interest of the patient then prolonging life. It is often more difficult for involved pet owners to terminate life supporting therapies than to initiate them and therefore the decision to use assisted feeding in a patient should bear in mind these ethical issues.
In general, diet selection is based on which of patient's problems can and should be addressed with nutrition and the nutritional requirements of the patient. While there have been many investigations of ways in which diet and specific nutrients may be used to slow or antagonize tumor growth, modulate immune function, or counteract the cancer cachexia syndrome, most of this research has been done in rodent models or human patients. There have been preliminary clinical investigations involving canine cancer patients, but none to date that have involved cats. A canned low carbohydrate diet that was fortified with fish oil and arginine was found to increase survival time and disease free interval in dogs with stage III lymphoma.26 With the exception of the additional fish oil, many conventional canned cat foods have a similar formulation to the diet that was used in this investigation.
Therefore, the major consideration for diet selection for cats with cancer should be acceptance by the patient. The diet should meet feline nutritional requirements and if it does not, it should be supplemented to address any deficiencies. Ideally, the diet should be of high caloric density, as this would aid in ensuring sufficient energy intake by the patient, especially in cases when appetite is decreased. In addition, if the patient has clinical signs or disease, either secondary or in addition to cancer, that would benefit from dietary management, efforts should be made to select and feed a diet formulated to address those conditions.
Lastly, in patients with alimentary neoplasia, in particular lymphoma, nutrient malabsorption can occur. While this can lead to generalized protein-calorie malnutrition, it can also lead to specific micronutrient deficiencies. One nutrient deficiency which has been reported in cats with gastrointestinal disease, including lymphoma, is cobalamin deficiency.27 Cats with inflammatory bowel disease complicated by cobalamin deficiency have shown improved weight gain and response to therapy with parenteral supplementation of this vitamin.28
In addition to treating the underlying malignancy with surgery, radiation therapy, chemotherapy or a combination of these modalities, additional medications may be indicated and necessary to reverse weight loss and improve quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) include several different drugs with anti-cyclooxygenase activity. These drugs have both analgesic and well as anti-inflammatory effects, and may therefore provide dual benefits to patients suffering from a painful non-resectable tumor and/or the systemic inflammatory effects of the tumor and cancer cachexia syndrome. The use of appetite stimulating drugs and anti-depressants may also be indicated in some patients. It can be very difficult and often impossible to distinguish between anorexia resulting from nausea and anorexia as part of the cancer cachexia syndrome. Therefore anti-emetics should always be considered first or in conjunction with drugs to stimulate appetite. Administering appetite stimulating drugs without providing effective anti-emetics may worsen nausea and cause more vomiting with the potential of creating a learned food aversion. It is also important to rule out and treat any physical causes of nausea, vomiting and subsequent anorexia such as gastrointestinal tumors, intestinal obstruction or chemotherapy-induced gastroenteritis prior to prescribing appetite stimulating drugs.
Human cancer studies have found that cachetic patients have a worse outcome, more complications and a lower response to therapy. The situation is likely similar in cats, as illustrated by one recently published investigation, where remission was positively correlated with a higher BCS and cats with solid tumors and lymphoma that had an underweight body condition had significantly shorter survival times than cats with a higher BCS.21
Weight loss and the associated reduced quality of life may not only have a negative impact on treatment, but may also have direct consequences for survival, because it may lead to a decision to euthanize. The ability, interest, and willingness to eat voluntarily are major components of having a good quality of life. Most owners and veterinarians will likely agree that a cat that does not eat voluntarily or adequately over long periods of time may not feel well and may be suffering. Therefore, providing effective nutritional support and offering the appropriate palliative medications to decrease nausea, improve appetite and facilitate voluntary food intake become crucial for prolonging survival. A study performed by the oncology service at the University of Pennsylvania found that the majority of cats with lymphoma lose weight in the induction phase of chemotherapy.29 Low body weight and low BCS in feline cancer patients has been found to have a negative impact on survival.21 A significant proportion of cats with lymphoma die or are euthanized within the first months of starting chemotherapy. These facts suggest that more focus should be directed towards ensuring adequate nutrition and preventing weight loss in these patients. Early nutritional intervention may not only improve quality of life in cats with cancer but may also have positive impact on survival.
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