An Overview of Cachexia in People With Cancer

Cachexia is the medical term for unintentional weight loss, progressive muscle wasting, and a loss of appetite. Cachexia is a syndrome that happens in people who are very sick with a chronic illness or serious disease.

People who have cancer often develop cachexia. The syndrome is thought to be directly responsible for 20% of cancer deaths in the United States. Cachexia occurs in at least 50% of people with advanced cancer. Cancer cachexia is also referred to as cancer anorexia cachexia syndrome.

Cachexia not only worsens survival for people with cancer, but it interferes with their quality of life. People with cachexia are less able to tolerate treatments, such as chemotherapy, and often have more side effects and complications after surgery. Cachexia also worsens cancer fatigue, one of the most annoying symptoms of cancer.

A number of treatment approaches have been evaluated ranging from diet to dietary supplements, to medications, but can be challenging as cachexia is more than just a lack of calories in the body. Newer research suggests that exercise, though counterintuitive, may help.

This article will go over the causes of cachexia in people with cancer. You will also learn about how cancer cachexia can affect treatment and how the syndrome can be managed.

Symptoms

Recent research suggests that cachexia often begins even before any weight loss occurs, so early on there may not be any symptoms. When symptoms occur, they include:

Involuntary (Unintentional) Weight Loss

Weight loss with cachexia is involuntary, meaning that it occurs without trying. Yet it goes further than unexplained weight loss. Weight loss may occur even though you are getting an adequate amount of calories in your diet, and if calorie intake outweighs output of energy. Unintentional weight loss is defined as the loss of 5% of body weight over a 6 month to 12 month period, but even smaller amounts of weight loss could be of concern.

Skeletal Muscle Wasting

Muscle wasting is a hallmark of cachexia and occurs along with a loss of fat. It can also be fairly insidious. In people who are overweight at the time of their diagnosis, significant loss of muscle mass can occur without an obvious outward appearance of weight loss.

Anorexia/Loss of Appetite

Loss of appetite is another symptom of cachexia, and again, this symptom is somewhat different than ordinary "loss of appetite" symptoms. With cachexia, it is not simply a decreased desire for food, but more of a loss of a desire to eat.

Lowered Quality of Life

Muscle wasting can diminish your ability to walk and participate in activities that would ordinarily be enjoyable.

Causes and Risk Factors

Cachexia may be caused by "tumor factors," substances manufactured and secreted by a tumor, or by the "host response." Host response simply means the body's response to a tumor. The response of the immune system to cancer and other causes of cachexia are being studied to try and understand the underlying factors behind cachexia.

Cachexia is dominated by catabolic metabolism. If you think of normal metabolism being the building of tissue and muscle (anabolic metabolism), the opposite is true with cachexia, which is the breakdown of normal bodily processes.

Cachexia is seen frequently with cancer but is also seen with diseases such as AIDS/HIV, heart failure, emphysema, and kidney failure. With regard to cancer, it is seen most frequently with lung cancer, pancreatic cancer, and stomach cancer, but may be seen with any type of advanced cancer.

Diagnosis

Even though the symptoms and signs of cachexia are usually noticed late in the course of cancer, we're learning that the process leading to muscle wasting begins very early on after a diagnosis of cancer. As such, cachexia is often present before any weight loss occurs.

There are several ways that cachexia can be evaluated. Some of these measures include:

• Body mass index (BMI):  Body mass index describes not only relative body weight but can give more information about a healthy weight. BMI is calculated using a formula of height and weight. Since BMI does not identify the proportions of muscle mass and fat, however, it is cannot be used alone to evaluate cachexia.
• Lean muscle mass: Measuring body composition can help determine the ratio of lean muscle mass to body fat. Tests used to do this may include skin folds and bioimpedance.
• Food intake diaries: Keeping a food diary is an important activity when looking to prevent or cope with cachexia. At the same time, it's important to keep in mind that the malnutrition of cachexia can occur even with an adequate intake of calories.
• Blood tests: Some lab tests that are useful in evaluating cachexia include white blood cell counts (WBC), serum albumin, transferrin levels, uric acid, and inflammatory markers, such as C-reactive protein (CRP).

There are a number of screening tools that look at combination of the above in order to identify cachexia, such as the Malnutrition Universal Screening Tool (MUST), though there is not yet a single screening tool that is effective in detecting cachexia in every case. Dividing cachexia into stages or grades can give healthcare providers a better of the natural history of cachexia, but of greatest concern is that cachexia is diagnosed as early as possible.

Despite the number of tools available, following a person over time and checking serial body weights can give a better idea of changes.

Diagnostic Criteria

Researchers have developed a cachexia staging score for people with advanced cancer. A different number of points are assigned to each component and added together to separate cachexia into three stages. These components include:

• Weight loss in the past 6 months (scored from 0-3)
• A questionnaire that addresses muscle function and sarcopenia (scored from 0-3)
• ECOG performance status (scored from 0-3). Performance status is a measure of
• Loss of appetite (scored from 0-2)
• Abnormal lab tests (scored 0-2)

Stages

Based on scoring, precachexia and cachexia can then be broken down into four stages:

• Non-Cachexia (a score from 0-2)
• Precachexia (score from 3-4): Overall weight loss is less than 5%, and people may have symptoms such as loss of appetite and impaired glucose tolerance
• Cachexia (score from 5-8): Weight loss is greater than 5% and other symptoms or conditions associated with cachexia are present
• Refractory Cachexia (score 9-12): This usually includes people who are no longer responding to cancer treatments, have a low-performance score, and have a life expectancy of less than 3 months

Grades

A study published in 2015 in the Journal of Clinical Oncology divided cancer cachexia into 5 grades. Researchers found that for each increase in grade, survival decreased significantly. Grades were as follows:

• Grade 0: No significant weight loss (a loss or gain of less than 2.4% of body weight), and a BMI of less than or equal to 25 kg/m2
• Grade 1: BMI of 20 to 25 and weight loss greater to or equal to 2.4%, or a BMI less than 28 with weight loss of 2.5% to 6%
• Grade 2: BMI of 20 to 28, with a weight loss of 2.5% to 6%, or a BMI less than or equal to 28 with a weight loss of 6% to 11%
• Grade 3: This includes people with a BMI less than 20 and weight loss of less than 6%, those with a BMI of 20 to 28 and a weight loss of 6% to 11%, a BMI of 22 to over 28 and weight loss of 11% to 15%, or a BMI less than 28 and weight loss more than 15%
• Grade 4: BMI less than 20 and weight stable or loss of 6% to 11%, a BMI of less than 22 and weight loss of 11% to 15%, or a BMI less than 28 and weight loss of over 15%

Treatment

The first step in treatment is to treat any physical symptoms or conditions that could lead to a decreased appetite or ability to eat. These include:

• Mouth sores
• Taste changes (especially with some chemotherapy drugs)
• Nausea and vomiting
• Constipation
• Pain
• Depression
• Gastroparesis

In many cases, simple changes in diet can reduce symptoms, such as eating with plastic utensils if you have "metal mouth" or choosing foods to manage gastroparesis.

An evaluation should also be done to rule out hyperthyroidism (thyroid conditions are common with cancer treatment), and conditions such as adrenal insufficiency or hypogonadism should also be considered.

Treating Cachexia

Treatment approaches to date have been fairly disappointing, and even with adequate calorie intake, it is difficult to reverse the process of cachexia.

At the current time, most researchers believe a combination of treatments (multimodality therapy) is essential. Treatment options include:

Diet

Contrary to what may seem obvious, replacing and supplementing calories in the diet has not made a big difference in the syndrome of cachexia. That said, it's very important to make sure that people coping with cancer (and similar conditions that cause cachexia) have a healthy diet. One important point to keep in mind is that if someone has not been eating much for a period of time, intake should be increased gradually. If calories are pushed too rapidly, a side effect called "overfeeding syndrome" may occur. When eating is not possible (or is limited) orally, a feeding tube may be recommended.

Nutrition counseling may be helpful in addressing any symptoms that lead to decreased intake and giving you ideas on foods to try that you may not have thought about.

Nutritional supplements such as ensure are often recommended, but should not be used as a substitute for meals. It's usually recommended that when used, these products should be consumed between meals.

Omega-3 Fatty Acids

It's ideal if nutrients can be obtained through food, but we know that's not always the case. Fish oil has been evaluated for its ability to treat cachexia with some studies (but not all) suggesting it may be helpful. In one study, adding a powder supplement of eicosapentaenoic acid (EPA), one of the main three omega-3 fatty acids that people get in their diets by eating fish, improved the levels of inflammatory markers that go along with cachexia. Supplements of EPA were also linked with shorter hospital stays and fewer infections and complications.

Amino Acid Supplements

Centers focused on recognizing and treating cachexia also often recommend amino acid supplements, particularly glutamine, L-Carnitine and L arginine, and these amino acids are being evaluated in combination with other therapies to assess their potential benefit.

Exercise

It may seem counterintuitive, but increasing activity (if possible) may help. An obvious benefit of exercise is increased appetite, but endurance training may go beyond eating habits to help slow the decline in muscle mass seen with cachexia. It's thought that exercise may reduce inflammation and also affect metabolism in muscles themselves.

Appetite Stimulants

Appetite stimulants have been used for treating cachexia, though their effects are unclear. These include:

• Corticosteroids such as prednisone and dexamethasaone, though significant side effects can occur
• Megace (megestrol): While Megace can result in weight gain, it hasn't thus far appeared to improve quality of life. Megace may also increase the risk of blood clots which are already common in people with cancer
• Medroxyprogesterone
• Testosterone

Anti-Inflammatory Medications

Anti-inflammatory medications such as Celebrex (celecoxib) have shown some promise, particularly if evidence of inflammation is present (for example, if C reactive protein is elevated). There is some evidence with head and neck cancer that these medications may improve prognosis.

Medical Marijuana

Thus far the evidence for the use of cannabis for cancer-related cachexia-anorexia is equivocal. Hopefully, with changes in regulations leading to a greater ability to study substances such as THC and CBD in clinical trials, the question of their efficacy will be answered.

Clinical Trials

A wide range of medications have been investigated to some degree for their potential role in addressing cachexia. Both selective androgen receptor modulators and medications that target the ghrelin receptor (ghrelin is the hunger hormone) are being studied. Drugs that target inflammatory compounds such as cytokines (cytokines contribute to muscle breakdown) are intriguing. The body produces cytokines to help kill cancer cells, but cytokines also tend to shift the body towards a state of catabolism (breakdown). Finally, as with many conditions, efforts to target gut bacteria deserves further study.

A Word From Verywell

As with so many issues regarding cancer, it's important to be your own advocate in your care. Studies tell us that cachexia in cancer is an unmet need, and that screening for and treatment approaches for cachexia vary widely around the country. If you are living with cancer, and especially if you have experienced a loss of appetite or any weight loss, talk to your healthcare provider about cachexia. While the intake of calories isn't the whole answer in preventing or treating cachexia, it does play a role. If you are struggling with your appetite, talking with an oncology nutritionist may help. If you have symptoms that are limiting your ability to eat, such as shortness of breath, difficulty swallowing, or more, talk to your healthcare provider. Sometimes working with a palliative care team can be invaluable in addressing the annoying symptoms related to cancer and cancer treatments, allowing people to live their best life possible with this disease.