Does Sugar Feed Cancer?

The SIO Research Committee is pleased to offer this first installment in a new blog series known as “Myths of Cancer”. In this series we will address some of the most common myths and misperceptions that arise around cancer risk and treatment related to diet and natural health products, as well as other complementary therapies such as yoga, acupuncture and meditation. If you have a question you’d like us to address or comments about this post, please send your suggestions to: info@integrtiveonc.org

We hope you enjoy the series!
Linda Carlson and Eugene Ahn, Research Co-Chairs.

Co-written by Eugene Ahn, MD and Kristen Trukova, MS, RD, LDN, CNSC, CSO
© 2016 Rising Tide

Eugene Ahn, MD is the medical director of clinical research and medical oncologist at Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center (Midwestern), and Kristen Trukova, MS, RD, LDN, CNSC, CSO is a clinical oncology dietitian at CTCA® at Midwestern. They are both SIO members and have a passion for education and keeping their communities up to speed on the latest in scientific research. Disclaimer: The opinions expressed here are the authors’ own, and not necessarily those of the Society of Integrative Oncology or Cancer Treatment Centers of America. The SIO and CTCA supports open dialogue between health care practitioners and patients to make sure patients can make informed decisions. As always, your comments and feedback are welcome.

There are so many questions we get from patients in our clinics that are provocative but lack simple answers, and today we tackle one of the most common questions: “Does sugar feed cancer?” To condense the topic into a blog entry, we will not address specifically a ketogenic diet (low carbohydrate and protein, high fat, caloric restriction and fasting diet), but will save that for another blog, so stay tuned!

Quick Answer Box

It’s complicated. But one should feel comfortable taking in sugars through fruits and vegetables due to their higher nutritional value and content that goes with the sugars. Some cancers might become more resistant to treatment with high sugar intake, but the science of predicting which cancers would benefit from a low sugar diet is too early in its infancy to make any general recommendations.

Let’s take a closer look at the science behind this question with the goal of determining a reasonable dietary change to impact both cancer risk and potentially cancer outcomes. One of the best principles in discerning the truth of information available on the internet is being mindful of our desire to over-simplify the complex. Answers given on the internet on this topic tend to make two erroneous assumptions 1) all cancers have the same biology and sensitivity to manipulation of sugar intake, and 2) because diet or excessive sugar consumption may increase risk of cancer, sugar cessation is an adequate treatment for cancer alone.

First, the answer to the question “does sugar feed cancer?” is yes, but it’s important to recognize that all of the cells in our bodies use glucose (blood sugar) for energy. In fact, the brain can only use glucose for energy. Even in a diet that contains absolutely no sugars or carbohydrates, our bodies have processes to convert some of the calories we consume from protein and fat into blood sugar so your brain and other tissues can function (thank goodness).

However, there is scientific evidence that high sugar intake is at least indirectly responsible for increased cancer risk. For example, research has shown that diets excessive in sugary beverages increase the risk of many cancer types (www.aicr.org). These studies point to excessive caloric intake from sugar that promotes weight gain and obesity (a known risk factor for several cancers) and secondarily increases insulin and other growth hormones in the body (which as we will learn later, is one of the proposed mechanisms by which high sugar intake could worsen cancer outcomes). What we know sugar does not do is directly damage DNA or cause cancer, but the secondary effects of excessive sugar intake – obesity and increased insulin and insulin-like growth factors – might create an environment where cancer evolution is more likely to occur.

Given that several cancers express the insulin growth factor family of receptors on its surface, it is biochemically plausible that reducing sugar intake and thereby reducing insulin and insulin growth factor levels could help improve cancer outcomes in cancers that gain survival/growth benefits through that signaling pathway. However, this has not been proven yet in rigorous, well-designed randomized clinical trials. The best evidence we have to support this concept comes from animal models. To highlight one study among several, mice implanted with prostate cancer cells that became palpable were randomized to high carbohydrate, high fat meals or low carbohydrate, high fat meals. The investigators found that the mice fed high carbohydrate meals had statistically significant higher insulin and IGF-1 (Insulin Growth Factor-1) levels and body weight as well as nearly two times greater prostate cancer cell growth (Venkateswaran V, 2007).

Evidence is less strong for human studies, but in a retrospective study, investigators found that consumption of sugary beverages correlated to shorter survival with cancers of the upper aero

-digestive tract (Miles FL, 2016). Also, individuals with Laron syndrome (mutations in the growth hormone receptor that lead to severe congenital IGF-1 deficiency, with decreased insulin/IGF-1 signaling) have reduced cancer risk.

The next question you might be asking is, why are these studies focusing on insulin levels and IGF-1 levels and not blood glucose? First, the blood glucose of these mice would likely have been normal. Our bodies have an intricate biochemical system to make sure blood glucose levels stay within a tight range (when out of balance, diabetes ensues) and insulin is a key regulator of this. But the current paradigm of understanding the harmful effects of high glucose intake is rooted in the concept of secondary hyper-insulinemia required to cope with such a lifestyle and the effects insulin, IGF-1 can have on both cancer growth and resistance to conventional treatment such as chemotherapy or hormone therapy.

For the most current understanding of how insulin, IGF1 affect cellular function, see Figure 1.

Sugar figure 1

Djiogue et al 2013 “Insulin resistance and cancer: the role of insulin and IGFs” Endocr Relat Cancer Feb 1 2013 R1-R17

The main point of showing this figure is to demonstrate the futility of making general statements like “sugar feeds cancer”, “insulin feeds cancer” or even “IGF1 feeds cancer”. The figure shows that there are several receptors that can bind insulin or IGF1. How a cancer cell reacts to insulin or IGF1 depends on the context of which, if any, of those receptors lies on its surface. For example, insulin could just simply mediate sugar metabolism (through Insulin Receptor B), or it could deliver proliferation signals through an Insulin Receptor A, IGFR-1 or a hybrid of these two receptors, and speed up cancer growth or make the cancer cells more resistant to conventional cancer treatment. Lastly, if the cell does not have Insulin Receptor A or IGFR-1 on its surface, no effects might be seen.

A closer look at the clinical relevance of the IGF signaling pathways

To avoid confusion, sugar does not specifically drive increased IGF-1 production, but the secondarily increased insulin does suppress production of insulin growth factor binding proteins, which makes IGF-1 more available to both normal and cancer cells (M, 2012). Also, drugs that have been studied in human clinical trials that target and block the IGF1R receptor have been disappointing and benefit has mainly been seen in the subset of patients who have high circulating IGF1 levels. One of the common explanations given for the disappointing results is the degree of “cross-talk” and “redundancy” between the different receptors and signaling pathways, where blocking IGF1R only inhibits one route of several by which cells are given growth stimuli. Additionally, the recent published preclinical study has demonstrated that sucrose and fructose overconsumption in mice greatly accelerates the onset and progression of breast tumors in three different mouse or human breast tumor models through modulation of inflammatory pathways, independent of weight change or blood sugar (Jiang Y, Cancer Research, 2016).

So what should I do about sugars?

Although not reviewed here, there are many long-term benefits of reducing sugar intake such as weight control. Several studies have shown women who gain weight after breast cancer diagnosis trend towards worse cancer specific outcomes and clear improvement in all-cause mortality (Playdon MC, 2015). The best anyone can say with the current science is that limiting sugar intake for someone dealing with cancer diagnosis will improve overall health and weight, and reduce side effects of cancer treatment (sugar intake can worsen hot flashes from anti-hormonal treatment). It might also enhance the benefits of conventional treatment (surgery, chemotherapy and radiation) and reduce risk of future cancer diagnoses. And for a subset of the cancers diagnosed, there might be a benefit in reducing sugar intake and secondary insulin and IGF1 availability as well as reducing inflammation on actual cancer outcomes, but the data is limited to animal studies and specific cancer cell lines.

So if one were inclined, the 2015 Dietary Guidelines for Americans encourage a limit of only 10 percent of calories per day from added sugars. For the average person, this means only 200 calories (50gm) from added sugars out of 2000 calories total should be consumed. This is a tough order. For example, a 12oz. can of soda or a single serving size of your favorite sweetened yogurt likely contains up to 40 gm of added sugars. One teaspoon of sugar is equal to four grams of sugar. Thus, sugary beverages which include soda, fruit juices, sports drinks, energy drinks and specialty sweetened coffees should be consumed only occasionally. Are these guidelines effective enough to harness a potential anti-cancer effect? We do not know. But, if your baseline sugar intake is greater than 50gm/day currently, chances are your overall health will eventually be compromised.

But thinking further, what does this mean for brown sugar, raw sugar, honey, molasses, maple syrup and jam? Beyond sweeteners, what about foods that contain natural sugars, as in fruits and plain yogurt, as well as added sugars, which include just about everything you can think of from ketchup to bread? What about carbohydrates, like starches, fruits and milks, which are broken down into sugars? What is left to eat?

Keep in mind that a plant-based diet has been found to be cancer protective. Choosing whole grains, vegetables, beans and fruits in the right portion provides important phytochemicals, antioxidants, electrolytes and fiber in addition to the carbohydrates. One key to success is to avoid “empty calories” such as soda, refined grains and highly processed foods, where very little nutritional value is being provided outside of the calories. And take the time to read the sugar content on the food labels. Find the cereals and yogurts with the least sugar possible. Eat your fruit to get more fiber/pulp in lieu of juices. And be aware that too much portions of a healthy food can still make it unhealthy from a caloric standpoint.

Finally, malnutrition and severe weight loss, especially muscle weight, is very common during cancer treatment. Adequate nutrition is critical. It has been shown that weight loss and malnutrition during cancer treatment decreases tolerability of cancer therapy and is associated with worse outcomes (Barret M, 2011). Any dietary change that results in a lower caloric intake should be reviewed by your health care provider, and other foods might be required to meet nutritional needs. Making weight loss the only end point for your dietary and lifestyle choices could lead to harmful outcomes, so please seek guidance from an available dietitian.v

Are Soy Foods Safe for Breast Cancer Patients?

The SIO Research Committee is pleased to offer this second installment in a new blog series known as “Myths of Cancer”. In this series we will address some of the most common myths and misperceptions that arise around cancer risk and treatment related to diet and natural health products, as well as other complementary therapies such as yoga, acupuncture and meditation. If you have a question you’d like us to address or comments about this post, please send your suggestions to: info@integrativeonc.org.

We hope you enjoy the series!
Linda Carlson and Eugene Ahn, Research Co-Chairs.

Written by Omer Kucuk, MD

Omer Kucuk, MD is a Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine/Winship Cancer Institute. He is a veteran member of SIO and has a primary research focus on nutrition and cancer, conducting preclinical and clinical studies with soy isoflavones, lycopene and other nutritional and botanical compounds for over 20 years. Disclaimer: The opinions expressed here are the author’s own, and not necessarily those of the Society of Integrative Oncology or Emory University School of Medicine. The SIO supports open dialogue between health care practitioners and patients to make sure patients can make informed decisions. As always, your comments and feedback are welcome.

Many women with breast cancer have been told to avoid soy foods. This warning is based on the assumption that plant estrogens (phytoestrogens) found in soybeans could be harmful. The assumption is that soy food sources of estrogens might somehow “feed” cancer cells and act in opposition to anti-estrogen medications like tamoxifen, thereby increasing breast cancer risk.

Quick Answer Box

The safety and health benefits of soy foods are well established and it is probably safe for women with breast cancer to consume soy foods. However, greater caution is advised regarding use of soy derived isoflavone supplements such as genistein.

But what really happens when women eat these soy products? Biologically, the isoflavones in soybeans are phytoestrogen particles that bind to both estrogen receptors alpha and beta, but with a preference for the latter. Therefore, they are selective estrogen receptor modulators (SERMs), similar to tamoxifen and raloxifene, drugs used in breast cancer treatment and prevention. Therefore, rather than “feeding” cancer cells and acting in opposition to SERM medications and aromatase inhibitors, dietary intake of soy foods would be expected to reduce breast cancer risk by having antiestrogenic effects. In fact, breast cancer risk is lower in countries where soy consumption is high.

Recent research also supports the idea that soy consumption is not only safe, but can be beneficial. A recently published study (Zhang FF 2017) showed an inverse association between dietary soy intake and all-cause mortality in a cohort of 6235 women with breast cancer in North America. Women with the highest dietary isoflavone intake had a 21% decrease in all-cause mortality compared to women with the lowest intake. Another study (Nechuta SJ 2012) found that soy food consumption after a diagnosis of breast cancer was associated with improved treatment outcomes and lower recurrence rates. They found that higher post-diagnosis soy intake was associated with a 25% reduction in tumor recurrence.

Keeping this in mind, how should health care providers respond to women with breast cancer who ask whether it is safe to consume soy foods? We now have the answer: It is probably safe (Kucuk O 2017). The general message to patients with cancer should be: “Be physically active, have a normal body weight, consume a healthy diet (rich in vegetables and low in sugar), and reduce stress.” Soy foods can be consumed as part of a healthy diet and a healthy lifestyle.

We are also beginning to get the question “How much soy should I eat to obtain the most benefit?” because many women have become aware of the results of recently published studies. A large variety of soy foods are readily available in stores including soy milk, edamame, tofu, and others. For example, an 8-ounce glass of soy milk typically provides 25-30 mg of soy isoflavones. Therefore, it should be easy to consume sufficient amount of soy foods as part of a healthy diet. The results of recent studies in North America showed that even small quantities of soy foods (containing 1-2 mg soy isoflavones) could improve the outcome of breast cancer treatments (Zhang FF 2017, Nechuta SJ 2012).

In summary, the safety and health benefits of soy foods are well established and suggest it is reasonably safe for women with breast cancer to consume soy foods. However, the use of soy isoflavone supplements has not been evaluated well in human studies and precautionary findings have been published regarding a specific isoflavone genistein (aglycone of the main soybean isoflavone genistin) in breast cancer animal models (Hsieh CY 1998, Andrade JE 2014). Therefore, caution is advised regarding the intake of soy isoflavone supplements in women with breast cancer, and dietary consumption of soy-containing foods is preferred.

References:

1 Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly M, Buys SS, John EM. Dietary Isoflavone Intake and All-Cause Mortality in Breast Cancer Survivors: the Breast Cancer Family Registry. Cancer 123(11): 2070-2079, 2017

2 Nechuta SJ, Caan BJ, Chen WY, Lu W, Chen Z, Kwan ML, Flatt SW, Zheng Y, Zheng W, Pierce JP, Shu XO. Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women. Am J Clin Nutr 96(1):123-132, 2012

3 Kucuk O. Soy foods, isoflavones and breast cancer (Editorial). Cancer. 123(11):1901-1903, 2017

4 Hsieh CY, Santell RC, Haslam SZ, Helferich WG. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58(17):3833-8, 1998

5 Andrade JE, Ju YH, Baker C, Doerge DR, Helferich WG. Long-term exposure to dietary sources of genistein induces estrogen-independence in the human breast cancer (MCF-7) xenograft model. Mol Nut Food Res. 59:413-23, 2014

The SIO Research Committee is pleased to offer this third installment in a new blog series known as “Myths of Cancer”. In this series we will address some of the most common myths and misperceptions that arise around cancer risk and treatment related to diet and natural health products, as well as other complementary therapies such as yoga, acupuncture and meditation. If you have a question you’d like us to address or comments about this post, please send your suggestions to: info@integrativeonc.org.

We hope you enjoy the series!
Linda Carlson and Eugene Ahn, Research Co-Chairs.

The Role for Hypnosis in Cancer Care: Overcoming Misconceptions to Engage in Evidence-Based Care

By: Eugene Ahn, MD, Linda Carlson, PhD, and Lorenzo Cohen, PhD

Quick Answer Box

There is a solid evidence-base to support the use of hypnosis in reducing distress, anxiety, nausea, pain and other symptoms during invasive medical procedures and reducing medical costs. Yet misconceptions related to the practice of hypnosis have limited its integration into cancer care.

Earlier this year, the critically acclaimed film Get Out (99% on Rotten Tomatoes) amassed $175 million at the box office winning audiences over with its mix of dark humor, horror, and social commentary. One of the plot twists (SPOILER ALERT) involves a psychiatrist who uses hypnosis to “mind-control” her guests. By tapping her cup of tea, she can sedate her clients into submission. To those who practice hypnosis or have trained in it, this representation of hypnosis is inaccurate and frustrating, requiring suspension of disbelief because those who know hypnosis well are aware that we cannot make a client do something they do not want to do. Yet this is the misunderstanding and fear of loss of control that hypnosis carries today.

Before delving into the research on hypnosis in an oncology setting, let’s first clarify the definition of hypnosis. Hypnosis is the procedure by which a person enters an altered state of consciousness resulting in increased suggestibility. Another term for this state of consciousness is “trance” and it can be differentiated from other states of consciousness such as being awake, sleep, dream state, or relaxation by an electroencephalogram (EEG), the electrical measurement of brain waves.

Hypnosis is an old practice and is mentioned in Hindu texts as “temple sleep” and by Avicenna (980-1037 AD) who wrote in The Book of Healing about the distinction between sleep and hypnosis. Despite its long history, hypnosis has had memorable runs of being stigmatized. One of the historical lightning-rod figures of hypnosis was Franz Anton Mesmer (1734-1815) who theorized that the benefits of hypnotic suggestions he saw in his practice were due to “animal magnetism”. He was particularly well known for healing “hysterical conditions” or what we now refer to as psychosomatic illness. In fact, the less often used synonym for hypnosis (due to its association with magnetism), “mesmerism”, originates from his work.

But over the past 15 years, several research groups have examined the impact of hypnosis on multiple patient outcomes when undergoing various medical procedures, including surgery1-3. Hypnosis in these studies involved inducing surgical patients into a hypnotic state through deep breathing, guided imagery, and a focus on a floating sensation4. In a variety of surgical populations, patients induced into hypnotic relaxation during their procedure report significantly less anxiety and pain and request less analgesic medication than controls1,3. Additionally, patients are more cooperative with providers and spend less time in the procedure room5,6, which has resulted in reduced costs associated with medical procedures6,7 or, in the case of breast biopsy, neutral costs even with the addition of the extra staff member delivering the intervention8. These studies have also demonstrated beneficial physiological responses to self-hypnosis, including decreased heart rate, lower blood pressure, and reduced cortisol8,9. In addition to the above benefits, hypnosis has consistently been shown not to increase side effects or complications from medical procedures, whereas staff simply “being nice” or “empathic” as a control arm in several hypnosis studies actually increased side effects and complications.10

Most of the studies have either been conducted prior to invasive surgical procedures, like breast cancer surgery, where patients are under general anesthesia, or during less invasive procedures, where the patients are conscious such as breast biopsy or bone marrow biopsy in children. For example, Montgomery, et al.11 found in a mixed population of women either undergoing hypnosis during biopsy or before lumpectomy surgery that the hypnosis group reported significantly less pain intensity. Furthermore, the hypnosis group used significantly less propofol and lidocaine pain medications than the control group and reported significantly less fatigue, discomfort, nausea, pain unpleasantness, and were less emotionally upset than the control group after the surgery was completed.

Meta-analyses by Schnur et al.3 and Tefikow et al.12(26 randomized controlled trials (RCTs) with 2342 participants and 34 RCTs with 2597 participants, respectively) suggest that hypnosis results in medium to large effect sizes on reduction of symptoms during and/or after a surgical procedure. Schnur et al. also noted that the effects were larger when hypnosis was delivered before and during the medical procedures (as well as greater effect size for children) compared to just before the procedure. Tefikow et al.12 reported a medium effect size for emotional distress, pain unpleasantness, pain intensity and medication consumption, and smaller but significant effect sizes for recovery, procedure time, and physiological parameters, with enhanced effects when the hypnosis was done before and during the procedures.

Given that there is a large evidence-base showing that patients who received hypnosis in multiple clinical settings have decreased medical costs (or net-even) and reduction in numerous patient reported symptom outcomes, the next question is why are we not utilizing hypnosis more frequently for surgical or diagnostic procedures? One common answer is that we need larger randomized clinical trials or “it worked fine at Harvard, but it is different here”. However, this argument ignores the quantity of the existing data, is not aligned with the practice of evidence-based medicine, and ignores the approximately 40% of patients with cancer who experience significant distress, pain and unmanaged symptoms.

Less openly expressed issues are the taboos associated with hypnosis that Get Out exemplifies: primarily the loss of control over self-will. However, this is an unfortunate misconception and in the research studies cited above, hypnosis is provided as a scripted and standardized intervention. Patients at no point lose personal will and it is not possible to hypnotize someone without their consent. Providers of medical hypnosis are usually mental health or medical professionals who have undergone specific training in medical hypnosis from a reputable training organization such as the American Society of Clinical Hypnosis (http://www.asch.net/), and will hold a certificate to practice. Patients seeking medical hypnosis should verify that practitioners have received appropriate training. Lastly, it is important to note that previous studies on hypnosis generally exclude patients with significant psychiatric illnesses like schizophrenia and therefore we cannot make statements of safety in such patients.

In summary, with hypnosis we have a proven, underutilized, and safe modality to help improve the patient experience. If we espouse the practice of evidence-based medicine, then it is time to start using hypnosis alongside the standard of care to improve the patient experience during the numerous medical procedures happening daily within our medical system.

References

• Flory N, Salazar GM, Lang EV: Hypnosis for acute distress management during medical procedures. Int J Clin Exp Hypn 55:303-17, 2007
• Montgomery GH, David D, Winkel G, et al: The effectiveness of adjunctive hypnosis with surgical patients: a meta-analysis. Anesth Analg 94:1639-45, table of contents, 2002
• Schnur JB, Kafer I, Marcus C, et al: Hypnosis to manage distress related to medical procedures: A meta-analysis. Contemp Hypn 25:114-128, 2008
• Schupp CJ, Berbaum K, Berbaum M, et al: Pain and anxiety during interventional radiologic procedures: effect of patients’ state anxiety at baseline and modulation by nonpharmacologic analgesia adjuncts. J Vasc Interv Radiol 16:1585-92, 2005
• Lang EV, Benotsch EG, Fick LJ, et al: Adjunctive non-pharmacological analgesia for invasive medical procedures: a randomised trial. Lancet 355:1486-90, 2000
• Lang EV, Rosen MP: Cost analysis of adjunct hypnosis with sedation during outpatient interventional radiologic procedures. Radiology 222:375-82, 2002
• Lang EV, Ward C, Laser E: Effect of team training on patients’ ability to complete MRI examinations. Acad Radiol 17:18-23, 2010
• Lang EV, Berbaum KS, Faintuch S, et al: Adjunctive self-hypnotic relaxation for outpatient medical procedures: a prospective randomized trial with women undergoing large core breast biopsy. Pain 126:155-64, 2006
• Martin ML, Lennox PH, Buckley BT: Pain and anxiety: two problems, two solutions. J Vasc Interv Radiol 16:1581-4, 2005
• Lang EV, Berbaum KS, Pauker SG, et al: Beneficial effects of hypnosis and adverse effects of empathic attention during percutaneous tumor treatment: When being nice does not suffice. J Vasc Interv Radiol 19:897-905, 2010
• Montgomery GH, Bovbjerg DH, Schnur JB, et al: A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. J Natl Cancer Inst 99:1304-12, 2007
• Tefikow S, Barth J, Maichrowitz S, et al: Efficacy of hypnosis in adults undergoing surgery or medical procedures: a meta-analysis of randomized controlled trials. Clin Psychol Rev 33:623-36, 2013
• Berliere M, Lamerant S, Piette P, et al: Abstract P2-18-03: Potential benefits of hypnosis sedation on different modalities of breast cancer treatment. Cancer Research 75:P2-18-03, 2015
• Barabasz AF. Whither spontaneous hypnosis: a critical issue for practitioners and researchers. Am J Clin Hypn 48:91-7 2005
• Cheek DB: Importance of recognizing that surgical patients behave as though hypnotized. Am J Clin Hypn 4: 227-31 1962

The SIO Research Committee is pleased to offer this fourth installment in a new blog series known as “Myths of Cancer”. In this series we will address some of the most common myths and misperceptions that arise around cancer risk and treatment related to diet and natural health products, as well as other complementary therapies such as yoga, acupuncture and meditation. If you have a question you’d like us to address or comments about this post, please send your suggestions to: info@integrativeonc.org.

We hope you enjoy the series!
Linda Carlson and Eugene Ahn, Research Co-Chairs.

5 Common Myths About Cancer and Cancer Treatment that Could Harm You

By: Eugene Ahn, MD

Quick Answer Box

Sometimes we can hold on to our belief systems too tightly. Below, we discuss some myths about cancer that evidence suggests may negatively impact a patient’s chances of surviving a cancer diagnosis. We have intentionally excluded controversies that will be addressed in future blog entries.

A new diagnosis of localized cancer can be an emotional rollercoaster of ups and downs, dread and optimism, fear and empowerment. Added to this distress is the seemingly impossible task of gathering sufficient information to make the best evidence-informed decision regarding an optimal individualized treatment plan. It is only natural (with the lack of any editorial oversight on most information posted on the Internet), that someone could accidentally pick up some erroneous beliefs about cancer and cancer treatment and likewise miss out on important new research insights that would improve cancer treatment outcomes. In this blog, we discuss myths that already have sufficient research to show they are not only incorrect, but also may harm a patient’s chances for thriving after a cancer diagnosis. We interviewed surgical oncologists, medical oncologists and other cancer care providers to identify the most common harmful myths that they encounter in their practice. These myths are listed in order of least to most harmful.

5. After completing treatment aimed at curing cancer, the most important thing to do is to have lab and imaging tests to make sure the cancer does not come back

There are some cancers where lab tests and routine imaging are important for optimal outcomes, such as testicular cancer. But for other cancer types, we are clearly over-testing without any evidence that such practices improve outcomes. For example,in the case of breast cancer, some practitioners or patients will insist on obtaining tumor markers (blood tests for proteins that can be elevated if the cancer expresses it) despite the fact it is already established as an unreliable screening marker for breast cancer. The negative side-effects of using such tests can be huge. Imagine having an elevated cancer marker and the emotional turmoil that you would experience thinking you have a possible cancer recurrence, only to find out one year later after repeated images and tumor markers (and likely biopsies) that it is not the case. It would be more impactful to focus on primary prevention: i.e. promotion of lifestyle behaviors that would help prevent another cancer, and in some cases, reduce chances of cancer recurrence. This includes a healthier diet, more physical activity and mind-body practices, and continued secondary prevention (such as a screening mammogram, when appropriate).

4. If my doctor recommends that I see a psychiatrist or psychologist for additional consultation, they must think I’m crazy.

One of the biggest remaining stigmas about cancer care is no longer the word “cancer”, but anything that begins with the letters “psych”. In fact, that is precisely one of the reasons why supportive care clinics are not called “psychosocial care” or “psychological support”, but use terms like quality of life or survivorship clinic. But it is really an unfounded fear. People with emotional distress who receive care from a qualified mind-body support professional do significantly better in terms of both cancer-related quality of life and minimizing side effects from treatment. In fact, the ones who need mind-body support the most, often tend to be the very ones who refuse to acknowledge this as a missing essential component in their healing plan. Oncologists know that cancer treatment can be tough physically and emotionally, and their referrals to a mind-body expert are basically their way of saying there are better, more qualified specialists who can help you with the emotional rollercoaster ride that is cancer. Those that receive care from a mind-body specialist often emerge from cancer treatment with what is called “post traumatic growth” or in simpler words, a silver lining to their cancer experience. This “positive meaning” to their cancer experience has huge implications in terms of emotional well being after cancer treatment is completed.

3. It’s not cancer that kills people, it’s the cancer treatment.

While it is true that injury and even death can occur with conventional medicine and/or errors made by personnel within cancer centers, it is in the striking minority. A common narrative on alternative health websites is that when patients have metastatic cancer and receive chemotherapy, that it is the chemotherapy that ultimately kills the patient, not the cancer. This is an easy hypothesis to test. If that were true, then you would have data that consistently shows patients with cancer who die, had chemotherapy in their last month of life. In fact, when you track most cancer centers, you will find that very few patients who die from cancer, received chemotherapy in their last month of life. In a study that garnered a lot of press attention, researchers found that in England, on average 8.4% of patients with lung cancer and 2.4% of patients with breast cancer died within a month of receiving chemotherapy (Wallington et al, Lancet Oncology 2016). In fact, chemotherapy given within the last month of life is a measure by which insurance companies will measure the quality of care given at a cancer center (less treatment in the last month of life is encouraged). According to this myth, we should also be seeing scores of patients in hospice care or self-care rebounding miraculously when freed from the toxicity of chemotherapy, but unfortunately that is not reflected in the statistics. It is true that a surprising number (35%) of oncologists polled on whether they would take chemotherapy (this was before the approval of immunotherapy) if diagnosed with metastatic non-small cell lung cancer would not. However, it is erroneous to assume that this data meant those physicians believed chemotherapy would kill them. They were simply willing to acknowledge that if they were dying, they would rather focus on the time left to connect with family and get their affairs in order.

2. I can think my cancer away with positive thoughts

Probably the greatest misunderstanding regarding mind-body medicine is that you can treat cancer by simply focusing on positive thoughts or imagery. Clinical trials looking at positive visualization have been negative for overall survival with cancer, but they do help reduce anxiety and improve some measures of quality of life and may even impact immune and other biological processes. However, there is no evidence that positive thoughts result in cancer regression or cure. The idea that having negative thoughts will bring back your cancer is simply wrong and can be very psychologically harmful. In fact, one of the most powerful mind-body therapies, mindfulness meditation, emphasizes becoming a non-judgmental curious observer of ALL that is transpiring in our ‘mind’, being inclusive of both “good” or “bad” emotions and thoughts. By embracing and not fearing our negative emotions or thoughts we can then gain personal insight into what is the real cause of those phenomena, and often it is discovered that these are conditioned responses, related to past experiences but not necessarily probable outcomes in the present. The healthiest way to relate to emotions is to acknowledge, accept and experience them as they are, allowing them to come and go as they will with the recognition that all things are passing and impermanent, and not harmful.

1. I can’t do surgery on my cancer because “oxygen will feed the cancer” and make it more aggressive.

Perhaps as expected, mainly the surgeons interviewed for this blog entry reported encountering this myth, which would clearly make a patient reluctant to have their cancer surgically removed or biopsied. There are a lot of reasons why surgery might not be the best option for you (for example, it is already metastatic and spread), but when it comes to curative intent treatment of almost all solid organ cancers, surgical removal is usually the most impactful intervention to achieve cure. In fact, for pre-cancerous lesions like colonic polyps and DCIS of the breast, surgical removal alone is highly effective for prevention of evolution into malignancy and it is known that without surgery and just observation the risk of these becoming more aggressive in biology and clinical stage increases the longer you wait to remove those lesions. This belief system is more often found in African-American and Latino patients (Ann Int Med 2003), and correlates to delay or refusal of surgery. If this belief were true, however, we would expect to rarely see cases of metastatic breast cancer in patients who did not have a prior biopsy or surgery for breast cancer. Unfortunately, we know that as many as 6-10% of patients who are diagnosed with breast cancer present with metastases without a prior biopsy or breast surgery. In summary, there are much more influential factors one should be worried about (biology of the disease, genomic changes in the cancer, lifestyle choices) than being afraid of surgery.

The SIO Research Committee is pleased to offer this fifth installment in a new blog series known as “Myths of Cancer”. In this series we will address some of the most common myths and misperceptions that arise around cancer risk and treatment related to diet and natural health products, as well as other complementary therapies such as yoga, acupuncture and meditation. If you have a question you’d like us to address or comments about the this post, please send your suggestions to: info@integrativeonc.org.

We hope you enjoy the series!
Linda Carlson and Eugene Ahn, Research Committee

“Disclaimer: The opinions expressed in this blog series are the authors’ own, and not necessarily those of the Society of Integrative Oncology or the authors’ host institution(s)”

Does Cannabis Cure Cancer?

By Eugene Ahn, MD

Quick Answer Box

In cell cultures and animal models, cannabis-derived cannabinoids, particularly THC and cannabidiol, can have activity against some cancers (but paradoxically also accelerate the growth of others). But none of these studies provide evidence that cannabis can cure cancer (many drugs look great in cell cultures and animal models but fail in definitive clinical trials). There are two early phase clinical trials published, one of which suggests it is possible cannabinoids might help treat a very aggressive type of brain cancer with few side effects. But it is irresponsible and harmful to say cannabis cures all types of cancer. Research also shows alternative medicine use may delay conventional treatment, resulting in worse cancer-specific outcomes. However, given its proven benefits helping treat cancer side effects such as loss of appetite, neuropathic pain, and nausea, it is reasonable to use as an integrative treatment for those indications, but not in lieu of conventional therapy, especially in curative intent situations.

I wish cannabis cured all cancers. I wish wishful thinking would make it true. As oncology health professionals, we are joyful when our patients are joyfully in remission, and we suffer when we see our patients suffer. If there is one thing we professionals have in common, it is that we welcome better cure probabilities and less side effects for our patients.

Over the past 18 years after having trained in both infectious diseases and oncology, I have taken care of many conditions that respond extremely well to cannabis or its psychoactive ingredient delta-9-tetrahydrocannibinol (THC), such as AIDS-related cachexia, chronic pain, nausea and loss of appetite from cancer or chemotherapy. I have also published case reports of extraordinary outcomes when they highlighted potential activity of an underappreciated intervention (for example, a case of Xeloda and graviola tea associated with a 5-year remission in a patient with metastatic breast cancer). I have a lot of patients who have utilized cannabis or its isolates in the hope it would cure their metastatic disease and assured them I would publish their case if they were successful. But I have yet to personally see a patient whose metastatic cancer went into miraculous remission with cannabis or cannabis products alone, although for most their quality of life was enhanced.

Dr. Donald Abrams, one of the earliest pioneers of cannabis research in supportive care, Professor of Clinical Medicine at University of California San Francisco and general oncologist at Zuckerberg San Francisco General Hospital, shared his clinical experience with medical cannabis in the state that first legalized it in 1996:

“As an oncologist in San Francisco for the past thirty-three years, I often say that I would venture to guess that the majority of the patients I have cared for have used cannabis during their treatment. Thus if cannabis cured cancer, I would have a lot more survivors. Granted, the plasma concentration of inhaled cannabis, as most of my patients have likely used in the past probably does not approach that which can be achieved with the highly concentrated oil preparations (no data available on this as of yet), but still, oncologists maintain that the plural of anecdote is not evidence! What saddens and disturbs me the most is when I see a patient in consultation with a potentially curable malignancy who is foregoing conventional cancer therapy in hopes that cannabis oil will be a kinder, gentler treatment. The fact remains that there is no evidence at this time to support such a decision.”

Dr. Abrams concludes, “That being said, what we do know is that cannabis is truly an amazing medicine for many cancer and treatment-related side effects — nausea, vomiting, loss of appetite, pain, depression, anxiety, insomnia.”

Dr. Abrams will be summarizing the scientific evidence of the benefits of cannabis and its isolates in an SIO webinar on Sept 13, 2018 in a way that only he can, having been on the leading edge of cannabis research in both HIV and cancer care. Not only will you learn about the science of cannabis, but also the sociopolitical challenges he navigated to research the plant’s benefits. I highly recommend signing up for this talk (link below) and it is free for SIO members and only $20 to register for non-members.

https://integrativeonc.org/news/sio-news/275-sio-webinar-september-13-12-30-1-30-pm-et

While cannabis is not a magic bullet for cancer, there is preclinical evidence in animal models and cell lines (cancer cells grown in petri dishes in the lab) to suggest cannabis might have an anti-cancer effect in humans. However, bear in mind that most drugs that perform similarly well in preclinical models turn out to not even shrink cancer or help people live longer when they are tested in definitive human trials.

To make sure the terminology in this blog is understood, allow me to run through a quick cannabis 101 review. The cannabis plant consists of primarily two species – C. sativa and C. indica – that contain more than 400 identified chemicals. For the sake of accuracy and relative simplicity, the relevant categories of its components are as follows:

Cannabinoids                                Non-Cannabinoids
THC                                                 Terpenoids

Cannabidiol (CBD)                       Flavonoids

And over 100 others

Cannabinoids are defined as chemical compounds that interact with the cannabinoid receptors, which in humans include CB1, predominantly expressed on neurons in the brain and central nervous system, and CB2 expressed in non-neuronal tissues such as immune cells. Cancer cells can express these receptors as well, and studies are mixed as to whether it can indicate a better or worse prognosis compared to cells that do not have the receptors. But the effects of cannabinoids on cancer are not limited to interaction with these receptors as several studies have documented effects that are not prevented by blocking these receptors. THC is the cannabinoid classically associated with the psychoactive and appetite-stimulating effects, although it is not exclusively so. Cannabidiol is another cannabinoid that also has been studied for anti-cancer effects and is often referred to as CBD.

The FDA has approved several drugs that we will call cannabinoid-based (i.e. they are not naturally derived but synthetic): dronabinol (Marinol and Syndros, delta-9-THC), and nabilone (Cesamet, THC-similar). As of June 25, 2018, the FDA approved Epidiolex (cannabidiol naturally derived from cannabis) for two rare and severe forms of epilepsy, marking the first time a non-synthetic cannabinoid has been approved in the United States. However, the first regulatory approval for a naturally-derived cannabis product in North America was given by Health Canada for nabiximols (Sativex) for symptomatic relief of neuropathic pain (2005) and muscle spasticity (2010) from multiple sclerosis. Nabiximols is a formulated extract of C. sativa with a THC:CBD ratio of 1:1 as well as other cannabinoid and non-cannabinoid components.

Terpenoids and flavonoids are responsible for the color and aroma of plants and also serve biological functions. Relative to cannabinoids, these two categories of chemicals are not as well researched for their effects on cancer and will be omitted for brevity except when we discuss the entourage effect at the end of this blog.

Regarding anecdotal evidence (and yes, I count anecdotal evidence as evidence, just not of very high quality if it is not reliably reproduced in others) for anti-cancer effects of cannabis, the case that is most often brought up by my patients is that of Rick Simpson. From the information that is available on the internet, Rick was diagnosed with several basal cell carcinomas of the skin (not metastatic) and based on preclinical studies decided to treat his skin cancer topically with a concentrated cannabis oil and left a bandage on the lesions for several days. The lesions disappeared. I acknowledge this is a pretty impressive result but we still don’t know if that was a placebo effect (keep in mind it is also well known duct tape can cure warts but no more so than placebo), correlation not causation (did he or those who have followed suit receive any other intervention?), and even if the oil really was the cause of the remission at best we can say the oil might be worthy of research in the treatment of basal cell carcinomas.

But to extrapolate from this case (and the preclinical evidence) that cannabis oil is a suppressed cure for all types and stages of cancer is, at best, an innocent inference (educated guess) and, at worst, a delusion that has gone viral on the internet and is endangering the lives of patients with curable cancer who might choose to take cannabis oil in lieu of conventional therapy without any scientific follow up with imaging or surgery. However, Rick Simpson’s case report does warrant further research, especially after cell line and animal model research suggests that skin cancers can have inhibited angiogenesis (blood vessel growth) mediated by CB1 and CB2 receptors (Casanova et al).

To date, we only have two prospective clinical trials where a cannabis preparation or its derivatives was tested for an anti-cancer effect. Guzman et al conducted a phase I (preliminary trial to establish safety of the new intervention) and showed that intracranial administration of THC into an aggressive brain cancer called glioblastoma multiforme had antiproliferative effects in some of the 9 patients who received it, but all patients eventually progressed and died (though not due to the THC).

The second study (Twelves et al) is to date only published as an abstract, not a full paper (which means it hasn’t passed the gold standard of rigorous peer review). In this randomized, double blinded placebo-controlled study (meaning the investigators and patients were blinded as to whether they were getting the real cannabinoid preparation or placebo, which is generally considered the best way to minimize bias/confounding factors) patients with recurrent glioblastoma multiforme received either temozolomide (Temodar) chemotherapy and placebo or temozolomide with a 1:1 THC:CBD oro-mucosal spray, nabiximols (Sativex). Only 20 patients were intended to be enrolled in the randomized part of the study. Safety not tumor response was the primary objective, so these results are not reliable to make any definitive conclusions. Also requiring caution is that the study randomized 12 to THC:CBD and only 9 to placebo without any explanation of the discrepancy between study arms. In a small study like this, one patient can radically change the significance of the results. Median survival in the placebo group was 369 days and >550 days for the THC:CBD group and 1-year survival (meaning odds of being alive 1 year after entering the study) were 56% and 83%, respectively. The combination of nabiximols with temozolomide appears to be safe, but a larger phase II study is indicated.

Another hypothesis that has received a lot of attention is that cannabis has benefits on cancer that is maximized by an ‘entourage effect’, meaning that all the individual components of the plant work together to create an effect that’s greater than the effect of any one component. Blasco-Benito et al published in 2018 a study that compared the antitumor effects of THC alone compared to a whole plant extract and found that the extract was more potent than THC in cell culture and animal models of ER+, HER+ and triple negative breast cancer. Likewise, the extract was synergistic with tamoxifen, lapatinib and cisplatin chemotherapy in those respective cancer types. The authors also identified that the enhanced potency of the extract did not appear to be due to the 5 most abundant terpenes in the extract, consistent with the theory that the potency was due to the cannabinoid content. Does this study mean all patients with breast cancer should be taking cannabis extracts? Hardly. Remember that most drugs that have great looking data in cell cultures and animal models do not pass the bar of human clinical trials, with only 10% ultimately getting approved, with over 50% of the failed cases due to lack of efficacy (Hay et al). That said, this study and additional ones provide reassuring data for patients with cancer who choose to integrate cannabis with their conventional treatment to reduce side effects from cancer treatment. For example, numerous preclinical studies have tested whether there would be antagonism or synergy combining cannabinoids with chemotherapy agents. Briefly, in studies on cell cultures of pancreatic, glioma, gastric, lung and colon cancers using gemcitabine, temozolomide, paclitaxel and 5 fluorouracil, synergy is the common theme (reviewed by Maida et al).

However, not all cannabinoid research points to harmlessness as some cancer cells grow faster with exposure and there could be immunosuppressive effects to reckon with as well. When cannabinoids interact with the CB2 receptor, which if you remember is mainly expressed on immune cells, interferon gamma production is inhibited, T-cell proliferation is suppressed, and the immune system shifts from a Th1 to a Th2 profile, which is generally believed to be less conducive to an effective anti-cancer immune response. The relevant studies are reviewed well by other authors (Sledzinski et al).

Until we have evidence of how these findings would interact with any type of immunotherapy (i.e. PD1/PDL1 inhibitors like nivolumab) intervention, discernment in the use of cannabis is recommended. In fact, Taha et al conducted a retrospective observational study and reviewed the charts of 140 patients with advanced melanoma, non-small cell lung cancer and renal cell carcinoma who received nivolumab. 89 patients received nivolumab and 51 patients received cannabis with nivolumab. The authors found that the only significant factor that lowered the response rate to immunotherapy was cannabis (37.5% for nivolumab, 15.9% who received both (odds ratio 3.13; 95% CI 1.24-8.13, p=0.02). However, progression-free survival and overall survival was not effected by cannabis. Since this is a retrospective study and subject to numerous confounding factors, it is mainly a precautionary study that warrants additional research before making any definitive conclusions.

In conclusion, we know more than ever through scientific research what cannabis and its cannabinoid compounds can do, and with more research it is possible we might be able to establish therapeutic indications for cannabinoids for certain types of cancer. Please attend the upcoming webinar by Dr. Donald Abrams to see in more depth the clinical research that has helped de-stigmatize cannabis by documenting its benefits in improving the quality of life of patients dealing with cancer and cancer treatment-related symptoms. You will at least walk away with a greater appreciation for the role of research in helping individuals make more informed decisions for their health. If you read this blog too late or are unable to attend, Dr. Abrams has published several excellent articles that are listed at the end of the references below. As legalization of medical marijuana shifts across North America, more research will continue to reveal how we can best utilize cannabis or its isolates/derivatives for medical purposes, and likewise assure a future of less treatment side effects, better quality of life, and better cure probabilities.

References

1. Abrams DI. Cannabis and cancer – decoding the connection. San Fran Med 89(5): 28-29 2016
2. Guindon J and Hohmann AG. The endocannabinoid system and cancer: therapeutic implication. Br J Pharm 163: 1447-63 2011
3. Casanova ML, Blazquez C, Martinez-Palacio J et al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest 111(1):43-50 2003
4. Guzman M, Duarte MJ, Blazquez C et al. A pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer 95:197-203 2006
5. Twelves C, Short S, Wright S et al. A two-part safety and exploratory efficacy randomized double-blind placebo-controlled study of a 1:1 ratio of the cannabinoids cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) plus dose-intense temozolomide in patients with recurrent glioblastoma multiforme (GB). J Clin Onc 35: 2046 (abstract) 2017
6. Blasco-Benito S, Seijo-Vila M, Caro-Villalobos M, et al. Appraising the ‘entourage effect’: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer. Biochem Pharm published online 6/27/18
7. Hay M, Thomas DW, Craighead JL et al. Clinical development success rates for investigational drugs. Nature Biotechnology 32:40-51 2014)
8. Taha T, Talhamy S, Wollner M, et al. The effect of cannabis use on tumor response to nivolumab in patients with advanced malignancies. Oral presentation at: ESMO 2017 Congress; Abstract 1545PD 2017
9. Maida V, Daeninck PJ. A user’s guide to cannabinoid therapies in oncology. Curr Onc 23(6): 398-406 2016
10. Sledzinski P, Zyeland J, Slomski R et al. The current state and future perspectives of cannabinoids in cancer biology. Cancer Med 7(3): 765-75 2018
11. Abrams DI. Using medical cannabis in an oncology practice. Onc J 1-4 2016
12. Abrams DI. Integrating cannabis into cancer care. Curr oncol 23(S2):S8-14 2016
13. Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharm Ther published online 2015