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From the Townsend Letter
August / September 2016

Six Pillars of Integrative Oncology
by Dr. Sean Devlin
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Western medicine treats cancer primarily with surgery, radiation therapy, and chemotherapy. This time-honored approach is based on best clinical evidence and scientific research.
However, this model is sometimes referred to crassly as the "cut/burn/poison" approach. For many patients and clinicians, this may be a far cry from how they really would like to approach cancer.
In the field of integrative oncology, medical practitioners aim for more personalized care, and they tend to look beyond the tumor to the overall health of the individual in front of them. They have at their disposal a full spectrum of specialty testing and the use of modalities including  naturopathy, homeopathy, Chinese/Eastern medicine, Ayurvedic medicine, as well as allopathic medicine. It is a suite of therapies with options that can best fit our patient's individual needs and respect their autonomy.
The integrated paradigm of cancer therapy includes six pillars:
Pillar One: Surgery for Tissue Debulking and Gathering of Pathologic Information
Sometimes it is best to start by simply debulking the tumor – get it out with a knife, rather than trying to whittle it down over time with drugs or radiation. Also, patients with a strong genetic predisposition to developing cancer in a given system, organ, or gland are often strong candidates for surgery. What is retrieved in the operating room gives us the opportunity to look at the tissue for pathology, genetic identification, and tumor staging.
Staging helps guide therapeutic options and tends to shape prognosis. What you would do for a stage 2 tumor is often different from what you believe that you need to do for a stage 4 tumor. The American Joint Commission on Cancer has developed the accepted staging system used in both standard Western medicine as well as in the field of integrative oncology. We are looking for the size of the tumor and its grade, the number of lymph nodes that contain the disease, and whether the tumor has metastasized. So, when you are told what stage you have, what does that mean?

Stage I: small, early cancer; the goal is to pick these up with timely screening/preventative testing.
Stage II: locally advanced with no positive nodes.
Stage III: regionally advanced with positive nodes (starting to spread).
Stage IV: metastatic disease beyond regional lymph nodes.
After surgery, patients will be told what stage their cancer is in, plus a "margin clarity," another number that reflects how much of the tumor was able to be removed:
R0: complete margin negative resection (the best result).
R1: complete gross resection, microscopically positive margin.
R2: gross disease, macroscopic/visible tissue left behind.
Surgery outcomes vary depending on technique, competency of the surgeon, and stage of the disease. Sometimes, residual cancer cells are left behind that may not have been clearly evident prior to declaring a patient disease free. Unfortunately, this may occur more often than we think.
A tumor's microenvironment is complex. Sometimes after surgery, the area is like a wound that doesn't heal. It is bathed in growth factors and can create its own internal environment, one that is devoid of normal cell growth.
When cancer returns after a period of remission, it's considered a recurrence. Roughly 75% of recurrences occur within the first 2 years of surgery. In this scenario, approximately 1/3 of patients will have a local recurrence, meaning that the cancer comes back in about the same location. Another third will have local recurrence plus distant disease simultaneously, meaning that the cancer shows up in the old location, plus it has metastasized to a new location. And 1/3 will develop distant disease, or metastasis, alone.
As expectations, goals, and results may greatly vary, clear communication is a must. Clarify the goal of the surgical operation. Is it aimed at curing the disease? Debulking the tumor burden in an effort to increase the odds of subsequent chemotherapy? Is it palliative, aimed at decreasing symptoms? For example, with advanced stage colon cancer, a colectomy may be performed to prevent a painful bowel obstruction. Or perhaps to reduce risk or sudden death, such as an advanced stage tumor placing pressure on the spinal cord creating a risk of paralysis or respiratory failure. Or is the surgery preventative, with the goal of avoiding future tumor growth at that location such as in a preventative mastectomy?
In oncology, the use of the word cure can be misleading. Most savvy oncologists refer to the disease as progressive, stable, in partial remission, or in complete remission with NED (no evidence of disease). Cancer diagnoses need a lifetime of surveillance, and for many it can become a chronic but stable condition.
On occasion, the goal of surgery is not curative but to serve as an adjunct to other care.
Pillar Two: Targeted, Fractionated Chemotherapy Based on Cancer Cell Genetics
In Western medicine, the use of chemotherapy is usually applied in a one-size-fits-all and in a dose-intensive fashion. Healthy cells are exposed along with cancer cells. However, we do know how to target chemotherapy to cancer cells, largely bypassing healthy cells. The technique has been used safely for decades.
In integrative oncology, we use insulin as a biological response modifier to target the chemotherapy. Since the 1930s, it has been known that cancer cells are adapted to use much more glucose (sugar) than healthy cells. We can administer insulin to lower the amount of sugar circulating in the patient's bloodstream, which makes the cancer cells thirsty for any sugar that they can find. Then we administer glucose plus the chemotherapy drugs, and cancer cells drink in the chemo in an effort to grab the glucose. Think of it as the Trojan horse effect. This technique is called insulin potentiated therapy – potentiated means facilitated.
The use of insulin to target drug delivery also allows for the use of a fractionated, or much smaller amount of chemotherapy – perhaps 1/10 the dose used in conventional oncology. Since these drugs can have significant side effects, minimizing their use is a worthy goal.
By using chemotherapy in a fractionated form we can deliver it in a metronomic fashion, allowing for us to inhibit or block new blood vessel formation which could help tumors grow and spread.
It is a rational approach to chemo-therapy that is often combined with genetic testing to reveal which chemotherapy drugs may be effective with a particular tumor and more importantly which drugs may lack effect.
Pillar Three: Radiation and Hyperthermia
When it comes to radiation, many patients fear what they do not know! Due to experiences from years ago, some people conjure up visions of horrific burns and ravaged bodies. That is an antiquated idea. Radiation has come a long way. Advances in imaging and targeting techniques make for more precise and effective procedures which can prevent much of the collateral damage in surrounding normal tissue.
Radiation is either ionizing or nonionizing. Nonionizing radiation is lower-energy radiation like that used in cell phones and wireless networks. It is called nonionizing because it does not have enough energy to alter the chemical bonds that hold molecules together.
Ionizing radiation has enough energy to detach electrons from atoms or molecules – that is the process of ionization. The goal here is to damage the DNA of cancer cells so they will commit suicide, a process called apoptosis. A beam of radiation (photon, electron, proton, neutron, or ion, but usually gamma rays from the cobalt-60 isotope) is carefully directed toward the malignant cancer cells with the goal of ionizing atoms that make up the DNA chain. This kills the cancer cells and/or slows down their growth.
Radiation oncologists measure exposure time and radiation intensity, and pinpoint a defined field of treatment when creating a plan for the patient. Radiation treatments are usually given daily for a period of 4 to 6 weeks, with each treatment session just taking a few minutes.
Recent studies have demonstrated that radiation induces the upregulation of MHC Class I molecules on both tumor cells and antigen-presenting cells (APCs), and improves antigen presentation and may enhance tumor cell recognition by activated CD8+ T cells, which hence may infiltrate the tumor at an increased rate. In other words, radiation can help the body's immune system work in a stronger fashion.
Hyperthermia is another approach and is considered by some the "fourth leg" of cancer treatment. It was historically reserved for the most severe or recurrent cases of cancer. Local hyperthermia has shown to be effective when combined with chemotherapy or radiation therapy for cancers such as breast, cervical, prostate, head and neck, melanoma, soft-tissue sarcoma, and rectal cancer, among others. However, there is more evidence now to support its use as a primary treatment.
With hyperthermia therapy, body tissue is exposed to temperatures of about 107 °F or 42 °C. Hyperthermia may kill or weaken tumor cells, with limited effects on healthy cells. Tumor cells have a disorganized and compact vascular structure, so they have difficulty dissipating heat. Hyperthermia may therefore cause cancerous cells to undergo apoptosis in direct response to applied heat.
If the cancerous cells do not die outright, they may become more susceptible to radiation therapy because the heat dilates blood vessels to the tumor, increasing oxygenation of the tumor, thereby making radiation therapy more effective. Radiation therapy can also increase the efficacy of certain chemotherapy drugs.
Heat shock proteins (HSPs) are another target for hyperthermia. HSPs are actively involved in tumor activities such as cell proliferation, invasion, and metastases. These proteins have been reported to be significantly elevated in a plethora of human cancers and their overexpression has been robustly associated with therapeutic resistance and poor survival. Hyperthermia can force molecular changes and degradation of these proteins, not only allowing for chemo and radiation therapies to be more effective, but also helping stimulate an immune response to the cancer.
Pillar Four: Functional Medicine Support
It is often said that conventional Western medicine treats the tumor, not the patient. Functional medicine, on the other hand, treats the underlying causes of disease by looking at the whole person and all the forces at play.
The practice of functional medicine requires time be spent with patients listening to their histories and looking at the interplay between genetic, environmental, and lifestyle factors that can influence long-term health and complex, chronic disease. Tests can be run to reveal chronic infections, a weak heart, food allergies, adrenal fatigue, hormone imbalances – whatever issues could affect a cancer patient's ability to tolerate their cancer and treatment. Tests may even reveal to us how the cancer developed in the first place.
Functional medicine often makes use of essential nutrients, herbs, and medicines to improve a patient's detoxification and nervous systems. Many cancer patients experience a "wasting away" effect called cachexia and need aggressive nutritional care. They may need control of hormonal imbalance, cytokine cascades, and global inflammation. Functional medicine techniques also encourage lifestyle changes that can alter the overall environment that made conditions ripe for cancer in the first place.
The overarching goal here is to bring the body and mind back to balance and to support the various systems of the body.
Pillar Five: Immunotherapy
This is also referred to as immuno-oncology. With cancer, a weak immune system fails to do its normal job of identifying and destroying cancer cells. The goal of immunotherapy is to reengage the immune system, or at least some part of it. Immunotherapies fall into three main groups: cellular, antibody, and cytokine. They exploit the fact that cancer cells often have subtly different molecules on their surface that can be detected by parts of the immune system.
Cellular therapies are better known by the term cancer vaccines. The immune cells specific for the tumor can be removed from the mass and taken to the lab, where they are activated, cultured, and then returned to the patient to attack the cancer. Involved in this process are natural killer cells, lymphokine-activated killer cells, cytotoxic T cells, and dendritic cells.
Antibody therapies are currently the most effective and widely used. Several antibody agents have come to market and have FDA-approved uses in some lung cancers and advanced-stage melanomas. Monoclonal antibodies, such as Keytruda (pembrolizumab), Opdivo (nivolumab), and Yervoy (ipilimumab), have been in the news lately. All received accelerated approval from the FDA because their results were impressive, although not all cancer patients respond to the drugs. All three are what are called "checkpoint inhibitors," meaning that they target the means by which cancer cells turn off the normal immune system response that would destroy them. Former President Jimmy Carter thinks that the drug Keytruda played a significant role in his remission from advanced melanoma.
Cytokines are part of the chemical language of the immune system. They facilitate communication between cells to trigger the immune system's normal seek and destroy capabilities. Classic cytokines used to direct immune system responses include interleukin and interferon.
Usually, these are not stand-alone therapies; they are integrated with chemotherapy. Immunotherapy is a rapidly evolving field. There is much hope that these kinds of targeted therapies will better harness the body's natural healing powers. As many practitioners and patients know, if long-term success with cancer is to be achieved, it will be with an intact and educated immune system.
Pillar Six: Psychosocial-Spiritual-Lifestyle-Diet Support
A patient's spirituality and belief system make up the core of who they are. It is very important to both respect and value the role they play in a patient's life.
Cancer patients can be very fearful when they receive their diagnosis and they can also experience trauma while going through treatment. Psychological states should be evaluated and patients should be told about coping mechanisms. Healthy psychological habits such as journaling, meditation, and EFT (Emotional Freedom Techniques) can be encouraged.
Exercise and physical activity are important too. Exercise helps cancer survivors cope with and recover from treatment; exercise may extend survival. Current thinking suggests that cancer patients who don't exercise should be given referrals to physical therapists who can tailor a suitable conditioning program.
Dietary recommendations cannot be overlooked. Research suggests that patients who have stable blood sugars within normal ranges fare better than patients who are insulin resistant or who have poorly controlled diabetes. Looking at an organic/whole food diet that is very low in simple carbs and higher in lean proteins and healthful fats may prove useful and tolerable to most cancer patients. Some evidence also suggests that intermittent fasting may help preserve the immune systems of patients undergoing chemotherapy.
Common recommendations include:

  • no commercial feedlot meat, especially red meat or charred meats (BBQ or smoked meats);
  • no processed food; eat non-GMO and organic and fresh foods rather than commercially manufactured foods with unhealthful oils and preservatives;
  • no sugar or high-glycemic carbs (grains, pasta, bread, fruit juice, flavored yogurts, etc.);
  • inclusion of raw food in the diet.

A variety of supplements has been recommended to support cancer patients or treat them directly, including curcumin, vitamin D3, resveratrol, melatonin, modified citrus pectin, systemic enzymes, and green tea extract.
Off-label prescription drugs also have some indications for use in cancer patients. They include metformin, low-dose naltrexone, and Celebrex.
Final Thoughts
As practitioners we must always be aware that "it takes a village to treat a villager," and we must recruit the efforts of other experts to our patient's team so we can to provide the best care and options available. Practitioners must develop working relationships with their colleagues in integrative medicine/oncology, traditional oncology, surgical oncology, radiation oncology, and ancillary care services. Fostering teamwork with clear and concise communication will yield better patient satisfaction and outcomes.
As doctors, we need to keep our eyes on the medical and basic science literature. Reading more than just the abstract, we need to thoroughly review the data.
Patients should not be afraid to ask questions, especially if information doesn't make sense or doesn't resonate with them.
And everybody: Have an open mind, but not so much that your brain falls out!
The practice of integrative oncology is an evolving dance between patients, their health-care team, and an ever-expanding pool of data. The six pillars laid out here are designed to encourage both clinicians and patients to start learning those dance moves, by engaging in an open and honest dialog.
Dr. Sean T. Devlin
2001 Santa Monica Blvd., Suite 1190
Santa Monica, California 90404
424-744-8314; fax 424-204-0714

Sean Devlin, DO, MD(H), MSSean T. Devlin, DO, MD(H), MS, is a board-certified and fellowship-trained physician with an integrative oncology practice in Santa Monica, California. He also sees patients at his office in Grass Valley, California. Dr. Devlin is the medical education director and a consultant for the International Organization of Integrative Cancer Physicians (IOICP) and the Institute for Integrative and Functional Oncology (I2FO).

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