Marc S. Micozzi, MD, PhD, Editor of Fundamentals of Complementary & Alternative Medicine, 5th ed. (2015), Elsevier Health Sciences, 759 pp; Editor of Complementary and Integrative Medicine in Cancer and Prevention: Foundations and Evidence-Based Interventions (2007), New York: Springer, 478 pp. www.drmicozzi.com

Q: Many, even millions, of Americans are living with advanced cancer. You are the author of the definitive text “Fundamentals of Complementary and Alternative Medicine,” now in its 5th edition. What forms of complementary and alternative medicine might be most useful for patients with advanced cancer?
A: In cancer treatment trials, both treatment and control groups receive treatment. Likewise, standard oncological treatments are not directly compared to various complementary/alternative (CAM) therapies. Rather CAM treatments are added, or not, to the standard oncological protocol. Thus, in research conducted, they are truly “complementary” as adjuncts to cancer treatment. Some trials on commonly occurring cancers have allowed observations of improvements in both survival times and quality of life in patients with advanced cancer. The most direct analogies to mainstream cancer treatments for research trials are dietary supplements (vitamin and mineral micronutrients, and botanicals) since they can be administered the same way as drug treatments.
Vitamin D shows strong clinical evidence of anti-cancer activity. In a recent study by Garland et al, people in the highest quantile of serum vitamin D had 17% less risk of developing advanced lung cancer compared with the lowest quantile. Men with blood serum vitamin D levels less than 30 ng/ml had 2.6 times greater likelihood of having an advanced form prostate cancer at time of diagnosis. People with lower vitamin D were four times more likely to develop aggressive melanoma. Women with malignant melanoma took in only 311 IU Vitamin D per day, about half the RDA of 600 IU/day. (Garland recommends 4000 IU daily; very few foods contain Vitamin D). In several clinical trials, women with advanced breast cancer administered Vitamin D dietary supplements showed significant improvements in quality of life and prolongation of survival time.
For Vitamin C, a key observation is that intravenous infusions are necessary to achieve the higher, steady state blood levels observed to benefit cancer patients. Clinical data suggest that high-dose Vitamin C infusions improve survival in advanced cancer patients. A study on IV vitamin C for cancer, conducted in 2012, focused on the inflammatory component of cancer. When cancer tumors are growing, there’s typically an inflammatory response in the local area. Elevated inflammation can worsen prognosis and shorten survival times in many forms of cancer. The researchers treated 45 patients with lymphoma or prostate, breast, bladder, pancreatic, lung, thyroid, or skin cancers with high-dose, IV vitamin C. In three-quarters of the patients, vitamin C treatment resulted in decreased levels of tumor markers which suggests that, over the long term, treatment with IV vitamin C would improve prognosis and survival rates in cancer patients. The study also tells us that it is probably impossible to achieve blood levels of vitamin C high enough to treat cancer by taking oral supplements.
Some cancer treatment studies had been conducted with Vitamin A (and analogue carotenoids and retinoids), which were limited by toxicity. Preliminary clinical studies suggest that micronutrients in combination are more effective than single ingredients.
A few botanical remedies, appropriate to consider this holiday season, include Boswellia, commonly known as Frankincense. It appears to distinguish cancer from normal cells, which could be helpful in targeting treatments, and avoiding toxicity of chemotherapy in advanced cancer. One study showed that frankincense could reduce the effective dose needed for cancer chemotherapy drugs. Its has been clinically demonstrated to reduce chronic inflammation, a sign of increased aggressiveness in advanced cancers. In a recent clinical trial, frankincense significantly reduced brain swelling in patients with advanced glioblastoma.
Mistletoe, or Iscador ®, is administered only by direct injection into or near the tumor site in advanced cancer patients. It is currently practiced in Germany and Switzerland, where over 80,000 patients have been treated over the past century. The evergreen tree, Pacific yew, from which the drug Taxol was derived, is used clinically for its activity against advanced breast and ovarian cancers.
Various mind-body therapies, such as biofeedback, hypnosis, mindfulness, meditation and yoga, have improved survival (through effects on cancer progression, primarily mediated by immune system), and quality of life (primarily through reduction of anxiety, depression, pain and stress, and side effects of chemotherapy), in advanced breast, prostate, and other cancers in multiple trials.
Clinical practice has yet to establish standard cancer treatment protocols routinely incorporating natural remedies, but available evidence suggests the value in CAM for advanced cancer. As Dr. George Lundberg says: what works is not ‘alternative,’ or ‘complementary;’ what works is just good medicine.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Helen Sadik, PhD, Scientific Knowledge Engineer, CollabRx

Q: Computers and artificial intelligence show both great progress and great promise in many fields. Can “Big Data”, A.I., and the Watson ilk devise a way to end cancer?
A: In 2011, a young and emotionless Watson grabbed the tech industry’s attention by dominating Jeopardy’s two greatest champions. That night, the show was not at all about the $1 million prize. Instead all eyes were on the one-of-a kind contestant: Watson, IBM’s supercomputer. Watson had just proved that intelligent machines can understand, process, and respond to questions posed in human language.
A few years later, artificial intelligence (AI) exploded into many information-intensive industries with its market expected to reach $47 billion by 2020. But young Watson had one main career in mind since its inception: healthcare. It entered medical school in 2011 and graduated in 2 years.
So how can AI change the oncology field? According to a paper published by Michael Schatz in the journal PLoS Biology, genomic data is likely to generate the most raw data in the next ten years–data which holds answers to many health questions. While understanding and finding patterns in this enormous amount of data might seem impossible for the human brain, cognitive computing capable of ingesting data that analyzes and self-learns without forgetting might hold the key to uncovering the answers.
AI can therefore revolutionize oncology care, save doctors time, and save patients’ lives. Because supercomputers store millions of oncological records which they can rapidly analyze and cross-reference, their deep learning ability has the potential to:

• understand the genetic profile of a patient and offer evidence-based, personalized treatment options
• provide accurate interpretation of medical images, faster diagnosis, and appropriate treatment options
• treat rare cancers
• advance resistance research
• improve and accelerate new drug discovery
• optimize patient identification and clinical trial matching
• assist in health management and remote patient monitoring
• democratize access to healthcare, and expand knowledge from one specialist to any doctor

It is important to emphasize that the success of AI and deep learning relies heavily on the existence of a large, accurate training dataset, which in turn, relies on human input and effort. Therefore strong collaboration and data sharing between supercomputer developers and healthcare systems are essential. Not surprisingly, for instance, IBM Watson Health is partnering with more than a dozen leading cancer institutes to develop Watson for Genomics.
As the excitement of using AI in healthcare grows, the concerns about AI will grow as well. These concerns display a general lack of trust in machines and include patient record privacy and confidentiality, effective analysis of precarious studies, and the potential for human replacement. The latter fear is augmented by warning from experts such as Stephen Hawking who caution that AI could evolve faster than the human race, and that “…success in creating AI would be the biggest event in human history. Unfortunately, it might also be the last.”
Although this point is beyond the scope of this article, it is worth mentioning that caring for a patient involves more than just finding a diagnosis and administering a cure. It is about evolving continuous relationships between the patient, the doctor and the health care team. Even if Watson and similar robots are starting to learn to act more human by analyzing emotions, tone, and personality, machines won’t be able to replace meaningful relationships between patients and practitioners because AI still lack real human feelings and morals.
Back to the main question: Can AI devise a way to end cancer?
AI is still in its infancy. Its biggest promise is to amplify human ability and augment their intelligence. It has the potential to become the doctor’s closest advisor, providing better and faster diagnostic and treatment tools to improve patient care and quality of life. But will it find an end to cancer? Only the future can tell. The hope is that it will speed up discovery and put us closer to the finish line.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Michael L. Millenson, President of Health Quality Advisors LLC and an Adjunct Associate Professor of Medicine at Northwestern’s Feinberg School of Medicine

Q: Donald Trump’s campaign for the presidency included a promise to repeal “Obamacare” in its entirety. If he succeeds in fulfilling that promise, what impact can we expect on American cancer prevention and cancer treatment?

A: Donald Trump, emboldened by eliminating ISIS, ending illegal immigration and energizing the economy, will eradicate cancer. Or at the very least, I predict, he will append it to his list of promised achievements as president.
Our current chief executive, dubbed “No Drama Obama” by his staff during the 2008 campaign, couldn’t resist the heady promise of a cancer “moonshot.” Trump, who’s declared, “I will take care of ISIS,” “close up those borders” and “jump-start America,” will likely rev up the rhetoric back to Nixonian “War on Cancer” levels.
A candidate whose campaign centered on his personal pledge to “make America great again” will surely be galvanized by the chance to make cancer care “great,” too.
The current Cancer Moonshot initiative, featured in President Barack Obama’s last State of the Union Address, is codified in a presidential memorandum of Jan. 28, 2016 and placed within the Office of the Vice President. While fighting cancer was of deep personal interest to Vice President Joe Biden, Vice President-elect Mike Pence was governor of Indiana, where pharmaceutical giant Eli Lilly has a major portfolio of oncology products. Coincidentally, Lilly in October introduced a new version of its PACE Continuous Innovation Indicator (CII), a customizable, online tool to review progress against cancer in order to inform public policy and accelerate innovation.
The current executive director of the Cancer Moonshot initiative, Greg Simon, was an aide to former Vice President Al Gore. But Simon is also a cancer survivor and entrepreneur who once worked for New York City-based Pfizer. He came to his current post from FasterCures, a foundation whose work has strong support among Congressional Republicans.
Whether enthusiasm for anti-cancer combat entails increased funding remains to be seen. However, a Trump administration may downplay cancer prevention. Recent research among a population of mostly white Americans aged 25 to 79 found that lifestyle changes related to smoking, drinking, diet and physical activity can reduce the risk of dying from cancer by 14 to 61 percent. Given the central role played in Trump’s electoral triumph by a working class population more prone to those behaviors, I wouldn’t expect a lot of new government nagging.
And while the Centers for Disease Control and Prevention has recommended that pre-teens be vaccinated against the HPV virus, linked to a series of cancers transmitted through sexual activity, I wouldn’t expect this to be an area where President Trump speaks out publicly, either.
Some current cancer patients are reportedly “frantic and scared” that Trump’s vow to ax Obamacare (a/k/a the Affordable Care Act) will sweep away its ban on lifetime dollar limits on coverage and its protection against denying coverage to those with pre-existing conditions. Trump has said he plans to keep both those prohibitions, but those who are sick remain worried. If the provisions are repealed, said a 32-year-old mom with breast cancer, “I can’t afford treatment and I die.”
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Vivek Subbiah, MD, Assistant Professor, Department of Investigational Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Q: You have exhausted surgical, radiation, and standard chemotherapy options for a patient with an advanced epithelial malignancy. Yet the patient has a strong will to live and to advance science during palliative care.  No active clinical trial is available. How would you evaluate pre-clinical data to try to identify an investigational drug for “expanded-compassionate” use?

A: Thank you for the question. This is a challenging situation. It is subjective and complex.
My answer – “it depends”. Let me give you 2 scenarios.
Scenario A: A 30-year-old surgeon, recently married with the love of his life who has just graduated from a neurosurgery residency, is expecting his first child and diagnosed with Stage IV non-small cell lung cancer. Has exhausted radiation, surgery, and standard chemotherapy. Has a strong will to live.
Scenario B: An 85-year-old man, who has a wife in the nursing home and a son in California and another son in Australia has been diagnosed with Stage IV non-small lung cancer. Has exhausted radiation, surgery, and standard chemotherapy. He lives alone and has a declining PS with multiple co-morbid conditions.
In the first case, yes, as an experimental investigator I would go to any lengths to try to provide investigational drug for expanded-compassionate use.
In the second case, I would likely arrange a family meeting to discuss the reality and lean towards providing best supportive palliative care.
Breakthroughs in oncology or any other field infers that successful outcome in the face of what was considered impossible. We all live in the future. If we do not take risky experiments, breakthroughs cannot be made. It could be argued that there is a 1 in 100 chance that the investigational agent for expanded compassionate use works. I would say that the chance is ONE and not zero. For his mother, father, wife and future child it is HOPE. It is with this hope that we live in.
How do I evaluate the pre-clinical and/ or clinical data for justifying compassionate use?
I refer you to the webpage of Personalized Cancer Therapy at MD Anderson. Here there are quite a few resources to define actionability of a gene. I am highlighting the main aspects from that site as below:
Actionable Gene: A gene is deemed actionable if 1) there are clinically available drugs that directly or indirectly target tumors with genomic alterations in the gene of interest with minimally preclinical evidence of their use in tumors with alterations in the gene of interest, and/or 2) there are clinical trials specifically selecting for patients with tumors harboring genomic alterations in the gene of interest.
Actionable Variant: A variant is deemed actionable if all of the following criteria are met: 1) the variant occurs in a gene deemed actionable, 2) the alteration type (mutations, amplification, etc) for that gene is deemed actionable, and 3) there is either published literature or data from the MD Anderson Zayed al Nahyan Institute for Personalized Cancer Therapy (IPCT) functional genomics platform that the alteration is likely to be tumor promoting (e.g. activating mutation in an oncogene or inactivating mutation in a tumor suppressor), or there is evidence that the variant confers sensitivity or resistance to a clinically available therapy.

Level 1
1A | Drug is FDA-approved for the same tumor type harboring a specific biomarker.
1B | An adequately powered, prospective study with biomarker selection/stratification, or a meta-analysis/overview demonstrates a biomarker, predicts tumor response to a drug or that the drug is clinically effective in a biomarker-selected cohort in the same tumor type.
Level 2
2A | Large-scale study demonstrates a biomarker is associated with tumor response to the drug in the same tumor type. This could be a prospective trial where biomarker study is the secondary objective or an adequately powered retrospective cohort study or a case-control study.
2B | Clinical data that the biomarker predicts tumor response to drug in a different tumor type.
Level 3
3A | Single or few unusual responder(s), or case studies, show a biomarker is associated with response to drug, supported by scientific rationale.
3B | Preclinical data (in vitro or in vivo models or functional genomics) demonstrates that a biomarker predicts response of cells to drug treatment.
Bottomline, is that clinical studies provide highest level of evidence and pre-clinical studies lowest level of evidence (but at least provide some evidence for hope in the face of nothing).
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Jared N. Schwartz, MD PhD LLC Past President, College of American Pathologists; Opinions his own; Charlotte, NC.

Q: Pathologists are faced with the need to set up additional lab tests routinely. Immunotherapy for cancer is the current rage. How does a pathologist decide whether and how to offer a new test such as PD-L1 Expression Testing?
A: The decision to introduce a new test or remove an old test is not as easy as one would think. There are many variables that must be taken into consideration. Concerning your question i.e. when to introduce a “new” test that may be used to direct therapy in a patient with cancer is an especially important task for the pathologist.
In my own experience using your example the subject would probably arise at a tumor board or multidisciplinary conference. This is setting where pathologists, oncologists, radiologists, surgeons and other medical specialists discuss possible or already identified cancer patients for input and recommendations on evaluation, more specific diagnostic information, treatment options and follow-up plans.
Today with the rapidly expanding complexities resulting from the introduction and availability of new biomarkers be they genomic, proteomic etc. that aid in diagnostic, prognostic and/or therapeutic decisions the burden of proof to introduce a test into your lab is very high. The more so if the “claims” being made are the specific biomarker results which are important and maybe critical in enhancing patient outcomes. The point is that the initial but critical decision of whether a new test should be available and introduced into your lab will be a team effort with input from users of test (the utility) and those responsible for ensuring the test can in fact be performed accurately in your specific lab environment (your validation).
The FDA has already approved PD-LD1. Its value is backed up by numerous clinical studies published in peer-reviewed journals, suggesting that “at this time” having the test results for PD-L1 are important for the treating physician to have in a timely manner.
Now the question is do you send the test request out to another laboratory or introduce it into your own? There are many questions to be answered by lab director in order to make that determination. A short example list of important questions below in no specific order:
What would the number of requests for PD-L1 be in your lab?
Are these numbers high enough to ensure on-going experience in performing test?
Does your lab have skilled staff that can be trained to perform test?
Do you have the resources to ensure your staff have the time to introduce, validate and ensure ongoing quality control of the test?
What will be the costs to provide the test in-house or sent to outside lab?
What is turn-around-time expected from your ordering physicians?
Do you have ability to meet their expectations?
If volume is questionable can an outside lab meet the turn-around time expectations?
What process would you use to select an outside testing lab?
If you decide to perform test what method would you select?
What process would you use to validate, maintain quality control and select appropriate ongoing proficiency and competency testing as per CLIA?
The answers to these questions and others depending on your clinical setting would help you and your colleagues determine if the test for PD-L1 should be performed in-house or sent to another laboratory.
Important to remember: this decision needs to be revisited depending on changes to the answers to above questions occurring over time.
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.