Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Challenging Oncology Therapies With Moonshot Price Tags

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Pramod John, PhD, CEO, VIVIO Health, San Leandro, CA;
Email: pramod@viviohealth.com

Q: Some American pharmaceutical companies are well-known for pricing drugs at “whatever the market will bear”. In oncology, some specialty drugs seem to have price tags completely unrelated to the proven effectiveness of the drug. Your company has been taking a lead in confronting this problem. What do you envision as possible solutions?

A: New oncology therapies carry astronomical price tags—most people know this. Receiving far less attention is the question of actual therapeutic value. Drug manufacturers spend billions on advertisements and PR, but unfortunately, real-world patient results are frequently unimpressive. Two recent articles in BMJ make this point, 1) No evidence of benefits for popular oncology therapies and 2) Do cancer drugs improve survival or quality of life?
Why do high-cost oncology therapies with questionable results continue to be prescribed? Let’s examine a situation my company is dealing with right now. VIVIO Health received a request for neratinib, an FDA-approved extended adjuvant therapy for early-stage HER2 positive breast cancer. Our system analyzed all available performance data from sources such as the FDA, ICER and NICE. The drug approval was based on a newly created surrogate endpoint called invasive Disease-Free Survival (iDFS), which only scored 94.2% vs. 91.9% in the placebo arm. Even worse, 29% of the patients dropped out of the trial due to adverse side effects, 16.8% for diarrhea alone. Not surprisingly, the FDA committee patient representatives voted against approval.
Neratinib’s manufacturer PUMA Biotechnologies provided data on the current standard of care, trastuzumab, showing a disease-free survival (DFS) rate of 89%. Interestingly, the use of iDFS as an endpoint led to an increase in the placebo arm of ~3%, which is larger than the neratinib-to-placebo arm difference of ~2%. Ultimately the creation of a new endpoint made a larger impact than the therapy itself. The trial design itself had been altered so many times; the FDA suspected the trial had been ‘unblinded’ and attempted to determine statistically whether unblinding had occurred. Even with these highly questionable results, the FDA approved Neratinib in July.
After being shown the questionable data and asked, “Why neratinib?” the requesting oncologist explained that it’s an FDA-approved drug and “MD Anderson is giving it to everyone.”
Granted it’s hard, but physicians should have the courage to do the right thing. In the context of high-dollar, high-tech therapies and billion-dollar windfalls for pharma execs like Puma CEO Alan Auerbach, physicians must be America’s frontline ensuring that only the right therapies get to the right patients. Using Neratinib as an example, here are seven steps every physician should consider before prescribing oncology therapies:

  1. Police endpoint games. Don’t allow drug companies to define arbitrary and meaningless endpoints for your patients. Prescribe medications with objective data on meaningful endpoints such as life expectancy. Anything less should be considered experimental at best and pharma should pay for that.
  2. Do the math. In the case of Neratinib, a 2% probability of potential benefit means that for every 2 patients that might be helped, 98 are subjected to real side effects or other harm. In the neratinib trial, this equates to the ‘lucky’ 33 out of 1,420 total patients, which is quite a needle in the haystack.
  3. Consider the actual cost. Spending $5M per patient ‘helped’ with such uncertain outcomes makes no sense.
  4. Consider societal opportunity cost. Spending money on therapies that don’t work diverts dollars away from developing therapies that do.
  5. Stop listening to key opinion leaders (KOL). Dig deeper and make your own decision. A KOL’s opinion isn’t data and is too often wrought with conflict.
  6. Require companion tests. Don’t prescribe low-probability therapies without some form of a companion diagnostic and insist that the drug company provide it for you.
  7. Prescribe therapies as if you’re the patient and you’re spending your own money.

Physicians, you hold the key to changing the cost curve for ineffective therapies. Drug companies will get the message when you refuse to prescribe treatments that don’t work and cost too much.

* * *
Pramod John is CEO of VIVIO Health, a specialty drug management company providing better outcomes at lower costs.
Pramod John’s contact info is included in the author affiliations at the top of this page.
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.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Accuracy and Precision Define Radiation Oncology

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Eddy Yang, MD, PhD, Professor and Vice Chair of Translational Sciences Department of Radiation Oncology; Deputy Director, Associate Director of Precision Oncology at the Hugh Kaul Precision Medicine Institute; Birmingham, AL;
Email: shyang@uabmc.edu

Q: You are a radiation oncologist with a particular interest in cancer of the prostate. How does the molecular study of prostate, as well as other cancers, including Next Generation Sequencing (NGS), help inform Precision Radiation Oncology?

A: Radiation oncology is a specialty where the accuracy and precision of treatment delivery is vital to the safety and outcomes of our patients. Many specialized techniques are utilized to enhance this precision, including intensity modulated radiation therapy, image-guided radiation therapy, and volumetric arc therapy. Emerging modalities such as proton and carbon therapy take advantage of the physics of heavy ions to potentially minimize normal tissue toxicity. With these methods, we are in essence, performing precision oncology, tailoring radiotherapy to each individual patient. However, precision oncology is much more than that, as novel technologies have expanded our understanding of the drivers of cancer that may be targetable or dictate response to treatment. Currently, emerging evidence has shown the benefits of biomarker-directed systemic treatments, but what about genomic markers to guide radiation therapy? Although the preclinical and retrospective data supports the notion of this possibility, results from prospective studies are not yet available.
Perhaps the most promising and straightforward example of biomarker-directed radiation therapy is in head and neck cancer (HNC). The human papilloma virus (HPV) has been identified as a cause of head and neck cancer. Compared to non-HPV induced HNCs, HPV associated HNCs have better outcomes due to their increased radiation sensitivity. Efforts to de-escalate radiation therapy in this population have yielded encouraging results, and prospective randomized studies are ongoing. However, more work is needed, as not all HPV-associated HNCs have good outcomes. Identifying this subset of patients using genomics and other information is crucial to optimize precision radiation therapy for these patients.
Along these lines, the prediction of tumor sensitivity to radiation would be a powerful tool for precision radiation oncology. The Radiation Sensitivity Index (RSI) is one such test. This molecular signature has been validated for colorectal, head and neck, esophageal, and breast cancers, and patients with tumors that have a radiosensitive signature had improved outcomes. Prospective trials incorporating the RSI to help inform treatment decisions are needed to validate the clinical utility of this signature.
In prostate cancer, a number of genomic signatures have also been reported that can identify more aggressive disease that is at high risk for metastasis or recurrence. Additionally, investigators recently reported the subtyping of prostate cancers using a genomic test approved in breast cancer that could potentially classify prostate cancers that respond well to androgen-deprivation therapy. Similar to the RSI, prospective validation of these findings is needed.
In summary, recent advances in tumor genomics have created potential opportunities to guide and optimize radiation treatment for cancer patients beyond traditional technical improvements. Results are promising, and prospective validation studies are currently ongoing. Given these exciting results, precision radiation oncology will be a part of the standard treatment algorithm in the near future.
Eddy Yang’s contact info is included in the author affiliations at the top of this page.
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.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Precision Oncology in the UK in 2017

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Justin Stebbing, MA FRCP FRCPath PhD, Professor of Cancer Medicine and Medical Oncology at the Imperial College/Imperial Healthcare NHS Trust Charing Cross Hospital, London, UK;
Email: j.stebbing@imperial.ac.uk

Q: Science is universal but the practice of medicine varies widely by geography, economics, and culture. The United Kingdom is an advanced developed country with universal healthcare. How does your country approach the issue of precision or molecular oncology?

A: Great Britain and its major cities such as London are steadily becoming one of the leading healthcare destinations in the world, for patients, their families, and the best researchers and doctors there are. The combination of individualised but multi-disciplinary care, led by our academics at universities, medical schools, collaborations with industry, and critical mass is already prolonging quality and quantity of life and increasing the cure rate for most diseases, whether they affect men or women, young or old, and are common or rare.
Within this, there is an emerging paradigm of precision cancer care in which the use of molecular data at the point of therapy directly impacts patient treatment and clinical decision-making that is joined up between the patient and their medical team. This has already had a substantial, clinical impact on many aspects of healthcare services but up until now these have been surprisingly infrequent. Times are changing now. Oncology and cancer care is now at the frontline of personalised medicine, moving beyond the previous model of giving cancer therapeutics based on trials of largely unselected patients beyond a simple phenotypic marker. We are leading the way in utilising the molecular profile of an individual’s cancer genome to optimise their disease management – to treat the right patient, at the right time, with the right tumour, with the right treatment – including combinations of medicines, surgery and targeted radiotherapy. At the centre of this is the patient, with personalised medicine offering the promise of delivering safe and efficacious cancer treatments that are targeted, biologically rational, and avoid over- and under-treatment common with traditional chemotherapy, thus reducing toxicities associated with non-specific modes of action of chemotherapy.
Advances in personalized cancer care on the medical side includes well-established molecularly targeted therapies for patients with different sub-type of cancer including HER2-positive breast cancer, BRAF-mutant metastatic melanoma, EGFR-mutant or ALK-translocated lung cancer, and  BCR–ABL-translocation-positive chronic myelogenous leukemia. Clinical trials in the UK and London have led to many advances in treating these tumour types, turning them into long-term diseases that people live with, as opposed to dying from; often after treatment, the life expectancy of that person returns to normal. In London we are introducing large-scale genomic technologies at the point of care to aim to: i) catalyse discoveries in translational oncology and drive new research that aims to dissect selective responses to targeted, combination immunotherapies and chemotherapies, ii) identify new targets for which therapies are now in development and, iii) establish in real time, without delays, the right therapy for that person. Indeed, generated by the ability to generate increasingly complex molecular data directly from patient tumor and germ-line (the underlying genetics of a person) samples, the cycle of translating discoveries into clinical practice is accelerating at supersonic speed. Using cell-free DNA, which includes DNA derived from every cell type in a person’s cancer, on a rapid ongoing basis should allow this to occur. Research at Imperial College is establishing the role of cell-free DNA in diagnosis, prognosis, and prediction in order to best treat someone, as well as follow the course of disease. Remarkably, there is an infinite requirement for this, as tumours can change by the second and no two tumour cells are exactly the same. Indeed, the stupidest cancer cell is cleverer than the cleverest oncologist. A molecular arms race to keep up would seem the safest strategy but this has been constrained for too long by cost. There are now many new discoveries in personalised and precision medicine to live a healthier, longer life but until recently even in an exceptionally well-heeled practice, most patients are not willing or able to pay enough for the doctors to devote as much attention to each individual patient, to acquire the necessary equipment, to employ sufficiently well-trained staff, and to spend the time and effort on continuing education to make such a practice viable. Going forward, the vision for world-leading healthcare in London is that each patient now would be an individual – a one size fits all approach would be relegated. This isn’t just for cancer, it applies to every specialty from primary care and paediatrics, to intensive care, endocrinology, gastroenterology, cardiology, neurology, rheumatology and all of the surgical specialties alongside which true multidisciplinary care occurs.
Clinical trials, both led by doctors and others led by biotechnology and pharmaceutical companies are moving to the forefront of care in London, for devices and techniques as well as drugs. In conjunction with NHS England, the 100,000 Genomes Project aims to bring the benefits of personalized medicine to the NHS and make this an everyday reality across diseases. To make sure patients benefit from innovations in genomics, the British Government has committed to sequencing 100,000 whole human genomes, from 70,000 patients, by the end of this year. Successful delivery of the 100,000 Genome Project will enable us to achieve a number of ambitions including: i) to be the first country in the world to sequence 100,000 whole human genomes for the treatment of patients with rare/inherited diseases or common cancers, ii) to have high consent rates from patients and public support for genomics, iii) to have established world leading genomics services within the NHS, iv) to have educated and trained health professionals within the NHS in genomics and its applications for improved patient care and treatment, raising broad awareness and understanding of the advantages genomic medicine offers to patient care in the NHS, v) to be the home of world-leading genomics companies which will work in partnership with the NHS and its academic research partners, and vi) to have stimulated the development of diagnostics, devices, medicines and treatments based on a new understanding of the genetic and molecular basis of disease. This is the ultimate in what’s called bench-to-bedside translational approaches, and we are leading the way here.
Some patients taking part in the 100,000 Genome Project will benefit because a conclusive diagnosis can be reached for a rare/inherited disease or because a “stratified” cancer treatment can be chosen that is most suitable to their individual cancer. For most, the benefit will be in knowing that they will be helping people with similar diseases in the future through research on the genome and associated clinical data they generously allow to be studied. Their involvement in the project will allow an infrastructure to be developed, which in the future will support genomic services to be applied more widely to patient care in the NHS and across many clinical specialties. This will naturally lead to benefits in the private sector because the same individuals work in both sectors in London. For example, I personally work at Imperial College where I have my research laboratory; I work at Imperial College Healthcare NHS Trust where I see NHS patients; and I have a small clinic on Harley Street where I see some private patients and am involved in a number of trials of new immunotherapy combinations. Many of my colleagues are simply the best in the world at what they do. Recently, the UK Government’s Chief Medical Officer Professor Dame Sally Davies’ report called “Generation Genome” discusses how we can offer DNA testing as standard care in so many diseases like cancer (we are already using this to identify and treat different infection strains). In my laboratory we are studying the way our genetic code is turned on or off (or regulated) and the way a cell can turn into a specific type of cell including stem cells and cancer cells. We hope to use this to benefit our patients. The combination with artificial intelligence and machine learning to help us both store and analyse multiple genomes will be critical here.
Our scientists at Imperial College, Oxford and Cambridge (a so-called ‘Golden Triangle’), the Crick, University College London, King’s are leading the way in new technologies such as CRISPR. Many human diseases are caused by the mutation of a stretch of DNA, even with one change in a single nucleotide. Adapted from a primitive bacterial immune system, CRISPR does its handiwork by first cutting the double-stranded DNA at a target site in a genome and in doing so, gives us an ability to greatly alter genetic material as a new therapy for diseases. This has been used in London to understand early embryonic development and use stem cells more reliably to treat disease. Whilst the main aim is to improve the lives of patients, there are potentially many economic benefits for the nation and ultimately the world we live in. Some may be unexpected, built on new, as yet undiscovered technologies that will emerge and we need to be patient. But such benefits may be improved diagnostic tests, better tailored treatments, and development of new treatments and medicines. The role of diet, exercise, complementary medicine utilising techniques from hyperthermia to metronomic chemotherapy, acupuncture to anti-oxidants (as per my own pieces in the Lancet Oncology on the subject of complementary medicines) would be at the forefront of care here, not relegated to an afterthought. It would place the patient’s psychologic state of wellbeing at the centre of their outcomes (in many ways this is as important as the surgery or medicines); one without the other is sub-optimal. Finally, we aim to prospectively collect data here, own those data, and link phenotype such as behaviour and history to the genetics of the cancer or any disease, and the individual as a whole. In doing so, we aim to transform the lives of our patients and their families, disrupt the course of disease, and offer the very best healthcare in the world. This is occurring in real time now, and data generated should benefit patients and their families for decades to come.
Justin Stebbing’s contact info is included in the author affiliations at the top of this page.
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.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Using Data Analytics to Make an Impact in Brain Cancer

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Lisandra West-Odell, PhD, Scientist and Product Manager, Cancer Commons, Los Altos, CA;
Email: lisandra@cancercommons.org

Q: Reflecting the current reality of a brain cancer diagnosis, how can Cancer Commonspositively impact the treatment and outcome of each patient diagnosed with brain cancer?

A: Just over two and a half years ago the March 30, 2015 issue of Time magazine arrived in my mailbox. The cover story “Closing the Cancer Gap” featured two women: “Both of these women have brain tumors…One of them is beating the odds”. In essence, the article compared two women diagnosed with glioblastoma and evaluated the impact of tumor genetic testing in their treatments and outcomes. The first was treated with standard of care chemotherapy. The second received the BRAF inhibitor vemurafenib in a basket trial after genetic testing identified a rare BRAF mutation in her cancer. Treatment with vemurafenib lead to unprecedented tumor regression with few side effects allowing her to beat the odds typical of glioblastoma – the most aggressive form of brain cancer.
I was gripped by this story because as a scientist (working at the time for CollabRx on the content and curation team mining treatment rationales for individual variants) it was apparent to me that treatment selection based on identification of predictive biomarkers has the potential to make a significant difference in outcomes for patients. But I saw the other side of the argument too. Comprehensive sequencing is expensive, identification of driving alterations is rare, and most often more questions are raised than answered. In my current position, scientist and product manager atCancer Commons (CC), I’d like to say a bit more about how a non-profit organization such as CC can move the needle in a landscape as bleak as brain cancer.
We must start collecting patient journeys before we understand how dozens of genetic abnormalities (or more, and their infinite combinations) propel growth, drive tumor evolution, and contribute to therapy response or evasion. I am reminded of the old adage: “Lessons come from the journey, not the destination.” Where one patient’s story can only exist as an anecdote, many stories can be organized into larger buckets or cohorts elevating them to a higher level of evidence. For this purpose, Cancer Commons is building an interactive Patient Registry that can accommodate both prospective and retrospective patient data. We are capturing a specific and limited set of data necessary to understand each patient’s diagnosis and treatment and match them to relevant treatment insights and clinical trials. We follow the patients over time to capture outcomes data so that we can inform future patients what worked and what didn’t.
Importantly, as a companion to the Patient Registry, we are building a case analytics exploratory tool. The case exploration tool allows us to display aggregate data in the registry in the form of graphs and statistics. We can thus visualize the distribution of treatments, the frequency of treatments given, and the outcomes associated with each. We can ask questions such as: Which treatments have been the most efficacious with the highest quality of life? Are any investigational drugs in trials performing well within a patient cohort? Do exceptional responders share any genetic features? What is the next best treatment option for this unique patient right now? All of this is being piloted in brain cancer as a proof of concept. But the approach of knowledge collection, analysis, and sharing will be extended to every cancer type.
I would like to invite YOU to get involved with the Cancer Commons – we are taking all comers. If you are an advocacy group, foundation, or health care organization, join our platform – we can white label our tools and services to support your patients. Share your de-identified data if you have it – the more data we have in our repository, the more powerful our analytics tool becomes. Physicians, key opinion leaders and researchers, contribute your treatment rationales and insights to collaborate on difficult cases, and help us understand how we can improve our data collection methods and interpret our findings. And finally, if you are the patient, all of this was built for you. No matter your cancer type or stage, or location or financial situation, our expert network can help you tap into the world’s collective cancer knowledge. There is a better way forward. Please come help us forge it.
Lisandra West’s contact info is included in the author affiliations at the top of this page.
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.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Life After Oncology

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Professor Michael Baum, Professor Emeritus of Surgery & Visiting Professor of Medical Humanities, University College, London, UK;
Email: baum.michael3@gmail.com

Q: You have recently decided to “withdraw from the field” after a distinguished multi-decade career in Surgical Oncology. Many of our readers will confront a similar choice. How do you see your life evolving from here on?

A: I qualified as a doctor in 1960 and was appointed to my first chair of surgery, at Kings College London 20 years later. In 1981, I established the first clinical trials center for cancer in the UK in my department. To succeed in that field, I needed to become cognizant of the latest teachings in moral and scientific philosophy. Ten years later I was headhunted for the chair of surgery at the Royal Marsden Hospital, the center for our National Institute of Cancer Research. Finally, I was tempted to take up an offer of a professorship at University College London in 1997, during which time I helped develop a course in “Medical Humanities”. In the UK, you are not encouraged to continue operating after the age of 70, so I relinquished my clinical chair but was kept on as visiting professor of Medical Humanities.
I continued my role in running RCTs for the treatment of solid tumors but had time to teach my students on the role of moral and scientific philosophy, history, literature, theatre and fine art, in the practice of medicine. I was also editor-in-chief of the International Journal of Surgery. I honed my skills in creative writing through the medium of my monthly editorials.
All my life I’ve loved drawing and painting, so I filled up the remainder of my time by studying painting in art schools. My ambition was to become a full-time author and artist when I eventually retired. Trouble was that the older I got, the more I became interested in the study of oncology! I then tried to combine my enthusiasm for science, art, and literature by writing provocative papers such as “Does breast cancer exist in a state of chaos?” [1] and “Why does the weeping willow weep?” [2] Eventually, as I was approaching my 80th birthday my family ganged up on me to abandon all my academic activities and long-haul trips to conferences, encouraging me to fully retire to write books and paint “great works of art”! My last trip was to deliver a talk on intraoperative radiotherapy in Las Vegas in early May and I’m happy to say that I survived that experience to celebrate my 80th on May 31st. Since then one of my art works has appeared on the cover of the Red J [3] and my second novel, “Aaron’s Rod” [4] (linked to my interests in Biblical archaeology) was published this month.
I consider myself lucky to have survived the rigors of a life in surgical oncology long enough to relaunch myself in a new career or two. I strongly recommend all oncologists to plan for their retirement, not only in financial terms, but also to maintain the health of their brain.
Professor Baum’s contact info is included in the author affiliations at the top of this page.

  1. Baum M, Chaplain M, Anderson A, Douek M, Vaidya JS. Does breast cancer exist in a state of chaos? Eur J Cancer 1999; 35: 886–91.
  2. Baum.M, Why Does the Weeping Willow Weep? Reconceptualizing Oncogenesis in Breast Cancer. N Engl J Med 373;13, September 24, 2015
  3. http://www.redjournal.org/cms/attachment/2098043502/2078526559/cover.tif.jpg
  4. https://www.amazon.co.uk/Aarons-Rod-Michael-Baumebook/dp/B075FJ5WPW/ref=sr_1_1?s=books&ie=UTF8&qid=1509097950&sr=1-1&keywords=Michael+Baum

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.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Huge Progress in Palliative Care

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Diane E. Meier, MD, FACP, Director, Center to Advance Palliative Care; Professor of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai; New York, NY;
Email: diane.meier@mssm.edu

Q: You wrote in MedGenMed in 2007 that palliative care was the job of all hospitals(MedGenMed 2007; 9(3) 6. July 7. PMCID:PMC2100088). In October 2017 you were honored at the National Academy of Medicine for your achievements in this field. How fully has your charge to hospitals in 2007 been realized?

A: Palliative care is a fairly new medical specialty devoted to reducing suffering and improving quality of life for people living with serious illness-whether the disease is curable, chronic, or life threatening and progressive. Palliative care teams work alongside disease treatment specialists to provide an added layer of support in service of pain and symptom management, family support, attention to the social determinants of health, and skilled communication about what to expect and what matters most to the patient in the context of the reality of the illness. Multiple studies demonstrate palliative care’s contribution to achievement of the triple aim: better experience of care, better care outcomes (including survival in several studies), and as an epiphenomenon of better care, much lower unnecessary utilization of 911 calls, ED visits, and hospitalization.
Until recently, palliative care was only available through hospice, a Medicare funded benefit limited by statute to people with a short (< 6 month) prognosis who agree to give up insurance coverage for treatment of their terminal illness. Not surprisingly, most people choose not to give up coverage for treatment and, as a result, the median length of stay in hospice is only 17 days with more than 30% of hospice patients receiving such care for less than a week. Hospitals are filled with patients pursuing disease treatment for one or more serious illness who are either not hospice eligible or not willing to give up treatment. The evidence of suffering- physical symptom distress, depression, anxiety, confusion about what to expect, family caregiver exhaustion- was growing in the medical literature and clinicians working in hospitals developed hospital palliative care teams to try to respond to this need. But by the year 2000, fewer than 20% of US hospitals reported any palliative care capacity. Today that number exceeds 80%- four out of five US hospitals now report a palliative care team, and among those hospitals with more than 300 beds (the tertiary and quaternary care settings that serve the sickest and most complex Americans), over 90% now have a palliative care team.
While growth in prevalence of hospital programs improves patient access (now 80% of all hospitalized patients in the US receive care in an organization with a palliative care team), access is not the same as quality. Only 39% of hospital palliative care programs meet guidelines for staffing levels and disciplines and fewer than 10% of 1,800 U.S. hospital palliative care teams have achieved the optional Joint Commission advanced certification in hospital palliative care, a marker of consistent guideline adherence and quality.
But there are challenges that go beyond the need for greater accountability for quality and standardization among hospital palliative care teams. The greatest current challenge in the field is the recognition that the great majority of people living with serious illness are neither dying (and are therefore ineligible for hospice) nor hospitalized- hence the real gap in access is in community settings including patient’s homes, nursing facilities, cancer centers, dialysis units, and office practices. The next 10 years of our organization’s work will be committed to both ensuring quality and standardization incentives and requirements for palliative care programs regardless of setting and in markedly improving access in American communities nationwide.
Diane E. Meier’s contact info is included in the author affiliations at the top of this page.
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.
Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

How I Survive Cancer

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Erin Maloney, Intrepid explorer, Amateur photographer, Aspiring leader; Toronto, ON;
Email: erinLmaloney@gmail.com

Q: You have recently disclosed that you have had a diagnosis of cancer and described your experience in some detail on Medium. What does it mean to you to be a “Cancer Survivor”?

A: Calling myself a survivor sometimes feels like an exaggeration. In 2016, I was diagnosed with Stage 1A2 squamous cell carcinoma of the cervix. It began with a routine pap smear and led to a robotic laparoscopic radical trachelectomy seven months later. Every procedure was challenging, and surgery was particularly arduous. However, I did not have to endure radiation, brachytherapy, or chemotherapy. I got to keep my hair, didn’t have to cope with nausea or worry about the lifelong maintenance required after radiation. So, in many ways, calling myself a survivor feels fraudulent. I have it too easy.
The physical recovery was relatively smooth but there is no preparation available for the mental toll of the Big C diagnosis. After the gynecologist shared the news, everything moved quickly. Within 10 days I had an MRI and was in consultation at Princess Margaret Cancer Hospital. It did not leave much room for preparation. In a very brief timeframe, I went from being a healthy 32-year old with no plans to have children to being a 33-year old who might not have a say in the matter.
People expect others to react in a binary way to that kind of news. There is a belief that one can choose to be optimistic or pessimistic, but that is a false dichotomy. Some days optimism abounds; most days, the fear brews below the surface unacknowledged. I mentally created a list of unanswerable questions (Would a hysterectomy be better? Would I feel like less of a woman? What if it comes back? How do I cope with this forever? Is this what kills me?). I researched and armed myself with information – a coping mechanism that allowed me to ignore my own terror.
I am not the same person I was a year ago. Prior to this, I was entrenched in the pitfalls of my Type A personality: a planner and organizer, domineering and determined, opinionated and unwilling to compromise. I had big ambitions and undaunted confidence. But our best-laid plans can be laid waste by a simple two-word sentence: “It’s cancer.” I wished I believed that this was part of some larger plan but it wasn’t. Instead, what it meant for me was that I had to change. My attitude needed to be different if I was going to come out the other side not completely broken.
Cancer took away my control. I could think of little else. Administrative inefficiencies rendered me powerless. I couldn’t get the answers I was seeking faster than they were willing to give them. For example, making decisions for myself was challenging when I needed answers from a busy surgeon. If I tried to use the same approach as I normally would, I would probably have ended up insane. So, I made the decision to adapt. I had to learn patience, to be more open to spontaneity, flexibility, and work on being able to ‘go with the flow.’ I try to allow humour and positivity to flow into impossible situations. I practice kindness and thoughtfulness as often as I can. I strive to think of others and notice their needs. Above all else, I try to treat people the way I want to be treated; to be more open and to deliver honesty without being cruel or callous.
There are many days when I fail at most of those things. Self-improvement is never easy. Imposed self-improvement as a survival mechanism is even more difficult. Finding and maintaining true positivity in the face of overwhelming terror has been the hardest task of all.
The depression that surfaced during recovery was different; it was borne out of a deep desire to live and the constant fear that I might not. I still don’t have certainty. The fear that surrounds each appointment will never abate. In a strange way, that has been inspiring. I want to live. I want a full, vibrant life that is technicolour. It doesn’t mean every day, and it doesn’t mean I get to tick off all those dreams immediately. Ultimately it means that I want to live better and that’s what makes me a survivor.
Erin Maloney’s contact info is included in the author affiliations at the top of this page.
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.
Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Who Owns Patient Data in Clinical Research?

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Charlotte J. Haug, MD, PhD, MSc, International Correspondent, New England Journal of Medicine; Senior Scientist, SINTEF Techology and Society; Adjunct Affiliate, Stanford Health Policy; Oslo, Norway;
Email: charlottejohanne@gmail.com

Q: Many people are coming to believe that active patient participation will be a key to more rapid movement forward in cancer research. Data sharing can help. But who owns the data? And what rights and responsibilities are thus conferred? Your recent NEJM article provides helpful background. Can you help us better understand?

A: Exchange of data between patients and doctors is essential for the practice of medicine – and patient data are essential for medical research and progress.
Traditionally, doctors collected patients’ health information (typically the medical history, laboratory tests, drugs prescribed, outcome of treatment, etc.) and sometimes shared that information, in confidence, with colleagues to seek advice and advance science. The medical record was the physician’s property, and still is in many countries and legislations. But do physicians own the patient data?
In clinical research, patient data from many sources must be collected and analyzed. Researchers must have explicit and informed consent from participating patients to do this, but when they have such consent they are free to use the trial data any way they wish. This is true even for commercial purposes – the norm for drug trials. But do researchers own the patient data?
Until quite recently the question of who owns patient data collected in clinical practice and clinical trials has not been discussed very much, mostly because it hasn’t been very important. Medical records and research results were analyzed and archived on paper. It was difficult, if not impossible, to reuse those data for anything else. Claiming ownership had no real value.
Internet, digitalization of medical records and datasets, and the vast increase in data-storage and data-processing power (especially over the last decade) has changed that. Since it is now possible to combine and reanalyze huge datasets quickly in totally new ways to create useful information about diseases and treatments, it is important to clarify who owns the data in order to clarify who can give permission to share and use data in ways beyond the original intent.
So far, the discussion about data sharing and data ownership has largely taken place between clinical trialists (who spend years collecting, curating, and analyzing data from clinical trials) and data scientists (who would like to add value to those data by reanalyzing and reusing them in novel ways). Both sides claim to have the patient’s and the public’s best interests at heart. But not many have asked patients what those interests are.
At a NEJM conference earlier this year, patients were asked this question. It turns out most of them want to share their data and to share them quickly, especially to ensure that other patients know about possible side effects. But they also want some control over how the data are shared. For example, they would be more hesitant to participate if commercial or other interests were involved. Which is unfortunately the case in most clinical trials. Something many of the patients didn’t seem to be aware of.
But the new “digital patients” also don’t want to be passive observers and sources of research data. They want to use the power of the Internet to engage in their own care, interact with clinicians and fellow patients, create new knowledge, and suggest new ways of delivering health care. They believe in sharing data and experiences to help themselves and fellow patients.
Patients want their data used responsibly and to take part in generating and curating the data. So perhaps the question needs to be rephrased: Who should control how data are distributed and used by others? The patients themselves? Doctors and researchers? Research institutions or governments?
Laws vary from country to country. In the United States, for example, absent specific language to the contrary in informed consent documents, research participants don’t have to give specific permission for their deidentified data to be used by other researchers. Europe is moving in the opposite direction — requiring explicit consent for reuse of data or data sharing and allowing patients to withdraw their consent at any time.
Perhaps the solution to the data-sharing and privacy struggle lies in shifting data ownership and control to individual patients everywhere.
Charlotte Haug’s contact info is included in the author affiliations at the top of this page.
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.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Nicotine Addiction: Harm Reduction by E-cigarettes and Snus

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Joel L. Nitzkin, MD, Public Health Physician, New Orleans, LA
Email: jlnitzkin@gmail.com

Q: Tobacco smoking remains the most preventable primary form of cancer causation in Americans. A recent Medscape column urged that harm reduction for confirmed nicotine addicts is the kindest and most effective strategy. How can products like “snus” be helpful?

A: As noted by Dr. Michael Russell in 1976, people smoke for the nicotine, but die from the tar. According to CDC, about half of long-term smokers will die of a smoking-related disease. They estimate that about 480,000 Americans die from cigarette smoking each year, including about 50,000 from the environmental tobacco smoke. According to our best current estimates, snus and the other smokeless products used by American men pose little or no risk of cancer of the mouth or any other cancer. E-cigarettes, having no combustion and no tobacco, are likely similarly low in risk.
Snus, e-cigarettes, and other smokeless nicotine delivery products offer an interesting and unusual approach to reducing the deadly toll of addition to cigarette smoke. Rather than present themselves as drugs to treat a deadly disease, these products offer recreational substitutes for cigarettes that already enable large numbers of smokers to satisfy their urge to smoke while reducing the risk of potentially fatal cigarette-related cancer and other diseases by more than 95% (likely more than 99%). This is a public health benefit that can be secured for many more smokers, (at no cost to the taxpayer) by simply advising them of this difference in risk. Sweden, where most men use snus rather than cigarettes to satisfy their urge for nicotine, has the lowest rate of lung cancer among men in the Western world. There is even one small study that shows that e-cigarettes can get smokers not interested in quitting to quit by switching to this much lower risk product. All it takes is informing them of this difference in risk.
American public health authorities recognize that snus and e-cigarettes are much lower in risk than cigarettes. Their objection to allowing manufacturers to claim lower risk, however, is based on a very different concern. They object on the basis that advertising these products as lower in risk might attract teens and other non-smokers to tobacco-related products; and from there to cigarettes. Research published this last decade provides substantial evidence that such advertising would not be likely to attract teens to these lower-risk products who otherwise would not have taken up smoking.
For many years, the goal of public anti-smoking programming has been “a tobacco-free society.”This goal has been based on the premise that all non-pharmaceutical nicotine products are so addictive and so hazardous that none should be tolerated. This goal has also been interpreted as ruling out any consideration of any non-pharmaceutical nicotine product in any public health initiative. Now that we know that we can communicate reduced risk without attracting teens who otherwise would not have taken up smoking, the time has come to use this knowledge to further reduce the burden of addiction, illness, and death that cigarettes have imposed both in the USA and worldwide.
Joel Nitzkin’s contact info is included in the author affiliations at the top of this page.
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.
Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Pharmacogenomics for Clinical Use of Cannabis

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Saeed K. Alzghari, M.S., M.B.A. (HOM), Pharm.D., BCPS, Director of Clinical Pharmacy, Gulfstream Genomics, LLC., Dallas, TX;
Email: salzghari@gulfdiagnostics.com

Q: Proper use of Pharmacogenomics can inform better patient care in many potential ways. Pain relief by use of Cannabis instead of opioids shows substantial promise. How do you think pharmacogenomic study could guide intelligent clinical use of Cannabis?

A: Over the past decade, pharmacogenomics (the study of how genes affects a person’s response to drugs) has gained much ground. More than 160 drugs currently have pharmacogenomic labeling by the Food & Drug Administration (FDA) and the list is growing. The excitement that surrounds pharmacogenomics and the applications associated with this technology are endless.
In order to understand the role of cannabis for pain pharmacogenomics, one must understand how pain is treated. In my experience as an oncology pharmacist, I have seen first-hand the unbelievable amounts of opioids a cancer patient may take just to gain some relief. Pain is treated according to the World Health Organization’s (WHO) Pain Relief Ladder where pain is treated in steps based on severity (Figure 1). Steps 2 and 3 of the pain ladder begin to include opioids as part of the treatment course since, when used properly, opioids offer the best chance at reducing pain.

An important consideration that is often forgotten is the use of adjuvant agents to help reduce the amount of opioids used when treating pain in general or to help with different types of pain such as neuropathic pain. In regards to cancer, the first clinical trial to show that an adjuvant therapy can help with chemotherapy-induced peripheral neuropathy was duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), typically indicated for depression.
The role of cannabis in pain management, in my opinion, will most likely be as an adjuvant. I do not see cannabis completely eliminating the need for opioids in patients with moderate-to-severe pain, but I believe cannabis can reduce the amount of opioids a patient may take. The main pharmacogenomic focus for cannabis is related to two primary cannabinoid receptors (CB1-R and CBR-2) that marijuana acts upon. Cannabinoid receptors are of great interest to researchers since our own body produces endocannabinoids that play a role in pain. Research associated with genetic polymorphisms in the cannabinoid receptor CNR1 and CNR2 genes are in preliminary stages; however, these genes hold promise to optimize and individualize therapies that act on the cannabinoid receptor. Other pharmacogenetic markers and their role in patients taking cannabis are also being investigated.
The largest barrier to research related to cannabis is that marijuana is classified as a Schedule I controlled substance by the U.S. Drug Enforcement Administration. Researchers are restricted on how marijuana is studied and is a deterrent to those wanting to perform trials in U.S.-respected organizations, such as the American Cancer Society, that have taken the position in supporting the need for more scientific research associated with cannabis to provide better patient care. If marijuana is rescheduled in the U.S., then its barriers to research will be lifted and more studies involving the pharmacogenomics of cannabis can be performed to improve patient care.
Saeed Alzghari’s contact info is included in the author affiliations at the top of this page.
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.