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.

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.

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.

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.

Pamela Wible, MD, Founder of the Ideal Medical Care movement; Author of Physician Suicide Letters—Answered; Family medicine practitioner in Oregon;

Q: Medical students and residents are among the most important human resources in the United States. Yet we lose many during training due to suicide. Have you information you can share with our readers about the mental health and psychiatric drug use of medical students?

A: I asked 220 doctors: “Have you ever been depressed as a physician?” Ninety percent stated yes. Yet few seek professional help. Here’s what depressed doctors do (when nobody’s looking). Some drink alcohol, exercise obsessively, even steal psychiatric meds. Still more shocking—I discovered that 75% of med students (and new doctors) are now on psychiatric medications.
“I was told by the psychologist at my med school’s campus assistance program, that 75% of the class of 175 people were on antidepressants,” shares psychiatrist Dr. Jaya V. Nair. “He wasn’t joking. How broken is the system, that doctors have to be pushed into illness in order to be trained to do their job?”
How many docs do we lose per year to suicide? The equivalent of one medical school full of students wiped out annually. In my 2016 TEDMED talk, I explain why doctors kill themselves. Personally, I lost both doctors I dated in med school to suicide and 8 physicians in my small town. In 2012 I decided to run a suicide hotline for doctors. I’ve heard from so many suicidal doctors that I published a book of their suicide letters.
In 1990, even I was severely depressed as a first-year med student. So my mom (a psychiatrist) mailed me a bottle of Trazodone. I thought I was the only one. Turns out occupationally-induced depression is rampant in medical training. Now schools dole out antidepressants like candy. Stimulants are used by med students like steroids in athletes. So where do we go from here? Should med schools distribute samples of Zoloft and Adderall during orientation?
The problem is physicians must answer mental health questions (right next to questions on felonies and DUIs) to secure a medical license, hospital privileges, and participate with insurance plans. Check the YES box and be forced to disclose your “confidential” medical history and defend yourself—again and again–for your entire career. You get treated like a criminal for taking meds to cope with the torment of medical training (and practice).
Maybe that’s why so many future (and current) physicians sneak drugs and go off-the-grid for mental health care.
“I’ve been in practice 20 years and have been on antidepressants and anxiolytics for all of that time,” says Jason. “I drive 300 miles to seek care and always pay in cash. I am forced to lie on my state relicensing every year. There is no way in hell I would ever disclose this to the medical board—they are not our friends.”
What if we stop the mental health witch hunt on our doctors? Why not replace threats and punishment with safe confidential care? What if we address the root of the problem—the great sickness in medical education—rather than shifting blame to 75% of medical students for not having enough serotonin or dopamine or norepinephrine in their brains?
As scientists, we can’t continue to approach medical education reform as a neurotransmitter deficiency in medical students. Can we?