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

How an Expert Would Manage His Own Stage 4 Pancreatic Cancer

John Strickler, MD
Associate Professor of Medicine at Duke University, Cancer Commons Advisor

When confronted with a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Cancer Commons Expert Physician Advisor John Strickler, MD, how he would handle his own diagnosis of metastatic pancreatic cancer. Dr. Strickler is Associate Professor of Medicine in the Division of Medical Oncology at Duke University and Co-Leader of the Duke Molecular Tumor Board.

Curious Dr. George: Cancer Commons provides information about treatment options to patients with advanced cancer, usually beyond the standard of curative care. As an experienced academic and practicing clinical oncologist at Duke University, you have particular interest, training, and experience in gastrointestinal cancer. What would you do if you personally were diagnosed with asymptomatic, unsuspected, ductal adenocarcinoma of the tail of the pancreas that had already metastasized to your liver?

Dr. Strickler: Pancreatic cancer is one of the most lethal malignancies. In most cases the disease presents as surgically incurable (locally advanced) or metastatic. Despite the grim survival statistics and poor prognosis associated with this disease, there is reason to have hope. In the past decade, advancements in supportive care, chemotherapy, and molecular diagnostics have allowed patients to live longer and live better. While we have a long way to go, finally progress is being made.

If I were diagnosed with metastatic (stage 4) pancreatic adenocarcinoma, the first thing I would do is find an experienced multi-disciplinary team with pancreatic cancer expertise. This team would give me the best outcomes possible. Members of this team would include experts in the following fields:

Medical Oncology: Although the primary function of a medical oncologist is to provide chemotherapy, typically he or she formulates the treatment plan and coordinates care. In my hypothetical case, the medical oncologist would recommend either gemcitabine alone, gemcitabine with nab-paclitaxel, or FOLFIRINOX. All of these treatments are reasonable, but combination chemotherapy (gemcitabine + nab-paclitaxel or FOLFIRINOX) offers the greatest disease control and longest survival.

Additionally, the medical oncologist would be responsible for ordering next-generation sequencing (NGS) on my tumor tissue to determine if my tumor harbors an “actionable” genetic alteration. Although these actionable genetic alterations are rare, they may make me eligible for immunotherapy or other targeted therapies.

Genetic counseling: Approximately 5% of all patients with pancreatic cancer have a germline (hereditary) mutation in BRCA1/2 or PALB2, and these hereditary mutations predict benefit from platinum-based chemotherapy and PARP inhibitors. Other rare germline mutations can also predispose a patient to pancreatic cancer. Current national guidelines advise germline testing in all patients diagnosed with pancreatic cancer, regardless of family history, age, or stage at diagnosis. Genetic counseling is advised for any patient who tests positive for a pathogenic germline mutation or has a strong family history.

Palliative care: Many patients are hesitant to consider palliative care. There is a misconception that palliative care represents end-of-life care. I hope that we can change this misconception. Pancreatic cancer often presents with complicated symptoms that are difficult to manage. Even if I present completely pain free, symptoms from pancreatic cancer can change rapidly. Given the incurable nature of this disease, it is helpful to have a team of doctors who can help me and my family prepare for the future. I view palliative care as a critical “extra layer of support” to fight a very difficult illness.

Other important members of the team: As a medical oncologist, I have learned that I am only as good as the people around me. I cannot overstate the importance of having experienced and dedicated nurses, advanced practice providers (NPs and PAs), and clinic staff to provide extra support. Additionally, by finding a skilled multi-disciplinary team for my hypothetical diagnosis, I would have access to other experts, including radiologists, pathologists, surgeons, radiation oncologists, and gastroenterologists. All of these physicians would be key to my health and symptom management.

Final thoughts: As a gastrointestinal medical oncologist, I have seen how difficult pancreatic cancer can be for patients and their loved ones. If I were facing this disease myself, I would recognize that it takes a community of dedicated clinicians to keep me living longer and living better. As a patient, I would make myself available to clinical trials and other research. It is through these research efforts that we will change the course of this terrible disease and improve outcomes.

More details about ways to support pancreatic cancer research and support patients and families fighting this disease can be found at the Pancreatic Cancer Action Network.

Requests for Dr. Strickler’s email address can be sent to Curious Dr. George at gdlundberg@gmail.com.

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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 an Expert Would Treat His Own Glioblastoma

Al Musella, DPM
President, Musella Foundation For Brain Tumor Research & Information, Inc.

Two years ago, our Curious Dr. George asked Al Musella, DPM, what he would do if he were diagnosed with glioblastoma multiforme (GBM). Here, he revisits that question. Dr. Musella is President of the Musella Foundation For Brain Tumor Research & Information, Inc.

Curious Dr. George: You direct an established foundation that supports research and information about brain tumors. What would you do if you yourself were diagnosed with GBM?

Dr. Musella: Now that GBMs are in the news again, I would like to discuss what I would do if it happened to me—a newly diagnosed GBM in an adult in otherwise good shape. There are several choices:

Standard of Care: Surgery, radiation, and the drug temozolomide; with this standard approach, the chance of 5-year survival is about 5%. However, standard of care plus Optune—a wearable device that uses electrical fields to treat GBM—bumps my chance of 5-year survival up to 24.9% (if used over 90% of the time) with no added toxicity.

Phase 3 Clinical Trials: There are now about four phase 3 trials for newly diagnosed GBM in the U.S. One involves intraoperative radiation therapy at the time of the initial surgery and looks worthwhile. The others involve treatments that in earlier trials improved survival by just a few months. They may be worth a try if they did not have two big downsides: 1) Most have a control group of patients who receive the old standard of care so that some of the participants do not get the experimental treatment. 2) Some do not allow you to use Optune, so you are trading a known benefit for a chance at an unknown benefit.

Historically, over the last 50 years or so, only a handful of phase 3 trials have been successful. Optune was the most successful phase 3 trial, and no other phase 3 trial has yet come close, so the chances of doing better in a phase 3 trial than Optune is low. What we thought were the most promising phase 3 trials over the last few years all failed. We are waiting for results from the phase 3 trial of DcVax—that may be a game changer, but this therapy is not available to the public right now.

Phase 1 or 2 Trials: About 150 phase 1 or 2 trials are currently active in the U.S. There are many interesting choices here, but we do not have enough data to make an informed decision on which one to try. We do have early results from some phase 1 trials, some of which are better than those seen with standard therapies, but it is not likely that any one of these alone will make a big difference in survival for most patients. We do not (under the current system) have the ongoing results of these trials—we only get the results a few months after the trial is over. And while inside the trial, we cannot combine them with other treatments.

Off-Label Use of Drugs Approved for Other Diseases: There are many choices here, and a rational approach might be to select a “cocktail of drugs” based on a genomic analysis of my tumor.

Cocktail Approach Involving Experimental and FDA-Approved Treatments: Right now, this is impossible or very difficult to obtain. However, if it were possible, this would be my approach. Especially if we had a registry of all of the patients, the treatments tried, and the outcomes so we can learn from every patient.

Getting Access to Experimental Therapies: There are a few pathways to getting experimental therapies. Currently, none are really practical on a large scale. I have tried to get expanded access/compassionate use/right-to-try access on the most promising experimental treatments, and it is very hard. Getting multiple drugs this way for a cocktail is just about impossible. We had high hopes for the Right To Try Act, which was passed last year, but it turned out not to help at all. Drug companies are not willing to use this pathway for brain tumor patients. However, even if we could get them, without tracking the results, we are not learning and are doomed to repeating the same failures.

My foundation is  working on a new bill that will solve this problem and speed up the search for the cure. Click here to learn more.

So, bottom line: What would I do?

Surgery: I would begin with surgery, trying for maximal safe resection, possibly using Gliolan (a dye that helps surgeons see small clusters of GBM cells) to increase chances of maximal resection. I would also consider insertion of Gliadel wafer (intraoperative chemotherapy) if the resection cavity is not up against the ventricles (and we are not planning on entering a trial that excludes prior use of Gliadel) or some type of intra-operative radiation.

Radiation: I would receive standard radiation or possibly proton beam radiation. This may be followed by some type of boost, possibly “leading-edge” radiosurgery.

Temozolomide: I would receive this drug during and after radiation, only if molecular testing of my tumor sample detects methylated MGMT. If the tumor is unmethylated, I would seek treatment with the drug Val-083, either in a trial or through a compassionate use/right-to-try program. The length of time to use temozolomide is controversial. The most commonly uses length of treatment is 6 months after radiation (as well as during radiation).

Immunotherapy: There are a few immunotherapies that have shown remarkable results in a minority of patients. A few of the early vaccine and gene therapy trials have tails of 20% or more of patients living over 5 years and with minimal or no side effects. I would try to get one (or maybe two) of these drugs. The polio vaccine trial (PVSRIPO) looks promising, as does the CMV vaccine, the Survaxin vaccine, and Gliovac.

Optune: We are put into a very tricky situation here. Many trials will disqualify you if you use Optune, but Optune has the highest survival rates in large trials. So as I said before, you are being asked to gamble a known benefit for an unknown experimental treatment that might or might not help, and you might even be assigned to a control group. The results with Optune alone are still not good enough. The results shown above were for newly diagnosed GBMs. For recurrent GBMs, they are not nearly as good, so it is important to use it early in the course of the disease. Ideally, I would combine Optune with one of the immunotherapy treatments in phase 2 or 3, but that is not possible yet. We really need to fix that. Why should I be allowed to die just to appease an archaic tradition of requiring standard phase 2 and 3 trials?

…The choices are overwhelming for me. And for someone new to brain tumors, it is impossible to decide. We—the Musella Foundation—have formed a collaboration with Cancer Commons to create a program to help patients find the best treatment options for their individual case, then help them get access. We track how these patients do so that we learn from every patient. To take advantage of this free program, click here.

Dr. Musella can be reached at musella@virtualtrials.com.

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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

Is Cancer the Best Way to Die?

Curious Dr. George
Cancer Commons Editor in Chief.

Richard Smith, CBE, FMedSci
Chair of the Lancet Commission on the Value of Death, Editor of The BMJ (1991–2004)

In 2014, the prestigious medical research journal The BMJ published a controversial piece called “Dying of cancer is the best death.” Here, our Curious Dr. George asks the author of that piece, Richard Smith, CBE, FMedSci, if and how his thoughts on death have since evolved. Dr. Smith was Editor of The BMJ from 1991 to 2004 and is currently Chair of the Lancet Commission on the Value of Death.

Curious Dr. George: Your 2014 BMJ blog post on dying of cancer precipitated quite a robust discussion. Since then, the fields of precision oncology and immunotherapy have developed a lot, although perhaps not yet realizing their full potential. You currently chair the Lancet Commission on the Value of Death, from which a report is forthcoming. Looking back at 2014, have developments in precision oncology and immunotherapy changed your thinking about death?

Dr. Smith: In 2014, as you note, I unintentionally created global furor by arguing in a blog post that cancer is the best way to die. Nothing else that I’ve ever written has created such a storm, but many physicians, aware of the three broad alternatives, agreed with me. Sudden death may seem attractive but can leave great pain among those you love. Organ failure is prolonged and messy, and the long, slow death of frailty and dementia is exhausting for everybody. Dying from cancer, I wrote: “You can say goodbye, reflect on your life, leave last messages, perhaps visit special places for a last time, listen to favorite pieces of music, read loved poems, and prepare, according to your beliefs, to meet your maker or enjoy eternal oblivion.” I recognized that I may have succumbed to romanticism, but I argued that such a death “is achievable with love, morphine, and whisky.” “But,” I warned, “stay away from overambitious oncologists.”

Now, you tell me that precision oncology and immunotherapy have developed and ask me if my attitude has changed. I have a friend with metastatic malignant melanoma who is kept alive by immunotherapy and would probably be dead if it were still 2014.

For the past three years, I have been chairing the Lancet Commission on the Value of Death, and we hope to publish our report in spring of next year. Our starting point is that medicine and society have developed an “unhealthy” relationship with death. We find that few health professionals disagree, and most people have stories of grisly deaths in hospital. Indeed, with the ongoing COVID-19 pandemic we have become used to people who are dying in intensive care communicating with their loved ones only through iPads and accompanied only by masked and gowned strangers.

What is wrong with how medicine and society approach death? Firstly, death, many would argue, is the most important event in our lives. Plato called philosophizing an apprenticeship for death, and the Irish thinker Kevin Toolis argues that “The world makes sense to us because we die, not because we don’t.” We can surely all agree that death is a community, family, and spiritual event—not simply a medical event. The job of culture, often assigned to religion, is to give meaning to death. Medicine cannot provide meaning, and yet in high-income countries (and increasingly in poorer ones) death has degenerated to a medical event with reduced family, community, and spiritual involvement. People are unfamiliar with death and dying, as the dying and the dead are hidden in hospitals. “The experiment of making mortality a medical experience is just decades old. It is young. And the evidence is it is failing,” wrote Atul Gawande in his book Being Mortal.

A second problem is that aggressive treatment may often prolong life but increase suffering. The American physician Eric J. Cassell taught us that persons, not bodies, suffer, and stretching out the process of dying and treating patients only hours from death with cytotoxic drugs, antibiotics, and even operations often increases suffering.

A third problem is the high and disproportionate expenditure at the end of life. Even if this expenditure were to benefit the individual, which it often doesn’t, it makes no sense to the broader community. Resources are diverted not only from more cost-effective health care but also from the factors that shape health—education, housing, urban design, and reducing poverty.

The answer of the Lancet Commission is to rebalance death and dying, shifting it from a medical event to something that is owned by families and communities with support from health professionals. In case such a vision seems Utopian, we can point to where it is already happening—in Kerala in South India and in Compassionate Community programs that are developing around the world.

What would such a vision mean for precision oncology and immunotherapy? I would favor them if they can prolong life without prolonging suffering and without increasing the division between the few in the world who have excellent end-of-life care and the majority who have no access to opiates and even the most basic palliative care. But are they part of medicine’s Faustian pursuit of immortality, which is explicit among well-funded companies in California and implicit in conventional medical research that attempts to cure every disease? And can precision oncology and immunotherapy be part of a world where health professionals are supporters not leaders at the end of life, and we regain some connection with the meaning of death? I’m not sure, but I’m skeptical.

Dr. Smith can be reached at richardswsmith@yahoo.co.uk.

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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

The Power of Precision Medicine is Exemplified by Tempus

Nike Beaubier, MD Vice President, Head of Translational Medicine at Tempus

Namratha Sastry, PhD
Scientific and Medical Writer at Tempus Labs

Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of our invitation-only column, “Curious Dr. George”

For some patients, a key step to finding their best treatment may be molecular testing of their tumor tissue. This type of test could reveal distinct features, such as genetic mutations, that can be targeted by specific treatments. To help facilitate molecular testing for the patients we serve, Cancer Commons has partnered with the company Tempus. Here, our Curious Dr. George asks Nike Beaubier, MD, Vice President, Head of Translational Medicine at Tempus; and Namratha Sastry, PhD, Scientific and Medical Writer at Tempus Labs, about how their company helps patients.

Curious Dr. George: Translational medicine has evolved to include personalized medicine and precision oncology. We have learned that all individual cancers may be unique, but that they do share some common “…omic” elements that can inform therapeutic decisions. Your company, Tempus, houses a diagnostic molecular laboratory but it is so much more. How may the many capabilities of Tempus help to improve care of patients with potentially lethal malignancies?

Drs. Beaubier and Sastry: Precision medicine is a powerful tool to tackle some of the most complex human diseases. Tempus is a technology company that has amassed the world’s largest library of clinical and molecular data and is using this platform to empower doctors to make data-driven decisions for their patients in real time. Our primary area of focus is oncology, but we have recently expanded into psychiatry, cardiology, and in the course of developing a response to COVID-19, infectious disease. By combining clinical sequencing, clinical data aggregation, and clinical trials services, we have developed a platform that derives personalized diagnostic and therapeutic insights. This platform is so powerful that we have initiated partnerships with 80% of the top hospitals in North America, and we were recently ranked #6 in the 2020 CNBC Disruptor 50 list.

Tempus has many capabilities designed to improve care for cancer patients. Our CAP-accredited and CLIA-certified lab is optimized for high-throughput clinical next-generation sequencing. We have developed three industry-leading, oncology gene sequencing panels to provide individual patient care as well as drive our data science and biomarker discovery efforts: 1. Tempus|xT (648 genes + whole transcriptome RNA-Seq); 2. Tempus|xF (105 gene liquid biopsy); and 3. Tempus|xE (whole exome + whole transcriptome RNA-Seq). We have curated data from hospitals, national cancer societies, and individual practices to create a real-world database of de-identified data to fuel research and discovery in disease. Additionally, our biological modeling lab, focused on patient-derived tumor organoids, serves as a high-throughput screening tool for testing drug sensitivities, validating real-world data, and identifying novel oncogenic pathways.

In addition to our laboratory teams, our data science teams build data-driven models to intelligently address research and clinical questions. Our data and analytics platform standardizes molecular and clinical data to identify and solve complex research questions. We organize unstructured clinical data by using optical character recognition, natural language processing, and manual curation. Importantly, these capabilities can also be extended to the clinic. We are developing a series of supervised and unsupervised machine-learning algorithms that combine clinical, sequencing, and imaging data, to identify prognostic indicators that can help physicians make optimal therapeutic decisions. Finally, our TIME Trial™ Program leverages Tempus’s real-world clinical and molecular data to identify patients eligible for clinical trials. It is estimated that only 3% of cancer patients enroll in clinical trials in the USA. TIME seeks to rapidly match patients largely in the community setting to targeted clinical trials, giving thousands of patients access to novel therapeutics.

At Tempus, we bring the power of large, multimodal data sets and machine learning, combined with state-of-the-art laboratory testing to help patients live longer and healthier lives. Our overall goal is to enable physicians to make the best therapeutic decisions and provide customized care to every patient, right now.

Dr. Beaubier can be reached at nike.beaubier@tempus.com, and Dr. Sastry at namratha.sastry@tempus.com.

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

Helping Cancer Patients Access their Own Health Data

Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of our invitation-only column, “Curious Dr. George”

Deven McGraw
Chief Regulatory Officer at Ciitizen

For many cancer patients, the ability to access one’s own medical records can aid their treatment decisions, or allow them to donate their personal data for research that could help other patients. But these records can be difficult to obtain and sort through. Here, our Curious Dr. George asks Deven McGraw, Chief Regulatory Officer at Ciitizen, how her company helps patients access and organize their own health information.

McGraw can be reached at deven@ciitizen.com.

Curious Dr. George: The medical records of an individual American patient are both precious and private. Access to them is of great importance for medical decision making. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) specifies ownership and conditions for sharing that information. How does your company facilitate both privacy and proper access? How do you measure success?

Deven McGraw: Medical records are created by providers of health care (for example, doctors, hospitals, clinical laboratories, and pharmacies). Providers use these records for multiple purposes, but most providers are subject to federal privacy and security rules governing how they use and disclose these records. HIPAA allows providers to use and disclose records for treatment, to be paid, for reporting to public health, and for research, to name just a few of HIPAA’s rules.

But HIPAA also provides patients with rights regarding these records, including the right to access and receive a copy of all of the health information collected or generated about you by your health care providers. For example, you have the right to copies of your images, lists of medications, lab test results (and the underlying data that informed the result, including for genomic testing), diagnoses, and the notes clinical providers record about your care. Most patients today have “portals” that give you access to some of your medical records, but what you have a right to receive under HIPAA is much more than what is typically available in portals.

Patients have the right to get this information:

  • Within 30 days of receipt of your request.
  • In the form and format you want, as long as the provider can readily produce it in this format (this means you can get digital copies of electronic medical records).
  • At zero or very low cost (providers can only charge you for the amount it takes them to make the copy).

You can even have records emailed to you if that’s what you want (and you are okay with any security risks associated with sending by regular email).

Although the HIPAA right of access has been a legal requirement for more than 20 years, it can be difficult for patients to get their records. In response, Ciitizen developed a Patient Record Scorecard rating how providers respond to patient requests under HIPAA for copies of their records.

Ciitizen was founded to make sure patients—beginning with cancer patients—could get all of their medical records in a private and secure personal health record. Ciitizen also organizes these records so cancer patients can: use them to seek the best possible care (for example, getting a treatment recommendation or second opinion, or determining eligibility for a clinical trial), share them with a caregiver, and donate them for research.

How do we measure success? When cancer patients have all of their relevant medical information at their fingertips and are able to drive change—for themselves and for others. Although Ciitizen is not yet open to the public, we are onboarding cancer patients. Come see us at www.ciitizen.com.

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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.

10th Annual Lundberg Institute Lecture: American Healthcare: What’s Left After COVID-19

Virtual Lecture: Further Details TBD

Moderator

George D Lundberg MS, MD, ScD (hon)
President and Chair of the Board of Directors, The Lundberg Institute;
Editor in Chief, Cancer Commons; Editor at Large, Medscape; Editor in Chief, Curious Dr. George blog; former Editor in Chief, JAMA (1982-1999)

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

How I Cope with the Tsunami of Cancer and COVID-19 Info

Kevin Knopf, MD

Oncologists worldwide face the challenge of staying on top of the latest treatments, research findings, and other information that could help them treat their patients more effectively. Now, they must do so in the context of COVID-19. Here, our Curious Dr. George asks Kevin Knopf, MD, MPH, Division Chief of Hematology/Oncology at Highland Hospital/Alameda Health Systems in Oakland, California, how he keeps up.

Dr. Knopf can be reached at kevinbknopf@gmail.com. Or follow him on Twitter: @drkevinknopf

Curious Dr. George: Even without COVID-19, the field of clinical oncology is changing so rapidly. How do you, as a practicing oncologist, keep up with new information about cancer and COVID-19? On a day-to-day basis, do you mostly rely on the best medical journals, emails from medical associations, government agencies, press releases, actual or virtual medical meetings, hospital conferences, mainstream media, social media, or what?

Kevin Knopf, MD, MPH: There are three key journals I read regularly: two weeklies—The New England Journal of Medicine and Blood (the journal of the American Society of Hematology)—and the thrice-monthly Journal of Clinical Oncology (American Society of Clinical Oncology or ASCO). They all have excellent updated guidelines on cancer care, including during COVID-19. Medscape Hematology – Oncology is a fourth online publication that I read daily. There are several other fine journals in oncology* that I read, but their web presentations are not quite as robust. Together, these four periodicals have done an outstanding job of curating scientific and clinical information about COVID-19 and publishing it quickly online prior to print publication.

As Division Chief of Hematology/Oncology, I must also set guidelines and policy that affect our entire hospital and health care system. We were quick to adapt our chemotherapy infusion suite for COVID-19 safety based in part on shared information. Triage of outpatients has been an ongoing challenge and an iterative process. ASCO guidelines and rapid publication of information have been key in my ability to care for our patients.

I’ve also discovered another fascinating development on keeping up with cancer care during COVID-19. I registered on the Twitter-based community #MEDTWITTER in 2013 to follow what was happening in academic oncology, see new clinical developments, and learn and interact with colleagues. On Twitter, we debate the latest findings in hematology/oncology and share articles with each other. For the record, I think one of the first physicians to predict the magnitude of the COVID-19 tragedy is Christos Argyropoulos, MD, (@ChristosArgyrop), a brilliant nephrologist and researcher in New Mexico who pondered the epidemiology of COVID-19 well before the first case in the United States. My friend Dan Goldstein, MD (@drdgoldstein), retweeted a video featuring Italian pulmonologist’s experience treating COVID-19 in Italy on March 10—the day things really sank in for me. A video on Twitter can be worth more than 1,000 words. Now, I follow the Twitter accounts of several epidemiologists and molecular biologists engaged in COVID-19 research.

While rapid information has been brought to bear on COVID-19 during this time of crisis, many shoddy and methodologically flawed scientific “studies” have been rushed to publication. For instance, recent discussion has focused on the retraction of some highly flawed publications on hydroxychloroquine. Journalists Jeanne Lenzer and Shannon Brownlee have written eloquently about these problems.

An illustrative and highly pertinent ongoing issue is whether we should change our clinical approach to treating COVID-19 patients who have acute blood clotting disorders—strokes, pulmonary embolism, and the like—who often die, even of disseminated intravascular coagulation. This question touches on not just the biology but the nature of clinical research; it is now known that patients in the intensive care unit with COVID-19 have a high incidence of thrombotic (clotting) complications, but whether and how to intervene is being debated.

In clinical medicine, when possible, we conduct prospective randomized controlled trials to minimize confounding and bias in order to get closer to the truth of whether an intervention helps or harms a patient. The principle is that while retrospective trials are hypothesis generating, prospective trials help to prove or disprove a hypothesis. In this context, several institutions have been interpreting the retrospective data to recommend more aggressive anticoagulation for patients with COVID-19. I’ve had to sit tight and believe what I believed before—that this doesn’t make sense. On Twitter this has been debated extensively, even with a picture of a patient who died from a bleed into the brain caused by excessive anticoagulation (arguing against this practice). For my institution, I have not recommended changing our approach of not anticoagulating COVID-19 patients, but I am monitoring the evidence daily.

So much is changing in our communication about cancer care as a result of COVID-19. I gave my first online lecture to an international conference on March 9. And, our usual ASCO meeting of 60,000 people in Chicago was instead held completely online while (coincidentally) peaceful protests and violence in the streets erupted over George Floyd’s death. The convention center for this meeting had been converted into a COVID-19 hospital in anticipation of a tsunami of cases in Chicago. Interestingly, the academic oncologists on Twitter are mostly commenting about how nice it is to not have to travel for a meeting; the only part we seem to miss are the social interactions with each other.

The internet has dramatically improved how we practice medicine and share knowledge in cancer care. Now, COVID-19 is another jolt to the system that will change how medical information is generated and disseminated. As a physician practicing at a county “safety net” hospital, I predict dramatic changes in cancer care as more than 27 million Americans have already lost their health insurance due to the pandemic. This erosion of coverage may herald a sea change towards more value-based cancer care as the finances of cancer care in 2020 and beyond are challenged.

*Additional important journals for hematologists/oncologists include The BMJ, The Lancet, The Lancet Oncology, JAMA Oncology, The Oncologist, Clinical Advances in Hematology & Oncology.

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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 the Coronavirus Pandemic Impacts Cancer Care: Our Survey Results

Lola Rahib, PhD

The ongoing COVID-19 pandemic presents unprecedented challenges to cancer patients. Many have experienced changes to their care, and some face increased risk of infection or worse prognosis if they are infected. In partnership with the company xCures, Cancer Commons is studying how COVID-19 impacts cancer patients.

Here, our Curious Dr. George asks Cancer Commons Director of Scientific and Clinical Affairs Lola Rahib, PhD, about our findings so far. Dr. Rahib can be reached at lola.rahib@cancercommons.org.

Curious Dr. GeorgeCancer is listed as one of the preexisting conditions that may result in increased susceptibility to the harm caused by COVID-19. In addition, the mass shutdown of many of society’s activities intended to mitigate the pandemic has major impacts on functions of medical care.

Cancer Commons has launched an FAQ page to inform cancer patients of these many interactions. In addition, you have performed a survey of cancer patients to identify their experiences during this pandemic. What are some of your main findings?

Lola Rahib, PhD: Our goal was to understand the impact of COVID-19 on cancer patients through a questionnaire completed by them or their caregiver. A total of 112 patients or caregivers completed the questionnaire from March 24 to April 15. Ninety of those who completed the survey had previously registered for Cancer Commons’ services and received the survey by email. The remaining 22 patients completed the survey through social media platforms.

Of the 112 patients and caregivers who completed the survey, 78 (70%) reported that they or the patient they care for was currently receiving cancer treatment. Canceled or postponed appointments due to COVID-19 were reported by 32 (29%) participants. Thirteen (12%) reported treatment delay because of COVID-19.

Six patients (5%) were newly diagnosed and had to make a treatment decision about a new cancer diagnosis during the COVID-19 pandemic. Twenty-one (19%) patients had to make a decision about a treatment change.

Eighty-three reported on whether COVID-19 affected any treatment decisions they had to make. Of these 83, 24 (29%) reported that COVID-19 affected their treatment decision, and 23 gave an explanation. The most common explanations of how COVID-19 affected treatment decisions were “changes to travel for treatment/change in place of treatment,” “changes in travel/living situations/other personal changes,” “changes to surveillance,” “changes, delays, or not receiving treatment to decrease risk of COVID-19 infection,” “continued on treatment that is not working,” and “did not continue to pursue a clinical trial.”

Symptoms of COVID-19 (coughing, fever, shortness of breath) were reported by 16 (14%) patients and caregivers. Six (5%) patients had COVID-19 testing, with one patient still awaiting results, and all of the other five tested negative. Increased anxiety about cancer treatment due to COVID-19 was reported by 72 (64%) participants.

Most of those who completed the survey were the patients themselves (72%), 13% were caregivers, and 15% did not report whether they were a patient or caregiver or played another role. Fourteen percent of the patients were 49 years old or younger (7% younger than 40), 48% were between the ages of 50 and 69, 13% were 70 to 79, 3% were 80 or older, and for 22% of the patients, their age was unknown. Most patients were female (66, or 59%), 30 (27%) were male, and for 14%, the sex was unknown. Thirteen types of cancers were reported, the most common cancer types being breast, lung, and colorectal cancer. Most of the participants were from the U.S. (70%) with 12 countries represented including Italy (7%), Canada (4%), Australia (3%), and the U.K. (3%).

To conclude, changes to appointments, treatment delays, and the impact of COVID-19 on treatment decisions were reported by patients and caregivers. The majority of patients (64%) reported increased anxiety about their cancer treatment during the COVID-19 pandemic.

Cancer Commons remains dedicated to helping patients and caregivers navigate their cancer journey and ensure they are able to access the best possible care. Get help now.

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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

The Challenges of Using Artificial Intelligence to Improve Cancer Treatment

Razelle Kurzrock, MD, and Jeff Shrager, PhD

In a previous post, CureMatch co-founder Razelle Kurzrock, MD, told us all about her company’s artificial intelligence (AI) platform that matches patients with treatments based on their cancer’s molecular profile. Here, AI expert Jeff Shrager, PhD, responds, and Kurzrock offers a rebuttal.

Shrager is Co-Founder and Director of Research at xCures, and was formerly Director of Research at Cancer Commons. He is also an Adjunct Professor of the Symbolic Systems Program at Stanford University. Email: jshrager@stanford.edu.

Kurzrock is Director of the Center for Personalized Cancer Therapy and the Rare Tumor Clinic at U.C. San Diego, and Co-Founder and Board Member of CureMatch, Inc. Email: razelle@curematch.com.

Shrager: Whereas I applaud Dr. Kurzrock and CureMatch for their efforts to apply machine learning in precision oncology, I want to offer a bit of a heads-up.

Whereas it is certainly true that “we live in the ‘big data’ generation,” two senses of that term are often conflated. Google and Facebook have enormous datasets with many independent observations across relatively few features. Medical data, especially at the molecular level, is exactly the opposite, having relatively few independent observations across an enormous feature space. Moreover, the settings in which modern AI (i.e., machine learning) has seen successes are those where there are either existence proofs of a solution, which can be drawn upon as a teacher, (e.g., self-driving cars, where even 16-year-olds drive cars adequately well), in closed systems for which we have excellent simulators (e.g., astrophysics), domains in which the roles are static (e.g., games), or in which experiments are basically free (games again, or any domain with a good simulator).

Medicine is completely different: We have essentially no simulations, medical experiments are extremely costly, we lack good treatments (which is why we’re bothering with this at all), and the treatment space changes rapidly. You can’t just teach your robot doctor to cure cancer by observing good doctors curing cancer, because there are no such doctors and cures—there may be some better and some worse doctors, but as far as I know, there isn’t one that can cure cancer “adequately well” who you can use as a guide; indeed, there may be no cure for cancer at all.

Heads up! Machine-learning applications in domains like medicine, where there are small numbers of samples that range over very high dimensionality feature spaces, and with the above-enumerated limitations, are exceedingly prone to getting stuck in non-optimal minima, preferring solutions that work well enough, over exploring solutions that might work better than the ones that have been observed or tried. The way out of this problem is active learning: Rather than taking the apparently best action in all cases, one must balance the strength of belief in one’s rankings against the information gain of trying something new. Doing this requires having a global view of the whole medical (or at least oncological) space, and working out some very difficult “statistico-ethical” questions. Indeed, this is what the clinical trial system is striving to do, although it is doing so horribly inefficiently, and will basically never get there. We can solve this problem, but it requires a much broader AI approach than simply treating each patient in accord with a locally-optimal solution.

(This commentary abbreviates the argument made in much greater detail in a paper I wrote with my colleagues at xCures last year for The Journal of Law, Medicine & Ethics: Is Cancer Solvable? Towards Efficient and Ethical Biomedical Science.) 

Kurzrock: I would like to thank Dr. Shrager for highlighting two excellent points pertaining to the use of AI in routine oncology practice and the inefficiency of clinical trials—I fully agree with him. Allow me to provide some brief comments.

First, I concur that current AI-containing software platforms are certainly not sophisticated enough to be “robot doctors” that could treat cancer. Indeed, decision-support platforms like CureMatch’s BionovTM are not here to replace oncologists. They are necessary tools that help oncologists process immensely complicated data, such as that revealed by next-generation sequencing of tumors. Decision-support platforms are rule-based systems that enable evaluation of complex information by utilizing prior knowledge, akin to the dimensional origami model Dr. Shrager referenced in his earlier work.

Moreover, some of the work that lends confidence to the decision-support platforms are clinical trials. I agree with Dr. Shrager’s point regarding clinical trials’ extreme inefficiency, the fact that they are indispensable to clinical oncology research, and the concept that new clinical strategies are needed, especially to address the questions raised by today’s precision medicine that utilizes complex molecular diagnostics. For example, the prospective cross-institutional I-PREDICT study demonstrated the value of customized, matched combination therapies (rather than scripted monotherapies) and of a matching score similar to that used by BionovTM. Other efforts, such as obtaining real-world data via a Master Observational Trial are also unique approaches that enhance the clinical trial process.

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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.