New Glioblastoma Trial Adds Whole-Brain Irradiation to Plerixafor

Lawrence Recht, MD
Martin Brown D.Phil, FASTRO

A Q&A with Martin Brown D.Phil, FASTRO, Emeritus Professor, and Lawrence Recht, MD, Professor, at Stanford University’s Department of Neurology

Q: The treatment of glioblastoma multiforme (GBM) is a serious challenge. Recurrence after initial surgery is common and subsequent treatment almost always unsuccessful. Just as “an army marches on its stomach,” GBM growth depends on blood supply. Successful use of the FDA-approved drug plerixafor (Mozobil) combined with irradiation for mouse model gliomas some years ago has lead to clinical trials in human GBM.

What is the current status of these investigations, and how could our readers help the effort?

A: A little over ten years ago, Dr. Brown began a series of preclinical studies to test the possibility that an important contributor to the recurrence of malignant brain tumors after radiation therapy was reconstitution of the tumor vasculature. Specifically, he hypothesized that this reconstitution stemmed at least in part from circulating pro-angiogenic cells not in the tumor at the time of radiation—a phenomenon known as “vasculogenesis.” In agreement with this concept, a finding common to all of the tumor models he tested was a major influx into the irradiated tumors of bone marrow-derived cells, most of which were macrophages, that correlated with when tumors began to grow two to three weeks after completion of radiation. Further, he demonstrated that the mechanism for this influx was a radiation-induced hypoxia that triggered a cascade that led to the secretion of stromal cell-derived factor-1 (SDF-1), which was instrumental in attracting these cells. The apparent importance of excluding these cells’ entry into tumors post-irradiation suggests a new treatment strategy, which we call macrophage exclusion radiation therapy (MERT). Continue reading…


Serious Caveats in Screening for Pancreatic Cancer

A Q&A with Rama Gullapalli, MD, PhD; a a physician-scientist in the departments of Pathology, Chemical and Biological Engineering at the University of New Mexico. His research lab focuses on the role of the environment in hepatobiliary cancers. He is also a practicing molecular pathologist with an interest in emerging molecular diagnostics, next generation sequencing and bioinformatics. Email: rgullapalli@salud.unm.edu 

Q: A recent New York Times op-ed piece from an NYU Langone Health professor urged an aggressive approach to screening for early-stage pancreatic cancer. Despite optimism, the history of cancer screening is rife with trouble, the harms often exceeding the benefits. What do you think is the best way to proceed?

A: Imagine a scenario.

A new cancer test hits the market with some impressive characteristics: a detection sensitivity of 95% and a specificity of an equally impressive 95%. If you were asked the question, “Given a positive test result, what are your chances of actually having cancer?” and you guessed a number of 80 or 90%, you would not be alone. But you’d be wrong.

The key missing information necessary to answer this question is the disease probability among the general population. The number of new cases of cancer detected every year in the U.S. is about 462 cases per 100,000 people. This means that the probability of a new cancer being detected in a member of the U.S. population annually is roughly 0.00462%. Incorporating this information leads to only an 8.1% chance of having cancer for a test that is positive! This is what is called an inverse probability problem. Continue reading…


Encouraging and Paying for Clinical Trials, Right to Try, and Expanded Access: Part Three

A Q&A with Mark Shapiro, PhD,Vice President of Clinical Development at xCures, Inc.Partner at Pharma Initiatives; mshapiro@xcures.com. This is the final installment in a three-part series in which Dr. Shapiro has shared his thoughts on the question below. Read part 1 and part 2.

Q: Treatment of Americans with advanced cancer is complex and challenging and can be very expensive. Many urge greater participation of such patients in clinical trials. In general, who pays the expenses of clinical trials? And, specifically, how are the costs for Right to Try and expanded-access approaches reimbursed?

A: In clinical research, agreements between the research sponsor and the treating institution define what aspects of a study protocol are charged as research or related administrative costs, and what items are considered standard-of-care; that is, eligible for billing to insurance. This is made by a coverage review at the institution. While the sponsors provide the study drug freely to the site and patients, they expect to receive valuable data in exchange. In expanded access, which is treatment rather than research—but stills follows a protocol approved by the U.S. Food and Drug Administration (FDA)— sponsors pay the required administrative costs and the free provision of the investigational drug. The drugs are expensive, and the sponsor incurs additional compliance costs when they make an investigational drug available. So, expanded access is largely a charitable act on behalf of the sponsor. While there are regulations allowing sponsors to recoup their costs under expanded access, these are rarely used. Most sponsors, especially larger companies, deliberately plan for expanded access when planning manufacturing campaigns during oncology drug development. In fact, large sponsors report that they approve about 95% of the expanded-access requests that they receive. Continue reading…


Encouraging and Paying for Clinical Trials, Right to Try, and Expanded Access: Part Two

A Q&A with Mark Shapiro, PhD,Vice President of Clinical Development at xCures, Inc.Partner at Pharma Initiatives; mshapiro@xcures.com. Last week, Dr. Shapiro shared his initial thoughts on the question below. Today, he discusses issues of cost and equitable access to care.

Q: Treatment of Americans with advanced cancer is complex and challenging and can be very expensive. Many urge greater participation of such patients in clinical trials. In general, who pays the expenses of clinical trials? And, specifically, how are the costs for Right to Try and expanded-access approaches reimbursed?

A: In late-stage cancer care, treatment is very expensive. While there is a great deal of focus on the cost of the drugs, many other costs are involved, including the cost of care, the cost of the facility, and the cost of laboratory and other tests. When you add clinical research on top of care, there are additional tasks, but it is normally the research sponsor that pays for those administrative and research costs, which are incurred by physicians and the institutions conducting the clinical trial.

Insurance companies also pay for at least some of the associated costs of care. In fact, sponsors of cancer trials strive to design studies that follow existing standards of care to minimize the additional costs of non-standard procedures. The Affordable Care Act (ACA) specified that standard-of-care procedures delivered during a clinical trial could be charged to insurance for studies conducted under an Investigational New Drug application. Before the ACA, insurers in many states did not cover procedures performed when the patient was in a clinical trial, so the passage of the ACA can be credited with the increase of access to and enrollment in cancer clinical trials in the past few years. Patients also bear many of the costs of their cancer care, even when they are in clinical trials, because they are responsible for insurance copays and deductibles. Continue reading…


Encouraging and Paying for Clinical Trials, Right to Try, and Expanded Access: Part One

A Q&A with Mark Shapiro, PhD,Vice President of Clinical Development at xCures, Inc.Partner at Pharma Initiatives; mshapiro@xcures.com

Q: Treatment of Americans with advanced cancer is complex and challenging and can be very expensive. Many urge greater participation of such patients in clinical trials. In general, who pays the expenses of clinical trials? And, specifically, how are the costs for Right to Try and expanded-access approaches reimbursed?

A: Incorporating clinical research into the clinical care of cancer patients may provide more options, and better outcomes, but participation is quite low. In 2004, only about 3% of American cancer patients participated in clinical trials.

More recent data suggest that the number may now be about 5%, although it is lower for women, children, minorities, and patients in community settings. The low figure should be of concern for a couple of reasons. First, patients are the scarcest resource in cancer research. Low participation in clinical trials represents a lost opportunity to learn and improve care. If every patient were part of systematic research, we could greatly accelerate the pace of cancer research findings. Second, most cancer treatment guidelines recommend a clinical trial as the standard-of-care at some stage in the course of disease. So, with current levels of participation, as many as 95% of American cancer patients are NOT receiving standard-of-care treatment at some point in their care. This deficit is partially attributed to the presence of comorbidities or poor function. Recent research suggests that liberalizing inclusion and exclusion criteria in clinical trials could increase enrollment by about 45%. In the study of common cancers, enrollment of patients with solid tumors could be increased from about 7% to 11%. Continue reading…


At Diagnosis, What Do Cancer Patients Want?

A Q&A with Laura Benson, RN, MS, ANP, president of Conversations in Care, LLC; LauraBensonRN@Gmail.com

Q: In our digital communication world of 2019, some patients may receive the initial message that YOU HAVE CANCER by cell phone, text, email, or even voice mail. When this happens, what do patients most want, and how can that best be accomplished?

A: When I first read your question, I was immediately brought back to a National Cancer Survivors Day around 1988. During the open microphone portion of the program, a patient bravely rose to address the audience. She proceeded to tell us she didn’t know she had cancer until she received the Survivors Day invitation, whereupon she turned to her attending physician and asked, “Well doctor, do I have cancer?” Since then, communication in today’s digital age has not seen a vast improvement. Indeed, a recent report out of California tells the tale of a patient and family learning he was dying via a video robot interaction.

What has not changed over the decades is the need for information that is easily understood, easily accessible, scientifically accurate, and delivered with compassion and connection. The dawn of the “Dr.Google” age has brought new and unique challenges. Continue reading…


Capturing Patients’ Real-World Experiences to Improve Cancer Research and Care

A Q&A with Grace Castillo-Soyao, founder and CEO of Self Care Catalysts; grace@selfcarecatalysts.com

Q: You are well known as a visionary in the field of Real World Experience-Evidence (RWEE). As the founder and CEO of Self Care Catalysts, headquartered in Toronto, how do you see RWEE evolving to favorably impact the field of oncology?

A: I started Self Care Catalysts with some very basic questions. Why is the patient at the farthest end of the care line, treated as simply the recipient of care? It’s a very industrial mindset, a bit like an assembly line; the patient as something to be acted upon. But patients are often experts at their own conditions, including the many kinds of cancer. Why are they not invited to become participants in their own care, in contributing their own experiences? Why are patient experiences not considered to be scientifically valid?

As noted physician Sir William Osler famously said, “It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has.” Continue reading…


The Crucial 90% Missed by Doctors on Computers

A Q&A with Kevin B. Knopf MD, MPH, chairman of hematology and oncology at Highland Hospital in Oakland, California; kevinbknopf@gmail.com

Q: A successful patient-physician relationship depends upon effective bidirectional attention and mutual understanding. Many patients and physicians believe that common current versions of mandated electronic health records (EHRs) severely impede that interaction, especially eye contact. How can a competent and caring clinical oncologist overcome that problem?

A: For all my faults as a doctor, and I’m sure there are many, there is one thing I think I do correctly, and that is I am never on a computer in front of a patient.

I hear from many colleagues that they can be efficient and personable while going back and forth from the patient to their electronic health record (EHR)—and it is true there are various levels of skill here. However, none do as well, in my opinion, as a computer-free patient environment. I say this from my side as a patient having seen dozens of doctors myself—nothing compares to a doctor who spends all of their time looking you in the eye and interacting face to face. This human contact costs nothing, and yet is so vital. Continue reading…


Challenging Oncology Therapies With Moonshot Price Tags

A Q&A with Pramod John, PhD, CEO of VIVIO Health, a specialty drug management company in San Leandro, CA, that aims to provide better outcomes at lower costs; pramod@viviohealth.com

Originally published December 13, 2017

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? Continue reading…