One must define the difference between the potential of a new test and its actual value. The first question that is usually asked: putting cost aside, how could more information hurt? It is, in fact, such an exciting time for medicine—particularly personalized/precision medicine in the era of genomics. Imagine not having to undergo the pain, risk, and expense of a tissue biopsy; instead, you just have a tube of blood taken. In addition to the more mundane search for circulating tumor cells&mdash;which has been used for decades in breast cancer to assess risk of recurrence&mdash;new technology allows for the detection of tumor-specific DNA using fast DNA sequencing machines.

Many physicians are excited by the possibility of following the evolving story of their patients’ cancer no longer through images including PET scans, but through changes in the molecular phenotype of their patients’ tumors. Questions raised are: what can the natural history of tumor evolution through blood biopsies tell me? Will it allow me to alter my therapy to prevent an outcome adverse to my patient? We just do not know for sure; and therein lies the problem.

When asked what harm blood biopsy information can do, let’s start with the clinical. It remains unclear what, if any, therapeutic action can change the natural history of a disease process that is already undergoing a specific therapy. There is no doubt that, in the prognostic sense, this information may be useful; however, we are nowhere near blood biopsies giving us actionable knowledge that would justify midstream changes in therapy. On the rare occasion when a new mutation shows up, then possibly a relevant targeted therapy change might be useful.

However, most times, a blood biopsy will show evidence of the same tumor-related DNA as before. If it were to increase in quantity or recur after abating and a patient is mid-cycle in therapy, what would a clinician and patient do? Stop therapy because it is futile, change therapy in a nondirected fashion, or ignore the test result altogether? In the context of clinical trials, to learn what should be done, promise remains. In the clinic, it is less clear.

Now let us discuss cost. This is not inconsequential.

We are facing a cost-of-care crisis in America. If we are going to add expensive tests—particularly if they are used frequently during the care of a patient&mdash;we must address how we are to pay for them. We are soon going to enter the zero-sum game in healthcare. Do we spend our resources on being able to predict relapse sooner or on new medications that hold promise? Doctors and patients will face these tough choices unless, together with clinical validation of blood biopsies, we also validate the economic value of the test to the patient and the payer.

Clonal evolution of malignancy, detection of minimal residual disease, and earlier detection of recurrence will all become routine with blood biopsy. To avoid becoming too enthusiastic about liquid biopsies, we need to focus on asking proper value-based questions to justify the excitement.

Articles

Many physicians are excited by the possibility of following
the evolving story of their patientsâ€™ cancer no longer
through images including PET scans, but through changes
in the molecular phenotype of their patientsâ€™ tumors.

Liquid Biopsy Mania Leaves Questions Unanswered

		Chief Innovations Officer, Professor, and Vice President of Cancer Services

		John Theurer Cancer Center at Hackensack University Medical Center

	Charles Dickens created a character in his 1844 novel, The Life and Adventures of Martin Chuzzlewit, who took money fraudulently from unsuspecting investors after promising extraordinary returns. Years later, a real-life figure, Charles Ponzi (1920), did the same, redistributing the investors’ own money as a return on their investment without actually investing it and fueling the enterprise with funds from subsequent investors. The fraud continued until there were insufficient new investors to fund returns for existing investors. In addition to a long jail sentence, Ponzi received the inglorious honor of having the fraudulent investment scheme named after him. More recently, Bernard Madoff refined the Ponzi scheme to an art form, resulting in estimated losses to investors of $18 billion.

	Eighteen billion dollars sure sounds like a lot of money until it is contrasted with the current $2.6 trillion at risk in the Social Security Trust Fund. Unlike a Ponzi scheme, here the money is invested, but at a rate of return of 4.6% (in 2010). This return is well below what the Social Security Board of Trustees project required to prevent the trust from exhausting by 2036. More staggering is the projection from the Trustees that an additional $6.5 trillion will be needed to pay all scheduled Social Security and disability benefits. Participation in Social Security is not optional, so Madoff’s scheme would appear that of a rank amateur in contrast. Presumably these facts, in part, prompted Texas Governor Rick Perry in a recent Republican debate to characterize Social Security as a “Ponzi scheme.” He was rightly criticized because unlike Madoff, the intent of Social Security is not to defraud investors (or in this case, taxpayers), but Perry is partly correct because we know that the program’s cost will soon exceed the current rate of return.

	A significantly greater problem is the increasing cost of healthcare. By spending 17% of the gross domestic product on healthcare annually in the United States, even $6.5 trillion seems like a small sum. Here are a few incontrovertible facts: our population is growing and aging; people are living longer; and care is more complex and applied for longer periods, so it is more costly. Add to this equation some social expectations: Everyone has a right to healthcare, and people can freely participate in costly health behaviors (eg, smoking tobacco). Together, these factors do not hold great promise for reducing the cost of healthcare.

	It is somewhat perplexing what our society finds acceptable to permit or to prohibit. We charge people more for automotive insurance if they have motor vehicle accidents or are at greater risk (eg, young drivers), but do not assess higher health insurance premiums for people who smoke tobacco, drink alcohol excessively, or do not have an ideal body weight. In contrast, we have no problem making it illegal for a 20-year-old to buy a bottle of beer, yet it is legal for him or her to vote in presidential elections, drive a car, marry and have children, and die in defense of our country.

	Similar to a Ponzi scheme, the healthcare expenditures of the Centers for Medicare & Medicaid Services (CMS) will soon outpace the revenue needed to support it, despite the legal requirement to contribute to the fund. The math requires that we change the expectations of our citizens and begin to ration healthcare in one form or another, or dramatically change our behaviors and assume some level of responsibility as individuals for the cost of care. Otherwise, CMS and healthcare in general may become the greatest “Ponzi scheme” of all time.

Here are a few incontrovertible facts: our population is growing and aging; people are living longer; and care is more complex and applied for longer periods, so it is more costly.

A Ponzi Scheme: Investments, Social Security, Healthcare

 (noun). A situation that requires a choice between options that are or seem mutually exclusive. 

Thorndike-Barnhart Comprehensive Desk Dictionary (1962)

	The current question facing patients, physicians, payers, and society is: Can we truly afford to provide each patient diagnosed with cancer comprehensive, state-of-the-art care until death? Or can we afford not to?

	In 1971, President Richard M. Nixon declared war on an enemy that each year claimed the second largest number of lives in the United States: a disease called cancer. At the time, little was known about the cause and biologic mechanisms of cancer, yet there was a national consensus that more information was needed to achieve victory over this dreaded disease. Consequently, President Nixon signed into law the National Cancer Act, which gave the National Cancer Institute (NCI) privileged autonomy and funding separate from the National Institutes of Health.

	As we celebrate the 40th anniversary of its signing, the National Cancer Act’s “societal benefits” remain in question, according to a comprehensive review published recently (

 2011;331[6024]:1539). President Nixon would be pleased to know that there is little doubt regarding the clinical benefits that have stemmed from the National Cancer Act. The incidence of cancer started dropping in 1990 and continues to do so, as do the overall mortality rates among patients with cancer. Surveillance, Epidemiology, and End Results (SEER) data confirm that age-adjusted death rates have dropped from over 200 per 100,000 pre-1971 to 178 per 100,000 in 2007. The prevalence of cancer has increased significantly as well, primarily due to the increased survivorship as a result of more effective therapies. Vincent T. DeVita, Jr, MD, former director of NCI, recently stated, “The War on Cancer did everything it was supposed to do…. Every benchmark of the mandate—better understanding of the biology, improved survival, lower incidence&mdash;was hit.”

	Despite the progress made in the War on Cancer, a President has another important duty: namely, to protect the integrity of our national economy. Data published in 1965 by the Centers for Medicare & Medicaid Services showed healthcare expenditures to be 5% of gross domestic product (GDP). Since then, healthcare expenditures have outpaced growth in GDP and are rapidly approaching 20%—a growth rate considered unsustainable by everyone on both sides of the aisle.

	The cost of cancer care is increasing dramatically in large part due to the fruits of the National Cancer Act. Until 1996, the standard use of 5-fluorouracil and leucovorin for metastatic colon cancer resulted in a median response rate of 12 months at a cost of $100 for 6 months of therapy. While a better understanding of the molecular basis of metastatic colon cancer has led to the development of new agents that have significantly increased patients’ median survival (now 21 months), these advances also come at a remarkable increase in cost. For example, the aggregate cost of treating metastatic colon cancer can easily exceed $150,000 for an additional year of survival, compared with 5-fluorouracil and leucovorin alone. Today, translational medicine is transforming outcomes for cancer patients. Recent drug approvals like sipuleucel-T (Provenge) for metastatic prostate cancer and ipilimumab (Yervoy) for metastatic melanoma significantly increase survival, but at a cost in excess of $100,000 for a single course of therapy.

	Economists use the term “moral hazard” to describe situations where consumers insulated from risk behave differently than those who bear the full risk. We often see this behavior in healthcare when insured patients who only pay a portion of the cost of treatment (ie, copays) actually drive up the demand for more—and even more expensive&mdash;care compared to patients who have to bear the full cost of care. To combat the effects of this type of moral hazard, the current healthcare dialogue now includes discussions with patients about things such as when the appropriate time is to initiate palliative care. Such discussions are designed, in part, to avoid unnecessary expenditures. In the UK, this dialogue has been elevated to the point where governmental agencies evaluate the costeffectiveness of a given therapy to determine if it is worth the investment, and then possibly deny the therapy even if it prolongs survival.

	One wonders what President Nixon would have done if he knew his actions would dramatically improve the outcomes for cancer patients, but at the same time put the nation at risk of becoming fiscally unsound and uncompetitive on a global scale, largely due to the dramatic increase of cancer care expenditures. Yogi Berra, the great philosopher and former New York Yankee, once said, “When you come to a fork in the road, take it.” We are clearly at a fork in the road. Do we limit access to lifeextending care or spend ourselves into insolvency? It is no longer President Nixon’s dilemma, it is ours.

	Hopefully, the broad use of evidence-based guidelines and the continued efforts in translational medicine to find cures—and not just therapies that extend survival&mdash;will allow every cancer patient to benefit from the intent of the National Cancer Act without the risk of a moral dilemma.

Can we truly afford to provide each patient diagnosed with cancer comprehensive, state-of-the-art care until death? Or can we afford not to?

President Nixon's Dilemma

It is my sincere honor and pleasure to initiate a partnership between Intellisphere’s Oncology Specialty Group and the John Theurer Cancer Center at Hackensack University Medical Center, and to assume the responsibility of editor-in-chief of 

	With its full slate of magazines, journals, special projects, and Web site, the Oncology Specialty Group has made its mission clear: To provide oncology specialists, including medical and surgical oncologists, hematologists, and radiologists, with the most current information about cancer and to explain how that information can be used to improve multiple aspects of your practice.

	The John Theurer Cancer Center is proud to be partnering with Intellisphere to advance this mission by overseeing editorial content development and helping to provide in-depth content, new learning opportunities, and bestpractice approaches to cancer care.

	Intellisphere’s presence in the oncology market has grown steadily during the past few years. That presence is best represented by its 4 main publications: 

Oncology & Biotech News, Contemporary Oncology, 

	The research and news published in print and online help bridge the gap between innovation and application in state-of-the-art cancer care. Intellisphere’s oncology publications make it easy for busy oncologists to keep abreast of the latest developments by providing timely, concise, and practical coverage of this dynamic field.

	It is for this reason—the ability to play an active role in delivering reliable information that helps improve cancer care&mdash;that we at the John Theurer Cancer Center immediately gravitated to this opportunity and were excited to form this partnership.

	During the past few years, the John Theurer Cancer Center has demonstrated its commitment to education by hosting our own professional conferences featuring international experts and by establishing a presence at national conferences, such as the American Society of Hematology (ASH), where our researchers presented more than 40 abstracts in 2010.

	Last fall, we hosted a conference entitled “Current and Innovative Modalities in the Management of Hematologic Malignancies” that brought some of the world’s experts to one stage. Speakers included Kenneth C. Anderson, MD, from the Dana-Farber Cancer Institute, Frederick R. Appelbaum, MD, from the Fred Hutchinson Cancer Research Center, James O. Armitage, MD, from the University of Nebraska, and many others. Highlights from the meeting were published in Oncology & Biotech News, and we look forward to expanding the coverage of these types of events and to bringing our readers innovative concepts, news stories, and research studies that explore current themes in oncology and hematology and how they relate to your practice.

Innovation and Advancement in Cancer Care

	Innovative approaches to cancer care are progressing with astounding rapidity. Recent research presented at the American Society of Clinical Oncology (ASCO) and ASH constitutes an inflection point in diagnostic and therapeutic advances, and the correlation of genomics to both of these areas.

	Tissue banks, personalized medicine, targeted therapies, and new devices represent just a few of the cutting-edge shifts in cancer care.

	These and many more are part of the fabric of the daily approach to fulfilling our own mission at the John Theurer Cancer Center: To provide extraordinary care to every patient who comes into contact with our professionals.

	For the past 10 years, I have been the chairman of the John Theurer Cancer Center and recently became the chief innovation officer for the Hackensack University Medical Center.

	I am proud of our current standing. Our team of researchers has published more than 100 peerreviewed articles within the past year. Plus, as one of the largest cancer centers in the country based on volume, we have taken a national leadership role in several key areas of cancer care.

	With 14 specialized divisions, leading innovative technologies such as TrueBeam™ and the da Vinci® Surgical System, one of the largest stem-cell programs in the country, and a tumor bank that strategically positions us for the movement toward personalized medicine and targeted therapies, we are constantly striving to treat not only the most common cancers, but also the most challenging cases.

	In a brand new 155,000-squarefoot cancer center specially designed to be patient-centric, we apply a multidisciplinary approach that offers some of the best nurses, allied health staff, and researchers in the nation.

	Patient satisfaction and the patient experience are also of utmost importance to us. Our second annual “Celebrating Life and Liberty” event on Ellis Island brought together more than 1500 patients, caregivers, and family members last fall. We also host many other events that provide patients and their loved ones the opportunity to access a tremendous support network and to understand how to cope with their treatment in the context of their daily lives. Intellisphere’s family of oncology publications shares that commitment to patient care by providing ongoing coverage of patient stories and sharing other cancer centers’ innovative strategies that have improved the patient experience.

	As we look to the future and assess where approaches to cancer are moving, there is a pressing need to continue the momentum that has been established through recent innovative techniques, and to ensure that all physicians have access to credible information so that the field continues to learn and advance.

	Our partnership with the Intellisphere Oncology Specialty Group is a tremendous opportunity to garner the latest advancements in cancer prevention, diagnosis, and treatment and apply them to daily practice in a way that is relevant and helpful. Moreover, as the national healthcare landscape rapidly evolves with the formation of accountable care organizations and as consumer demand for transparent, value-based healthcare increases, we will provide a running, informative commentary to keep you abreast of the changes and to help you best position your practice.

	To that end, we invite the readers of these publications to participate as much as possible. We want to ensure that the material we provide brings together what is occurring at the bench, in the clinic, and in the marketplace to address the real challenges, obstacles, and opportunities that you experience in your practice.

	We look forward to hearing from you. Together we hope to promote a better understanding of the wide-ranging approaches to cancer care and, just as importantly, their implications for our daily practices and our patients.

The John Theurer Cancer Center is proud to be partnering with Intellisphere to advance this mission by overseeing editorial content development and helping to provide in-depth content, new learning opportunities, and bestpractice approaches to cancer care.

Andrew Pecora, MD

Articles

Liquid Biopsy Mania Leaves Questions Unanswered

A Ponzi Scheme: Investments, Social Security, Healthcare

President Nixon's Dilemma

Announcing a New Partnership and an Opportunity for Growth