Despite the quantity and diversity of research that will improve the future for people with gastrointestinal (GI) cancers, the present is not a happy place for them, said John L. Marshall, MD, Chief, Division of Hematology and Oncology and Director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers at Lombardi Comprehensive Cancer Center. He moderated the symposium, "Molecular Diagnostics Drive Personalized Medicine: State of the Art 2010," which was held at Lombardi in early November.

"There is no continuum of treatment for the 275,720 people newly diagnosed with GI cancers last year (and the more than 135,300 deaths), and development of blockbuster drugs has just about stopped," he said. Not only are there upwards of 50 genetic mutations, we have barely begun to figure out their patterns. "Moreover, NCCN guidelines are no longer just guidelines; they have become 'the law of the land.' We give 97% of all patients the same treatment regimen (about 3% are in clinical trials), and 80% of them die regardless. The standard of care is less than adequate-far less."

With that gloomy preamble, Dr. Marshall introduced speakers who discussed the impact of personalized medicine on the health-care system. They approached the issues from different perspectives, but their messages were similar: Although new treatments for GI cancers are desperately needed, the endeavor must be approached thoughtfully, with attention paid to ethical ramifications and the ultimate value to patients of this very costly research.

Medicare Wants Treatments that Work

Louis Jacques, MD, Director of the Centers for Medicare & Medicaid Services (CMS) Coverage and Analysis Group, explained that cancer policy includes treatment with both curative and palliative intent, supportive care for complications and adverse events, and use of biomarkers for drug and/or biologic discovery and development.
When reviewing clinical evidence, CMS asks if the patient is better, if there is an increased chance of survival, and whether he or she can continue to function reasonably normally.

Dr. Jacques described some of CMS's challenges in molecular testing and biomarker development: standards and techniques that are not FDA approved ("home brews"), tests that may be used during drug development but that are not commercially available for clinical practice, and the problems posed by molecular testing when there is no simple way to recognize an erroneous or misleading test result.

How do these factors affect outcome? Is the patient better or worse off?

To evaluate these issues, or at least determine which questions are appropriate, CMS and other agencies use a process developed by the Centers for Disease Control and Prevention (CDC) for evaluating genetic tests. It's called ACCE and consists of:

• • Analytic validity: how accurately and reliably a test measures a genotype.
• • Clinical validity: how consistently and accurately a test detects or predicts intermediate or final outcomes.
• • Clinical utility: how likely the test is to significantly improve patient outcomes.
• • Ethical, legal, and social issues that arise in the context of using a test.

Bioethical Implications

In September 2007, when personalized medicine became the acknowledged wave of the future in cancer treatment, then Secretary of the U.S. Department of Health and Human Services (HHS) Michael Levitt coined a motto for it: The right treatment for the right person at the right time. (Andrew C. von Eschenbach, MD, former NCI Director and FDA Commissioner, would add: for the right reason and the right outcome.)

What does this mean? asked Kevin T. FitzGerald, SJ, PhD, Research Associate Professor and David Lauler Chair for Catholic Health Ethics, Georgetown University. "Who, after all, wants the wrong treatment-at any time?"

Public airing of Secretary Levitt's somewhat indistinct goal highlighted its elementary status and inherent challenges:

• • Health-care disparities are widespread in the United States, especially with regard to genetic endowment. This results in significant variance in response to drugs and biologicals.
• • Issues of race, sociology, and biogeographics also affect the way people respond to treatment-and whether they receive treatment at all.
• • All problems regarding privacy, informed consent, and liability were not resolved by GINA (Genetic Information Nondiscrimination Act). "People see these issues very differently, and they have widely varying views about benefit, risk, and harm," said Dr. FitzGerald.

Health-care Reform and Cancer Treatment

The Lombardi seminar took place 2 days after House Democrats received a shellacking at the polls, and Dr. von Eschenbach, now Senior Director for Strategic Initiatives at the Center for Health Transformation, Washington, DC, wondered aloud about implications of the election for health-care reform. "The Democrats who lost are conservatives, but the Republicans who took their places are even more so."

He thinks that at least for the next 2 years, the country will focus on the economy and jobs, as well as an effort to repeal the health-care reform law. He said that 54% of Americans are in favor of getting rid of the law, and there probably won't be much discussion about which parts of it should be saved and which can be ditched. "The emphasis is on repeal, repeal, repeal-rather than on the challenges of implementation and on the economics of change. President Obama is going to be hard put to save his signature legislation."

Dr. von Eschenbach believes that all decisions about health-care reform will have serious economic consequences for cancer research and cancer care, especially the pressure to lower costs. Finding new funds is just about impossible now. "We're broke," he said flatly.

Therefore, ensuring that all Americans have access to the health care they need requires what he calls the three As:

• • Availability. "If care doesn't exist, it obviously isn't available; therefore, innovation is imperative."
• • Affordability. "We need to be more disciplined stewards of our resources."
• • Appropriateness. "No one likes change, but we must create value for the research dollars we spend, and we have to generate jobs in the process." Moreover, the mass migration of innovation out of the United States and into China, India, and the rest of the world is having catastrophic effects on our economy. "We must foster innovation and development, and we must decrease cost and improve quality. This will engender profound and complex change over the next few years, but it's not just necessary, it's a matter of life and death." ■