OncologyLive® is the flagship publication of OncLive®. Each issue delivers expert insights and clinical oncology news and updates, which impact the day-to-day clinical practice of oncology professionals who work tirelessly to help improve patient outcomes.

Despite the importance of the recently enacted federal healthcare law, a remarkable 50% of the public does not know its current status, according to a recent poll. This alarming example illustrates why scientists and public health officials must use the Internet to fill the need for reliable sources.

	How does one explain the results of a Kaiser Family Foundation poll conducted among the general public about the specific status of the recently enacted federal healthcare reform legislation?

	Nearly one-quarter of those surveyed believed the law had been repealed, and another quarter was not sure of the status. Remarkably, despite the enormous impact this law will have on the future direction of healthcare for every American, approximately 50% of those surveyed were unaware of the current status of this massive initiative.

	As important as this legislation is to the future of healthcare delivery in the United States, it is clear that there is considerable confusion and misunderstanding. Is this the result of information overload, an inability of many members of the public to understand the relevance of the complex debate, too little time to absorb the nuances of legislative maneuvers, or the apparent absence of information sources that are recognized as unbiased and authoritative?

	While it is most unlikely that a single factor or even a limited group of factors will be identified that can explain the apparent inadequacy of public knowledge regarding facts so vital to their own futures and their children’s futures, it is reasonable to conclude that information overload, both the total content and the proliferation of purported sources of such information, are major contributors to the rather alarming status quo.

	Unfortunately, the impressively democratic nature of the Internet, which makes this spectacular form of communication such a powerful educational tool, does not ensure the quality, objectivity, or even the basic safety of its content.

Vice President of Patient Oncology Services and National Director for Medical Oncology

		Cancer Treatment Centers of America, Eastern Regional Medical Center

	Consider, for example, the use of the Internet to promote truly dangerous “stem cell clinics,”

 to intensely market unsubstantiated claims for unregulated e-cigarettes,

 or to suggest health benefits from a “miracle mineral solution” that the FDA warns becomes a “potent bleach when mixed according to package directions.

	In fact, the Internet has become a major force in the marketing strategies of the legitimate pharmaceutical industry, with one report noting a billion dollars has been spent employing this form of direct-to-consumer advertising.

	Unfortunately, the actual ability to effectively regulate what is stated on the Internet will be very difficult, as will the ability to monitor and control what patients and the public ultimately purchase. Finally, in the absence of physician oversight of such practices, adverse events will likely be substantially underreported, further negatively impacting the effects of promoted strategies on the well being of individuals and the general public.

	As has been noted previously in this column, the Internet is completely agnostic to quality or facts. But despite the potential for genuine harm to result from the activities of unscrupulous individuals, the Internet can truly become the focus of effective and intense communication strategies undertaken by highly reputable health-related organizations that desire to present factual data objectively and to educate the public and patients regarding complex and potentially difficult, as well as emotional, topics.

	In this regard, one only needs to look as far as the recent events in Japan and the understandable concern about the risk of exposure to radiation among populations far from the heavily damaged nuclear power plants. Internet sites with scientifically accurate and easily understandable information regarding risks and potential strategies that might reduce that risk (eg, potassium iodide pills)

	The health-related information flow may be both fast and massive, but that does not mean it will be easy to separate the valid from the invalid, and the frankly truly dangerous. In this, and many other circumstances, one can only hope that the community of scientists and public health officials can effectively employ the Internet to fill a concerning void.

			Haberkorn J. Repeal has Americans flummoxed. 

			Mitka M. Troubled by “stem cell tourism” claims, group launches Web-based guidance. 

			Yamin CK, Bitton A, Bates DW. E-cigarettes: a rapidly growing Internet phenomenon. 

			FDA Consumer Health Information. ‘Miracle’ treatment turns into potent bleach. 

. Published October 2010. Accessed May 26, 2011.

			Liang BA, Mackey T. Direct-to-consumer advertising with interactive Internet media: global regulation and public health issues. 

			Rockoff JD. Potassium iodide runs low as Americans seek it out. 

Articles

Despite the importance of the recently enacted federal healthcare law, a remarkable 50% of the public does not know its current status.

The Internet Dilemma: Awash in Information, Drowning in Ignorance

	Martine J. Piccart-Gebhart, MD, right, discusses developments in breast cancer with Gabriel N. Hortobagyi, MD, FACP, left, and Alan S. Coates, MD, center, at the American Society of Clinical Oncology’s 41st Annual Meeting in Orlando, Florida, in 2005.

Martine Piccart-Gebhart, MD, PhD is a professor of oncology at the Université Libre de Bruxelles and director of the Medicine department at the Jules Bordet Institute in Brussels, Belgium. She is also a founder and chair of the Breast International Group (BIG) and a past president of the European Organization for Research and Treatment of Cancer (EORTC). She is the recipient of numerous awards in recognition of her clinical research into breast cancer.

			What role does HER2 signaling play in normal cells?

		HER2 is a cell membrane surface-bound receptor tyrosine kinase and is involved in the signal transduction pathways leading to cell growth and differentiation. HER2 is important for growth and repair of normal cells and has a particularly critical role in normal breast and cardiac tissue.

			How important is it in cancer development?

		HER2 is probably very important in breast cancer development as it is expressed in over 50% of in situ tumors and only around 15% of invasive breast cancer, suggesting that it has a role in the initiation of breast tumors.

			What is the current status of HER2-targeted therapies?

		Trastuzumab is still the only registered anti-HER2 therapy for early breast cancer. Lapatinib is currently registered in the metastatic setting after failure of trastuzumab. With the results of the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) study due in the next few years, lapatinib may become incorporated into the standard of care.

		A new trial evaluating the combination of pertuzumab and trastuzumab versus trastuzumab alone is expected to start for early breast cancer patients with HER2 breast cancer late this year. Recent results from the neoadjuvant setting evaluating doublets—pertuzumab and trastuzumab (NeoSPHERE) and lapatinib and trastuzumab (NeoALTTO)&mdash;suggest that combination anti-HER2 therapy may be significantly better than single-agent HER2 blockade.

		There are a number of agents inhibiting the PI3K pathway currently in early- phase testing, which may also be promising in the future in combination with trastuzumab.

			What is the future for HER2 signaling in cancer research?

		We are in a very exciting era for anti-HER2 agents as there are many promising new agents in development. Clinicians will need to determine the best agents and combinations to test and use.

		The natural history of HER2 breast cancer has radically changed in the last 10 years, and we should not slow this progress. It is becoming evident that breast cancer patients who overexpress HER2 may not require intensive traditional cytotoxic chemotherapy if given potent anti-HER2 agents. Also, we see different response rates between those HER2 breast cancer patients that are positive or negative for the expression of the estrogen receptor (ER); therefore, different therapeutic approaches and trial design may be required dependent on ER status.

		Another issue that has yet to be explored is the contribution of the host immune system to clinical outcome with anti-HER2 agents. Trastuzumab has known immunotherapeutic effects, and it is unclear how important these are for the patient, or if certain women derive different benefit from a monoclonal antibody depending on their immune system. New agents that “boost” host immunity against tumor cells are currently available and should be explored.

Martine Piccart-Gebhart, MD, PhD is a professor of oncology at the Universite Libre de Bruxelles and director of the Medicine department at the Jules Bordet Institute in Brussels, Belgium.

4 Questions for Martine Piccart-Gebhart, MD, PhD: Noted Breast Cancer Researcher Has Bright Hopes for HER2 Targets

	The first drug that successfully targeted the HER2 pathway in cancer treatment generated much excitement. In an unprecedented break from the typically sober language of scientific journals, the breast cancer drug Herceptin (trastuzumab) was touted as “a dramatic and perhaps permanent perturbation in the history of the disease, maybe even a cure” in a 2005 

	Since its approval in 1998, Herceptin, which targets the HER2 protein, has become one of the most common therapeutic agents used in the treatment of breast cancer. Now, researchers are seeking to build upon the drug’s success by exploring its potential in combination therapy, sharpening the methods of identifying HER2 overexpression, and developing biomarkers to better identify patients who would benefit from the therapy.

	HER2 is a member of the human epidermal growth factor receptor (EGFR) family, along with 3 other proteins: HER1 or EGFR, HER3, and HER4, all of which are receptor tyrosine kinases that feed into a complex biological signaling network controlling numerous cellular processes, including proliferation, survival, differentiation, angiogenesis, invasion, and metastasis.

	Dimerization, the process through which two receptors such as HER2 join, plays a crucial role in receptor signaling. Multiple ligands bind to the different HER receptors with different binding specificity, exposing an extracellular dimerization domain and enabling 1 receptor molecule to pair with another.

	The paired receptor molecules phosphorylate one another on tyrosine residues on their intracellular domains. The activated receptors are then able to bind to intracellular signaling molecules and initiate a variety of signaling pathways, including the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway.

	HER2 has no known ligand, and therefore relies for activation on heterodimerization with other HER receptors, or homodimerization with itself when it is expressed at very high levels on the cell surface. The HER2 receptor remains in a constitutively active conformation. Consequently, HER2 is the preferred partner for other members of the HER family.

	Herceptin may activate an immune response, leading to cell death.

	HER2-containing heterodimers are the most prevalent and active of all the receptor pair combinations. For this reason, the HER2 signaling pathway is a target of significant interest for cancer researchers. Since the discovery of the 

 oncogene in 1979, a high frequency and broad spectrum of aberrations in this pathway have been observed in human tumors.

	Axel Ullrich, PhD, and H. Michael Shepard, PhD, researchers at the then-fledgling biotech company Genentech, identified the protein produced by this gene in 1984 and, together with Dennis Slamon, MD, PhD, discovered that the HER2 receptor is overexpressed in between 25% to 30% of breast cancers and is associated with more aggressive disease and a poorer outcome. More recent clinical data also support the role of HER2 in other tumor types, including gastric, thyroid, and head and neck cancers.

	Defining the number of HER2 receptors remains controversial.

	Interest in the HER2 pathway was stimulated, and in 1989, Ullrich and colleagues identified a monoclonal antibody that selectively bound to the extracellular domain of HER2, which specifically inhibited the growth of breast cancer cells overexpressing the HER2 receptor. This antibody was developed into the renowned drug trastuzumab (Herceptin, Genentech).

	A wealth of clinical trials has demonstrated the efficacy of trastuzumab in combination with numerous chemotherapeutic agents. It became the first HER2-targeted therapy to gain FDA approval for the treatment of HER2-positive breast cancer. Landmark phase III trials reported in 

 in 2005 demonstrated that trastuzumab given after primary therapy (including surgery and chemotherapy) reduced recurrence rates by approximately 50%.

	Despite the success of trastuzumab in treating both early- and advanced-stage HER2-positive breast cancer—at least as a single, first-line agent&mdash;it did not prove to be the “cure” that many hoped it would be, with objective response rates of only 26%. Furthermore, many patients treated with trastuzumab experience relapse or progression, mainly due to the development of drug resistance via a number of possible mechanisms.

	First, trastuzumab does not block heterodimer formation, and therefore does not prevent ligand-dependent formation of the most potent HER2/HER3 signaling dimers. Second, a truncated form of HER2, known as p95, which lacks the extracellular domain to which trastuzumab binds, is commonly detected in HER2-positive breast cancer. Finally, secondary mutations in signaling components downstream of HER2, such as PI3K/Akt, may also drive trastuzumab resistance.

	As a result, efforts are underway to develop other HER2-targeted therapies to overcome these issues. A small-molecule tyrosine kinase inhibitor (TKI), lapatinib (Tykerb, GlaxoSmithKline), is the only other HER2-targeted therapy currently on the market. It was approved as a second-line therapy for HER2-positive disease in 2007, following reports that its addition to capecitabine (Xeloda, Genentech) improved patient survival over capecitabine alone. Lapatinib is a dual-action TKI, targeting the intracellular domain of HER2 and HER1, and, as such, may be particularly useful in patients with p95 truncations.

	Pertuzumab (Roche) is a humanized monoclonal antibody, the first in a new class of HER dimerization inhibitors. Pertuzumab binds to a different epitope of the HER2 extracellular domain than trastuzumab and is able to block HER2 dimerization. It is currently undergoing phase III clinical trials for use in combination with trastuzumab, following earlier trials suggesting that patients progressing while taking trastuzumab may benefit from the addition of pertuzumab therapy, with close to a 30% response rate.

	Trastuzumab emtansine (T-DM1 [Roche Holding, AG]), an antibody-drug conjugate currently in development, is a combination of trastuzumab conjugated to a potent cytotoxic agent (mytansine derivative [ImmunoGen, Inc]) by a stable thioether linker. Clinical trials have demonstrated that trastuzumab-resistant patients are sensitive to this drug, with response rates of approximately 30%.

	Other HER2-targeted therapies in development include: AEE788 (Novartis Pharmaceuticals), a multitargeted HER1/2 and vascular endothelial growth factor receptor inhibitor, currently in phase I and phase II trials; afatinib (Boehringer Ingelheim), an EGFR/HER2 inhibitor in phase III trials; and canertinib (Pfizer Inc), a pan-HER TKI, in phase II trials. Additionally, the HER2 TKIs CP-724, 714 (Axon Medchem BV) and neratinib (Pfizer Inc), and TAK-285 (Millennium/Takeda Pharmaceutical Company Ltd), a dual HER2/EGFR TKI, are currently undergoing phase I and phase II clinical development.

	The kinetic pace of trastuzumab development highlights 2 significant findings that are already shaping the future of targeted therapies: (1) single agents are not sufficient to completely target complex signaling networks; numerous clinical trials are now exploring the efficacy of trastuzumab in combination with other targeted agents, including PI3K and Hsp90 inhibitors, as well as antiestrogen and antiangiogenic therapies; and (2) it is vital to identify patients who will most likely respond to targeted therapies via molecular testing.

	Considerable controversy exists over defining HER2 overexpression. Studies suggest up to 20% of current HER2 testing worldwide may deliver false positives or false negatives, according to the American Society of Clinical Oncology (ASCO). Edith A. Perez, MD, deputy director of the Mayo Clinic Cancer Center in Jacksonville, Florida, aims to help settle this question through the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial.

	There are currently several FDA-approved methods for evaluating HER2 expression: fluorescence in situ hybridization (FISH) and immunohistochemistry via HerceptTest™ (Dako), or the HER2/neu rabbit monoclonal antibody test (Ventana Medical Systems, Inc).

	The FDA recently approved a new test for detecting HER2 overexpression. 

New Genetic Test Aids Detection of HER2 Positive Breast Cancer

			Adams CW, Allison DE, Flagella K, et al. Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab. 

			Arteaga CL. Role of the HER2 pathway in cancer and cancer therapy. Medscape CME/CE. 

			Chang JC. HER2 inhibition: From discovery to clinical practice. 

			Gutierrez C. and Schiff R. HER2: biology, detection and clinical implications. 

			Hortobagyi GN. Trastuzumab in the treatment of breast cancer. 

			Holbro T, Civenni G, Hynes NE. The ErbB receptors and their role in cancer progression. 

			Murphy CG, Modi S. HER2 breast cancer therapies: a review. 

			Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. 

			Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. 

The first drug that successfully targeted the HER2 pathway in cancer treatment generated much excitement.

HER2 Signaling Beckons: Dimerization Process, Combination Therapies Highlight New Research

	The number of adverse drug events (ADEs) disclosed on prescription drug labels has increased dramatically, with oncology-hematology medicines averaging 76 ADEs per label, according to an analysis by researchers from the Regenstrief Institute and the Indiana University School of Medicine (

 2011;171[10]:944-946.doi:10.1001/archinternmed.2011.182).

	ADEs for oncology-hematology drugs ranged from 15 to 273 per label. Across all specialties, the average label contained 70 different ADEs, with more commonly prescribed drugs averaging approximately 100 side effects.

	The researchers called for less complexity, noting that, “While a high number of labeled ADEs is not necessarily indicative of a drug’s true toxicity, the presence of such excess data still may induce information overload and reduce physician comprehension of important safety warnings.”

	Pancreatic Treatment Choices Expand Again

	The FDA approved sunitinib (Sutent) for the treatment of patients with unresectable, locally advanced, or metastatic pancreatic neuroendocrine tumors (pNETs). Sunitinib joins everolimus (Afinitor), approved for pNET earlier this month, as the first new treatments for the rare disease in nearly 30 years. The manufacturer, Pfizer Inc, said sunitinib is already approved for a pNET indication in Europe and 9 other countries. 

	Cell Therapeutics, Inc said the FDA has agreed to meet in June to discuss the resubmission of an accelerated new drug application (NDA) for pixantrone, a novel aza-anthracenedione under investigation as a treatment for relapsed or refractory aggressive non-Hodgkin lymphoma. The company is appealing the agency’s finding last year that another clinical trial was needed for the NDA to move forward. 

FDA digest from June discussing warning labels, pancreatic treatment choices, and the quest for a lymphoma drug.

OncLive June 2011 FDA Digest

 Internationally known experts will discuss the latest research in breast and lung cancers at 2 conferences that the Physicians’ Education Resource (PER) is hosting in California in August.

	Joyce O’Shaughnessy, MD, co-director of Breast Cancer Research at the Baylor Charles A. Sammons Cancer Center at Texas Oncology in Dallas, will chair the 10th International Congress on the Future of Breast Cancer from August 4-7 in Coronado. The conference will focus on the clinical implications of breast cancer genetic and phenotypic subtyping, as well as novel agents and strategies.

	David Gandara, MD, director of the Thoracic Oncology Program and associate director of Clinical Research at the University of California Davis Cancer Center in Sacramento, and Roy Herbst, MD, PhD, chief of Medical Oncology at the Yale Comprehensive Cancer Center, Smilow Cancer Hospital at Yale-New Haven Yale School of Medicine in Connecticut, will chair the 12th International Lung Cancer Congress from August 11-14 in Carlsbad. An update on research from major Cooperative Groups from the United States, Europe, and Asia will be among the highlights.

Internationally known experts will discuss the latest research in breast and lung cancers at 2 conferences that the Physicians' Education Resource (PER) is hosting in California in August.

PER Gatherings Focus on Breast, Lung Cancers

During the past 20 years, disease management (DM) systems have mushroomed in medicine, expanding from call centers staffed by nurses to electronic devices that collect streams of data to pump into doctors’ offices. Heart patients are strapping on wristband monitors, and diabetics are checking their glucose meters; there’s even an “intelligence toilet” system that tracks several health indicators.

	Now, as many cancers evolve into chronic diseases, momentum is building for DM systems in oncology that, among other things, remind patients to get diagnostic tests, help them manage adverse events, and talk them through their bouts with depression. One trade group estimates that nearly a fifth of cancer patients already use some form of DM and, collectively, spend $250 million a year on it.

	Amid the growth, though, questions persist about whether DM can deliver on its goals: better quality of life and treatment outcomes for patients, more efficient systems for busy physician practices, and cost efficiencies for healthcare payers. Indeed, studies conducted thus far have concluded that DM does nothing to cut medical bills and little to improve health outcomes in chronic illnesses far less complex than cancer.

	"As much as the studies show questionable benefits, the alternative of having people hung out to dry is not acceptable to most health plans and employers. That’s why you have this growth."

 —Al Lewis, president of the Disease Management Purchasing Consortium International

	Such disappointments have spurred efforts to design better DM tools, but they have hardly dampened overall enthusiasm. The idea that you can keep patients healthier with better communication and smart tools makes so much intuitive sense that the DM market keeps booming.

	Annual revenues for independent DM vendors have jumped from $78 million in 1997 to $1.2 billion in 2006 and to $2.8 billion today, according to the Disease Management Purchasing Consortium. Add in the money that insurance companies spend on their own systems and it’s a $5 billion industry, the group says.

	Looking forward, analysts expect DM to grow 10% a year. Oncology DM is growing faster still—even without experimental technology that would boost growth higher and software systems that would allow oncology practices to make sense of the data collected.

	“As much as the studies show questionable benefits, the alternative of having people hung out to dry is not acceptable to most health plans and employers,” said Al Lewis, president of the consortium. “That’s why you have this growth.”

	Human Touch Is Part of Electronic Advantage

	The concept of DM began 2 decades ago with cardiology patients. Several small trials identified patients who came to major academic hospitals with heart failure. After these patients were sent home, the teams they’d worked with at the hospital followed up regularly, both over the phone and face to face, asking what patients had done over the past few days and reminding them of what they needed to do over the next few days.

	Repeat hospital visits fell. Patients developed healthier habits. Medical costs dropped. And a movement was born. DM began to boom—not because doctors embraced it, but because employers and insurance companies thought it might cut costs by keeping chronically ill patients out of the hospital.

	Rather than using the hospital staff for the follow-up work, the larger programs created by insurers or DM vendors—those that are being increasingly employed in oncology&mdash;find it far more efficient to use teams of nurses who work in call centers and do all of their work over the phone.

	But such changes, DM skeptics say, eliminated benefits that came with initial trials, where doctors and nurses tapped their relationships with patients and knowledge of their needs.

	“After a decade of market experimentation with limited success, new thinking is called for in the design of DM programs,” argued Brenda R. Motheral, PhD, in a review of telephone-based models in 

	“Targeting of specific patients and activity combinations based on risk, actionability, and treatment and program effectiveness has the potential to deliver a cost-saving DM program if combined with an outreach model that brings the care manager much closer to the patient and physician,” she said.

	"We can see when two medications prescribed by different doctors will interact. We can see if patients actually fill the prescriptions that doctors write them. We can see when a patient is due for a certain test and remind them to get it."

—Scott Josephs, MD, a national medical officer at Cigna Corporation

	Indeed, Miaskowski et al found pain intensity scores decreased significantly for patients with cancer randomly assigned to an intervention program while patients in standard care experienced an increase (

	The trial, which included 174 patients, tested a program in which specially trained nurses taught patients how to use a pillbox and discuss pain with their doctors through 2 in-home visits and 3 phone calls.

	Insurers counter that some big benefits come from operating their own DM systems, rather than relying on doctors to do whatever is necessary.

	“We can see the whole patient in a way that’s hard for individual doctors, and that allows us to provide real value,” said Scott Josephs, MD, national medical officer for Total Health Management at Cigna Corporation.

	“We can see when two medications prescribed by different doctors will interact. We can see if patients actually fill the prescriptions that doctors write them. We can see when a patient is due for a certain test and remind them to get it.”

	But the real value of DM may be yet to come, starting with technology designed to convince patients with cancer to take their medicine.

	In 1990, virtually all cancer treatment occurred at a doctor’s office. By 2008, 20% of all money spent on oncology went to oral cancer medications, and the number was growing by 25% a year, according to independent pharmacy consultant Barbara Hawes, RpH, MBA.

	Oral cancer treatments, generally designed to be taken daily at home over long periods of time, have one major drawback: Many patients do not take medication exactly as directed. Ruddy et al found that adherence and persistence rates were as low as 16%, depending upon the type of cancer and the medication (

	It is a problem that everyone wants to solve.

Barbara Rapchak, founder of Leap of Faith Technologies, developed eMedonline (inset).

	For example, the National Cancer Institute paid Leap of Faith Technologies, a small company in suburban Chicago, to develop a system that uses smart phones, radio-frequency identification technology, and the Internet to ensure patients take their medicines.

	The Leap of Faith system, called eMedonline, stores all the information about what a patient needs to take and when. It then alerts the patient at the proper times and has the patient scan the medication into the phone as he takes it. Failure to take the right medication at the right time leads to a phone call, first an automated one, and, if necessary, a live one.

	The eMedonline system has boosted compliance to >95% in trials and is ready for commercial use.

	“It can handle any amount of complexity,” said Barbara Rapchak, who founded Leap of Faith 21 years ago. “We had one patient on 27 meds a day, all intricately timed.”

	The eMedonline system sounds an alert and forces the patient to scan the medication at the correct time. Other tools take automation further still.

	Doctors ask patients with many diseases, including some types of cancer, to track their weight and report any significant changes. The traditional tracking tool was a handwritten log, while the traditional reporting tool was a telephone. Now there are scales that automatically send figures to computer programs that pass all the information on to doctors.

	The smart toilet system, which a Japanese company sells for up to $6000, can track and report not only the sugar in urine but also the weight, body fat, and blood pressure of any user. For children, there’s a blood glucose monitoring device that plugs into a videogame system so young patients can register their readings while they play.

The eMedonline system, left, tracks patient care.

		MIT researchers work on implantable nanosensors, right.

	Looking ahead, researchers are developing tools that require even less of users.

	Researchers around the globe are working on nanoparticles that continuously monitor cancer patients for substances related to their particular cancer and transmit wireless information about what they find.

	Implantable devices are already commercially available for some conditions. Pacemakers have been gathering data for well over a decade, and the first implantable blood sugar sensor hit the market in 2005.

		Disease Management in Oncology Settings

 The bedrock idea of disease management (DM) has always been that greater communication will help patients take better care of themselves while providing medical professionals with more of the information they need to spot and treat problems early. Rather than paying a patient’s own doctors and nurses to call regularly, insurance companies pay DM vendors to maintain call centers stocked with nurses who are connected to patients at intervals determined by software.

 The single most important home treatment for most diseases is prescription medication, properly taken. Unfortunately, surveys suggest roughly half of all patients don’t take medicine properly if left to their own devices, which is why the market abounds with high-tech helpers. Beyond the plastic day-of-the-week pillboxes, vendors have developed systems that call a patient’s phone when it’s time to take a pill, pill bottles that e-mail the doctor if the patient doesn’t open them frequently enough, and even in-pill microchips that transmit information about when the patient swallows them.

 If a medical device exists, some vendor has devised a version that connects with a computer every time it is used, stores each measurement in a journal of some kind, and alerts someone about worrisome numbers. Scales, thermometers, pedometers, heart rate monitors, blood pressure cuffs—the list is endless. Adoption has been slow because doctors don’t yet have the technology to sort so much data and because many devices work only with their own software rather than larger DM systems.

 Each disease comes with its own therapeutic recommendations, dietary restrictions, and key indicators, which might be weight or blood pressure, or any other biological marker. Smart programs can be tweaked to keep motivated patients organized and motivate reluctant ones. These programs ask patients if they’re experiencing problems that are common to individual diseases and their treatments. They also help coordinate treatment for multiple chronic diseases, pointing out that the vigorous exercise that helps a diabetic might not be as beneficial for the same patient’s heart condition.

 Some exist already, but the future will see tiny products designed to rest somewhere inside the human body gathering data, looking for problems, and streaming information out to computers.

 The mountain of data that such devices provide will overwhelm physicians’ capacity for analysis—and his or her time. The real value will come with software that can analyze patterns in data from thousands of patients and spot clinically important trends.

	Cancer presents a more difficult challenge because researchers are still seeking the relevant biomarkers for many types of tumors, and even markers that are known may appear in different parts of the body that are often quite inaccessible.

	Still, doctors and scientists at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology think they’ll change oncology with implantable nanosensors that will tell doctors exactly how they need to treat individual tumors and evaluate whether the treatment worked.

	The nanoparticles are made of iron oxide. Antibodies are attached to the surface of the particles. The specific antibodies are chosen to bind to proteins that are secreted by the tumor cells.

	“The radiation dose that is appropriate for a tumor depends on the concentration of oxygen in the tumor,” said Michael C. Cima, PhD, an engineering professor who leads the project. “If we have a sensor there, we can measure the oxygen before deciding on the radiation and then get the dosage right.”

	After treatment, implantable devices could stay in the patient for years, looking for any sign of new tumors. Cima hopes such products will begin clinical use in 5 years.

	The sheer number of networked devices on the market and in the works will generate an astonishing amount of data and create a massive potential for improving patient health. But even the biggest boosters of DM worry that much of that potential will go untapped because the various tools implemented by medical practices and insurance companies won’t talk to one another.

	“Very little is truly automated right now,” said Lewis, of the Disease Management Consortium. “No DM software receives information from the pharmacy about a new heart medication the patient just got, calculates that it interacts with his cancer medications, and alerts doctors automatically. A human must pick up the phone and that limits how much information gets shared.”

	“The nurses at one insurer’s DM system might spend a couple years figuring out a great system to motivate a particular patient to live healthy, but if that patient gets a new job, the nurses at the next insurer’s system will have to start from scratch because insurers can’t share information,” Lewis said. “It makes sense to limit what insurers can say to one another, but regulators have a real opportunity to improve patient health if they can make rules that allow practical information to be shared while still protecting privacy.”

	Solving such problems requires not only that dozens of manufacturers agree on standards, but also that politicians and regulators find smart ways to update privacy safeguards for the information age.

	If DM makers can solve these problems— insurers, researchers, and observers agree&mdash;it will grow faster still.

	Andrew D. Smith is a freelance technology journalist based in New Jersey.

During the past 20 years, disease management systems have mushroomed in medicine

June 2011 | Oncology Live®

The Internet Dilemma: Awash in Information, Drowning in Ignorance

4 Questions for Martine Piccart-Gebhart, MD, PhD: Noted Breast Cancer Researcher Has Bright Hopes for HER2 Targets

HER2 Signaling Beckons: Dimerization Process, Combination Therapies Highlight New Research

OncLive June 2011 FDA Digest

PER Gatherings Focus on Breast, Lung Cancers

Smart Moves? E-patient Systems Rise Amid Skepticism