Use of such precision diagnostics offer ‘early detection, localization, and the opportunity to monitor response to therapy,’ say the MIT scientists
Oncologists and medical laboratory scientists know that most clinical laboratory tests currently used to diagnose cancer are either based on medical imaging technologies—such as CT scans and mammography—or on molecular diagnostics that detect cancer molecules in the body’s urine or blood.
Now, in a study being conducted at the Massachusetts Institute of Technology (MIT), researchers have developed diagnostic nanoparticles that can not only detect cancer cells in bodily fluids but also image the cancer’s location. This is the latest example of how scientists are combining technologies in new ways in their efforts to develop more sensitive diagnostic tests that clinical laboratories and other providers can use to detect cancer and other health conditions.
Precision diagnostics such as molecular, imaging, and analytics technologies are key tools in the pursuit of precision medicine.
“Therapeutic outcomes in oncology may be aided by precision diagnostics that offer early detection, localization, and the opportunity to monitor response to therapy,” the authors wrote, adding, “Through tailored target specificities, this modular platform has the capacity to be engineered as a pan-cancer test that may guide treatment decisions for numerous tumor type.”
Development of Multimodal Diagnostics
The MIT scientists are developing a “multimodal” diagnostic that uses molecular screening combined with imaging techniques to locate where a cancer began in the body and any metastases that are present.
“In principle, this diagnostic could be used to detect cancer anywhere in the body, including tumors that have metastasized from their original locations,” an MIT new release noted.
“This is a really broad sensor intended to respond to both primary tumors and their metastases,” said biological engineer Sangeeta Bhatia, MD, PhD (above), in the news release. Bhatia is the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT and senior author of the study.
“It can trigger a urinary signal and also allow us to visualize where the tumors are,” she added. Bhatia previously worked on the development of cancer diagnostics that can produce synthetic biomarkers which are detectable in urine samples.
“The vision is that you could use this in a screening paradigm—alone or in conjunction with other tests—and we could collectively reach patients that do not have access to costly screening infrastructure today,” said Sangeeta Bhatia, MD, PhD (above), in the MIT news release. “Every year you could get a urine test as part of a general check-up. You would do an imaging study only if the urine test turns positive to then find out where the signal is coming from. We have a lot more work to do on the science to get there, but that’s where we would like to go in the long run.” (Photo copyright: NBC News.)
Precision Diagnostic Assists Assessment of Response to Cancer Therapy
For their research, the scientists added a radioactive tracer known as copper-64 to the nanoparticles. This enabled the particles to be used for positron emission tomography (PET) imaging. The particles were coated with a peptide that induced them to accumulate at tumor sites and insert themselves into cell membranes, producing a strong imaging signal for tumor detection.
The researchers tested their diagnostic nanoparticles in mouse models of metastatic colon cancer where tumor cells had traversed to the liver or the lungs. After treating the cancer cells with a chemotherapy regimen, the team successfully used both urine and imaging to determine how the tumors were responding to the treatment.
Bhatia is hopeful that this type of diagnostic could be utilized in assessing how patients are responding to treatment therapies and the monitoring of tumor recurrence or metastasis, especially for colon cancer.
What is unique about the approach used by Bhatia’s team is that one application of the copper-64 tracer can be used in vivo, in combination with imaging technology. The other application of the copper-64 tracer is in vitro in a urine specimen that can be tested by clinical laboratories.
“Those patients could be monitored with the urinary version of the test every six months, for instance. If the urine test is positive, they could follow up with a radioactive version of the same agent for an imaging study that could indicate where the disease had spread,” Bhatia said in the news release. “We also believe the regulatory path may be accelerated with both modes of testing leveraging a single formulation.”
The graphic above, taken from the MIT news release, shows how “multimodal nanosensors (1) are engineered to target and respond to hallmarks in the tumor microenvironment. The nanosensors provide both a noninvasive urinary monitoring tool (2) and an on-demand medical imaging agent (3) to localize tumor metastasis and assess response to therapy,” the news release states. (Photo and caption copyright: Massachusetts Institute of Technology.)
Precision Medicine Cancer Screening Using Nano Technologies
Bhatia hopes that the nanoparticle technology may be used as a screening tool in the future to detect any type of cancer.
Her previous research with nanoparticle technology determined that a simple urine test could diagnose bacterial pneumonia and indicate if antibiotics could successfully treat that illness, the news release noted.
Nanoparticle-based technology might be adapted in the future to be part of a screening assay that determines if cancer cells are present in a patient. In such a scenario, clinical laboratories would be performing tests on urine samples while imaging techniques are simultaneously being used to diagnose and monitor cancers.
Surgical pathologists may also want to monitor the progress of this research, as it has the potential to be an effective tool for monitoring cancer patients following surgery, chemotherapy, or radiation therapy.
New study analyzes the dramatic decline in the utilization of imaging diagnostics between 2008 and 2014 and suggests that reductions in imaging use could be the result of changes in federal policy, increased deductibles, and cost-cutting focuses
Anatomic pathologists have experienced sustained cuts to reimbursements for both technical component and professional component services during the past eight to 10 years. But what has not happened to pathology is a 33% decline in the volume of biopsies referred to diagnosis. Yet that is what some studies say has happened to imaging reimbursement since 2006.
Using Medicare data for Part B imaging procedures covering the years 2001 to 2014, researchers at a major university identified that, beginning in 2006, the total reimbursement for imaging procedures declined at a steady rate throughout the following eight years covered by the study. It is unclear what implications the finding of this study of imaging utilization might predict for the utilization of advance anatomic pathology services.
Routine Use of Imaging in Diagnostics is Slowing Down
The researchers calculated utilization rates for “advanced” imaging modalities and component relative value unit (RVU) rates for all imaging modalities. They determined that trends in imaging rates and RVU rates rose between 2000 and 2008, but then sharply declined from 2008 to 2014. The researchers theorized that the reduction might have been due to changes in federal policy, increasing deductibles, and focus on cost-cutting by hospitals and healthcare providers.
Levin, along with Thomas Jefferson University associates Vijay M. Rao, MD, FACR, current Chair of Radiology, and Laurence Parker, PhD, Associate Professor of Radiology; and University of Wisconsin-Madison statistics Professor Charles D. Palit, PhD, argue that the decrease in imaging orders might reduce diagnostic costs, but also could negatively impact surgical pathologists, radiologists, medical researchers, and patients themselves.
In a Modern Healthcare article, Levin states that the reduction in utilization of imaging and radiology could be a slippery slope leading to decreased access to life-saving diagnostic tools that could leave patients “not getting the scans they probably need.”
What’s Fueling the Multi-Year Decline in Utilization of Imaging and Radiology?
Using data acquired from Medicare part B databases, the authors reported that total reimbursements for NDI peaked at $11.9 billion in 2006, but saw a steep decline of 33% to just over $8 billion in 2015. They attribute some of this decline as a result of the Deficit Reduction Act of 2005, which went into effect in 2007, as well as other cuts to NDI reimbursement funding. Reimbursement to radiologists, according to Levin et al, dropped by more than 19.5%, and reimbursement to cardiologists dropped nearly 45% between 2006 and 2015.
Surgical pathologists may see parallels in the total reimbursement for imaging during the years 2002-2015 compared to pathology technical component and professional component reimbursement during those same years. Taken from the Thomas Jefferson University study, the graphic above shows “total Part B payments for non-invasive diagnostic imaging to all physicians under the Medicare Physician Fee Schedule, 2002 to 2015. Vertical axis shows billions of dollars. The abrupt decline in 2007 was due to the Deficit Reduction Act. The declines in 2009, 2010, and 2011 were due largely to code bundling in, respectively, transthoracic echocardiography, radionuclide myocardial perfusion imaging, and CT of the abdomen and pelvis.” (Caption and image copyright: Thomas Jefferson University.)
According to Levin and Rao, the Choosing Wisely initiative was intended “to reduce the use of tests and treatments that were felt to be overused or often unnecessary.” Imaging examinations were included in the list of tests that were deemed to be “of limited value” in many situations. Levin and Rao suggested that there might have been a need to curtail testing pushed by payers, policymakers, and physicians at the time, but that the Choosing Wisely initiative could have added to a decline in imaging testing spurred on by the confusion physicians felt when attempting to access unclear scenarios and recommendations for the 124 imaging tests listed.
Imaging Decline Could Have Unintended Consequences for Providers and Patients
In a Radiology Business article, Levin outlined some of the unintended consequences facing healthcare due to the reduction in imaging utilization. He states that “private imaging facilities are starting to close down” and “MRI and other advanced imaging exams are beginning to shift into hospital outpatient facilities.” He predicts that the shift from private facilities to hospital facilities could cause imaging costs to increase for customers and healthcare providers.
Levin suggests that Medicare could “raise the fees a little and make the private offices a little more viable.” The profit margins, Levin argues, “are so low right now that you basically can’t run a business.” Medicare as a program might be seeing huge savings, Levin notes in several articles, but physicians, laboratories, and patients are feeling the pinch as a result.
In an interview with Physicians Practice, Rao echoed Levin’s concerns. “Policy makers lack understanding of the value of imaging and spectrum of the services provided by radiologists,” he declared. “On an institutional level, under the new payment models, radiology is transitioning to a cost center and radiologists often don’t have a seat at the table.”
Rao points out that this devaluing of radiologists’ work affects not only healthcare facilities, but patients themselves. Radiologists provide “major contributions to patient care by making accurate diagnoses, and doing minimally invasive treatments given many technological advances leading to appropriate management and improved outcomes,” he argues. How long before Pathology follows a similar track?
Balancing Cost and Quality in Testing Without Sacrificing Patient Needs
The fear seems to be that the push to lower costs by eliminating unnecessary imaging is inhibiting radiologists and diagnosticians from providing necessary imaging for patients. And that delaying diagnoses affects the ability of healthcare providers to provide adequate and timely patient care. Rao suggests, however, that physicians’ use of medical imaging could simply be evolving.
“There were other factors that also helped limit the rapid growth, such as greater attention by physicians to practice guidelines, concerns about radiation exposure to patients, and the Great Recession of 2007 to 2009,” Rao noted in a Thomas Jefferson University news release. “However, we expect that additional changes, such as the advent of lung cancer and other screening programs, and the use of computerized clinical decision support, will continue to promote and support appropriate use of imaging technology.”
The drive to reduce healthcare expenditures should not be dismissed. We may soon see parallels in the rise and fall of imaging utilization for genetic testing, surgical pathology, and other new and expensive clinical laboratory technologies as policymakers attempt to balance increased spending against the clinical value of these diagnostic tools.
Big data offers new opportunities for healthcare providers, clinical laboratories, and pathology groups, and this new alliance hopes to accelerate big data capabilities
Big data has the potential to deliver unprecedented insight into optimizing the patient care experience and managing outcomes for healthcare providers. That is particularly true for clinical laboratories, and pathology groups. Yet, with the sheer amount of data generated by today’s ever-expanding menus of diagnostic procedures, communicating this data between systems and analyzing data at high-levels still presents challenges.
To help healthcare organizations jumpstart their Big Data programs, key stakeholders are joining forces. One such alliance involves Siemens Healthineers and IBM Watson Health. In an October 2016 press release, the two organizations announced a five-year global strategic alliance aimed at helping healthcare professionals optimize value-based care that leverages increasingly complex data collected for use in precision medicine.
What should intrigue pathologists and medical laboratory managers about this new alliance is the fact that Siemens Healthineers owns two of the world’s largest businesses in radiology/imaging and in vitro (IVD). Thus, it can be expected that the alliance will be looking to identify ways to combine radiology data with clinical laboratory data that produce knowledge that can be applied to clinical care. (more…)
