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Collaboration needed to make molecular imaging a reality for precision oncology
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Molecular imaging can be a “complementary approach” to traditional diagnosis and monitoring methods to help ensure the key goal of precision oncology — using more effective and less toxic treatments — is achieved, according to a review published in JAMA Oncology.
Further, new molecular imaging techniques — which can measure regional expression of therapeutic targets, drug pharmacokinetics and therapy pharmacodynamics — may be more distinct than CT scanning.
“New methods and applications hold great promise, not only for more specific diagnosis but to also help guide therapeutic choices, especially for more advanced disease,” David A. Mankoff, MD, PhD, Gerd Muehllehner professor of radiology and director of the PET Center of Perelman School of Medicine at University of Pennsylvania, told HemOnc Today. “As a clinical method to help guide precision oncology, molecular imaging will have its most compelling use in application to drugs that are either toxic, expensive or both, where better treatment selection will lead to better patient outcomes and lower cost.”
Despite this potential, the idea that molecular imaging can be used both to stage patients and also to choose therapy has not been widely accepted.
Most trials of molecular imaging only have been conducted in small populations at single centers. Further, collaboration between oncologists and imagers will be necessary to fully implement this unique, cost-effective approach to patient care, Mankoff and colleagues wrote.
In their review, Mankoff and colleagues discussed how molecular imaging can be used to help identify patients most likely to benefit from targeted therapy, monitor patients undergoing treatment to guide dosing and evaluate efficacy, and provide information to predict a patient’s prognosis.
Molecular imaging as a biomarker
Precision cancer care focuses on identifying specific biomarkers of a patient’s cancer, which can help clinicians make decisions about the best therapy for each patient.
Biopsy is the traditional method used for biological characterization of a tumor; however, molecular imaging offers distinct capabilities from biopsy, Mankoff and colleagues wrote. For instance, molecular imaging can measure biologic properties across the entire burden of disease, measure regional heterogeneity, and be used serially due its noninvasive nature.
Molecular imaging — which largely has been based on PET or single-photon emission CT — injects special imaging compounds into a patient to highlight a desired molecular target in a tissue of interest.
FDG-PET, one of the few molecular imaging techniques used in oncology, uses an FDG probe with a radioactive isotope of fluorine. After injection into the bloodstream, the FDG probe accumulates in tumors, lighting them up on a PET scan.
New probes in development have the potential to expand the use of molecular imaging; however, challenges exist when using molecular imaging beyond cancer detection and staging.
“It requires a validated approach, typically validated by comparison to a tissue-based reference assay, [and] the ability to localize lesions and measure probe uptake independently,” Mankoff said. “For instance, the absence of a particular feature (eg, ER expression) may be more important than its presence and requires an independent method to localize active tumor sites and measure an ER–specific probe. This task can be accomplished by hybrid imaging (eg, PET/CT or PET/MR), or by pairing studies to another test that can detect active tumor sites (eg, FDG PET/CT combined with ER– or HER-2–targeted PET/CT).”
Probes that bind to estrogen and HER-2 receptors can enable clinicians to detect these markers in patients with breast, uterine and ovarian cancers, helping inform treatment decisions, monitor tumor for changes, and evaluate how well a treatment is hitting the receptor targets.
Other new PET probes could reveal receptors to additional tumor-related markers at metastatic sites, such as the bone, which can be harder to biopsy.
“The most important feature of molecular imaging is its ability to assess in vivo cancer biology noninvasively and without perturbing the system,” Mankoff said. “For example, molecular imaging can measure the expression of a target molecule, not possible by standard anatomic or function imaging, such as CT. The unique feature of molecular imaging methods is the ability to measure the molecular and biochemical features of cancer either directly (eg, magnetic resonance spectroscopy) or by the use of ultrasensitive molecular imaging probes (eg, PET).”
Overcoming barriers
Perceptions about molecular imaging may limit the technique’s use in clinical practice.
“Both imagers and oncologists think of imaging — including molecular imaging — as a test for cancer detection, staging and restaging,” Mankoff said. “Using an imaging test to choose therapy — much as we do for pathology tests — is not an idea that either oncologists or imagers are yet used to.”
Cost and logistical challenges also may hinder implementation.
“The need for FDA approval of imaging agents, payer reimbursement, and challenging distribution channels of short-lived imaging agents are factors that lead to higher costs and sometimes more limited availability,” Mankoff said. “Treating physicians perceive molecular imaging as being expensive. However, used wisely in the context of treatment selection, judicious use of imaging could lead to considerable overall saving by avoiding expensive drugs that are unlikely to work. Targeted drugs are becoming considerably more costly than PET imaging, and wise use of imaging to direct them to patients most likely to benefit could lead to cost savings, even when considering the price of the imaging tests.”
There also is a need for procedure standardization across centers and more physician training, Mankoff said.
“Right now, it is largely only nuclear medicine–trained physicians who have the knowledge base to interpret novel molecular imaging studies — or novel applications of molecular imaging — in the clinic,” he said.
These challenges have limited the study of new molecular imaging probes to small, single-center clinical trials.
However, Mankoff and colleagues presented specific solutions to overcoming these barriers to translate novel imaging clinical studies into clinical practice. They include:
Imagers and oncologists should work together to determine how best to achieve these goals and validate imaging biomarkers for clinical decision-making, Mankoff and colleagues wrote.
“Both imagers and oncologists need to consider imaging biomarkers in a broader context than their current use for detection and staging,” they wrote. “Both the imaging and oncology communities must support evolving frameworks for rigorous trials of molecular imaging biomarkers that can provide level-one evidence for clinical practice.
“Both pharma and imaging manufacturers need to support clinical trials to promote more efficient and effective application of imaging and therapy,” they added. “Only when these forces align will molecular imaging reach its true clinical potential.” – by Melinda Stevens
Reference:
Mankoff DA, et al. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.5084.
For more information:
David A. Mankoff, MD, PhD, can be reached at Perelman School of Medicine at University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104; email: david.mankoff@uphs.upenn.edu.
Disclosure: The researchers report no relevant financial disclosures.