Science & Education
October 2012 • Volume 4, Number 2
In this issue:
IN MY OPINIONWhy FDG-PET is a Useful Biomarker of Tumor ResponseBy RICHARD L. WAHL, MD
ANALYSIS TOOLS AND TECHNIQUES Challenges in Tackling Quantitative UltrasoundBy PAUL L. CARSON, PhD, QIBA Scientific Coordinator
FOCUS ON• QIBA Fifth Annual Working Meeting• QIBA Metrology Workshop Update
QI / IMAGING BIOMARKERS IN THE LITERATUREPubMed Search on Why FDG-PET is a Useful Biomarker of Tumor Response
IN MY OPINION
Why FDG-PET is a Useful Biomarker of Tumor Response
By RICHARD L. WAHL, MD
In oncology there is great interest in using FDG-PET to monitor treatment response across a wide range of cancer types. A large and still increasing body of literature indicates that rapid declines in tumor FDG uptake during many types of treatment are associated with favorable outcomes. Patients whose tumors do not have a major decline in FDG uptake—or a rise in FDG uptake—during treatment are likely to have poorer outcomes.
Evidence supports the power of the early FDG-PET assessment. FDG uptake changes during treatment can contribute information regarding outcome that is at least as and sometimes more informative than PET imaging at the end of treatment. Since FDG uptake in tumors is correlated with the number of viable cancer cells in a given tumor, the FDG signal is related to viable cell number. Large drops in tumor FDG uptake are seen in cancers where many cancer cells have been killed by cytotoxic agents.
FDG-PET scans at the end of therapy also indicate, with reasonable certainty, whether a treatment has been effective. A negative PET scan may lead to a clinical decision to observe a patient without additional therapy while a positive PET scan may lead to more treatment, more intense follow up, or biopsy.
Because more cancer therapies are being developed, the historical paradigm of treating a patient for two months with an anti-cancer therapy regimen and then assessing change in tumor size has limitations. This could potentially expose a patient to months of ineffective treatment with attendant side effects, cost, and the lost opportunity to treat with a more effective agent. Early identification of non-efficacy of a cancer treatment regimen would be desirable, so that treatments can be changed sooner to agents which may be more likely to be effective. To make such early assessments with high certainty, e.g. after two weeks or so of treatment, it is quite probable that quantification of the PET images will be needed. The need for quantification is likely to be greater when the patient is still undergoing treatment than at the end of treatment when PET is commonly assessed for completeness of response both visually and qualitatively.
Rigorous standards and quality control are necessary to precisely quantify PET imaging of cancer with FDG. The QIBA approach has helped focus practitioners of FDG-PET on a more standardized imaging approach. Standardized methods, such as those of the UPICT 1.0 and the FDG-PET/CT Profile 1.0 and with more robust analytical approaches such as the PERCIST 1.0, are now being used.
Quantitative FDG-PET/CT at baseline and soon after treatment is emerging as a potent quantitative, non-invasive method to phenotype tumors and observe the effects of a specific treatment. Efficacy or non-efficacy can be predicted by early scans with increasing certainty. With this approach, cancer treatments that aren’t working could be changed to more effective therapies that could potentially be implemented sooner than with traditional anatomic imaging approaches. Resources would not be wasted on expensive treatments with a low probability of efficacy, but money and effort could be applied to using the right treatment in the right patient.
Whether the SUV peak, SUV max, metabolic tumor volume or total lesion glycolysis is the most important parameter to assess remains under study, as does the optimal cut-off thresholds for therapeutic non-efficacy for specific cancers and treatments. While much work remains, there is worldwide interest in using PET with FDG to promptly assess treatment efficacy in a wide range of cancer types and treatments. The QIBA approach—which extends from consistent dose calibration to scanner specifics, to software, patient selection and physician expertise—applies rigor and consistency to these increasingly quantitative imaging approaches. With these paradigms, cancer treatment will be changed so that each patient is assured that the drug predicted to help battle their disease is actually working. This can be assured by sequential, quantitative, FDG-PET providing non-invasive phenotyping of cancers and their response to therapy.
Richard L. Wahl, MD, is the director of nuclear medicine at Johns Hopkins University School of Medicine in Baltimore, Md., and vice-chairman of radiology for technology and new business development. He is a professor of radiology and oncology as well as the first Henry N. Wagner, Jr. Professor of Nuclear Medicine. His scientific interests focus on cancer imaging and therapy with targeted radiopharmaceuticals. Dr. Wahl pioneered the use of [18-F] FDG for tumor imaging with PET. He and his colleagues developed the SUV-lean body mass, quantitative PET treatment response approaches and the PERCIST criteria for treatment response in PET.
He is one of the inventors of radioimmunotherapy of lymphoma with anti CD20 antibodies and of patient individualized dosimetry based on whole body clearance rates. Dr. Wahl has written/edited five major textbooks and authored more than 350 peer- reviewed publications. He has lectured throughout the world and has been honored with multiple professional awards and named lectureships including being named the "most influential radiology researcher" in 2005 in the "Minnie" awards.
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ANALYSIS TOOLS & TECHNIQUES
Challenges in Tackling Quantitative
By PAUL L. CARSON, PhD, QIBA Scientific Coordinator
Eighteen key researchers, physicians, and/or industry representatives in ultrasound and QIBA and RSNA leaders attended a two-hour meeting at the 2011 RSNA Annual Meeting in Chicago to establish a Quantitative Ultrasound Biomarker Committee within QIBA. After explaining the QIBA process, leaders in each of six possible quantitative ultrasound imaging modes spoke briefly on how a mode might serve as the target for QIBA profile development. Possible target areas for a QIBA biomarker and speakers were:
Following this meeting, a newly formed organizing committee arranged a planning meeting in March 2012 prior to the American Institute of Ultrasound in Medicine meeting in Phoenix, to select one high-priority area for a QIBA effort to improve ultrasound’s quantitative reproducibility and fidelity to reference standards. Speakers on the narrowed field of four contending topics are in Table 1. Many of their presentations are available publicly in the QIBA Wiki, or specifically the Ultrasound Wiki.
Table 2Ballot employed in first votes
Before substantial comparative discussion by the entire group, a vote was taken in which all participants ranked each measurement area by the criteria on the ballot in Table 2. The expectation was to continue with increasingly deep discussion in a Delphi-like process until one topic was selected. The spread was greatest in the first ballot in which one topic was eliminated. It then became apparent that all of the proposed measures, including the eliminated morphometry, were thought of as nearly equally appropriate for QIBA efforts. By the end of the meeting a reasonable preference was expressed for elastography in the form of shear wave speed, or elastic modulus estimated therefrom. The choice of medical problem was not clearly defined, though discrimination of fatty and fibrous liver infiltration and breast cancer diagnosis were the two most prominent applications discussed. The need in liver is quite strong, as the current diagnostic standard in the U.S. is quite invasive (Figure 1).
It was clear throughout the discussions that all of the six original topics are exciting areas of research and clinical development and nearly all are ready for a QIBA-type effort. A QIBA Shear Wave Speed Ultrasound Technical Committee (SWS-US-TC) was formed, led by co-chairs Brian Garra, MD, Andrzej Milkowski, MS, and Timothy Hall, PhD. The current 70 members in this open committee are listed on the Wiki. They have formed three subcommittees and bold goals are being discussed for greatly reducing cross-platform variability in SWS measurements in the liver.
Paul L. Carson, PhD, is a collegiate professor of basic radiological sciences (BRS), Department of Radiology, a professor of biomedical engineering, and member of applied physics at the University of Michigan. Dr. Carson’s research and clinical support interests include quantitative imaging, medical ultrasound (functional imaging, equipment performance, safety, new or improved diagnostic and therapeutic instrumentation and applications including microbubble creation and drug delivery in body fluids in vivo), multimodality breast imaging and therapy including combined-X-ray tomosynthesis / ultrasound / photoacoustics and microwave / ultrasound systems. He serves as QIBA Scientific Coordinator.
Profiles developed by the PDF-MRI and CT Volumetry Technical Committees have been released for implementation and are accessible on the QIBA webpage of the RSNA website.
Implementation instructions and the feedback form may be found here.
QIBA Fifth Annual Working Meeting in Chicago
Hyatt Regency O’Hare, Rosemont
More than 75 people attended the fifth annual Quantitative Imaging Biomarkers Alliance (QIBA) meeting held in May in Chicago to foster stakeholder collaboration and information sharing. The meeting also provided an opportunity for strategic planning and review of funded and non-funded projects undertaken by the various Technical Committees. New for this year was a panel discussion of industry and clinical experts on the perceived value of quantitative imaging. The second day of the meeting was dedicated to technical and modality-based committee work groups.
Summaries of QIBA meetings and ongoing committee work are posted on the QIBA wiki. QIBA welcomes new committee participants. Contact QIBA@rsna.org for more information.
QIBA Metrology Workshop Update
In early April, the RSNA Department of Research hosted the QIBA Metrology Workshop at RSNA Headquarters in Oak Brook, Ill, where 37 statisticians and radiologists joined to discuss the best use of terms as well as methodological issues that must be addressed in data collection and interpretation. The group seeks to establish standard terminology for clinical practice to continue moving toward the overall goal of QIBA: “to improve the value and practicality of quantitative imaging biomarkers by reducing variability across devices, patients and time.”
Over the past four years, QIBA Technical Committees have encountered frequent ambiguities and differences of opinion about the terms and methods used for measuring, describing and comparing the various components of imaging tests. Metrology Workshop participants plan to develop guidelines and definitions to help standardize the approach of and improve communication between QIBA groups, and the greater imaging community.
The three respective Metrology working groups continue to meet regularly via teleconferences to discuss terminology for metrology concepts, algorithm comparisons, and technical performance of an imaging assay. The members of these all-volunteer groups are enthusiastically continuing their work toward standardization in these areas and have planned a follow-up workshop in Washington, D.C., in October 2012.
QI/IMAGING BIOMARKERS IN THE LITERATURE
PubMed Search on: “Why FDG-PET is a Useful Biomarker of Tumor Response”
Each issue of QIBA Newsletter features a link to a dynamic search in PubMed, the National Library of Medicine's interface to its MEDLINE database. Link to articles on: “Why FDG-PET is a Useful Biomarker of Tumor Response” here.
QIBA and QI / Imaging Biomarkers in the Literature
This list of references showcases articles that mention QIBA, quantitative imaging, or quantitative imaging biomarkers.
QIBA in the Literature
New submissions are welcome and may be directed to QIBA@rsna.org.
QIBA MISSION Improve the value and practicality of quantitative imaging biomarkers by reducing variability across devices, patients and time.
Quantitative Imaging Biomarkers Alliance (QIBA)
Contact usComments & suggestions welcome
Daniel C. Sullivan, MDRSNA Science Advisor