Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Positron emission tomography/computed tomography (PET/CT) is commonly used to assess cancer in children. What potential risks are associated with the radiation exposure from using this technology in children?
There have been a number of scientific publications recently that suggest that the radiation exposure from imaging tests can induce secondary cancers later in life.
For example, a recent Lancet article by Pearce and coworkers reported that cumulative doses from diagnostic CT scans for tumor staging in children almost tripled the risk of secondary leukemia and brain cancer later in life; and another study in the BMJ (british medical journal) by Mathews and coworkers reported a 24% increase in cancer incidence in a study on 11 million Australians who underwent CT scans for cancer staging during childhood and adolescence.
This is a highly controversially discussed field to date. There is no question that CT scans can save lives by providing us with the information needed to cure a child with a newly diagnosed tumor.
Radiation-induced secondary cancers are developing many years after the radiation incident, so it is difficult to determine exactly if and how much radiation can cause secondary cancers.
We do know that children are more susceptible to radiation incidents than adults. What we do to them now, will last their lifetime. So, when we image children, we do our best to expose them to the least possible radiation that can provide us with an accurate diagnosis.
Why are children more radiosensitive than adults?
Children are more sensitive to radiation than adults, because they absorb more radiation per volume of tissue and the dividing cells in their growing body are more radiosensitive than senescent or non-dividing cells in an adult.
In addition, children live long enough to encounter secondary tumors, which typically occur decades after a radiation event.
Please can you outline the new scanning technique, recently reported in The Lancet Oncology, which enhances tumor visibility by using an iron supplement?
The novel concept of our approach is that we combined anatomical and functional images, similar to current approaches that integrate radiotracer scans and CT (PET/CT): We first acquired MR scans that showed the anatomy of the patient very well and we then acquired MR scans that depict tumors as bright spots with little or not background information. We did that by using an iron supplement as a contrast agent, which improved tumor detection and vessel delineation on the MR scans. We then fused the anatomical scans with the tumor scans.
One could compare this to highlighting roads and points of interests (the tumors) simultaneously on a geographic map. Previous MR imaging approaches have either shown the point of interest very well or the anatomical map, but not both.
By fusing MR scans that highlight the tumor with MR scans that provide a very detailed anatomical map of the body, we created radiation-free images that shows us very clearly, where tumors are in relation to anatomical landmarks.
Did the iron supplement have any adverse reactions?
None of our patients showed any adverse effects so far and in fact, our patients reported that ferumoxytol did not cause any uncomfortable sensations (e.g. CT contrast agents can cause "hot flush" sensations).
Other contrast agents can cause allergic reactions as well and gadolinium chelates, used as standard contrast agents for MR imaging, can cause an irreversible skin fibrosis (nephrogenic sclerosis) in patients with markedly impaired renal function.
The FDA has acquired comprehensive safety data for ferumoxytol as an iron supplement. It has been reported that few patients had serious anaphylactic reactions to ferumoxytol. Although rare, this is a valid concern.
We use the same agent, concentration, route of administration and same or lower dose as for anemia treatment, so the same data can be informative for us - although we evaluate younger patients.
Ferumoxytol is composed of iron oxide nanoparticles, which are coated by a dextran derivative. Other dextran-containing drugs have been reported to produce allergic reactions as well. We screen our patients carefully for any history of allergies to iron or dextran and we monitor our patients throughout the study for any signs of an allergic reaction.
For health professionals who may read this: It is important to inject ferumoxytol (and any iron compound for that matter) very slowly as iron compounds can cause serious hypotensive reactions if injected as a bolus. We wondered, if some of the previously reported allergic reactions were rather such hypotensive reactions.
How did the diagnostic accuracy of whole-body MRI compare to the standard PET/CT techniques?
Our radiation free MR imaging technique detected 158 of 174 malignant tumors and the standard test FDG-PET/CT detected 163 of 174 malignant tumors.
We missed some abnormal lymph nodes with either technique. However, the tumor staging results showed very good agreement between both imaging modalities, i.e. we classified each patient into the same tumor stage. If treatment decisions had been made based on either of these scans, the decision would have been the same.
So far how many children have been scanned using whole-body MRI and are there plans to confirm your results in larger groups?
Cancer is fortunately rare in children and young adults and the study in our single Children’s Hospital was performed in a limited number of 22 patients.
We have continued to examine more patients at Stanford since then and we are in the process of initiating a multi-center study in at least six major Children’s hospital throughout the country, in order to evaluate new whole body staging tests in a larger cohort of patients.
Do you think whole-body MRI will replace PET/CT imaging for assessing cancer in children going forwards?
I believe that there is no “one fits all” imaging test for everybody. In the era of personalized medicine, we are trying to create the most accurate, most efficient and most cost-effective imaging test for each individual patient.
For some patients, the radiation-free test will provide all needed information, especially if initial staging is concerned. We may still need information from metabolic PET scans to determine the response of certain tumor types to chemotherapy.
We are in the process of performing additional studies that evaluate the value of WB-DW MR scans with and without addition of PET data for treatment monitoring. A combination of PET and MR data would still eliminate radiation exposure from CT scans and substantially reduce radiation exposure by about 80%.
Future studies will have to show, which patients will benefit most from a completely radiation-free whole body imaging test, as described in our article, versus new integrated, ultra low dose (ULD) PET/MR imaging tests. This is a major focus of our future multi-institutional research efforts.
Is there a need to replace PET/CT imaging in adults?
Our oncologists actually asked us to include few young adults as well. There is no magic barrier at 18 or 21 years of age. Relatively young adult patients will certainly benefit from a radiation-free imaging test as well.
We also received a request from a pregnant patient with newly diagnosed lymphoma to be included in the study. However, it is important to note that every patient and every tumor is different. There will be situations where other imaging tests are more appropriate.
If you are a patient, I would strongly suggest to follow the suggestions of your oncologist. He/she needs to be comfortable with the scans that he/she gets for their therapeutic decisions.
Where can readers find more information?
More info can be found on the image gently website: http://www.imagegently.org
About Dr. Heike E. Daldrup-Link
Dr. Daldrup-Link is a physician-scientist at Stanford University, devoting 50% of her time to clinical work as a pediatric radiologist and 50% to translational (“bench-to-bedside”) cellular imaging research.
Dr. Daldrup-Link earned her medical degree from the University of Munster, Germany, in 1992 and completed a radiology residency and a 2-year fellowship in Pediatric Radiology at the Technical University of Munich, Germany.
From 2001-2003, she completed a PD thesis in MRI Contrast Media Research and Molecular MR Imaging, which received Ph.D. equivalence certification from the Center for Educational Documentation Inc. in Boston, MA.
From 2003 to 2010, Dr. Daldrup-Link worked as an assistant professor (2003-2006) and associate professor (2006-2010) of Radiology and Pediatrics at the University of California, San Francisco, (UCSF).
Since 2010, she worked at Stanford University. Dr. Daldrup-Link has published more than 100 peer reviewed scientific articles, 22 review articles and four books.
Dr. Daldrup-Link is member of the NIH Cancer Immunology and Immunotherapy Study Section and member of the editorial boards of Radiology, Pediatric Radiology and European Radiology.
Dr. Daldrup-Link leads an NIH funded research program on the development of cellular imaging techniques, with focus on cancer and stem cell imaging. More information can be found on her research teams’ website: http://daldrup-link-lab.stanford.edu/