Invisible Scars of Childhood Chemotherapy Revealed
Cancer treatment can lead to further health problems; early detection with PET and MRI scans may stave these off.
Cancer patients can’t think too far ahead because their futures are so uncertain. This is especially true for children, who may recover from cancer but face a lifetime of increased risk for chemotherapy-induced diseases. These can include heart problems, bone loss and neurocognitive impairments.
Researchers at Stanford University tested a combined positron emission tomography (PET) and magnetic resonance imaging (MRI) scanning process for childhood cancer survivors to detect such issues early. The patients had been treated for leukemias, lymphomas and sarcomas. All had received varying doses and combinations of the chemotherapy drugs anthracycline, prednisone and methotrexate. The study did not examine the consequences of radiation treatment.
PET and MRI scans require patients to hold still for long periods, which is difficult for children. To minimize this stress, three teams separately developed 30-minute scanning protocols for the three organs most susceptible to damage -- heart, bone and brain -- so that the total test time would not exceed 90 minutes.
The researchers achieved this goal, establishing that the combined scans offer more efficient testing and less stress for the patient compared to separate scans following standard procedures. However, the other results of the study were less encouraging. Of 10 patients, eight showed abnormal findings in heart, bone and brain tissue. Two of the eight had no clinical symptoms. The scans found 25 bone lesions total in five patients and damage to brain white matter in six patients. Higher chemotherapy doses correlated with increased heart damage, but not to bone or brain damage. Compared to controls, patients who had received methotrexate had significantly less blood flow to the brain and lower metabolism in key brain areas such as the cerebral cortex and hippocampus.
The researchers noted that standard care includes post-treatment surveillance based on the strength of drug doses, but because patients vary in their sensitivity to drugs and the current study found some damage not correlated with dose, this standard may need to be revised. Ashok Theruvath, lead author of the study and a postdoctoral research fellow at Stanford, said the scanning method could help detect tissue damage early -- before symptoms appear -- and follow-up could be tailored to the patient. For example, beta blockers can ameliorate chemotherapy-induced heart damage.
“The take-home is that this type of imaging approach can be done,” said Noah Sabin, a neuroradiologist at St. Jude Children’s Hospital in Memphis, Tennessee. “Beyond that, larger amounts of patients and a more detailed assessment of the correlates” of chemotherapy will be necessary to determine the utility of the combined PET and MRI scans, Sabin added.
The study underlined the risks childhood cancer survivors face for many decades longer than most adult cancer patients. Sabin, who studies adult survivors of childhood brain chemotherapy, said brain effects are most common during and right after treatment, but even acute symptoms often resolve. He was not surprised to see the number of abnormalities observed in the current study, and noted that many of these are asymptomatic in the brain scans he analyzes from adult survivors.
Now that the feasibility of the procedure is established, “Our next step is to do the test in more patients, a larger cohort with maybe different types of tumors, so we can analyze subgroups,” said Theruvath. After that, whether this kind of monitoring can lead to robust early rescue or prevention of chemotherapy-induced damage remains to be seen. The study was published in the December issue of Radiology.