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Science Highlight: June 11, 2013

Radiation Test Run Predicts Outcome of Lymphoma Treatment

A “test run” of radiation therapy in patients with non-Hodgkin lymphoma can show how much radiation is likely to be absorbed by a tumor during actual treatment. This information may help doctors to estimate the dose needed for effective treatment more precisely than currently used measures, such as a person’s height and weight. Ensuring proper radiation dosages reduces damage to healthy tissues and may also prevent tumor growth for a longer period of time.

Non-Hodgkin lymphoma refers to a broad class of cancers that begin in cells of the immune system, most commonly B cells. Depending on the specific type, stage, and growth rate of the cancer, radioimmunotherapy may be a promising treatment option.

Radioimmunotherapy combines a radioactive substance with an antibody that targets specific cancer cells. Once injected into the body, the radiolabeled antibodies bind to tumors, where the radioactive substance gives off radiation, which may help kill the cancer cells. This type of targeted treatment also helps limit radiation exposure to healthy tissue.

color coded map of radiation dose distribution in a tumor

3D, color-coded dose distribution map within a tumor, obtained by coupling SPECT/CT images with the Monte Carlo algorithm.
Source: Yuni Dewaraja, Ph.D., University of Michigan

Before beginning radioimmunotherapy, patients are injected with a very small amount of the radiolabeled antibody for an imaging scan. Because the antibodies go directly to cancer cells, imaging technologies that pick up radiation, like single-photon emission computed tomography (SPECT), can show where tumors are located. Doctors then consider the patient’s height and weight, how quickly a particular radioactive marker is cleared from the body, or other factors to calculate the radiation dose that will be used during treatment. Even with such careful planning, however, doctors and patients cannot be certain how a particular tumor will respond to radiation until treatment begins.
 

NIBIB grantee Yuni Dewaraja, Ph.D., and her research team at the University of Michigan sought not just to address this issue, but also to find out if the pre-treatment scan could predict tumor shrinkage and progression-free survival—how long a patient lived without further tumor growth. If so, radiation treatment plans could be based on personalized patient tumor data rather than more general guidelines.

To explore these questions, the researchers assessed 130 B-cell non-Hodgkin tumors in 39 study participants. The participants received a pre-treatment dose of a radio-labeled antibody — specifically, 131I-tositumomab — and then underwent anatomic (computed tomography, or CT) and functional (SPECT) imaging on a combined SPECT/CT system. From these scans, an advanced computer program created detailed 3D pictures showing the pattern of radiation absorption throughout a particular tumor. The programs for SPECT image reconstruction and absorbed dose calculation were also developed by this group with past funding from NIBIB.

 

Eight days after pre-treatment, the participants received their full treatment doses. To evaluate outcomes, they were re-scanned two and six months after treatment, and then every six months afterward for up to four years. For the follow-up scans, the researchers used a different imaging system combining CT with positron emission tomography (PET), which produces higher resolution images than SPECT/CT but can’t be used in radioimmunotherapy for this type of cancer because it does not detect the radiation emitted by 131I-tositumomab.

Graph showing the change in tumor activity at different imaging time points, with data from tracer imaging (blue diamonds) and from therapy imaging (red squares). Correlation between tracer and therapy curves indicate that the tracer study can be used to predict the therapy absorbed dose.Source: Yuni Dewaraja, Ph.D., University of Michigan

Graph showing the change in tumor activity at different imaging time points, with data from tracer imaging (blue diamonds) and from therapy imaging (red squares). Correlation between tracer and therapy curves indicate that the tracer study can be used to predict the therapy absorbed dose.
Source: Yuni Dewaraja, Ph.D., University of Michigan

The researchers considered a range of factors likely to affect treatment outcomes, including size of the tumor before treatment, number of past treatments, and the presence of genes that may make the tumor cells more resistant to radiation. Of all the factors studied, the one most closely associated with progression-free survival was the amount of radiation absorbed by a tumor, which was predicted by the pre-treatment scan.
 

“This elegant study shows that careful quantitation of the amount of radiation absorbed by the tumor, when incorporated in treatment planning, serves not just as a predictor of progression-free survival, but also lays the foundation for future, more effective patient-specific treatments. This is a novel way in which dosimetry in nuclear medicine can contribute to the goal of personalized medicine,” said Antonio Sastre, Ph.D., who oversees NIBIB-funded research involving nuclear medicine and other imaging technologies.

Further, the researchers found that a dose of at least 200 cGy (centigray, a unit of radiation absorption) to the tumor provided longer periods of progression-free survival. On average, participants whose tumor absorbed 200 cGy or more survived nearly 14 months without additional tumor growth, while those whose tumor absorbed less than 200 cGy experienced only about 2 months without tumor growth.

“This is an exciting finding since it shows that patients can clearly benefit from highly individualized treatment planning based on patient-specific tumor dosimetry,” said Mark Kaminski, M.D., a co-investigator on the study. Dr. Kaminski is also one of the co-developers of the 131I-tositumomab treatment.Peter Roberson, Ph.D., a member of the University of Michigan research team, presented the group’s findings at the 2013 annual meeting of the Society of Nuclear Medicine and Molecular Imaging.

 

Superimposed SPECT and CT images show radioactivity uptake—red areas denote greater absorbed dose—on the day of the pre-treatment tracer dose and two days after the full treatment dose. The tumor is outlined in green.Source: Yuni Dewaraja, Ph.D., University of Michigan

Superimposed SPECT and CT images show radioactivity uptake—red areas denote greater absorbed dose—on the day of the pre-treatment tracer dose and two days after the full treatment dose. The tumor is outlined in green.
Source: Yuni Dewaraja, Ph.D., University of Michigan

Graph showing progression-free survival (PFS) as related to tumor absorbed dose. Longer PFS was seen in patients that received more than 200 centigray of tumor absorbed dose.Source: Yuni Dewaraja, Ph.D., University of Michigan

Graph showing progression-free survival (PFS) as related to tumor absorbed dose. Longer PFS was seen in patients that received more than 200 centigray of tumor absorbed dose.
Source: Yuni Dewaraja, Ph.D., University of Michigan

 

 

 

 

 

Program Area: 
Health Terms: 
Cancer,
CT,
Modeling and Simulation,
PET/SPECT