Jim Kling

June 10, 2013

VANCOUVER, British Columbia —Tumor-absorbed dose predicts progression-free survival in patients undergoing I-131 radioimmunotherapy treatment for non-Hodgkin's lymphoma, a new study suggests.

The approach could potentially be used to customize treatment, researchers say.

The SPECT/CT instrument collects all images in a single session and at a single time point. The approach is 3-dimensional; previous techniques used 2-dimensional planar imaging and different instruments at separate imaging sessions to collect images that had to be superimposed.

That difference might explain why previous studies of tumor-absorbed dose failed to show an advantage, Yuni Dewaraja, PhD, from the University of Michigan in Ann Arbor, told reporters attending a news conference here at the Society of Nuclear Medicine and Molecular Imaging 2013 Annual Meeting.

"You would think that the higher the radiation dose to the tumor, the better the outcome, but that hasn't been shown in past studies," Dr. Dewaraja told Medscape Medical News. "There is always noise, and there hasn't been a clear statistical correlation between radiation dose and response. We believe that's because of inaccuracies in the imaging studies and approximations."

Dr. Dewaraja explained that the team tried to make a more accurate calculation using state-of-the art imaging. They worked to determine patient-specific dosimetric and nondosimetric factors that could predict postradioimmunotherapy progression-free survival in patients with non-Hodgkin's lymphoma.

They used SPECT/CT imaging and Monte Carlo simulation of radiation transport to estimate 3-dimensional dosimetric parameters, including tracer-predicted and therapy-delivered mean tumor-absorbed dose, minimum dose, dose to 80% of the tumor, and dose to 99% of the tumor.

Is it really the radiation dose that is beneficial, or is it the increase in antibody uptake.

They calculated the equivalent biologic effect to determine the biologic influences of the nonuniform absorbed dose and the cold antibody, proliferation, and radiosensitivity.

The researchers used biopsy samples, baseline tumor burden, and treatment history to determine nondosimetric parameters, including Ki-67 and p53 molecular markers. End points included tumor shrinkage at 2-month follow-up, overall response at 6 months, and progression-free survival.

The study involved 39 patients with 130 tumors (tumor dose, 94 to 711 cGy; mean, 295 cGy). Predicted tumor dose correlated strongly with delivered tumor dose (r = 0.85; < .0001).

Univariate analyses revealed that all dosimetric parameters, as well as equivalent biologic effect, correlated with tumor shrinkage (r = 0.19 to 0.51; < .03). There were no correlations with the nondosimetric parameters. In addition, logistic regression showed that dosimetric parameters and equivalent biologic effect had correlations with overall response and progression-free survival (< .05). The only nondosimetric parameter that correlated with overall response and progression-free survival was tumor burden (= .0146).

Tumor-absorbed dose conferred a clear survival advantage, the researchers report. Each 50 cGy increase in tumor-dose led to a 25% reduction in risk for progression. The researchers found that 200 cGy was the optimal dose for differentiating progression-free survival.

The team is currently studying the ability of the approach to determine bone marrow irradiation.

Protocols often limit whole-body dose to 75 cGy. "Right now, there is quite a conservative approach to whole-body doses, without taking into consideration dose to the tumor or dose to the bone marrow," Dr. Dewaraja said. I think this study shows that treatments can be tailored."

Asked by Medscape Medical News to comment on the study, Robert Francois Hobbs, PhD, from Johns Hopkins in Baltimore, Maryland explained that "this is a follow-up of some of the studies they did in which they tried to correlate dose with tumor response, such as shrinkage, and they've been relatively successful at it. The interesting thing about this study is that it's looking at long-term progression-free survival. That's very promising," he said.

"The potential critique is that all you're really showing is that tumors that had more uptake had a more beneficial outcome," Dr. Hobbs pointed out. "Is it really the radiation dose that is beneficial, or is it the increase in antibody uptake? It's still ambiguous."

This study was funded by the National Institutes of Health. One of the study authors, Mark Kaminski, reports receiving research support from GlaxoSmithKline and royalties from Bexxar. Dr. Hobbs has disclosed no relevant financial relationships.

Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2013 Annual Meeting: Abstract 51. Presented June 9, 2013.


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