Combination PET/CT helps trackslow tumor response earlier

Desist using just RECIST when monitoring neuroendocrine tumors. A combined imaging approach that draws on both molecular and morphological information provides a much better measure of early treatment response, according to a leading German nuclear medicine specialist.

Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization criteria for classifying tumor response work best with fast-growing cancers and when therapeutic agents are cytotoxic rather than cytostatic. Treatment evaluation of slow-growing neuroendocrine tumors based on size changes alone is far more difficult, however, Prof. Richard Baum told delegates at September's World Molecular Imaging Congress in Nice, France.

A high percentage of neuroendocrine tumors are nonfunctional, and clinical response parameters are often insufficient, said Baum, chair and director of the nuclear medicine department and the Center for PET/CT at the Zentralklinik in Bad Berka, Germany. Biochemical markers such as CgA and 5-HIAA may also be misleading, owing to their poor sensitivity. FDGPET is often unsuitable for follow-up in this type of malignancy, because glucose metabolism does not necessarily increase in slow-growing, well-differentiated tumors.

Neuroendocrine tumors are increasingly being treated with peptide receptor radionuclide therapy (PRRT). Researchers from the Zentralklinik in Bad Berka, together with colleagues from Seoul National University Hospital, have now shown that PET/CT imaging with the radioisotope gallium- 68 DOTA-NOC is an effective marker of early response to this type of treatment.

Investigators selected 25 subjects at random from a group of 505 patients with metastasized neuroendocrine cancer who were scheduled for treatment with PRRT (138 lesions). They compared pre- and post-treatment images acquired using Ga-68 DOTA-NOC PET/CT (molecular response), FDGPET/ CT (metabolic response), and contrast-enhanced CT (morphological response). A response index was calculated for each lesion from PET images based on the pre- and posttreatment maximum standard uptake value. RECIST criteria were applied to the contrast-enhanced CT data. All lesions were categorized as partial responders, stable disease, or progressive disease.

Researchers observed no correlation between any of the three modalities. For example, Ga-68 DOTA-NOC PET classified 70.6% of the lesions as partial responders, while FDG-PET put 43.8% into this category, and CT just 17.6%. The sensitivity and specificity of Ga-68 DOTA-NOC PET to predict response to radiopeptide therapy were calculated as 89% and 71%, respectively.

The take-home message is that molecular response precedes morphology. "Ga-68 DOTA-NOC PET/CT is a novel and accurate molecular imaging tool and superior to morphologic imaging for the early assessment of response to PRRT in metastatic neuroendocrine tumors," Baum said.

Intense metabolic activity, reflected on FDG-PET scans, can still be an important prognostic indicator, he said. An observed increase in glucose uptake may be related to an outgrowth of aggressive tumor clones, suggesting a poor prognosis.

-By Paula Gould