PERCIST bests EORTC for monitoring response to therapy

PET Response Criteria in Solid Tumors (PERCIST) provides similar outcomes to the European Organization for Research and Treatment of Cancer (EORTC) criteria for quantifying response to anticancer treatment using PET/CT, but PERCIST may provide a clearer protocol conducive for widespread adoption, according to a review of the two models published in the April edition of the Journal of Nuclear Medicine.

Kristin Skougaard, MD, from the department of oncology at Copenhagen University Hospital Herlev in Herlev, Denmark, and colleagues, applied both the PERCIST and EORTC criteria for quantitative FDG PET/CT evaluations of colorectal cancer patient response to cycles of irinotecan and cetuximab anticancer treatment to test the two models’ effectiveness and impact on overall patient survival.

“F-18 FDG PET/CT examination is today recommended for preoperative staging and detection of recurrence, and there is growing research attention to expanding the use of F-18 FDG PET/CT in evaluating the response of metastatic disease,” wrote Skougaard et al. “To create the reproducibility that is needed for comparison of response rates between trials, the use of F-18 FDG PET/CT in the setting of metastatic disease requires a fundamental standardization and consensus on response quantification methodology. Otherwise, the potential benefit for patients and for anticancer drug development could be lost.”

Results of the study showed that when applying the EORTC criteria quantitative FDG PET/CT evaluations revealed a 62 percent rate of response to treatment. The PERCIST method showed similar, with a 56 percent rate of response to irinotecan and cetuximab.

“A reasonable explanation for the very similar results is that both sets of criteria confine measurements to the most metabolically active part of the patient’s tumor burden, which is regarded as the most viable and aggressive disease fragment, determining for disease development according to cancer stem cell theory,” explained the authors. “Additionally, the similar results reflect the robustness of SUV for assessment of treatment response.”

The prospective study included evaluations for 61 patients with metastatic colorectal cancer recruited between 2006 and 2009 given a combination of 180 mg/m2 of irinotecan and 500 mg/m2 of the monoclonal antibody cetuximab every two weeks as a third line of anticancer therapy. Patients underwent a total of 203 PET/CT scans with F-18 FDG from one to 14 days before the first treatment and after every fourth round of treatment until progression was confirmed with CT. All patients were split into four categories of best overall metabolic response (BOmR): progressive metabolic disease (PMD), partial metabolic response (PMR), stable metabolic disease (SMD) and complete metabolic response (CMR). PET/CT scans were then evaluated separately using both PERCIST and EORTC criteria.

Using the PERCIST model of quantification, seven patients were PMD, 34 patients were categorized as PMR, and 20 patients were considered SMD. Comparatively, with the EORTC criteria, seven were noted as PMD, 38 as PMR, 16 were determined to be SMD and none from either method were considered CMR.

“EORTC criteria and PERCIST disagreed on the BOmR of eight patients with either PMR or SMD,” concluded the authors. “The discrepancies were explained by the differences in approach (multiple lesions or single lesion) and in response cutoff values. From a clinical perspective, these distribution differences would not have had implications for the involved patients, as treatment would have been continued with both outcomes.”

The two criteria differed in subtle ways. The most active tumors were the focus of the EORTC criteria. ROI volumes and sites with high F-18 FDG uptake as well as whole tumor uptake were registered at baseline and then data collected on resulting scans, but there is little advice given about the number of lesions to be targeted and measured and whether mean or max SUV should be applied.

“The degree of observer-dependent aspects is considerable and modes of application numerous, rendering the EORTC criteria more susceptible to interobserver differences than PERCIST,” the authors added. “Possibly, these interobserver-sensitive elements will be clarified in the next revised version of the EORTC criteria.”

PERCIST looks at the most active part of the tumor with the most F-18 FDG uptake occurring. Alternatively, as many as five of the most F-18 FDG–active tumors can be the focus of evaluation. SULmean was recommended and found to have a better test–retest variability of  8 -10 percent than SULmax, which had a variability of 11–12 percent and definitions of target lesion uptake of F-18 FDG are outlined in relation to background. The authors noted that some of these differences are due to the sophistication of the technology as it has developed since the original publishing of the EORTC criteria in 1999. PERCIST emerged ten years later in 2009 and could stand to gain more universal acceptance. 

“Without the discipline to use the same criteria internationally, consensus will not be achieved and advances in cancer treatment will be hampered,” wrote the authors. “In our opinion, PERCIST holds the potential to create this consensus and comparability whereas the EORTC criteria, in their current form, can be applied in too many different ways to fulfill this task.”

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