Impact of the definition of peak standardized uptake value on quantification of treatment response

Abstract

PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUV(max)), which is adversely affected by noise. Peak SUV (SUV(peak)) has been recommended as a more robust alternative, but its associated region of interest (ROI(peak)) is not uniquely defined. We investigated the impact of different ROI(peak) definitions on quantification of SUV(peak) and tumor response.

Methods: Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. (18)F-FLT-avid lesions (∼2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUV(peak). For each tumor, 24 different SUV(peaks) were determined by changing ROI(peak) shape (circles vs. spheres), size (7.5-20 mm), and location (centered on SUV(max) vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUV(peaks) and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROI(peak) definition, a population average SUV(peak) and tumor response were determined over all tumors.

Results: A substantial variation in both SUV(peak) and tumor response resulted from changing the ROI(peak) definition. The variable ROI(peak) definition led to an intratumor SUV(peak) variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUV(peak) response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROI(peak) definition led to a population average SUV(peak) variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUV(peak) response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROI(peak) caused more variation in intratumor response than did the location or shape of ROI(peak). Population average tumor response was independent of size, shape, and location of ROI(peak).

Conclusion: Quantification of individual tumor response using SUV(peak) is highly sensitive to the ROI(peak) definition, which can significantly affect the use of SUV(peak) for assessment of treatment response. Clinical trials are necessary to compare the efficacy of SUV(peak) and SUV(max) for quantification of response to therapy.

FIGURE 1

Multiple definitions of ROI_peak. In this schematic PET image of radiotracer uptake in tumor (purple outline), ROI_peaks of different sizes and in different locations are shown. Shape of ROI_peak can vary too (only circles are shown).

FIGURE 2

Varying ROI_peak. Shape, location, and size of ROI_peak were varied as shown to yield 24 different SUV_peaks for each tumor.

FIGURE 3

Variation in tumor response for retroperitoneal lesion (lesion 11). (Left) 24 different SUV_peak tumor responses (mean response, dashed line) arising from 24 different ROI_peak definitions. Response was ambiguously classified as either stable disease (above −30%, green line) or partial response (below −30%). SUV_max response is also shown. (Right) Box represents SD, whiskers show range, and solid line depicts median of SUV_peak response.

FIGURE 4

Intratumor variation in SUV_peak responses. (Left) Responses of 31 tumors (ordered from smallest to largest) arising from different ROI_peak definitions. Responses of 12 tumors (in blue) were ambiguously classified as either progressive disease/stable disease (130%, solid red line) or stable disease/partial response (-30%, solid green line). SUV_max response and SUV_peak PERCIST response (1.25-cm-diameter sphere in highest-uptake region) are also shown. (Right) Overall variation in intratumor response and variation associated with changing size, location, and shape of ROI_peak. Boxes represent SD, whiskers show range, and solid line depicts median of response values.

FIGURE 5

Variation in intratumor response vs. response. Variation in intratumor response tended to increase as response increased (i.e., as response worsened from partial response to stable disease to progressive disease).

FIGURE 6

Small vs. large variation in intratumor SUV_peak response. ¹⁸F-FLT PET/CT images of periaortic lesion (left, lesion 24) and pelvic tumor (right, lesion 30) at baseline (top) and during treatment (bottom). Lesions are indicated by white circles. Periaortic lesion responded well, exhibiting fairly uniform reduction of ¹⁸F-FLT uptake in higher-uptake regions. Consequently, there was little variation in SUV_peak response. In contrast, pelvic tumor responded poorly, with heterogeneous response in higher-uptake regions, resulting in large variation in SUV_peak response.

FIGURE 7

Variation in average tumor response in population. (Left and middle) For each ROI_peak definition, tumor response was averaged over all tumors, resulting in population average response (mean response, dashed line). SUV_max response is also shown. (Right) Overall variation in population average response and variation associated with changing size, location, and shape of ROI_peak. Boxes represent SD, whiskers show range, and solid line depicts median. Variation in population average response is extremely small (~2%).