Rationale and Objectives
The purpose of this study is to evaluate the reproducibility and agreement of tumor necrosis quantification performed by two-dimensional and volumetric methods in a cohort of patients with hepatocellular carcinoma (HCC) treated with yttrium-90 ( 90 Y) radioembolization.
Materials and Methods
Twenty-nine consecutive patients (21 men, 8 women; mean age 66.6 years; age range, 44–90 years) with HCC treated with 90 Y radioembolization that underwent liver multidetector computed tomography (MDCT) were included. Two independent radiologists evaluated the necrosis proportion of the lesions with two-dimensional (2D) measurements according to the European Association for the Study of the Liver guidelines, and with a volumetric method using a voxel-by-voxel analysis. Interobserver reproducibility for each method was assessed by using within-subject coefficients of variation (WSCV), intraclass correlation coefficients (ICC), and Lin’s concordance correlation coefficients (LCC). Agreement between both methods was assessed by using the Bland-Altman plot and the paired t -test.
Results
The volumetric method was more reproducible (WSCV = 27.8%; ICC = 0.914; LCC = 0.909) than the 2D (WSCV = 43.8%; ICC = 0.723; LCC = 0.841). There was a significant difference in the mean calculated necrosis proportions based on 2D and volumetric methods ( P = .0129).
Conclusion
Voxel-by-voxel quantification of HCC necrosis is a more reproducible method than 2D analysis.
Hepatocellular carcinoma (HCC) is potentially curable by surgical resection or transplantation , but usually only 15%–25% of the patients are candidates for surgery . Because most chemotherapeutic agents have marginal antitumoral effects , a significant portion of patients are treated with target-directed therapies, such as radiofrequency ablation, transcatheter arterial chemoembolization (TACE), or yttrium-90 ( 90 Y) radioembolization .
Multidetector-row computed tomography (MDCT) has been widely used for assessing tumor response after therapy . To develop a common language and standardize the response evaluation, several criteria were developed, such as the World Health Organization (WHO) guidelines, the Response Evaluation Criteria in Solid Tumors (RECIST), and its more recent update, RECIST 1.1 . These guidelines require decrease of the tumor size as a marker for a positive response . Response to locoregional therapy, however, may not lead to a reduction in tumor volume . Indeed, with directed therapy, tumoral tissue may undergo necrosis, which may even lead to an increase in the size of the lesion . Therefore, the European Association for the Study of the Liver (EASL) has published a guideline recommending that the reduction in the amount of tumor viable tissue should be used to assess tumor response to localized treatment (where viable tissue means tumor regions that did not undergo necrosis) . Since then, the evaluation of tumor viable tissue has been increasingly used as a surrogate marker to assess response to locoregional therapies. The EASL guidelines recommend quantifying the amount of necrosis as a way to estimate the amount of viable tumor tissue. Most investigators have applied the two-dimensional (2D) measurements modified from WHO guidelines on a single axial plane to quantify necrosis . The modified RECIST proposed by the American Association for the Study of Liver Diseases uses the single longest axial diameter of the necrotic area to assess response to locoregional therapy, but it has not yet been widely validated; however, a new report suggests that modified RECIST may be superior to RECIST1.1 .
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Materials and methods
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Patients
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90 Y Radioembolization
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Computed Tomography Technique
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Lesion Selection and Evaluation
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2D Measurement
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V=43πr3, V
=
4
3
π
r
3
,
and the area A of a circle of radius r is calculated by:
A=πr2 A
=
π
r
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Pv=VnVt=4/3πN34/3πT3=(NT)3 P
v
=
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n
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in which Vn = necrosis volume and Vt = tumor volume.
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Pb=AnAt=πN2πT2=(NT)2 P
b
=
A
n
A
t
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in which Pb = two-dimensional proportion, An = necrotic area, and At = tumor area.
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NT=Pb−−−√2 N
T
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and substituting into the first equation we arrive at:
Pv=(NT)3=(Pb−−−√2)3 P
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thus being able to convert 2D necrosis proportions to volumetric-equivalent necrosis proportions.
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Volumetric Quantification
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Statistical Analysis
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Results
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Interobserver Reproducibility
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Table 1
Parameters Used to Assess Reproducibility for Two Independent Observers Estimating the Proportion of Necrosis within a Tumor by Two Different Methods
Statistics Parameter Measurement Method Two-dimensional Measurements Volumetric Quantification Mean difference ± SD −0.03 ± 0.14 −0.08 ± 0.10 WSCV 43.8% 27.8% ICC 0.8454 0.9138 LCC 0.8407 0.9089
ICC, intraclass correlation coefficient; LCC, Lin’s concordance coefficient; WSCV, within-subject coefficient of variation.
Data pertain to two independent observers.
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Assessment of Agreement between Methods
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Discussion
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