Pedram Rezai

Response to Treatment Series: Part 2, Tumor Response Assessment—Using New and Conventional Criteria

OBJECTIVE Conventional anatomic imaging biomarkers, including World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), although effective, have limitations. This article will discuss the conventional and newer morphologic imaging biomarkers for the assessment of tumor response to therapy. CONCLUSION Applying established methods of assessing tumor response to therapy allows consistency in image interpretation and facilitates communication with oncologists. Because of the new methods of treatment, assessment of necrosis and volumetric information will need to be incorporated into size-based criteria.

Does Multidetector CT Attenuation Change in Colon Cancer Liver Metastases Treated with 90Y Help Predict Metabolic Activity at FDG PET

PURPOSE To evaluate the correlation between change in attenuation and tumor metabolic activity assessed by using fluorodeoxyglucose (FDG) positron emission tomography (PET) in colon cancer liver metastases treated with yttrium 90 ((90)Y) radioembolization. MATERIALS AND METHODS This Health Insurance Portability and Accountability Act-compliant retrospective study was approved by the institutional review board; patient informed consent was waived. Unresectable chemorefractory colon cancer liver metastases treated with (90)Y radioembolization in 28 patients were evaluated at pre- and posttreatment multidetector computed tomographic (CT) and FDG PET scans. Maximum cross-sectional diameter, volume, and overall attenuation of target lesions were calculated. The percentage change (%Delta) in these parameters after treatment was calculated and correlated with the standardized uptake value (SUV) analysis at FDG PET. The accuracy of the radiologic parameters in helping predict response to treatment at FDG PET was assessed. Data were analyzed by using the Student t, Wilcoxon matched pair, Mann-Whitney, Spearman rank correlation, and chi(2) tests. The significance level was set at .05. RESULTS Seventy-four metastatic lesions in 10 women and 18 men (mean age, 61.5 years +/- 14.3 [standard deviation]) were evaluated. Mean follow-up interval for multidetector CT after treatment was 30 days. A significant reduction in maximum cross-sectional diameter, volume, and attenuation was observed from pre- to posttreatment multidetector CT (P < .05). The %Delta in attenuation had higher correlation with %Delta in SUV (r = 0.61) than diameter (r = 0.39) or volume (r = 0.49) and also predicted the metabolic activity at FDG PET with higher sensitivity (P < .001). By using a threshold level of a reduction in attenuation of 15% or greater, attenuation showed 84.2% sensitivity and 83.3% specificity in predicting response at FDG PET evaluation. CONCLUSION Changes in attenuation of colon cancer liver metastases treated with (90)Y radioembolization correlate highly with metabolic activity at FDG PET and may be useful as an early surrogate marker for assessing treatment response.

Hepatic Tumors: Region-of-Interest versus Volumetric Analysis for Quantification of Attenuation at CT

PURPOSE To evaluate the reproducibility of liver tumor attenuation measurement performed by using the routinely used manual region-of-interest (ROI) method and that of measurement performed by using a semiautomated volumetric approach at computed tomography (CT). MATERIALS AND METHODS This HIPAA-compliant retrospective study had institutional review board approval. The requirement for patient informed consent was waived. Attenuation of colon cancer liver metastases in 208 patients was measured on portal venous phase multidetector CT images by using a single ROI, the average measurement in three ROIs on a single section, and with semiautomated segmentation of the entire tumor volume (volumetric attenuation) to evaluate intermethod agreement. Intraobserver and interobserver reproducibility were evaluated in the first 70 patients. Measurements were repeated after 30 days to assess intraobserver reproducibility. Differences between methods were tested by using repeated-measures analysis of variance. Intermethod, intraobserver, and interobserver agreements were tested by using Bland-Altman analysis and the Lin concordance correlation coefficient (ρc). P < .05 was considered to indicate a significant difference. RESULTS A total of 208 pathologically proven colon cancer hepatic metastases larger than 20 mm in diameter in 100 women and 108 men (mean age, 61.6 years ± 11.6 [standard deviation]; range, 28-87 years) were evaluated. Attenuation was significantly different between the three methods of measurement (P < .001 for all). Volumetric measurements had better intraobserver agreement (precision = 3.3%, ρc = 0.996, P < .001) than single-ROI measurements (precision = 12.0%, ρc = 0.947, P < .001) and measurements averaged over three ROIs (precision = 9.3%, ρc = 0.965, P < .001). Volumetric measurements also had better interobserver agreement (precision = 3.6%, ρc = 0.993, P < .001) than single-ROI measurements (precision = 11.3%, ρc = 0.957, P < .001) and the average measurement in three ROIs (precision = 8.5%, ρc = 0.976, P < .001). CONCLUSION Measurements of hepatic tumor attenuation at multidetector CT are reproducible. An approach based on the evaluation of whole-lesion attenuation demonstrated better reproducibility than ROI measurements.

Splenic Volume Model Constructed From Standardized One-Dimensional MDCT Measurements

OBJECTIVE The purposes of this study were to construct a model for estimation of splenic volume from standardized one-dimensional diameters of the spleen and to compare that model with the ellipsoid model for estimation of splenic volume. MATERIALS AND METHODS In this retrospective study, segmentation software was used for semiautomated quantification of splenic volume by counting CT voxels in 193 consecutively registered patients. For standardization of one-dimensional measurements, the software was used to measure transaxial diameter in the slice with the largest splenic cross-sectional area. By incorporation of splenic volume and the product of width, thickness, and length into the linear regression equation, a model for estimation of splenic volume was constructed, and its performance was externally assessed. Splenic volume also was calculated with the formula for a prolate ellipsoid. The ellipsoid volume and best-fit volumes were compared with segmented splenic volume by use of Bland-Altman plot and Lin concordance correlation. A value of p < 0.05 denoted statistical significance. RESULTS Splenic width was the best one-dimensional predictor of splenic volume (r = 0.84, p < 0.05). The linear regression fitted model for estimation of splenic volume (V(R)) in the initial 100 patients was V(R) = (0.36 × W × T × L) + 28, where W is width, T is thickness, and L is length (R(2) = 0.91, p < 0.05) and was externally validated by estimation of splenic volume in the other 93 patients. Compared with that observed with use of the ellipsoid formula, mean bias decreased from 22.57% to 0.93%, and the Lin coefficient increased from 0.81 to 0.96 with application of the best-fit model for calculation of splenic volume. CONCLUSION The best-fit model V(R) = (0.36 × W × T × L) + 28 is more optimized than the ellipsoid formula and is associated with less bias for estimation of splenic volume.

Morphological analysis of pancreatic adenocarcinoma on multidetector row computed tomography: implications for treatment response evaluation.

Objectives: Response Evaluation Criteria in Solid Tumors (RECIST) guidelines assume spherical shape of tumors. Morphology of pancreatic adenocarcinoma (PAC) on multidetector row computed tomography was investigated to evaluate the applicability of RECIST guidelines. Methods: Study population comprised 16 patients with histologically confirmed localized PAC enrolled in a phase II clinical trial of chemoradiation. Pancreatic adenocarcinomas were segmented on baseline and follow-up multidetector row computed tomography with commercially available software. Tumor volumes (mL), RECIST diameter (mm), volume equivalent sphere diameter (VESD, mm), maximum 3-dimensional diameter (M3DD, mm), and elongation value were obtained. RECIST diameter, VESD and M3DD of the tumors at baseline and follow-up were compared to determine differences. Elongation values were analyzed. The significance level was set at P less than 0.05. Results: Mean volume, RECIST diameter, VESD, M3DD, and elongation for baseline versus follow-up studies were 23.12 mL versus 19.43 mL (P > 0.05), 41.86 mm versus 39.35 mm (P > 0.05), 33.14 mm versus 32.1 mm (P > 0.05), 51.76 mm versus 51.73 mm (P > 0.05), and 0.67 versus 0.76 (P > 0.05), respectively. There was a significant difference at baseline and follow-up between RECIST diameter, VESD, and M3DD (P < 0.05, in all instances). Conclusions: Our results suggest that PACs are not spherical in shape. Evaluation of PAC treatment response based on RECIST guidelines may not be accurate.

Morphological Analysis of Pancreatic Cystic Masses

RATIONALE AND OBJECTIVES The aim of this study was to analyze the morphology of pancreatic cystic masses detected on multi-detector row computed tomography (MDCT) to determine whether single-dimension measurements of these masses are accurate reflections of their volumes. MATERIALS AND METHODS Twenty-five pancreatic cystic masses detected on MDCT in 25 patients were evaluated. Pancreatic cysts were segmented on MDCT using commercially available software. All measurements were obtained twice by two independent investigators, and the means of values for segmented cyst volume (Vs) (milliliters), maximum transaxial diameter (millimeters), and elongation value (defined as 1 - [width/length], where 1 = ellipsoid and 0 = spherical) were reported for each cystic lesion. The volume of each cyst was also calculated (Vc) using the maximum transaxial diameter, with the hypothesis that the cyst was spherical. Students t test was used to analyze the differences between values of Vs and Vc. Bland-Altman plots and Lins concordance correlation were used to assess agreement between different measurement techniques. A P value < .05 denoted statistical significance. Interobserver variability was also determined using the Bland-Altman method. RESULTS There was a significant difference between Vs and Vc (P < .0001). The elongation values ranged from 0.28 to 0.83 (mean, 0.57 +/- 0.12; median, 0.56). Mean interobserver variability was 1.7% (95% confidence interval, -4.89% to 8.30%). CONCLUSIONS The results suggest that pancreatic cystic masses are not spherical. Therefore, a cysts single largest transaxial dimension is not an accurate surrogate of its actual volume.

Change in the growth rate of localized pancreatic adenocarcinoma in response to gemcitabine, bevacizumab, and radiation therapy on MDCT.

PURPOSE To depict treatment response to chemoradiotherapy by comparing tumor growth rate between treated and untreated patients and to compare depicted response with objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guideline. METHODS AND MATERIALS This Health Insurance Portability and Accountability Act-compliant, retrospective study was approved by the institutional review board. Volume doubling time (DT) of histologically confirmed locally advanced pancreatic adenocarcinoma was calculated in 16 patients treated with chemoradiotherapy and 10 untreated patients by incorporating interscan interval (Δt) and tumor volume at baseline (V0) and follow-up (V1) obtained by semiautomated segmentation into the following equation: DT = Δt · log 2/log (V1/V0). Reciprocal of doubling time (RDT), which is the linear representation of tumor growth rate, was calculated by use of the following equation: RDT = 365/DT. The lowest RDT value of 2.42 in untreated patients was considered as the cutoff value for depiction of treatment response. Depicted response rate was defined as the proportion of patients with an RDT value of less than 2.42. Depicted response was compared with objective response according to the RECIST 1.1 guideline. The significance level was set at p < 0.05. RESULTS There was a significant difference in mean RDT between treated (range, -7.12 to 3.27; mean, -1.27; median, -1.30) and untreated (range, 2.42 to 10.74; mean, 5.33; median, 4.26) patients (p < 0.05). Reciprocal of doubling time was less than 2.42 in 14 treated patients, which corresponded to a depicted response rate of 87.50% as opposed to the objective response rate of 18.75% according to the RECIST 1.1 guideline (p < 0.05) and carbohydrate antigen 19-9 response rate of 62.50% (p > 0.05). Carbohydrate antigen 19-9 response was concordant with RDT and RECIST response in 12 patients (75.00%) (κ, 0.38) and 9 patients (56.25%) (κ, 0.24), respectively. CONCLUSIONS There was a significant difference between depicted response according to RDT and objective response according to RECIST. Reciprocal of doubling time might serve as a valuable biomarker for evaluation of treatment response when depiction of small changes in tumor size is concerned.

A Radiologist's Guide to Treatment Response Criteria in Oncologic Imaging: Functional, Molecular, and Disease-Specific Imaging Biomarkers

OBJECTIVE This article reviews the functional, molecular, and disease-specific imaging biomarkers of treatment response. CONCLUSION Substantial progress has been made in the evolution of drugs directed at specific targets of the tumor lifecycle. These novel agents are predominantly cytostatic, and their efficacy may be optimally evaluated by functional, molecular, and disease-specific imaging biomarkers.

A Radiologist's Guide to Treatment Response Criteria in Oncologic Imaging: Anatomic Imaging Biomarkers

OBJECTIVE The purpose of this article is to describe the imaging biomarkers of treatment response and provide an overview of anatomic imaging biomarkers. CONCLUSION Imaging biomarkers of treatment response have evolved into the primary endpoint of response in most phase 2 studies. Anatomic imaging biomarkers are applied to depict change in tumor size in response to treatment and are currently the most commonly applied method of treatment response evaluation.

Pancreatic Mucinous Cystic Neoplasm Size Using CT Volumetry, Spherical and Ellipsoid Formulas: Validation Study

CONTEXT The accuracy for determining pancreatic cyst volume with commonly used spherical and ellipsoid methods is unknown. The role of CT volumetry in volumetric assessment of pancreatic cysts needs to be explored. OBJECTIVES To compare volumes of the pancreatic cysts by CT volumetry, spherical and ellipsoid methods and determine their accuracy by correlating with actual volume as determined by EUS-guided aspiration. Setting This is a retrospective analysis performed at a tertiary care center. Patients Seventy-eight pathologically proven pancreatic cysts evaluated with CT and endoscopic ultrasound (EUS) were included. Design The volume of fourteen cysts that had been fully aspirated by EUS was compared to CT volumetry and the routinely used methods (ellipsoid and spherical volume). Two independent observers measured all cysts using commercially available software to evaluate inter-observer reproducibility for CT volumetry. MAIN OUTCOME MEASURES The volume of pancreatic cysts as determined by various methods was compared using repeated measures analysis of variance. Bland-Altman plot and intraclass correlation coefficient were used to determine mean difference and correlation between observers and methods. The error was calculated as the percentage of the difference between the CT estimated volumes and the aspirated volume divided by the aspirated one. RESULTS CT volumetry was comparable to aspirated volume (P=0.396) with very high intraclass correlation (r=0.891, P<0.001) and small mean difference (0.22 mL) and error (8.1%). Mean difference with aspirated volume and error were larger for ellipsoid (0.89 mL, 30.4%; P=0.024) and spherical (1.73 mL, 55.5%; P=0.004) volumes than CT volumetry. There was excellent inter-observer correlation in volumetry of the entire cohort (r=0.997, P<0.001). CONCLUSIONS CT volumetry is accurate and reproducible. Ellipsoid and spherical volume overestimate the true volume of pancreatic cysts.