Performance of tumor growth kinetics as an imaging biomarker for response assessment in colorectal liver metastases: correlation with FDG PET.

PURPOSE: To correlate RECIST, volumetric criteria, and tumor growth kinetics at multidetector-computed tomography with tumor metabolic activity at FDG PET in colorectal liver metastases (CRCLM) treated with bevacizumab-based chemotherapy. METHODS: Thirty-two CRCLM in 20 patients treated with bevacizumab-based chemotherapy were evaluated. Pre- and post-treatment CT scans were used to calculate reciprocal of doubling time (RDT), percentage change in the lesion's longest transaxial diameter (RECIST 1.1), and percentage change in the tumor volume. The accuracy of these parameters in predicting response based on standard uptake value analysis at FDG PET was assessed. Data were analyzed using Spearman's correlation, student's t, Mann-Whitney, Wilcoxon signed-rank, and Fisher's exact tests. RESULTS: According to FDG PET, 24/32 (75%) lesions were categorized as responders and 8/32 (25%) lesions as nonresponders. Based on RDT, 26/32 (81.25%) lesions were classified as responders and 6/32 (18.75%) lesions as nonresponders. Response classification according to RDT and FDG PET was concordant in 30/32 (93.75%) lesions, whereas RECIST 1.1 and volumetric criteria were concordant with FDG PET for 20/32 (62.5%) and 21/32 (65.63%) lesions, respectively. A strong association was found between RDT and response based on FDG PET (odds ratio = 127.4; 95% CI 5.54-2997; P < 0.0001). CONCLUSIONS: Tumor growth kinetics may be an effective imaging biomarker for response evaluation in CRCLM.

Colorectal liver metastasis after 90Y radioembolization therapy: pilot study of change in MDCT attenuation as a surrogate marker for future FDG PET response.

OBJECTIVE: The purpose of this study was to investigate whether changes in attenuation and size of liver metastatic lesions of colorectal cancer at MDCT 1 month after (90)Y radioembolization treatment are predictive of response at FDG PET 3 months after treatment. MATERIALS AND METHODS: Twenty patients with colorectal liver metastasis consecutively treated with (90)Y radioembolization underwent triphasic MDCT of the liver at baseline and 1 and 3 months after treatment and FDG PET at baseline and 3 months after treatment. Percentage change in tumor attenuation at MDCT (volumetric attenuation), tumor size at MDCT (according to Response Evaluation Criteria in Solid Tumors [RECIST] and World health Organization [WHO] criteria), and volume-weighted maximum standardized uptake value at FDG PET were evaluated. The correlation between FDG PET response 3 months after treatment and response according to RECIST, WHO criteria, and attenuation 1 month after treatment was evaluated. RESULTS: Only 13.3% of patients with FDG PET findings of response 3 months after treatment were identified according to RECIST and WHO criteria 1 month after treatment. According to attenuation criteria at 1 month, however, 53.3% of patients with an FDG PET response at 3 months were identified. A strong association was found between FDG PET response at 3 months and response based on attenuation criteria (odds ratio, 12.4; 95% CI, 0.58-265.3; p = 0.05). CONCLUSION: Early changes in the attenuation of liver metastatic lesions of colon cancer after (90)Y radioembolization treatment may be predictive of future response at FDG PET.

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.

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.

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.

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.

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.