| ObjectiveColorectal cancer is the second most common tumor in the world. The liver is the most common site of metastases from digestive system, with a frequence of 20% to 30% of patients at diagnosis, and up to 60% during the course of disease. Transarterial chemoembolization (TACE) is one of the effective therapeutic methods for patients with unresectable liver metastases. However, only about 60% of the patients can benefit from TACE and some patients may develop severe complications. Therefore, for oncologists, early evaluating the treatment response to and predicting survival with TACE are critical for promptly discriminating non-responders from treated patients and timely changing to other therapeutic options. The purpose of this study is to prospectively evaluate the ability of computed tomography perfusion imaging (CTPI) in predicting early response to and survival with TACE for patients with colorectal cancer liver metastases (CRLM).Materials and MethodsA total of 68 consecutive CRLM patients who were planning for TACE were enrolled from January 2012 to December 2013. Among them,7 patients were excluded from this study due to the TACE contraindications; therefore,61 patients were included in the current study. CTPI was performed 2-5 days before TACE in 61 patients (41 men and 20 women; mean age,56.9 ± 14.7 years). The observed parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial fraction (HAF), hepatic arterial perfusion (HAP), and portal vein perfusion (PVP).All of the TACE procedures were performed by three experienced interventional radiologists in accordance with the standard protocol. The selective hepatic artery angiographies and indirect portographies were performed. An emulsion of 5 to 15 mL lipiodol and mitomycin C (8 mg/m2) was mixed and infused into the feeding arteries through the micro-catheter. The choice of chemotherapeutic agents for TACE was dependent on the previously administered chemotherapeutics, which consisted of mitomycin (n=29), mitomycin and gemcitabine (n=15) or mitomycin and irinotecan (n =17).CTPI was performed in all of 61 patients 1 month after TACE using the same scanning protocols as those before TACE. CT images were transferred to the GE Advantage Windows 4.4 workstation, and the data were processed applying the Body Liver Tumor software.In each patient, one or up to two lesions (multiple lesions) were selected as the target lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) guideline. Treatment response was evaluated on the CT scans 4 months after TACE and the patients were divided into responders and non-responders based on the RECIST (version 1.1) guideline. The overall survival was calculated from the start of TACE. The patients were observed for survival until death or until December 2014 (at least 360 days).A paired t test was used to compare the difference between the CTPI parameters of the target lesions and those of the normal liver parenchyma before TACE, as well as the difference between the CTPI parameters in the target lesions before TACE and that 1 month after TACE.The Wilcoxon signed-rank test was conducted to compare the percentage change in the CTPI parameters from 1 month after to before TACE in the target lesions of responders and non-responders. Logistic regression analysis was used to determine which CTPI parameter obtained at a 1 month follow-up best enabled us to predict the therapeutic response. Receiver operating characteristic curves (ROC) were plotted to identify the cutoff value of the percentage change in the screened CTPI parameter for identifying the non-responders. The patients were then divided into two subgroups according to the cutoff value. Kaplan-Meier curves were plotted to illustrate the overall survival rates, and a log-rank test was used to compare the overall survival rates of the two subgroups. P<0.05 indicates a significant difference.ResultsBefore TACE, in the hypervascular lesions (n=24), a heterogeneous hyperperfusion was present in HBF and HAF maps and a hypoperfusion was found in HBV, MTT and PS maps. An early wash-in and early wash-out was observed in time-density curve (TDC) map. Meanwhile, in the hypovascular lesions (n=37), a heterogeneous hypoperfusion was found in HBF, HBV, MTT and PS maps. Hyperperfusion was found in HAF map, and a flat perfusion curve was displayed in TDC map. Meanwhile, the mean HBF, HBV, MTT and PVP values in the target lesions were significantly lower (P=0.026, P=0.017, P=0.021 and P=0.002, respectively), but the HAF and HAP values were significantly higher (P<0.001 and P=0.011, respectively) than those in the normal liver parenchyma. No statistical difference was found between the PS values (P=0.056).One month after TACE, the perfusion of lipiodol-retention portions in target lesions decreased or disappeared in HBF and HAF maps. However, the unretentive portions remained unchanged. The mean HBF, HBV, PS, HAF, and HAP values of the target lesions significantly decreased (P=0.030, P<0.001, P<0.001, P<0.001, and P=0.002, respectively); By contrast, the mean MTT value significantly increased relative to its value before TACE (P<0.001). No statistical difference was observed in the PVP value (P=0.209).Four-month images were obtained from 58 patients. Responders accounted for 39.66%(n=23), non-responders accounted for 60.34%(n=35). The further stratifying study revealed that the responders had a greater decrease in percentage changes in HBF, HBV, PS, HAF, and HAP (P<0.001,P<0.005, P<0.003,P<0.007 and P=0.001, respectively), but had a greater increase in MTT than the non-responders(P<0.05). No statistical difference was observed in PVP (P=0.598)The percentage change of HAP 1 month after TACE was the optimal predicting parameter (P=0.003). The best cut-off value for predicting early response was -21.51% with a corresponding sensitivity of 94.4% and a specificity of 84.0%. The study cohort was then divided into two subgroups:Subgroup A, with a decrease of HAP≥21.51%, and Subgroup B, with<21.51% decrease. The 6-,12-, and 18-month survival rates in Subgroup A were 96.32%(95% CI,89.24%-100%),74.45%(95% CI,56.62% 92.26%), and 24.47%(95% CI,0-51.43%), respectively. The survival rates in Subgroup B were 70.60%(95% CI,55.32%-85.92%),28%(95% CI,12.75%-43.38%), and 18.76%(95% CI,4.72%-36.93%), respectively. Subgroup A had significantly higher overall survival [mean survival time,455.24 d (95% CI,411.30-499.13 d)] than Subgroup B [mean survival time,295.19 d (95% CI,237.73-352.66 d)] (χ2=13.169, P< 0.001).ConclusionCTPI can accurately reflect the hemodynamic characteristics before and after TACE in patients with CRLM, and can quantitatively detect the changes of internal structure and the blood supply of the treated CRLM with TACE. This study suggests that TACE can significantly decrease the blood supply of the CRLM, and extend the time of the blood flow passing through the tumor capillaries. The percentage change in HAP is the optimal CTPI parameter for predicting the early therapeutic response to and survival with TACE of patients with CRLM. A greater decrease in the percentage change in HAP (≥21.51%) in the target lesions 1 month after TACE is associated with a higher overall survival rate than those with a lower decrease. CTPI can predict the early therapeutic response to and survival with TACE of patients with CRLM. This study is of great significance for the therapeutic strategies in patients with CRLM. |
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