1669
Extracellular volume fraction on Gd-EOB-DTPA-enhanced MRI for predicting overall survival in patients with metastatic pancreatic adenocarcinoma1Kagoshima University Graduate School of Medical and Dental Sciences, kagoshima, Japan
Synopsis
This study focused on the potential of extracellular volume (ECV) fraction measured by Gd-EOB-DTPA-enhanced MRI as a prognostic factor in patients with metastatic pancreatic adenocarcinomas. The effect on survival of variables including age, sex, tumor location, tumor size, TNM factors, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels and tumor ECV fraction was assessed in patients with metastatic adenocarcinoma. Our results showed that pancreatic adenocarcinoma with higher ECV fraction had
Introduction
Pancreatic adenocarcinoma is the fourth leading cause of cancer-related deaths in the United States. Although only margin negative surgical resection is considered to be potentially curative treatment, >50% of patients have distant metastases at the time of diagnosis. For patients with distant metastases, the primary treatment is systemic chemotherapy. However, even identical chemotherapy regimens bring about different outcomes in different patients. Therefore, identifying reliable pretreatment imaging biomarkers for metastatic pancreatic adenocarcinoma is a key imperative, which may help adapt treatment approaches.
Extracellular volume (ECV) fraction denotes a theoretical space which consists of the intravascular and extravascular extracellular spaces.1 We previously reported that the usefulness of tumor ECV fraction determined by equilibrium phase contrast-enhanced CT for predicting outcomes of unresectable pancreatic adenocarcinoma patients treated with chemotherapy. To our knowledge, however, no attempts have been made to apply the ECV fraction quantified with Gd-EOB-DTPA-enhanced MRI to oncologic assessment.
Purpose
The purpose of this study was to determine whether ECV fraction on Gd-EOB-DTPA-enhanced MRI can predict outcomes for patients with metastatic pancreatic adenocarcinoma.Methods
Fifty-two patients (24 men and 28 women; mean age, 69.5 years; age range, 46–86 years) with histologically confirmed pancreatic adenocarcinoma underwent Gd-EOB-DTPA-enhanced MRI. For T1 mapping, Look-Locker sequences (single slice multiphase imaging using gradient-echo sequence with inversion recovery pulseļ¼ repetition time, 7 ms; echo time, 1.7ms; flip angle, 7o; number of phases, 42; shot interval, 63 ms; field of view, 350 mm; matrix, 144 x 144; thickness, 10 mm; acquisition time, 12 s; turbo factor, 9; acceleration factor, 2.4) were obtained before and 5 min after Gd-EOB-DTPA administration. The sequence was obtained as only one axial slice at the level of the maximum diameter of tumor.
Circular or oval regions of interest (ROIs) were placed as large as possible within the pancreatic adenocarcinoma and the aorta on T1 maps before and 5 min after Gd-EOB-DTPA administration. ECV fraction of tumor was calculated using the following formula: ECV= (1-Hct) x [R1 (tumor pre) - R1 (tumor 5min)] / [T1 (aorta pre) - R1 (aorta 5min)]. Where R1 = 1/T1; R1 (tumor pre) and R1 (tumor 5min) are R1 values of the tumor before and 5 min after Gd-EOB-DTPA administration, respectively; R1 (aorta pre) and R1 (aorta 5min) are R1 values of the aorta before and 5 min after Gd-EOB-DTPA administration, respectively. The effect on survival of ECV fraction was analyzed in univariate analysis using the log-rank test. Overall survival curves were drawn using the Kaplan–Meier method.
The effect on survival of variables including age, sex, tumor location, tumor size, TNM factors, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels, and tumor ECV fraction was assessed on univariate analysis using the log-rank test. Further, multivariate analysis using Cox proportional hazards regression model was performed to identify factors that showed a significant association with survival.
Results
Median survival for the entire patient population was 11.4 months. Median survival time for patients with tumor ECV fraction ≥ 0.38 was 12.7 months, compared to 9.9 months in patients with ECV fraction < 0.38 (Fig. 1). No significant influence of patient age (P = 0.838), sex (P = 0.488), tumor location (P = 0.150), tumor size (P = 0.986), T factors (P = 0.190), N factors (P = 0.289), M factors (P = 0.336-0.892), serum CA 19-9 (P = 0.889) or CEA levels (P = 0.820) on patient survival. Tumor ECV fraction (P = 0.005) is an independent predictor of patient survival in multivariate analysis (Fig. 2).Discussion
Previous researchers have reported that pancreatic adenocarcinoma showing lower contrast enhancement has poor prognosis.2,3 Tumor hypoxia caused by a chaotic and poorly regulated blood supply has been considered to be an important factor selecting for the development of aggressive phenotype and is accepted as a major contributor to resistance against chemotherapy. The uptake of anticancer drugs has been reported to be higher in tumors with high extravascular extracellular volume fraction than in tumors with low extravascular extracellular volume fraction. No research on predictive value of tumor ECV fraction on Gd-EOB-DTPA-enhanced MRI for survival in patients with metastatic pancreatic adenocarcinoma has been reported. In this study, patients with metastatic pancreatic adenocarcinoma with lower tumor ECV fraction value showed significantly shorter survival than those with higher fraction value. Therefore, our study results suggest pancreatic adenocarcinomas with lower ECV fraction on Gd-EOB-DTPA-enhanced MRI is associated with reduced patient survival.Conclusion
Pretreatment ECV fraction measured by Gd-EOB-DTPA-enhanced MRI can predict overall survival in patients with metastatic pancreatic adenocarcinoma.Acknowledgements
No acknowledgement found.References
- Flett AS, Hayward MP, Ashworth MT, et al. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 2010; 122:138–144.
- Kim JH, Park SH, Yu ES, et al. Visually isoattenuating pancreatic adenocarcinoma at dynamic-enhanced CT: frequency, clinical and pathologic characteristics, and diagnosis at imaging examinations. Radiology 2010; 257:87–96.
- Fukukura Y, Takumi K, Higashi M, et al. Contrast-enhanced CT and diffusion-weighted MR imaging: performance as a prognostic factor in patients with pancreatic ductal adenocarcinoma. Eur J Radiol. 2014; 83:612-619.
Figures
