Multiparametric PET/MR imaging biomarkers are associated with overall survival in patients with pancreatic cancer
To correlate the overall survival (OS) with the imaging biomarkers of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy, and glucose metabolic activity derived from integrated fluorine 18 fluorodeoxyglucose positron emission tomography (18F–FDG PET)/MRI in patients with pancreatic cancer.
This prospective study was approved by the institutional review board and informed consent was obtained from all participants. Sixty-three consecutive patients (mean age, 62.7 ± 12 y; men/women, 40/23) with pancreatic cancer underwent PET/MRI before treatment. The imaging biomarkers were comprised of DCE-MRI parameters (peak, IAUC 60 , K trans , k ep , v e ), the minimum apparent diffusion coefficient (ADCmin), choline level, standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) of the tumors. The relationships between these imaging biomarkers with OS were evaluated with the Kaplan-Meier and Cox proportional hazard models.
Seventeen (27%) patients received curative surgery, with the median follow-up duration being 638 days. Univariate analysis showed that patients at a low TNM stage (≦3, P = 0.041), high peak (P = 0.006), high ADCmin (P = 0.002) and low TLG (P = 0.01) had better OS. Moreover, high TLG/peak ratio was associated with poor OS (P = 0.016). Multivariate analysis indicated that ADCmin (P = 0.011) and TLG/peak ratio (P = 0.006) were independent predictors of OS after adjustment for age, gender, tumor size, and TNM stage. The TLG/peak ratio was an independent predictor of OS in a subgroup of patients who did not receive curative surgery (P = 0.013).
The flow-metabolism mismatch reflected by the TLG/peak ratio may better predict OS than other imaging biomarkers from PET/MRI in pancreatic cancer patients.
KeywordsPET/MR Pancreatic cancer Dynamic contrast-enhanced MRI Diffusion weighted MRI MR spectroscopy Overall survival
The study is funded by National Taiwan University Hospital, Taipei, Taiwan: A1 project No. NTUH103-A124; Ministry of Science and Technology (MOST): No. 104–2314-B-002-080-MY3
Compliance with ethical standards
Conflict of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 7.Joo I, Lee JM, Lee DH, Lee ES, Paeng JC, Lee SJ, et al. Preoperative assessment of pancreatic cancer with FDG PET/MR imaging versus FDG PET/CT plus contrast-enhanced multidetector CT: a prospective preliminary study. Radiology. 2017;282:149–59. https://doi.org/10.1148/radiol.2016152798.CrossRefPubMedGoogle Scholar
- 9.Komar G, Kauhanen S, Liukko K, Seppanen M, Kajander S, Ovaska J, et al. Decreased blood flow with increased metabolic activity: a novel sign of pancreatic tumor aggressiveness. Clin Canc Res : Off J Am Assoc Canc Res. 2009;15:5511–7. https://doi.org/10.1158/1078-0432.CCR-09-0414.CrossRefGoogle Scholar
- 13.Shen G, Ma H, Liu B, Ren P, Kuang A. Correlation of the apparent diffusion coefficient and the standardized uptake value in neoplastic lesions: a meta-analysis. Nucl Med Commun. 20176; https://doi.org/10.1097/MNM.0000000000000746.
- 14.Rakheja R, Chandarana H, DeMello L, Jackson K, Geppert C, Faul D, et al. Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI. AJR Am J Roentgenol. 2013;201:1115–9. https://doi.org/10.2214/AJR.13.11304.CrossRefPubMedGoogle Scholar
- 15.Sakane M, Tatsumi M, Kim T, Hori M, Onishi H, Nakamoto A, et al. Correlation between apparent diffusion coefficients on diffusion-weighted MRI and standardized uptake value on FDG-PET/CT in pancreatic adenocarcinoma. Acta Radiol. 2015;56:1034–41. https://doi.org/10.1177/0284185114549825.CrossRefPubMedGoogle Scholar
- 16.Chen BB, Tien YW, Chang MC, Cheng MF, Chang YT, Wu CH, et al. PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis. Eur J Nucl Med Mol Imaging. 2016;43:1753–64. https://doi.org/10.1007/s00259-016-3356-y.CrossRefPubMedGoogle Scholar
- 17.Chen BB, Hsu CY, Yu CW, Liang PC, Hsu C, Hsu CH, et al. Dynamic contrast-enhanced MR imaging of advanced Hepatocellular carcinoma: comparison with the liver parenchyma and correlation with the survival of patients receiving systemic therapy. Radiology. 2016;281:454–64. https://doi.org/10.1148/radiol.2016152659.CrossRefPubMedGoogle Scholar
- 27.Ma W, Li N, Zhao W, Ren J, Wei M, Yang Y, et al. Apparent diffusion coefficient and dynamic contrast-enhanced magnetic resonance imaging in pancreatic cancer: characteristics and correlation with Histopathologic parameters. J Comput Assist Tomogr. 2016;40:709–16. https://doi.org/10.1097/RCT.0000000000000434.CrossRefPubMedGoogle Scholar
- 29.Kurosawa J, Tawada K, Mikata R, Ishihara T, Tsuyuguchi T, Saito M, et al. Prognostic relevance of apparent diffusion coefficient obtained by diffusion-weighted MRI in pancreatic cancer. J Magnet Res Imaging : JMRI. 2015; https://doi.org/10.1002/jmri.24939.
- 31.Battini S, Faitot F, Imperiale A, Cicek AE, Heimburger C, Averous G, et al. Metabolomics approaches in pancreatic adenocarcinoma: tumor metabolism profiling predicts clinical outcome of patients. BMC Med. 2017;15:56. https://doi.org/10.1186/s12916-017-0810-z.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Chaika NV, Gebregiworgis T, Lewallen ME, Purohit V, Radhakrishnan P, Liu X, et al. MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer. Proc Natl Acad Sci U S A. 2012;109:13787–92. https://doi.org/10.1073/pnas.1203339109.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Li N, Li Y, Li Z, Huang C, Yang Y, Lang M, et al. Hypoxia inducible factor 1 (HIF-1) recruits macrophage to activate pancreatic Stellate cells in pancreatic Ductal Adenocarcinoma. Int J Mol Sci. 2016;17 https://doi.org/10.3390/ijms17060799.
- 36.Bali MA, Metens T, Denolin V, Delhaye M, Demetter P, Closset J, et al. Tumoral and nontumoral pancreas: correlation between quantitative dynamic contrast-enhanced MR imaging and histopathologic parameters. Radiology. 2011;261:456–66. https://doi.org/10.1148/radiol.11103515.CrossRefPubMedGoogle Scholar