Abstract
Purpose
18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of 18F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and 18F-FDG PET/CT parameters.
Methods
A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative 18F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each 18F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and 18F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence.
Results
Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the 18F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19–9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0.001, respectively) demonstrated significant results.
Conclusions
The heterogeneity index obtained using the linear regression slope, could be an effective predictor of pancreatic cancer recurrence after pancreatic cancer surgery, in addition to 18F-FDG PET/CT volumetric parameters and clinicopathologic parameters.
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References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.
Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223:273–9.
Osayi SN, Bloomston M, Schmidt CM, Ellison EC, Muscarella P. Biomarkers as predictors of recurrence following curative resection for pancreatic ductal adenocarcinoma: a review. Biomed Res Int. 2014;2014:468959.
Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008;49:480–508.
Wang Z, Chen J-Q, Liu J-L, Qin X-G, Huang Y. FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: a meta-analysis. World J Gastroenterol. 2013;19:4808–17.
Dibble EH, Karantanis D, Mercier G, Peller PJ, Kachnic LA, Subramaniam RM. PET/CT of cancer patients: part 1, pancreatic neoplasms. AJR Am J Roentgenol. 2012;199:952–67.
Yamamoto T, Sugiura T, Mizuno T, Okamura Y, Aramaki T, Endo M, et al. Preoperative FDG-PET predicts early recurrence and a poor prognosis after resection of pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22:677–84.
Kang CM, Lee SH, Hwang HK, Yun M, Lee WJ. Preoperative volume-based PET parameter, MTV2. 5, as a potential surrogate marker for tumor biology and recurrence in resected pancreatic cancer. Medicine (Baltimore). 2016;95:e2595.
Parlak C, Topkan E, Onal C, Reyhan M, Selek U. Prognostic value of gross tumor volume delineated by FDG-PET-CT based radiotherapy treatment planning in patients with locally advanced pancreatic cancer treated with chemoradiotherapy. Radiat Oncol. 2012;7:37.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883–92.
Asselin M-C, O’Connor JP, Boellaard R, Thacker NA, Jackson A. Quantifying heterogeneity in human tumours using MRI and PET. Eur J Cancer. 2012;48:447–55.
Huang B, Chan T, Kwong DL-W, Chan WKS, Khong P-L. Nasopharyngeal carcinoma: investigation of intratumoral heterogeneity with FDG PET/CT. AJR Am J Roentgenol. 2012;199:169–74.
Chung HH, Kang SY, Ha S, Kim J-W, Park N-H, Song YS, et al. Prognostic value of preoperative intratumoral FDG uptake heterogeneity in early stage uterine cervical cancer. J Gynecol Oncol. 2015;27:e15.
Kim TH, Yoon J-K, Kang DK, Lee SJ, Jung YS, Yim H, et al. Correlation between F-18 fluorodeoxyglucose positron emission tomography metabolic parameters and dynamic contrast-enhanced MRI-derived perfusion data in patients with invasive ductal breast carcinoma. Ann Surg Oncol. 2015;22:3866–72.
Kwon SH, Yoon JK, An YS, Shin YS, Kim CH, Lee DH, et al. Prognostic significance of the intratumoral heterogeneity of 18F-FDG uptake in oral cavity cancer. J Surg Oncol. 2014;110:702–6.
Lee M, Lee H, Cheon GJ, Kim HS, Chung HH, Kim J-W, et al. Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer. Eur Radiol. 2017;27:16–23.
Lucignani G. SUV and segmentation: pressing challenges in tumour assessment and treatment. Eur J Nucl Med Mol Imaging. 2009;36:715–20.
Chicklore S, Goh V, Siddique M, Roy A, Marsden PK, Cook GJ. Quantifying tumour heterogeneity in 18F-FDG PET/CT imaging by texture analysis. Eur J Nucl Med Mol Imaging. 2013;40:133–40.
Hatt M, Majdoub M, Vallières M, Tixier F, Le Rest CC, Groheux D, et al. 18F-FDG PET uptake characterization through texture analysis: investigating the complementary nature of heterogeneity and functional tumor volume in a multi–cancer site patient cohort. J Nucl Med. 2015;56:38–44.
Cook GJ, O’Brien ME, Siddique M, Chicklore S, Loi HY, Sharma B, et al. Non–small cell lung cancer treated with erlotinib: heterogeneity of 18F-FDG uptake at PET—association with treatment response and prognosis. Radiology. 2015;276:883–93.
Hyun SH, Kim HS, Choi SH, Choi DW, Lee JK, Lee KH, et al. Intratumoral heterogeneity of 18F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging. 2016;43:1461–8.
Wang S-L, Cao S, Sun Y-N, Wu R, Chi F, Tang M-Y, et al. Standardized uptake value on positron emission tomography/computed tomography predicts prognosis in patients with locally advanced pancreatic cancer. Abdom Imaging. 2015;40:3117–21.
Sun Y, Duan Q, Wang S, Yuecan ZW. Diagnosis of pancreatic cancer using 18F-FDG PET/CT and CA19-9 with SUVmax association to clinical characteristics. J BUON. 2015;20:452–9.
Chirindel A, Alluri KC, Chaudhry MA, Wahl RL, Pawlik TM, Herman JM, et al. Prognostic value of FDG PET/CT–derived parameters in pancreatic adenocarcinoma at initial PET/CT staging. AJR Am J Roentgenol. 2015;204:1093–9.
Choi HJ, Kang CM, Jo K, Lee WJ, Lee J-H, Ryu YH, et al. Prognostic significance of standardized uptake value on preoperative 18F-FDG PET/CT in patients with ampullary adenocarcinoma. Eur J Nucl Med Mol Imaging. 2015;42:841–7.
Thie JA. Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med. 2004;45:1431–4.
Y-i K, Paeng JC, Cheon GJ, Suh K-S, Lee DS, Chung J-K, et al. Prediction of posttransplantation recurrence of hepatocellular carcinoma using metabolic and volumetric indices of 18F-FDG PET/CT. J Nucl Med. 2016;57:1045–51.
Lee JW, Kang CM, Choi HJ, Lee WJ, Song SY, Lee J-H, et al. Prognostic value of metabolic tumor volume and total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with pancreatic cancer. J Nucl Med. 2014;55:898–904.
Xu H-X, Chen T, Wang W-Q, Wu C-T, Liu C, Long J, et al. Metabolic tumour burden assessed by 18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection. Eur J Nucl Med Mol Imaging. 2014;41:1093–102.
Shimada K, Sakamoto Y, Sano T, Kosuge T. Prognostic factors after distal pancreatectomy with extended lymphadenectomy for invasive pancreatic adenocarcinoma of the body and tail. Surgery. 2006;139:288–95.
Nakagohri T, Kinoshita T, Konishi M, Inoue K, Takahashi S. Survival benefits of portal vein resection for pancreatic cancer. Am J Surg. 2003;186:149–53.
Ishikawa O, Ohigashi H, Imaoka S, Furukawa H, Sasaki Y, Fujita M, et al. Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein. Ann Surg. 1992;215:231–6.
Acknowledgements
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of education (2009-0093820), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1072), and by a grant of the Research Driven Hospital R&D project, funded by the CHA Bundang Medical Center (grant number: BDCHA R&D 2017-018).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Kim, Yi., Kim, Y.J., Paeng, J.C. et al. Heterogeneity index evaluated by slope of linear regression on 18F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging 44, 1995–2003 (2017). https://doi.org/10.1007/s00259-017-3755-8
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DOI: https://doi.org/10.1007/s00259-017-3755-8