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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-11-2017 | Original Article

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

Authors: Yong-il Kim, Yong Joong Kim, Jin Chul Paeng, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, Keon Wook Kang

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2017

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.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRef

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.CrossRefPubMedPubMedCentral

10.

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.CrossRefPubMedPubMedCentral

11.

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.CrossRefPubMed

12.

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.CrossRefPubMed

13.

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.CrossRefPubMedCentral

14.

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.CrossRefPubMed

15.

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.CrossRefPubMed

16.

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.CrossRefPubMed

17.

Lucignani G. SUV and segmentation: pressing challenges in tumour assessment and treatment. Eur J Nucl Med Mol Imaging. 2009;36:715–20.CrossRefPubMed

18.

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.CrossRefPubMed

19.

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.CrossRefPubMed

20.

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.CrossRefPubMed

21.

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.CrossRefPubMed

22.

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.CrossRefPubMed

23.

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.PubMed

24.

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.CrossRefPubMed

25.

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.CrossRefPubMed

26.

Thie JA. Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med. 2004;45:1431–4.PubMed

27.

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.CrossRef

28.

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.CrossRefPubMed

29.

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.CrossRefPubMed

30.

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.CrossRefPubMed

31.

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.CrossRefPubMed

32.

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.CrossRefPubMedPubMedCentral

Title: 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
Authors: Yong-il Kim
Yong Joong Kim
Jin Chul Paeng
Gi Jeong Cheon
Dong Soo Lee
June-Key Chung
Keon Wook Kang
Publication date: 01-11-2017
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-017-3755-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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