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. 2019 May 9;9(1):39.
doi: 10.1186/s13550-019-0507-8.

[18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer

Tomohiko Yamane  1 , Masayasu Aikawa  2 , Masanori Yasuda  3 , Kenji Fukushima  4 , Akira Seto  4 , Koujun Okamoto  2 , Isamu Koyama  2 , Ichiei Kuji  4
Affiliations

[18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer

Tomohiko Yamane et al. EJNMMI Res. .

Abstract

Background: While [18F]fluoromisonidazole (FMISO), a representative PET tracer to detect hypoxia, is reported to be able to prospect the prognosis after treatment for various types of cancers, the relation is unclear for pancreatic cancer. The aim of this study is to assess the feasibility of [18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer.

Methods: Patients with pancreatic cancer who had been initially planned for surgery received [18F]FMISO PET/CT. Peak standardized uptake value (SUV) of the pancreatic tumor was divided by SUVpeak of the aorta, and tumor blood ratio using SUVpeak (TBRpeak) was calculated. After preoperative examination, surgeons finally decided the operability of the patients. TBRpeak was compared with hypoxia-inducible factor (HIF)-1α immunohistochemistry when the tissues were available. Furthermore, correlation of TBRpeak with the recurrence-free survival and the overall survival were evaluated by Kaplan-Meyer methods.

Results: We analyzed 25 patients with pancreatic adenocarcinoma (11 women and 14 men, median age, 73 years; range, 58-81 years), and observed for 39-1101 days (median, 369 days). Nine cases (36.0%) were identified as visually positive of pancreatic cancer on [18F]FMISO PET/CT images. TBRpeak of the negative cases was significantly lower than that of the positive cases (median 1.08, interquartile range (IQR) 1.02-1.15 vs median 1.50, IQR 1.25-1.73, p < 0.001), and the cutoff TBRpeak was calculated as 1.24. Five patients were finally considered inoperable. There was no significant difference in TBRpeak of inoperable and operable patients (median 1.48, IQR 1.06-1.98 vs median 1.12, IQR 1.05-1.21, p = 0.10). There was no significant difference between TBRpeak and HIF-1α expression (p = 0.22). The patients were dichotomized by the TBRpeak cutoff, and the higher group showed significantly shorter recurrence-free survival than the other (median 218 vs 441 days, p = 0.002). As for overall survival of 20 cases of operated patients, the higher TBRpeak group showed significantly shorter overall survival than the other (median survival, 415 vs > 1000 days, p = 0.04).

Conclusions: [18F]FMISO PET/CT has the possibility to be a preoperative prognostic factor in patients with pancreatic cancer.

Keywords: F-18 fluoromisonidazole (F-18 FMISO); HIF-1 alfa; Hypoxia; Operation; Pancreas; Pancreatectomy; Surgery.

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Conflict of interest statement

Ethics approval and consent to participate

Our institutional review board approved the protocol of this study (Registration #14-110). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or 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.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Box plots of TBRpeak by the results of visual evaluation of [18F]FMISO PET/CT (a), TBRpeak of operable and inoperable patients (c), TBRpeak by HIF-1α immunohistochemical expressions evaluated by 4 categories (0, 1, 2, and 3) (d), and 2 categories (low and high) (e). Red horizontal dot lines indicate TBRpeak = 1.24 calculated by the receiver operating characteristic analysis (b). Lines on whiskers and boxes in box blots indicate maximum, upper quartile, median, lower quartile, and minimum, respectively
Fig. 2
Fig. 2
Representative [18F]FMISO PET/CT images (a, b, c) and HIF-1α immunohistochemical images (d, e) of pancreatic cancer. A color bar from 0 to 3 indicates standardize uptake value (SUV) of fused [18F]FMISO images. The first case with increased [18F]FMISO uptake on the primary tumor (a, arrows) was finally decided as inoperable. The second case with moderate [18F]FMISO uptake (b, arrows) received operation, and the immunohistochemistry shows strong HIF-1α expression (d). The third case with low [18F]FMISO uptake (c, arrows) also received operation, and the immunohistochemistry shows no apparent HIF-1α expression (e)
Fig. 3
Fig. 3
Kaplan-Meyer survival curves about the recurrence-free survival rate (a) and the overall survival rates of low-TBRpeak (blue lines) and high-TBRpeak (red lines). For the overall survival, curves of all cases including inoperable (b) and of only operable cases (c) are shown. TBR tumor blood ratio
See this image and copyright information in PMC

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