J Gastric Cancer.  2018 Sep;18(3):218-229. 10.5230/jgc.2018.18.e23.

Preoperative Nodal ¹⁸F-FDG Avidity Rather than Primary Tumor Avidity Determines the Prognosis of Patients with Advanced Gastric Cancer

• Kwon HW
• An L
• Kwon HR
• Park S
• Kim S

• KMID: 2420782
• DOI: http://doi.org/10.5230/jgc.2018.18.e23

Abstract

PURPOSE
This study investigated whether the metabolic avidity of primary tumors and/or metastatic lymph nodes (LNs) measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was related to survival after surgery in patients with advanced gastric cancer (AGC).
MATERIALS AND METHODS
One hundred sixty-eight patients with AGC who underwent preoperative 18F-FDG PET/CT and curative resection were included. The 18F-FDG avidity of the primary gastric tumor and LNs was determined quantitatively and qualitatively. The diagnostic performance of 18F-FDG PET/CT was calculated, and the prognostic significance of 18F-FDG avidity for recurrence-free survival (RFS) and overall survival (OS) was assessed.
RESULTS
In all, 51 (30.4%) patients experienced recurrence, and 32 (19.0%) died during follow-up (median follow-up duration, 35 months; range, 3-81 months); 119 (70.8%) and 33 (19.6%) patients showed 18F-FDG-avid primary tumors and LNs, respectively. 18F-FDG PET/CT showed high sensitivity (73.8%) for the detection of advanced pathologic T (pT ≥3) stage and high specificity (92.2%) for the detection of advanced pN (≥2) stage. 18F-FDG avidity of LNs was significantly associated with RFS (P=0.012), whereas that of primary tumors did not show significance (P=0.532). Univariate and multivariate analyses revealed that 18F-FDG avidity of LNs was an independent prognostic factor for RFS (hazard ratio=2.068; P=0.029).
CONCLUSIONS
18F-FDG avidity of LNs is an independent prognostic factor for predicting RFS. Preoperative 18F-FDG PET/CT can be used to determine the risk and prognosis of patients with AGC after curative resection.

Keyword

Gastric cancer; ¹⁸F-fluorodeoxyglucose; Positron Emission Tomography Computed Tomography; Recurrence

MeSH Terms

Electrons
Fluorodeoxyglucose F18
Follow-Up Studies
Humans
Lymph Nodes
Multivariate Analysis
Positron-Emission Tomography and Computed Tomography
Prognosis*
Recurrence
Sensitivity and Specificity
Stomach Neoplasms*
Fluorodeoxyglucose F18

Figure

• 

  Fig. 1 Representative cases of 18F-FDG-avid primary tumor (A, left) and LNs (A, right), non-avid primary tumor (B), and non-avid LN (C). The metabolic tumor volume of the primary tumor and LNs in the patient (A) was 18.8 cm3 and 0.2 cm3, respectively (yellow arrow: primary tumor, red arrow: LN). 18F-FDG = 18F-fluorodeoxyglucose; LN = lymph node.

• 

  Fig. 2 Cumulative RFS curve according to the 18F-FDG avidity of (A) primary tumors and (B) LNs in enrolled patients (red: non-avid group, blue: 18F-FDG-avid group). RFS = recurrence-free survival; LN = lymph node.

Reference

1. Jung KW, Won YJ, Oh CM, Kong HJ, Lee DH, Lee KH, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2014. Cancer Res Treat. 2017; 49:292–305.

2. Katanoda K, Hori M, Matsuda T, Shibata A, Nishino Y, Hattori M, et al. An updated report on the trends in cancer incidence and mortality in Japan, 1958–2013. Jpn J Clin Oncol. 2015; 45:390–401.

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

4. Maehara Y, Hasuda S, Koga T, Tokunaga E, Kakeji Y, Sugimachi K. Postoperative outcome and sites of recurrence in patients following curative resection of gastric cancer. Br J Surg. 2000; 87:353–357.

5. Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012; 61:673–684.

6. Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, Shim B, et al. Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res. 2012; 72:4383–4393.

7. Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016; 14:1286–1312.

8. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016; 27:v38–v49.

9. Smyth E, Schöder H, Strong VE, Capanu M, Kelsen DP, Coit DG, et al. A prospective evaluation of the utility of 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. Cancer. 2012; 118:5481–5488.

10. Baiocchi GL, Marrelli D, Verlato G, Morgagni P, Giacopuzzi S, Coniglio A, et al. Follow-up after gastrectomy for cancer: an appraisal of the Italian research group for gastric cancer. Ann Surg Oncol. 2014; 21:2005–2011.

11. Lee JW, Jo K, Cho A, Noh SH, Lee JD, Yun M. Relationship between ¹⁸F-FDG uptake on PET and recurrence patterns after curative surgical resection in patients with advanced gastric cancer. J Nucl Med. 2015; 56:1494–1500.

12. Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007; 8:797–805.

13. Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006; 24:4692–4698.

14. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010; 17:3077–3079.

15. Song BI, Kim HW, Won KS, Ryu SW, Sohn SS, Kang YN. Preoperative standardized uptake value of metastatic lymph nodes measured by ¹⁸F-FDG PET/CT improves the prediction of prognosis in gastric cancer. Medicine (Baltimore). 2015; 94:e1037.

16. Cerfolio RJ, Bryant AS. Ratio of the maximum standardized uptake value on FDG-PET of the mediastinal (N2) lymph nodes to the primary tumor may be a universal predictor of nodal malignancy in patients with nonsmall-cell lung cancer. Ann Thorac Surg. 2007; 83:1826–1830.

17. Park J, Byun BH, Noh WC, Lee SS, Kim HA, Kim EK, et al. Lymph node to primary tumor SUV ratio by ¹⁸F-FDG PET/CT and the prediction of axillary lymph node metastases in breast cancer. Clin Nucl Med. 2014; 39:e249–e253.

18. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011; 14:101–112.

19. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010; 11:439–449.

20. Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010; 28:1547–1553.

21. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007; 357:1810–1820.

22. Abbas M, Habib M, Naveed M, Karthik K, Dhama K, Shi M, et al. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice. Biomed Pharmacother. 2017; 95:1082–1090.

23. Deng JY, Liang H. Clinical significance of lymph node metastasis in gastric cancer. World J Gastroenterol. 2014; 20:3967–3975.

24. Sarela AI, Turnbull AD, Coit DG, Klimstra D, Brennan MF, Karpeh MS. Accurate lymph node staging is of greater prognostic importance than subclassification of the T2 category for gastric adenocarcinoma. Ann Surg Oncol. 2003; 10:783–791.

25. Ichikura T, Tomimatsu S, Okusa Y, Uefuji K, Tamakuma S. Comparison of the prognostic significance between the number of metastatic lymph nodes and nodal stage based on their location in patients with gastric cancer. J Clin Oncol. 1993; 11:1894–1900.

26. Ahn HS, Lee HJ, Yoo MW, Kim SG, Im JP, Kim SH, et al. Diagnostic accuracy of T and N stages with endoscopy, stomach protocol CT, and endoscopic ultrasonography in early gastric cancer. J Surg Oncol. 2009; 99:20–27.

27. Hwang SW, Lee DH. Is endoscopic ultrasonography still the modality of choice in preoperative staging of gastric cancer? World J Gastroenterol. 2014; 20:13775–13782.

28. Kim SH, Kim JJ, Lee JS, Kim SH, Kim BS, Maeng YH, et al. Preoperative N staging of gastric cancer by stomach protocol computed tomography. J Gastric Cancer. 2013; 13:149–156.

29. Kim SK, Kang KW, Lee JS, Kim HK, Chang HJ, Choi JY, et al. Assessment of lymph node metastases using ¹⁸F-FDG PET in patients with advanced gastric cancer. Eur J Nucl Med Mol Imaging. 2006; 33:148–155.

30. Kim EY, Lee WJ, Choi D, Lee SJ, Choi JY, Kim BT, et al. The value of PET/CT for preoperative staging of advanced gastric cancer: comparison with contrast-enhanced CT. Eur J Radiol. 2011; 79:183–188.

31. Yun M, Lim JS, Noh SH, Hyung WJ, Cheong JH, Bong JK, et al. Lymph node staging of gastric cancer using ¹⁸F-FDG PET: a comparison study with CT. J Nucl Med. 2005; 46:1582–1588.

32. Coupe NA, Karikios D, Chong S, Yap J, Ng W, Merrett N, et al. Metabolic information on staging FDG-PET-CT as a prognostic tool in the evaluation of 97 patients with gastric cancer. Ann Nucl Med. 2014; 28:128–135.

33. Lee JW, Lee SM, Lee MS, Shin HC. Role of ¹⁸F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection. Eur J Nucl Med Mol Imaging. 2012; 39:1425–1434.

34. Mochiki E, Kuwano H, Katoh H, Asao T, Oriuchi N, Endo K. Evaluation of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography for gastric cancer. World J Surg. 2004; 28:247–253.

35. Stahl A, Ott K, Weber WA, Becker K, Link T, Siewert JR, et al. FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings. Eur J Nucl Med Mol Imaging. 2003; 30:288–295.

36. Kim J, Lim ST, Na CJ, Han YH, Kim CY, Jeong HJ, et al. Pretreatment F-18 FDG PET/CT parameters to evaluate progression-free survival in gastric cancer. Nucl Med Mol Imaging. 2014; 48:33–40.

37. Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007; 48:932–945.