Dual-time point 18F-FDG PET/CT for the staging of oesophageal cancer: the best diagnostic performance by retention index for N-staging in non-calcified lymph nodes

  • Sohyun Park
  • Jin Chul Paeng
  • Chang Hyun KangEmail author
  • Gi Jeong CheonEmail author
  • Keon Wook Kang
  • June-Key Chung
  • Dong Soo Lee
Original Article



The purpose of this study is to investigate the role of dual time point (DTP) 18F-FDG PET/CT in the staging of oesophageal cancer, especially in lymph node metastasis.


A total of 35 patients with oesophageal squamous cell carcinoma who underwent surgical treatment without neoadjuvant chemotherapy were enrolled as a test set and another 19 patients were enrolled as a validation set. The DTP PET/CT scans were obtained in dual time points at 60 and 120 min each, following the administration of 18F-FDG. Visual analysis was performed and semiquantitative analysis was performed using several PET parameters such as maximal standardized uptake values (SUVmax), peak SUV (SUVpeak) and retention indexes using SUVmax (RImax) and SUVpeak (RIpeak).


Primary oesophageal lesions exhibited a significant difference for SUVmax at each time point scan (ANOVA, p < 0.001). For nodal staging, a total of 276 non-calcified nodal stations of the test set were evaluated. Sensitivity, specificity and accuracy of visual analysis were 32.0% (8 of 25), 96.8% (243 of 251) and 90.9% (251 of 276) in the test set. Using ROC analysis, RImax had the largest area under the curve (AUC) to detect metastatic lymphadenopathy at the optimal cut-off value of 6% (AUC 0.853, P < 0.001) in the test set (sensitivity, specificity and accuracy; 80.0% (20 of 25), 94.8% (238 of 251) and 93.5% (258 of 276)). In the validation set (179 non-calcified nodal stations), sensitivity, specificity and accuracy of RImax at the optimal cut-off of 6% were 71.4% (5 of 7), 99.4% (171 of 172) and 98.4% (176 of 179), whereas those of visual analysis were 14.3% (1 of 7), 98.8% (170 of 172) and 95.5% (171 of 179).


The best diagnostic performance of nodal staging in patients with oesophageal cancer was achieved by application of RImax with a cut-off of more than 6% on DTP 18F-FDG PET/CT with the exclusion of calcified lymph nodes. Optimal clinical management in surgically-candidate oesophageal cancer patients could be achieved using the diagnostic flow on DTP 18F-FDG PET/CT.


Oesophageal cancer Staging 18F-FDG PET/CT Dual-time point PET/CT 



This research was supported by an intramural research fund from Seoul National University Hospital (SNUH 04-2013-0670) and grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare (grant number:HI14C1072) and the National Research Foundation of Korea (NRF) grant for the Global Core Research Center (GCRC) funded by the Korea MSIP (Ministry of Science, ICT & Futher Planning)(No. NRF-2011-0030001).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures were performed in accordance with the principles of the 1975 Declaration of Helsinki (2000 revision). The study design and exemption from informed consent were approved by the Institutional Review Board of Seoul National University Hospital (1306-088-498).

Informed consent

Informed consent was waived because of the retrospective nature of this study.

Supplementary material

259_2018_3981_MOESM1_ESM.docx (942 kb)
ESM 1 (DOCX 942 kb)


  1. 1.
    Zhang Y. Epidemiology of esophageal cancer. World J Gastroenterol. 2013;19:5598–606.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 381:400–12.Google Scholar
  3. 3.
    Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Matsubara T, Ueda M, Nakajima T. Preoperative assessment of lymph nodes in the prediction of disease spread and outcome in cancer of the thoracic oesophagus. Br J Surg. 1995;82:356–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Hosch SB, Stoecklein NH, Pichlmeier U, Rehders A, Scheunemann P, Niendorf A, et al. Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. J Clin Oncol. 2001;19:1970–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Isono K, Sato H, Nakayama K. Results of a nationwide study on the three-field lymph node dissection of esophageal cancer. Oncology. 1991;48:411–20.CrossRefPubMedGoogle Scholar
  7. 7.
    Miyata H, Yamasaki M, Makino T, Tatsumi M, Miyazaki Y, Takahashi T, et al. Impact of number of [(18)F]fluorodeoxyglucose-PET-positive lymph nodes on survival of patients receiving neoadjuvant chemotherapy and surgery for oesophageal cancer. Br J Surg. 2016;103:97–104.CrossRefPubMedGoogle Scholar
  8. 8.
    Souquet JC, Napoleon B, Pujol B, Keriven O, Ponchon T, Descos F, et al. Endoscopic ultrasonography in the preoperative staging of esophageal cancer. Endoscopy. 1994;26:764–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Kalantzis N, Kallimanis G, Laoudi F, Papavasiliou E, Gabriel G. Endoscopic ultrasonography and computed tomography in preoperative (TNM) classification of oesophageal carcinoma [abstr]. Endoscopy. 1992;24:653.Google Scholar
  10. 10.
    Walker AJ, Spier BJ, Perlman SB, Stangl JR, Frick TJ, Gopal DV, et al. Integrated PET/CT fusion imaging and endoscopic ultrasound in the pre-operative staging and evaluation of esophageal cancer. Mol Imaging Biol. 2011;13:166–71.CrossRefPubMedGoogle Scholar
  11. 11.
    Hong SJ, Kim TJ, Nam KB, Lee IS, Yang HC, Cho S, et al. New TNM staging system for esophageal cancer: what chest radiologists need to know. Radiographics. 2014;34:1722–40.CrossRefPubMedGoogle Scholar
  12. 12.
    Kumar P, Damle NA, Bal C. Role of F18-FDG PET/CT in the staging and restaging of esophageal cancer: a comparison with CECT. Indian J Surg Oncol. 2011;2:343–50.CrossRefPubMedGoogle Scholar
  13. 13.
    Barber TW, Duong CP, Leong T, Bressel M, Drummond EG, Hicks RJ. 18F-FDG PET/CT has a high impact on patient management and provides powerful prognostic stratification in the primary staging of esophageal cancer: a prospective study with mature survival data. J Nucl Med. 2012;53:864–71.CrossRefPubMedGoogle Scholar
  14. 14.
    van Westreenen HL, Westerterp M, Bossuyt PM, Pruim J, Sloof GW, van Lanschot JJ, et al. Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer. J Clin Oncol. 2004;22:3805–12.CrossRefPubMedGoogle Scholar
  15. 15.
    Okada M, Murakami T, Kumano S, Kuwabara M, Shimono T, Hosono M, et al. Integrated FDGPET/CT compared with intravenous contrast-enhanced CT for evaluation of metastatic regional lymph nodes in patients with resectable early stage esophageal cancer. Ann Nucl Med. 2009;23:73–80.CrossRefPubMedGoogle Scholar
  16. 16.
    van Vliet EP, Heijenbrok-Kal MH, Hunink MG, Kuipers EJ, Siersema PD. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. 2008;98:547–57.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Schillaci O. Use of dual-point fluorodeoxyglucose imaging to enhance sensitivity and specificity. Semin Nucl Med. 2012;42:267–80.CrossRefPubMedGoogle Scholar
  18. 18.
    Cheng G, Torigian DA, Zhuang H, Alavi A. When should we recommend use of dual time-point and delayed time-point imaging techniques in FDG PET? Eur J Nucl Med Mol Imaging. 2013;40:779–87.CrossRefPubMedGoogle Scholar
  19. 19.
    Kubota K, Itoh M, Ozaki K, Ono S, Tashiro M, Yamaguchi K, et al. Advantage of delayed wholebody FDG-PET imaging for tumour detection. Eur J Nucl Med. 2001;28:696–703.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med. 2001;42:1412–7.PubMedGoogle Scholar
  21. 21.
    Hildebrandt MG, Gerke O, Baun C, Falch K, Hansen JA, Farahani ZA, et al. [18F]Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) in suspected recurrent breast cancer: a prospective comparative study of dual-time-point FDGPET/CT, contrast-enhanced CT, and bone scintigraphy. J Clin Oncol. 2016;34:1889–97.CrossRefPubMedGoogle Scholar
  22. 22.
    Shen G, Hu S, Deng H, Jia Z. Diagnostic value of dual time-point 18F-FDG PET/CT versus single time-point imaging for detection of mediastinal nodal metastasis in non-small cell lung cancer patients: a meta-analysis. Acta Radiol. 2015;56:681–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Hu M, Han A, Xing L, Yang W, Fu Z, Huang C, et al. Value of dual-time-point FDG PET/CT for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity. Clin Nucl Med. 2011;36:429–33.CrossRefPubMedGoogle Scholar
  24. 24.
    Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Kim YK, Lee KS, Kim BT, Choi JY, Kim H, Kwon OJ, et al. Mediastinal nodal staging of nonsmall cell lung cancer using integrated 18F-FDG PET/CT in a tuberculosis-endemic country: diagnostic efficacy in 674 patients. Cancer. 2007;109:1068–77.CrossRefPubMedGoogle Scholar
  26. 26.
    Karam M, Roberts-Klein S, Shet N, Chang J, Feustel P. Bilateral hilar foci on 18F-FDG PET scan in patients without lung cancer: variables associated with benign and malignant etiology. J Nucl Med. 2008;49:1429–36.CrossRefPubMedGoogle Scholar
  27. 27.
    Lee JW, Kim BS, Lee DS, Chung JK, Lee MC, Kim S, et al. 18F-FDG PET/CT in mediastinal lymph node staging of non-small-cell lung cancer in a tuberculosis-endemic country: consideration of lymph node calcification and distribution pattern to improve specificity. Eur J Nucl Med Mol Imaging. 2009;36:1794–802.CrossRefPubMedGoogle Scholar
  28. 28.
    Suga K, Kawakami Y, Hiyama A, Sugi K, Okabe K, Matsumoto T, et al. Differential diagnosis between (18)F-FDG-avid metastatic lymph nodes in non-small cell lung cancer and benign nodes on dual-time point PET/CT scan. Ann Nucl Med. 2009;23:523–31.CrossRefPubMedGoogle Scholar
  29. 29.
    Shum WY, Hsieh TC, Yeh JJ, Chen JH, Su CC, Liang JA, et al. Clinical usefulness of dual-time FDG PET-CT in assessment of esophageal squamous cell carcinoma. Eur J Radiol. 2012;81:1024–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Nakamura S, Okochi K, Kurabayashi T. Dual-time-point fluorodeoxyglucose positron emission tomography for diagnosis of cervical lymph node metastases in patients with head and neck squamous cell carcinoma. J Comput Assist Tomogr. 2011;35:303–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932–45.CrossRefPubMedGoogle Scholar
  32. 32.
    Sakaguchi Y, Mizoguchi N, Mitsumoto T, Mitsumoto K, Himuro K, Ohya N, et al. A simple table lookup method for PET/CT partial volume correction using a point-spread function in diagnosing lymph node metastasis. Ann Nucl Med. 2010;24:585–91.CrossRefPubMedGoogle Scholar
  33. 33.
    Gallivanone F, Canevari C, Gianolli L, Salvatore C, Della Rosa PA, Gilardi MC, et al. A partial volume effect correction tailored for (18)F-FDG-PET oncological studies. Biomed Res Int. 2013;2013:780458.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Manabe O, Hattori N, Hirata K, Itoh K, Hosokawa M, Takahashi H, et al. Diagnostic accuracy of lymph node metastasis depends on metabolic activity of the primary lesion in thoracic squamous esophageal cancer. J Nucl Med. 2013;54:670–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Moon SH, Kim HS, Hyun SH, Choi YS, Zo JI, Shim YM, et al. Prediction of occult lymph node metastasis by metabolic parameters in patients with clinically N0 esophageal squamous cell carcinoma. J Nucl Med. 2014;55:743–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Yoon YC, Lee KS, Shim YM, Kim BT, Kim K, Kim TS. Metastasis to regional lymph nodes in patients with esophageal squamous cell carcinoma: CT versus FDG PET for presurgical detection prospective study. Radiology. 2003;227:764–70.CrossRefPubMedGoogle Scholar
  37. 37.
    Konishi J, Yamazaki K, Tsukamoto E, Tamaki N, Onodera Y, Otake T, et al. Mediastinal lymph node staging by FDG-PET in patients with non-small cell lung cancer: analysis of false-positive FDG PET findings. Respiration. 2003;70:500–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Shim SS, Lee KS, Kim BT, Chung MJ, Lee EJ, Han J, et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology. 2005;236:1011–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Kim BT, Lee KS, Shim SS, Choi JY, Kwon OJ, Kim H, et al. Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with integrated FDG PET/CT--a prospective study. Radiology. 2006;241:501–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Chen S, Li X, Chen M, Yin Y, Li N, Li Y. Limited diagnostic value of dual-time-point 18F-FDG PET/CT imaging for classifying solitary pulmonary nodules in granuloma-endemic regions both at visual and quantitative analyses. Eur J Radiol. 85:1744–9.Google Scholar
  41. 41.
    Kim DW, Park SA, Kim CG. Dual-time-point positron emission tomography findings of benign mediastinal fluorine-18-fluorodeoxyglucose uptake in tuberculosis-endemic region. Indian J Nucl Med. 2011;26:3–6.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Yen RF, Chen KC, Lee JM, Chang YC, Wang J, Cheng MF, et al. 18F-FDG PET for the lymph node staging of non-small cell lung cancer in a tuberculosis-endemic country: is dual time point imaging worth the effort? Eur J Nucl Med Mol Imaging. 2008;35:1305–15.CrossRefPubMedGoogle Scholar
  43. 43.
    Park YS, Hong SJ, Boo YK, Hwang ES, Kim HJ, Cho SH, et al. The national status of tuberculosis using nationwide medical records survey of patients with tuberculosis in Korea. Tuberc Respir Dis. 2012;73:48–55.CrossRefGoogle Scholar
  44. 44.
    Kang CH, Kim YT, Jeon S-H, Sung S-W, Kim JH. Lymphadenectomy extent is closely related to long-term survival in esophageal cancer. Eur J Cardiothorac Surg. 2007;31:154–60.CrossRefPubMedGoogle Scholar
  45. 45.
    Lagergren J, Mattsson F, Zylstra J, Chang F, Gossage J, Mason R, et al. Extent of lymphadenectomy and prognosis after esophageal cancer surgery. JAMA Surg. 2016;151:32–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Nuclear MedicineNational Cancer CenterSeoulSouth Korea
  2. 2.Department of Nuclear MedicineSeoul National University Hospital, College of MedicineSeoulSouth Korea
  3. 3.Radiation Medicine Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  4. 4.Department of Thoracic and Cardiovascular SurgerySeoul National University Hospital, College of MedicineSeoulSouth Korea
  5. 5.Cancer Research InstituteSeoul National UniversitySeoulSouth Korea
  6. 6.Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulSouth Korea

Personalised recommendations