Confirmation of the prognostic value of pretherapeutic tumor SUR and MTV in patients with esophageal squamous cell carcinoma

  • Frank HofheinzEmail author
  • Yimin Li
  • Ingo G. Steffen
  • Qin Lin
  • Chen Lili
  • Wu Hua
  • Jörg van den Hoff
  • Sebastian Zschaeck
Original Article



The prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. In a recent publication, we were able to show that PET can provide independent prognostic information in such a patient group and that the tumor-to-blood standard uptake ratio (SUR) can improve the prognostic value of tracer uptake values. The present investigation addresses the question of whether the distinctly improved prognostic value of SUR can be confirmed in a similar patient group that was examined and treated at a different site.


18F-FDG PET/CT was performed in 147 consecutive patients (115 male, 32 female, mean age: 62 years) with newly diagnosed esophageal squamous cell carcinoma prior to definitive radiochemotherapy. In the PET images, the metabolic active volume (MTV) of the primary tumor was delineated with an adaptive threshold method. For the resulting ROIs, SUVmax and total lesion glycolysis (TLG = MTV × SUVmean) were computed. The blood SUV was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as ratio of tumor SUV and blood SUV. Univariate Cox regression and Kaplan–Meier analysis with respect to overall survival (OS), distant-metastases-free survival (DM), and locoregional control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed.


Univariate Cox regression revealed MTV, TLG, and SURmax as significant prognostic factors for OS. MTV as well as TLG were significant prognostic factors for LRC while SURmax showed only a trend for significance. None of the PET parameters was prognostic for DM. In univariate analysis, SUVmax was not prognostic for any of the investigated clinical endpoints. In multivariate analysis (T-stage, N-stage, MTV, and SURmax), MTV was an independent prognostic factor for OS and showed a trend for significance for LRC. SURmax was not an independent predictor for OS or LRC. When including the PET parameters separately in multivariate analysis, MTV as well as SURmax were prognostic factors for OS indicating that SURmax is independent from the clinical parameters but not from MTV. In addition, MTV was an independent prognostic factor for LRC in this separate analysis.


Our study revealed a clearly improved prognostic value of tumor SUR compared to tumor SUV and confirms our previously published findings regarding OS. Furthermore, SUR delivers prognostic information beyond that provided by the clinical parameters alone, but does not add prognostic information beyond that provided by MTV in this patient group. Therefore, our results suggest that pretherapeutic MTV is the parameter of choice for PET-based risk stratification in the considered setting but further investigations are necessary to demonstrate that this suggestion is correct.


PET Esophageal cancer Definitive radiochemotherapy SUV SUR 


Author Contributions

FH and SZ provided ideas for the study. FH, YL, JVDH and SZ performed the analysis and drafted the manuscript. FH and IS designed the figures and calculated the underlying statistics. YL, QL, CL, and WH were responsible for treatment, imaging, collection of patient data, and follow-up. All authors read and approved the final manuscript.


This work was partly supported by the Major Projects of Fujian Natural Science Foundation (NO. 2008-59-11), the Nature Science Foundation of China (No. 81471684), the Xiamen city science and technology project guidance (3502Z20164009) and the Berliner Krebsgesellschaft (ZSF201720).

Compliance with Ethical Standards

Conflict of interests


Ethical approval

The study was approved by the Institutional Ethics Committees.

Informed Consent

All patients provided signed written informed consent.


  1. 1.
    Herskovic A, Martz K, Al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–98.CrossRefGoogle Scholar
  2. 2.
    Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999;281(17):1623–27.CrossRefGoogle Scholar
  3. 3.
    Sudo K, Xiao L, Wadhwa R, Shiozaki H, Elimova E, Taketa T, et al. Importance of surveillance and success of salvage strategies after definitive chemoradiation in patients with esophageal cancer. J Clin Oncol 2014;32(30):3400.CrossRefGoogle Scholar
  4. 4.
    Kranzfelder M, Schuster T, Geinitz H, Friess H, Büchler P. Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. Br J Surg 2011;98(6): 768–83.CrossRefGoogle Scholar
  5. 5.
    Naik KB, Liu Y, Goodman M, Gillespie TW, Pickens A, Force SD, et al. Concurrent chemoradiotherapy with or without surgery for patients with resectable esophageal cancer: an analysis of the National Cancer Data Base. Cancer 2017;123(18):3476–85.CrossRefGoogle Scholar
  6. 6.
    Talsma AK, Lingsma HF, Steyerberg EW, Wijnhoven BP, Van Lanschot JJB. The 30-day versus in-hospital and 90-day mortality after esophagectomy as indicators for quality of care. Ann Surg 2014;260(2):267–73.CrossRefGoogle Scholar
  7. 7.
    Zhou C, Zhang L, Wang H, Ma X, Shi B, Chen W, et al. Superiority of minimally invasive oesophagectomy in reducing in-hospital mortality of patients with resectable oesophageal cancer: a meta-analysis. PLoS One 2015;10(7):e0132889.CrossRefGoogle Scholar
  8. 8.
    Yibulayin W, Abulizi S, Lv H, Sun W. Minimally invasive oesophagectomy versus open esophagectomy for resectable esophageal cancer: a meta-analysis. World J Surg Oncol 2016;14(1):304.CrossRefGoogle Scholar
  9. 9.
    van Hagen P, Hulshof M, Van Lanschot J, Steyerberg E, Henegouwen MvB, Wijnhoven B, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366(22):2074–84.CrossRefGoogle Scholar
  10. 10.
    Kroese T, Goense L, van Hillegersberg R, de Keizer B, Mook S, Ruurda J, et al. Detection of distant interval metastases after neoadjuvant therapy for esophageal cancer with 18F-FDG PET (/CT): a systematic review and meta-analysis. Dis Esophagus 2018;31(12):doy055.CrossRefGoogle Scholar
  11. 11.
    Venkat P, Shridhar R, Naghavi A, Hoffe S, Almhanna K, Pimiento J, et al. Dose escalated neoadjuvant chemoradiotherapy with dose-painting intensity-modulated radiation therapy and improved pathologic complete response in locally advanced esophageal cancer. Dis of the Esophagus 2017;30(7):1–9.CrossRefGoogle Scholar
  12. 12.
    Elimova E, Wang X, Etchebehere E, Shiozaki H, Shimodaira Y, Wadhwa R, et al. 18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients. Eur J Cancer 2015;51(17):2545–52.CrossRefGoogle Scholar
  13. 13.
    Malik V, Lucey JA, Duffy GJ, Wilson L, McNamara L, Keogan M, et al. Early repeated 18f-FDG PET scans during neoadjuvant chemoradiation fail to predict histopathologic response or survival benefit in adenocarcinoma of the esophagus. J Nucl Med 2010;51(12):1863–69.CrossRefGoogle Scholar
  14. 14.
    Palie O, Michel P, Ménard JF, Rousseau C, Rio E, Bridji B, et al. The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3). Eur J Nucl Med Mol Imaging 2013;40(9):1345–55.CrossRefGoogle Scholar
  15. 15.
    Lemarignier C, Di Fiore F, Marre C, Hapdey S, Modzelewski R, Gouel P, et al. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma. Eur J Nucl Med Mol Imaging 2014;41(11):2008–16.CrossRefGoogle Scholar
  16. 16.
    Suzuki A, Xiao L, Hayashi Y, Macapinlac HA, Welsh J, Lin SH, et al. Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy. Cancer 2011;117(21):4823–33.CrossRefGoogle Scholar
  17. 17.
    Hamberg L, Hunter G, Alpert N, Choi N, Babich J, Fischman A. The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification? J Nucl Med 1994;35(8):1308–12.Google Scholar
  18. 18.
    Keyes J Jr. Standard uptake or silly useless value? J Nucl Med 1995;36(10):1836–39.Google Scholar
  19. 19.
    Huang S. Anatomy of SUV. Nucl Med Biol 2000;27(7):643–6.CrossRefGoogle Scholar
  20. 20.
    van den Hoff J, Oehme L, Schramm G, Maus J, Lougovski A, Petr J, et al. The PET-derived tumor-to-blood standard uptake ratio (SUR) is superior to tumor SUV as a surrogate parameter of the metabolic rate of FDG. EJNMMI Res 2013;3(1):77.CrossRefGoogle Scholar
  21. 21.
    van den Hoff J, Lougovski A, Schramm G, Maus J, Oehme L, Petr J, et al. Correction of scan time dependence of standard uptake values in oncological PET. EJNMMI Res 2014;4(1):18.CrossRefGoogle Scholar
  22. 22.
    Hofheinz F, van den Hoff J, Steffen IG, Lougovski A, Ego K, Amthauer H, et al. Comparative evaluation of SUV, tumor-to-blood standard uptake ratio (SUR), and dual time point measurements for assessment of the metabolic uptake rate in FDG PET. EJNMMI Res 2016;6(1):1–9.CrossRefGoogle Scholar
  23. 23.
    Hofheinz F, Apostolova I, Oehme L, Kotzerke J, Van den Hoff J. Test–retest variability in lesion SUV and lesion SUR in 18F-FDG PET: an analysis of data from two prospective multicenter trials. J Nucl Med 2017; 58(11):1770–5.CrossRefGoogle Scholar
  24. 24.
    Bütof R, Hofheinz F, Zöphel K, Stadelmann T, Schmollack J, Jentsch C, et al. Prognostic value of pretherapeutic tumor-to-blood standardized uptake ratio in patients with esophageal carcinoma. J Nucl Med 2015;56(8):1150–6.CrossRefGoogle Scholar
  25. 25.
    Hofheinz F, Bütof R, Apostolova I, Zöphel K, Steffen IG, Amthauer H, et al. An investigation of the relation between tumor-to-liver ratio (TLR) and tumor-to-blood standard uptake ratio (SUR) in oncological FDG PET. EJNMMI Res 2016;6(1):1.CrossRefGoogle Scholar
  26. 26.
    Bütof R, Hofheinz F, Zöphel K, Schmollack J, Jentsch C, Zschaeck S, et al. Prognostic value of SUR in patients with trimodality treatment of locally advanced esophageal carcinoma. J Nucl Med. 2018:jnumed–117.Google Scholar
  27. 27.
    Li Y, Lin Q, Luo Z, Zhao L, Zhu L, Sun L, et al. Value of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in prediction of the overall survival of esophageal cancer patients treated with chemoradiotherapy. Int J Clin Exp Med 2015;8(7):10947.Google Scholar
  28. 28.
    Li Y, Hofheinz F, Furth C, Lili C, Hua W, Ghadjar P, et al. Increased evidence for the prognostic value of FDG uptake on late-treatment PET in non-tumour-affected oesophagus in irradiated patients with oesophageal carcinoma Eur J Nucl Med Mol Imaging. 2018:1–10.Google Scholar
  29. 29.
    Hofheinz F, Pötzsch C, Oehme L, Beuthien-Baumann B, Steinbach J, Kotzerke J, et al. Automatic volume delineation in oncological PET. Evaluation of a dedicated software tool and comparison with manual delineation in clinical data sets. Nuklearmedizin 2012;51:9–16.CrossRefGoogle Scholar
  30. 30.
    Hofheinz F, Langner J, Petr J, Beuthien-Baumann B, Steinbach J, Kotzerke J, et al. An automatic method for accurate volume delineation of heterogeneous tumors in PET. Med Phys 2013;40(8):082503.CrossRefGoogle Scholar
  31. 31.
    R Core Team. 2018. R: a language and environment for statistical computing. R foundation for statistical computing. Vienna, Austria.Google Scholar
  32. 32.
    Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (radiation therapy oncology group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 2002;20(5):1167–74.CrossRefGoogle Scholar
  33. 33.
    Herrmann E, Mertineit N, De Bari B, Hoeng L, Caparotti F, Leiser D, et al. Outcome of proximal esophageal cancer after definitive combined chemo-radiation: a Swiss multicenter retrospective study. Radiation oncology 2017;12(1):97.CrossRefGoogle Scholar
  34. 34.
    Suh YG, Lee IJ, Koom WS, Cha J, Lee JY, Kim SK, et al. High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II–III esophageal cancer. Jpn J Clin Oncol 2014;44(6):534–40.CrossRefGoogle Scholar
  35. 35.
    Chen Y, Zhu HP, Wang T, Sun CJ, Ge XL, Min LF, et al. What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis. Oncotarget 2017;8(51):89095.Google Scholar
  36. 36.
    He L, Allen PK, Potter A, Wang J, Chang JY, Gomez DR, et al. Re-evaluating the optimal radiation dose for definitive chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Oncol 2014;9(9): 1398–405.CrossRefGoogle Scholar
  37. 37.
    Ma J, Wang Z, Wang C, Chen E, Dong Y, Song Y, et al. Individualized radiation dose escalation based on the decrease in tumor FDG uptake and normal tissue constraints improve survival in patients with esophageal carcinoma. Technol Cancer Res Treat 2017;16(1):75–80.CrossRefGoogle Scholar
  38. 38.
    Ku GY, Kriplani A, Janjigian YY, Kelsen DP, Rusch VW, Bains M, et al. Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma. Cancer 2016;122(13):2083–90.CrossRefGoogle Scholar
  39. 39.
    expert group of nonoperative esophageal cancer staging C. Standard clinical staging of nonoperative therapy of esophageal cancer (Draft). Chin J Radiat Oncol 2010;19(3):179–80.Google Scholar
  40. 40.
    Berry MF. Esophageal cancer: staging system and guidelines for staging and treatment. Journal of Thoracic Disease 2014;6(Suppl 3):S289.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Helmholtz-Zentrum Dresden-Rossendorf, PET CenterInstitute of Radiopharmaceutical Cancer ResearchDresdenGermany
  2. 2.Department of Radiation OncologyXiamen Cancer Hospital, The First Affiliated Hospital of Xiamen UniversityXiamenChina
  3. 3.Charite – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nuclear MedicineBerlinGermany
  4. 4.Department of Nuclear MedicineXiamen Cancer Hospital, The First Affiliated Hospital of Xiamen UniversityXiamenChina
  5. 5.Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin, Institute of Health, Department of Radiation OncologyBerlinGermany
  6. 6.Berlin Institute of Health (BIH)BerlinGermany

Personalised recommendations