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Molecular Imaging of Proliferation and Glucose Utilization: Utility for Monitoring Response and Prognosis after Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Annals of Surgical Oncology volume 18, pages 3316–3323 (2011)Cite this article

Abstract

Background

Metabolic imaging of gastric cancer is limited due to the 30% of primary tumors that are not 18F-fluorodeoxyglucose (FDG) avid. In contrast, the proliferation marker 18F-fluorothymidine (FLT) has been shown to visualize also non-FDG-avid gastric tumors. In this study we tested whether FLT-positron emission tomography (PET) can improve the predictive potential of molecular imaging for assessing response to neoadjuvant therapy in gastric cancer compared with FDG-PET.

Methods

45 patients with gastric cancer underwent FDG- and FLT-PET before and 2 weeks after initiation of chemotherapy. FDG/FLT-PET findings and Ki67 immunohistochemistry were correlated with clinical and histopathological response and survival.

Results

14 patients had non-FDG-avid tumors, whereas all tumors could be visualized by FLT-PET. No significant association of clinical or histopathological response with any of the analyzed metabolic parameters [initial standardized uptake value (SUV), SUV after 2 weeks, change of SUV for FDG/FLT] was found. Univariate Cox regression analysis for Ki67 and metabolic parameters revealed significant prognostic impact for survival only for FLT SUVmean day 14 (p = 0.048) and Ki67 (p = 0.006). Multivariate Cox regression analysis (including clinical response, Lauren type, ypN category, and FLT SUVmean day 14) revealed Lauren type and FLT SUVmean day 14 as the only significant prognostic factors (p = 0.006, p = 0.002).

Conclusions

FLT uptake 2 weeks after initiation of therapy was shown to be the only imaging parameter with significant prognostic impact. Neither FLT-PET nor FDG-PET were correlated with histopathological or clinical response. However, these data must be interpreted with caution due to the single-center trial study design, relatively short follow-up, poor response rates, and unfavorable prognosis.

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References

  1. Boige V, Pignon J, Saint-Aubert B, et al. Final results of a randomized trial comparing preoperative 5-Fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial [Abstract]. J Clin Oncol (supplement). 2007;25(18 Suppl):15123.

    Google Scholar 

  2. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.

    PubMed  Article  CAS  Google Scholar 

  3. Lowy AM, Mansfield PF, Leach SD, et al. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999;229(3):303–8.

    PubMed  Article  CAS  Google Scholar 

  4. Lordick F, Ott K, Krause BJ, 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(9):797-805.

    PubMed  Article  Google Scholar 

  5. Siewert JR, Lordick F, Ott K, et al. Induction chemotherapy in Barrett cancer: influence on surgical risk and outcome. Ann Surg. 2007;246(4):624–8 (discussion 628–31).

    PubMed  Article  Google Scholar 

  6. Chen J, Cheong JH, Yun MJ, et al. Improvement in preoperative staging of gastric adenocarcinoma with positron emission tomography. Cancer. 2005;103(11):2383–90.

    PubMed  Article  Google Scholar 

  7. Kim SK, Kang KW, Lee JS, 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(2):148–55.

    PubMed  Article  Google Scholar 

  8. Mochiki E, Kuwano H, Katoh H, et al. Evaluation of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography for gastric cancer. World J Surg. 2004;28(3):247–53.

    PubMed  Article  Google Scholar 

  9. Yoshioka T, Yamaguchi K, Kubota K, et al. Evaluation of 18F-FDG PET in patients with advanced, metastatic, or recurrent gastric cancer. J Nucl Med. 2003;44(5):690–9.

    PubMed  CAS  Google Scholar 

  10. Yun M, Lim JS, Noh SH, et al. Lymph node staging of gastric cancer using (18)F-FDG PET: a comparison study with CT. J Nucl Med. 2005;46(10):1582–8.

    PubMed  Google Scholar 

  11. Ott K, Fink U, Becker K, et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol. 2003;21(24):4604–10.

    PubMed  Article  CAS  Google Scholar 

  12. Ott K, Herrmann K, Lordick F, et al. Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res. 2008;14(7):2012–8.

    PubMed  Article  CAS  Google Scholar 

  13. Herrmann K, Ott K, Buck AK, et al. Imaging gastric cancer with PET and the radiotracers 18F-FLT and 18F-FDG: a comparative analysis. J Nucl Med. 2007;48(12):1945–50.

    PubMed  Article  CAS  Google Scholar 

  14. Kameyama R, Yamamoto Y, Izuishi K, et al. Detection of gastric cancer using 18F-FLT PET: comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2009;36(3):382–8.

    PubMed  Article  Google Scholar 

  15. Weber G, Nagai M, Natsumeda Y, et al. Regulation of de novo and salvage pathways in chemotherapy. Adv Enzyme Regul. 1991;31:45–67.

    PubMed  Article  CAS  Google Scholar 

  16. Wells P, Aboagye E, Gunn RN, et al. 2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337. J Natl Cancer Inst. 2003;95(9):675–82.

    PubMed  Article  CAS  Google Scholar 

  17. Wittekind C, Compton CC, Greene FL, Sobin LH. TNM residual tumor classification revisited. Cancer. 2002;94(9):2511–6.

    PubMed  Article  Google Scholar 

  18. Ott K, Sendler A, Becker K, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6(3):159–67.

    PubMed  Article  CAS  Google Scholar 

  19. Ott K, Weber WA, Lordick F, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006;24(29):4692–8.

    PubMed  Article  Google Scholar 

  20. Machulla HJ, Blocher A, Kuntzsch M, et al. simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]Fluorothymidine ([18F]FLT). J Radioanal Nucl Chem. 2000;243(3):843–846.

    Article  CAS  Google Scholar 

  21. Herrmann K, Wieder HA, Buck AK, et al. Early response assessment using 3′-deoxy-3′-[18F]fluorothymidine-positron emission tomography in high-grade non-Hodgkin’s lymphoma. Clin Cancer Res. 2007;13(12):3552–8.

    PubMed  Article  CAS  Google Scholar 

  22. Weber WA, Ziegler SI, Thodtmann R, et al. Reproducibility of metabolic measurements in malignant tumors using FDG PET. J Nucl Med. 1999;40(11):1771–7.

    PubMed  CAS  Google Scholar 

  23. Weber WA, Ott K, Becker K, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001;19(12):3058–65.

    PubMed  CAS  Google Scholar 

  24. Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98(7):1521–30.

    PubMed  Article  Google Scholar 

  25. Roder JD, Bottcher K, Siewert JR, et al. Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992. Cancer. 1993;72(7):2089–97.

    PubMed  Article  CAS  Google Scholar 

  26. Siewert JR, Stein HJ, Sendler A, Fink U. Surgical resection for cancer of the cardia. Semin Surg Oncol. 1999;17(2):125–31.

    PubMed  Article  CAS  Google Scholar 

  27. Therneau TM, Grambsch PM, Fleming TR. Martingale-based residuals for survival models. Biometrika. 1990;1(77):147–160.

    Article  Google Scholar 

  28. Shah MA, Yeung H, Coit D, et al. A phase II study of preoperative chemotherapy with irinotecan(CPT) and cisplatin(CIS) for gastric cancer(NCI 5917): FDG-PET/CT predicts patient outcome. J Clin Oncol. 2007;25:4502

    Article  Google Scholar 

  29. Vallbohmer D, Holscher AH, Schneider PM, et al. [18F]-fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemotherapy in gastric cancer. J Surg Oncol. 2010;102(2):135–40.

    Google Scholar 

  30. Stahl A, Ott K, Weber WA, et al. FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings. Eur J Nucl Med Mol Imaging. 2003;30(2):288–95.

    PubMed  Article  CAS  Google Scholar 

  31. Mukai K, Ishida Y, Okajima K, et al. Usefulness of preoperative FDG-PET for detection of gastric cancer. Gastric Cancer. 2006;9(3):192–6.

    PubMed  Article  Google Scholar 

  32. Kenny L, Coombes RC, Vigushin DM, et al. Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging. 2007;34(9):1339–47.

    PubMed  Article  Google Scholar 

  33. Chen W, Delaloye S, Silverman DH, et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol. 2007;25(30):4714–21.

    PubMed  Article  CAS  Google Scholar 

  34. Wieder HA, Geinitz H, Rosenberg R, et al. PET imaging with [18F]3’-deoxy-3’-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer. Eur J Nucl Med Mol Imaging. 2007;34(6):878–83.

    PubMed  Article  CAS  Google Scholar 

  35. Linecker A, Kermer C, Sulzbacher I, et al. Uptake of (18)F-FLT and (18)F-FDG in primary head and neck cancer correlates with survival. Nuklearmedizin. 2008;47(2):80–5 (quiz N12).

    PubMed  CAS  Google Scholar 

  36. van Westreenen HL, Cobben DC, Jager PL, et al. Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer. J Nucl Med. 2005;46(3):400–4.

    PubMed  Google Scholar 

Download references

Acknowledgment

K.H. and M.P.A.E. were supported by the collaborative research center SFB 824, TP B1, German Research Foundation (DFG) “Imaging for Selection, Monitoring and Individualization of Cancer Therapies”.

Author information

Affiliations

  1. Department of Surgery, University of Heidelberg, Heidelberg, Germany

    Katja Ott MD

  2. Department of Nuclear Medicine, Technische Universitaet Muenchen, Munich, Germany

    Ken Herrmann MD, Hans-Jürgen Wester PhD, Andreas K. Buck MD, Markus Schwaiger MD & Bernd Joachim Krause MD

  3. Institute of Medical Statistics and Epidemiology, Technische Universitaet Muenchen, Munich, Germany

    Tibor Schuster PhD

  4. Institute of Pathology, Technische Universitaet Muenchen, Munich, Germany

    Rupert Langer MD & Karen Becker MD

  5. Institute of Radiology, Technische Universitaet Muenchen, Munich, Germany

    Hinrich A. Wieder MD

  6. Directorate, University of Heidelberg, Heidelberg, Germany

    Jörg-Rüdiger Siewert MD

  7. Department of Internal Medicine III (Hematology/Oncology), Technische Universitaet Muenchen, Munich, Germany

    Christian Meyer zum Büschenfelde MD & Christian Peschel MD

  8. Department of Surgery, Technische Universitaet Muenchen, Munich, Germany

    Dirk Wilhelm MD

  9. Department of Internal Medicine II (Gastroenterology), Technische Universitaet Muenchen, Munich, Germany

    Matthias P. A. Ebert MD

  10. Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Heidelberg, Germany

    Matthias P. A. Ebert MD

  11. Medizinische Klinik III, Klinikum Braunschweig, Brunswick, Germany

    Florian Lordick MD

Authors
  1. Katja Ott MD
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  2. Ken Herrmann MD
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  3. Tibor Schuster PhD
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  4. Rupert Langer MD
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  5. Karen Becker MD
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  6. Hinrich A. Wieder MD
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  7. Hans-Jürgen Wester PhD
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  8. Jörg-Rüdiger Siewert MD
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  9. Christian Meyer zum Büschenfelde MD
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  10. Andreas K. Buck MD
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  11. Dirk Wilhelm MD
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  12. Matthias P. A. Ebert MD
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  13. Christian Peschel MD
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  14. Markus Schwaiger MD
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  15. Florian Lordick MD
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  16. Bernd Joachim Krause MD
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Corresponding author

Correspondence to Ken Herrmann MD.

Additional information

Katja Ott and Ken Herrmann contributed equally to this article.

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Ott, K., Herrmann, K., Schuster, T. et al. Molecular Imaging of Proliferation and Glucose Utilization: Utility for Monitoring Response and Prognosis after Neoadjuvant Therapy in Locally Advanced Gastric Cancer. Ann Surg Oncol 18, 3316–3323 (2011). https://doi.org/10.1245/s10434-011-1743-y

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  • DOI: https://doi.org/10.1245/s10434-011-1743-y

Keywords

  • Gastric Cancer
  • Standardize Uptake Value
  • Advanced Gastric Cancer
  • Histopathological Response
  • Significant Prognostic Impact