Skip to main content
Log in

Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell Lung Cancer

  • Original Article
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

We evaluated the value of variable 18F-FDG PET/CT parameters for the prediction of disease progression after concurrent chemoradiotherapy (CCRT) in patients with inoperable stage III non-small-cell lung cancer (NSCLC).

Methods

One hundred sixteen pretreatment FDG PET/CT scans of inoperable stage III NSCLC were retrospectively reviewed (stage IIIA: 51; stage IIIB: 65). The volume of interest was automatically drawn for each primary lung tumor, and PET parameters were assessed as follows: maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) using the boundaries presenting SUV intensity exceeding 3.0, and the area under the curve of the cumulative SUV-volume histograms (AUC-CSH), which is known to reflect the tumor heterogeneity. Progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared with each PET and clinical parameters by univariate and multivariate survival analysis.

Results

In the ROC analysis, the optimal cutoff values of SUVmax, MTV (cm3), and AUC-CSH for prediction of PFS were determined as 21.5, 27.7, and 4,800, respectively. In univariate analysis, PFS was statistically significantly reduced in those with AUC-CSH < 4,800 (p = 0.004). In multivariate analysis, AUC-CSH and SUVmax were statistically significant independent prognostic factors (HR 3.35, 95 % CI 1.79–6.28, p < 0.001; HR 0.25, 95 % CI 0.09–0.70, p = 0.008, respectively). Multivariate analysis showed that AUC-CSH was the most significant independent prognostic factor for LRFS and DMFS (HR 3.27, 95 % CI 1.54–6.94, p = 0.002; HR 2.79, 95 % CI 1.42–5.50, p = 0.003).

Conclusions

Intratumoral metabolic heterogeneity of primary lung tumor in 18F-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. World Health Organization. The global burden of disease: 2004 update (2008); Available at http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_part2.pdf. Accessed 7 Feb 2011.

  2. American Cancer Society (2010) Cancer Facts and Figures 2010. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf. Accessed 7 Feb 2011.

  3. Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.

    Article  PubMed  Google Scholar 

  4. O’Rourke N, Roqué I, Figuls M, Farré Bernadó N, Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. 2010;16:CD002140.

    Google Scholar 

  5. Berghmans T, Paesmans M, Sculier JP. Prognostic factors in stage III non-small cell lung cancer: a review of conventional, metabolic and new biological variables. Ther Adv Med Oncol. 2011;3:127–38.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Berghmans T, Dusart M, Paesmans M, Hossein-Foucher C, Buvat I, Castaigne C, et al. Primary tumor standardized uptake value (SUVmax) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) is of prognostic value for survival in non-small cell lung cancer (NSCLC). A systematic review and meta-analysis (MA) by the European Lung Cancer Working Party for the IASLC lung cancer staging project. J Thorac Oncol. 2008;3:6–12.

    Article  PubMed  Google Scholar 

  7. Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2012;39:27–38.

    Article  CAS  PubMed  Google Scholar 

  8. Yoo SW, Kim J, Chong A, Kwon SY, Min JJ, Song HC, et al. Metabolic tumor volume measured by F-18 FDG PET/CT can further stratify the prognosis of patients with stage IV non-small cell lung cancer. Nucl Med Mol Imaging. 2012;46:286–93.

    Article  CAS  Google Scholar 

  9. Huang W, Zhou T, Ma L, Sun H, Gong H, Wang J, et al. Standard uptake value and metabolic tumor volume of 18F-FDG PET/CT predict short-term outcome early in the course of chemoradiotherapy in advanced non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2011;38:1628–35.

    Article  CAS  PubMed  Google Scholar 

  10. Lopez Guerra JL, Gladish G, Komaki R, Gomez D, Zhuang Y, Liao Z. Large decreases in standardized uptake values after definitive radiation are associated with better survival of patients with locally advanced non-small cell lung cancer. J Nucl Med. 2012;53:225–33.

    Article  PubMed  Google Scholar 

  11. Hoang JK, Hoagland LF, Coleman RE, Coan AD, Herndon 2nd JE, Patz Jr EF. Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography imaging in patients with advanced-stage non–small-cell lung carcinoma. J Clin Oncol. 2008;26:1459–64.

    Article  PubMed  Google Scholar 

  12. Tixier F, Le Rest CC, Albarghach N, Pradier O, Metges JP, Corcos L, et al. Intratumor heterogeneity characterized by textural features on baseline 18F-FDG PET images predicts response to concomitant radiochemotherapy in esophageal cancer. J Nucl Med. 2011;52:369–78.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Velden FH, Cheebsumon P, Yaqub M, Smit EF, Hoekstra OS, Lammertsma AA, et al. Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies. Eur J Nucl Med Mol Imaging. 2011;38:1636–47.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Lee HY, Lee KS, Park J, Han J, Kim BT, Kwon OJ, et al. Baseline SUVmax at PET-CT in stage IIIA non-small-cell lung cancer patients undergoing surgery after neoadjuvant therapy: prognostic implication focused on histopathologic subtypes. Acad Radiol. 2012;19:440–5.

    Article  PubMed  Google Scholar 

  15. Ohno Y, Koyama H, Yoshikawa T, Matsumoto K, Aoyama N, Onishi Y, et al. Diffusion-weighted MRI versus 18F-FDG PET/CT: performance as predictors of tumor treatment response and patient survival in patients with non–small cell lung cancer receiving chemoradiotherapy. Am J Roentgenol. 2012;198:75–82.

    Article  Google Scholar 

  16. Ganeshan B, Panayiotou E, Burnand K, Dizdarevic S, Miles K. Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival. Eur Radiol. 2012;22:796–802.

    Article  PubMed  Google Scholar 

  17. Wouters A, Pauwels B, Lardon F, Vermorken JB. Review: implications of in vitro research on the effect of radiotherapy and chemotherapy under hypoxic conditions. Oncologist. 2007;12:690–712.

    Article  CAS  PubMed  Google Scholar 

  18. O’Flaherty JD, Barr M, Fennell D, Richard D, Reynolds J, O’Leary J, et al. The cancer stem-cell hypothesis: its emerging role in lung cancer biology and its relevance for future therapy. J Thorac Oncol. 2012;7:1880–90.

    Article  PubMed  Google Scholar 

  19. Kubota R, Kubota K, Yamada S, Tada M, Ido T, Tamahashi N, et al. Microautoradiographic study for the differentiation of intratumoral macrophages, granulation tissues and cancer cells by the dynamics of fluorine-18-fluorodeoxyglucose uptake. J Nucl Med. 1994;35:104–12.

    CAS  PubMed  Google Scholar 

  20. Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL, et al. Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma. I. Are inflammatory cells important? J Nucl Med. 1995;36:1854–61.

    CAS  PubMed  Google Scholar 

  21. Vlashi E, Lagadec C, Vergnes L, Matsutani T, Masui K, Poulou M, et al. Metabolic state of glioma stem cells and nontumorigenic cells. Proc Natl Acad Sci USA. 2011;108:3983–8.

    Article  Google Scholar 

  22. Rajendran JG, Schwartz DL, O’Sullivan J, Peterson LM, Ng P, Scharnhorst J, et al. Tumour hypoxia imaging with 18F fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res. 2006;12:5435–41.

    Article  CAS  PubMed  Google Scholar 

  23. Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, et al. Over expression of Glut-1 and increased glucose metabolism in tumours are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer. 2003;97:1015–24.

    Article  CAS  PubMed  Google Scholar 

  24. Swinson DE, Jones JL, Richardson D, Cox G, Edwards JG, O’Byrne KJ. Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables. Lung Cancer. 2002;37:235–40.

    Article  PubMed  Google Scholar 

  25. Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol. 1991;9:1618–26.

    CAS  PubMed  Google Scholar 

  26. O’Connell JP, Kris MG, Gralla RJ, Groshen S, Trust A, Fiore JJ, et al. Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy. J Clin Oncol. 1986;4:1604–14.

    PubMed  Google Scholar 

  27. Firth JD, Ebert BL, Ratcliffe PJ. Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem. 1995;270:21021–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ho-Chun Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kang, SR., Song, HC., Byun, B.H. et al. Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell Lung Cancer. Nucl Med Mol Imaging 48, 16–25 (2014). https://doi.org/10.1007/s13139-013-0231-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-013-0231-7

Keywords

Navigation