Advertisement

Comparison of prognostic values of primary tumor and nodal 18F-fluorodeoxyglucose uptake in non-small cell lung cancer with N1 disease

  • Chae Hong Lim
  • Seung Hyup Hyun
  • Seung Hwan Moon
  • Young Seok Cho
  • Joon Young Choi
  • Kyung-Han LeeEmail author
Nuclear Medicine
  • 34 Downloads

Abstract

Introduction

We hypothesized that, in non-small cell lung cancer (NSCLC) with N1 metastasis, N1 nodal 18F-fluorodeoxyglucose (FDG) status offers independent and incremental prognostic value.

Methods

We enrolled 106 NSCLC patients with pathology-confirmed N1 metastasis. N1 node FDG positivity, primary tumor maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Kaplan-Meier method and Cox regression analyses were performed for cancer-specific survival (CSS) and disease-free survival (DFS).

Results

Subjects were 67 males and 39 females (61.9 ± 9.4 years). Eighty-one (76.4%) and 25 (23.6%) had pathologic stage IIB and IIIA NSCLC, respectively. All underwent complete tumor resection. FDG-positive N1 nodes were larger and had higher primary tumor SUVmax. During a follow-up of 42 months, there were 56 recurrences and 31 cancer deaths. Significant univariate predictors were stage, no adjuvant therapy, and FDG-positive nodes for DFS, and stage, no adjuvant therapy, node size, tumor MTV, TLG, and SUVmax, and FDG-positive nodes for CSS. Independent predictors on multivariate analyses were FDG-positive nodes (HR = 3.071, p = 0.003), greater tumor TLG (HR = 3.224, p = 0.002), and no adjuvant therapy (HR = 3.631, p < 0.001) for poor CSS, and FDG-positive nodes (HR = 1.771, p = 0.040) and no adjuvant therapy (HR = 2.666, p = 0.002) for poor DFS. Harrell’s concordance and net reclassification improvement tests showed that CSS prediction was significantly improved by the addition of N1 FDG status to a model containing tumor TLG.

Conclusion

N1 node FDG status can be useful for predicting the outcome of NSCLC patients with N1 metastasis beyond that provided by other prognostic variables.

Key Points

• In NSCLC with N1 disease, N1 node FDG status is useful as a prognostic predictor.

• FDG-positive N1 nodes provide additional prognostic value beyond TLG of primary tumor.

• Combining TLG of primary tumor and N1 node uptake can stratify the survival of patients.

Keywords

Lung cancer Positron emission tomography Fluorodeoxyglucose F18 Lymph nodes 

Abbreviations

C-index

Concordance index

CSS

Cancer-specific survival

DFS

Disease-free survival

ECOG

Eastern Cooperative Group

FDG

18F-Fluorodeoxyglucose

LNs

Lymph nodes

MTV

Metabolic tumor volume

NRI

Net reclassification improvement

NSCLC

Non-small cell lung cancer

PET/CT

Positron emission tomography/computed tomography

ROC

Receiver operating characteristics

SUVmax

Maximum standard uptake value

TLG

Total lesion glycolysis

Notes

Funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (# 2016R1C1B2013411).

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Kyung-Han Lee.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

This work was supported by Kyunga Kim, Biostatics, Samsung Medical Center.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• Retrospective

• Diagnostic or prognostic study

• Performed at one institution

References

  1. 1.
    Deng XF, Jiang L, Liu QX et al (2016) Lymph node micrometastases are associated with disease recurrence and poor survival for early-stage non-small cell lung cancer patients: a meta-analysis. J Cardiothorac Surg 11:28CrossRefGoogle Scholar
  2. 2.
    Asamura H, Chansky K, Crowley J et al (2015) The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol 10:1675–1684CrossRefGoogle Scholar
  3. 3.
    Nakao M, Yoshida J, Ishii G et al (2010) Prognostic impact of node involvement pattern in pN1 non-small cell lung cancer patients. J Thorac Oncol 5:1576–1582CrossRefGoogle Scholar
  4. 4.
    Nakao M, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K (2010) Prognostic impact of node involvement pattern in pulmonary pN1 squamous cell carcinoma patients. J Thorac Oncol 5:504–509CrossRefGoogle Scholar
  5. 5.
    Yano T, Yokoyama H, Inoue T, Asoh H, Tayama K, Ichinose Y (1994) Surgical results and prognostic factors of pathologic N1 disease in non-small-cell carcinoma of the lung. Significance of N1 level: lobar or hilar nodes. J Thorac Cardiovasc Surg 107:1398–1402Google Scholar
  6. 6.
    van Velzen E, Snijder RJ, Brutel de la Riviere A, Elbers HJ, van den Bosch JM (1996) Type of lymph node involvement influences survival rates in T1N1M0 non-small cell lung carcinoma. Lymph node involvement by direct extension compared with lobar and hilar node metastases. Chest 110:1469–1473CrossRefGoogle Scholar
  7. 7.
    Sawyer TE, Bonner JA, Gould PM et al (1999) Factors predicting patterns of recurrence after resection of N1 non-small cell lung carcinoma. Ann Thorac Surg 68:1171–1176CrossRefGoogle Scholar
  8. 8.
    Riquet M, Manac’h D, Le Pimpec-Barthes F, Dujon A, Chehab A (1999) Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg 67:1572–1576CrossRefGoogle Scholar
  9. 9.
    Yoshino I, Nakanishi R, Osaki T et al (1999) Unfavorable prognosis of patients with stage II non-small cell lung cancer associated with macroscopic nodal metastases. Chest 116:144–149CrossRefGoogle Scholar
  10. 10.
    Tanaka F, Yanagihara K, Otake Y et al (2001) Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). Eur J Cardiothorac Surg 19:555–561CrossRefGoogle Scholar
  11. 11.
    Liu J, Dong M, Sun X, Li W, Xing L, Yu J (2016) Prognostic value of 18F-FDG PET/CT in surgical non-small cell lung cancer: a meta-analysis. PLoS One 11:e0146195CrossRefGoogle Scholar
  12. 12.
    Im HJ, Pak K, Cheon GJ et al (2015) Prognostic value of volumetric parameters of (18)F-FDG PET in non-small-cell lung cancer: a meta-analysis. Eur J Nucl Med Mol Imaging 42:241–251CrossRefGoogle Scholar
  13. 13.
    Yoo Ie R, Chung SK, Park HL et al (2014) Prognostic value of SUVmax and metabolic tumor volume on 18F-FDG PET/CT in early stage non-small cell lung cancer patients without LN metastasis. Biomed Mater Eng 24:3091–3103Google Scholar
  14. 14.
    Zhang H, Wroblewski K, Appelbaum D, Pu Y (2013) Independent prognostic value of whole-body metabolic tumor burden from FDG-PET in non-small cell lung cancer. Int J Comput Assist Radiol Surg 8:181–191CrossRefGoogle Scholar
  15. 15.
    Shin S, Kim HK, Choi YS, Kim K, Kim J, Shim YM (2013) Prognosis of unexpected and expected pathologic N1 non-small cell lung cancer. Ann Thorac Surg 96:969–975 discussion 975-966CrossRefGoogle Scholar
  16. 16.
    FE H (2001) Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. SpringerGoogle Scholar
  17. 17.
    Pencina MJ, D’Agostino RB Sr, D'Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172 discussion 207-112CrossRefGoogle Scholar
  18. 18.
    Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT (2017) The eighth edition lung cancer stage classification. Chest 151:193–203CrossRefGoogle Scholar
  19. 19.
    Higashi K, Ueda Y, Ayabe K et al (2000) FDG PET in the evaluation of the aggressiveness of pulmonary adenocarcinoma: correlation with histopathological features. Nucl Med Commun 21:707–714CrossRefGoogle Scholar
  20. 20.
    Dhital K, Saunders CA, Seed PT, O'Doherty MJ, Dussek J (2000) [(18)F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer. Eur J Cardiothorac Surg 18:425–428CrossRefGoogle Scholar
  21. 21.
    Ahuja V, Coleman RE, Herndon J, Patz EF Jr (1998) The prognostic significance of fluorodeoxyglucose positron emission tomography imaging for patients with nonsmall cell lung carcinoma. Cancer 83:918–924CrossRefGoogle Scholar
  22. 22.
    Vansteenkiste JF, Stroobants SG, Dupont PJ et al (1999) Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non-small-cell lung cancer: an analysis of 125 cases. Leuven Lung Cancer Group. J Clin Oncol 17:3201–3206CrossRefGoogle Scholar
  23. 23.
    Zhang C, Liao C, Penney BC, Appelbaum DE, Simon CA, Pu Y (2015) Relationship between overall survival of patients with non-small cell lung cancer and whole-body metabolic tumor burden seen on postsurgical fluorodeoxyglucose PET images. Radiology 275:862–869CrossRefGoogle Scholar
  24. 24.
    Hyun SH, Ahn HK, Kim H et al (2014) Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging 41:50–58CrossRefGoogle Scholar
  25. 25.
    Liao S, Penney BC, Wroblewski K et al (2012) 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 39:27–38CrossRefGoogle Scholar
  26. 26.
    Zhang S, Li S, Pei Y et al (2017) Impact of maximum standardized uptake value of non-small cell lung cancer on detecting lymph node involvement in potential stereotactic body radiotherapy candidates. J Thorac Dis 9:1023–1031CrossRefGoogle Scholar
  27. 27.
    Okereke IC, Gangadharan SP, Kent MS, Nicotera SP, Shen C, DeCamp MM (2009) Standard uptake value predicts survival in non-small cell lung cancer. Ann Thorac Surg 88:911–915 discussion 915-916CrossRefGoogle Scholar
  28. 28.
    Hellwig D, Graeter TP, Ukena D et al (2007) 18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense? J Nucl Med 48:1761–1766CrossRefGoogle Scholar
  29. 29.
    Kaseda K, Watanabe K, Asakura K, Kazama A, Ozawa Y (2016) Identification of false-negative and false-positive diagnoses of lymph node metastases in non-small cell lung cancer patients staged by integrated (18F-)fluorodeoxyglucose-positron emission tomography/computed tomography: a retrospective cohort study. Thorac Cancer 7:473–480CrossRefGoogle Scholar
  30. 30.
    Kim YK, Lee KS, Kim BT et al (2007) 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 109:1068–1077CrossRefGoogle Scholar
  31. 31.
    Kim BT, Lee KS, Shim SS et al (2006) Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with integrated FDG PET/CT--a prospective study. Radiology 241:501–509CrossRefGoogle Scholar
  32. 32.
    Higashi K, Ueda Y, Yagishita M et al (2000) FDG PET measurement of the proliferative potential of non-small cell lung cancer. J Nucl Med 41:85–92Google Scholar
  33. 33.
    Duhaylongsod FG, Lowe VJ, Patz EF Jr, Vaughn AL, Coleman RE, Wolfe WG (1995) Lung tumor growth correlates with glucose metabolism measured by fluoride-18 fluorodeoxyglucose positron emission tomography. Ann Thorac Surg 60:1348–1352CrossRefGoogle Scholar
  34. 34.
    Vesselle H, Schmidt RA, Pugsley JM et al (2000) Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 6:3837–3844Google Scholar
  35. 35.
    Pisters KM, Evans WK, Azzoli CG et al (2007) Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non small-cell lung cancer guideline. J Clin Oncol 25:5506–5518CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Chae Hong Lim
    • 1
  • Seung Hyup Hyun
    • 1
  • Seung Hwan Moon
    • 1
  • Young Seok Cho
    • 1
  • Joon Young Choi
    • 1
  • Kyung-Han Lee
    • 1
    Email author
  1. 1.Department of Nuclear Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea

Personalised recommendations