Prediction of lymph node metastase in NSCLC

Summary

Purpose: To distinguish between benign and malignant mediastinal lymph nodes in patients with NSCLC by comparing 2D and semiautomated 3D measurements in FDG-PET-CT.

Patients, material, methods: FDG-PET-CT was performed in 46 patients prior to therapy. 299 mediastinal lymph-nodes were evaluated independently by two radiologists, both manually and by semi-automatic segmentation software. Longest-axial-diameter (LAD), shortest-axial-diameter (SAD), maximal-3D-diameter, elongation and volume were obtained. FDG-PET-CT and clinical/FDG-PET-CT follow up examinations and/or histology served as the reference standard. Statistical analysis encompassed intra-class-correlation-coefficients and receiver-operator-characteristics-curves (ROC). Results: The standard of reference revealed involvement in 87 (29%) of 299 lymph nodes. Manually and semi-automatically measured 2D parameters (LAD and SAD) showed a good correlation with mean

Zusammenfassung

Ziel: Vergleich von 2D und semi-automatischen 3D-Messungen in der FDG-PET/CT zur Unterscheidung von benignen und malignen media-stinalen Lymphknoten bei Patienten mit NSCLC. Patienten, Methoden: Bei 46 Patienten wurde vor Therapieaufnahme eine FDG-PET/CT angefertigt. 299 mediastinale Lymphknoten wurden von zwei Radiologen unabhängig voneinander sowohl manuell als auch unter Verwendung einer semi-automatischen Software ausgewertet. Langachsen-Durchmesser (LAD), Kurzachsen-Durchmesser (SAD), maximaler 3D-Durchmesser, Elongation (Längs-zu-Quer-Verhältnis) und Volumen der Lymphknoten wurden bestimmt. PET-CT, PET-CT-Verlaufskontrollen und klinische Verlaufsuntersuchungen und/oder Histologie dienten als Referenz. Die statistische Auswertung erfolgte mittels Intra-Class-Korrelationskoeffizienten und ROC (receiver operator characteristics curves). Ergebnisse: 87 (29%) von 299 Lymphknoten wurden anhand der Referenz als maligne eingestuft. Manuell und semi-automatisch bestimmte 2D-Parameter (LAD und SAD) zeigten eine gute Korrelation mit mittleren Intraclass-Koeffizienten von 0,8 und 0,72. Die Lymphknotenanalyse basie-rend auf der semi-automatischen Auswertung wies die größte Area-under-the-ROC-curve (AUC) für das Volumen (0,75, 95%CI: 0,69–0,81) und den SAD (0,75, 95%CI: 0,70–0,81) auf. Die AUC für LAD und den maximalen 3D-Durchmesser betrug 0,68. Die Elongation von Lymphknoten zeigte eine substanziell geringere AUC (0,57, 95%CI: 0,50–0,64). Schlussfolgerung: In der Unterscheidung von benignen und malignen Lymphknoten kann die semi-automatische 3D-Auswertung die PET/CT beim NSCLC nicht ergänzen. Der SAD ist weiterhin der am einfachsten zu bestimmende morphologische Parameter für die Beurteilung von lymphonodulären Targetläsionen beim NSCLC.

Keywords

Lung cancer - computed tomography - positron emission tomography - diagnosis - China - imaging

Schlüsselwörter

Lungenkrebs - Computertomographie - Positronenemissionstomographie - Diagnose - China - bildgebende Verfahren

^* F. B. und B. B. trugen gleichwertig zu dieser Studie bei.

• References

• 1 Birim O, Kappetein AP, Stijnen T, Bogers AJ. Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer. Ann Thorac Surg 2005; 79: 375-382.
• 2 Bollen EC, Goei R, van’t Hof-Grootenboer BE. et al. Interobserver variability and accuracy of computed tomographic assessment of nodal status in lung cancer. Ann Thorac Surg 1994; 58: 158-162.
• 3 Bolte H, Riedel C, Jahnke T. et al. Reproducibility of computer-aided volumetry of artificial small pulmonary nodules in ex vivo porcine lungs. Invest Radiol 2006; 41: 28-35.
• 4 Cheson BD, Horning SJ, Coiffier B. et al. Report of an international workshop to standardize response criteria for non-Hodgkin‘s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17: 1244.
• 5 Cymbalista M, Waysberg A, Zacharias C. et al. CT demonstration of the 1996 AJCC-UICC regional lymph node classification for lung cancer staging. Radiographics 1999; 19: 899-900.
• 6 Das M, Ley-Zaporozhan J, Gietema HA. et al. Accuracy of automated volumetry of pulmonary nodules across different multislice CT scanners. Eur Radiol 2007; 17: 1979-1984.
• 7 Das M, Muhlenbruch G, Katoh M. et al. Automated volumetry of solid pulmonary nodules in a phantom: accuracy across different CT scanner technologies. Invest Radiol 2007; 42: 297-302.
• 8 De Wever W, Meylaerts L, De Ceuninck L. et al. Additional value of integrated PET-CT in the detection and characterization of lung metastases: correlation with CT alone and PET alone. Eur Radiol 2007; 17: 467-473.
• 9 Dwamena BA, Sonnad SS, Angobaldo JO, Wahl RL. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s--meta-analytic comparison of PET and CT. Radiology 1999; 213: 530-536.
• 10 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247.
• 11 Erasmus JJ, Gladish GW, Broemeling L. et al. Inter-observer and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response. J Clin Oncol 2003; 21: 2574-2582.
• 12 Ettinger DS. Overview and state of the art in the management of lung cancer. Oncology 2004; 18 7 Suppl 4 3-9.
• 13 Fabel M, von Tengg-Kobligk H, Giesel FL. et al. Semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma stage III/IV – a feasibility study. Eur Radiol 2008; 18: 1114-1122.
• 14 Franzius C. FDG PET: advantages for staging the mediastinum?. Lung Cancer 2004; 45 Suppl 2 S69-S74.
• 15 Gould MK, Kuschner WG, Rydzak CE. et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 2003; 139: 879-892.
• 16 Greene F, Page D, Fleming I. et al. AJCC Cancer Staging Manual. Heidelberg New York: Springer; 2002: 165-177.
• 17 Hellwig D, Baum RP, Kirsch C. FDG-PET, PET/CT and conventional nuclear medicine procedures in the evaluation of lung cancer: a systematic review. Nuklearmedizin 2009; 48: 59-69.
• 18 Hellwig D, Groschel A, Graeter TP. et al. Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer. Eur J Nucl Med Mol Imaging 2006; 33: 13-21.
• 19 Heussel CP, Meier S, Wittelsberger S. et al. Follow-up CT measurement of liver malignoma according to RECIST and WHO vs. volumetry. Fortschr Roentgen 2007; 179: 958-964.
• 20 Mahr A, Levegrun S, Bahner ML. et al. Usability of semiautomatic segmentation algorithms for tumor volume determination. Invest Radiol 1999; 34: 143-150.
• 21 Marten K, Auer F, Schmidt S. et al. Inadequacy of manual measurements compared to automated CT volumetry in assessment of treatment response of pulmonary metastases using RECIST criteria. Eur Radiol 2006; 16: 781-790.
• 22 McLoud TC, Bourgouin PM, Greenberg RW. et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992; 182: 319-323.
• 23 Moltz J, Bornemann L, Kuhnigk J. Advanced segmentation techniques for lung nodules, liver meta-stases, and enlarges lymph nodes in CT scans. IEEE Trans Med Imag 2009; 1: 122-134.
• 24 Schaefer NG, Hany TF, Taverna C. et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging--do we need contrast-enhanced CT?. Radiology 2004; 232: 823-829.
• 25 Schwartz LH, Bogaerts J, Ford R. et al. Evaluation of lymph nodes with RECIST 1.1. Eur J Cancer 2009; 45: 261-267.
• 26 Schwartz LH, Mazumdar M, Brown W. et al. Variability in response assessment in solid tumors: effect of number of lesions chosen for measurement. Clin Cancer Res 2003; 9: 4318-4323.
• 27 Silvestri GA, Gould MK, Margolis ML. et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2^nd ed). Chest 2007; 132 3 Suppl 178S-201S.
• 28 Steinkamp HJ, Cornehl M, Hosten N. et al. Cervical lymphadenopathy: ratio of long- to short-axis dia -meter as a predictor of malignancy. Br J Radiol 1995; 68: 266-270.
• 29 Steinkamp HJ, Hosten N, Richter C. et al. Enlarged cervical lymph nodes at helical CT. Radiology 1994; 191: 795-798.
• 30 Steinkamp HJ, Keske U, Schedel J. et al. The spiral CT of cervical lymph node enlargements. The initial clinical results. Röfo 1994; 160: 500-505.
• 31 Strobel K, Dummer R, Husarik DB. et al. High-risk melanoma: accuracy of FDG PET/CT with added CT morphologic information for detection of metastases. Radiology 2007; 244: 566-574.
• 32 Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003; 123 1 Suppl 137S-146S.
• 33 Vassallo P, Wernecke K, Roos N, Peters PE. Differentiation of benign from malignant superficial lymphadenopathy: the role of high-resolution US. Radiology 1992; 183: 215-220.
• 34 Vorwerk H, Obenauer S, Schmidberger H. et al. The significance of a uniform definition of pathological lymph nodes in Hodgkin lymphoma: impact of different thresholds for positive lymph nodes in CT imaging on staging and therapy. Radiother Oncol 2008; 87: 74-81.
• 35 Wormanns D, Kohl G, Klotz E. et al. Volumetric measurements of pulmonary nodules at multi-row detector CT: in vivo reproducibility. Eur Radiol 2004; 14: 86-92.
• 36 Yankelevitz DF, Reeves AP, Kostis WJ. et al. Small pulmonary nodules: volumetrically determined growth rates based on CT evaluation. Radiology 2000; 217: 251-256.