FDG-PET, PET/CT and conventional nuclear medicine procedures in the evaluation of lung cancer

Summary

Aim: Currently, the German and Austrian S3 guidelines on the evaluation and treatment of lung cancer are about to be published whereas the American Colleague of Chest Physicians (ACCP) guidelines were already presented in 2007. An important part of the diagnostic workup of lung cancer will be the evaluation of indeterminate lung lesions and the mediastinal and extrathoracic staging using FDG-PET or PET/CT. The results from the literature on FDG-PET and PET/ CT as well as on conventional nuclear medicine staging procedures and the clinical implications are presented. Methods: The literature data was amassed in analogy to the metaanalyses drawn for the current ACCP guidelines. In addition, relevant more recent publications were also considered. To answer the important question for the extent of pathological confirmation needed, the residual risk of mediastinal metastases was calculated for certain constellations of FDG-PET and CT findings. Suggested recommendations were characterized with the level of evidence. Results: FDG-PET (PET/CT) allows the differentiation of indeterminate lung lesions with high accuracy. FDG-PET (PET/ CT) is the most accurate non-invasive procedure to assess the mediastinal nodal stage, for non-small cell as well as for small cell lung cancer. It is justified to omit invasive evaluation of enlarged but FDG-PET negative lymph nodes under certain circumstances. Unexpected extrathoracic metastases detected by FDG-PET imply important changes in therapeutic management. Conclusion: The upcoming S3 guideline on lung cancer will recommend FDG-PET in several indications due to its clinical efficacy well proven by data from literature (high level of evidence). The selected use of conventional nuclear medicine procedures remains beyond doubt. FDG-PET (PET/CT) belongs to the standard of care in lung cancer.

Zusammenfassung

Ziel: Momentan steht die Publikation der durch die deutschen und österreichischen Fachgesellschaften erstellten S3-Leitlinie zum Lungenkarzinom an, nachdem die ACCP bereits 2007 ihre Leitlinien aktualisiert hat. Wesentlicher Teil der Diagnostik bei Lungenkarzinomen werden die Dignitätsbeurteilung von unklaren Lungenherden sowie die mediastinale und extrathorakale Ausbreitungsdiagnostik mittels FDG-PET bzw. PET/CT sein. Hierzu und zu konventionellen nuklearmedizinischen Staging-Untersuchungen werden die zugrunde liegenden Literaturergebnisse und die resultierenden klinischen Konsequenzen dargestellt. Methodik: Die Zusammenstellung der Literaturdaten erfolgte analog zu den Metaanalysen, die für die aktuellen ACCPLeitlinien herangezogen wurden. Zusätzlich wurden relevante aktuelle Arbeiten berücksichtigt. Zur wichtigen Frage des Ausmaßes der pathologischen Sicherung erfolgte eine Berechnung des Restrisikos einer mediastinalen Lymphknoten- Metastasierung bei verschiedenen Befundkonstellationen von FDG-PET und CT. Den vorgeschlagenen Empfehlungen wurden durch die Datenlage der Literatur bestimmte Evidenzlevel zugeordnet. Ergebnisse: FDG-PET (PET/CT) erlaubt die Dignitätsbeurteilung von Lungenherden mit sehr hoher Treffsicherheit. FDG-PET (PET/CT) ist die genaueste nicht-invasive Methode zur Erfassung des mediastinalen Lymphknoten-Status, sowohl für das nichtkleinzellige als auch für das kleinzellige Lungenkarzinom. Unter bestimmten Voraussetzungen ist der Verzicht auf eine invasive Abklärung vergrößerter, FDG-PET negativer mediastinaler Lymphknoten möglich. Mit FDG-PET (PET/ CT) gefundene unerwartete Fernmetastasen bedingen wesentliche änderungen der geplanten Therapie. Schlussfolgerung: Die aktuellen Empfehlungen zum Einsatz der FDG-PET (PET/CT) beim Lungenkarzinom sind durch Literaturdaten sehr gut belegt (hoher Evidenzlevel). Der gezielte Einsatz konventioneller nuklearmedizinischer Untersuchungen bleibt unstrittig. FDG-PET (PET/CT) gehört zum Versorgungsstandard des Lungenkarzinoms.

Keywords

Lung cancer - systematic review - FDG-PET - PET/CT - skeletal scintigraphy - somatostatin receptor scintigraphy

Schlüsselwörter

Lungenkrebs - übersichtsarbeit - FDG-PET - PET/CT - Skelett szintigraphie - Somatostatinrezeptor-Szintigraphie

• References

• 1 Alberts WM. Diagnosis and management of lung cancer executive summary: ACCP evidence-based clinical practice guidelines (2nd ed). Chest 2007; 132 (3 Suppl) 1S-19S.
• 2 Baum RP, Hellwig D, Mezzetti M. Position of nuclear medicine modalities in the diagnostic workup of cancer patients: lung cancer. Q J Nucl Med 2004; 48: 119-142.
• 3 Baum RP, Prasad V. Stellenwert der PET bzw. PET/CT mit ¹⁸F-FDG beim kleinzelligen Lungenkarzinom. Onkologe 2008; 774-782.
• 4 Baum RP, Prasad V, Hommann M. et al. Receptor PET/CT imaging of neuroendocrine tumors. Recent Results Cancer Res 2008; 170: 225-242.
• 5 Bini A, Grazia M, Stella F. et al. The role of somatostatin receptor scintigraphy (Octreoscan) during follow-up of patients after bronchial carcinoid resection. A prospective study. J Cardiovasc Surg (Torino) 2005; 46: 318-319.
• 6 Birim O, Kappetein AP, Stijnen T. et al. Meta- analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in non-small cell lung cancer. Ann Thorac Surg 2005; 79: 375-382.
• 7 Brink I, Schumacher T, Mix M. et al. Impact of [¹⁸F]FDG-PET on the primary staging of small-cell lung cancer. Eur J Nucl Med Mol Imaging 2004; 31: 1614-1620.
• 8 Cerfolio RJ, Ojha B, Bryant AS. et al. The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsm- all cell lung cancer. Ann Thorac Surg 2004; 78: 1017-1023.
• 9 DESTATIS. Todesursachen in Deutschland 2007. In: Fachserie 12, Reihe 4. Wiesbaden: Statistisches Bundesamt; 2008
• 10 Detterbeck FC, Jantz MA, Wallace M. et al. Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd ed). Chest 2007; 132 (3 Suppl) 202S-220S.
• 11 Earnest Ft, Ryu JH, Miller GM. et al. Suspected non-small cell lung cancer: incidence of occult brain and skeletal metastases and effectiveness of imaging for detection-pilot study. Radiology 1999; 211: 137-145.
• 12 Fischer BM, Mortensen J, Hojgaard L. Positron emission tomography in the diagnosis and staging of lung cancer: a systematic, quantitative review. Lancet Oncol 2001; 2: 659-666.
• 13 Fischer BM, Mortensen J, Langer SW. et al. A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis. Ann Oncol 2007; 18: 338-345.
• 14 Giraud P, De Rycke Y, Lavole A. et al. Probability ofmediastinal involvement in non-small-cell lung cancer: a statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy?. Int J Radiat Oncol Biol Phys 2006; 64: 127-135.
• 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 Gould MK, Maclean CC, Kuschner WG. et al. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001; 285: 914-924.
• 17 Granberg D, Sundin A, Janson ET. et al. Octreoscan in patients with bronchial carcinoid tumours. Clin Endocrinol (Oxf) 2003; 59: 793-799.
• 18 Grgic A, Nestle U, Schaefer-Schuler A. et al. FDG- PET-based radiotherapy planning in lung cancer: Optimum breathing protocol and patient positioning. Int J Radiat Oncol Biol Phys. 2008 doi: 10.1016/j.ijrobp.2008.03.063.
• 19 Griffeth LK, Rich KM, Dehdashti F. et al. Brain metastases from non-central nervous system tumors: evaluation with PET. Radiology 1993; 186: 37-44.
• 20 Halpern BS, Schiepers C, Weber WA. et al. Presur- gical staging of non-small cell lung cancer: Positron emission tomography, integrated positron emission tomography/CT, and software image fusion. Chest 2005; 128: 2289-2297.
• 21 Hellwig D. Systematische Metaanalyse zum Lymphknoten-Staging mittels FDG-PET. In: Habilitationsschrift Medizinische Fakultät, editor. Die Positronen-Emissions-Tomographie mit ¹⁸F-Fluorodesoxyglukose beim nichtkleinzelligen Bronchialkarzinom: Bedeutung in der Diagnostik, Therapieplanung und Prognoseabschätzung. Homburg/Saar: Universität des Saarlandes; 2006: 62-80.
• 22 Hellwig D, Graeter TP, Ukena D. et al. ¹⁸F-FDG PET for mediastinal staging of lung cancer: Which SUV threshold makes sense?. J Nucl Med 2007; 48: 1761-1766.
• 23 Hellwig D, Gröschel 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.
• 24 Hellwig D, Ukena D, Paulsen F. et al. Metaanalyse zum Stellenwert der Positronenemissionstomographie mit ¹⁸F-Fluorodesoxyglukose (FDG- PET) bei Lungentumoren. Diskussionsbasis der deutschen Konsensus-Konferenz Onko-PET 2000. Pneumologie 2001; 55: 367-377.
• 25 Herder GJ, Kramer H, Hoekstra OS. et al. Traditional versus up-front [¹⁸F] fluorodeoxyglucose- positron emission tomography staging of non- small-cell lung cancer: a Dutch cooperative randomized study. J Clin Oncol 2006; 24: 1800-1806.
• 26 Keidar Z, Haim N, Guralnik L. et al. PET/CT using ¹⁸F-FDG in suspected lung cancer recurrence: diagnostic value and impact on patient management. J Nucl Med 2004; 45: 1640-1646.
• 27 Krause BJ, Beyer T, Bockisch A. et al. FDG-PET/ CT in oncology. German Guideline. Nuklearmedizin 2007; 46: 291-301.
• 28 Kut V, Spies W, Spies S. et al. Staging and monitoring of small cell lung cancer using [¹⁸F]fluoro- 2-deoxy-D-glucose-positron emission tomography (FDG-PET). Am J Clin Oncol 2007; 30: 45-50.
• 29 Lardinois D, Weder W, Hany TF. et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003; 348: 2500-2507.
• 30 MacManus MP, Hicks RJ, Matthews JP. et al. High rate of detection of unsuspected distant metastases by pet in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy. Int J Radiat Oncol Biol Phys 2001; 50: 287-293.
• 31 Marom EM, McAdams HP, Erasmus JJ. et al. Staging non-small cell lung cancer with whole-body PET. Radiology 1999; 212: 803-809.
• 32 Mayor S. NICE issues guidance for diagnosis and treatment of lung cancer. Br Med J. 2005 330. 439.
• 33 Musi M, Carbone RG, Bertocchi C. et al. Bronchial carcinoid tumours: a study on clinicopath- ological features and role of octreotide scintigraphy. Lung Cancer 1998; 22: 97-102.
• 34 Nestle U, Kremp S, Grosu AL. Practical integration of [¹⁸F]-FDG-PET and PET-CT in the planning of radiotherapy for non-small cell lung cancer (NSCLC): the technical basis, ICRU-target volumes, problems, perspectives. Radiother Oncol 2006; 81: 209-225.
• 35 Niho S, Fujii H, Murakami K. et al. Detection of unsuspected distant metastases and/or regional nodes by FDG-PET in LD-SCLC scan in apparent limited-disease small-cell lung cancer. Lung Cancer 2007; 57: 328-333.
• 36 Nomori H, Watanabe K, Ohtsuka T. et al. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer 2004; 45: 19-27.
• 37 Palm I, Hellwig D, Leutz M. et al. Diagnostische Aussagekraft der Positronenemissionstomographie (PET) bei zerebralen Metastasen von Bronchialkarzinomen. Med Klin 1999; 94: 224-227.
• 38 Perleth M, Gerhardus A, Velasco-Garrido M. Positronenemissionstomographie: Systematische übersichten zur Wirksamkeit bei ausgewählten Indikationen. In: Health Technology Assessment, Schriftenreihe des Deutschen Instituts für Medizinische Dokumentation und Information im Auftrag des Bundesministeriums für Gesundheit und Soziale Sicherung. Sankt Augustin: Asgard; 2003
• 39 Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med 2006; 36: 228-247.
• 40 Shafazand S, Gould MK. A clinical prediction rule to estimate the probability of mediastinal metastasis in patients with non-small cell lung cancer. J Thorac Oncol 2006; 1: 953-959.
• 41 Silvestri GA, Gould MK, Margolis ML. et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd ed). Chest 2007; 132 (3 Suppl) 178S-201S.
• 42 Toloza EM, Harpole L, McCrory DC. Noninvasive staging ofnon-small cell lung cancer: a review of the current evidence. Chest 2003; 123 (1 Suppl) 137S-146S.
• 43 Ung YC, Maziak DE, Vanderveen JA. et al. ¹⁸F-fluor- odeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review. J Natl Cancer Inst 2007; 99: 1753-1767.
• 44 van Tinteren H, Hoekstra OS, Smit EF. et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet 2002; 359: 1388-1393.
• 45 Vansteenkiste J, Fischer BM, Dooms C. et al. Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: systematic review. Lancet Oncol 2004; 5: 531-540.
• 46 Vesselle H, Turcotte E, Wiens L. et al. Application of a neural network to improve nodal staging accuracy with ¹⁸F-FDG PET in non-small cell lung cancer. J Nucl Med 2003; 44: 1918-1926.
• 47 Viney RC, Boyer MJ, King MT. et al. Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 2004; 22: 2357-2362.
• 48 Wahidi MM, Govert JA, Goudar RK. et al. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd ed). Chest 2007; 132 (3 Suppl) 94S-107S.
• 49 Weber WA, Dietlein M, Hellwig D. et al. PET mit ¹⁸F-Fluorodeoxyglukose in der Diagnostik des nicht kleinzelligen Bronchialkarzinoms: evidenzbasierte Empfehlungen und Kosten/Nutzenabwägungen. Nuklearmedizin 2003; 42: 135-144.
• 50 Yellin A, Zwas ST, Rozenman J. et al. Experience with somatostatin receptor scintigraphy in the management of pulmonary carcinoid tumors. Isr Med Assoc J 2005; 7: 712-716.