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Lung Cancer


Figure 3: The Three Clinical–Radiological Phenotypes of Non-small-cell Lung Cancer


Peripheral T1 (N2 probability <20%) Phenotype 1 Surgery allowed when either:


CT negative or


PET negative


metastasis 40–60%), negative PET would not exclude with a sufficient safety margin the presence of mediastinal metastasis (probability 12–17%). Cytological study of the mediastinum must therefore be performed regardless of the PET result. Furthermore, if PET is positive, a negative cytology would not be sufficient and mediastinoscopy will be mandatory. As in any mathematical product, no matter which test (PET or TBNA) is performed first, the result will be the same.


We can therefore identify three main clinical–radiological phenotypes in NSCLC (see Figure 3):


Peripheral T2, central T, ↑CEA, ADK with


pleural involvement (N2 probability 30–40%)


Phenotype 2 Surgery allowed when both:


CT negative and


PET negative


• Phenotype a: The probability of mediastinal metastasis is <20%. In this case, negativity on either CT or PET authorises surgery.


• Phenotype b: The probability of mediastinal metastasis is about 30–40%. In this case, surgery may be suggested when both CT and PET are negative.


N1


(N2 probability 40–60%) Phenotype 3


Surgery allowed when both:


PET negative and


Cytology negative


ADK = adenocarcinoma; CEA = carcinoembryonic antigen; CT = computed tomography; PET = positron emission tomography; T = tumour.


predictive value of the test. Recently,73 we suggested a mathematical


model using Bayes’ theorem that enables the probability of nodal metastasis to be predicted after a certain number of diagnostic procedures has been performed, providing a simple way of evaluating when a patient can undergo surgery or, conversely, whether further investigations are required.


Figure 1 shows a flowchart focusing on a reasoned study of mediastinum using probability calculations. Figure 2 provides a simplified algorithm in which the pre-test probability of metastasis and the predictive value of each examination (in the case of a positive or negative result) are taken into account for each indicated choice. Surgery is considered a possible choice whenever the probability of mediastinal metastasis falls below 10%.


For example (see Figure 2), in peripheral T1, a CT-negative mediastinum indicates a <10% probability of metastasis; in this case, immediate resort to surgery may be considered reasonable. Positive CT indicates a probability of metastasis of up to about 40%; in this case, negative PET would authorise surgery (1–7% probability of mediastinal metastasis). Conversely, in clinical stage 2 (pre-test probability of mediastinal


1. De Leyn P, Lardinois D, Van Schil PE, et al., ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer, Eur J Cardiothorac Surg, 2007;32:1–8.


2. Guyatt GH, Lefcoe M, Walter S, et al., Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group, Chest, 1995;107;116–9.


3. Arita T, Matsumoto T, Kuramitsu T, et al., Is it possible to differentiate malignant mediastinal nodes from benign nodes by size? Reevaluation by CT, transesophageal echocardiography, and nodal specimen, Chest, 1996;110;1004–8.


4. Kerr KM, Lamb D, Wathen CG, et al., Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging, Thorax, 1992;47:337–41.


5. Detterbeck FC, Jantz MA, Wallace M, et al., Invasive mediastinal staging of lung cancer. ACCP evidence-based clinical practice guidelines (2nd edition), Chest, 2007;132:202–22.


6. Vansteenkiste JF, Stroobants SG, De Leyn PR, et al., Mediastinal lymph node staging with FDG-PET scan in


• Phenotype c: The probability of mediastinal metastasis is >40%. In this case, surgery is indicated only when both PET and cytology are negative. In any other case, surgical confirmation is necessary.


Conclusions


Mediastinal staging is crucial to ensure the best therapeutic option is chosen for each patient. A diagnosed stage N0 after CT and PET requires surgery, except in cases of unfavourable grading, large or central tumours or a very high SUV of the primary tumour, given the major probability of metastasis in the mediastinal lymph node even in the case of negative CT and PET. For the same reason, clinical stage N1 suggests the need for minimally invasive and/or surgical biopsy techniques. A negative result of a needle aspiration technique is not considered final since micro-metastasis remains a risk and plagued lymph nodes may be situated next to unaffected ones; therefore, a negative cytological sample generally requires surgical confirmation. However, diagnostic surgery could be avoided in the case of a low post-test probability of neoplastic localisation. To obtain this assessment we have developed a staging proposal on the basis of data provided by the literature and plain statistical concepts using Bayes’ theorem; the resulting algorithm may provide a rational opportunity to tackle the challenge of mediastinal staging in lung cancer. The application of this protocol would lead to a better use of available resources (in terms of costs/benefits) by enabling a more precise step-by-step analysis of the staging sequence. Although it may be accepted that irrational use of limited resources is unbearable, we may nonetheless consider that application of multiple (unnecessary) examinations may lead to ambiguity. Nevertheless, the suggested protocol represents a simulation based on statistical projections. We have started a clinical trial to validate our theoretical construct. n


patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases, Chest, 1997;112:1480–6.


7. Poncelet AJ, Lonneux M, Coche E, et al., PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung carcinoma, Eur J Cardiothorac Surg, 2001;20:468–74.


8. Farrel MA, McAdams HP, Herndon JE, Patz EF Jr, Non-small cell lung cancer: FDG-PET for nodal staging in patients with stage I disease, Radiology, 2000;215:886–90.


9. Maziak DE, Darling GE, Inculet RI, et al., Positron emission tomography in staging early lung cancer. A randomized trial, Ann Intern Med, 2009;151:221–8.


10. Vansteenkiste JF, Stroohants SG, De Leyn PR, et al., Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases, Chest, 1997;112:1480–6.


11. Poncelet AJ, Lonneux M, Coche E, et al., PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung carcinoma, Eur J Cardiothorac Surg, 2001;20:468–74.


12. Farrel MA, McAdams HP, Herndon JE, Patz EF Jr, Non-small cell lung cancer: FDG-PET for nodal staging in patients with stage I disease, Radiology, 2000;215:886–90.


13. De Langen AJ, Raijmakers P, Riphagen I, et al., The size of mediastinal lymph nodes and its relation with metastatic involvement: a meta-analysis, Eur J Cardiothorac Surg, 2006;29:26–9.


14. Tasc E, Tezela C, Orkia A, et al., The role of integrated positron emission tomography and computed tomography in the assessment of nodal spread in cases with non-small cell lung cancer, Interact Cardiovas Thorac Surg, 2010;10:200–3.


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;139:879–92.


16. Scott WJ, Globar LS, Terry JD, et al., Mediastinal lymph node staging of non-small cell lung cancer: a prospective comparison of computed tomography and positron emission tomography, J Thorac Cardiovasc Surg, 1996;111:642–8.


17. Verhagen AF, Bootsma GP, Tjan-Heijnen VC, et al., FDG-PET


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EUROPEAN ONCOLOGY & HAEMATOLOGY


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