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E. Hsiao



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    MS22 - The Mediastinum 2013 (ID 39)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      MS22.2 - Further Staging Using Imaging - PET, MRI and PET/CT (ID 563)

      14:00 - 15:30  |  Author(s): E. Hsiao

      • Abstract
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      Abstract
      PET and PET/CT FDG PET scans have shown high sensitivity and specificity in detecting mediastinal nodal involvement. It works by detecting increased accumulation of F-18 fluorodeoxyglucose (FDG) in the neoplastic cells which have a deranged glucose metabolism. FDG undergoes similar uptake and metabolic pathway glucose molecules. The accumulation of positron emitting F-18 isotope can then be used to localise these hypermetabolic neoplastic tissue. Both 2003 and 2007 guidelines of the American College of Chest Physicians (ACCP) endorsed the use of PET imaging as a non-invasive staging tool for non-small cell lung cancer[1, 2]. FDG PET scan has become the standard of care in staging primary lung cancer. It is recognised as the most accurate non-invasive tool in the staging of lung cancer. It is also widely accepted that PET scanning improves detection of distant metastatic disease as well as unsuspected N2 or N3 disease particularly in the high-risk patients. Therefore, several series have shown that the use of PET imaging reduces unnecessary or futile surgical resection. Traditionally, a standard uptake value (SUVmax) of 2.5 or above is used as a threshold for malignancy, but this was initially based on the uptake of peripheral lung masses with diameter >2cm. Whether this can be applied to mediastinal nodes is questionable. The special resolution of a current generation PET scanner is approximately 7mm. Nonetheless, small or non-enlarged lymph nodes with highly aggressive tumour metastasis may be detected based on the higher intensity of uptake compared to the background. While FDG PET is clinically useful, it is an imperfect technique. The meta-analysis carried out by Silvestri et al [3]in the third edition of ACCP guideline demonstrated that the median sensitivity and specificity for detecting mediastinal metastases were 80% and 88% respectively. The findings demonstrate that PET is more accurate than CT scanning (median sensitivity 55% and median specificity 81%) [3]. However, it is important to know that neither technique is perfect. Interestingly, an increasing number of recent studies were performed using integrated PET/CT scanner. The meta-analysis by the ACCP showed a median sensitivity of 62% and median specificity of 90%[3]. The specificity is slightly higher although the sensitivity is lower. The reason for this observation remains unclear. Nonetheless, PET/CT hybrid cameras have superseded the role of stand alone PET scanners in nowadays. False negative results are more often seen with adenocarcinoma in situ, well-differentiated invasive adenocarcinoma, and typical carcinoid tumours. Small volume or micrometastasis can also be missed due to the finite spatial resolution of PET and perhaps by all imaging techniques. Studies have demonstrated that PET scanning is less sensitive for lymph nodes measuring <7-10mm diameter, and micrometastases have been detected in non enlarged lymph nodes without abnormal FDG uptake by invasive sampling[4]. Furthermore, in the presence of a central FDG avid lung cancer, N1 disease can be missed by FDG PET imaging in up to 25% of cases[5]. In the evolution of a peripheral T1A lesion particularly if the density of the nodule is ground glass or sub-solid. It is well known that these types of neoplasms have low incidence of mediastinal metastasis though the risk is not nil. It is important that the interpretation of a negative PET scan to be combined with clinical judgement as well as the pre-test likelihood of mediastinal metastasis. Furthermore the local availability and expertise in invasive biopsy procedures are also important factors. False positive findings are often due to infection or inflammation. Common causes include sarcoidosis, silicosis, reactive changes, fungal or mycobacterial infections. In summary, it is important to confirm N2 and N3 disease with tissue sampling to avoid delay or missing potentially curative surgery. In the presence of negative of PET and CT findings in the mediastinum, that the decision to operate or to have invasive tissue sampling requires careful consideration and clinical judgement. Combined with invasive mediastinal staging techniques Transbronchial biopsy has shown a median sensitivity of 78% and specificity of 100% in a systemic review. The sensitivity has been reported to be high in patients with positive CT or PET/CT findings. Occasional false positive results have been reported to be approximately 7%. The median negative predictive value in this systemic review is 77%. Endobronchial ultrasound with needle aspiration can achieve a median negative predicted value of 91%. This is further improved with combined EBUS and EUS which have a median negative predictive value is 96%[3]. For most patients undergoing PET/CT staging, the need of invasive mediastinal staging is not eliminated. It is important to confirm the presence of N2 or N3 disease in patients without evidence of metastatic disease to avoid withholding potentially curative surgery. FDG PET/CT can guide needle biopsy as to which nodal stations are considered high risk. Targeting lymph nodes with a higher pretest probability further decreases the inherent false negative rate of needle biopsy. The location of FDG avid nodal stations is important as to which technique will be most appropriate. For example, the identification of an FDG supraclavicular node (N3) can lead to ultrasound guided percutaneous biopsy. An FDG avid aortopulmonary lymph node may be sampled by using Chamberlain procedure, CT guided fine needle aspiration, or extended cervical mediastinoscopy. In cases with enlarged mediastinal lymph node with negative PET, confirmation by invasive techniques is also advised, as up to 21% of these can still have nodal involvement[4, 6]. There are two exceptions to the rule. First, it is known that in a patient with a peripheral T1 tumour (<3 cm), negative FDG uptake and no enlarged lymph node in the mediastinum carries a high negative predicted value with false negative rate being only 4%[3]. Therefore invasive staging is not recommended in these patients given the similar negative predicted value in a combined EBUS and EUS needle biopsy. Secondly, in lung cancer patients with infiltrative mediastinal mass on CT or PET/CT either from overt T4 disease or bulky nodal disease would not require invasive mediastinal staging. MRI and emerging Techniques MR imaging has mainly been used to evaluate non-small cell lung carcinoma when there is possible involvement of superior sulcus or brachial plexus. It is currently not a routine clinical tool in mediastinal nodal staging. New studies albeit with relatively smaller patient sample size have shown that MRI can detect nodal metastasis particularly using STIR and diffusion weighted imaging (DWI) [7, 8]. Several studies have shown comparable efficacy in relation to the PET/CT staging techniques[9]. Diffusion weighted imaging detect random thermal motion of water molecules, known as Brownian motion. Tissues with restricted diffusion will have a lower apparent diffusion coefficient (ADC) values. Hypercellular density, larger cellular nuclei and dense tumour cell membranes are known to cause restricted diffusion in malignant tissue. A study has confirmed the negative relationship between the SUV on FDG PET/CT scans and the lower ADC values on MRI[10]. Furthermore, MRI has the ability to differentiate tumour tissue from vasculature and mediastinal fat. It is therefore potentially useful to delineate direct tumour invasion of the mediastinum, chest wall, diaphragm or spinal column. More research is required in this field of MR mediastinal staging. The latest development in PET/MR imaging technique [11]using hybrid scanner will provide a fertile ground for future research in the use of non-invasive mediastinal staging. References 1. Silvestri, G.A., M.K. Gould, M.L. Margolis, et al., Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest, 2007. 132(3 Suppl): p. 178S-201S. 2. Physicians, A.C.o.C. and H.a.S.P. Committee, Diagnosis and management of lung cancer: ACCP evidence-based guidelines. American College of Chest Physicians. Chest, 2003. 123(1 Suppl): p. D-G, 1S-337S. 3. Silvestri, G.A., A.V. Gonzalez, M.A. Jantz, et al., Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013. 143(5 Suppl): p. e211S-250S. 4. de Langen, A.J., P. Raijmakers, I. Riphagen, et al., The size of mediastinal lymph nodes and its relation with metastatic involvement: a meta-analysis. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2006. 29(1): p. 26-29. 5. Pozo-Rodríguez, F., J.L. Martín de Nicolás, M.A. Sánchez-Nistal, et al., Accuracy of helical computed tomography and [18F] fluorodeoxyglucose positron emission tomography for identifying lymph node mediastinal metastases in potentially resectable non-small-cell lung cancer. J Clin Oncol, 2005. 23(33): p. 8348-8356. 6. De Leyn, P., D. Lardinois, P.E. Van Schil, et al., ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2007. 32(1): p. 1-8. 7. Usuda, K., X.-T. Zhao, M. Sagawa, et al., Diffusion-weighted imaging is superior to positron emission tomography in the detection and nodal assessment of lung cancers. Ann Thorac Surg, 2011. 91(6): p. 1689-1695. 8. Ohno, Y., H. Koyama, M. Nogami, et al., STIR turbo SE MR imaging vs. coregistered FDG-PET/CT: quantitative and qualitative assessment of N-stage in non-small-cell lung cancer patients. J Magn Reson Imaging, 2007. 26(4): p. 1071-1080. 9. Pauls, S., S.A. Schmidt, M.S. Juchems, et al., Diffusion-weighted MR imaging in comparison to integrated [¹⁸F]-FDG PET/CT for N-staging in patients with lung cancer. European Journal of Radiology, 2012. 81(1): p. 178-182. 10. Heusch, P., C. Buchbender, J. Köhler, et al., Correlation of the Apparent Diffusion Coefficient (ADC) with the Standardized Uptake Value (SUV) in Hybrid 18F-FDG PET/MRI in Non-Small Cell Lung Cancer (NSCLC) Lesions: Initial Results. Rofo, 2013. 11. Kohan, A.A., J.A. Kolthammer, J.L. Vercher-Conejero, et al., N staging of lung cancer patients with PET/MRI using a three-segment model attenuation correction algorithm: Initial experience. Eur Radiol, 2013.

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