Utility of PET-CT for detection of N2 or N3 nodal mestastases in the mediastinum in patients with non-small cell lung cancer (NSCLC)

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Utility of PET-CT for detection of N2 or N3 nodal mestastases in the mediastinum in patients with non-small cell lung cancer (NSCLC) Poster No.: C-1360 Congress: ECR 2015 Type: Scientific Exhibit Authors: P. Navin, J. Das, J. Bruzzi; Galway/IE Keywords: Thorax, Lymph nodes, Oncology, PET-CT, Diagnostic procedure, Staging, Cancer DOI: 10.1594/ecr2015/C-1360 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 13

Aims and objectives Lung cancer is the leading cause of cancer death in Ireland representing 18% of female 1 and 22% of male cancer deaths. Positron emission tomography (PET) with Computed Tomography (CT) has been shown to be more accurate than CT alone for detection of 2 nodal metastases. There is significant variance in the results of studies assessing this 3 accuracy however. The aim of this study is to evaluate the diagnostic utility of PET-CT for staging of the mediastinum in patients with non-small-cell lung cancer (NSCLC) in a tertiary-referral oncology centre. Page 2 of 13

Images for this section: Fig. 1: Figure 1. Contrast enhanced CT demonstrating nodal mass in subaortic area in individual with Non Small Cell Lung Cancer Page 3 of 13

Fig. 2: Figure 2. Corresponding slice on PET-CT demonstrating FDG avidity in this nodal mass. Patient confirmed N2 staging post surgical resection Page 4 of 13

Methods and materials This was a retrospective study of patients with NSCLC who underwent baseline staging of the mediastinum by PET-CT and invasive sampling [mediastinoscopy, surgical dissection, or endobronchial ultrasound guided biopsy (EBUS)]. PET-CT was performed on a Philips Gemini scanner using approximately 400 MBq of 18-F fluorodeoxyglucose (FDG). Histopathological and cytopathological results were correlated with findings at PET-CT. The diagnostic accuracy of PET-CT was recorded in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) on a pern stage basis. Page 5 of 13

Results A total of 95 patients with NSCLC were included in the study. All patients had baseline PET-CT scan, followed by invasive nodal sampling of the mediastinum. Baseline PETCT was negative for N2 or N3 nodal metastases in 72 (75.79%) patients, and suggested positive N2 nodes in 22 (23.16%) patients and positive N3 nodes in 6 (6.32%) patients. 76 patients underwent surgical resection. Compared to a combination of EBUS and surgical dissection, PET-CT had a sensitivity of 52%, specificity 89%, PPV 32%, NPV 95% for the detection of N2 or N3 metastatic lymph nodes. False negative rate was 11.6% with a false positive rate of 23.1%. The average width in short axis of a false positive node was 11.9mm +/- 3.4mm and a false negative node 6.8mm +/- 1.2mm (P<0.05) Page 6 of 13

Images for this section: Fig. 3: Figure 3. PET-CT of a patient with ultimately T1aN2 NSCLC following surgical resection. Image demonstrating primary lesion with FDG avidity. Page 7 of 13

Fig. 4: Figure 4. Contrast enhanced CT of same patient with lymph node measuring 7mm in the subaortic region. Page 8 of 13

Fig. 5: Figure 5. PET-CT demonstrated no significant mediastinal FDG uptake, particularly in the sub aortic region. Following resection this lymph node was found to be positive for malignancy (False Negative). Page 9 of 13

Conclusion The inconsistent performance of PET-CT in evaluating mediastinal lymph nodes is once again evident in this study. Notably, the sensitivity of PET CT in assessing mediastinal lymph nodes is lower than 3 average, according to a recent Cochrane review (81.3% v 52%). In this review, higher sensitivity rates were associated with geographical location, type of PET-CT scanner, presence of adenocarcinoma and using more than 500 MBq of 18-F FDG. It was postulated in the same review however, that any attempt to increase sensitivity may alter specificity inversely. For instance although sensitivity increased with MBq greater than 500, specificity decreased. In our study, specificity of 89% is higher than the average of 3 79.4% in the Cochrane review. It may be argued that a balance must be reached to sustain adequate sensitivity with acceptable specificity. The false negative rate encountered in our study is comparable to other studies 4, 5, 6 (7-16%). Factors which lead to increased false negative rate include presence of adenocarcinoma, large tumour size, tumour located centrally or in the right upper lobe, high SUVmax of the primary tumour, positive N1 nodes on PET and poorly differentiated histology 4, 5, 7. The accuracy of PET-CT in assessing sub-centimetre lymph nodes has 8 also previously been criticised. This is also evident in our study with all false negative lymph nodes having dimensions in short axis less than 1cm. False positive rates are a known burden of PET-CT imaging due to factors such as 9 reactive hyperplasia or active inflammation. Our figure of 23.1% is clinically relevant with almost a quarter of all patients potentially denied surgical intervention. This compares 9 with a false positive rate of 16% in another study comparing PET-CT to CT alone. This however, is still favourable to CT with a false positive rate of 31%. PET-CT is a relatively novel staging method of mediastinal metastatic nodal disease in Non-Small Cell Lung Cancer. Based on current evidence however, it is not accurate enough to direct management but more triage those who require further surgical staging in the form of mediastinocopy or EBUS. This is particularly evident in lymph nodes less than 1cm. Page 10 of 13

Images for this section: Fig. 6: Figure 6. PET-CT demonstrating FDG avidity of a left lower lobe mass measuring 4.5cm (T2a) Page 11 of 13

Fig. 7: Figure 7. PET CT demonstrating increased take in a paraoesophegeal lymph node measuring 1cm; therefore radiologically N2 disease. This lymph node was resected at surgery with no malignancy detected (False Positive) Page 12 of 13

References 1. 2. 3. 4. 5. 6. 7. 8. 9. Cancer in Ireland 2013: Annual report of the National Cancer Registry Lardinois D, Weder W, Hany T, et al. Staging of non-small-cell lung cancer with integrated positron-emission-tomography and computed tomography. N Engl J Med 2003;348:2500-7. Schmidt-Hansen M, Baldwin DR, Hasler E, et al. PET-CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer. Cochrane Database of Systematic Reviews 2014, Issue 11. Al-Sarraf N, Aziz R, Gately K, Lucey J, Wilson L et al. Pattern and predictors of occult mediastinal lymph node involvement in non-small cell lung cancer patients with negative mediastinal uptake on positron emission tomography. Eur J Cardiothorac Surg 2008 33: 104-109. Lee PC, Port JL, Korst RJ, Liss Y, Meherally DN et al. Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer. Ann Thorac Surg 2007 84: 177-181. Cerfolio RJ, Bryant AS, Ohja B, et al. The maximum standardized uptake values on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg 2005 130: 151-159. Cerfolio RJ, Bryant AS, Eloubeidi MA Routine mediastinoscopy and esophageal ultrasound fine-needle aspiration in patients with non-small cell lung cancer who are clinically N2 negative: a prospective study. Chest 2006 130: 1791-1795. Perigaud C, B, JC, et alprospective preoperative mediastinal lymph node staging by integrated positron emission tomography-computerised tomography in patients with non-small-cell lung cancer Shim SS, Lee KS, Kim BT, Chung MJ, Lee EJ et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 2005 236: 1011-1019 Page 13 of 13