Combined Transbronchial Needle Aspiration And PET/CT For Mediastinal Staging Of Lung Cancer Şermin Börekçi 1, Osman Elbek 1, Nazan Bayram 1, Nevin Uysal 1, Kemal Bakır 2 1 Department of Pulmonary Diseases, University of Gaziantep, School of Medicine 2 Department of Pathology, University of Gaziantep, School of Medicine

1.INTRODUCTION AND AIM-I The most common cancer is lung cancer on the world Lung cancer responsible for %12.8 of all cancer cases, %17.8 of all death due to cancer on the world, acording to 1999’s datas The Turkish Thoracic Society. The guide for diagnosis and treatment of lung cancer. Thorax Journal. 2006;7(2):1-35.

1.INTRODUCTION AND AIM-II The %70 of all lung cancer cases are at advanced (stage IV) or localy advanced stage (stage IIIA and IIIB) when diagnosed and they have no chance to surgery options for radical treatment The Turkish Thoracic Society. The guide for diagnosis and treatment of lung cancer. Thorax Journal. 2006;7(2):1-35.

1.INTRODUCTION AND AIM-III Staging of patient is important for;  Evoluation of patient for surgery  Planning of treatment options  Determination of prognosis Detterbeck FC, DeCamp MM, Kohman LJ, Silvestri GA. Lung cancer. Invasive staging: the guidelines. Chest 2003; 123 (suppl): 167S-75S.

1.INTRODUCTION AND AIM-IV Procedures for mediastinal staging are clasified into two groups as Invasive and noninvasive Noninvasive procedures;  Thorax CT, Thorax MRG, PET İnvasive procedures;  TBNA, TTNA, EUS-NA  Mediastinoscopy / Mediastinostomi, VATS

Mediastinoscopy is gold standart for mediastinal staging;  İnvasive  General anesthesia  Usually hospitalization 1.INTRODUCTION AND AIM-V Bayram N, Borekci S, Uyar M, Bakır K and Elbek O. Transbronchial needle aspiration in the diagnosis and staging of lung cancer. Indian J Chest Dis Allied Sci 2008; 50:

1949; Schieppati:  The first sampling from tracheal carina by using rigid bronchoscopy 1978; Wang:  Paratracheal lymph node sampling by TBNA 1979; Oho:  Using of flexible neddle with Fiberoptic bronchoscopy 1983; Wang:  Mapping and new kind of neddle for TBNA 1.INTRODUCTION AND AIM-VI

FACTORS FOR SUCCESS Cell type of Cancer (small cell) Right sided lesions Large lymph nodes and masses Localization of lesions (paratracheal, subcarinal) Experience Harrow E. Chest, Haponik EF. Am J Respir Crit Care Med, Harrow EM. Am J Respir Crit Care Med, Herth FJ. Eur Respir J, 2006.

1.INTRODUCTION AND AIM-VII A limited studies were present abouth using PET/CT instead of CT with TBNA to increase the success of TBNA. Hsu LH, Ko JS, You DL, Liu CC, Chu NM. Respirology 2007; 12: Bernasconi, Gambazzi F, Bubendorf L, Rasch H, Kneilfel S, Tamm M. Eur Respir J 2006; 27:

1.INTRODUCTION AND AIM-VIII In our study we aimed to determine;  The role of TBNA with thorax CT and PET/CT for lung staging  The comparision with mediastinoscopy  If this approach can reduce to need for mediastinoscopy.

2. MATERIAL AND METHODS-I Prospective, invasive, uncontrolled study Department of Pulmonary Diseases, University of Gaziantep From march 2006 to March 2008  The patients who suspected lung cancer  Enlarged mediastinal lymph nodes (≥ 1 cm) localized on CT  Underwent PET/CT scanning  Consecutive 25 patients

2. MATERIAL AND METHODS-II TBNA sampling:  Flexible bronchoscopy  Thorax CT and PET/CT combination  Acording to Wang’s map of lymph node  22 Gauge aspiration needle  4 sampling from each lymph node station  Starting from the lymph node that the most advanced stage  The other kind of sampling procedures were done after TBNA sampling

2. MATERIAL AND METHODS-III Evaluation of samples:  Adequate Sample: presence of numerous benign lymphoid cells  Negative Malignite: absence of malignant cells  Positive Malignite: presence of malignant cells

2. MATERIAL AND METHODS-IV Statistical Analysis:  Mediastinoscopy was used as “gold standart”.  The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy rate for prediction of lymph node staging of PET/CT combined TBNA were calculated.  Descriptive statistics were expressed as mean±standart deviation (SD), interquartile range (IQR) or percent (%) according to kind of data.

2. MATERIAL AND METHODS-V Statistical Analysis:  The factors that might effect positive TBNA result were analysed through logistic regression model  P value less than 0.05 was deemed statistically significant.  The statistical analysis was performed using SPSS 13.0 for Windows

3.RESULTS-I Age (year, mean±SD) 58.7±7.6 Gender Male (n,%) 25 (100) Female 0 (0) Smoking (n,%) 25 (100) Smoking (pack/year) (median, IQR) 40 (30-55) Comorbidities (n,%) DM 2 (8) COPD 1 (4) HT 3 (12) Karnofsky performance score (mean±SD) 80.4±10.6 ECOG (mean±SD) 0.9±0.6 Characteristics of the patients

3.RESULTS-II Clinical properties of patients Symptoms (n,%) cough 23 (92) increase of sputum amount 10 (40) shortness of breath 22 (88) Hemoptizi 9 (36) lack of appetite 11 (44) loss of weight (total amount/last 2 month) 11 (44) loss of weight (median±SD) 11.4±6.2 Weakness 11 (44) back pain 2 (8) chest pain 8 (32) Paraneoplastik syndroms 1 (4) Karnofsky’s score 80.4±10.6 ECOG (median±SD) 0.9±0.6

3.RESULTS-III

3.RESULTS-IV

3.RESULTS-V Total 43 enlarged mediastinal lymph nodes were sampled from 25 patients

3.RESULTS-VI

3.RESULTS-VII

3.RESULTS-VIII

3.RESULTS-IX

3.RESULTS-X p > 0.05

3.RESULTS-XI p > 0.05

3.RESULTS-XII Mediastinocopy Malign Mediastinoscopy Benign TBNA Malign140 TBNA Benign21719 Total TBNA Sensitivity%87 TBİA Specificity %100 Positive predictive value%100 Negative predictive value%89 TBNA false positivity%0 TBNA false negativity%12

3.RESULTS-XIII The clinical factors that might effect positive TBNA result Factor p Lymph node location0.18 LAP on CT 0.33 PET SUV Max ≥5<0.05* Broncoscopic properties ( precence of direct or indirect findings) 0.10 Adequate or inadequate TBNA sampling0.09 Tumor tissue group0.37 * The PET SUV max≥5 was 11 times increased positive TBNA results [OR=10.68 ( ), P<0.01

3.RESULTS-XIV

3.RESULTS-XV  Tissue diagnosis could done by TBNA for all 14 lymph node (%100) stations with malign result

3.RESULTS-XVI The staging was completed with TBNA in 5/19 (%26) patients without mediastinoscopy.

T he clinical nodal staging of patients before and after TBNA, and final surgical nodal staging after mediastinoscopy Patient No Before TBNA # After TBNAAfter mediastinoscopy 1&1& T2N2M0N 2 (negative) 2T4N2M0N 2 (positive)N 2 (poszitive) ϯ 3&3& T2N2M0N 2 (negative) 5&5& T2N2M0N 2 (negative) 8&8& T2N2M0N 2 (negative) 9&*9&*T2N2M0 N 2 (negative)N 2 (positive) 10 & *T2N2M0 N 2 (negative)N 2 (positive) 11 & T3N2M0N 2 (negative) 13 & T2N2M0N 2 (negative) 14 & T3N1M0N 2 (negative) 15 & T3N2M0N 2 (negative) 16 & T4N1M0N 2 (negative) 17 & T4N2M0N 2 (negative) 20 & T2N2M0N 2 (negative) 21T2N2M0N 2 (positive) Initial staging was changed after TBNA in 13/19 (%69) The correct diagnosis was done in 17/19 (%89) with TBNA 22T3N2M0N 2 (positive) 23T3N2M0N 2 (positive) 24T2N2M0N 2 (positive) 25T2N2M0N 2 (positive)

Treatments Patient N o T reatment 1 Opera tion 2 Neoadjuvant chemoradiotherapy 3 Opera tion Neoadjuvant chemoradiotherapy 10 Neoadjuvant chemoradiotherapy 11 Opera tion 12 CT 13 Opera tion 14 Opera tion 15 Opera tion 16 Opera tion 17 Opera tion 18 Neoadjuvant chemoradiotherapy 19 Neoadjuvant chemoradiotherapy 20 Opera tion 21 Neoadjuvant chemoradiotherapy 22 CT+RT 23 CT 24 Neoadjuvant chemoradiotherapy 25 CT

4. DISCUSSION-I TBNA could done during first broncoscopic procedure with local anestezia, could decrease to need adding procedure for staging so good for patient’s comfort and cost effective. In our study staging of 5 (%26) in 19 patients were done without mediastinoscopy and TBNA decreased the need of mediastinoscopy.

4. DISCUSSION-II Acording to literatures lymph node location can effect TBNA result. Patelli and collagues showed that, TBNA sensitivity was %52 for left paratracheal, %84 for right paratracheal and %84 for subcarinal lymph node (Patelli M, et al. Ann Thoracic Surg, 2002). In our study there is no statistical differance between lymph node location and TBNA positivity (p>0.05).

4. DISCUSSION-III If combination of PET with TBNA increase the succes of diagnosis is unknown. There is limited study to show that this combination is increase the succes of diagnosis (Bernasconi, et al. Eur Respir J, 2006 ve Hsu LH, et al. Respirology, 2007). In our study the sencitivity, spesificity, PPV, NPV of the procedure that combined PET/CT with TBNA were found very high like Bernasconi’s and Hsu’s study (respectively %87, %100, %100, %89).

4.DISCUSSION-IV The clinical factors that might effect positive TBNA result Factor p Lymph node location0.18 LAP on CT 0.33 PET SUV Max ≥5<0.05* Broncoscopic properties ( precence of direct or indirect findings) 0.10 Adequate or inadequate TBNA sampling0.09 Tumor tissue group0.37 * The PET SUV max≥5 was 11 times increased positive TBNA results [OR=10.68 ( ), P<0.01

4. DISCUSSION-V In previous study tahat we done in our clinic we found that sencitivity of TBNA combined with CT were %58 (Bayram N, et al. Indian J Chest Dis Allied Sci, 2008). And also now, we found that sensitivity of of TBNA combined with PET/CT is incresed to %87. This positive result may be due to increase of TBNA experience and olso due to PET/BT that shows details.

4. DISCUSSION-VI It is showed that TBNA combined with PET can reduce the %57 of mediastinoscopy need (Bernasconi, et al. Eur Respir J, 2006). In our study this ratio was %26. This lower ratio than Bernasconi’s is may be due to most of our patients were operable and toracotomy was carried out after mediastinoscopy in the same operation session.

5. LIMITATIONS There is no control group The distribution of lymph node station were right There were no rapid on-site cytological examination.

6. RESULTS-I TBNA is less invasive and has less complication than mediastinoscopy and can be used for correct staging of lung cancer.

6. RESULTS-II Combination of TBNA with PET/CT can increase sensitivity Increse of TBNA positivity is meningfull on lymph nodes with SUV Max ≥ 5 TBNA decreased the need of mediastinoscopy

SUGGESTION Our experience suggest that TBNA should be routinly performed during the standart diagnostic bronchoscopy for staging of lung cancer to all patients with mediastinal lympadenopathy on CT and/or PET/CT.

THANKS