The Need for Accurate Lung Cancer Staging Peter Baik, DO Thoracic Surgery Cancer Treatment Centers of America Oklahoma Osteopathic Association 115th Annual Convention Financial Disclosures: None 2 Objectives 1. Introduction 2. Case Presentation 3. Current Staging & Guidelines 4. Methods of Staging 5. Recommendations & Summary 3 1
Introduction National Cancer Institute (seer.cancer.org) - Lung cancer: the 2 nd most common cancer in both men and women - In 2013, estimated: - 228,190 new cases (M 118,080/F 110,110) - 159,480 deaths (M 87,260/F 72,220) - 27% of all cancer deaths - Average age at time of diagnosis: 70 4 Introduction 5 Introduction 2004-2010 Overall 5-year Lung cancer survival rate: 16.8% Colon cancer 64.7% Stomach cancer 28.3% Breast cancer 89.2% Pancreatic cancer 6.7% Prostate cancer 98.9% Liver/Biliary cancer 16.6% Endometrial cancer 81.5% Esophageal cancer 17.5% Renal cancer 72.4% Brain cancer 33.4% Leukemia 57.2% Melanoma cancer 91.3% Thyroid cancer 97.8% (Seer.cancer.gov) 6 2
Introduction Death due to lung cancer > colon + breast + prostate (Seer.cancer.gov) 7 Introduction Colon: 48.6% -> 65.9% Breast: 75.2% -> 90.6% Liver: 3% -> 16.8% (Seer.cancer.gov) 8 Introduction IASLC (International Association for the Study of Lung Cancer) Journal of Thoracic Oncology August 2007 9 3
Case Presentation 45-year-old female from Arkansas Chief complaint: hemoptysis PMHx: HTN, GERD PSHx: c-section, tubal ligation Social Hx: 60 pack-year history of smoking, no drugs, moderate alcohol use Occupation: Nurse at a prison ECOG (Eastern Cooperative Oncology Group) performance status: 0 10 Case Presentation PET/CT: Left upper lobe mass SUV: 34g/dL Left hilar mass (2.5cm) SUV: 64g/dL Right paratracheal node SUV: 3g/dL 11 Case Presentation, Continued Transthoracic biopsy of left upper lobe nodule: moderately differentiated adenocarcinoma (TTF-1 positive, CK 5/6 negative) Brain MRI: negative Clinical stage IIIB (T1bN3M0) by PET/CT - N3 due to FDG-avid right paratracheal node Treatment: Cisplatin and Etoposide concurrently with radiation therapy 12 4
13 14 15 5
Per NCCN guidelines (simplified) Stage I & II operable resection inoperable if N0, Radiation if N1, chemoradiation Stage IIIa Surgery +/- chemoradiation or chemotherapy Neoadjuvant chemoradiation Restage +/- Surgery +/- chemotherapy Stage IIIb Chemoradiation Stage IV Chemotherapy 16 Positron Emission Tomography (PET) Should be performed before biopsy FDG (fluorodeoxyglucose) with radiolabeled fluorine18(18f) FDG phosphorylated into FDG-6-PO4. FDG-6-PO4 accumulates in malignant cells False positive due to inflammatory/infectious lesions (granuloma, sarcoidosis, active infections) FDG-6-PO 4 accumulates in malignant cells False negative due to small or low-metabolism lesions Sensitivity 56-93% Specificity 77-98% 17 IIA 19/25 38 24% 6 th edition IIA 318/483 34 36% 7 th edition IASLC (International Association for the Study of Lung Cancer) Journal of Thoracic Oncology August 2007 18 6
Post-obstructive pneumonia 19 PET/CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer. (Cochrane Database Syst Rev. 2014; Nov 13, 2014) Review of 45 studies If activity > background: sensitivity 77.4%, specificity 90.1% If max SUV 2.5: sensitivity 81.3%, specificity 79.4% Conclusion: Management cannot be based on PET/CT alone 20 Accuracy of FDG-PET within the clinical practice of the ACOSOG Z4301 trial to diagnose clinical stage I NSCLC (Ann Thorac Surg. 2014; 97:1142-1148). - 682 patients in sub-analysis, 83% prevalence - Sensitivity/specificity: 82%/31% - Positive predictive value: 85% - negative predictive value: 26% - 69% of false positive: granuloma 21 7
Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: A metaanalysis. (JAMA 2014;312: 1227-1236) Reviewed 1979 articles that can be used to calculate sensitivity/specificity Included 70 studies, 10 studies documented endemic infectious lung disease Pooled sensitivity/specificity among 70 studies: 89%/75% Pooled specificity among 10 studies: 54% Significant heterogeneity among studies 22 23 PET may underestimate the extent of thoracic disease in lung cancer patients. (Eur J Cardiothoracic Surg 2009;35: 781-785) Retrospective review PET/CT results compared to mediastinoscopy or formal resection 200 patients Correctly Staged Over Staged PET/CT 49.5% 29.5% (18.4% had 3A or higher stage) Under Staged 21% 24 8
25 Transthoracic biopsy of left upper lobe nodule: - moderately differentiated adenocarcinoma (TTF-1 positive, CK 5/6 negative) Brain MRI: negative Clinical stage 3B? (T1bN3M0) Treatment: Cisplatin and Etoposide concurrently with radiation therapy 26 27 9
Methods of Mediastinal Lymph Node Sampling Endobronchial Ultrasound (EBUS) Endoscopic ultrasound (EUS) Cervical mediastinoscopy Anterior mediastinotomy (Chamberlain procedure) Thoracoscopic biopsy (VATS or Robotic) Thoracotomy 28 Methods of Mediastinal Lymph Node Sampling Endobronchial Ultrasound - Useful for stations 1, 2, 4, 7 and 10 nodes - Sensitivity 79-95% - Specificity 100% CTSnet.org thelungconsultant.co.uk 29 Methods of Mediastinal Lymph Node Sampling Endoscopic Ultrasound Xx - -Useful for stations: 5 (AP window) 7 (Subcarinal) 8 (below carina) 9 (Inferior pulmonary ligam -Biopsy of left adrenal gland gland -Sensitivity 61-100% -Specificity 98-100% National Cancer Institute 30 10
Methods of Mediastinal Lymph Node Sampling Video Cervical Mediastinoscopy - Gold standard - Stations 1, 2, 4, 7, 10R - Sensitivity >90% - Specificity 100% 31 Methods of Mediastinal Lymph Node Sampling Video Cervical Mediastinoscopy Station 4L node Left recurrent laryngeal nerve 32 Methods of Mediastinal Lymph Node Sampling 33 11
Methods of Mediastinal Lymph Node Sampling Complications of cervical mediastinoscopy - Mortality: 0.05% - Morbidity: 1-5% - Left recurrent nerve injury: 1-5% - Pneumothorax: <1% - Tracheal injury: <1% - Esophageal injury: <1% - Major vascular injury: <0.1% - Will need median sternotomy 34 Methods of Mediastinal Lymph Node Sampling Anterior Mediastinotomy - Reliability not extensively documented - Sensitivity 33-52% - Specificity 100% For station 5 (aortopulmonary) nodes National Cancer Institute 2011 Rising Tide 35 Methods of Mediastinal Lymph Node Sampling Thoracoscopy - VATS Video Assisted Thoracic Surgery - Robotic 36 12
Methods of Mediastinal Lymph Node Sampling Management of clinical stage IIIA primary lung cancers in the national cancer database. (Ann Thorac Surg 2014;98:424-32) 83,913 patients with clinical IIIA with N2 disease, prior to therapy 1998-2011 Rate of mediastinal lymph node biopsy Non-surgically treated: 23% Surgically treated: 56% 37 Recommendations and Summary Many patients are treated based on staging by imaging only PET/CT cannot distinguish malignant versus non-malignant node Correct staging is crucial in evaluating prognosis and optimizing care Lung cancer staging what is the histologic nodal status? 38 Recommendations and Summary iphone App: Lung Cancer Stage 39 13
Questions? 2015 Rising Tide 40 14