Lung Cancer Update. Disclosures. None
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1 Lung Cancer Update Ronald J Servi DO FCCP Adjunct Assistant Professor Department of Pulmonary Medicine University of Texas MD Anderson Cancer Center Banner MD Anderson Cancer Center Gilbert, Arizona Disclosures None
2 Learning Objectives Understand today s options for prevention and screening for lung cancer. Understand the correct approach for diagnosis and staging of lung cancer. Understand the rapidly changing treatment options for lung cancer in Approach to Lung Cancer in 2018 Prevention Screening Diagnosis/Staging Treatment Chemotherapy: Newer Approaches Targeted Therapy Immunotherapy Radiation Therapy Surgical Therapy Combined Therapies
3 Lung Cancer Epidemiology 2017 Expected New Cancer Cases
4 2017 Expected Cancer Cases and Deaths An Ounce of Prevention
5 Prevention Lung Cancer Screening
6 Lung Cancer Leading cause of cancer death More deaths than colon, breast, prostate and pancreatic cancers combined Stage I: Five year survival 61% Stage IV: Five year survival 13% Overall 5 year survival is about 18% 75% present with locally advanced/metastatic More effective strategy of early detection should lead to earlier stage and better outcomes Lung Cancer Screening is Not New
7 Chest CT Routine Low-dose 938mGy/cm 15.9 msv 88mGy/cm 1.5 msv Smith-Bindman, N Engl J Med 2010; Lung Cancer Screening
8 The National Lung Screening Trial Research Team N Engl J Med Volume 365(5): August 4, 2011 National Lung Screening Trial (NLST) Prospective, Randomized, Multicenter Low Dose CT vs CXR High Risk Patients years old 30 pack years Active smokers or quit < 15 years ago Low dose CT or CXR baseline then annually for two years N = 53,454
9 NLST - Screen Positivity Rate LDCT # of exams # of positives %of positives T0 26,314 7, T1 24,718 6, T2 24,104 4, ** Total 75,136 18, A positive screen is one that may be suspicious for lung cancer **A suspicious abnormality that has been stable for 3 rounds may be called negative NEJM Aug 4, 2011 Lung Cancer Screening: False Positives % Lung Cancer LDCT % False Positive T T T Total NEJM Aug 4, 2011
10 NEJM Aug 4, 2011 Causes of Death 6.2% decrease in all cause mortality in LDCT
11 Lung Cancer Screening Complications LDCT 1.4% at least one complication 96.4% false positive CXR 1.6% at least one complication 94.5% false positive 16 deaths within 60 days of procedure Included are 6 patients without cancer
12 Medicare Coverage: LDCT Coverage for Medicare Beneficiaries as of 2/5/ years old At least 30 pack year history Current smokers or quit within the last 15 years Written order and follow up visit Counseling Patient Radiologists and imaging facilities must meet quality standards Collect and submit required data elements to a CMS-approved national registry Lung Cancer Diagnosis and Staging
13 Staging Accurate staging is critical Provides a common language when discussing cases Treatment options are stage dependent Prognosis is based upon stage Enrollment in clinical trials by stage Allows for study of large cohorts of patients Size of Tumor
14 Intrathoracic Lymph Node Anatomy Gen Thorac Cardiovasc Surg (2008) 56: Nodes
15 Staging Noninvasive Lung Cancer Staging Noninvasive Staging CT Chest PET Scan
16 Invasive Lung Cancer Staging Surgical (Mediastinoscopy) Invasive Staging Non Surgical (EBUS) Noninvasive Staging Limitations PET CT is the Swiss Army Knife of Oncology PET CT is not the Holy Grail False Positive False Negative Quality of PET CT Scans Varies Quality of PET CT Interpretations Varies
17 Noninvasive Mediastinal Staging Test Sensitivity Specificity CT (N=7368) 55% 81% PET (N=4105) 80% 88% Pooled data from 43 CT and 45 PET trials Imaging modalities are neither sensitive nor specific enough for definitive mediastinal staging CHEST 2013; 143(5)(Suppl):e211S e250s Accuracy of Invasive Staging Tests Test # Studies #Patients Sensitivity Specificity Mediastinoscopy 35 10, EUS 26 2, EBUS 26 2, EBUS/EUS CHEST 2013; 143(5)(Suppl):e211S e250s
18 Traditional Linear Process NSCLC diagnosis Imaging Non Invasive Staging CT Chest/CT-PET scan CT/MRI Brain Invasive Staging Tissue sampling Treatment Plan Parallel Process Treatment decisions require both tissue diagnosis and staging information Non invasive mediastinal staging is neither sensitive nor specific enough to make treatment decisions. Tissue confirmation is recommended for suspected mediastinal nodal disease Whenever possible obtain both staging and diagnostic information at the same time (parallel process) Is it cancer? Treatment Decision What stage?
19 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines 2013 Diagnosis & staging should be done efficiently. Tissue diagnosis should be obtained from the site that defines the highest stage if feasible. In patients with enlarged discrete mediastinal lymph nodes on CT scans further evaluation of the mediastinum should be performed If there is evidence of intra-thoracic nodal disease and no evidence of distant metastases, this should be the initial target for tissue sampling rather than biopsy of the lung parenchymal lesion. Ost DE. Chest May;143(5 Suppl):e121S 41S 137 consecutive patients referred for mediastinal staging of NSCLC Only 22% received guideline consistent care Guideline consistent care had 1.3 tests/patient vs 2.3 tests/patient EBUS would have been sufficient for diagnosis and staging in 64% Guideline consistent care had fewer complications (0 of 30, 0% vs 18 of %) 2/3 complications could have been avoided just by changing test sequencing Almeida FA. Chest Dec;144(6):
20 EBUS Mediastinal Staging EBUS-TBNA Fairly new diagnostic procedure (1999) -2002: Convex probe (real-time guidance) Developed for lymph node staging Other diagnostic uses Intrapulmonary tumors Unknown hilar or mediastinal LAD Mediastinal tumors
21 EBUS-TBNA Images obtained by attaching a balloon and inflating with normal saline Image is processed Lesions can be measured Images can be frozen and photographed Doppler Mode 19,21,22 gauge needle
22 EBUS Navani N, Brown JM, Nankivel M et al. Am J Respir Crit Care Med 2012;185(12):
23 Case Presentations Intrathoracic Lymph Node Anatomy Gen Thorac Cardiovasc Surg (2008) 56:
24 65 year old male Case Report: YY Trivial Smoking History History of TB Evaluation of abnormal PET CT LUL SPN: 2.7 x 1.8 cm (SUV 6.4) Left hilum (SUV 3.2) Enlarged LN 4R and LN 7: Not FDG avid YY 5/21/ YEAR M OUTCOMP PET/CT SCAN Fused Transverse [WB_CTAC] Body 6/27/2014 3:59:41 PM 6/27/2014 3:59:42 AM OUTCOMP279554A
25 EBUS: YY LN 11L, LN 11R, negative LN 7, LN 4R positive for malignancy Stage T1bN3Mx = Stage IIIB Case Report: CC 70 year old former smoker Normal PFT PET CT 7 cm RLL Mass SUV 7.6 Needle Biopsy: Mucinous Adenocarcinoma No other abnormalities
26 Case Report: CC EBUS: CC LN 11L, LN 11R, LN 4R all negative LN 7 positive for malignancy Stage T3N2Mx = Stage IIIA
27 Case Report: DS 69 year old smoker Biopsy RLL Mass : Adenocarcinoma Referred for EBUS Staging Case Report: DS
28 DS Adenocarcinoma (Lung) 4R and 4L Positive Stage IIIB: T2b N3 M0 Case Report: BV 76 year old never smoker CT for evaluation of abdominal pain
29 BV BV: PET 4R, 4L
30 BV: PET 10R BV Final Results Pre-EBUS T1N2M0 (Stage IIIA) Post-EBUS T1N0M0 (Stage IA) RLL resection with LND Stage IA Adenocarcinoma confirmed
31 Lung Cancer Treatment Overview of NSCLC Treatment Stage I Stage II Stage III Stage IV or Recurrent Disease Surgery (Radiation if inoperable) Surgery With Adjuvant Chemotherapy Radiation Chemotherapy Immunotherapy?Surgery Chemotherapy Targeted Therapy Immunotherapy
32 Lung Cancer Treatment Timeline Katerina Politi, and Roy S. Herbst Clin Cancer Res 2015;21: Treatment: Targeted Therapy
33 The Rise of Targeted Therapy Therapeutic Targeting
34 NSCLC Heterogeneity Winer et al. JCO Feb ;5(10): Squamous Cell Carcinoma Am J Respir Crit Care Med Aug 1; 192(3):
35 Patient with EGFR Mutation Deletion Exon 19 Treatment with Erlotinib Courtesy of Dr. Anne Tsao Standard Approach To Genetic Testing Targeted therapy not yet indicated in stage I or II outside clinical trials Molecular testing should be performed for more advanced disease (stage III or IV) Mutation panels are now readily available at reasonable cost EBUS TBNA specimens are adequate for mutational analysis Emerging roles for liquid biopsies Ettinger et al, NCCN Guidelines 2012.
36 Treatment: Immunotherapy Rise of Immunotherapy Long-term disease control against recalcitrant cancers Game-changing discoveries more coming Ipilimumab introduced for melanoma Pembrolizumab, nivolumab approved for melanoma PD-1/L-1 drugs benefit even more of cancers 2016 ASCO Advance of the Year
37 Rise of Immunotherapy On the Horizon: CART-cell therapy Customized vaccines Radiation Therapy
38 Stereotactic Radiotherapy (SBRT) Courtesy of Dr Dan Chamberlain SBRT vs Wedge Resection Journal of Clinical Oncology 28, no. 6 (February 2010)
39 Surgical Treatment Video Assisted Thoracic Surgery (VATS)
40 Combined Therapies Case Report: RJ 9/5/ YEAR F A CT Lung Screening CHEST 2.5MM STND 10/7/ :44:42 AM LOC : THK: 2.50 FFS 9/5/ YEAR F A CT Lung Screening CHEST 2.5MM STND 10/7/ :44:42 AM LOC : -215 THK: 2.50 FFS R L R L RD: 360 Tilt: 0 ma: 222 KVp: 100 Acq no: 1 Page: 49 of 136 P cm Z: 1 C: -585 W: 1800 DFOV:36x36cm Compressed 8:1 IM: 49 SE: 2 RD: 360 Tilt: 0 ma: 227 KVp: 100 Acq no: 1 Page: 82 of 136 P cm Z: 1 C: -585 W: 1800 DFOV:36x36cm Compressed 8:1 IM: 82 SE: 2
41 PET CT: RJ Case Report RJ Bronchoscopy with EBUS 10/21/14 RUL Mass Brush: Squamous Cell Carcinoma EBUS of 4R, 7, 11L: Negative Needle Biopsy LLL Mass Squamous Cell Carcinoma Treatment RUL Lobectomy 12/5/14 SBRT LLL 11 mm SPN LLL 3/23/17 Adenocarcinoma treated SBRT NED January 2018
42 Summary Prevention Screening Diagnosis/Staging Treatment Chemotherapy: Newer Approaches Targeted Therapy Immunotherapy Radiation Therapy Surgical Therapy Combined Therapies
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