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Andrea McKee, M.D. Chairman Department Radiation Oncology Sophia Gordon Cancer Center Lahey Clinic May 15, 2012. Disclosures. None. Outline. Lung Cancer Background Incidence/Mortality National Lung Screening Trial (NLST) National Comprehensive Cancer Network (NCCN)
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Andrea McKee, M.D. Chairman Department Radiation Oncology Sophia Gordon Cancer Center Lahey Clinic May 15, 2012
Disclosures • None
Outline • Lung Cancer Background • Incidence/Mortality • National Lung Screening Trial (NLST) • National Comprehensive Cancer Network (NCCN) • Lung Cancer Screening at Lahey Clinic • Program Structure • Structured Reporting • LUNG-RADS Classification System • Challenges • Rescue Lung, Rescue Life
Lung CancerIncidence/Mortality: US • Number one cause of cancer-related death in the US and World • Kills more women than Breast, Ovarian, and Uterus Cancer Combined 200K new cases/yr 160K deaths/yr
Tobacco Trends • History of tobacco use • <20% in 2006 • 42% in 1965 • Demonization campaign • Higher prevalence • Military (1 in 3) vs (1 in 5) • Less educated • Higher risk • Rescue workers • Occupational exposure
Tobacco Trends Competition has been tough - tobacco industry, Hollywood, press Guard against withholding of health care services or advocacy based on social history – slippery slope
Lung CancerIncidence/Mortality: US • Primary Prevention (Smoking Cessation) Success • Decreased number of overall lung cancer deaths in US • Despite success 160K still die every year from lung cancer • Most people who die from lung cancer now are FORMER SMOKERS
Lung CancerIncidence/Mortality: US • Primary Prevention (Smoking Cessation) Success • Decreased number of overall lung cancer deaths in US • Despite success 160K still die every year from lung cancer • Most people who die from lung cancer now are FORMER SMOKERS • 35% of Lung Cancer Diagnosis Current Smokers • 50% of Lung Cancer Diagnosis Former Smokers • 15% of Lung Cancer Diagnosis Never Smokers • Lung Cancer 5-Year Overall Survival Remains Unchanged • 1975 12%, Current 15%
Lung CancerIncidence/Mortality: US • Primary Prevention (Smoking Cessation) Success • Decreased number of overall lung cancer deaths in US • Despite success 160K still die every year from lung cancer • Most people who die from lung cancer now are FORMER SMOKERS • Lung Cancer 5-Year Overall Survival • 1975 12%, Current 15% • Stagnant survival result of absent Secondary Prevention • FORMER SMOKERS cannot benefit from PRIMARY PREVENTION • Secondary Prevention = LUNG SCREENING • LUNG SCREENING Find disease at early more treatable stage • LUNG SCREENING GOAL Decrease Mortality not Incidence
Lung Cancer ScreeningData to support screening been around awhile • NEJM October 2006 • 31,567 patients baseline screened with low dose CT from 1993-2005 • 484 lung cancers detected (85% clinical stage I) • 10 year survival 92% for those having surgery • 8 patients refusing therapy died within 5 years of diagnosis
Lung Cancer TreatmentNSCLC: Unscreened Population NSCLC Stage I, II, IIIA Potential Cure Surgical resection Radiotherapy Chemotherapy Stage IIIB/IV Palliative Goldstraw P, Crowley J, Chansky K, et al. (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714.
Stage IV NSCLC <1% = 5 year OS
Incidental Finding on CXR Stage T1BN0 58% 5-year Overall Survival Goldstraw P, Crowley J, Chansky K, et al. (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714.
Annals of Internal MedicineOctober 2011 • 62 year-old female with a history of well-controlled hypertension presents for routine follow-up. She is asymptomatic and feels well. She has jogged 3 miles 3 times weekly for years with no recent change in exercise tolerance. She has a 30 pack-year history of tobacco use but quit 10 years ago. Normal physical exam. She read a recent study that found a benefit to screening with LDCT and inquires if this is appropriate for her? • What should you recommend?
Secondary PreventionPreclinical Diagnosis: Screening Awareness 5mm nodule 6 month fu diagnostic CT recommended 7mm NSCLC treated with lobectomy and nodal evaluation T1aN0 (screened) What is this patient’s 5-year overall survival?
Secondary PreventionPreclinical Diagnosis: Screening Awareness 92% = 5 year OS
Secondary PreventionPreclinical Diagnosis: Screening Awareness 85% of patients in screened population have stage I lung cancer Asymptomatic 58% 5-year OS Screening Symptomatic Stage I 92% 10-year OS Stage IV 1% 5-year OS
US Cancer Mortality RatesSecondary Prevention U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2007 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2010. Available at: www.cdc.gov/uscs.
US Cancer Mortality RatesSecondary Prevention PSA Mammography Colonoscopy U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2007 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2010. Available at: www.cdc.gov/uscs.
National Lung Screening Trial(NLST): 6/29/2011 National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.
National Lung Screening TrialDesign Overview • Multicenter Randomized Controlled Trial • Sponsor: NCI Division of Cancer Treatment and Diagnosis • 33 US Screening Centers • NCI Division of Cancer Prevention (LSS) • American College of Radiology Imaging Network (ACRIN) • $300,000,000 +
National Lung Screening TrialDesign Overview • 53,456 participants • Enrolled 2002 – 2004 • Ages 55-74 • Greater than 30 pack-year smoking history • Active or quit < 15 years • Exclusions • Metallic implants chest or back • Treatment or evidence of cancer in previous 5 years • History of lung cancer • Prior lung resection except needle biopsy • Home O2 requirement • Symptoms: Hemoptysis, weight loss, treated respiratory infection within past 12 weeks • Chest CT within previous 18 months • Participation in other cancer screening/prevention trial • Unable to lie on back with arms above head National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.
National Lung Screening TrialDesign Overview • Treatment Arms: • Low Dose Chest CT (1.5 mSv) • PA Chest Radiograph (0.02 mSv) • Screening Intervals: • T0: Baseline prevalence screen • T1: Year 1 incidence screen • T2: Year 2 incidence screen • Positive Test • Non-calcified nodule greater than 4mm in mean diameter • Other findings suspicious for lung cancer (adenopathy, effusion…) • Workup of positives determined by PCPs not NLST • NLST reading radiologist recommendation available
National Lung Screening TrialResults: Mortality • Lung cancer specific mortality • 20% reduction in lung cancer specific mortality • LDCT = 356 deaths, CXR = 443 deaths • Median follow-up 6.5 years • Overall mortality • 6.6% reduction in overall mortality • LDCT = 1877 deaths, CXR = 2000 deaths • Not statistically significant when lung cancer deaths excluded National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.
National Lung Screening TrialResults: Other • Lung cancer prevalence: 1% • 1 in 100 at risk patients have cancer • Lung cancer annual incidence: 0.5 – 0.8% • Decrease in # of late stage cancers in CT group vs CXR • Real stage shift not just overdiagnosis • Small cell lung cancer • Not detected at earlier stage • Overrepresented as interval cancers • Number Needed to Screen (NNS) is 320 National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.
National Lung Screening TrialResults: Rate of Positive ScreeningsAq • CT (24.2%) > 3x more sensitive than CXR (6.9%) • T0 & T1 Rate: 27-28% • T2 Rate: 16.8% • 2 year stability benign (Fleischner Guidelines) • Expected rate for ongoing LDCT screening • At least one positive result (3 screens): 39.1% • Significant incidental finding: 7.5% • Not screening everyone – highly selected group (3%) National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365(5):395–409.
National Lung Screening TrialResults: Positive Workup/Adverse Events • False Positives • Most have noninvasive imaging follow-up • CXR: 14.4% • Chest CT: 49.8% • PET/CT: 8.3% • Invasive diagnostic procedures: 2.6 % • Complication rate: 1.4% • Major complication rate: 0.06% • True Positives • Invasive procedure major complication: 11.2% • Surgical resection mortality: 1%
NLSTResults: False Positive Workup/Adverse Events • False Positive Rate: • 20-25%: Chance you will end up with a false positive • ~10-12% for Mammography (“Call back”) • False Discovery Rate (1-PPV): • 96%: Chance if you are positive you do not have cancer • Same as mammography • False Positive Biopsy Rate • 0.4-2.4%: Chance if screened you will have an unnecessary invasive procedure (LDCT) • 7-15%: Chance if you end up having a biopsy it will be negative (mammography).
NLST NEJM 6/29/2011 NCCN 10/26/2011 • NLST Summary • 20% lung cancer mortality benefit • 7% overall mortality benefit • 1 in 100 has lung cancer • NNT = 320 • Opportunity to save 30,000 lives/yr • NCCN Considerations • Prolonged debate • Cost to Society • Patient anxiety • Radiation exposure • False positives/informed consent • Operational concerns
National Comprehensive Cancer Network (NCCN): 10/26/2011 NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org
NCCN RecommendationCategories NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org
NCCN RecommendationCategories NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org
NCCN High-Risk Group 2Risk Factors • Personal Cancer History • Lung, lymphoma, smoking related cancers • Family History Lung Cancer in 1st Degree Relative • Chronic Lung Disease • Emphysema • Pulmonary Fibrosis • Carcinogen Exposure • Arsenic, asbestos, cadmium, chromium, diesel fumes, nickel, radon, silica
NCCN GuidelinesSolid or Part Solid Nodules Follow-up NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org
Lung Cancer ScreeningRisks and Benefits (NCCN) NCCN Guidelines® for Lung Cancer Screening (V.1.2012) www.nccn.org
Overdiagnosis, Survival, Mortality Survival Diagnosis Death
Overdiagnosis, Survival, Mortality Survival Mortality Diagnosis Death
Lung Cancer Mortality Survival Mortality 365 Death due to lung cancer = 20% 443 Diagnosis Death
Overall Mortality Survival Mortality 1877 Death due to any cause across entire group= 6.6% 2000 Diagnosis Death
Overall Survival Benefit 7%Adjuvant Therapy Reduces Risk • Breast cancer • ACT chemotherapy • 5 years anti-estrogen therapy • Post-mastectomy RT • Prostate Cancer • Post prostatectomy RT • Head and Neck cancer • Post-operative chemoRT • Cervix Cancer • Post-operative chemoRT • Medical-legal consequences
OverdiagnosisDetermine time and cause of death in those patients diagnosed and treated for lung cancer Mortality Diagnosis Death
CT Lung Cancer ScreeningMorbidity • Radiation exposure • MDCT resolution allows for dose reduction • LDCT <1mSv, Mammography 0.7mSv 1 mSv 10 mSv
Radiation Exposure 10 -30 year latency period to develop secondary malignancies from RT exposure Average age of patients in screening trials is 62
LUNG-RADSOverview • Purpose: Establish a standardized quality assurance tool to mirror the tool widely utilized in Mammography (BI-RADS). • Objectives: • Standardize terminology • Organized reporting and assessment structure • Data collection tool to facilitate outcome monitoring
LUNG RADS Lung Number Category “S” Category Positive for extra-pulmonary finding not suspicious for lung cancer but requiring clinical follow-up Thyroid mass Aneurysm Kidney Mass • Category 1: Negative (12mo) • Category 2: Negative with benign pulmonary findings (12mo) • Category 3: Positive/likely benign (follow-up per NCCN guidelines) • Category 4: Positive/suspicious for malignancy • Category 5: Known cancer
LUNG RADS Lung Number Category “S” Category Positive for extra-pulmonary finding not suspicious for lung cancer but requiring clinical follow-up Thyroid mass Aneurysm Kidney Mass Fracture • Category 1: Negative (12mo) • Category 2: Negative with benign pulmonary findings (12mo) • Category 3: Positive/likely benign (FU per NCCN guidelines) • Category 4: Positive/suspicious for malignancy • Category 5: Known cancer
An Actuarial Analysis Shows That Offering Lung Cancer Screening As An Insurance Benefit Would Save Lives At Relatively Low Cost • Cost per life-year saved would be below $19,000 Pyenson et al, Health Affairs 31, No.4 770-779: April 2012