Lung Cancer John Entwistle, MD PhD Associate Professor of Cardiothoracic Surgery Drexel University College of Medicine

Cancer Information

Epidemiology 15% of all cancer 15% of all cancer Leading cancer killer in U.S. Leading cancer killer in U.S. M:F almost 1:1 M:F almost 1:1 Smoking causes 87% Smoking causes 87% Radon - 12% Radon - 12% 10 Years after quitting risk is ½ to 1/3 rd that of current smokers 10 Years after quitting risk is ½ to 1/3 rd that of current smokers

Solitary Pulmonary Nodule (SPN) “Coin Lesion” < 3 cm diameter < 3 cm diameter Surrounded by aerated lung tissue Surrounded by aerated lung tissue No effusion, nodes, atelectasis No effusion, nodes, atelectasis 40% cancer 40% cancer 40% granulomas 40% granulomas 20% other (hamartoma, carcinoid, pulmonary infarct, etc) 20% other (hamartoma, carcinoid, pulmonary infarct, etc)

Clues to Etiology of SPN Clues to Etiology of SPN Age Age Age > 50 – malignant > benign Age > 50 – malignant > benign Smoking history Smoking history Current smokers have 10x risk than nonsmokers Current smokers have 10x risk than nonsmokers Nodule size Nodule size Larger suggests malignancy Larger suggests malignancy Nodule growth rate Nodule growth rate Infection > malignancy > benign lesion Infection > malignancy > benign lesion X-ray features X-ray features

Patterns of Calcification CentralLaminatedDiffuse PopcornStippledEccentric From Lillington GA. Pulmonary Disease and Disorders (1988) p.1947

Eccentric Calcification Medcyclopaedia.com

Evaluation of SPN History and physical History and physical CBC, Chem 7, LFTs CBC, Chem 7, LFTs Old x-rays Old x-rays Mayo Lung Project: 45 of 50 detected lung cancers on screening CXR were previously present in retrospect Mayo Lung Project: 45 of 50 detected lung cancers on screening CXR were previously present in retrospect CT scan of chest CT scan of chest

PET Scan and SPN “Identifies” nodule by quantifying glucose metabolism “Identifies” nodule by quantifying glucose metabolism Up to % sensitive Up to % sensitive Up to 80-90% specific Up to 80-90% specific Unproven clinical use Unproven clinical use Should not replace clinical judgment or sound medical decision-making Should not replace clinical judgment or sound medical decision-making

PET Scan and SPN Recommended for SPN 8 to 10 mm with low-to-moderate pre-test probability of lung cancer Recommended for SPN 8 to 10 mm with low-to-moderate pre-test probability of lung cancer Not recommended for: Not recommended for: Nodule < 8 mm Nodule < 8 mm Patient with high pre-test probability for lung cancer Patient with high pre-test probability for lung cancer

Predicting Probability of Malignancy Age = age in years; Smoke = 1 for current or former smoker; Cancer = 1 for extrathoracic malignancy > 5 yr ago; Diameter = diameter in mm; Spiculation = 1 if edges spiculated; Location = 1 if upper lobe Swenson et al, Arch Intern Med 1997;157:

Management of SPN Appears benign Appears benign Follow-up with serial imaging Follow-up with serial imaging Appears malignant Appears malignant Biopsy with or without resection, or Biopsy with or without resection, or Resection without biopsy Resection without biopsy Indeterminate diagnosis Indeterminate diagnosis Serial exams, or Serial exams, or Biopsy, or Biopsy, or Resection Resection

Tissue Diagnosis for SPN Sputum cytology Sputum cytology Very low yield Very low yield Bronchoscopy Bronchoscopy Size/location dependent Size/location dependent Yield as low as 10-20% Yield as low as 10-20% Transthoracic needle biopsy Transthoracic needle biopsy Positive in 75-95% of malignancies Positive in 75-95% of malignancies “Negative” result not helpful “Negative” result not helpful VATS VATS

SPN Patient #1 – M.D. 55 year old female 55 year old female “Light” smoker “Light” smoker Nodule seen on routine chest x-ray Nodule seen on routine chest x-ray Asymptomatic Asymptomatic

Initial CT Scan

3 Month Repeat Scan *

Now What? Repeat CT Scan? Repeat CT Scan? Bronchoscopy? Bronchoscopy? Needle biopsy? Needle biopsy? PET Scan? PET Scan? Surgery? Surgery?

Operative Specimen

SPN Patient #2 – C.B. 53 year old male 53 year old male Chronic smoker Chronic smoker Cough with mild hemoptysis Cough with mild hemoptysis Nodule seen on chest x-ray Nodule seen on chest x-ray

Initial CT Scan *

Now What? Repeat CT Scan? Repeat CT Scan? Bronchoscopy? Bronchoscopy? Needle biopsy? Needle biopsy? PET Scan? PET Scan? Surgery? Surgery?

4 Month Repeat Scan *

Now What? Repeat CT Scan? Repeat CT Scan? Bronchoscopy? Bronchoscopy? Needle biopsy? Needle biopsy? PET Scan? PET Scan? Surgery? Surgery?

7 Month Repeat Scan *

Now What? Repeat CT Scan? Repeat CT Scan? Bronchoscopy? Bronchoscopy? Needle biopsy? Needle biopsy? PET Scan? PET Scan? Surgery? Surgery?

Patient #3 43 year old male 43 year old male Heavy smoker Heavy smoker Chronic (“smoker’s”) mild cough, no hemoptysis Chronic (“smoker’s”) mild cough, no hemoptysis CXR showed RUL mass CXR showed RUL mass

CT Scan

PET Scan *

Now What? Repeat CT Scan? Repeat CT Scan? Bronchoscopy? Bronchoscopy? Needle biopsy? Needle biopsy? PET Scan? PET Scan? Surgery? Surgery?

Types of Lung Cancer Primary Primary Non-small cell cancer (NSSC) – 80% Non-small cell cancer (NSSC) – 80% Adenocarcinoma Adenocarcinoma Squamous cell Squamous cell Large cell Large cell Small cell (SCCA) – 20% Small cell (SCCA) – 20% Metastatic Metastatic Sarcomas Sarcomas Other Other

U.S. Male Cancer Death Rates Jemal et al. CA Cancer J Clin 2003;53:5-26

U.S. Female Cancer Death Rates Jemal et al. CA Cancer J Clin 2003;53:5-26

Lung Cancer Screening Sputum cytology – no benefit Sputum cytology – no benefit Chest x-ray Chest x-ray Detection rate low Detection rate low > 50% false positive (not detected on CT) > 50% false positive (not detected on CT) Low-dose CT scan Low-dose CT scan Detects large number of benign nodules Detects large number of benign nodules Does not decrease rate of late-stage ling cancer or death from lung cancer Does not decrease rate of late-stage ling cancer or death from lung cancer Estimated up to 10% of all cancers in future will be due to radiation from CT scans Estimated up to 10% of all cancers in future will be due to radiation from CT scans

Symptoms Pulmonary – dyspnea, cough, hemoptysis, wheeze, pneumonia Pulmonary – dyspnea, cough, hemoptysis, wheeze, pneumonia Non-pulmonary thoracic – chest pain, SVC syndrome, Pancoast syndrome Non-pulmonary thoracic – chest pain, SVC syndrome, Pancoast syndrome Paraneoplastic – joint pain, clubbing, muscular weakness Paraneoplastic – joint pain, clubbing, muscular weakness Metastatic – bone pain, neuro changes, weight loss Metastatic – bone pain, neuro changes, weight loss Nonspecific – anorexia, fatigue, weight loss Nonspecific – anorexia, fatigue, weight loss

Paraneoplastic Syndromes 2% of all lung cancer patients 2% of all lung cancer patients Small cell and squamous predominate Small cell and squamous predominate HPO – proliferating periostitis involving distal ends of long bones and clubbing (rare in Small cell) HPO – proliferating periostitis involving distal ends of long bones and clubbing (rare in Small cell) SIADH – hyponatremia, low serum osmolality, UOsm > 500. Usually in Small cell SIADH – hyponatremia, low serum osmolality, UOsm > 500. Usually in Small cell Hypercalcemia – with hypophosphatemia, due to ectopic PTH, usually with Squamous cell Hypercalcemia – with hypophosphatemia, due to ectopic PTH, usually with Squamous cell

Hypertrophic Pulmonary Osteoarthropathy (HPO)

Clubbing

Paraneoplastic Syndromes Myopathic and Neurologic Syndromes – most common group of paraneoplastic syndromes in lung Ca. Tend to occur late in disease Myopathic and Neurologic Syndromes – most common group of paraneoplastic syndromes in lung Ca. Tend to occur late in disease Carcinomatous myopathies – Eaton-Lambert (usually in small cell) Carcinomatous myopathies – Eaton-Lambert (usually in small cell) Cushing’s – ectopic ACTH-like substance. Not suppressible by dexamethasone (usually in small cell) Cushing’s – ectopic ACTH-like substance. Not suppressible by dexamethasone (usually in small cell)

Staging Studies Blood work (CBC, LFTs) Blood work (CBC, LFTs) Head CT Head CT If indicated by symptoms If indicated by symptoms If small cell carcinoma If small cell carcinoma Abdominal CT – to look at liver/adrenals Abdominal CT – to look at liver/adrenals Unsuspected liver or adrenal mets in 3-7% Unsuspected liver or adrenal mets in 3-7% Bone scan Bone scan If indicated by symptoms If indicated by symptoms If small cell carcinoma If small cell carcinoma PET scan – limited use PET scan – limited use

Survival by Stage

Lung Cancer Staging by Size Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9

Lung Cancer Staging by Location Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9

Staging of Multiple Nodules Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9

Lung Cancer Staging by Location

Nodal Staging Map Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9 N1

Nodal Staging Map Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9 N2

Nodal Staging Map Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9 N3

Stage by TNM Rice TW et al. J Thorac Cardiovasc Surg 2010;139:826-9

Other Studies Pulmonary function tests Pulmonary function tests Necessary if undergoing surgical resection Necessary if undergoing surgical resection MRI MRI Useful in limited situations Useful in limited situations Pancoast tumor to look at brachial plexus Pancoast tumor to look at brachial plexus Evaluation of involvement of spinal column Evaluation of involvement of spinal column

Patient #1 – Initial Presentation 65 y.o. male 65 y.o. male Cough, minimal hemoptysis Cough, minimal hemoptysis Smokes 2 ppd x 45 years Smokes 2 ppd x 45 years Bilateral leg pain Bilateral leg pain PEx: Thin, bilateral wheeze, clubbing of digits PEx: Thin, bilateral wheeze, clubbing of digits CXR: 2 cm RUL mass (new since last CXR) CXR: 2 cm RUL mass (new since last CXR) CT: 2 cm RUL mass with 1.5 cm pretracheal lymph nodes CT: 2 cm RUL mass with 1.5 cm pretracheal lymph nodes

Diagnosis/Staging Transthoracic needle biopsy Transthoracic needle biopsy Bronchoscopy Bronchoscopy Staging and tissue diagnosis Staging and tissue diagnosis Cervical mediastinoscopy Cervical mediastinoscopy Selective or routine Selective or routine Metastatic evaluation Metastatic evaluation

Mediastinoscopy

Mediastinoscopy

Patient #1 - Treatment T1N0M0 NSCCa T1N0M0 NSCCa 85% 5-year survival with surgical therapy 85% 5-year survival with surgical therapy Preoperative PFTs Preoperative PFTs Post-operative FEV1 > cc Post-operative FEV1 > cc Lobectomy vs. lesser resection Lobectomy vs. lesser resection Effect on pulmonary function Effect on pulmonary function Effect on local recurrence Effect on local recurrence Effect on survival Effect on survival

Patient #2 - Presentation 58 y.o. male 58 y.o. male Steady, severe shoulder pain radiating into ulnar aspect of right arm Steady, severe shoulder pain radiating into ulnar aspect of right arm Former smoker Former smoker PEx: No pain on motion of right shoulder, Horner’s syndrome PEx: No pain on motion of right shoulder, Horner’s syndrome CXR: Small shadow at apex of right lung CXR: Small shadow at apex of right lung

Pancoast Tumor

Patient #2 - Evaluation CT of chest – confirm mass lesion CT of chest – confirm mass lesion MRI – evaluate relationship of tumor to brachial plexus MRI – evaluate relationship of tumor to brachial plexus CT-guided needle biopsy (r/o SCCa) CT-guided needle biopsy (r/o SCCa) Mediastinoscopy if needed Mediastinoscopy if needed N2 patients are not candidates for resection N2 patients are not candidates for resection Possible arteriography/venography Possible arteriography/venography

Patient #2 - Treatment Preoperative radiotherapy – 30 to 45 Gy Preoperative radiotherapy – 30 to 45 Gy Resection via posterolateral thoracotomy Resection via posterolateral thoracotomy Enter chest below lowest rib to be resected Enter chest below lowest rib to be resected Confirm resectability Confirm resectability Resect ribs, intercostal m. en bloc w/ tumor Resect ribs, intercostal m. en bloc w/ tumor Divide T1 (and C8, if needed) Divide T1 (and C8, if needed) Ligate SC Vein, repair SC artery, if needed Ligate SC Vein, repair SC artery, if needed Upper lobectomy Upper lobectomy

Pancoast Tumor Resection

Complications of Pancoast Resection CSF leak CSF leak Horner’s syndrome Horner’s syndrome Atrophic paralysis of forearm and intrinsic muscles of hand (if C8 resected) Atrophic paralysis of forearm and intrinsic muscles of hand (if C8 resected) Chylothorax Chylothorax Arm edema (if SC vein divided) Arm edema (if SC vein divided)

Patient #3 – Initial Presentation 62 y.o. female 62 y.o. female Left sided chest pain, constant, dull Left sided chest pain, constant, dull Chest CT – mass in LUL, adherent to chest wall with obliteration of tissue planes Chest CT – mass in LUL, adherent to chest wall with obliteration of tissue planes T3N0M0 tumor T3N0M0 tumor 40% five-year survival if completely resected 40% five-year survival if completely resected

Chest Wall Resection Must resect chest wall en bloc with primary tumor Must resect chest wall en bloc with primary tumor Some will do extrapleural dissection if tumor only goes to parietal pleura Some will do extrapleural dissection if tumor only goes to parietal pleura Reconstruction of chest wall Reconstruction of chest wall For larger defects For larger defects For anterior defects For anterior defects For lower posterior defects For lower posterior defects

Patient #4 – Presentation 53 y.o. male 53 y.o. male Cough, dyspnea Cough, dyspnea Smokes 2 ppd x 45 years Smokes 2 ppd x 45 years CXR: Right hilar mass CXR: Right hilar mass Bronchoscopy: Tumor involving orifice of RUL bronchus Bronchoscopy: Tumor involving orifice of RUL bronchus CT scan: 1.5 cm nodes CT scan: 1.5 cm nodes Mediastinoscopy: reactive nodes Mediastinoscopy: reactive nodes PFTs: FEV1 1.3 PFTs: FEV1 1.3

Right Hilar Mass

Endobronchial Lesion

Management Options Lobectomy – will leave residual tumor Lobectomy – will leave residual tumor Pneumonectomy – unable to tolerate Pneumonectomy – unable to tolerate Chemo-radiation therapy as sole treatment – poor survival results Chemo-radiation therapy as sole treatment – poor survival results Sleeve resection of RUL – will leave functioning RML and RLL Sleeve resection of RUL – will leave functioning RML and RLL

Sleeve Lobectomy Lower morbidity and mortality than pneumonectomy Lower morbidity and mortality than pneumonectomy Comparable cure rates to pneumonectomy if it can be completely resected Comparable cure rates to pneumonectomy if it can be completely resected Not possible if there is peribronchial lymphatic invasion Not possible if there is peribronchial lymphatic invasion

Sleeve Resections

Advanced-Stage Lung Cancer Not amenable to surgical resection if: Not amenable to surgical resection if: “Bulky” mediastinal adenopathy “Bulky” mediastinal adenopathy Invasion of non-resectable structures Invasion of non-resectable structures Supraclavicular or contralateral nodes Supraclavicular or contralateral nodes Malignant pleural effusion Malignant pleural effusion Treated with chemo-radiation therapy Treated with chemo-radiation therapy May consider post-treatment resection for responders with excellent risk factors May consider post-treatment resection for responders with excellent risk factors

Isolated Brain Metastasis Median survival less than 3 months Median survival less than 3 months If sole site of mets, may undergo resection of brain met followed by resection of lung primary If sole site of mets, may undergo resection of brain met followed by resection of lung primary 20% 5-year survival 20% 5-year survival

Patient # 5 - Presentation 65 y.o male 65 y.o male Former smoker (40 pack-years) Former smoker (40 pack-years) Routine CXR (for preop clearance) shows 2 cm nodule centrally located Routine CXR (for preop clearance) shows 2 cm nodule centrally located CT scan: Mediastinal adenopathy CT scan: Mediastinal adenopathy Mediastinoscopy: Small cell carcinoma Mediastinoscopy: Small cell carcinoma

Small Cell Carcinoma Staging: Limited vs. Extensive disease Staging: Limited vs. Extensive disease “Limited” is ipsilateral lung with thoracic nodes (may include contralateral hilar) “Limited” is ipsilateral lung with thoracic nodes (may include contralateral hilar) Frequently metastatic Frequently metastatic CBC, LFTs, bone scan, CT abd CBC, LFTs, bone scan, CT abd Bone marrow if abnormal hematologic studies Bone marrow if abnormal hematologic studies Always treated with chemotherapy Always treated with chemotherapy 70% response rate to multi-agent Rx (31% complete) 70% response rate to multi-agent Rx (31% complete) Radiation is added to responders with limited disease Radiation is added to responders with limited disease