Educational Objectives. Managing Lung Cancer From the Solitary Pulmonary Nodule to Complex Cases: A Multidisciplinary Approach.

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Managing Lung Cancer From the Solitary Pulmonary Nodule to Complex Cases: A Multidisciplinary Approach Robert A. Meguid, MD, MPH, FACS Assistant Professor of Cardiothoracic Surgery Surgical Director, Surgical Outcomes & Applied Research Surgeon Champion, UCH NSQIP No Disclosures Educational Objectives Review work up of solitary lung nodules Utility of the multidisciplinary approach to lung cancer management

Case 1 A 67 year old woman Undergoes annual chest X-ray for routine follow up of lymphoma New 2.5cm lung nodule in the right upper medial lung field Case 1 History: HPI: Intermittent dry cough No weight loss, fever, chills, fatigue, change in voice PMHx: Non-Hodgkins Lymphoma 2011, s/p Chemotherapy Overweight, unable to loose weight Hypertension SHx: Used to smoke 1 pack of cigarettes per day for 33 years, quit 14 years ago. (33 pack years) Case 1 History: FHx: Father died of MI @ 63 yrs Mother died of breast cancer @ 72 yrs Brother died in work injury @ 47 yrs All: NKDA Meds: HCTZ 25mg Multivitamins ROS: non-contributory

Case 1 Physical Exam: Vitals: 37.6F, 82 bpm, 150/70 mm Hg General: overweight, older woman HEENT: normocephalic, no adenopathy Pulm: Lungs clear to auscultation bilaterally Cor: RRR, no M/R/G Abd: soft, non-tender, non-distended Extr: warm, well perfused, no edema Next Step in Workup Interested in RUL lung nodule Lab studies? Imaging? Pulmonary function testing? Lung Nodule Workup: Imaging Characterize lesion radiographically Appearance Location Any other findings? Nodules, enlarged lymph nodes, infiltrates, effusion Appearance of remainder of lung Guide future steps in workup

Lung Nodule Workup: Imaging Chest X-ray Limited resolution, may not be able to see medial structures Does not provide detailed 3-D location Does not provide many details about character of lesion Radiologists & other providers not as adept at reading these days... Lung Nodule Workup: Imaging PET-CT Positron Emission Tomography-CT Demonstrates areas of fluorodeoxyglucose (FDG) uptake Highlights metabolically active cells» Brain, cardiac muscle, kidneys» Tumor cells» Infections Can t distinguish between malignant and inflammatory/ infectious nodules 1 cm is current limit of resolution No breath hold, takes time for scan Lung imaging may be obscured by breathing motion artifact Useful after tissue diagnosis of cancer: evaluating mediastinal nodes and elsewhere in body for metastatic disease Lung Nodule Workup: Imaging Non-contrast CT scan of chest Breath hold protocol to optimize resolution of lung Characterize lesion radiographically Appearance Location Any other findings:» Other lung nodules» Mediastinal & parenchymal Lymph Nodes» Infiltrates» Effusion Appearance of remainder of lung» Bullous emphysema/ bronchiectasis

Case 1: Chest X-Ray Case 1: PET-CT Case 1: Non-contrast Chest CT

Case 1: Non-contrast Chest CT demonstrates 23 x 20 mm RUL nodule No axillary, supraclavicular, mediastinal or hilar lymphadenopathy Enlargement of R pulmonary artery Efficient in work up of a Lung Nodule: Tissue diagnosis guides therapy Inflammatory No additional treatment, +/- surveillance Infectious Additional treatment Antibiotics/ antifungals Resection? Malignancy Type of cancer Differentiate between metastatic to lung & primary lung Ca Stage-driven treatment Efficient in work up of a Lung Nodule: Obtaining tissue diagnosis: Trans-thoracic needle biopsy Fine-needle aspiration Core needle biopsy Endobronchial ultrasound-guided needle biopsy Navigational bronchoscopic-guided biopsy Video-Assisted Thoracic Surgery (VATS) excisional biopsy

Trans-Thoracic Needle Biopsy CT-guided biopsy Usually peripheral lesions Limitations/ Contraindications: Emphysematous lung Central lesions Adjacent vasculature Accuracy based on experience of interventionalist What to do with a negative biopsy? Endobronchial Ultrasound (EBUS) Useful for lesions adjacent to trachea or mainstem bronchi Mainly used for sampling mediastinal lymph nodes Endoscopic Ultrasound (trans-esophageal) useful for lesions adjacent to distal esophagus Limitations/ Contraindications: Distal & peripheral lesions Adjacent vasculature Accuracy based on experience of interventionalist What to do with a negative biopsy? Navigational Bronchoscopy Electromagnetic Navigational Bronchoscopy Useful for lesions in proximal to middle lung Limitations/ Contraindications: Distal lesions (mark with fiducial) Adjacent vasculature Medial apical/ basal lesions Accuracy based on experience of interventionalist What to do with a negative biopsy?

Video-Assisted Thoracic Surgery (VATS) Biopsy & Treatment Core needle biopsy Resect nodule Resect anatomic segment or lobe Can reach lesions throughout lungs Can concurrently sample LNs, pleura, pleural fluid Limitations/ Contraindications: Pt wont tolerate surgery Prior to surgery: Pulmonary Function Testing to ensure adequate postop predicted function Non-malignant biopsy usually conclusive Case 1: PFTs: FEV1 1.9L (103%), DLCO/VA 111% TTE: no pulmonary artery HTN Right VATS wedge resection Right upper lobe nodule Visible on surface of visceral pleura 2.5 x 1.7 x 1.2cm Squamous Cell Carcinoma with visceral pleural involvement Treatment: Lobectomy Mediastinal lymph node sampling Complete staging Hilar nodes, mediastinal nodes (4R, 7, 8R, 9R) Case 1: Postoperative course: Uneventful Chest tube removed POD#2 Discharged on POD#4 on oxycodone Final pathology: Stage IB (T2aN0M0) squamous cell carcinoma 0/26 lymph nodes positive Treatment: follow up with CT imaging Q6 mo x 2 yrs, then yearly (NCCN guidelines)

Non-Small Cell Lung Cancer Staging * AJCC 7 th Edition Mediastinal Lymph Nodes * Mountain-Dressler regional lymph node classification Non-Small Cell Lung Cancer Treatment * Spira, Ettinger, NEJM 2004

Case 2: 72 yo M 60 pack year former smoker Enlarging right middle lobe nodule on CT PET-CT performed, no distant disease PFTs: FEV1 74%, DLCO/VA 63% TTE: normal EF, no pulmonary artery HTN Case 2: Underwent VATS right middle lobectomy & mediastinal LN biopsy 5 day hospital stay Pathology: 2.9 x 2.3 x 2.0 cm Squamous Cell Carcinoma with multiple hilar nodes with tumor Stage IIA (T1bN1M0) Referral to Med Onc for adjuvant chemotherapy Case 3: 75 yo F 45 pack year smoker Multiple lung nodules on screening chest CT RUL nodule 1: 14x12 mm RUL nodule 2: 12x11 mm

Case 3: 75 yo F 45 pack year smoker Multiple lung nodules on screening chest CT RUL nodule 1: 14x12 mm RUL nodule 2: 12x11 mm LLL ground glass opacity: 17 mm LLL cavitary nodule: 15mm Enlarged R hilar and paratracheal lymph nodes Case 3: Review at Lung Cancer Multidisciplinary Conference: RUL nodules suspicious for cancer Recommend: CT-guided biopsy If positive for cancer: PET-CT, MRI brain, PFTs, TTE LLL cavitary nodule indeterminate Recommend: watching LLL GGO Recommend: watching Case 3: CT-guided Needle Bx: RUL nodule 1: Adenocarcinoma RUL nodule 2: nondiagnostic PET-CT: 2 RUL nodules FDG-avid (SUV 9.1 & 8.8) R paratracheal LN (station 4R) FDG-avid No FDG-avidity elsewhere (including other nodules) MRI brain: no suspicious findings PFTs: FEV1 1.9L (99%), DLCO/VA 79% TTE: normal EF, no pulmonary artery HTN

Case 3: Review at Lung Cancer Multidisciplinary Conference: RUL adenocarcinoma (T3 - multiple nodules in same lobe) Plan: Sample of suspicious right hilar & paratracheal lymph nodes If positive for cancer, reimage then proceed to induction chemo/radiotherapy Case 3: EBUS: 10R lymph node with adenocarcinoma (N1) Other mediastinal lymph nodes nondiagnostic Mediastinoscopy: Multiple LNs with adenocarcinoma at station 4R N2 2R, 2L, 4L, 7 no tumor in lymph nodes (not N3) Stage?: IIIA (T3 N2 M0) assumes L disease not related IV (T3 N2 M1a) assumes L tumor nodule met from R Case 3: Repeat chest CT ~3 mo after initial CT, prior to induction chemo/radiotherapy: RUL nodules slightly larger LLL GGO lesion smaller without intervention Does not appear to be a cancer - shrinking LLL cavitary lesion smaller without intervention Does not appear to be a cancer - shrinking Undergoes neoadjuvant chemo/radiotherapy: Cisplatin & etoposide XRT to mediastinum 46 Gy

Case 3: Repeat chest CT after Chemo/Radiotherapy: RUL nodules stable Mediastinal LNs decreased in size LLL GGO lesion smaller LLL cavitary lesion smaller Reviewed at Lung Cancer MDC Suspect L-sided disease not related to R-sided cancer Proceed to surgical management of R tumor(s) Proceed to VATS right upper lobectomy & mediastinal LN dissection Case 3: Postoperative course uneventful Chest tube removed POD#3 Discharged home POD#5 Pathology: RUL nodule 1: 16mm adeno, <10% viable tumor RUL nodule 2: 17mm adeno, pleural invasion, >10% viable tumor No viable cancer in any of 10 lymph nodes Molecular testing confirmed same mutation in lymph nodes from EBUS & mediastinoscopy as in RUL nodule 1, different from RUL nodule 2. Plan: Meet with Med Onc to discuss further treatment Ongoing surveillance for recurrence/ L-sided lesions Summary Work up of solitary lung nodules > 1 cm: Obtain high quality imaging Noncontrast Chest CT Review at multidisciplinary tumor board If suspicious, obtain tissue Trans-thoracic needle biopsy Endobronchial ultrasound-guided needle biopsy Navigational bronchoscopic biopsy VATS excisional biopsy Tissue & suspicion guides management

Summary Utility of the multidisciplinary approach to lung cancer management Review patients with suspicious findings Review patients with new diagnosis of cancer Determine plan for workup of staging Discuss management options Patients range from s imple to c omplex Discuss options for involvement in cancer trials Review patients with recurrent cancers Discuss management options Discuss options for involvement in cancer trials Thank you CU Thoracic Surgery Team: 1-855-LUNG-UCH Thoracic Surgeons: John Mitchell, MD Michael Weyant, MD Robert Meguid, MD MPH Nursing and Support Staff: Tammy Bosch, RN, Thoracic Surgery Clinic Coordinator Julie Bishop, MPH, Office Coordinator Shantel Ho, Office Coordinator