Lung Cancer 2017 Standard of Care Screening, Diagnosis, Management Jeremiah Martin MBBCh FRCSI MSCRD

DISCLOSURE The speaker and members of the planning committee do not have a conflict of interest in this topic. There is no commercial support for this program.

Now we will turn our attention to cancer mortality Now we will turn our attention to cancer mortality. Lung cancer is by far the leading cause of cancer death among males (27%), followed by prostate (8%) and colorectal (8%) cancers. Among females, lung (26%), breast (14%), and colorectal (8%) cancers are the leading causes of cancer death.

Smoking as a risk factor

Smoking Cessation

Smoking Demographics

Lung Cancer Age-Adjusted Incidence Rates by State Data Source: CDC http://www.cdc.gov/cancer/lung/statistics/state.htm

Lung Cancer Age-Adjusted Mortality Rates by State Data Source: CDC http://www.cdc.gov/cancer/lung/statistics/state.htm

Incidence by Area Development District Data Source: Kentucky Cancer Registry http://www.cancer-rates.info/ky

What is cancer? In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues.

Numbers… … we can change

15% Survival at 5 years

Patients discovered with stage III / IV 70% Patients discovered with stage III / IV

Patients stage I/ II don’t get surgery 40% Patients stage I/ II don’t get surgery

Lung Cancer Survival Dependent on cell type Non-Small Cell (NSCLC) Adenocarcinoma / Squamous Cell Large Cell Neuroendocrine Small Cell Represents 15% of lung cancers 6% 5-year survival Treatment can add 6-12 months

Improving Outcomes in Lung Cancer Increase Awareness Decrease risk factors Early detection Clinical suspicion Screening Early stage-directed therapy

Lung Neoplasms Where do they come from?

Differential Diagnosis Pulmonary Nodule Benign Infectious Treat Inflamm. Observe Malignant Carcinoma Staging

Differential Diagnosis Structural / Inflammatory Possibilities (benign) Arteriovenous Malformation Atelectasis Rheumatoid nodule Sarcoidosis Wegener Granulomatosis

Differential Diagnosis Infectious Possibilities (benign) Aspergillosis Blastomycosis Coccidiomycosis Histoplasmosis Hydatid Cysts Lung Abscess Nocardiosis Tuberculosis

Differential Diagnosis Malignancy Non small cell lung cancer Small cell lung cancer Carcinoid tumor

Imaging Tools CXR CT PET MRI

Diagnostic / Therapeutic Tools Needle biopsy Bronchoscopy Endobronchial Ultrasound Mediastinoscopy VATS (Video-assisted thoracic surgery) Thoracotomy Less Invasive More Invasive

Workup of a pulmonary nodule History Generally asymptomatic May have cough Occasionally may present with pain, hemoptysis, weight loss, neurologic symptoms - concern for advanced disease Any prior malignancy? Smoking history? Exposure history?

Workup of a pulmonary nodule History Look for smoking-associated diseases Coronary artery disease Peripheral vascular disease Ask about general health screening (possibility of metastatic disease) Colonoscopy Mammography in women

Workup of a pulmonary nodule Physical Examination General appearance Signs of smoking Lymphadenopathy Detailed pulmonary examination

Workup of a pulmonary nodule Look at all available images, and ask for old studies for comparison At this point consider referral for evaluation by a thoracic surgeon

Workup of a pulmonary nodule LIKELY BENIGN LIKELY MALIGNANT

Workup of a pulmonary nodule If it’s cancer: Treatment depends on stage, type If it’s an infectious nodule: May need treatment, may resolve If it’s old scar tissue: It will remain the same

Which is most likely?

Risk Assessment Age Gender Smoking history History of prior malignancy Surgical risk Cardiac risk assessment Pulmonary function testing

“assume the worst hope for the best!” Risk Assessment “assume the worst hope for the best!”

Stage-Based Treatment of Cancer LOCAL THERAPY SYSTEMIC THERAPY Surgery Radiation Chemotherapy I II III IV

Stage-Based Treatment http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

“TNM” staging system Tumor Nodes Metastases Lung Cancer Staging “TNM” staging system Tumor Nodes Metastases

Chart illustrates the descriptors from the 7th edition of the TNM staging system for lung cancer. UyBico S J et al. Radiographics 2010;30:1163-1181 ©2010 by Radiological Society of North America

Lung Cancer Staging From a clinical perspective: work by outruling the worst possibilities: 1) Metastatic Disease 2) Nodal Disease 3) Local Tumor Invasion / Surgical Candidacy

Lung Cancer Staging Look for evidence of metastatic disease PET scan Brain MRI If Mets present: confirm tissue diagnosis by least invasive means possible then definitive chemo-/radiation therapy

Lung Cancer Staging Most common sites for metastases Other lung Brain Bone Adrenal glands Liver

Lung Cancer Staging Primary Tumor Mediastinal Lymph Node Adrenal metastases Left iliac bony metastasis

Lung Cancer Staging Look for evidence of nodal disease EBUS Mediastinoscopy If N2 disease present: refer for chemo-/radiation therapy may be a candidate for resection depending on response to treatment

Mediastinal Staging N3 N1 N2 Tumor N1 – Ipsilateral (Intrapulmonary) N2 – Ipsilateral medistinal and subcarinal N3 – Contralateral mediastinal

Mediastinal Staging Better if directed towards target EBUS Non-invasive Immediate results Mediastinoscopy More invasive (still outpatient) ‘Gold standard’ More tissue

Lung Cancer Staging Clinical Stage: Pathologic Stage: Operative candidate? Pathologic Stage: Final resected specimen and lymph nodes

Multi-Disciplinary Care Radiology Pulmonology Thoracic Surgery Medical Oncology Radiation Oncology

Lung Cancer Staging Clinical Stage: Pathologic Stage: Operative candidate? Pathologic Stage: Final resected specimen and lymph nodes

Surgical Management Anatomic dissection of the hilum Remove the entire lobe Remove draining lymph nodes Multi-specialty discussion of treatment plan

Surgical Approach

Minimally Invasive Surgery Video Assisted Thoracoscopy (VATS) Variety of techniques Common feature: Thoracoscope anatomic hilar dissection no rib spreading Anterior two-incision approach video

VATS / Thoracoscopic Lobectomy Video File https://www.dropbox.com/s/ma98k0ob0wle3nv/ MiddleLobectomy.wmv?dl=0

Advantages of VATS Better tolerated in the elderly with fewer complications Increased likelihood of compliance with adjuvant therapy Decreased length of stay, decreased hospital cost Quicker return to function / less pain Cattaneo SM, et al. "Use of video-assisted thoracic surgery for lobectomy in the elderly results in fewer complications". Ann. Thorac. Surg. 85 (1): 231–5; Nicastri DG, et al. "Thoracoscopic lobectomy: report on safety, discharge independence, pain, and chemotherapy tolerance". J Thorac Cardiovasc Surg 135 (3): 642–7. Casali G, et al. "Video-assisted thoracic surgery lobectomy: can we afford it?". Eur J Cardiothorac Surg 35 (3): 423–8.

Advantages of VATS 3 weeks postoperatively Todd L Demmy, Jackie J Curtis, Minimally invasive lobectomy directed toward frail and high-risk patients: a case-control study, The Annals of Thoracic Surgery, Volume 68, Issue 1, July 1999, Pages 194-200,

Why is VATS not standard of care National adoption is very slow Only 50% of anatomic resections in the US are performed using minimally invasive techniques Learning curve Robotics is helping

KCR Data 2010-2012 Review of Kentucky Cancer Registry data Robust pathology information Survival data updated with linkage to external sources

Results

Results All p1a 12 mo 24 mo VATS 94% 86% Open 88% 79%

Other New Technologies Navigational Bronchoscopy Allows biopsy of peripheral nodules

Lung Cancer Surgery – The Future Minimally Invasive VATS Robotics Parenchymal Sparing operations Segmentectomy Extended wedge-resection

Advances in Radiation / Chemotherapy Stereotactic radiation (SBRT) Cyberknife

SBRT Large radiation dose per fraction Precisely delivered to target area Minimal damage to surrounding tissues Disadvantage – no tissue, no lymph nodes

SBRT Treatment of choice for early stage, medically inoperable patients. Control of symptomatic metastases. Ongoing trials: SBRT vs Surgery for small peripheral tumors RTOG 0236: 59 biopsy proven T1/2N0M0 3-year primary control rate was 98% 3-year disease free survival was 48% Distant relapse

Advances in Chemotherapy Traditional management: Platinum based chemotherapy Systemic toxicities high, tolerance poor Poor response rate, particularly in NSCLCA

Advances in Chemotherapy NSCLCA Adenocarcinoma EGFR expression seen in 15 % Erlotinib – 150mg PO daily EML4-ALK gene rearrangements / fusion seen in 4% Crizotinib – 250mg PO BID Newer targets: RAS, BRAF, MET, RET etc.

Advances in Chemotherapy Immunotherapy Nivolumab (approved March 2015) Pembrolizumab (approved October 2015)

Advances in Chemotherapy Immunotherapy Nivolumab (approved March 2015) Pembrolizumab (approved October 2015)

Lung Cancer Screening National Lung Screening Trial 55 – 74 years of age 30 pack-year history of smoking Low-dose helical CT scanning Mortality reduction of 20% when compared with CXR screening How to implement this…

Lung Cancer Screening

Lung Cancer Screening Program Positive Referral to Surgeon Consultation Counselling Smoking Cessation Intermediate Short Followup CT-Scan Negative Return in 1 year AACR Database

Summary Lung cancer is the most common cause of cancer death in the US Smoking is the biggest risk factor Prevention, risk factor modification are the keys to improving survival

Summary Screening may effect a stage-shift in lung cancer diagnosis Early stage-directed therapy is key Significant advances in Surgery, Chemotherapy, and Radiation therapy for lung cancer

Safety  Quality  Service  Relationships  Performance Any Questions? Jeremiah Martin Marion Hochstetler (740) 356-8772 martinjt@somc.org Safety  Quality  Service  Relationships  Performance