Lung Cancer. Current Therapy JEREMIAH MARTIN MBBCh FRCSI MSCRD

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Lung Cancer Current Therapy JEREMIAH MARTIN MBBCh FRCSI MSCRD

Objectives Describe risk factors, early detection & work-up of lung cancer. Define the role of modern treatment options, minimally invasive surgery, chemotherapy & stereotactic radiation in the setting of guideline directed care. Consider opportunities for patients, provider & public education.

Smoking as a risk factor

Smoking Cessation

Smoking Demographics http://www.countyhealthrankings.org/app/ohio/2017/measure/factors/9/map Scioto county has one of the highest smoking rates in the country

% Survival at 5 years All stages, NSCLC overall

% Patients discovered with stage III / IV Most patients present with advanced disease, limited options

% Patients stage I/ II don t get surgery Data from Kentucky Cancer Registry missed opportunity

Scioto County Data from ODH OCISS Lung cancer has the highest incidence, and is responsible for the greatest number of cancer deaths in our county

Scioto County Data from ODH OCISS Incidence * Mortality * Early Stage # Scioto Ohio US Scioto Ohio US Scioto Ohio US Breast 120.0 123.8 124.9 20.6 23.0 21.2 74.2 68.9 70.9 Lung 87.9 69.9 55.8 71.6 52.7 44.7 19.0 18.0 19.0 * - Data are number of patients per 100,000 population # - Data are proportion / percentage 1 Source of Ohio data: Ohio Cancer Incidence Surveillance System and the Bureau of Vital Statistics, Ohio Department of Health, 2017. 2 Source of U.S. data: Surveillance, Epidemiology and End Results Program, National Cancer Institute and the National Center for Health Statistics, 2017. 3 Rates are per 100,000 and age-adjusted to the 2000 U.S. standard population. Rates are sex specific for cancers of the breast,

Why is lung cancer so lethal? No symptoms Stigma smoking, self-inflicted, experience with family members Access to care Screening Pulmonology, Thoracic Surgery, Medical Oncology, Radiation Oncology

History of Lung Cancer Screening Frequent chest x-rays Sputum cytology Chest CT screening Sputum tumor markers Breath analysis Genomics / Proteomics

Lung Cancer Screening National Lung Screening Trial (NLST) 53,454 patients enrolled 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? Cost effectiveness? Launched in 2002, the initial findings were released in November 2010

Lung Cancer Screening Draft Recommendations, August 2013 http://www.uspreventiveservicestaskforce.org/uspstf/uspslung.htm#update

NLST The Downside

Lung Cancer Screening Program Initial consultation: risk assessment risk / benefit of scan; smoking cessation CT scan Likely cancer: thoracic surgeon Intermediate / Low Risk Ongoing evaluation, 2-6 months Normal scan Repeat annual scan

Time matters - detection to diagnosis - detection to treatment These are our key metrics for the ACCC OCCM project

A Multidisciplinary Effort Medical Oncology Radiation Oncology Local/Referri ng Physicians Lung Cancer Screening Program Thoracic Surgery Radiology Smoking Cessation

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

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

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

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

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 1. 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 2. 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 Tumor N1 N2 N3 N1 Ipsilateral (Intrapulmonary) N2 Ipsilateral medistinal and subcarinal N3 Contralateral mediastinal

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

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

Pulmonary Artery Anterior View

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

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,

Patient expectation VATS Lobectomy 1-2 hour operation 3-4 days in hospital 2-3 weeks to normal activity

Video https://youtu.be/3sfiv3yy2fg

Advances in Radiation Stereotactic radiation (SBRT) Cyberknife

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

SBRT / SABR 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)

Metabolomics: New Targets, New Tests Warburg effect aerobic glycolysis despite plentiful oxygen

Summary Lung cancer is the most common cause of cancer death in the US Smoking is the biggest risk factor, Kentucky has the highest incidence of smoking in the US Prevention, risk factor modification are the keys to improving survival Currently overall survival is 15%

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

Lung Cancer What are we doing at SOMC? Clinical Priority for Cancer Center, 2017 November activities Community screening events ACCC / OCCM Detection to Diagnosis Diagnosis to Treatment Surgical Services Scioto county and beyond

Lung Cancer Survival 5 year survival All comers most common III 18% Stage IA1 90% Incredible opportunity for lives saved if we can find cancer early; and in the process educate and improve health behaviors.

Any Questions? (740) 356-8772 martinjt@somc.org Safety Quality Service Relationships Performance