Advances in Lung Cancer Treatment Stereotactic Radiotherapy Pre-Planning Meeting - May 27, 2014 Drew Moghanaki, MD, MPH Hunter Holmes McGuire Veterans Affairs Medical Center Director of Clinical Radiation Oncology Research VCU Massey Cancer Center Associate Professor Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

This talk does not represent the views of the VA, or the US Government Disclosures Research Funding VA Cooperative Studies Program Bristol Myers Squibb Foundation Honoraria & Travel Support Varian Medical Systems This talk does not represent the views of the VA, or the US Government Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Introduction

Today’s Standard of Care Operable Surgery Borderline Operable Less Surgery Medically Inoperable Stereotactic Radiotherapy Non-Small Cell Lung Cancer Stage I Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Surgical Outcomes Rely on Size Pathological Group Stage 0-10 mm = Stage IA1 (n=1486) 11-20 mm = Stage IA2 (n=6348) 21-30 mm = Stage IA3 (n=5415) 31-40 mm = Stage IB (n=8906) 41-50 mm = Stage IIA (n=2631) Overall Survival Goldstraw, J Thor Oncol 2015 Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Advances in Surgery - VATS Randomized data vs Open Thoracotomy Reduced operative time Reduced perioperative blood loss Reduced postoperative air leaks Shorter duration of epidural anesthesia Shorter hospital stay Less postoperative pain Improved quality of life No improvements in long-term survival Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Importance of Surgical Expertise 30-Day Mortality Rates Depends on patient selection, range from <1% to 29% Specialization 25% = board certified w/ focus on thoracic surgery 45% = board certified w/ focus on cardiac surgery 25% = general surgeons Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Postoperative Mortality – Remains a Problem Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017 Senthi & Senan, Eur J Cancer 2014

Elderly Patients Concerns Limited physiological capacity to heal Impaired vision and hearing Urinary incontinence, falls, depression, poor baseline nutrition Cognitive disorders such as dementia and delirium. Recovery is occasionally prolonged, can take up to months Discharges frequently to skilled nursing facilities Mortality rates 4x in patients ≥75 years (5.3% v 1.3%, p<0.01). Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Dilemma of Developing More Lung Cancers Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Treatment Options for Early Stage NSCLC Minimally Invasive Surgery Minimally Invasive Radiotherapy Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Stereotactic Radiotherapy

Conventional Radiation Stereotactic Radiotherapy Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

This is “large field” radiotherapy Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Phase I - A Serendipitous Finding Indiana University Indianapolis VA Medical Center It’s been >20 years since SBRT The findings surprised everyone MADE POSSIBLE: NCI, enrolled pts at VA Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017 Timmerman, Chest 2003

Confirmatory Findings - Dutch Series LC rates reproduced around world REPRODUCED with many LINACS Fueled ENTHUSIASM in Radonc field Figures courtesy of BJ Slotman Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Post-Treatment Scanxiety & Potential Harms 18 Gy x 3 6 mo 12 mo 15 mo Could lead to harms MD Anderson series Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Matched Comparisons Matched 251 Matched 6,295 SEER NCDB Shirvani, JAMA Surgery 2014 Yerokun, JCTS 2017 Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Screened Population Buckstein , J Radiat Oncol 2014 Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Graveyard of Randomized Trials Surgeon Surgery Pulmonologist RadOnc SBRT 2008-10 ROSEL; NCT00687986 Randomized 22 of 960 2009-13 STARS: NCT00840749 Randomized 36 of 420 2011-13 RTOG: NCT01336894 Randomized 10 of 420 2012-?? Mayo Trial: NCT01622621 Randomized 0 of 96 2015-13 SABRTooth: NCT02629458 Randomized 23 of 54 TOTAL Randomized 91 of 1,950 = 4.6% Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

The Pooled Randomized Trials /1480 (4%) J Chang, Lancet Oncology 2015 Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Yet, preferences are shifting anyway Surgery Radiation SEER, Stage IA (n=32,000) Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017 Haque, AJCO 2016

Surgery is the standard of care if operative mortality rate <1.5% Treatment without biopsy can be considered Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Active Randomized Trials for Operable Stage I Surgery SBRT? VALOR (n=670) Borderline Operable STABLE-MATES (n=258) Less Surgery SBRT? RTOG 3502 (n=76) Medically Inoperable SBRT Drew Moghanaki | Cancer Action Collation of Virginia | Richmond – Sept 14, 2017

Veterans Affairs Lung Cancer Surgery or Stereotactic Radiotherapy Trial Surgeon Surgery Pulmonologist R A N D O M I Z E OVERALL SURVIVAL N=670 Positive Bx Clinical IA v IB Central v Peripheral SECONDARY ENDPOINTS: pt-reported QOL, changes in PFTs PROSPECTIVELY CAPTURING Patterns of failure with uniform def’n Type & tolerance of secondary treatments (2nd MALIGNANCY) Cause of death SBRT RadOnc

Take Home Points Surgery remains a great option for early stage lung cancer “Surgery for all” is a fading paradigm Stereotactic radiotherapy can be considered without biopsy Post radiotherapy scanxiety can be a problem Salvage surgeries appear safe

Questions @DrewMoghanaki