Ablative Lung Cancer Therapies

Jeremiah T. Martin MBBCh FRCSI MSCRDPortsmouth, Ohio

No Disclosures

Introduction

Introduction

Scioto CountyData from ODH OCISS

Incidence* Mortality* Early Stage#

Scioto Ohio US Scioto Ohio US Scioto Ohio USLung 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,

Current Landscape

Kentucky Cancer Registry:2010 – 2012:

Surgical Patients 1

30% Minimally Invasive

2005 – 2014: Intent-to-treat (cI/cII) 2

60% Surgical

25% Radiation / Local Therapy

15% No local therapy

1. Martin, Jeremiah T., et al. "Nodal upstaging during lung cancer resection is associated with surgical approach." The Annals of thoracic surgery 101.1 (2016): 238-245.

2. Martin, Jeremiah T. “Disparities in stage-appropriate therapy for resectable non-small cell lung cancer in kentucky”. In Preparation.

Early Stage Lung Cancer

Early Detection

Early Therapy

Local Therapy

SurgeryOpen

VATS

Robot

AblationThermal

RFA

Laser

Microwave

Cryotherapy

Electroporation

RadiationSAbR / SBRT

Proton

Ablation

Radiofrequency Ablation

• Oscillating voltage: 375 - 500 kHz image-guided electrode

• Frictional heat, impedance is measured

Image: upmc.com

Radiofrequency Ablation

ACSOG Z4033Published 2015

51 patients, cIA NSCLCImage-guided RFA, retreatment of any local recurrence

86.3% at 1 year 69.8% at 2 yearsRecurrence free: 68.9% and 69.8%

Dupuy DE, Fernando HC, Hillman S, Ng T, Tan AD, Sharma A, et al. Radiofrequency ablation of stage IA non-small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial. Cancer. 2015;121(19):3491-8.

Radiofrequency Ablation

Potential Advantages:

• Well tolerated in frail patients

• Retreatment is possible

• Comparable outcomes to SBRT

Limitations:

• Technical – heat-sink, poor conduction

Angiodynamics StarBurst

Microwave Ablation

• Percutaneous / Bronchoscopic

• Local MW heating - > 60C

• EM energy: 300MHz - 300GHz

Image courtesy NeuWave

Microwave Ablation

Microwave Ablation of Lung Neoplasms2016

Retrospective review: 108 patients

- Primary success in 80%- More likely with tumors < 3cm- 62% of tumors > 3cm- vs 23%-40% in RFA

OS: 78% 1y 54% 2y 39% 3y

Healey TT, March BT, Baird G, Dupuy DE. Microwave Ablation for Lung Neoplasms: A Retrospective Analysis of Long-Term Results. J Vasc Interv Radiol. 2016.

Cryoablation

Cell death < -40ºC

Less discomfort than RF

Five Year Survival after CryoablationPublished 2015

47 cI patients 2006-2011

67% at 5 years

Moore W, Talati R, Bhattacharji P, Bilfinger T. Five-year survival after cryoablation of stage I non-small cell lung cancer in medically inoperable patients. J Vasc Interv Radiol. 2015;26(3):312-9.

“Contact” ablation

• Percutaneous• More precise

• Invasive

• Pneumothorax

• Bronchoscopic• Less invasive

• Less precise

… is there anything else

on the horizon?

Stereotactic Radiation

• Stereotactic radiation (SBRT)/(SABR)

SBRT

• Radiation: • minimize collateral damage: fractionation

• 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.

• RTOG 0236: 59 biopsy proven T1/2N0M0• 3-year primary control rate was 98%

• 3-year disease free survival was 48%• Distant relapse

Particle Therapy

Conventional radiation X-Rays (Photons) - Linear Accelerator

Proton therapyProton beam - cyclotron

Hydrogen

Particle Therapy

Protons carry a charge and have mass

Bragg PeakProtons slow down…

Deliver a burst of energy

Particle Therapy

• Protons carry a charge and have mass

• Bragg Peak• Protons slow down

• Deliver a burst of energy

Proton Therapy

1946 – Proposed as a therapy

1954 – MGH Harvard Cyclotron Laboratory

1990 – First US hospital based center: Loma Linda

Today:27 centers in the USA

14 more in development

http://www.ptcog.ch/index.php/facilities-in-operation

Cost and Infrastructure

Mevion S250

With permission: from MevionMevion S250 Hyperscan

Clinical Trials

Source: clinicaltrials.gov

Stable-mates Trial

A Randomized Phase III Study of SublobarResection (SR) versus Stereotactic Ablative Radiotherapy (SAbR) in High Risk Patients with Stage I Non-Small Cell Lung Cancer (NSCLC)

To Determine if SAbR improves survival over SR in High Risk Operable Stage I NSCLC

Stable-mates Trial

84 patients enrolled as of March 2018; Goal 272

Limitations of Ablation

• Tissue• Medical oncology

• Imaging• Microscopic tumor extension

• Lymph-vascular invasion

• Lymph node involvement (N1)

Summary

Ablation and Surgerycomplementary roles

Surgeons must remain engaged

Summary

Ideal Local Therapy

Minimal / No pain

Minimal loss of quality of life

High success rate

Reproducible / Generalizable

Cost effective

Ablative Lung Cancer Therapies

Safety Quality Service Relationships Performance

Jeremiah T Martinmartinjt@somc.org