Stereotactic Radiotherapy (SBRT) for Lung Cancer

Roy Decker, MD, PhD

Professor & Vice Chair

Department of Therapeutic Radiology

Yale School of Medicine

Disclosures:Research Support: Merck

Advisor/Consulting: Merck, Astra Zeneca, Regeneron, Cybrexa, Noxopharm, Sanofi, Novocure

Speaker: Astra Zeneca

Early Stage NSCLC

-Blomgren et al,

Acta Oncol 1995

First use of “stereotactic radiation” was for metastatic lesions

Phase II Trial including peripheral and central lesionsFakiris et al, IJROBP 2009

Timmerman et al, JCO 2006

• 70 patients with T1 or T2 NSCLC treated to 60 Gy in 3 fractions

• 4 local failures

• 6 nodal failures 15 patients

• 9 distant failures

• 12 Grade 3 to 5 toxicities

3 year LC 88.1%

G 3 to 5 toxicity

27% (central) v 10% (peripheral)

Not statistically significant

http://jco.ascopubs.org/content/vol24/issue30/images/large/zlj0300652580001.jpeg

RTOG 0236 with median follow-up of 4 years (7.2 years for alive)…

-Timmerman et al, JAMA 2010 and Proc ASTRO 2014

• 4 local (in-field) failure

93% 5-year Local Control

• 9 failures in same lobe

80% 5-year Lobar Control

• 7 regional failures

• 15 distant metastatic failures

• Grade 3 toxicity 15 patients

• Grade 4 toxicity 2 patients

5-year OS 40%Majority died non-cancer death

• 93% local control at 5 years for T1 peripheral tumors

• Lower expectations for larger tumors, or when the dose is limited

Beyond “medically inoperable” patients, we frequently offer SBRT in the “high risk” operable population

-Ann Oncol 2013

SBRT for Operable PatientsProspective Trials

Single-Arm• JCOG 0403, single arm, reported ASTRO 2010

– 3-year local control 86%, overall survival 76%Randomized

• ROSEL Closed due to poor accruallobectomy versus SBRT

• STARS Closed due to poor accruallobectomy versus SBRT (cyberknife)

• ACOSOG Z4099/RTOG 1021 Closed due to poor accrualsub-lobar resection versus SBRT

• SABR-Tooth –ongoing, but• STABLEMATES-ongoing, but• VALOR - ongoing…

Combined analysis of 2 trials

Total of 58 patients

-Lancet Oncology 2015

3-year OS 95% v 79% (p=0.037) 3-year RFS 86% v 80% (p=0.54)

both favoring SBRT

-Lancet Oncology 2015

408 patients with T1 or T2 NSCLCRefused surgery and had SBRTMajority had significant comorbidities

Local failure < 10%3 year OS 51%

-Radiotherapy & Oncology, 2019

From the NCDB:

More than 15000 patients with Charlson-Deyo Score of 0

(excludes patients with prior MI, CHF, CVA, COPD, CTD, liver disease, diabetes, renal disease)

In a propensity matched analysis, significant better OS with surgery

-J Thoracic Cardiovasc Surgery, 2016

SBRT for operable patients

• For a low-risk surgical patient, lobectomy is going to be superior to SBRT

– Better local control

– Resection of remaining lobe, nodal dissection, etc

• As the surgical risk increases, they become equivalent, and for the highest risk patients SBRT is likely superior

Opening in New Haven in July:

KEYNOTE 867

Effect of SBRT on Pulmonary Function

-IJROBP 2014

-JTO 2012

423 patients treated with SBRTStratified by pre-treatment PF

PF declined by 3.6% at 6 monthsby 6.8% at 24 months

PF improved for patients with worst baseline PF

Largest PF decline seen in patients with best baseline PF

Oligometastatic Disease

Gomez et al, Lancet Oncology 2016

Gomez et al, Lancet Oncology 2016

citations

citations

Iyengar et al, JAMA Oncol 2018

Single Institution phase 2 randomized trial

29 patients enrolled with PR or SD after first-line chemotherapy, with up to 5 sites of metastatic disease

9.7 vs 3.5 months PFS

• SBRT is the non-invasive standard of care for early-stage NSCLC patients who are not eligible for surgery

• SBRT is a reasonable alternative to surgery for select high-risk patients

• SBRT has a growing role in the treatment of oligometastaticdisease

Thank You