jeffrey d. bradley, m.d. s. lee kling professor of radiation oncology
DESCRIPTION
Approaching Early-Stage Disease: Strategizing Various T herapeutic Options (Surgery vs. SBRT vs. RFA). Jeffrey D. Bradley, M.D. S. Lee Kling Professor of Radiation Oncology Alvin J Siteman Cancer Center. Disclosures. No financial relationships to disclose - PowerPoint PPT PresentationTRANSCRIPT
Approaching Early-Stage Disease: Strategizing Various Therapeutic
Options (Surgery vs. SBRT vs. RFA)
Jeffrey D. Bradley, M.D.S. Lee Kling Professor of Radiation Oncology
Alvin J Siteman Cancer Center
Department of Radiation Oncology
Disclosures
• No financial relationships to disclose
• Chair of NRG Oncology Lung Cancer Committee (modest stipend)
Department of Radiation Oncology
Case 1: LB
• Referred by cardiologist to Dr. Meyers for evaluation of a LUL lung nodule
• Recent drug-eluting stent placed in coronary artery. On clopidrogel
• FDG-PET showed moderately increased FDG uptake with max SUV of 2.5. No other findings
• PFTs showed FEV1 of 2.64 (83%) and FEV1/FVC of 74.7 (100%)
• CT-guided needle Bx: NSCLC favor SCCA
Department of Radiation Oncology
LB SABR Images
Department of Radiation Oncology
LB: 5 Year Follow-up Images
Department of Radiation Oncology
Stage I NSCLC - Options
• Surgery• Lobectomy/ pneumonectomy• Sublobar resection
(segmentectomy, wedge)
• Radiation• SBRT• EBRT
• Observation
Medically operable
Medically inoperable
Borderline medically operable
Wouldn’t touch with a 10-foot pole
???
??
?
Department of Radiation Oncology
Results of Surgery
• IASLC project – AJCC 7th addition• 100,869 patients from 46 sources from
19 countries• 67,725 NSCLC treated between 1990-
2000
• American College of Surgeons Z4032• Randomized Phase III study of sublobar
resection +/- brachytherapy in high-risk patients with NSCLC, 3 cm or smaller (ongoing)
Department of Radiation Oncology
Department of Radiation Oncology
Department of Radiation Oncology
Stage I NSCLC - OptionsStage I NSCLC - Options• Surgery
5y LR(LCSG 1995)
6%
18%
Department of Radiation Oncology
ACOSCOG Z0432ACOSCOG Z0432
Department of Radiation Oncology
Stereotactic Body Radiation Stereotactic Body Radiation TherapyTherapy
• Not a machine, but a type of radiation delivery.
• Stereotactic = precise positioning of the target volume in 3 dimensions.
• Has become synonymous with high dose per fraction.
• Different delivery techniques (arcs, static fields, protons)
Department of Radiation Oncology
Loca
l Con
trol (
%)
0
25
50
75
100
Months after Start of SBRT0 6 12 18 24 30 36
0
25
50
75
100
0 6 12 18 24 30 36
Patientsat Risk 55 54 47 46 39 34 23
Fail: 1Total: 55
/ / / / / /// / / // / // / / / / / // / // // // //
Challenges?......What Challenges?RTOG 0236
• 1 failure within PTV, 0 within 1 cm of PTV
36 month
Primary tumor control = 98% (CI: 84-100%)
Lobar tumor control = 94%
Timmerman et al. JAMA 2010
Department of Radiation Oncology
Thermal Ablation for lung cancersThermal Ablation for lung cancers
Department of Radiation Oncology
Radiofrequency Ablation – Schneider et al. 2013Radiofrequency Ablation – Schneider et al. 2013
Department of Radiation Oncology
Radiofrequency AblationRadiofrequency Ablation
• Follow up data are now projecting 5-year results for percutaneous thermal ablation
• Pneumothorax and chest drain rates are very high
• Local recurrence rates are poor (11-57%)• Industry and investigators are evaluating
bronchoscopic ablation techniques• Consider for SBRT failures?• First-line RFA cannot be recommended
Department of Radiation Oncology
Randomized Trials comparing surgery to SBRT
• Lobectomy• Netherlands ROSEL Trial – closed due to lack of accrual• Accuray Cyberknife – closed due to lack of accrual
• High Risk• ACOSOG Z4099/RTOG 1021 – closed due to lack of
accrual• TMSC rejected amendment for cluster randomization
(5/9/13)
• One last hope?VA Medical System – VALOR TrialLobectomy vs SBRTDrew Moghanaki - PI
Department of Radiation Oncology
Histological confirmation NSCLC
and confirmatio
n N2/N3 negative lymph nodes
Registration and
Randomization
ARM 1:Sublobar
Resection ± Brachythera
py (SR)
ARM 2:Stereotactic
Body Radiation Therapy
(SBRT) 18 Gy X 3 = 54
Gy
FOLLOW
UP
ACOSOG Z4099/RTOG 1021 ACOSOG Z4099/RTOG 1021 Phase III Trial for High-risk patientsPhase III Trial for High-risk patientsOpened June 2011Opened June 2011
Endpoint: 3 year OS
Accrual = 420 patients
Department of Radiation Oncology
Histological confirmation NSCLC
and confirmatio
n N2/N3 negative lymph nodes
Registration and
Randomization
ARM 1:Sublobar
Resection ± Brachythera
py (SR)
ARM 2:Stereotactic
Body Radiation Therapy
(SBRT) 18 Gy X 3 = 54
Gy
FOLLOW
UP
ACOSOG Z4099/RTOG 1021 ACOSOG Z4099/RTOG 1021 Phase III Trial for High-risk patientsPhase III Trial for High-risk patientsOpened June 2011Opened June 2011
Endpoint: 3 year OS
Accrual = 420 patients
Closed
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLC
• Rough comparison of OS
cT1N0 cT2N0
3y OS 5y OS 3y OS 5y OS
Surgery AJCC 6th ed 71% 61% 46% 38%
AJCC 7th ed ~68% (1a)
~58% (1b)
53% (1a)
47% (1b)
~50% (2a)
~45% (2b)
~30% (3; ≥ 7 cm)
43% (2a)
36% (2b)
26% (3; ≥ 7 cm)
SBRT RTOG 0236 (60Gy/3)
(55.8%; T1/T2)
? (55.8%; T1/T2)
?
U. Indiana (60-66Gy/3)
~50% ~20% ~35% ?
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLC• Problem #1. . .
• Treatment groups are inherently different!
Vs.
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLC• Problem #2. . .
• Definition of “medically operable”?
???FEV1
Diabetes
Cardiac Co-morbidity
DLCOPerformance Status
Predicted Postoperative Pulmonary Reserve
SmokingFVC
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLC
• Medically operable• Uematsu, IJROBP 2001• Onishi, J Thorac Oncol 2007 / IJROBP 2010
• Medically inoperable / High risk operable• William Beaumont
• Grills, JCO 2010 - Wedge vs. SBRT• Cornell
• Parashar, Cancer 2010 – Wedge+Brachy vs. SBRT• Wash U
• Crabtree, J Thorac Cardiovasc Surg 2010 - Any surgery vs. SBRT
• Robinson, JTO 2012– Lobectomy/Pneumonectomy vs. SBRT
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLCMedically operable - Onishi, J Thorac Oncol 2007
• Median F/U 38 mo (2-128 mo)
OS by medical operability
3y ~40%, 5y 35%
3y ~70%, 5y 64.8%
All 257 pts
3y 5y
OS 56.8% 47.2%
CSS 76.9% 73.2%
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLCMedically operable - Onishi, J Thorac Oncol 2007
≥ 100Gy = 64.8%
5y overall survival 19.7% 53.9% sig
Control rates by BED10 for all pts
Department of Radiation Oncology
What dose for peripheral lung cancers?
Medically operable - Onishi, J Thorac Oncol 2007
5y OS by BED10 in medically operable
<100Gy3y ~65%, 5y ~50%
≥100 Gy3y 80.4%, 5y 70.8%
BED = nd(1+d//)Schemes >100 Gy:16 Gy x 312 Gy x 410 Gy x 5
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLCMedically operable - Onishi, IJROBP 2010
• 87 pts w/medically operable, path proven T1 (n=65) or T2 (n=22) N0 NSCLC tx’d w/SBRT to BED > 100Gy from 1995-2004 at 14 Japanese institutions.• Subset from original 2007 study with longer follow-
up.• SBRT was 42-72.5 Gy / 3-10 fx via a variety of
stereotactic techniques.• No chemo
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLCMedically operable - Onishi, IJROBP 2010
• Median F/U 55 mo
Local control Overall survival
5y LC 86.7% (All) 5y OS 69.5% (All) CSS 76.l%
Department of Radiation Oncology
Local Recurrence by Prescription Dose
• 2-year LR of 15% for low dose vs 4% for high dose• Grills IS et al. JTO 2012;7(9):1382-93• Elekta Consortium
1.0
0.8
0.2
0.4
0.6
0
0 4 6 82Time (Years)
Local
Recu
rren
ce
Rx BED10 ≥ 105 Gy
Rx BED10 < 105 Gy
p<0.001
Department of Radiation Oncology
SBRT vs. surgery for clinical stage I NSCLCMedically operable - Onishi, IJROBP 2010
• Median F/U 55 mo
Local control Overall survival
5y LC 86.7% (All) 5y OS 69.5% (All) CSS 76.l%
Department of Radiation Oncology
SBRT vs. surgery for SBRT vs. surgery for clinical stage I NSCLCclinical stage I NSCLCMedically inoperable / High risk operable - Grills, JCO
2010 • Median potential F/U 30 mo
Department of Radiation Oncology
J Thorac Oncol 2013; 8:192-201
Department of Radiation Oncology
Department of Radiation Oncology
RTOG 0915 Overall Survival
Videtic et al. ASTRO and IASLC 2013
Department of Radiation Oncology
Centrally-located lung cancersCentrally-located lung cancers
Department of Radiation Oncology
Reported Toxicity for Central Lung Reported Toxicity for Central Lung CancersCancers
Timmerman R. et al JCO 2006
Timmerman et al. JCO 2006
Department of Radiation Oncology
RTOG 0813 - SBRT Dose LevelsRTOG 0813 - SBRT Dose LevelsTrial completed, await f/uTrial completed, await f/u
Level 1 10 Gy x 5 50 GyLevel 2 10.5 Gy x 5 52.5 GyLevel 3 11 Gy x 5 55 GyLevel 4 11.5 Gy x 5 57.5 GyLevel 5 12 Gy x 5 60 GyDesign: Continual Reassessment Monitoring (CRM)Endpoints:
Phase I – Any Tx-related Grade 3 or greater toxicity
Phase II – 2-year primary tumor control rate
Phase I/II Dose Escalation study (N=94)
Department of Radiation Oncology
WU Data on Local ControlWU Data on Local Control
Olsen, Robinson, Bradley et al. IJROBP 2011
Department of Radiation Oncology
Conclusions: Surgery versus SBRTConclusions: Surgery versus SBRT
• Surgery is the gold standard for operable patients
• For inoperable or marginally operable patients with Stage I lung cancer, SBRT offers excellent local control and similar survival to surgical approaches
• SBRT results will be similar, regardless of delivery device. Differences are method of imaging, +/- fiducials, treatment time, etc.
• Randomized trials have failed to accrue for various reasons; patients and surgeons