Approaching early stage disease strategizing various t herapeutic options surgery vs sbrt vs rfa
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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

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Approaching early stage disease strategizing various t herapeutic options surgery vs sbrt vs rfa

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


Disclosures
Disclosures

  • No financial relationships to disclose

  • Chair of NRG Oncology Lung Cancer Committee (modest stipend)


Case 1 lb
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




Stage i nsclc options

Surgery

Lobectomy/

pneumonectomy

Sublobar resection (segmentectomy, wedge)

Radiation

SBRT

EBRT

Observation

Stage I NSCLC - Options

Medically operable

???

Borderline medically operable

??

Medically inoperable

?

Wouldn’t touch with a 10-foot pole


Results of surgery
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)


Stage i nsclc options1

5y LR

(LCSG 1995)

6%

18%

Stage I NSCLC - Options

  • Surgery



Stereotactic body radiation therapy
Stereotactic Body Radiation Therapy

  • 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)


Challenges what challenges rtog 0236

1 failure within PTV, 0 within 1 cm of PTV

36 month

Primary tumor control =

98% (CI: 84-100%)

Challenges?......What Challenges?RTOG 0236

Lobar tumor control = 94%

Timmerman et al. JAMA 2010




Radiofrequency ablation
Radiofrequency 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


Randomized trials comparing surgery to sbrt
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 Trial

    Lobectomy vs SBRT

    Drew Moghanaki - PI


Acosog z4099 rtog 1021 phase iii trial for high risk patients opened june 2011
ACOSOG Z4099/RTOG 1021 Phase III Trial for High-risk patientsOpened June 2011

ARM 1:

Sublobar Resection ± Brachytherapy (SR)

Histological confirmation NSCLC and confirmation N2/N3 negative lymph nodes

F

O

L

L

O

W

U

P

Registration and Randomization

ARM 2:

Stereotactic Body Radiation Therapy (SBRT) 18 Gy X 3 = 54 Gy

Endpoint: 3 year OS

Accrual = 420 patients


Acosog z4099 rtog 1021 phase iii trial for high risk patients opened june 20111
ACOSOG Z4099/RTOG 1021 Phase III Trial for High-risk patientsOpened June 2011

ARM 1:

Sublobar Resection ± Brachytherapy (SR)

Histological confirmation NSCLC and confirmation N2/N3 negative lymph nodes

F

O

L

L

O

W

U

P

Registration and Randomization

ARM 2:

Stereotactic Body Radiation Therapy (SBRT) 18 Gy X 3 = 54 Gy

Closed

Endpoint: 3 year OS

Accrual = 420 patients


Sbrt vs surgery for clinical stage i nsclc

Rough comparison of OS

SBRT vs. surgery for clinical stage I NSCLC


Sbrt vs surgery for clinical stage i nsclc1
SBRT vs. surgery for clinical stage I NSCLC

  • Problem #1. . .

    • Treatment groups are inherently different!

Vs.


Sbrt vs surgery for clinical stage i nsclc2
SBRT vs. surgery for clinical stage I NSCLC

  • Problem #2. . .

    • Definition of “medically operable”?

FVC

FEV1

Smoking

Diabetes

???

Performance Status

DLCO

Cardiac Co-morbidity

Predicted Postoperative Pulmonary Reserve


Sbrt vs surgery for clinical stage i nsclc3
SBRT vs. surgery for clinical 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 - Wedgevs. SBRT

    • Cornell

      • Parashar, Cancer 2010 –Wedge+Brachyvs. SBRT

    • Wash U

      • Crabtree, J Thorac Cardiovasc Surg 2010 - Any surgeryvs. SBRT

      • Robinson, JTO 2012– Lobectomy/Pneumonectomyvs. SBRT


Sbrt vs surgery for clinical stage i nsclc4
SBRT vs. surgery for clinical stage I NSCLC

Medically operable - Onishi, J Thorac Oncol 2007

  • Median F/U 38 mo (2-128 mo)

All 257 pts

OS by medical operability

3y ~70%, 5y 64.8%

3y ~40%, 5y 35%


Sbrt vs surgery for clinical stage i nsclc5
SBRT vs. surgery for clinical stage I NSCLC

Medically operable - Onishi, J Thorac Oncol 2007

Control rates by BED10 for all pts

≥ 100Gy = 64.8%

19.7%

sig

53.9%

5y overall survival


What dose for peripheral lung cancers
What dose for peripheral lung cancers?

Medically operable - Onishi, J Thorac Oncol 2007

5y OS by BED10 in medically operable

≥100 Gy

3y 80.4%, 5y 70.8%

BED = nd(1+d//)

Schemes >100 Gy:

16 Gy x 3

12 Gy x 4

10 Gy x 5

<100Gy

3y ~65%, 5y ~50%


Sbrt vs surgery for clinical stage i nsclc6
SBRT vs. surgery for clinical stage I NSCLC

Medically 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


Sbrt vs surgery for clinical stage i nsclc7
SBRT vs. surgery for clinical stage I NSCLC

Medically 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%


Local recurrence by prescription dose
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

0.6

Local Recurrence

Rx BED10< 105 Gy

0.4

p<0.001

0.2

Rx BED10≥ 105 Gy

0

0

2

4

6

8

Time (Years)


Sbrt vs surgery for clinical stage i nsclc8
SBRT vs. surgery for clinical stage I NSCLC

Medically 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%


Sbrt vs surgery for clinical stage i nsclc9
SBRT vs. surgery for clinical stage I NSCLC

Medically inoperable / High risk operable -Grills, JCO 2010

  • Median potential F/U 30 mo



Rtog 0915 overall survival
RTOG 0915 Overall Survival

Videtic et al. ASTRO and IASLC 2013



Reported toxicity for central lung cancers
Reported Toxicity for Central Lung Cancers

Timmerman et al. JCO 2006

Timmerman R. et al JCO 2006


Rtog 0813 sbrt dose levels trial completed await f u
RTOG 0813 - SBRT Dose LevelsTrial completed, await f/u

Phase I/II Dose Escalation study (N=94)

Level 1 10 Gy x 5 50 Gy

Level 2 10.5 Gy x 5 52.5 Gy

Level 3 11 Gy x 5 55 Gy

Level 4 11.5 Gy x 5 57.5 Gy

Level 5 12 Gy x 5 60 Gy

Design: Continual Reassessment Monitoring (CRM)

Endpoints:

Phase I – Any Tx-related Grade 3 or greater toxicity

Phase II – 2-year primary tumor control rate


Wu data on local control
WU Data on Local Control

Olsen, Robinson, Bradley et al. IJROBP 2011


Conclusions surgery versus sbrt
Conclusions: 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


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