1. Pulmonary Stereotactic Ablative Radiotherapy:
Current Implementation and Future Directions
CTOP Conference 2014
Philip Schaner M.D., Ph.D

2. I have no conflicts of interest to report

3. Definition of Stereotactic Body Radiotherapy
Method of delivering external beam radiotherapy (EBRT)
Particles (proton) or photon
Accurately delivers EBRT with a high degree of conformality
Spatial and Temporal resolution of target and organs at risk
Maintenance of high spatial targeting accuracy throughout the entire treatment
Immobilization
High frequency position monitoring through integrated image guidance
Respiratory Motion Management
Dose per Fraction: at least equivalent to radical doses in conventional fractionation: 5 – 34 gray (Gy) [Conventional Fractionation: 1.8 – 2 Gy]
Few fractions:
Nomenclature:
Stereotactic ablative radiotherapy (SABR)
Stereotactic body radiotherapy (SBRT)

4. SBRT LUNG

5. Subset of NSCLC appropriate for SBRT
Stage I subset:
typically < 5 cm in maximal dimension
Not invading outside the chest (can be touching pleura)
Not invading into lobar bronchus
Minimal associated lung collapse
Mass well delineated

6. Subset of NSCLC appropriate for SBRT
Mass too large, invading into nearby structures
Primary acceptable but nodal disease present

7. Treatment Planning
Highly conformal dose distribution with rapid dose fall off
Maximally spare adjacent organs
Low dose spill
High dose spill

8. Accurate Delivery
Target localization
Lung cancer is a moving target….

9. 4D Treatment Delivery
Patient Breaths Normally – Control when XRT is on

10. Multi-institutional Phase II Data: RTOG 0236
Clinical
Multi-institutional Phase II Data: RTOG 0236
Inclusion:
NSCLC
T1 or T2, N0,M0
Peripheral: > 2 cm from proximal bronchial tree
Medically inoperable: FEV1 <40%, DCLO < 40%
Methodology:
All tumors received 18 Gy x 3 fractions (54 Gy)
Accrual: 55 pts
Timmerman et al. JAMA 2010

11. 3 yr = 97.3% (one T2 tumor progressed in-field)
Clinical
RTOG 0236
Results:
Local control:
3 yr = 97.3% (one T2 tumor progressed in-field)
Regional control:
3 yr = 87.2%% (2 nodal failures, both around 35 months post SABR)
Distant Failure:
3 yr T1: 14.7%
3 yr T2: 47%
Toxicity:
12.7% Grade 3 toxicity
3.6% Grade 4 toxicity
Timmerman et al. JAMA 2010

12. Any primary tumor except germ cell, leukemia, lymphoma
Clinical
Treatment of oligometastatic disease: Stage IV cancer with ≤ 5 metastatic lesions
Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases
Inclusion:
Any primary tumor except germ cell, leukemia, lymphoma
Max cumulative tumor diameter < 7 cm
Extrathoracic disease allowed: low burden, potentially treatable with 1st or 2nd line standard therapy
Adequate lung function: FEV1 >40%, DCLO >40%
Methodology:
Dose escalation to 20 Gy x 3 fractions (60 Gy)
Accrual: 38 pts => 63 lesions
Rusthoven et al. JCO 2009

13. Patient characteristics
Clinical
Results:
Local control:
2 yr = 96%
Patient characteristics
Toxicity:
Grade 3: 8%
Grade 4-5: 0%
Rusthoven et al. JCO 2009

14. Areas of Investigation
What is the appropriate SABR dose for peripheral lesions?

15. Areas of Investigation
RTOG 0915 interim outcomes:
N=94
Median FU 20.6 months
No significant difference with respect to toxicity in both arms:
9.8% 34 Gy vs 13.3% 48 Gy > Gr 3 toxicities.
Local Control at 1 yr 97% both arms.
Winner? Need longer term follow up
Local Failure increases over time in many series, one year is not enough follow up.

16. Areas of Investigation
What is the appropriate SABR dose for centrally located lesions?

17. Terminated due to poor accrual
Areas of Investigation
Measuring SABR against Surgery
ROSEL Trial (Netherlands)
Stage IA NSCLC
Peripheral lesion
ARM 1:
Anatomical surgical resection with LN dsxn
ARM 2:
SABR
20 Gy x 3
12 Gy x 5 F O L W U P
Terminated due to poor accrual

18. Lobectomy or pneumonectomy
Areas of Investigation
Measuring SABR against Surgery
Lung Cancer STARS trial:
phase III, endpoint 3 yr OS
Stage I NSCLC
< 4 cm
Good surgical candidate
FEV1 > 40% pred
DLCO > 40% pred
Post-op predicted FEV1 > 30%
ARM 1:
Lobectomy or pneumonectomy
ARM 2:
SABR using Cyberknife
Peripheral: 20 Gy x 4
Central: 15 Gy x 4 F O L W U P

19. ACOSOG Z4099/RTOG 1021 Phase III Trial Opened June 2011
Areas of Investigation
Measuring SABR against Surgery
ACOSOG Z4099/RTOG Phase III Trial Opened June 2011
Histological confirmation NSCLC and confirmation N2/N3 negative lymph nodes
T < 3 cm
Peripheral
High risk for surgery
Major
FEV1 ≤50% pred
DLCO ≤50% pred
Minor
Age ≥75 years
FEV % pred
DLCO 51-60% pred
ARM 1:
Sublobar Resection ± Brachytherapy (SR)
ARM 2:
Stereotactic Body Radiation Therapy (SBRT) 18 Gy X 3 = 54 Gy F O L W U P

20. Areas of Investigation
Combining radiofrequency ablation with SABR
UNM: RFA combined with SABR for large lung tumors
T2-4N0 > 3 cm; N1-3 if M1 eligible
40 Gy/5 fractions escalating to 50 Gy/5 fractions f/b RFA procedure
Using SBRT as a boost for Stage II/III NSCLC
U Kentucky: Stage IIA – selected III-B
59.4 Gy chemoradiotherapy => if residual disease: boost 10 Gy x 2 (peripheral)
Proton vs Photon SBRT
SBRT combined with chemotherapy
Maintenance chemotherapy vs consolidative SBRT for Stage IV NSCLC
UTSW: 1st line chemo (no biologics) => up to six discrete extracranial lesions
U Kentucky: T1-T3N0 NSLC => SBRT then adjuvant cisplatin + docetaxel or pemetrexed

21. Questions….