Pulmonary Stereotactic Ablative Radiotherapy:
Current Implementation and Future Directions
CTOP Conference 2014
Philip Schaner M.D., Ph.D
I have no conflicts of interest to report
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: 1 - 10
• Nomenclature:
• Stereotactic ablative radiotherapy (SABR)
• Stereotactic body radiotherapy (SBRT)
SBRT LUNG
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
Subset of NSCLC appropriate for SBRT
• Mass too large, invading into nearby structures
• Primary acceptable but nodal disease present
Treatment Planning
• Highly conformal dose distribution with rapid dose fall off
• Maximally spare adjacent organs
• Low dose spill
• High dose spill
Accurate Delivery
• Target localization
• Lung cancer is a moving target….
4D Treatment Delivery
• Patient Breaths Normally – Control when XRT is on
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
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
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
Clinical
• Results:
• Local control:
•2 yr = 96%
• Patient characteristics
• Toxicity:
• Grade 3: 8%
• Grade 4-5: 0%
Rusthoven et al. JCO 2009
Areas of Investigation
• What is the appropriate SABR dose for peripheral lesions?
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.
Areas of Investigation
• What is the appropriate SABR dose for centrally located lesions?
Areas of Investigation
• Measuring SABR against Surgery
ROSEL Trial (Netherlands)
Stage IA
NSCLC
ARM 1:
Anatomical
surgical
resection with
LN dsxn
F
O
L
L
O
W
Terminated
due to poor accrual
Peripheral
lesion
ARM 2:
SABR
20 Gy x 3
12 Gy x 5
U
P
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
L
O
W
U
P
Areas of Investigation
• Measuring SABR against Surgery
ACOSOG Z4099/RTOG 1021
Phase III Trial
Opened June 2011
•T < 3 cm
• Peripheral
• High risk for surgery
• Major
• FEV1 ≤50% pred
• DLCO ≤50% pred
• Minor
• Age ≥75 years
• FEV1 51-60% pred
• DLCO 51-60% pred
Histological
confirmation
NSCLC and
confirmation
N2/N3 negative
lymph nodes
ARM 1:
Sublobar
Resection ±
Brachytherapy
(SR)
ARM 2:
Stereotactic
Body Radiation
Therapy (SBRT)
18 Gy X 3 = 54
Gy
F
O
L
L
O
W
U
P
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
Questions….