3Definition of Stereotactic Body Radiotherapy Method of delivering external beam radiotherapy (EBRT)Particles (proton) or photonAccurately delivers EBRT with a high degree of conformalitySpatial and Temporal resolution of target and organs at riskMaintenance of high spatial targeting accuracy throughout the entire treatmentImmobilizationHigh frequency position monitoring through integrated image guidanceRespiratory Motion ManagementDose 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)
5Subset of NSCLC appropriate for SBRT Stage I subset:typically < 5 cm in maximal dimensionNot invading outside the chest (can be touching pleura)Not invading into lobar bronchusMinimal associated lung collapseMass well delineated
6Subset of NSCLC appropriate for SBRT Mass too large, invading into nearby structuresPrimary acceptable but nodal disease present
7Treatment PlanningHighly conformal dose distribution with rapid dose fall offMaximally spare adjacent organsLow dose spillHigh dose spill
8Accurate DeliveryTarget localizationLung cancer is a moving target….
94D Treatment DeliveryPatient Breaths Normally – Control when XRT is on
10Multi-institutional Phase II Data: RTOG 0236 ClinicalMulti-institutional Phase II Data: RTOG 0236Inclusion:NSCLCT1 or T2, N0,M0Peripheral: > 2 cm from proximal bronchial treeMedically inoperable: FEV1 <40%, DCLO < 40%Methodology:All tumors received 18 Gy x 3 fractions (54 Gy)Accrual: 55 ptsTimmerman et al. JAMA 2010
113 yr = 97.3% (one T2 tumor progressed in-field) ClinicalRTOG 0236Results: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 toxicity3.6% Grade 4 toxicityTimmerman et al. JAMA 2010
12Any primary tumor except germ cell, leukemia, lymphoma ClinicalTreatment of oligometastatic disease: Stage IV cancer with ≤ 5 metastatic lesionsMulti-institutional phase I/II trial of stereotactic body radiation therapy for lung metastasesInclusion:Any primary tumor except germ cell, leukemia, lymphomaMax cumulative tumor diameter < 7 cmExtrathoracic disease allowed: low burden, potentially treatable with 1st or 2nd line standard therapyAdequate lung function: FEV1 >40%, DCLO >40%Methodology:Dose escalation to 20 Gy x 3 fractions (60 Gy)Accrual: 38 pts => 63 lesionsRusthoven et al. JCO 2009
13Patient characteristics ClinicalResults:Local control:2 yr = 96%Patient characteristicsToxicity:Grade 3: 8%Grade 4-5: 0%Rusthoven et al. JCO 2009
14Areas of Investigation What is the appropriate SABR dose for peripheral lesions?
15Areas of Investigation RTOG 0915 interim outcomes:N=94Median FU 20.6 monthsNo 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 upLocal Failure increases over time in many series, one year is not enough follow up.
16Areas of Investigation What is the appropriate SABR dose for centrally located lesions?
17Terminated due to poor accrual Areas of InvestigationMeasuring SABR against SurgeryROSEL Trial (Netherlands)Stage IA NSCLCPeripheral lesionARM 1:Anatomical surgical resection with LN dsxnARM 2:SABR20 Gy x 312 Gy x 5FOLWUPTerminated due to poor accrual
18Lobectomy or pneumonectomy Areas of InvestigationMeasuring SABR against SurgeryLung Cancer STARS trial:phase III, endpoint 3 yr OSStage I NSCLC< 4 cmGood surgical candidateFEV1 > 40% predDLCO > 40% predPost-op predicted FEV1 > 30%ARM 1:Lobectomy or pneumonectomyARM 2:SABR using CyberknifePeripheral: 20 Gy x 4Central: 15 Gy x 4FOLWUP
19ACOSOG Z4099/RTOG 1021 Phase III Trial Opened June 2011 Areas of InvestigationMeasuring SABR against SurgeryACOSOG Z4099/RTOG Phase III Trial Opened June 2011Histological confirmation NSCLC and confirmation N2/N3 negative lymph nodesT < 3 cmPeripheralHigh risk for surgeryMajorFEV1 ≤50% predDLCO ≤50% predMinorAge ≥75 yearsFEV % predDLCO 51-60% predARM 1:Sublobar Resection ± Brachytherapy (SR)ARM 2:Stereotactic Body Radiation Therapy (SBRT) 18 Gy X 3 = 54 GyFOLWUP
20Areas of Investigation Combining radiofrequency ablation with SABRUNM: RFA combined with SABR for large lung tumorsT2-4N0 > 3 cm; N1-3 if M1 eligible40 Gy/5 fractions escalating to 50 Gy/5 fractions f/b RFA procedureUsing SBRT as a boost for Stage II/III NSCLCU Kentucky: Stage IIA – selected III-B59.4 Gy chemoradiotherapy => if residual disease: boost 10 Gy x 2 (peripheral)Proton vs Photon SBRTSBRT combined with chemotherapyMaintenance chemotherapy vs consolidative SBRT for Stage IV NSCLCUTSW: 1st line chemo (no biologics) => up to six discrete extracranial lesionsU Kentucky: T1-T3N0 NSLC => SBRT then adjuvant cisplatin + docetaxel or pemetrexed