SBRT Stage I NSCLC Therapy of Non-Operable early stage NSCLC Dr. Adnan Al-Hebshi MD, FRCR(UK), FRCP(C), ABR King Faisal Specialist Hospital & Research Centre
This is our territory
Early Stages NSCLC Surgical resection is the standard of care 70% cure rate if the patient fit for surgery BUT 20% can not tolerate surgery ( medical problems) Standard alternative is conventional XRT 10 30% OS 45 65% local control Asamura H, J Thorac Oncol, 2008 Dosoretz D Seminal Radat Oncol, 1996
Stage I & II Radiotherapy STAGE I Median survival 21 mos. Vs. 14 mos. STAGE II Median survival 14mos. Vs. 9 mos. Juan P, CHEST - 2008
XRT for stage I/II Not sufficiently fit for or declining surgery (medically inoperable). Review included 2000 medically un-resectable patients from 26 non-randomized studies. Cancer S S. @2y 54 93%, @5y 13 39% Overall S. @ 2y 22 72%, @ 5y 0 42% Following XRT 11 43% died from noncancerous causes. Reflecting Poor health status Most of them staged clinically. Rowell NP, Cochrane Database Syst Rev. 2001
Stereotactic Ablative (SABR) STEREOTACTIC BODY (SBRT)
Stereotactic Radiosurgery Stereo In Greek means 3 Dimensional Tact = In Latin means to touch It mean 3D arrangement to touch It is a technique of delivering high dose radiation therapy to a specific target while delivering minimal dose to surrounding tissues.
Radiosurgery & Radiotherapy Radiosurgery Radiotherapy Dose per # 6 25 Gy 1.8 2 Gy Number of # 1 5 fractions 30 Fractions Beams/# 150 200 Beams Targeting accuracy 5 10 Beams < 1mm 3 20 mm Clinical intent Tumor ablation Tumor control
Radiosurgery High Precision high degree of reproducible spatial correlation of the target and radiation dose High accuracy (<1mm) delivering the intended dose within 1mm of planned position Rapid fall off of radiation dose at the periphery of the target minimal dose to the normal tissue in proximity to the target High dose conformity
Japanese Multiinstitutional study N= 245 (13 institutions) Stage I NSCLC (T1= 155, T2= 90) The median Biological effective dose (BED) =108Gy. Median duration of F/U 24 months Local recurrence rate 8.1% 3y OS for operable pt. 88.4% Hiroshi Onishi Cancer 2004
OS Operability and the Dose of XRT Hiroshi Onishi Cancer 2004
Operability and the Dose of XRT 88% 68% Hiroshi Onishi Cancer 2004
Bronchial Tree Anatomy
Thoracic SBRT- Toxicity Timmerman,et al., J Clin Oncol 2006
RTOG 0236 (Phase II) N=55 ( T1 44, T2 11) biopsy proven Between 2004 2009 3 y primary control 98 % 3 y DFS 48% OS 56% Only one patient had recurrence or progression at primary site 3 patients had recurrence within the involved lobe. Toxicity 12% G3, 17% G4 ( no G5) Timmerman, JAMA 2010
(n= 33) Operable by Tho. Surgeon utilizing specific criteria 26 evaluable pts.( T1 23, T2 3 ) - biopsy proven Dose was 18 Gy X 3 # in 1½-2 weeks. Median age was 72 years. Median FEV 1 72%, DLCO 68% predicted. Median follow-up was 25 months 2-year primary tumor failure rate of 7.7%. Timmerman,et al., ASCO Annual meeting 2013 - Abstract 7523
RTOG 0618 (Phase II) Only one patient was eligible for attempted surgical salvage and underwent lobectomy 1.2 years post SBR. 2 year PFS 65.4% (95% CI: 44.0%, 80.3%) 2 year OS 84.4% (95% CI: 63.7%, 93.9%) SBRT associated with a high rate of PTC moderate treatment related morbidity infrequent need for surgical salvage in operable early stage lung cancer pts with peripheral lesions.
Prospective phase II trial of medically inoperable stage I - NSCLC N=57 T1N0M0 (70%) and T2N0M0 (30%) 7 centers in Sweden, Norway, and Denmark Observed up to 36 months Dose : 15Gy x3 @ 67% isodose line 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-theart treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances. Baumann J Clin Oncol. 2009 Jul 10;27(20):3290-6
Patterns of Rec. after SBRT Retrospective analysis N=676 between 2003 2011 Median OS. 41 mos. Local control 89% @ 5y The pattern of failure was distant relapse 66% (Isolated mets. 46%) Senthi S 2012 Lancet Oncol
BED 151 to 244 85 113 120 113 180 211 105 120-149 80
May 27 th 2014
Meta-Analysis 40 SBRT studies (4850 pts.) M F/u 28 mos. 23 surgical studies (7071 pts.) M F/u 37 mos. OS and DFS are similar if adjusted for Age and operability Median age for SBRT 74y and 66 for surgery The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy.
Evidences coming CHINA Meta-analysis Retrospective -JAPAN Europe (Phase II (RTOG 0618)Phase II(operable) (RTG 0235)Phase II(inoperable)
Evidence coming Phase III
What are we waiting for? Optimum dose remains uncertain Dose fractionation schemes We are waiting for Phase III trials
The greatest difficulty in the world is not for people to accept new ideas, but to make them forget about old ideas. John Maynard Keynes
The greatest difficulty in the world is not for Surgeons to accept new treatment, but to make them forget about old treatment. Adnan S. Al-Hebshi
RTOG 1021/ACSOG Z4099 Phase III Study Closed Sublobar Resection Vs. SBRT in High Risk Patients with Stage I (NSCLC) Permanently terminated due to poor accrual May 2013. SBRT
This is your territory
(SBRT)
What about Lung movement?
Tumor Motion During Respiration Tumor Cross-sectional View of Patient s Chest Tumor Some motion is mostly Anterior / Posterior Some motion is mostly Superior / Inferior
Tumor volume in 3D CRT ICRU-62 ITV = CTV + IM (Internal motion) PTV = ITV + SM (Setup Margin)
Stereotactic Radiosurgery(SRS) Stereotactic Body Frame
Gated Radiation Therapy (4D)
Synchrony
How does the CyberKnife Treat Lung Cancer? Tracks and automatically corrects for respiratory motion
Before 4 months after SRS
Before 6 mons. 9 mons.
SBRT for T1-T2N0 5# over 1-2 weeks or 1 single fraction as radiosurgery. Recent data report local control rates of 90%. < 10% of all patients develop isolated tumor recurrences in regional lymph nodes. 3y survival is significantly improved to more than 80% when BED > 100 Gy. Systemic tumor recurrence still is a major problem. Zimmerman F 2010
THANK YOU Standard of care is surgery and SBRT the second option