Therapy of Non-Operable early stage NSCLC

Transcription

1 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

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3 This is our territory

4 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

5 Stage I & II Radiotherapy STAGE I Median survival 21 mos. Vs. 14 mos. STAGE II Median survival 14mos. Vs. 9 mos. Juan P, CHEST

6 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 % Overall 2y 22 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

7 Stereotactic Ablative (SABR) STEREOTACTIC BODY (SBRT)

8 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.

9 Radiosurgery & Radiotherapy Radiosurgery Radiotherapy Dose per # 6 25 Gy Gy Number of # 1 5 fractions 30 Fractions Beams/# Beams Targeting accuracy 5 10 Beams < 1mm 3 20 mm Clinical intent Tumor ablation Tumor control

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11 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

12 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

13 OS Operability and the Dose of XRT Hiroshi Onishi Cancer 2004

14 Operability and the Dose of XRT 88% 68% Hiroshi Onishi Cancer 2004

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17 Bronchial Tree Anatomy

18 Thoracic SBRT- Toxicity Timmerman,et al., J Clin Oncol 2006

19 RTOG 0236 (Phase II) N=55 ( T1 44, T2 11) biopsy proven Between 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

20 (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 Abstract 7523

21 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.

22 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 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 Jul 10;27(20):3290-6

23 Patterns of Rec. after SBRT Retrospective analysis N=676 between Median OS. 41 mos. Local control 5y The pattern of failure was distant relapse 66% (Isolated mets. 46%) Senthi S 2012 Lancet Oncol

24 BED 151 to

25 May 27 th 2014

26 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.

27 Evidences coming CHINA Meta-analysis Retrospective -JAPAN Europe (Phase II (RTOG 0618)Phase II(operable) (RTG 0235)Phase II(inoperable)

28 Evidence coming Phase III

29 What are we waiting for? Optimum dose remains uncertain Dose fractionation schemes We are waiting for Phase III trials

30 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

31 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

32 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 SBRT

33 This is your territory

34 (SBRT)

35 What about Lung movement?

36 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

37 Tumor volume in 3D CRT ICRU-62 ITV = CTV + IM (Internal motion) PTV = ITV + SM (Setup Margin)

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39 Stereotactic Radiosurgery(SRS) Stereotactic Body Frame

40 Gated Radiation Therapy (4D)

41 Synchrony

42 How does the CyberKnife Treat Lung Cancer? Tracks and automatically corrects for respiratory motion

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47 Before 4 months after SRS

48 Before 6 mons. 9 mons.

49 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

50 THANK YOU Standard of care is surgery and SBRT the second option