Results of Stereotactic radiotherapy for Stage I and II NSCLC Is There a Need for Image Guidance?

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1 Results of Stereotactic radiotherapy for Stage I and II NSCLC Is There a Need for Image Guidance? Frank Zimmermann Institute of Radiation Oncolgy University Clinic Basel Petersgraben 4 CH 4031 Basel radioonkologiebasel.ch

2 Techniques in Radiation Therapy Conformal RT Intensity modulated RT (IMRT) Stereotactic RT (brain: SRT; body: SBRT) Image-guided RT (IGRT) Protons Heavy Ions Neutrons

3 Image-guidance by frame: a 3-D-room Y Z X System creates a 3-D-area: - strong correlation of xyz-coordinates in patient and in frame - precise fixation of the patient!!!!

4 Fixation

5 Fixation systems: mean precision Invasive frame Stereotactic mask Body fixation devices Skin markers < 1 mm < 2 mm < 4 mm < 10 mm

6 SBRT: Immobilization Different systems: none proven superior!

7 Precision of SBRT-immobilization Yeung et al. IJROBP 2009

8 Positioning with Infrared-System Systems from BrainLab and Cyberknife

9 Techniques available Pure stereotactic treatment (Bodyfix a.o.) Pure image-guidance (cone-beam-ct, Novalis, Cyberknife, Tomotherapy a.o.) Mixed stereotactic positioning and image-guidance (most use today) Breath-hold and 4-D-CT Nothing at all

10 Competition and Problems Companies with their products Increasing speed of development of techniques we never asked for Quality assurance? Radiation-oncology institutions Internet-platform Pressure of reimbursement Increasing number of systems Pure image-guidance increasing Patients demands Although not reasonable

11 Navigation

12 Navigation: Frame and Laser

13 Navigation in Japan Nagata Y, et al. IJROBP 2009

14 Navigation with conventional X-ray + Integrating image-guidance in treatment room: precision with bony landmarks about 2 mm! Need for special fixation?

15 Breath Control and X-ray-IGRT Systems from Cyberknife and BrainLab

16 Breath control and CT-IGRT

17 Influence of breathing control in IGRT Masi et al. Acta Oncol 2008

18 Influence of IGRT on bone-target-relation Tumor positioning errors are reduced by breathing control Masi et al. Acta Oncol 2008

19 Electromagnetic navigation Optical System with Optical 3 Infrared System Cameras with 3 Infrared Cameras 4D Electromagnetic Array 4D Electromagnetic Array 4D Tracking Station 4D Tracking Station Implanted Beacon Implanted Electromagnetic Beacon Electromagnetic Transponders Transponders 4D Console 4D Console Calypso-System

20 Calypso-System Implanted marker Via Bronchoscopy Low toxicity, high precision

21 Works in Progress

22 Plenty of techniques, but clinical data???

23 Fractionation schedules in SBRT Hypofractionated RT (2-5 fractions) Single fraction (radiosurgery) But: In literature often not correct Combination with IGRT common

24 Radiosurgery with Linac Gy in isocenter, 80%-Isodose surrounding 42 patients, median follow-up: 15 months Hof et al., Cancer 2007

25 Radiosurgery with linac 30 Gy in isocenter Median follow-up: 20 months Local control: 81 % at 3 years Fritz et al., Lung Cancer 2008

26 Side effects with fixation but without IGRT 64,3 % lung tissue alterations 0 % toxizity CTC III-IV Hof et al., Cancer 2007

27 Lung function Fritz et al., Lung Cancer 2008

28 Required dose: > 1 x 30 Gy PTV-including Low toxicity Optimal dose? Image-guidance??? Timmerman et al., J Thorac Surg 2007

29 Importance of dose Local control rate 1 TTLP=1.6 +/- 1.4 y BED > 100 Gy (n=228) 5-y LC :84.3% p< BED < 100 Gy (n=72) 5-y LC : 57.1% Time (years) H Onishi et al. 2007

30 Mean results at 5 years worldwide Overall survival 47 % Cancer-specific survival 57 % Local control 86 % Local control with BED > 100 ~ 95 % Side effects III-IV < 3 % 35 studies between Median follow-up months 1000 patients BED > 100 Gy for T1 BED > 140 Gy for T2 Chi et al. Radiother Oncol 2010

31 Most results with normal linac

32 RTOG Data (with comparable simple technique) Amerikanische Ergebnisse Necessary dose: 3 x Gy in including 80 %-isodose Timmerman et al., J Thorac Surg 2007

33 Own Data (Munich, Basel) 92 patients ct 1-2 cn 0 functional not operable Histogramm mit Matte vor CT Age 76 years Mean total dose (60 %) 37.5 Gy Follow-up 32 Months Relative Häufig keit 0,50 0,40 0,30 0,20 0,10 0,00-4,0-3,0-2,0-1,0 0,0 1,0 2,0 3,0 4,0 5,0 Intervall Anzahl n 29 Mittelwert -0,09 Varianz 3,36

34 Follow-up with FDG-PET-CT CR vs. PR? (follow-up o.k.) (follow-up, repeated biopsies, second FDG-PET-CT negativ)

35 Follow-up FDG-PET-CT-scan if persistent solide tumor > 12 months new solide tumor (vs. pneumonitis) suspicious LN in CT-scan With SUV < 3 = CR With SUV > 7 = PD

36 Results Patients at risk (%) 1 0,8 0,6 0,4 0,2 Local Control Overall survival Disease specific survival LR-free Surv. 96, 88, 88, 83 % CS-Surv. 96, 82, 73, 53 % Months Patients at risk (total patients n=68) OS 83, 71, 51, 29 % Local Control Disease free survival Overall survival according to Kaplan Meier Zimmermann et al. Acta oncol 2006 Andratschke et al. Radiother Oncol 2011

37 Munich/Basel data stage II Concept: Local control rate: Side effects: 5 x 7-8 Gy (60%-isodose) > 80 % after 1.5 years similar as in stage I

38 Side effects (%) Type RT 4 W 8 W 4 M 12 M Fatigue ,1 3,4 3,4 Shivering 5,7 1, Nausea 3,4 6, Dysphagia 1, Dermatitis 3,4 3,4 3,4 3,4 0 Zimmermann et al., 2010

39 Pneumonitis ( % ) Grade RT 4 W 8 W 4 M 6 M > 12 M I 1,1 22,0 16,3 12,8 12,0 15,0 II 0 6,8 16,3 35,8 16,6 19,2 III ,6 2,8 3,0

40 With very simple technique Immobilization free to usual local custom, no IGRT! Dose escalation by hypofractionation: Local control > 85 %, low toxicity! Bogart et al. JCO 2010

41 More technique? More money! Improvement by more technique not documented (for the patient) VOLUME PERCENT VOLUME PERCENT DOSE DOSE PERCENT

42 Conclusion High local control: optimal fractionation schedule? total dose? Few severe side effects Statistical difference to 3 %? Immoblization reasonable No system proven superior More complex techniques not better (yet?)