SBRT in early stage NSCLC Optimal technique and tumor dose Frank Zimmermann Clinic of Radiotherapy and Radiation Oncology University Hospital Basel Petersgraben 4 CH 4031 Basel radioonkologiebasel.ch
Techniques in Radiation Therapy Conformal RT Intensity modulated RT (IMRT) Stereotactic RT (brain: SRT; body: SBRT / SABR) Image-guided RT (IGRT) Protons Heavy Ions Neutrons
Indications for stereotactic radiotherapy Brain metastases Recurrent glioma Non-small-cell lung cancer stage I (and II?) Lung metastases Liver metastases Pancreatic cancer Prostate cancer
Frame for - biopsies - radiosurgery Coming from neurosurgery
Definition of 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!!!!
No Relevance Type of beam: Linac Cyberknife Tomotherapy Protons Neutrons Heavy particles
No Relevance Fractionation schedule: Conventional fractionation Hypofractionation Hyperfractionation
No relevance Beam: Shape Direction Number
Relevant Type of isocenter definition Type of immobilization
Isocenter definition and immobilisation Y Z X System creates a 3-D-area: - precise fixation of the patient!!!!
Navigation: Frame and Laser
Precision of SBRT-immobilization Yeung et al. IJROBP 2009
Techniques available Pure stereotactic treatment Pure image-guidance Mixed stereotactic positioning and imageguidance Breath-hold and 4-D-CT Nothing at all
SBRT and IGRT + Integrating image-guidance in treatment room: precision with bony landmarks about 2 mm! Need for special fixation? Only body mask systems!
Body fixation + Image-guided RT (IGRT) + Integrating image-guidance in treatment room or CT: precision around 3 mm Further techniques needed?
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 re-financing Increasing number of systems Pure image-guidance increasing Patients demands Although not reasonable
SBRT: Immobilization Different systems: none proven superior!
SBRT: Immobilization systems in Japan Nagata Y, et al. IJROBP 2009
SBRT: documentation of pos. in Japan Nagata Y, et al. IJROBP 2009
Breath control + IGRT
Influence of breathing control in IGRT Masi et al. Acta Oncol 2008
Fractionation schedules in SBRT Hypofractionated RT (2-10 fractions) Single fraction (radiosurgery) But: In literature often not correct Combination with IGRT common
Radiosurgery: single fraction
Radiosurgery with Linac 19-30 Gy in isocenter, 80%-Isodose surrounding 42 patients, median follow-up: 15 months Hof et al., Cancer 2007
Side effects 64,3 % lung tissue alterations 0 % toxizity CTC III-IV Hof et al., Cancer 2007
Radiosurgery with linac 30 Gy in isocenter Median follow-up: 20 months Local control: 81 % at 3 years Fritz et al., Lung Cancer 2008
Required dose: > 1 x 30 Gy PTV-including Timmerman et al., J Thorac Surg 2007
Fractionated SBRT
Importance of dose Local control rate 1 TTLP=1.6 +/- 1.4 y 0.8 0.6 0.4 BED > 100 Gy (n=228) 5-y LC :84.3% p<0.01 0.2 BED < 100 Gy (n=72) 5-y LC : 57.1% 0 0 2 4 6 8 10 12 Time (years) H Onishi et al. 2007
Mean results at 5 years worldwide Overall survival 47 % Cancer-specific survival 57 % Local control 86 % 35 studies between 2002 2009 Median follow-up 11 90 months 1000 patients BED > 100 Gy for T1 BED > 140 Gy for T2 Chi et al. Radiother Oncol 2010 Zimmermann et al. Sem RT 2010
RTOG Data Amerikanische Ergebnisse Necessary dose: 3 x 20-22 Gy in including 80 %-isodose Timmerman et al., J Thorac Surg 2007
Side effects (%) Type RT 4 W 8 W 4 M 12 M Fatigue 15 11 7,1 3,4 3,4 Shivering 5,7 1,1 0 0 0 Nausea 3,4 6,8 0 0 0 Dysphagia 1,1 0 0 0 0 Dermatitis 3,4 3,4 3,4 3,4 0
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 0 0 0 2,6 2,8 3,0
More technique? More money! 100 100 80 80 VOLUME PERCENT 60 40 VOLUME PERCENT 60 40 20 20 0 0 20 40 60 80 100 120 DOSE 0 0 20 40 60 80 100 120 DOSE PERCENT
With very simple technique Immobilization free to usual local custom! Dose escalation by hypofractionation: Local control > 85 % Bogart et al. JCO 2010
Conclusion High local control: 1 x 40 Gy (not proven) 3 x 20 Gy (prosp. II-trial) 4 x 12 Gy (retrosp.) 5 x 11 Gy (prosp.) 10 x 7 Gy (not proven) Few side effects Immoblization reasonable More complex techniques not proven better