Stereotactic radiotherapy Influence of patient positioning and fixation on treatment planning - clinical results Frank Zimmermann Institut für Radioonkologie Universitätsspital Basel Petersgraben 4 CH 4031 Basel radioonkologiebasel.ch
Techniques in Radiation Therapy Conformal RT Intensity modulated RT (IMRT) Stereotactic RT (brain: SRT; body: SBRT) 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!!!! Image from BrainLab
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
Fixation systems: precision Invasive frame Stereotactic mask Body masks Conventional head mask Skin markers < 1 mm < 2 mm < 5 mm < 5 mm < 10 mm
SBRT and IGRT + Integrating image-guidance in treatment room: precision with bony landmarks about 2 mm! Need for special fixation? Only body mask systems! Images from BrainLab and Elekta
Body
Techniques available Pure stereotactic treatment Pure image-guidance Mixed stereotactic positioning and imageguidance Breath-hold and 4-D-CT Nothing at all
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 DRGs and Tarmed Increasing number of systems Pure image-guidance increasing Patients demands Although not reasonable
SBRT: Immobilization Different systems: none proven superior!
Navigation: Frame and Laser
Precision of SBRT-immobilization Yeung et al. IJROBP 2009
Body fixation + Image-guided RT (IGRT) + Integrating image-guidance in treatment room or CT: precision around 3 mm Further techniques needed?
SBRT: Immobilization systems in Japan Nagata Y, et al. IJROBP 2009
SBRT: Immobilization systems in Japan Nagata Y, et al. IJROBP 2009 Upper image from J. Wulf
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
Influence of IGRT on bone-target-relation Tumor positioning errors are reduced by breathing control Masi et al. Acta Oncol 2008
Clinical data
Fractionation schedules in SBRT Hypofractionated RT (2-5 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
Cancer-specific survival 57 % 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
Most results with normal linac
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! Improvement by more technique not documented (for the patient) 100 100 80 80 60 40 VOLUME PERCENT 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 Images from Elekta, BrainLab, Cyberknife, Internet
With very simple technique Immobilization free to usual local custom! Dose escalation by hypofractionation: Local control > 85 % Bogart et al. JCO 2010
Follow-up with FDG-PET-CT CR vs. PR? (follow-up o.k.) (follow-up, repeated biopsies, 2. FDG-PET-CT negative)
Follow-up concept FDG-PET-CT-scan if Persistent tumor > 12 months New tumor (vs. pneumonitis) Suspicious LN in CT-scan With SUV < 3,0 = CR With SUV > 4,05 = PD (27 pats.: ROC-Analysis; sensitivity / specifity 100 % each)
Conclusion High local control Few side effects Immoblization reasonable More complex techniques not proven better
Randomised trial in pancreatic cacner RCT vs. supportive therapy Author Year Pats. Therapy M-OS (months) OS (1 year) p Sinchi 2002 31 RT (50,4 Gy) + 5-FU 13,2 53,3 0,009 0 6,4 0 RCT > BSC in inoperable/unresectable cancer
RCT vs. CTx RCT for local pain and dominant local problems Otherwise systemic chemotherapy
Studies on SBRT Phase I-study, 15 patients (Koong et al. 2004): - 1 x 15, 1 x 20, 1 x 25 Gy escalation: Distant metastases only problem, 0 % CTC III tox. Phase II-study, 19 patients (Koong et al. 2005): - 45 Gy IMRT and 1 x 25 Gy: 15 % 1-OS, > 90 % local control, 10 % CTC III tox. Phase II-study, 22 patients (Hoyer et al. 2005): - 3 x 15 Gy: 5 % 1-JÜL, < 50 % local control, 23 % CTC III-IV tox.
Concept of IMRT-SBRT Fractionation 5 x 5,0 Gy margin of target volume 5 x 7,0 Gy in tumor center / at large vessels Target volume Tumor in soft tissue window margin of 5 mm axial margin of 5-15 mm cc
Dose distribution of IMRT-SBRT Dose escalation retroperitoneal paravascular
Definitive RCT Palliation: improvement of - local control (40 % LRR) - OS (plus ca. 4 Monate) - Pain (in 70 % of patients) Low toxicity, but long treatment Best combined concept? - Radiotherapy: Hypofractionation? - 5-FU / Gemcitabine / Platinum? Development of SBRT?