1. Learn More At: www.DoctorVermeulen.com CyberKnife Radiosurgery in the Treatment of Early and Advanced (Oligo-Metastases) Breast Cancer Sandra Vermeulen, MD Co- Director, Seattle CyberKnife Center Seattle, Wa

2. Learn More At: www.DoctorVermeulen.com Disclosures Accuray (vendor of Cyberknife)

3. Learn More At: www.DoctorVermeulen.com Breast Conservation Therapy Treatment Objectives Acceptable cosmesis Local control of disease Minimal treatment complications

4. Learn More At: www.DoctorVermeulen.com In 2000 the National Cancer Data Base reported that only 50% of eligible candidates received conservative surgery followed by radiation therapy

5. Learn More At: www.DoctorVermeulen.com Prospective Randomized Trials BCS + RT vs MRM Trial LR % Survival % F/U BCT vs MRM BCT vs MRM Years NSABP 14 v 10 47 v 46 20 Milan 9 v 2 59 v 59 20

6. Learn More At: www.DoctorVermeulen.com External Beam Irradiation

7. Learn More At: www.DoctorVermeulen.com External Beam Coverage of the Breast and Inclusion of Normal Tissues

8. Learn More At: www.DoctorVermeulen.com Advantages of Partial Breast Irradiation over Whole Breast Treatment Decreased time and inconvenience Decreased acute and chronic toxicity Improved radiation therapy underutilization

9. Learn More At: www.DoctorVermeulen.com Regional Failures within the Breast TrialCS AloneCS + RT NSABP2.7 17/6363.8 24/629 Ontario3.5 15/4210.9 4/416 Milan2.8 8/2800.6 2/299 Finland5.5 4/725.0 4/80 Sweden1.5 3/1940.5 1/187 Range (%)1.5-5.50.5-5.0

10. Learn More At: www.DoctorVermeulen.com Techniques for Partial Breast Irradiation 3-D conformal external beam radiotherapy Multi-catheter brachytherapy Balloon catheter brachytherapy Intra-operative Radiotherapy

11. Learn More At: www.DoctorVermeulen.com Multi-Catheter Brachytherapy

12. Learn More At: www.DoctorVermeulen.com Multi-Catheter Brachytherapy

13. Learn More At: www.DoctorVermeulen.com 3-D Conformal Irradiation Technique

14. Learn More At: www.DoctorVermeulen.com Balloon Catheter Brachytherapy

15. Learn More At: www.DoctorVermeulen.com IORT Veronesi et al: A preliminary report of IORT in limited stage breast cancers that are conservatively treated. Eur J Cancer. 2001 Nov;37(17):2178-83 Mobile linear accelerator 3-9 Mev eb 10-21 Gy in 103 patient No complications

16. Learn More At: www.DoctorVermeulen.com NSABP Protocol B-39 RTOG Protocol 0413 A randomized Phase III Study of Conventional Whole Breast Irradiation vs Partial Breast Irradiation for Women with Stage 0, I, II Breast Cancer

17. Learn More At: www.DoctorVermeulen.com NSABP Dose Prescription 3D Conformal External Beam Radiotherapy 38.00 Gy total dose at 3.85 Gy per fraction delivered twice daily in 10 fractions over 5 treatment days Multi-Catheter and Balloon catheter Brachytherapy 34 Gy total dose at 3.4 Gy per fraction delivered twice daily in 10 fractions over 5 treatment days

18. Learn More At: www.DoctorVermeulen.com NSABP Target Volume for 3D-CRT patient motion The CTV is defined by expanding the excision cavity volume by 15 mm. The PTV includes a 10 mm expansion of the CTV to compensate for patient motion and variability of treatment set-up

19. Learn More At: www.DoctorVermeulen.com Novel Techniques for Partial Breast Irradiation CyberKnife

20. Learn More At: www.DoctorVermeulen.com

21. CyberKnife Approved by the FDA since 2001 Nearly 30,000 patients treated worldwide More than 200 peer review papers have been published More than 80 hospitals and medical centers provide CyberKnife technology

22. Learn More At: www.DoctorVermeulen.com How is the technology different? Advanced interactive robotics Real-time imaging Dynamic automated motion tracking Flexible and accurate linac multiple-beam radiation delivery

23. Learn More At: www.DoctorVermeulen.com Methods for tracking motion Skull and spine tracking: bony landmarks are tracked Fiducial tracking: radio-opaque marker are placed near soft tissue targets and tracked Respiratory tracking (Synchrony): with respiration, LED’s on the exterior of the patient are correlated with the movement of the target/tumor and fiducials

24. Learn More At: www.DoctorVermeulen.com Fiducial Tracking Gold seeds 5.0 mm x 0.9-1.2 mm

25. Learn More At: www.DoctorVermeulen.com Respiratory Tracking Beam Off Beam On Treatment Field 1.2. 3.4. Gating Synchrony TM Treatment beam is turned on and off as tumor enters and exits a static treatment field Dynamic treatment field follows the tumor while the treatment beam is turned on = Over-treated healthy tissue

26. Learn More At: www.DoctorVermeulen.com Accuracy When used properly, Synchrony™ provides a degree of accuracy of better than 1.5mm –Allows reduced planning margins for lesions that move with respiration Gating and breath holding require margins of 5-10mm to compensate for setup and targeting uncertainty

27. Learn More At: www.DoctorVermeulen.com Cyberknife Demonstration

28. Learn More At: www.DoctorVermeulen.com Cyberknife Beam Profile

29. Learn More At: www.DoctorVermeulen.com Indications for Cyberknife Intracranial lesions: single fraction, or fractionated Head and neck: –Nasopharynx & base of skull, primary or recurrent –Other sites, as boost following conventional RT, or recurrent Spine: where surgery indicated but not feasible, and conventional RT less effective or not possible Lung: where surgery indicated but not feasible Liver: where surgery indicated but not feasible Pancreas: unresectable but localized tumors Kidney: where surgery indicated but not feasible Previously irradiated tumors: retreatment w/ conventional RT not possible, for severe symptoms, Karnofsky > 40

30. Learn More At: www.DoctorVermeulen.com A phase II Study of CyberKnife Radiosurgery delivered to the Partial Breast for Women with Stage 0, I, II Breast Cancer Seattle CyberKnife

31. Learn More At: www.DoctorVermeulen.com Primary and Secondary Aims of Study This study will evaluate the technical feasibility of PBI with the CyberKnife as well as evaluate QOL issues that relate to treatment side- effects, cosmetic outcomes and patient convenience

32. Learn More At: www.DoctorVermeulen.com Patient Eligibility Stage 0, I, II non-lobular breast cancer Cancer must be ≤ 3 cm Surgical treatment must be a lumpectomy Margins must be > 2mm for both DCIS and invasive disease Negative sentinel Lymph node(s) or an axillary dissection Lumpectomy cavity must be clearly delineated

33. Learn More At: www.DoctorVermeulen.com Justification of Radiosurgical Dose By applying the linear-quadratic cell survival model with an alpha-beta ratio of 4, a dose of 30 Gy given in 5 stages of 6 Gy between 5 to 10 days is radiobiologically equivalent in tumor control and late breast tissue complications as the whole breast doses used by NSABP

34. Learn More At: www.DoctorVermeulen.com Partial Breast Planning for CyberKnife The CTV is the excision rim plus a 10 mm margin in all directions The PTV is defined as the CTV plus a 5mm margin The dose is will be delivered to the 70 - 85% isodose prescription line

35. Learn More At: www.DoctorVermeulen.com Cyberknife PBI Treatment Volume

36. Learn More At: www.DoctorVermeulen.com Cyberknife Radiosurgery for Early Breast Cancer: a pilot investigation to determine the feasibility of Synchrony imaging and fiducial identification for motion tracking Seattle Cyberknife Fresno Community Regional Medical Center

37. Learn More At: www.DoctorVermeulen.com Protocol Objectives To determine if there is sufficient geometric stability of gold markers in the breast for Synchrony motion tracking To determine the optimal patient treatment position for Synchrony motion tracking

38. Learn More At: www.DoctorVermeulen.com Seattle CyberKnife Summary Greater than 140 sites treated including primary tumors of the lung, brain, prostate and metastases to the lung, liver, brain and bone June 2007 to begin a breast pilot to determine the feasibility of Synchrony motion tracking January 2008 planned open enrollment for a multi-institutional PBI protocol using Cyberknife