1. NCI Workshop Advanced Technologies for Breast Cancer

2. Radiation of Intact Breast Excellent LOCAL CONTROL (95 % at 5 years) achieved with standard dose 50 Gy Whole Breast plus boost to primary site NO NEED to Dose Escalate OARs: Skin, Lung, Heart (Left sided cases) and “Cosmetic Outcome”

3. Intact Breast Phase III Trial Vancouver/Toronto Study comparing IMRT to Standard Wedge 2 D Planning Presented at ASTRO 2006 358 patients entered/331 analyzed for acute toxicity up to 6 weeks Results: IMRT plans showed improved dose homogeneity and clinically associated with reduced incidence moist desquamation (31% vs 48%, p=0.0019)

4. Prone IMRT at MSKCC Minimize radiation to the heart and lungs by utilizing gravity effect on mobile breast Specify beam direction (Two tangent fields) before inverse planning process to avoid an increase in integral dose Bring dose intensity pattern to field edge to account for minimal edema thru treatment

5. Figure 1a. Customized prone breast board with adjustable aperture and wedge for contralateral breast. Figure 1b. Ipsilateral breast and anterior chest wall hang in a dependent fashion away from the thorax while the ipsilateral arm is placed above the head 1a1b Goodman

6. Figure 6. Left breast irradiation using prone breast IMRT technique can spare left ventricle and coronary arteries. Goodman

7. IMRT Conventional Figure 4a. Transverse Dose Distributions 1131081009050 Isodose in % 10210 Goodman

8. IMRT Conventional Figure 4b. Sagittal Dose Distributions 1171081009050 Isodose in % 10210 Goodman

9. Figures 3a and 3b. Dose-Volume Histogram (DVH) for prone breast IMRT technique Fig 3a. 5mm skin was excluded from the PTV. IMRT: Intensity modulated radiation therapy CONV: Conventional tangents Fig. 3b. Buildup region was included in the PTV. IMRT: Intensity modulated radiation therapy CONV: Conventional tangents IMRT CONV IMRT CONV Goodman

10. Figure 5. Maximum Dose as a Function of Breast Depth for Simplified IMRT and Conventional Tangent Plans. Goodman

12. Intensity Map of a Typical Breast IMRT Field skin flash depressed intensity through the lung volume ‘wedge-like’ intensity distribution

13. Breast IMRT at MSKCC Viewed (based on prostate model) as an improved method of dose delivery to primary Therefore change in technology simply executed in the department

14. Integrated Boost Freedman et al (Fox Chase) have demonstrated feasibility of doing concomitant “boost” during whole breast IMRT with “Dose Painting” This is under consideration has an RTOG Phase II trial

15. Partial Breast RT RTOG/NSABP Phase III Trial open since 2005 to compare Standard Whole Breast RT to Partial Breast RT using 10 fx in 5 days Accrual well past 2000 of 3000 planned In women randomized to “PBI”, over 70% are receiving RT by 3D XRT, 20 % by MammoSite and 5% by Brachy

16. MGH PBI/Protons 20 Stage I patients in Phase I/II Trial Results: (Median F/U 12 months) No local failures Side Effects: “Moderate to severe skin color changes in 79 %, moderate to severe moist desquamation in 22 %, skin telangiectasia in 3 patients and rib tenderness in 3 patients

19. Post-Mastectomy RT/1 If breast reconstruction present, similar issues to intact breast Chest wall: Multiple techniques, including tangent fields, electron beam, and combinations. SKIN is part of the target, so “skin-sparing” not an advantage

20. Post Mastectomy RT/2 Supraclavicular Nodal RT always given Internal Mammary Nodal RT highly controversial in standard adjuvant settings (NCCN guidelines Level 3) OAR include lung, heart, brachial plexus and esophagus, depending on technique

21. Post Mastectomy RT/3 NCI-funded Phase III trial now ongoing at U. of Michigan Will compare IMRT to 3D Conformal in the post-mastectomy setting, including regional nodes No IMRT used off study in this clinical situation PI: Lori Pierce

22. Hypothetic Plan IMRT/Protons Lomax et al at PSI Target included breast, and regional nodes including IMN chain IMRT plan had increased target homogeneity compared to 2D, but with increased dose to critical neighboring organs 2 field, energy modulated Proton plan appeared superior to IMRT

23. Other Clinical Scenarios Inoperable presentations Bulky, non-resectable recurrent cancer IMRT plans have sometimes looked significantly better than 3D conformal, on a CASE BY CASE basis

24. Conclusions/Breast One Phase III trial demonstrates superiority of IMRT over standard treatment, for acute side effects in the intact breast Modest decrease in late cardiac and lung toxicity likely with IMRT (With 2 field tx) Improvement in local control unlikely, since it is already at 95 % at 5 years

25. More Conclusions Limited single institution center studies on IMRT and Proton use for PBI Imaging the PTV daily likely needed, given the tight margins, daily set-up error, organ deformation (edema) and target mobility with breathing