Current Practice in Partial Breast Irradiation

1. Current Practice in Partial Breast Irradiation

2. Objectives • Justification for Partial Breast Irradiation (PBI) • Current Breast Irradiation Techniques • Whole breast external beam • Multi-catheter interstitial • Single-catheter interstitial • 3D-CRT • MammoSite

3. Six randomized trials have been conducted attempting to determine if RT can be omitted after breast conserving surgery No subset of patients has yet been identified that can conclusively be treated with surgery alone RT after breast conserving surgery remains the ‘standard of care’ Necessity for Radiation Therapy

4. Prospective Randomized Trials of Lumpectomy +/- Radiotherapy Trial % of Patients With % Reduction Recurrence Recurrence (CS vs. CS + RT) CS Alone CS + RT NSABP B - 06 * 36 12 67 Milan*3 6 24 75 Scottish 25 6 76 24 9 63 Uppsala-Orebro* Ontario 35 11 69 English 35 13 63 * Recently Updated

5. Why? Physician bias Patient choice More complex and prolonged treatment course 6 weeks – daily treatment Monday to Friday Can be inconvenient or prohibitive for those with poor access to a radiation facility, the elderly and working women. Rationale For Partial Breast Irradiation (PBI) • Up to 40% of patients who are candidates for breast conservation therapy do not receive it 1 1 Nattinger, et al. 2000.

6. Improve documented underutilization of BCT Decrease time and inconvenience of BCT Improve quality of life Eliminate scheduling problems with systemic chemotherapy Intensifying radiotherapy to the tissue at greatest risk for subclinical disease May further reduce local recurrence rates Potentially reduce acute and chronic toxicity Cosmetic outcome may be improved because skin and integral breast parenchymal doses are lower, especially for women with large breasts Advantages of Partial Breast Irradiation (PBI)

7. A broad spectrum of clinical studies supports the ability to achieve local control with PBI, including: Studies identifying disease extension and margin assessment Impact of RT on “elsewhere failures” Brachytherapy clinical data Rationale for PBI

8. Impact of RT on ‘Elsewhere’ Failures-Randomized Trials Comparing BCS vs. BCS Plus RT- • No impact of radiation on ‘elsewhere’ failures

9. Site / Study # Patients Follow-up (mos.) Radiation source Local recurrence rate William Beaumont 199 65 HDR/LDR 1.0% Ochsner Clinic 52 75 HDR/LDR 2.0% Virginia Commonweath Univ. 44 42 HDR/LDR 0.0% NIO– (Hungary: Phase I/II) 45 60 HDR 4.4% NIO – (Hungary: Phase III) 181 30 HDR 1.1% Tuft’s/New England Medical Ctr. 32 33 HDR 4.0% Keisch et al. (multi-institution) 43 21 HDR 0.0% University of Kansas 24 37 LDR 0.0% Cionini (Florence, Italy) 90 27 LDR 4.4% Total 710 Published Contemporary Data on Partial Breast Irradiation as Primary Treatment NSABP-B06: 77% of in-breast failures occurred within 5 years of treatment. After 5 years, almost equal number of recurrences developed with or without whole breast radiation therapy.

10. Age >45 >50 Diagnosis Unifocal, invasive ductal carcinoma Invasive ductal carcinoma or DCIS Tumor size < 3cm < 2cm Surgical margins Negative microscopic surgical margins of excision Negative microscopic surgical margins of at least 2mm in all directions Nodal status N0 N0 Patient Selection Criteria ABS Recommendations1ASBS Recommendations2 1Arthur, et al. Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society. Brachytherapy, 1:184-190, 2003. 2Consensus statement for accelerated partial breast irradiation. The American Society of Breast Surgeons. April 30, 2003.

11. External Beam Treats “whole breast” Large volume of incidental tissues Requires protracted (6—7 week) delivery Breast Irradiation Technique

12. Interstitial Multi-Catheter Treats quadrant or less Effective in properly selected patients Requires special skill Breast Irradiation Technique

13. Breast Irradiation Technique MammoSite • Distends cavity • Very conformal • Prescription limited by doses to skin and balloon surface

14. 3D CRT Requires added margin (breathing) Not as simple as it looks No clinical data Investigational Technique

15. Spherical 4-5 and 5-6 Recently FDA approved ellipsoidal sizes will broaden ability to implant different sized/shaped cavities Available Q3 2004 MammoSite Product Line

16. MammoSite Dosing 95.79% 4.21% 28.57% 33.33% 38.1%

17. CT Image of MammoSite Tissue Conformance Skin Spacing Balloon Diameter & Symmetry 3-Dimensional rendering of applicator surface

18. Appropriateness For Treatment Treatment Planning QA CT Planning or Orthogonal Plane Films Evaluate via CT or ultrasound for skin spacing, tissue conformance, symmetry Orthogonal Plane Films and/or Appositional Plane film for Constancy Check Patient Procedure Overview Treatment Planning

19. Plane film or ultrasound verification A.M. Fraction Plane film or ultrasound verification > 6 hrs later PM Fraction Patient Procedure Overview Radiation Treatment Delivery Begins

20. Final 2 Fractions* Explant Catheter Dress Exit Site Patient Procedure Overview Explant *Total 10 fractions delivered over 5 days

21. Randomized controlled study comparing whole breast external beam irradiation to accelerated partial breast irradiation MammoSite Interstitial catheter 3D conformal 3000 patients planned Initiated Q3 2004 NSABP/RTOG Phase III Study