NCI Workshop

Advanced Technologies for Breast Cancer

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”

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)

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

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

1a 1b

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

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IMRT Conventional

Figure 4a. Transverse Dose Distributions

113 108 100 90 50Isodose in %

102 10

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IMRT Conventional

Figure 4b. Sagittal Dose Distributions

117 108 100 90 50Isodose in %

102 10

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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 therapyCONV: Conventional tangents

Fig. 3b. Buildup region was included in the PTV.IMRT: Intensity modulated radiation therapyCONV: Conventional tangents

IMRT

CONV

IMRT

CONV

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100

105

110

115

120

125

5 10 15 20

Breast Depth (cm)

Dm

ax D

ose

(%

)

Dmax IMRT Dmax Conv

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

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StandardIMRT x

IMRT x + e

DVH: Coronary Artery Region

Intensity Map of a Typical Breast IMRT Field

skin flash

depressed intensity

through the lung

volume

‘wedge-like’ intensity distribution

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

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

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

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

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

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

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

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

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

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

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