breast cancer radiotherapy

What’sWhat’s NewNew ininBreastBreast CancerCancer RadiotherapyRadiotherapy??

Roger M. Macklis, M.D.Cleveland Clinic Lerner College of Medicine

Cleveland Clinic Healthcare System

What’s New in What’s New in Breast Cancer Radiotherapy?Breast Cancer Radiotherapy?

Recent Meta-Analysis from“Lancet”

Partial Breast Irradiation

Intensity Modulated Radiation Therapy (IMRT)

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BREAST CANCER COMMANDS ATTENTIONBREAST CANCER COMMANDS ATTENTION

“Few topics in medicine engender as much emotional response as the treatment of primarybreast cancer.”

- Levene, Harris, HellmanCancer (1977)

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Early InvestigationsEarly Investigations

Charles H. Moore, 1867 (surgeon to the Middlesex Hospital, London).

“ … Cancer of the breast requires the carefulextirpation of the entire organ; that the situationin which this operation is most likely to beincomplete is at the edge of the mamma near the sternum …”

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William Halsted, 1852-1922(surgeon to the Johns Hopkins Hospital, Baltimore).

“ Most of us have heard our teacher in surgery admitthat they never cured a case of cancer of the breast …Everyone knows how dreadful the end-results were before cleaning out the axilla became recognized as an essential part of the operation.”

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Sir Geoffrey Keynes, 1920s(St. Bartholomew Hospital, London).

Interstitial radium implants of tumor bed andsurrounding regions of the breast. “ … treatmentof choice for very advanced breast cancer.”

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Breast Cancer: Critical Benchmark StudiesBreast Cancer: Critical Benchmark Studies

NASBP (NEJM 2002: 347 1233-1241)20 year F/U shows lumpectomy + XRT 14% LRRlumpectomy alone 39.2% LRR

Milan (Ann Oncol 2001 12: 997-1003)Quadrantectomy + XRT 5.8% LRRQuadrantectomy alone 23.5% LRRQuadrantectomy alone 23.5% LRR

New Meta-Analysis from Lancet 12/05

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New Meta-Analysis Data on Breast Radiotherapy

strongly suggests that in addition to improving

local control, radiotherapy ALSO improves survival

MetaMeta--Analysis of Breast Cancer XRTAnalysis of Breast Cancer XRT

Title: Effects of radiotherapy and of differencesin the extent of surgery for early breast canceron local recurrence and 15-year survival: anoverview of the randomised trials

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)Lancet 366:2087-2106 (2005)Published Dec. 17, 2005

MetaMeta--Analysis of Breast Cancer XRTAnalysis of Breast Cancer XRT

Meta-Analysis of 78 randomized controlled trialsbeginning by 1995. These trials included approximately42,000 women and roughly ¾ were involved in XRT vsno XRT trials for either conservation therapy (intactbreast) or post-mastectomy therapy. Trials separated into groups showing > or < 10% difference in LR.

Data from Lancet MetaData from Lancet Meta--Analysis Analysis (N=42,000)(N=42,000)

XRT No XRT5 year local recurrence: 7% 26%(conservation-intact breast)

Post-Mastectomy (LN+) 6% 23%

15 year breast cancer mortality 30.5% 35.9%(intact breast)

15 year breast cancer mortality 54.7% 60.1%(post-mastectomy LN+)

• Overall all-cause reduction in mortality approx 4.4%!• Similar proportional reductions in all groups• Major XRT-related toxicities included cardiac disease (RR 1.27)

lung ca (RR 1.78) and contralateral breast ca (RR 1.18)

Interpretation of MetaInterpretation of Meta--Analysis Data:Analysis Data:

“Differences in local treatment that substantially affectlocal recurrence rates would, in the hypothetical absenceof any other causes of death, avoid about one breastcancer death over the next 15 years for every four localrecurrences avoided, and should reduce 15-year overallmortality.” Lancet 366:2087 (2005)

Will new treatment approaches further improve this Will new treatment approaches further improve this data set?data set?

CRITICAL QUESTIONS ON CRITICAL QUESTIONS ON PARTIAL BREAST IRRADIATIONPARTIAL BREAST IRRADIATION

Can less than the entire breast be treated?If so, for which types of cases? Which portion of the breast? How big a margin? External beam vs. brachytherapy? What about overall cosmesis? What about adjuvant systemic therapy?

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General Approaches to General Approaches to Partial Breast RadiotherapyPartial Breast Radiotherapy

Interstitial implant brachytherapyIntra-Operative RadiotherapyExternal beam radiotherapyMammoSite brachytherapy

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Interstitial Implant Breast BrachytherapyInterstitial Implant Breast Brachytherapy

1. Ochsner Clinic Team (King et al, 2000)

50 pts: Tis, T1, T2 up to 4 cmӨ margins; ≤ 3 ⊕ LNTarget Tissue: tumor surgical bed plus 2-3 cm marginEither LDR or HDR techniqueDose: 45 Gy LDR or 32 Gy (4 day BID) HDRWith median f/u 75 months, 1 breast and 3 LN recurrences seenCosmetic Outcomes: 75% good to excellent(less than 85-90% for external beam)

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Interstitial Implant Breast BrachytherapyInterstitial Implant Breast Brachytherapy

2. William Beaumont Team (Vicini et al, 2003)

198 pts: Tis, T1, T2 ≤ 3 cmӨ margins; age >40; Ө LNTarget similar to Ochsner groupDose: LDR 50 Gy or LDR 3.4 Gy BID x 5 daysCosmetic Outcome “good to excellent” 99%!!Local recurrence rate 1% at 5 yearsBasis for subsequent RTOG trial whichopened in 1997

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IntraIntra--Operative Breast IrradiationOperative Breast Irradiation

London study using Intrabeam device (PhotoElectron, now owned by Zeiss)Spherical applicators of different sizes50 kv orthovoltage beam producing 5 Gy at 1 cm from application surfaceClinical trial by Tobias et al. now underway;each site chooses its own entrance criteria.Other intra-op programs at MSK, etc.CCF used for boost only. Veronesi (Milan)just published results of 590 pts treated withintra-op electron beam; 21 Gy single fraction.3% breast fibrosis, 6/590 ipsilat. recurrenceafter 2-year median f/u. [Ann. Surg 242:101(2005)]

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External Beam Partial Breast IrradiationExternal Beam Partial Breast Irradiation

William Beaumont group – developed as non-invasive analog to implant studies3D conformal XRTTarget Tissue: tumor bed plus 2-3 cm (breathing margin)34-38.5 Gy BID over 5-7 daysRTOG 95-17 phase II protocol: 38.5 Gy BID over 5-7 daysExcellent results led to current RTOG/NSABP PBI trial

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MammoSiteMammoSite Balloon BrachytherapyBalloon Brachytherapy

Catheter resembling Foley but with 2channels: one for saline (expander) anda second for radioactive source (Ir-192)Placed directly in lumpectomy cavityeither at time of original lumpectomy orin a second procedure (single scar)Dose: 34 Gy BID in 5-7 daysWith median F/U 29 months, local failurerate 0% and cosmesis good-to-excellentin 84%.FDA clearance granted 2002Said to be the most rapidly growing breastcancer radiation procedure in the USA.

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MammoSiteMammoSite: Coming to a Clinic Near You!: Coming to a Clinic Near You!

Current RTOG / NSABP TrialCurrent RTOG / NSABP Trial

Phase III randomized comparison of whole breastvs. short-course partial breast XRTStage 0, I, or II with T<3cmNo more than 3 histologically positive nodesPost-surgical CT evaluations of lumpectomy cavityDefined ratios of partial-breast to whole-breastvolumesEither interstitial catheters, Mammo Site, or 3D conformal (NOT IMRT) radiotherapyTwice daily for 10 fractions over 5-7 daysNo data available yet

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BREAST IMRTBREAST IMRT

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Breast IMRTBreast IMRT

Intensity Modulated Radiation Therapy (IMRT) refers to aset of related processes involving both radiation treatment planning and beam delivery. Unlike conventional radiationtreatments, which often strive to deliver uniform radiationdoses to large regions of tissue, IMRT allows small beamlets to be used to change the shape and intensity of the radiation field (sort of like a dot-matrix printer). Thisallows the radiation team to focus the field more intenselyon tumor deposits and limit the dose to nearly normaltissues.

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CCF Breast IMRT (T. CCF Breast IMRT (T. DjemilDjemil, Ph.D.), Ph.D.)

“Breast Forward IMRT Planning”Start with routine tangential fields and then adjust each segmentof the plan to minimize hot spotsNumber of segments related to hot spot location and intensity

RM 9/05CCF Multislice Coplanar Breast IMRTCCF Multislice Coplanar Breast IMRTWith Concurrent Boost to Tumor BedWith Concurrent Boost to Tumor Bed

Usually 4-5 segments per field or 10 segments total


Basic Principles of Ochsner Approach

6 Field Treatment technique

3 Medial Fields + 3 Lateral Fields

Left Breast: 300, 315, 340, 110, 125, 150 Degrees

Right Breast: 200, 230, 250, 20, 45, 60 Degrees

No immobilization used

Same margins as 3D conformal technique used for IMRT

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Breast IMRT

6 Fld Technique

Note that veryperipheral deepportion of breast may be under-treated but amount of heart and lung irradiated is very small.

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BREAST IMRTBREAST IMRT RM 9/05


Breast IMRT

Boost to deep lesions

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Breast IMRT:Breast IMRT:Why do we need it?Why do we need it?

More conformal dose to breast

Lower doses to lungs and heart

Lower doses to contralateral breast

Field within a field (“concurrent boost”)

Inclusion of regional nodes

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More conformal dose to breastMore conformal dose to breastLower doses to lungs and heartLower doses to contralateral breastField within a field (“concurrent boost”)Inclusion of regional nodes

More Conformal Dose to BreastMore Conformal Dose to Breast

The natural taper of the breast produces hot spots of 3-20% unless customized wedge compensators utilized.IMRT can dramatically reduce these hot spots.

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More conformal dose to breastLower doses to lungs and heartLower doses to lungs and heartLower doses to contralateral breastField within a field (“concurrent boost”)Inclusion of regional nodes

Lower Doses to Lungs and HeartLower Doses to Lungs and Heart

Dose is ordinarily fairly low even using routine tangential fields.Typical CCF case of left sided breast cancer shows that total median dose to left lung and left ventricle will be ≤ 500 cGy.For cases of abnormal anatomy or serious pre-existing organ damage, this improvement may be significant.MSK treatment position is prone, so natural weight ofbreasts pull target away from lung and heart tissue.

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More conformal dose to breastLower doses to lungs and heartLower doses to contralateral breastLower doses to contralateral breastField within a field (“concurrent boost”)Inclusion of regional nodes

Lower Doses to Contralateral BreastLower Doses to Contralateral Breast

Dose to contralateral breast typically 2-5 Gy from a routine course of tangent field XRT.Recent data from Netherlands presented at ASCO covered 999 cases of metachronous contralateral breast ca. Use of XRT associated with 60% increase in risk for patients <40!!

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More conformal dose to breastLower doses to lungs and heartLower doses to contralateral breastField within a field (“concurrent Field within a field (“concurrent boost”)boost”)Inclusion of regional nodes

Field Within a Field (“Concurrent Boost”)Field Within a Field (“Concurrent Boost”)

Strategic use of dose inhomogeneity is one of the strong arguments for IMRT at many body sites.

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More conformal dose to breastLower doses to lungs and heartLower doses to contralateral breastField within a field (“concurrent boost”)Inclusion of regional nodesInclusion of regional nodes

Inclusion of Regional NodesInclusion of Regional Nodes

Current investigational work ongoing for inclusion of internal mammary nodes.Significant dose to adjacent areas in many cases.

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Controversies Involving Controversies Involving Partial Breast IrradiationPartial Breast Irradiation

How much treatment margin necessary? (remember Milan quadrantectomy trial yielded 23% LRR)Which patients appropriate?(young age is powerful risk factor for local recurrence; important limitationof MammoSite device is that breast tissue must be greater than 3cm in thickness where the device is placed and there must be at least 7-to-10 mm of distance between the MammoSite balloon and skin to prevent skin injury and possible wound breakdown.)Because local recurrence has minimal impact on survival, could we define a patient group with a low enough risk that no XRT (i.e., hormonetherapy only) is necessary? (recent data for women >70 shows LRR 4%without XRT and 1% with XRT)Will the excellent 3-5 year results for each of these partial breast treatmenttechniques hold up over time?To what degree should we be driven by patient “consumerist” desires forshort-course treatment?

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What’sWhat’s NewNew ininBreastBreast CancerCancer RadiotherapyRadiotherapy??

Roger M. Macklis, M.D.Cleveland Clinic Lerner College of Medicine

Cleveland Clinic Healthcare System

breast cancer radiotherapy

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