Breast Cancer Radiotherapy
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Breast Cancer Radiotherapy

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    Breast Cancer Radiotherapy Breast Cancer Radiotherapy Presentation Transcript

    • What’s New in Breast Cancer Radiotherapy? Roger M. Macklis, M.D. Cleveland Clinic Lerner College of Medicine Cleveland Clinic Healthcare System
    • RM 9/05 What’s New in Breast Cancer Radiotherapy? Recent Meta-Analysis from “Lancet” Partial Breast Irradiation Intensity Modulated Radiation Therapy (IMRT)
    • RM 9/05 BREAST CANCER COMMANDS ATTENTION “Few topics in medicine engender as much emotional response as the treatment of primary breast cancer.” - Levene, Harris, Hellman Cancer (1977)
    • RM 9/05 Early Investigations Charles H. Moore, 1867 (surgeon to the Middlesex Hospital, London). “ … Cancer of the breast requires the careful extirpation of the entire organ; that the situation in which this operation is most likely to be incomplete is at the edge of the mamma near the sternum …”
    • RM 9/05 Early Investigations William Halsted, 1852-1922 (surgeon to the Johns Hopkins Hospital, Baltimore). “ Most of us have heard our teacher in surgery admit that 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.”
    • RM 9/05 Early Investigations Sir Geoffrey Keynes, 1920s (St. Bartholomew Hospital, London). Interstitial radium implants of tumor bed and surrounding regions of the breast. “ … treatment of choice for very advanced breast cancer.”
    • RM 9/05 Breast Cancer: Critical Benchmark Studies NASBP (NEJM 2002: 347 1233-1241) 20 year F/U shows lumpectomy + XRT 14% LRR lumpectomy alone 39.2% LRR Milan (Ann Oncol 2001 12: 997-1003) Quadrantectomy + XRT 5.8% LRR Quadrantectomy alone 23.5% LRR New Meta-Analysis from Lancet 12/05
    • New Meta-Analysis Data on Breast Radiotherapy strongly suggests that in addition to improving local control, radiotherapy ALSO improves survival
    • Meta-Analysis of Breast Cancer XRT Title: Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Lancet 366:2087-2106 (2005) Published Dec. 17, 2005
    • Meta-Analysis of Breast Cancer XRT Meta-Analysis of 78 randomized controlled trials beginning by 1995. These trials included approximately 42,000 women and roughly ¾ were involved in XRT vs no XRT trials for either conservation therapy (intact breast) or post-mastectomy therapy. Trials separated into groups showing > or < 10% difference in LR.
    • Data from Lancet Meta-Analysis (N=42,000) XRT No XRT 5 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 Meta-Analysis Data: “Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.” Lancet 366:2087 (2005) Will new treatment approaches further improve this data set?
    • RM 9/05 CRITICAL QUESTIONS ON PARTIAL 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?
    • RM 9/05 General Approaches to Partial Breast Radiotherapy Interstitial implant brachytherapy Intra-Operative Radiotherapy External beam radiotherapy MammoSite brachytherapy
    • RM 9/05 Interstitial Implant Breast Brachytherapy 1. Ochsner Clinic Team (King et al, 2000) 50 pts: Tis, T1, T2 up to 4 cm Ө margins; ≤ 3 ⊕ LN Target Tissue: tumor surgical bed plus 2-3 cm margin Either LDR or HDR technique Dose: 45 Gy LDR or 32 Gy (4 day BID) HDR With median f/u 75 months, 1 breast and 3 LN recurrences seen Cosmetic Outcomes: 75% good to excellent (less than 85-90% for external beam)
    • RM 9/05 Interstitial Implant Breast Brachytherapy 2. William Beaumont Team (Vicini et al, 2003) 198 pts: Tis, T1, T2 ≤ 3 cm Ө margins; age >40; Ө LN Target similar to Ochsner group Dose: LDR 50 Gy or LDR 3.4 Gy BID x 5 days Cosmetic Outcome “good to excellent” 99%!! Local recurrence rate 1% at 5 years Basis for subsequent RTOG trial which opened in 1997
    • RM 9/05 Intra-Operative Breast Irradiation London study using Intrabeam device (Photo Electron, now owned by Zeiss) Spherical applicators of different sizes 50 kv orthovoltage beam producing 5 Gy at 1 cm from application surface Clinical 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 with intra-op electron beam; 21 Gy single fraction. 3% breast fibrosis, 6/590 ipsilat. recurrence after 2-year median f/u. [Ann. Surg 242:101 (2005)]
    • RM 9/05 External Beam Partial Breast Irradiation William Beaumont group – developed as non-invasive analog to implant studies 3D conformal XRT Target Tissue: tumor bed plus 2-3 cm (breathing margin) 34-38.5 Gy BID over 5-7 days RTOG 95-17 phase II protocol: 38.5 Gy BID over 5-7 days Excellent results led to current RTOG/ NSABP PBI trial
    • RM 9/05 MammoSite Balloon Brachytherapy Catheter resembling Foley but with 2 channels: one for saline (expander) and a second for radioactive source (Ir-192) Placed directly in lumpectomy cavity either at time of original lumpectomy or in a second procedure (single scar) Dose: 34 Gy BID in 5-7 days With median F/U 29 months, local failure rate 0% and cosmesis good-to-excellent in 84%. FDA clearance granted 2002 Said to be the most rapidly growing breast cancer radiation procedure in the USA.
    • RM 9/05 MammoSite: Coming to a Clinic Near You!
    • RM 9/05 Current RTOG / NSABP Trial Phase III randomized comparison of whole breast vs. short-course partial breast XRT Stage 0, I, or II with T<3cm No more than 3 histologically positive nodes Post-surgical CT evaluations of lumpectomy cavity Defined ratios of partial-breast to whole-breast volumes Either interstitial catheters, Mammo Site, or 3D conformal (NOT IMRT) radiotherapy Twice daily for 10 fractions over 5-7 days No data available yet
    • RM 9/05 BREAST IMRT
    • RM 9/05 Breast IMRT Intensity Modulated Radiation Therapy (IMRT) refers to a set of related processes involving both radiation treatment planning and beam delivery. Unlike conventional radiation treatments, which often strive to deliver uniform radiation doses 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). This allows the radiation team to focus the field more intensely on tumor deposits and limit the dose to nearly normal tissues.
    • RM 9/05 CCF Breast IMRT (T. Djemil, Ph.D.) “Breast Forward IMRT Planning” Start with routine tangential fields and then adjust each segment of the plan to minimize hot spots Number of segments related to hot spot location and intensity
    • RM 9/05 CCF Multislice Coplanar Breast IMRT With Concurrent Boost to Tumor Bed Usually 4-5 segments per field or 10 segments total
    • RM 9/05 BREAST IMRT 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
    • BREAST IMRT RM 9/05 Breast IMRT 6 Fld Technique Note that very peripheral deep portion of breast may be under- treated but amount of heart and lung irradiated is very small.
    • BREAST IMRT RM 9/05
    • BREAST IMRT RM 9/05 Breast IMRT Boost to deep lesions
    • RM 9/05 Breast IMRT: 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
    • RM 9/05 Breast IMRT: 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 More 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.
    • RM 9/05 Breast IMRT: 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 Lower 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 of breasts pull target away from lung and heart tissue.
    • RM 9/05 Breast IMRT: 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 Lower 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!!
    • RM 9/05 Breast IMRT: 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 Field Within a Field (“Concurrent Boost”) Strategic use of dose inhomogeneity is one of the strong arguments for IMRT at many body sites.
    • RM 9/05 Breast IMRT: 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 Inclusion of Regional Nodes Current investigational work ongoing for inclusion of internal mammary nodes. Significant dose to adjacent areas in many cases.
    • Controversies Involving RM 9/05 Partial 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 limitation of 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., hormone therapy 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 treatment techniques hold up over time? To what degree should we be driven by patient “consumerist” desires for short-course treatment?
    • What’s New in Breast Cancer Radiotherapy? Roger M. Macklis, M.D. Cleveland Clinic Lerner College of Medicine Cleveland Clinic Healthcare System