New techniques in breast radiotherapy


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New techniques in breast radiotherapy

  2. 2. Historical Perspective<br />Interstitial Radium Brachytherapy for Breast Cancer, 1917<br />Radiotherapy for Breast Cancer, London Hospital, c. 1917<br />
  3. 3. Prospective Randomized Trials of Lumpectomy +/- Radiotherapy<br />
  4. 4. Radiation Therapy for Early Stage Breast Cancer Following Lumpectomy<br />Whole Breast Irradiation<br />Rationale: Addition of whole breast irradiation following lumpectomy yields local control rates comparable to mastectomy<br />Treatment: Whole breast irradiation<br /><ul><li> 45-50 Gy to the entire breast
  5. 5. 60 Gy to the lumpectomy cavity + margin
  6. 6. 1.8 – 2 Gy fraction given 5 days/ week
  7. 7. 5 – 7 week total treatment duration</li></li></ul><li>Breast Irradiation Technique<br />External Beam<br />Treats “whole breast”<br />Large volume of incidental tissues<br />Requires protracted (6—7 week) delivery <br />
  8. 8.
  9. 9.
  10. 10. Image-based Conformal Radiation Therapy: <br />60 Gy<br />62 Gy<br />50 Gy<br />20 Gy<br />45 Gy<br />axial<br />sagittal<br />Left Breast<br />
  11. 11.
  12. 12. Accelerated Whole Breast Irradiation:Reducing the burden of care<br />Canadian Phase III Randomized Trial:<br />42.5 Gy – 16 fractions – 22 days vs.<br /> 50 Gy – 25 fractions – 35 days<br />1,234 patients - T1 – T2, N 0 (80% T1)- ER positive - 71% - Median F/U: 69 months<br />
  13. 13. Randomized Boost Trials<br />
  14. 14.
  15. 15. Accelerated Whole Breast Irradiation:A Phase II clinical trial of a 4 week course of RT for breast cancer using hypo fractionated IMRT with a concomitant boost.<br />4 week course – 20 treatments<br /> 45 Gy whole breast dose<br /> 56 Gy boost dose<br />Results:<br /> 16 patients treated<br /> Acute toxicity: Grade I 57%, Grade II 43%<br />
  16. 16.
  17. 17. Regional Nodal RTAwaiting results of two large trials (France and EORTC)<br />
  18. 18. Regional Nodal RT in BCS Ongoing Trials<br />
  19. 19. Axillary Treatment with CS<br />
  20. 20.
  21. 21.
  22. 22.
  23. 23. Full SCLV Field<br />
  24. 24. IM Nodal Radiation Technique<br />
  25. 25. IM Nodal Radiation Technique<br />
  26. 26.
  27. 27.
  28. 28. Cured from<br />Breast Cancer<br />Died of Cardiac<br />Toxicity <br />Adapted from Larry Marks, Duke<br />
  29. 29. Overall survival: radical mastectomy + / - RT<br />First 10 years<br />Next 25 years<br />Cuzick et al: Recent Results Cancer Research 111:108-129, 1988<br />
  30. 30. XRT worse<br />XRT better<br />XRT better<br />XRT worse<br />XRT better<br />XRT worse<br />Overall Survival<br />Cardiac Mortality<br />Breast Ca Mortality<br />Cuzick JCO 12:452, 1994<br />
  31. 31.
  32. 32.
  33. 33. The shape of the breast and the position of the heart in relation to the chest wall can vary enormously<br />
  34. 34. Decrease cardiac Exposure to RT<br />Partial Breast Irradiation<br />Decubitus or Prone positions<br />Breath Hold Technique<br />Respiratory gating technique<br />Proton therapy<br />
  35. 35. Patient’s Position<br />Prone and IMRT<br />Lateral Decubitus<br />Campana et al 2005<br />DeWyngaert et al 2007<br />
  36. 36. Radiation techniques<br />Active Breathing Control + IMRT <br />Breath hold in deep inspiration<br />Remouchamps et al 2003<br />Lu et al et al 2000<br />
  37. 37. Cardiac Sparing<br />V5 Volume receiving 5% of the dose<br />
  38. 38. Heart Block Examples<br />Midline<br />Heart Block<br />Recent Patient<br />Marks IJROBP 1994.<br />Marks et al<br />
  39. 39. Late cardiac morbidity(EBCTCG,Lancet 2000;355:1757-1770)<br /> field<br />Breast cancer mortality reduced by 13%<br />Increase in annual mortality rate from other causes by 21%<br />Increase primarily due to excess deaths from cardiovascular causes<br />Cardiac effects may not emerge until 15 yrs after treatment<br />Breast<br />contour<br />Heart<br />contour<br />Maximum Heart Distance (MHD)<br />
  40. 40.
  41. 41. Prone Breast RT<br />
  42. 42.
  43. 43. Prone Breast RT<br />
  44. 44. Goodman<br />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<br />
  45. 45. Goodman<br />Figure 6. Left breast irradiation using prone breast IMRT technique can spare left ventricle and coronary arteries.<br />
  46. 46. 3-DCRT for left prone breast radiation:<br />Improved targeting and avoidance of lung<br />Sagittal<br />45 Gy<br />60 Gy<br />Lumpectomy<br />50 Gy<br />PTV<br />Transaxial<br />
  47. 47. Pattern of In-Breast Cancer Recurrences Following Breast Conserving Therapy<br />The majority of cancer recurrences in the treated breast occur at the lumpectomy site<br />
  48. 48. Potential Benefits of Partial Breast Irradiation<br />Reduce time and inconvenience of BCT<br />Improve documented underutilization of breast conserving therapy (BCT)?<br />Potentially reduce acute and chronic toxicity<br />Reduce burden of care for patients<br />Eliminate scheduling problems with systemic chemotherapy<br />
  49. 49. Rationale for Partial Breast Irradiation (PBI)<br />10%-40% of those who are candidates for breast conservation therapy actually do not receive it.<br />Why?<br />Patient’s choice<br />Complex and prolonged treatment course can be inconvenient for those with poor access to a radiation facility, the elderly and working women<br />Physician bias<br />
  50. 50. Techniques for PBI<br />Interstitial brachytherapy with HDR or LDR<br />Intracavitarybrachytherapy with Mammosite<br />Intraoperative electron beam therapy<br />3D conformal radiation therapy<br />Proton beam<br />
  51. 51. Partial breast irradiation techniques<br />
  52. 52. Three Established Methods For PBI<br />Mammosite®<br />Multi Catheter<br />3-D Conformal<br />
  53. 53. Accelerated Partial Breast Irradiation<br />Treatments delivered twice daily (with treatments separated by six hours) for 10 treatments delivered in 5 treatment days.<br />Delivery of radiation limited to lumpectomy site with a margin of normal tissue.<br />Each treatment takes approximately 10 minutes to deliver.<br />
  54. 54. Target definition<br />
  55. 55. Accelerated Partial Breast Irradiation<br />Benefits:<br />Limited radiation exposure to normal tissue<br />Treatments completed in one week instead of six weeks<br />
  56. 56. Accelerated Partial Breast Irradiation<br />Limitations:<br />May require additional surgical procedure <br />Requires twice daily treatment<br />Newer modality with far fewer patients treated and much shorter follow-up<br />As of now, no direct comparison with standard radiation<br />
  57. 57.
  58. 58. Who is eligible for PBI? (Off study)<br />Tumors < 3 cm<br />Negative margins (> 2mm)<br />Node negative<br />Invasive ductal carcinoma or DCIS<br />Older women (>45 yrs)<br />Revised Consensus Statement for Accelerated Partial Breast Irradiation, 12/8/05<br />
  59. 59. Interstitial brachytherapy<br />Catheters are placed intraoperatively or later; usually 2 planes<br />Typical doses with HDR = 30-36 Gy and LDR = 45-60 Gy<br />Treatment delivered over one week.<br />
  60. 60. Breast Brachytherapy<br />
  61. 61. Multi-Catheter Brachytherapy<br />
  62. 62. Dose Distribution of MultiCatheter PBI<br />PTV<br />100% isodose<br />
  63. 63. Breast Appearance Following Multi-catheter Brachytherapy<br />5 years post treatment<br />
  64. 64. Patient Selection for Breast Brachytherapy<br />Patients older than 45<br />Tumors less than 2 cm. in size<br />>2mm. Margins<br />Preferably Infiltrating Ductal or loclized low grade DCIS. No Lobular CA<br />There must be at least 7mm. of tissue between the catheter surface and the skin of the breast.<br />
  65. 65. Advantages of Breast Brachytherapy vs. External Beam RT<br />6 weeks (30 fractions)<br />Homogeneous dose<br />Logistical problem for patients<br />Difficult for frail, elderly, or chronically ill patients<br />Interferes with schedule of working women<br />Some BCT candidates will opt for mastectomy<br />5 days (10 fractions)<br />Dose is higher to tissue at greatest risk for sub-clinical malignant cells<br />Reduction in skin, cardiac and lung dose<br />Ideal for patients who live far from RT Center<br />Convenient<br />May increase number of women treated with BCT<br />
  66. 66. Disadvantages of Breast Brachytherapy vs. External Beam RT<br />Noninvasive<br />Can cover nodal regions<br />Treats multi-centric carcinoma<br />Low complication rate<br />Linear accelerators widely available<br />Most radiation oncologists experienced <br />Invasive<br />Not useful for treatment of nodal basins<br />May miss tumor foci in other quadrants<br />Low, but definite risk of infection and/or fat necrosis<br />Requires special skills for performing; in placing catheters and dosimetry<br />
  67. 67. MultiCatheter PBI:HDR/ LDR<br />61 mo.<br />5%<br />89%<br />61 y<br />1.4 cm<br />17.5%<br />Average:<br />
  68. 68. Breast Brachytherapy<br />There has got to be a better way than all of those needles.<br />Mammosite device from Proxima Therapeutics may be the answer.<br />FDA approved the device in May 2002<br />
  69. 69. MammoSite PBI<br />Mammosite® Breast Brachytherapy Applicator<br /><ul><li>Simplified brachytherapy method for PBI
  70. 70. Dual lumen single catheter with expandable balloon at end
  71. 71. Balloon expands to fill the lumpectomy cavity
  72. 72. Radiation dose prescribed to 1 cm beyond balloon surface
  73. 73. Uses 192Ir (HDR) as the source
  74. 74. FDA approval May 2002</li></li></ul><li>
  75. 75. 5th Int. Meeting ISIORT Madrid, June 2008<br />GTV<br />PTV<br />Skin<br />Volume Definition<br />PTV: GTV + 1.5 – 2.0 (clinical margin) + 0.5 (setup margin)<br /> excluding skin and chest wall<br />Skin: 5 mm depth below skin surface<br />
  76. 76. Difficulties with Mammosite<br />Balloon must conform to cavity shape without air gaps. Device explanted in ~ 10-15% of pts.<br />Ideal is to have 7 mm b/w balloon and skin to decrease risk of erythema.<br />Very dependent on surgical placement.<br />
  77. 77. CT Planning for MammositeBrachytherapy<br />Isodose Lines<br />50%<br />80%<br />100%<br />120%<br />140%<br />200%<br />Mammosite® balloon<br />
  78. 78. Prescription Dose<br /><ul><li>34 Gy
  79. 79. 10 fractions over 5 -7days</li></ul>3-Dimensional rendering of applicator surface and prescription dose cloud.<br />
  80. 80. Day 2 on treatment<br />
  81. 81. Day 2 on treatment<br />
  82. 82. 2 weeks post treatment<br />
  83. 83. 4 months after PBI<br />
  84. 84. Breast Appearance after MammoSite®<br />3 years post treatment<br />
  85. 85. MammoSite PBI<br />Average:<br />4%<br />0%<br />83%<br />64 y<br />26 mo<br />1 cm<br />
  86. 86. Toxicities of Mammosite<br />Seroma formation: Risk is increased with open technique for placement. In Beaumont series, found 60% risk with open cavity vs. 30% in closed cavity; overall rate of 45%, with 10% symptomatic.<br />Fat necrosis: Risk may be slightly lower than with HDR and no difference with placement technique.<br />
  87. 87. Conclusion<br />The MammoSite RTS is the most commonly used PBI technique<br />MammoSite is minimally invasive, offers acceptable cosmetic results, and induces mild side effects<br />The duration of treatment is only five days making it more convenient for patients <br />The MammoSite RTS has criteria which prevent some patients from eligibility<br />New devices such as SAVI, ClearPath, and Contura are overcoming those limitations<br />
  88. 88. … and Mammosite begat ….<br />Contura<br />ClearPath™<br />SAVI<br />5th Int. Meeting ISIORT Madrid, June 2008<br />
  89. 89. PBI: 3D-CRT Target definition<br />
  90. 90. PBI: 3D-CRT Beam Arrangement<br />3.85 Gy BID x 10 fractions<br />
  91. 91. PBI: 3D-CRT Isodose Distribution<br />3850 3752 3655 3557 3460<br />axial<br />sagittal<br />coronal<br />
  92. 92. 3-DCRT PBI<br />Summary:<br />273<br />63<br />21<br />0.9<br />< 1<br />0<br />
  93. 93. Accelerated Partial Breast Irradiation:Summary<br />Accelerated partial breast irradiation allows patients to complete a course of treatment in one week as opposed to the standard six weeks.<br />Treatment limited to part of the breast may be associated with less morbidity of treatment and better cosmetic outcome.<br />Hopefully, the randomized, prospective NSABP trial will answer the question of equivalence of partial and standard breast irradiation.<br />
  94. 94. Stage 0, I-II breast cancer treated by lumpectomy<br />Randomization<br />WBI<br /><ul><li>50-50.4 Gy (1.8-2.0 Gy)</li></ul>Fractions to the whole breast <br />followed by boost to 60 -66.6 Gy<br />PBI<br /><ul><li>34 Gy in 3.4 Gy fxs bid</li></ul>Mammosite® or <br />Multicatheter brachytherapy <br />OR<br /><ul><li> 38.5 Gy in 3.85 Gy fxs bid</li></ul>3D-CRT<br />NSABP B-39/RTOG 0413 TrialPhase III<br />
  95. 95. Endpoints<br /><ul><li>Primary: in-breast tumor recurrence
  96. 96. Secondary:</li></ul>Distant disease-free survival<br />Overall survival<br />QOL: Cosmesis, fatigue, symptoms, burden of care<br />
  97. 97. 5th Int. Meeting ISIORT Madrid, June 2008<br />ZeissIntrabeam®<br /><ul><li>50 kV x-ray source at the end of a 15 cm long, 3.5 mm diameter tube.
  98. 98. Spherical applicators with diameters of 15-50 mm in steps of 5 mm
  99. 99. Dose rate of about 2 Gy/min at 1 cm in water</li></li></ul><li>Spherical applicators<br />1.5 to 5cm diameter in 0.5cm steps<br />Uniform surface dose-rate<br />
  100. 100. The pliable breast tissue is wrapped around the applicator. Subcutaneous stitches aid conformation, while ensuring that the skin is at least 1cm from the applicator surface.<br />
  101. 101.
  102. 102.
  103. 103. Intraoperative Radiation Therapy (IORT) for PBI<br />TARGIT trial is comparing whole breast irradiation to IORT delivering a single dose of 20 Gy. Primary accrual is in Europe.<br />Using the Intrabeam Photon Radiosurgery System, 50 kV x-rays.<br />Trial has enrolled 900 patients with target of 2200 patients. <br />
  104. 104. Trials of partial breast RT<br />
  105. 105. Intensity Modulated Radiation Therapy (IMRT)<br />Dose distribution to breast with standard tangential fields<br />Dose distribution to breast using IMRT<br />
  106. 106. Intensity Modulated Radiation Therapy (IMRT)<br />
  107. 107. IMRT for Early Breast<br />
  108. 108. Intensity Modulated Radiation Therapy (IMRT)<br />Phase III Randomized Study of Intensity Modulated Radiation Therapy Versus Standard Wedging Technique for Adjuvant Breast Radiotherapy<br />J. Pignol, et. al.<br />Toronto, ON and Victoria, BC<br />Presented ASTRO 2006, Plenary Session<br />
  109. 109. Tangential Fields vs IMRT<br />358 patients randomized to standard breast irradiation or IMRT<br />Dose of up to 50 Gy+ 16 Gy boost<br />Endpoints of acute skin reaction and incidence of moist desquamation<br />
  110. 110. Tangential Fields vs IMRT<br />311 Patients included in analysis<br />Decreased moist desquamation with IMRT- 31% vs 48% (p=0.0019)<br />Decreased moist desquamation in inframammary fold with IMRT- 26% vs 43% (p=0.0012)<br />IMRT lowers the dose of radiation to the lung and to the heart (in patients with left sided breast cancers).<br />
  111. 111. Moist Desquamation<br />
  112. 112. Intensity Modulated Radiation Therapy (IMRT)- Summary<br />We would not expect to see any differences in terms of recurrence or survival with IMRT<br />We would hope to see improvement in side effect profile<br />It may take years or decades to document a benefit in terms of cardiac toxicity<br />
  113. 113. Goodman<br />Figure 4a. Transverse Dose Distributions<br />IMRT<br />Conventional<br />Isodose<br /> in %<br />113<br />108<br />100<br />90<br />50<br />102<br />10<br />
  114. 114. DVH – Coronary artery region <br />
  115. 115. Other Clinical Scenarios<br />Inoperable presentations<br />Bulky, non-resectable recurrent cancer<br />IMRT plans have sometimes looked significantly better than 3D conformal, on a CASE BY CASE basis<br />
  116. 116. 5th Int. Meeting ISIORT Madrid, June 2008<br />Proton/Photon Comparison<br />Figure 1: Two-field proton PBI plan in axial, coronal, and sagittal views<br />Figure 1: Two-field proton PBI plan in axial, coronal, and sagittal views<br />Figure 1: Two-field proton PBI plan in axial, coronal, and sagittal views<br />Figure 1: Two-field proton PBI plan in axial, coronal, and sagittal views<br />Figure 1: Two-field proton PBI plan in axial, coronal, and sagittal views<br />Figure 1: Two-field proton PBI plan in axial, coronal, and sagittal views<br />Photon<br />Photon<br />Proton<br />Proton<br />Isodose lines<br />— 103%<br />— 100%<br />— 75%<br />— 50%<br />— 25%<br />
  117. 117.
  118. 118. 5th Int. Meeting ISIORT Madrid, June 2008<br />Conclusions from Proton Therapy Study<br />- Protons spare non target breast tissue - reduction of 40%-45% vs. mixed modality<br />- Protons also spare contralateral lung & heart<br />- May permit retreat for pts with ipsilateral recurrence outside original field.<br /><ul><li>Dose escalation?
  119. 119. Effect of neutrons in passively scattered proton beams (Hall et. al.), but not in IMPT</li></li></ul><li>5th Int. Meeting ISIORT Madrid, June 2008<br />IMRT<br />Protons<br />Photons<br />El Ghamry et. Al. IJROBP 2002<br />
  120. 120. 5th Int. Meeting ISIORT Madrid, June 2008<br />Dose to Heart<br />
  121. 121. 5th Int. Meeting ISIORT Madrid, June 2008<br />Dose to Lung<br />
  122. 122. 5th Int. Meeting ISIORT Madrid, June 2008<br />Cost vs. Benefit: Protons vs. Photons<br />Benefit: Volume of non-target breast tissue receiving 50% of the prescribed dose is reduced 40% to 45%<br />Cost: WBI+B $10.6K<br /> 3D-CPBI proton $13.2K (+25%)<br /> 3D-CPBI-photon $5.3K (-50%)<br />A. Taghian et. al. IJROBP. 65:1404-1410; 2006<br />