Who Benefits From Apbi March2009


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Accelerated Parial Breast Irradiation- Who Benefits From APBI?

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Who Benefits From Apbi March2009

  1. 1. Who Can Benefit From APBI & The Changing Treatment Landscape Joe L. Meadows, M.S. Medical Physicist The Lacks Cancer Center Saint Mary’s Health Care Grand Rapids, MI Joe Meadows M.S. St Mary’s March 2009 Joe Meadows M.S. St Mary’s March 2009
  2. 2. Objectives <ul><li>Overview of Partial Breast Irradiation (PBI) and patient selection criteria </li></ul><ul><li>Who can benefit from APBI </li></ul><ul><li>Review of patient selection criteria </li></ul><ul><li>Review of Techniques: Mammosite, Contura, Xoft, and 3D-EBRT PBI, and Single-fraction, intra-operative PBI </li></ul>Joe Meadows M.S. St Mary’s March 2009
  3. 3. Joe Meadows M.S. St Mary’s March 2009 Breast Conservation Therapy (BCT) is a standard of care supported by years of data. <ul><li>BCT refers to breast-conserving surgery (BCS) + RT. </li></ul><ul><li>27+ years of data supports BCT as a standard. </li></ul><ul><li>Six modern, prospective randomized trials found no significant differences when comparing BCT to mastectomy. </li></ul><ul><ul><li>Clinical trials compared local recurrence, distant metastasis, and long-term survival. </li></ul></ul>
  4. 4. Joe Meadows M.S. St Mary’s March 2009 Prospective Randomized Trials: BCT vs.Mastectomy
  5. 5. Joe Meadows M.S. St Mary’s March 2009 Prospective Randomized Trials: Lumpectomy +/- Radiation Therapy
  6. 6. Joe Meadows M.S. St Mary’s March 2009 So although BCT is equivalent to mastectomy in terms of recurrence and survival rates, it is still very underutilized. But even today, more than 15 years later, many women eligible for breast-conserving surgery are getting mastectomies. <ul><li>2007 Cancer Facts & Figures American Cancer Society. </li></ul><ul><li>U.S. Department of Health and Human Services, Office on Women’s Health. </li></ul><ul><li>SEER Data 2000-2004 Incidence Rates, NCI. </li></ul><ul><li>The National Institutes of Health Consensus Statement on Treatment of Early-Stage Breast Cancer states: “Breast Conservation Surgery plus radiotherapy is preferable to total mastectomy because it provides survival equivalence while preserving the breast.” (Consensus statement on treatment of early-stage breast cancer. National Institutes of Health, 1992). </li></ul>In 2007, upwards of 180,000 women will be eligible for breast conservation therapy. However, according to SEER data, only about 40% of eligible women receive BCT each year. Another 41% receive mastectomy and 19% get a lumpectomy without follow-up radiation therapy. In 2007, this means that over 108,000 women may not receive the preferred method of treatment for their early-stage breast cancer. And sadly, over 34,000 are risking recurrence by not having their recommended course of radiation therapy. An idea behind MammoSite Targeted Radiation Therapy and other forms of APBI is that this treatment modality can help increase the number of women who receive breast conservation therapy and help reduce the numbers of women who receive mastectomy and lumpectomy only. Under-Utilization of BCT 240,000 Breast Cancer Cases in 2007 1 ~180,000 Eligible for Breast Conservation Therapy (BCT) 2 ~72,153 40% ~34,273 19% ~73,957 41% Mastectomy BCT Lumpectomy No Radiation 108,230 3 No Radiation
  7. 7. Benefit of Post Op Treatment Doctors in some parts of the United States may be more old-fashioned and less likely to offer lumpectomy with radiation as an option for their patients, particularly their older patients . Such doctors may urge mastectomy , even for women who should be offered the choice. But recent research has shown that women 75 or older who get radiation after lumpectomy are more likely to live longer and remain free of breast cancer longer than women who do not get radiation. http://www.breastcancer.org/treatment/surgery/lumpectomy/index.jsp Joe Meadows M.S. St Mary’s March 2009
  8. 8. Standard Of Care <ul><li>Is lumpectomy &quot;good&quot; breast cancer treatment? </li></ul><ul><li>A general principle of cancer treatment is that almost always, the &quot;whole&quot; breast must be treated for breast cancer. This can be accomplished by: </li></ul><ul><li>Mastectomy (removal of the whole breast), or </li></ul><ul><li>Lumpectomy AND Radiation Therapy to the rest of the breast. </li></ul>http://www.breastcancer.org/treatment/surgery/lumpectomy/index.jsp Joe Meadows M.S. St Mary’s March 2009
  9. 9. Breast Conserving Therapy <ul><li>The evidence shows that lumpectomy followed by radiation is likely to be equally as effective as mastectomy for women with: </li></ul><ul><li>Only one site of cancer in their breast, and </li></ul><ul><li>Tumor under four centimeters, removed with clear margins (no cancer cells in the tissue surrounding the tumor). </li></ul>Joe Meadows M.S. St Mary’s March 2009
  10. 10. Breast Conserving Therapy + = BCT candidate Joe Meadows M.S. St Mary’s March 2009 A. Tumor B. Lumpectomy specimen
  11. 11. Whole Breast or Partial? For patients with node-negative breast cancer who undergo breast conserving surgery (BCS), RT to the whole breast is standard adjuvant local treatment. Clearly demonstrated in randomized trials to provide local control and survival comparable to mastectomy . h ttp://www.medscape.com/viewprogram/8355
  12. 12. A ccelerated P artial B reast I rradiation <ul><li>Delivery of larger doses/fraction of radiation therapy (RT) to the lumpectomy cavity (plus 1-2 cm margin) after breast conserving surgery (BCT) </li></ul><ul><ul><li>Patients : </li></ul></ul><ul><ul><ul><li>Stage (0, I, II) breast cancer </li></ul></ul></ul><ul><ul><li>Radiation Modalities : </li></ul></ul><ul><ul><ul><li>Brachytherapy </li></ul></ul></ul><ul><ul><ul><li>External beam techniques </li></ul></ul></ul>Dr.F.Vicini Beaumont Hospital Joe Meadows M.S. St Mary’s March 2009
  13. 13. A ccelerated P artial B reast I rradiation <ul><ul><li>Goal </li></ul></ul><ul><ul><ul><li>Complete RT in < 4-5 days after lumpectomy versus conventional of 6-7 weeks </li></ul></ul></ul><ul><ul><ul><li>In many ways APBI is to current whole breast radiotherapy what a lumpectomy is to a mastectomy . </li></ul></ul></ul><ul><ul><ul><li>The goal is to use a less invasive more focused treatment without compromising survival . </li></ul></ul></ul>Dr.F.Vicini Beaumont Hospital Joe Meadows M.S. St Mary’s March 2009
  14. 14. A ccelerated P artial B reast I rradiation <ul><li> Time and Inconvenience of BCT </li></ul><ul><li>Improve Documented Underutilization of BCT (studies have shown distance to a facility is critical) </li></ul><ul><li>Potentially Reduce Acute and Chronic Toxicity </li></ul><ul><li>Improve Quality of Life of Patients </li></ul><ul><li>Eliminate Scheduling Problems With Systemic Chemotherapy </li></ul>Dr.F.Vicini Beaumont Hospital Joe Meadows M.S. St Mary’s March 2009
  15. 15. Changing Paradigm? <ul><li>Improved Patient Selection for BCT : </li></ul><ul><ul><li>Screening mammography, ultrasound and MRI have resulted in more highly selected patients with earlier stage disease (smaller tumors) </li></ul></ul><ul><ul><li>Patients are less likely to have occult (multi-centric) cancer in remote areas of the breast </li></ul></ul>
  16. 16. A ccelerated P artial B reast I rradiation <ul><li>Assumptions: </li></ul><ul><li>Whole breast radiation is not needed in appropriately selected patients </li></ul><ul><li>Radiation can be targeted only to a smaller area of the breast (lumpectomy cavity plus a margin) with similar local control rates and cosmetic results </li></ul><ul><li>‘Targeted radiation’ can be delivered faster (accelerated - less fractions) with similar tumor control and acute and late toxicity </li></ul>Dr.F.Vicini Beaumont Hospital
  17. 17. National Protocol 127 Pages !! Easy Reading
  18. 18. National Protocol
  19. 19. NSABP B-39/RTOG 0413 <ul><li>Open : </li></ul><ul><ul><li>March 21, 2005 </li></ul></ul><ul><li>Accrual : </li></ul><ul><ul><li>April 25, 2008: 3075 (I don’t have any more recent data) </li></ul></ul><ul><li>Participating Sites : </li></ul><ul><ul><li>78 – NSABP </li></ul></ul><ul><ul><li>142 – RTOG/CTSU </li></ul></ul><ul><li>PBI Technique </li></ul><ul><ul><li>71.0%: 3D Conformal </li></ul></ul><ul><ul><li>23.3 %: MammoSite </li></ul></ul><ul><ul><li>5.7%: Interstitial </li></ul></ul>
  20. 20. Patient Selection Criteria NØ; N1 (1-3 nodes) NØ NØ Nodal status Negative microscopic surgical margins of excision by NSABP definition Negative microscopic surgical margins of excision Negative microscopic surgical margins of excision Surgical margins < 3cm < 3cm < 3cm Tumor size Invasive adenocarcinoma or DCIS Invasive ductal carcinoma or DCIS Infiltrating ductal carcinoma Diagnosis > 18 > 45 > 50 Age *NSABP B39 - RTOG 0413 Eligibility Criteria ASBS Recommendations (Updated December 2005) ABS Recommendations (Updated February 2007)
  21. 21. APBI -InterstitialCatheter <ul><li>The most mature single institutional studies have utilized interstitial brachytherapy as the PBI delivery methods. The 10-year results from these studies revealed excellent outcomes. [22] </li></ul>(22).IJROBP 2007;68(2) 341-6 Vicini FA et al <ul><li>Guy’s Hospital (n=27) 1987 </li></ul><ul><li>Florence, Italy (n=115) </li></ul><ul><li>Oschner Clinic (n=300) </li></ul><ul><li>London Regional Cancer Center (n=39) </li></ul><ul><li>William Beaumont Hospital (n=199) </li></ul><ul><li>Orebro Medical Center (n=45) </li></ul><ul><li>Virginia Commonwealth University (n=59) </li></ul><ul><li>National Institute of Oncology – Hungary (n=245) </li></ul><ul><li>University of Kansas (n=24) </li></ul><ul><li>RTOG 95-17 (n=99) </li></ul><ul><li>Massachusetts General Hospital (n=48) </li></ul><ul><li>Tufts/Brown University (n=79) </li></ul><ul><li>German/Austrian Trial (n=156) </li></ul><ul><li>William Beaumont Hospital (199) 2008 </li></ul>Published Interstitial APBI Data
  22. 22. Interstitial Experience - Selected APBI Studies - <ul><li>RTOG 95-17 : </li></ul><ul><ul><li>Phase I/II PBI Trial </li></ul></ul><ul><ul><li>12 institutions </li></ul></ul><ul><ul><li>99 patients enrolled </li></ul></ul><ul><ul><li>Median f/u: 6.14 yrs </li></ul></ul><ul><ul><li>5-yr actuarial local recurrence rate: 4% </li></ul></ul><ul><ul><li>Int J Radiat Oncol Biol Phys </li></ul></ul><ul><li>William Beaumont Hospital: </li></ul><ul><ul><li>199 patients (LDR/HDR brachytherapy) </li></ul></ul><ul><ul><li>Median follow-up: 8.6 yrs </li></ul></ul><ul><ul><li>10-yr actuarial local recurrence: 3.8% </li></ul></ul><ul><ul><li>Int J Radiat Oncol Biol Phys 68 (2): 341-6, 2007 </li></ul></ul>Dr.F.Vicini Beaumont Hospital
  23. 23. Dr.F.Vicini Beaumont Hospital WBH Data: Matched Pair Analysis 12 Yr Actuarial Outcome - APBI vs. WBRT 0.1 96% 99% Cosmesis (excellent/good) 0.6 2 % 2 % Clonally Distinct / Elsewhere 0.5 4 % 5 % IBTR 0.1 67 % 75 % 5 yr DFS after IBTR 0.3 93 % 95 % Cause-Specific Survival 0.4 87 % 91 % Freedom From Failure 0.08 90 % 95 % Distant Metastases Free Survival 0.3 0.5 % 2 % Regional Nodal Failure 0.2 8 % 6 % Contralateral Failure 0.6 2 % 3 % Clonally Related / TRMM p WBRT (n=199) APBI (n=199) 12 Year Outcome Measure
  24. 24. APBI Criteria 3-Dimensional rendering of applicator surface Tissue Conformance- <10% air Skin Spacing- Min 5mm to skin Balloon Diameter & Symmetry- <2mm
  25. 25. APBI Techniques <ul><li>Catheter based brachytherapy </li></ul><ul><li>MammoSite TM Balloon Device </li></ul><ul><li>Contura TM Multiple Lumen Balloon (MLB) </li></ul><ul><li>3D Conformal external beam radiation therapy </li></ul><ul><li>Intra-Operative PBI </li></ul>
  26. 26. APBI -InterstitialCatheter <ul><li>Six of 199 patients had Ipsilateral Breast Tumor Recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. </li></ul><ul><li>These numbers are considered to be equivalent to Whole Breast RT following BCS. </li></ul><ul><li>Requires most expertise ! </li></ul><ul><li>(NOT for the faint of heart) </li></ul>(22).IJROBP 2007;68(2) 341-6 Vicini FA et al
  27. 27. APBI –InterstitialCatheter “Our” First Experience <ul><li>It was the first approach to APBI in Radiation Oncology. </li></ul><ul><li>This technique has the longest follow-up data to date. </li></ul><ul><li>This technique is still in use today at certain (not many) medical centers around the country. </li></ul><ul><li>The post-lumpectomy bed is “sandwiched” between two planes of needles to provide adequate dosing to it’s periphery </li></ul><ul><li>PROBLEM - Not many Residency programs today teach this level of brachytherapy expertise. Therefore, to emulate this positive experience required a re-engineering of the approach to breast APBI Brachytherapy </li></ul>
  28. 28. APBI - Mammosite  HDR Unit * **Over 60,000 patients have been treated to date with Mammosite! <ul><li>The device is placed in the post-lumpectomy cavity and inflated with saline and contrast to a volume at least as large as the lumpectomy cavity if not larger. </li></ul><ul><li>The larger the balloon fill volume, the better the dosimetric advantage of depth-dose since the Rx is 1cm beyond the balloon surface. </li></ul><ul><li>MammoSite  Balloon Device </li></ul><ul><li>Simplified approach compared interstitial since it doesn’t require “creating” a cavity for the device. </li></ul>
  29. 29. APBI - Mammosite  Various balloon shapes/sizes offer ability to implant a broad range of cavity shapes/volumes. 5 – 6 cm Sphere 4 x 6 cm Ellipsoidal 4 – 5 cm Sphere Balloon Configuration
  30. 30. APBI - Mammosite  <ul><li>CT is performed for Treatment Planning </li></ul><ul><li>Central lumen for HDR source </li></ul><ul><li>Treatment delivery ~ 5 min </li></ul><ul><li>Patient receives 5 days of BID treatments separated by 6 hrs </li></ul><ul><li>Device is deflated and removed following last fraction </li></ul>
  31. 31. Mammosite  - Problems That Can Occur <ul><li>Too much AIR surrounding balloon </li></ul><ul><li>Balloon Asymmetry </li></ul><ul><li>Too close to skin </li></ul><ul><li>Seroma too large (treated the same was as AIR, must be <10%) </li></ul>
  32. 32. APBI – Contura TM Multiple Lumen Balloon (MLB) <ul><li>Has the advantage of maintaining the fixed balloon filled geometry but can optimize the dosimetry </li></ul><ul><li>The 5 multiple channels can be turned “on” and “off” to pull the isodose shape away from ribs and skin. </li></ul><ul><li>Skin distance no longer an issue! </li></ul>
  33. 33. APBI External Beam Radiotherapy ( EBRT) <ul><li>3D Conformal - EBRT </li></ul><ul><li>This was the technique utilized in over 70 % of the RTOG protocol cases in the beginning . </li></ul>LINAC Tomotherapy <ul><li>“When all you have is a hammer, everything looks like a nail”! </li></ul>
  34. 34. APBI - EBRT <ul><li>Lumpectomy cavity is the “ Target ” </li></ul><ul><li>Multiple beams are used to avoid critical structures (heart,lung) </li></ul><ul><li>High dose surrounding Target </li></ul><ul><li>Dose fall-off surrounding Target </li></ul><ul><li>Treatment delivery- Approx. 5-10 mi n </li></ul><ul><li>Efficacy being judged on protocol </li></ul>
  35. 35. APBI - Xoft  <ul><li>Electronic” Brachytherapy </li></ul><ul><li>40 kVp x-ray tube that is water cooled </li></ul><ul><li>Applicator is a balloon device with the tube in center </li></ul>X-ray Tube HV Cable D (Gy) 34 Red 17 Orange 10.2 Yellow 6.8 Green 5.1 Blue 3.4 Dark Blue 1.7 Magenta 40 kV source in BrachyVision® D (Gy) 34 Red 17 Orange 10.2 Yellow 6.8 Green 5.1 Blue 3.4 Dark Blue 1.7 Magenta
  36. 36. APBI - Xoft  Film dosimetry around this miniaturized x-ray tube shows a nearly spherical distribution of radiation http://www.xoftinc.com/images/pdf/posters/Poster_4.pdf <ul><li>Miniature X-ray source inserted into a flexible cooling catheter </li></ul><ul><li>Water cooled, high vacuum X-ray tube technology </li></ul><ul><li>40-50 kV operating potential </li></ul><ul><li>Output: ~1 Gy/min. 1cm into tissue </li></ul><ul><li>Fully disposable device </li></ul>
  37. 37. APBI - Xoft  <ul><li>Target V 100% - 96.5% </li></ul><ul><li>Breast V 50% - 19.8% </li></ul><ul><li>Lung V 30% - 3.7% </li></ul><ul><li>Heart V 5% - 59.2% </li></ul><ul><li>Target V 100% - 96.5% </li></ul><ul><li>Breast V 50% - 13.0% </li></ul><ul><li>Lung V 30% - 1.1% </li></ul><ul><li>Heart V 5% - 9.4% </li></ul>Xoft 50kV MammoSite Ir 192 HDR
  38. 38. APBI - SAVI <ul><li>Multi-catheter applicator, expandable bundle of catheters </li></ul><ul><li>Combines the skin-sparing dosimetry of interstitial brachytherapy with the single-entry ease of balloon brachytherapy. </li></ul><ul><li>Ability to “ sculpt” the radiation dose based on patient anatomy </li></ul><ul><li>This may reduce radiation damage to the skin or chest wall </li></ul><ul><li>Might permit treatment of certain patients who were previously ineligible for other methods </li></ul>
  39. 39. APBI - SAVI  <ul><li>Strut Adjusted Volume Implant (SAVI) </li></ul><ul><li>Struts are adjusted to occupy the post lumpectomy cavity </li></ul><ul><li>Water filled balloon geometry is not used in this device </li></ul><ul><li>The source positions are in very close contact with breast tissue </li></ul><ul><li>Some have experienced issues of the tines being caught in the tissue upon device extraction causing trauma. </li></ul>
  40. 40. APBI - IORT <ul><li>Intraoperative Radiation Therapy (IORT) </li></ul><ul><li>MammoSite Balloon Device </li></ul><ul><li>3D Conformal External Beam Radiation Therapy </li></ul><ul><li>“ Electronic” Brachytherapy </li></ul><ul><li>SAVI </li></ul><ul><li>Catheter based brachytherapy </li></ul>
  41. 41. APBI - IORT(Mobetron) <ul><li>Delivers a single dose of electrons to the tissue around the lumpectomy cavity during surgery </li></ul><ul><li>Lead plate is placed to protect underlying tissues </li></ul><ul><li>Skin is moved out of the way of the radiation beam. </li></ul><ul><li>Very expensive technology of limited use </li></ul>What happens if the FINAL pathology comes back with a + margin?? Aetna considers intraoperative radiation therapy experimental and investigational for the treatment of brain tumors, breast cancer , pancreatic cancer, cholangiocarcinoma, retroperitoneal sarcoma, osteosarcoma, and all other indications.
  42. 42. FDA Trial: Updated Results Benitez et al: ASBS April 2007 Am J Surg 194(4):456-62, 2007 <ul><li>36 (out of 43) evaluable patients/T1N0 </li></ul><ul><li>Median follow-up: 66 months </li></ul><ul><li>83% Excellent/Good Cosmesis </li></ul><ul><li>No local or regional recurrences </li></ul><ul><li>Fat Necrosis: 9.3% (all asymptomatic) </li></ul><ul><li>Infection rate: 9.3% </li></ul><ul><li>Seromas: 32.6% (12% symptomatic) </li></ul>
  43. 43. Published APBI Results - All APBI Techniques - Dr.F.Vicini Beaumont Hospital Technique # Series # Patients Follow-Up (Range) % IBTR (Range) Interstitial 14 1166 27-113 0-9% Mammosite 12 3332 2-66 0-6% 3D Conformal 3D Conformal 7 367 10-36 0-2% Totals Totals 33 4865 2-113 0-9%
  44. 44. NSABP B-39/RTOG 0413 Dr.F.Vicini Beaumont Hospital <ul><li>Open : </li></ul><ul><ul><li>March 21, 2005 </li></ul></ul><ul><li>Accrual : </li></ul><ul><ul><li>April 25, 2008: 3075 </li></ul></ul><ul><li>Participating Sites : </li></ul><ul><ul><li>78 – NSABP </li></ul></ul><ul><ul><li>142 – RTOG/CTSU </li></ul></ul><ul><li>PBI Technique </li></ul><ul><ul><li>71.0%: 3D Conformal </li></ul></ul><ul><ul><li>23.3 %: MammoSite  </li></ul></ul><ul><ul><li>5.7%: Interstitial </li></ul></ul>
  45. 45. NSABP B-39/RTOG 0413 - Current Status - Dr.F.Vicini Beaumont Hospital <ul><li>Significant enrollment of low risk patients (greater than anticipated) </li></ul><ul><li>Sample size increased because of enrollment of low-risk patients </li></ul><ul><ul><li>Accrual increased by 1300 patients (4300 total) </li></ul></ul><ul><ul><li>Low risk patients now excluded (January 1, 2007): </li></ul></ul><ul><li>Anticipated closure: 2011 </li></ul>https://silver1.phila.acr.org/Clinical_RTOG/FileRendering.pdf
  46. 46. APBI Conclusions Dr.F.Vicini Beaumont Hospital <ul><li>Majority of interstitial APBI data in low risk patients are excellent </li></ul><ul><li>-10-year results available </li></ul><ul><li>Preliminary MammoSite data looks good </li></ul><ul><ul><li>-Monitor for new toxicities/efficacy </li></ul></ul><ul><li>Insufficient 3D Conformal PBI data available to draw any conclusions </li></ul><ul><li>First completed/published contemporary phase III PBI trial using interstitial APBI shows equivalent results to WBI at 5-years </li></ul>
  47. 47. APBI Conclusions Dr.F.Vicini Beaumont Hospital <ul><li>Remaining Questions : </li></ul><ul><ul><li>Mature phase III data will not be available for several years (2015-2020) </li></ul></ul><ul><ul><li>What should we do until additional phase III data are available? </li></ul></ul><ul><ul><li>ASBS & ABS provide guidelines for the use of APBI off-protocol in selected patients </li></ul></ul><ul><ul><li>ASTRO consensus conference planned with published guidelines to be developed </li></ul></ul>