Ioert To The Tumor Bed

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Ioert To The Tumor Bed

  1. 1. ISIORT Europe IOERT to the tumor bed, followed by whole breast irradiation: Update of the Pooled Analysis on the BIO-Boost Sedlmayer F, Fastner G, Merz F, Reitsamer R, Menzel C Salzburg / A Ciabattoni A, Petrucci A Rom SGF Neri / I Hagen E Klagenfurt / A Willich N, Schuck A, Brinkmann M Münster / D Orecchia R Mailand /I Valentini V Rom UC Gemelli/I
  2. 2. BIO-Boost: Linac-based IORT with Electrons 9-10 Gy IORT Boost + 50 Gy Whole-Breast
  3. 3. ISIORT Europe Breast Intraoperative Boost (BIO- Boost) : Pooled Analysis* 10/98 – 12/05: 1200 treatments Salzburg 870 SFN/Rom 142 Klagenfurt 74 Mailand 65 Münster 38 UC Gemelli/Rom 11 *4/07
  4. 4. Patients ISIORT BIO-Boost Pooled Analysis „ Best Selection“: T1-2 N0 G1-2, >50a: 331 Patients (30%) N-positive and/or G3 and/or T3 and/or Age<45a. 716 Pat. (60%) Age: 57,3 a (22,5 – 89,9) 62   29   21 n.st. 3 Gx 9 Nx 7 T3 284 G3 7 N3 295 T2 538 G2 32 N2 695 T1 143 G1 343 N1 5 T0     611 N0 8 Dcis Grading N   T  
  5. 5. IOERT in Breast Cancer: <ul><li>Positive Needle-Biopsie , </li></ul><ul><li>BCT likely </li></ul><ul><li>Frozen section (margins), </li></ul><ul><li>Ev. Re-excision (Telepathology) </li></ul><ul><li>Approximation </li></ul><ul><li>of excision hole </li></ul><ul><li>Sonography for depth dose prescription </li></ul><ul><li>IORT: 10 Gy Reference-Dose </li></ul><ul><li>(90% Dmin) </li></ul><ul><li>Clip-Demarcation for </li></ul><ul><li>PTV-documentation </li></ul>
  6. 7. Analysis 5/08 ISIORT BIO-Boost PA <ul><li>1200 Pat; IORT 10/98 – 12/05 </li></ul><ul><ul><li>60 Pats.: secondary mastectomy </li></ul></ul><ul><ul><li>9 Pat. : refused WBRT </li></ul></ul><ul><ul><li>10 pats. lost to FU </li></ul></ul><ul><ul><li>Remaining: 1121 Patients </li></ul></ul><ul><li>Med FU: 59,6 mths. (1 – 114) </li></ul>
  7. 8. Analysis 5/08 ISIORT BIO-Boost PA <ul><li>8 In-Breast Recurrences </li></ul><ul><li>In-Breast Tumor Control Rate: 99,3 % </li></ul><ul><li>93 patients developed metastases </li></ul><ul><li>DFS (7a): 87,7 % </li></ul><ul><li>DSS 94,5 % </li></ul><ul><li>OS 90,2 % </li></ul>
  8. 9. In-Breast Recurrences
  9. 10. In-Breast Recurrences
  10. 11. In-Breast Recurrences
  11. 12. In-Breast Recurrences
  12. 13. In-Breast Recurrences
  13. 14. In-Breast Recurrences - Summary <ul><li>3 True Local Recurrences </li></ul><ul><ul><li>All G3, </li></ul></ul><ul><ul><li>close margin status / R1, </li></ul></ul><ul><ul><li>time to recurrence: 12 – 29,3 months (med 22) </li></ul></ul><ul><li>5 Out-Quadrant Recurences </li></ul><ul><ul><li>3/5 multicentric </li></ul></ul><ul><ul><li>time to recurrence: 17 – 83 months (med. 41) </li></ul></ul><ul><li>All NO </li></ul><ul><li>Prominent DCIS in 6/8 </li></ul><ul><li>No time gap Influence IORT/XRT </li></ul>ISIORT Europe BIO-Boost Analysis 5/08:
  14. 15. Disease Free Survival (7a): N0: 93,2 % N1: 82,9 % N2: 69,1% T1 : 91,7 % T2 : 85 %
  15. 16. Follow-up 2/08: Disease Specific Survival (7a) 7 a: 94,8% (all)
  16. 17. Follow-up 4/07: Overall Survival (7a) 5 a: 95,6% 7 a: 91,5% (all)
  17. 18. Boost-RT for everybody ?
  18. 19. Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882 Antonini N, …. Bartelink H Radiotherapy and Oncology 82 (2007) 265–271 Boost (16 Gy) versus No-Boost following WBRT with 50 Gy n = 5.318 Pat. Re-Analysis at 77,5 Mo med FU: Boost-advantage for all age groups
  19. 20. Spline Kurve for age and risk for developement of a local recurrence LN-Transformation function in terms of Hazard Risk ratios (5-a-steps) 1. Age-independent boost effect : halfened LR-Rates 2. Reduced absolute LR-Risk with growing age 3. Highest absolute gain at ages < 45 a
  20. 21. IOERT with 10 Gy has an iso-effect of at least 17 Gy in standard fractionation IOERT vs. postop. Boost Int J Cancer 2006 In-Breast Tumor Recurrence after 5 a: 4,3 vs. 0 % P < 0,01
  21. 22. Why BIO-Boost 10 Gy and not Single Modality (ELIOT) 22 Gy ? <ul><li>No “low risk” selection , normal case mix </li></ul><ul><li>LQ model not tested for doses > 20 Gy for equal tumor effects, but predicts significant more normal tissue reaction (fibrosis / necrosis). </li></ul><ul><li>Different Surgical techniques : </li></ul><ul><ul><li>Tumorectomy </li></ul></ul><ul><ul><li>≠ </li></ul></ul><ul><ul><li>(modified) Quadrantectomy </li></ul></ul>
  22. 23. Bio-Boost Milano/ELIOT Veronesi, Orecchia et al Ann Surg 2005
  23. 24. Why Boost and not Single Modality? <ul><li>Incidence of out-quadrant tumor foci ? </li></ul><ul><ul><li>unclear, 30- 80% in pathologic series, MRI, </li></ul></ul><ul><ul><li>50 Gy WB-RT usually controls out-quadrant low tumor burden </li></ul></ul><ul><ul><li>Distant quadrant IBTR occur later than true LRs ! </li></ul></ul>
  24. 25. In-Breast Recurrence : changing topography with time I <ul><li>Freedman et al , IJROBP 2005: 1190 Pat . following WBRT </li></ul><ul><li>„ True“ Local Recurrence </li></ul><ul><li>2%, 5%, and 7% after 5, 10, and 15 a, </li></ul><ul><li>Recurrence „ elsewhere “ : </li></ul><ul><li>1%, 2%, and 6 % nach 5, 10, and 15 a </li></ul>
  25. 26. <ul><li>Krauss et al. IJROBP 2004 : </li></ul><ul><ul><li>1448 Pat. > 60 Gy, med. FU 8.5 a </li></ul></ul><ul><li>79 In-Breast Recurrences : </li></ul><ul><ul><li>59 IBR (74.7%) “true” LR / Marginal misses, </li></ul></ul><ul><ul><li>20 (25.3%) Out-Quadrant </li></ul></ul><ul><li>Occurence of “distant-quadrant” recurrences: 39% (5-10 y), und 27% (10-15 y) </li></ul>In-Breast Recurrence : changing topography with time II
  26. 27. PATTERN OF LOCAL RECURRENCE AFTER CONSERVATIVE SURGERY AND WHOLE-BREAST IRRADIATION True local recurrence rates: 2%, 5%, and 7% (5–9%) at 5, 10, and 15 years, In-Breast-Recurrences „elsewhere“ : rare at 5 (1%) and 10 (2%) years, but increased to 6 (3–9%) at 15 years (same rates!) Different times to recurrence : Freedman et al, IJROBP 2005 1190 pts. IBTR „elsewhere“ is counterbalanced by HT, but: without WBRT ???
  27. 28. <ul><li>Change in temporal patterns of local failure after breast-conserving therapy and their prognostic implications. </li></ul><ul><li>Krauss DJ, Kestin LL, Mitchell C et al., IJROBP 60:731-40, 2004 </li></ul><ul><li>WBH, 1980-1997, 1448 patients, > 60 Gy; median FU 8.5 yrs </li></ul><ul><li>79 IBR, </li></ul><ul><li>corresponding to 5-, 10- and 15-a act. rate of 2%, 7% and 10% </li></ul><ul><li>59 IBR (74.7%) were TR/MM* , 20 (25.3%) Out-Quadrant </li></ul><ul><li>Out-Quadrant failures were 7% (0-5 y), 39% (5-10 y), and 27% (10-15 y) </li></ul>*TR/MM: True recurrence, Marginal Miss
  28. 29. Statement 24a of the S3 guidelines of the German Cancer Society <ul><li>“ Accelerated partial breast irradiation as a sole intraoperative or postoperative radiotherapy instead of whole breast radiotherapy is an experimental method and should not be performed except in studies (LoE 3, GR A)” </li></ul>

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