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Best of SABCS 2012 Radiation Oncology

Best of SABCS 2012 Radiation Oncology. Catherine Park, M.D. UCSF Department of Radiation Oncology. Content. Hypofractionation APBI IORT Local Treatment in Stage IV disease. Content. [S4 - 1] The UK START ( Standardisation of Breast Radiotherapy) Trials: 10-Year Follow-Up Results

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Best of SABCS 2012 Radiation Oncology

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  1. Best of SABCS 2012Radiation Oncology Catherine Park, M.D. UCSF Department of Radiation Oncology

  2. Content • Hypofractionation • APBI • IORT • Local Treatment in Stage IV disease

  3. Content • [S4-1] The UK START (Standardisation of Breast Radiotherapy) Trials: 10-Year Follow-Up Results • [S4-2] Targeted Intraoperative Radiotherapy for Early Breast Cancer: TARGIT-A Trial- Updated Analysis of Local Recurrence and First Analysis of Survival • [P4-16-08] Intraoperative Electron Radiotherapy in Early Stage Breast Cancer. A Single-Institution Experience • [P4-16-03] Patterns of Failure after Accelerated Partial Breast Irradiation by Consensus Panel Group: A Pooled Analysis of William Beaumont Hospital and the American Society of Breast Surgeons Trial Data • [P4-16-06] Radiotherapy To the Primary Tumor Is Associated with Improved Survival in Stage IV Breast Cancer

  4. Hypofractionated Breast RT Change in DOSE: *Hypofractionatedlarger dose per fraction *Same time vs. shorter time versus versus

  5. S4-1: The UK START (Standardisation of Breast Radiotherapy) Trials: 10-Year Follow-Up Results • JS Haviland, RK Agrawal, E Aird, J Barrett, P Barrett-Lee, J Brown, J Dewar, J Dobbs, P Hopwood, P Hoskin, P Lawton, B Magee, J Mills, D Morgan,JROwen, S Simmons, MA Sydenham, K Venables, JM Bliss, JR Yarnoldon behalf of the START Trialists

  6. Background • International standard adjuvant radiotherapy regimens following primary surgery for early breast cancer have historically delivered a high total dose (50Gy) in 25 small daily doses (fractions)over 5 weeks. • However, randomised trials, including START, indicate that a lower total dose delivered in fewer, larger fractions (Fr) is likely to be at least as safe and effective (START Trialists’ Group, Lancet 2008 & Lancet Oncol 2008). • Here, we report 10-year follow-up of the UK START Trials testing 13- and 15-Fr regimens in terms of local cancer control and late adverse effects.

  7. Methods • Between 1999 and 2002, 4451 women with completely excised invasive breast cancer (T1-3, N0-1, M0) were randomisedafter primary surgery to comparisons of: • 50Gy in 25Fr over 5 weeks vs41·6Gy or 39Gy in 13Fr over 5 weeks (START A) • or 50Gy in 25Fr over 5 weeks vs 40Gy in 15Fr over 3 weeks (START B) • Womenwere eligible if aged over 18 years and did not have an immediate surgical reconstruction. ~85% START A and >90% START B had lumpectomy. • Protocol-specified principal endpoints were local-regional (LR) tumour relapse and late normal tissue effects.

  8. Methods T1-3, N0-1 M0 breast cancer Primary endpoint: Local-regional relapse Secondary: Normal tissue effects Disease-free and OS 35 UK centers 1999-2002 Median F/U: START A- 9.3 yrs START B- 9.9 yrs

  9. Findings: START A • Median F/U in survivors is now 9.3 years in START A and 139 LRs • In START A, the 10-year rate of LR relapse was

  10. Findings: START B • Median F/U in survivors is now 9.9 years in START B and 95 LR’s • In START A, the 10-year rate of LR relapse was

  11. Findings START A

  12. Findings START B

  13. Findings: Cosmesis • Clinician assessments suggested lower 10-year rates of any moderate/marked late normal tissue effects after 39Gy (43.9%; 95%CI 39.3-48.7) and similar rates after 41.6Gy (49.5%;95%CI 44.9-54.3) compared with 50Gy (50.4%; 95%CI 45.8-55.3) in START A • and lower rates after 40Gy in START B (37.9%; 95%CI 34.5-41.5) compared with 50Gy (45.3%; 95%CI 41.7-49.0). • From a planned meta-analysis of START A and the START pilot trial (Owen et al, Lancet Oncol 2006), the adjusted estimate of α/β value for tumourcontrol was 3.5Gy (95% CI 1.2-5.7) and for late change inphotographicbreast appearance was 3.1Gy (95% CI 2.0-4.2).

  14. Findings START A: Physicians’ assessment of cosmesis

  15. Findings START B: Physicians’ assessment of cosmesis

  16. Conclusions

  17. Discussion

  18. Discussion Node-negative clear margins after lumpectomy exclusion of very large breast size no boost 10% chemo

  19. Change in DOSE: *Hypofractionatedlarger dose per fraction *Shorter timeless time Change in VOLUME: *limited volume less tissue treated versus Accelerated Partial Breast RT

  20. Intraoperative Radiotherapy Trials

  21. [S4-2] Targeted Intraoperative Radiotherapy for Early Breast Cancer: TARGIT-A Trial- Updated Analysis of Local Recurrence and First Analysis of Survival Lancet 2010

  22. Intrabeam™ for Targeted Intraoperative Radiotherapy

  23. Intraoperative Technique Physical Dose Profile BED= Physical Dose x [1+ (dose/fx) / a/b)] a/b = 10 (early effects conventional EBRT) a/b= 1.5 (assumed for TARGiT device) Vaidya et al, Annals of Oncol, 2001; 12: 1075-1080

  24. Trial schema

  25. Findings

  26. Update: Methods • 3451 women aged 45 years or older with invasive ductal carcinoma were enrolled from 33 centres in 10 countries between 2000 and 2012. • Randomisation to TARGIT or EBRT arm was done either before lumpectomy (pre-pathology) or after lumpectomy (postpathology). • The primary outcome was ipsilateral within breast recurrence (IBR) with an absolute non-inferiority margin of 2.5% at 5 years and secondary outcome was survival.

  27. Updated Results • 1721 patients were randomly allocated to receive TARGIT and 1730 to EBRT. • 1010 patients have a minimum 4 years follow up and 611 patients have minimum 5 years follow up. 1222 patients with median F/U of 5 years. Primary events have increased from 13 to 34 since 2010.

  28. Updated Results • For the primary outcome of ipsilateral breast recurrence, the absolute difference at 5-years was 2.0%, which was higher with TARGIT and reached the conventional levels of statistical significance (p=0.042), but was within the pre-specified non-inferiority margin; • in prepathology the absolute difference in 5-year IBR was 1%; in postpathology it was 3.7%.

  29. Updated Results • For the secondary outcome, there was a non-significant trend for improved overall survival with TARGIT (HR = 0.70(0.46-1.07)) due to fewer non-breast cancer deaths (17 vs. 35, HR 0.47 (0.26-0.84)). Cardiovascular deaths were 1 vs. 10 and deaths from cancers other than breast were 7 vs.16.

  30. [P4-16-08] Intraoperative Electron Radiotherapy in Early Stage Breast Cancer. A Single-Institution Experience • Dall'Oglio S, Maluta S, Marciai N, Gabbani M, Franchini Z, Pietrarota P, Meliadò G, Guariglia S, Cavedon C. University Hospital, Verona, Italy

  31. Methods • From July 2006 to December 2009, 226 patients suitable for BCT were enrolled in a phase II trial with IOERT as radical treatment immediately after surgical resection. • After the surgeon temporarily re-approximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed with a margin of 2 cm laterally.

  32. Methods

  33. Methods

  34. Methods

  35. Methods

  36. Methods

  37. Results

  38. Results

  39. ELectronIntraoperativeRadio Therapy= ELIOT Fig 1. After the upper-outer quadrantectomy of left breast, a medial glandular flap is performed. The breast is separated, superficially by the skin, and deeply by the pectoralis muscle. Fig 2. The mobilization of the breast target is concluded preparing the lateral glandular flap. Fig 3. The gland is reconstructed over the aluminum and lead disks to expose the correct portion of the breast to be irradiated. The disks (outlined) appear between the restored breast and the pectoralis muscle. Intra…Veronesi et al Surgery September 2006

  40. Electrons Intraoperative Therapy: ELIOT Trial Fig 4. Sagittal plane of the breast. The sterile collimator of the linear accelerator is introduced through the skin incision and placed directly in contact with the breast target. The aluminum and lead disks are located between gland and pectoralis muscle, exactly on the line of the collimator. The disk size must be at least equal or superior to the breast target size. Veronesi et al, Ann Surg 2005;242: 101–106

  41. ELIOT results 2010 • 1822 pts with ELIOT from Jan 2000 to Dec 2008 • 1800 pts received 21 Gyrx to 90% isodose • 1381 received endocrine therapy • 176 chemotherapy alone • 198 chemotherapy and endocrine therapy • 67 had no adjuvant treatment • 58 women since 2005 received Herceptin • Mean f/u 36.1 months Veronesi, Br Can Res Tr 2010

  42. ELIOT results 2010

  43. ELIOT results 2010

  44. ELIOT results 2010

  45. ELIOT Multivariate Model for LR

  46. ELIOT trial results 2010

  47. ELIOT trial results 2010

  48. How much is tumor biology driving local recurrence risk? 1.2 cm, grade 1, ER/PR +, Her2+ “luminal” type 1.2 cm, grade 3, ER/PR-,Her2- “basal” type 1Nguyen et al, JCO 26:2373, 2008 Harvard 2Millar et al, JCO 27: 4701, 2009 Australian 3Freedman et al, Cancer 115: 946, 2009 FCCC 4Albert et al, IJROBP 77:1296, 2010: Stage T1a,b N0 BCT 62% MDAH 5Voduc et al, JCO 28: 1684, 2010 British Columbia and UNC; ^Lum Her2 6Haffty et al, JCO 24:5652, 2006 Yale * Pre-Herceptin era

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