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GUENTHER GRUBER Institut für Radio-Onkologie Klinik Hirslanden, Zuerich guenther.gruber @ hirslanden.ch

KONTROVERSEN IN DER RADIOTHERAPIE DES MAMMAKARZINOMS. GUENTHER GRUBER Institut für Radio-Onkologie Klinik Hirslanden, Zuerich guenther.gruber @ hirslanden.ch. KONTROVERSEN - RT. INDIKATION VOLUMINA RT - PLANUNG RT – APPLIKATION. KONTROVERSEN – RT BRUSTERHALTUNG.

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GUENTHER GRUBER Institut für Radio-Onkologie Klinik Hirslanden, Zuerich guenther.gruber @ hirslanden.ch

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  1. KONTROVERSEN IN DER RADIOTHERAPIE DES MAMMAKARZINOMS GUENTHER GRUBER Institut für Radio-Onkologie Klinik Hirslanden, Zuerich guenther.gruber @ hirslanden.ch

  2. KONTROVERSEN - RT • INDIKATION • VOLUMINA • RT - PLANUNG • RT – APPLIKATION

  3. KONTROVERSEN – RT BRUSTERHALTUNG Bei welchen Pat. kann auf eine RT nach Brusterhaltung verzichtet werden?

  4. BREAST CONSERVATION EBCTCG 2000 RT metaanalysis, Lancet 12/05 N0 N+/N? n=6097 n=1214 % p<0.00001p=0.006 p<0.00001 p<0.01

  5. BREAST CONSERVATION

  6. BREAST CONSERVATION CONCLUSION • BC surgery: No omission of RT !

  7. BREAST CONSERVATION INVASIVE CANCER • Omission of RT in ‚low risk‘ ?

  8. BREAST CONSERVATION BC surgery +/- RT Swedish Breast Cancer Group, EJC 2003 median tu-size: 12mm; n=1187; median F-up: 8J 14% 4%

  9. BREAST CONSERVATION BC surgery +/- RT, pT1a/pT1b pN0 16.5 9.3 p<0.0001 p=0.01 2.8 NSABP B-21, n=1009; JCO 2002

  10. BREAST CONSERVATION Local relapse rates, pT1a/pT1b pN0 Age 70+ ? Therapy,-ies n LR TAM 43 3 (7%) RT 59 5 (8%) TAM+RT 57 0 RT vs. TAM => HR 1.06 (0.25-4.46) ! NSABP B-21, n=1009 JCO, 2002

  11. BREAST CONSERVATION … in T1, N0, R0, ER+ (in 97%), >70yrs CALGB, RTOG, ECOG (Hughes et al. NEJM, 9/2004) n=636 (75+ years: 55%) median F-up: 5J LOCAL RELAPSE with tamoxifen 4% with tamoxifen and RT 1% p<0.001

  12. BREAST CONSERVATION T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.) 5yrs LR -2cm, R0, HR+ n=611 Tam 3.2% Tam + WB-RT 0.4% (p<0.001) -1cm, R0, HR+ n=263 Tam 2.6% Tam + WB-RT 0% (p=0.02) Files et al., NEJM 2004

  13. BREAST CONSERVATION T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.) 5yrs LR 8yrs LR -2cm, R0, HR+ n=611 Tam 3.2% 15.2% Tam + WB-RT 0.4% (p<0.001)3.6% -1cm, R0, HR+ n=263 Tam 2.6% Tam + WB-RT 0% (p=0.02) + 3J x 5 ! Files et al., NEJM 2004

  14. BREAST CONSERVATION T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.) 5yrs LR 8yrs LR -2cm, R0, HR+ n=611 (B21) Tam 3.2% 15.2%(16.5%) Tam + WB-RT 0.4% (p<0.001)3.6%( 2.8%) -1cm, R0, HR+ n=263 Tam 2.6% Tam + WB-RT 0% (p=0.02) + 3J x 5 ! Files et al., NEJM 2004

  15. BREAST CONSERVATION postmenop., T <3cm, N0, ER+ and/or PR+ ABCSG 8 (8A) (Pötter et al. ASTRO, OEGRO, ECCO 13, 11/2005) n=826 (60+ years: about two thirds) median F-up: 42 mo LOCAL RELAPSE 5yrs with Tamoxifen/AI 4.5% with Tamoxifen/AI and RT 0.6% p=0.001

  16. BREAST CONSERVATION „low risk“ – studies summary Follow up still too short ! No subgroup of pts. which does not profit from RT! IMPORTANT: Trade-offs ! If overall survival > 5yrs: RT !

  17. BREAST CONSERVATION CONCLUSION • BC surgery: No omission of RT ! • No omission of RT in ‚low risk‘ !

  18. BREAST CONSERVATION INVASIVE CANCER • Breast conserving surgery: Omission of RT ? • Omission of RT in ‚low risk‘ ? • PBI for ‚low risk‘ ?

  19. BREAST CONSERVATION CONCLUSION • BCT + Mastectomy equivalent ! • BC surgery: No omission of RT ! • No omission of RT in ‚low risk‘ ! • The target is the whole breast !

  20. BREAST CONSERVATION INVASIVE CANCER • BCT vs mastectomy ? • Breast conserving surgery: Omission of RT ? • Omission of RT in ‚low risk‘ ? • PBI for ‚low risk‘ ? • Altered fractionation?

  21. BREAST CONSERVATION altered fractionation Stage I/II n=1234 R 42.5Gy/2.65Gy 22 days n=622 50Gy/2Gy 35 days n=612 median f-up : 69 months Whelan et al., JNCI 94, 2002

  22. BREAST CONSERVATION altered fractionation LRFS DFS 100% 95% Whelan et al., JNCI 94, 2002

  23. BREAST CONSERVATION altered fractionation T1-3 N0-1 n=1410 R 39Gy/3Gy 5 wks n=474 42.9Gy/3.3Gy 5 wks n=466 50Gy/2Gy 5 wks n=470 median f-up : 9.7 years Owen et al., Lancet Oncol, 2006

  24. BREAST CONSERVATION altered fractionation Owen et al., Lancet Oncol, 2006

  25. BREAST CONSERVATION CONCLUSION • BC surgery: No omission of RT ! • No omission of RT in ‚low risk‘ ! • The target is the whole breast ! • There are equivalent schedules !

  26. BREAST CONSERVATION INVASIVE CANCER • Breast conserving surgery: Omission of RT ? • Omission of RT in ‚low risk‘ ? • PBI for ‚low risk‘ ? • Altered fractionation? • Increase of dose (boost) ?

  27. BREAST CONSERVATION Local recurrences after BCS + RT BOOST versus NO BOOST no boost boost H.R. • Lyon 5 y 4.5 % 3.6 % (10 Gy) 0.80 p = 0.044 n = 1024 • French M.C. 5 y 6.8 % 3.6 % (16Gy) 0.53 p = 0.13 n = 664 • EORTC 10801 5 y 6.8 % 3.4 % (15Gy) 0.59 p = 0.0001 n = 5569

  28. BREAST CONSERVATION BREAST-RT +/- BOOST - 40J (n=449) 41-50J (n=1334) p=0.02 p=0.002 51-60J (n=1803) > 60J (n=1732) p=0.07 p=0.11 Bartelink et al., NEJM 2001

  29. BREAST CONSERVATION CONCLUSION • BCT + Mastectomy equivalent ! • BC surgery: No omission of RT ! • No omission of RT in ‚low risk‘ ! • The target is the whole breast ! • There are equivalent schedules ! • Boost efficient (! <50yrs !)

  30. RT – BREAST CANCER ‚TIMING‘ RT – Tamoxifen: simultaneous vs sequential Journal of Clinical Oncology, Vol 23, No 1, 2005 * 3 (small) retrospective studies z.B. Ahn et al, 2005 OS LRFS

  31. RT – BREAST CANCER ‚TIMING‘ RT – Tamoxifen: simultaneous vs sequential Lokalrezidiv Bentzen, S. M. et al. JCO; 23:6266-6267 2005

  32. RT – BREAST CANCER ‚TIMING‘ RT – 6xCMF: ‚RT first‘ vs ,CMF first‘ Breast conservation; n=244 DFS No significant difference! Bellon, J. R. et al. JCO; 23:1934-1940; 2005

  33. RT – BREAST CANCER ‚TIMING‘ RT – 6xCMF: ‚RT first‘ vs ,CMF first‘ Breast conservation; n=244 DFS DMFS No significant difference! Bellon, J. R. et al. JCO; 23:1934-1940; 2005

  34. RT – BREAST CANCER ‚TIMING‘ RT – 6xCMF: ‚RT first‘ vs ,CMF first‘ Breast conservation; n=244 DFS DMFS OS No significant difference! Bellon, J. R. et al. JCO; 23:1934-1940; 2005

  35. RT – BREAST CANCER ‚TIMING‘ ‚ChT => RT‘ vs ,simChT/RT‘ ChT= mitoxantrone, 5-FU, cyclophosphamide; 6 cycles RT= 50Gy/2Gy; +/- boost ARCOSEIN III trial (n=214 for late toxicity) ! No difference in acute toxicity ! (skin, esophagus, infections, neutropenia) ! No statistical difference in grade 2 or higher breast edema, lymphedema, pain ! ! simChT/RT: Significant more breast atrophy, subcutaneous fibrosis, teleangiectasia, skin pigmentation ! Toledano et al.; Int J Radiat Oncol Biol Phys; 2006

  36. RT – BREAST CANCER ‚TIMING‘ RT – Herceptin ® N9831: AC->T->H vs AC->TH->H RT (after BCS or Mx4+LN sim to H allowed) 1460 available for adverse events analyses median f-up: 1.5yrs • Skin reaction (p=0.78); pneumonitis (p=0.78), dyspnea (p=0.87) • Cough (p=0.54); dysphagea (p=0.26); neutropenia (p=0.16) • Concurrent H-RT is not associated with acute RT adverse events • Further follow up is needed for late adverse events Halyard MY et al. ASCO; 2006

  37. RT – BREAST CANCER ‚TIMING‘ How to combine RT with systemic therapies ? Individual HT: simultaneous possible ChT : In most centers: ChT -> RT simultaneous RChT possible but more side effects! => Not recommended Herc: simultaneous possible (heart!)

  38. BREAST CONSERVATION TECHNIQUE / RT APPLICATION

  39. BREAST CONSERVATION

  40. BREAST CONSERVATION Hurkmans et al., 2001 Lung HEART 42 mm

  41. BREAST CONSERVATION IMRT „Open“ homogeneous beam (OB) Intensity modulatedbeam (IMB)

  42. BREAST CONSERVATION IMRT IMRT IMRT

  43. BREAST CONSERVATION IMRT n=306 R Standard 2D 3D IMRT 5yrs – Differences in breast appearence (Photos) 60% 48% p=0.06 (QoL no difference) Yarnold et al., ECCO 13; 2005

  44. BREAST CONSERVATION 6MV + 12e Protons IMRT IMRT Lomax et al. IJROBP 2003

  45. TARGET VOLUME ? SCHLUSSFOLGERUNG

  46. TARGET VOLUME ? MAMMARIA INTERNA – RT: SFRO trial PATIENTS / METHODS RESULTS n=1281 (1/91 – 12/97); MI-RT+ MI-RT Median f-up: 65mo Death 19% 19% Mastectomy Cancer 11% 11% LR 4% 3% Meta 17% 20% CW+Supra CW+Supra+MI R

  47. RT – BREAST CANCER RE-IRRADIATION

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