1 / 51

35 th SABCS 2012 Highlights Loco-Regional Therapy

35 th SABCS 2012 Highlights Loco-Regional Therapy. Patrick Neven MBC, UZ Leuven. 35th SABCS 2012 Loco-Regional Therapy. Atypical lesions on core biopsy WLE? Upgrade to malignant lesions (frequency, nomogram) WLE for DCIS Re-excise if + margins (predictors residual DCIS)

stacie
Download Presentation

35 th SABCS 2012 Highlights Loco-Regional Therapy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 35th SABCS 2012 Highlights Loco-Regional Therapy Patrick Neven MBC, UZ Leuven

  2. 35th SABCS 2012 Loco-Regional Therapy • Atypical lesions on core biopsyWLE? • Upgrade to malignant lesions (frequency, nomogram) • WLE for DCIS • Re-excise if + margins (predictors residual DCIS) • Predictors relapse (subtype, gene expression profile) • WLE for IBC • Tumor localisation, 2ary WLE • Sentinel lymph node • Value in post-neoadjuvant setting • Radiotherapy • START (hypofractionation) • APBI - IORT / ELIOT • Local relapse: Secondary adjuvant chemotherapy

  3. 35th SABCS 2012 Loco-Regional Therapy • Atypical lesions on core biopsyWLE? • Upgrade to malignant lesions (frequency, nomogram)

  4. WLE if atypical lesions on core biopsy? MESSAGE Wide Excision = Standard • Flat epithelial atypia on core biopsy • Loyola, USA (P1-02-01) 2009-2011 726 core biopsies • 21.4% (3/14) upgraded to DCIS or IBC • 3 Dutch hospitals (P5-01-13) 2009-2011 104 core biopsies • R/ ranged from observation to mastectomy • Of those excised: 20.4% had DCIS or IBC • ADH on vacuum biopsy • Centre Oscar Lambret, Lille (P4-14-10) 2003-2010 • 52/298 WE/3159 VAB = 17.5% had DCIS or IBC • No prognostic marker identified for upstaging

  5. A nomogram ~ clinic, imaging & histology to predict upgrade to malignancy (WLE) LCIS, ADH, ALH, FEA (corebiopsy P4-12-01 Uzan et al. 50/205WLE -21 DCIS -20 IDA -9 ILA • Sens 77.8%, Sp 66.1%, PPV40%, NPV 91.1%

  6. 35th SABCS 2012 Loco-Regional Therapy • Atypicallesions on corebiopsyWLE? • Upgrade tomalignantlesions (frequency, nomogram) • WLE for DCIS • Residual DCIS if re-excisionfor + margins • Predictorsfor relapse (~ subtype, gene expression profile) • Ki-67 (continuous variable) ~LRR after BCS & RT & HT? • PD-04-07 – Pruneri et al. EIO, Milan • 872 pts, [356 RT, 506 TAM] and 86/12 FU • RT only of value if Ki-67 > 14% • HT only of value if lum A/B (not lum HER-2) MESSAGE

  7. Residual DCIS after re-excision following WLE for DCIS? MESSAGE • IBC:Margin index predicts residual cancer • P3-14-06 – AS Aneja S. et al. • 87 re-excision after WLE (18 rDCIS) • Index: closest margin (mm)/ extent of DCIS (mm) • Index > margin distance • PR most predictive

  8. Local Relapse after BCS (DCIS) • Surrogate phenotypes ~ recurrence (PD-04-06) • 314 pts (1990 – 2010) 74 months FU • Radiotherapy? High risk recurrence?

  9. Predictors for IBC if relapse Luminal A 1 - - Luminal B 14.38 1.8-113.6 0.011 HER-2 type 17.69 2.1-147.0 0.008 Triple Negative 15.23 1.8-126.6 0.012

  10. Molecular predictors type LR: BCS for DCIS PD-04-05 • Local relapse DCIS vs IBC +/- DCIS • 1991-2006, 1873 pts, 40m FU, 190 relapsed (10%), 108 blocks: 66 rDCIS & 42 rIBC qmRNA • Initial unsupervised hierarchical clustering of 32 genes: • 2 groups: rDCIS & rIBC enriched • 14 genes w/ sig differential expression: • rDCIS “only” : highest levels of AKT3, EGFR, CDKN2A, MKI67, typical of basal like tumors

  11. Molecular predictors type LRR: BCS for DCIS

  12. Molecular Predictor type LRR BCS for DCIS

  13. 35th SABCS 2012 Loco-Regional Therapy • Atypical lesions on core biopsyWLE? • Upgrade to malignant lesions (frequency, nomogram) • WLE for DCIS • Re-excise if + margins (predictors residual DCIS) • Predictors relapse (subtype, gene expression profile) • WLE for IBC • Tumor localisation • 2nd WLE

  14. IBC: Breast conservation surgery • Patient selection • BCS rates in SEER(PD-04-04) • Stage I-II IBC 2006-2011: 77248 cases BCS: 64.8% & stable • Patients choice > Availability RT/Reconstr/Volume per Unit • BCS in young women (Sydney)(PD-04-01) • N=2250 & 70/12 FU: Age <40 & BCS indep.predictors for LR • Technique • Intraoperative ultrasound (PD-04-01) • P4-14-08 278 not-palpable lesions USS vswire guided = feasible • 2ary WLE in irradiated breast (P4-15-01)

  15. BCS: Role of intraoperative ultrasound (IOUS) palpable lesions • PD-04-01: RCT USS (65) vs PGS (69) • 2010-2012, 6 centers, T1-2 palp IBC Less volume excised in USS Less margin involved 17% vs 3% USS Less likely additional therapy

  16. Patients with IBTR: 2ary BCS? Clinical Practice Changing • Second BCS-RT trial (P4-15-01) GEC-ESTRO • Patients from 8 European Institutions: • WLE + MIB (Multicatheter Interstitial Brachytherapy) • Is 2ary BCT safe for IBTR? • 2000-2010: 217 pts repeat BCS + MIB. • Median time interval Primary – IBTR = 9.4 yrs [1.1-35.4] • Median f/u after IBTR = 3.9 years [after 2ary BCS]. • Mean T = 11mm • 5 and 10 year actuarial • LR rates 5.6% and 7.2% • OSS 88.7% and 76.4% • No severe complications but fibrosis. • Long term cosmesis?

  17. 35th SABCS 2012 Loco-Regional Therapy • Atypical lesions on core biopsyWLE? • Upgrade to malignant lesions (frequency, nomogram) • WLE for DCIS • Re-excise if + margins (predictors residual DCIS) • Predictors relapse (subtype, gene expression profile) • WLE for IBC • Tumor localisation, 2nd WLE • Sentinel lymph node • Value in post-neoadjuvant setting

  18. SLN Biopsy after Neoadjuvant Chemotherapy • S2-1 (ACOSOG) • S2-2 (SENTINA trial)

  19. Background SLNB ~ axillary status if cN0 -pN status tailors L/R adjuvant therapy Role of SLNB with NACT is unclear -cN0: prior to or after NACT if pN status not informative? -cN+: downstaging to cN0 [SLN (-) enough]? -current data -small series -retrospective data

  20. SLN Biopsy after Neoadjuvant Chemotherapy • S2-1 (ACOSOG) • S2-2 (SENTINA trial)

  21. Sentinel Node Biopsy after NACACOSOG Z-0171 (2009-2011) 756 included 708 evaluable FNR: 14.0% Clip Placement ? 172 pts FNR = 7% • pT0-4N1-2M0: NAC  SN and ALND (136 institutions) • T1 (14%); T2 (55%); T3 (25%) • HR+/Her2- (45%); • Her2+ (30%); • Trip neg (24%); • Anthracycline +/- taxane (80%), taxane based (17%) • SN detection rate • cN1 (92.9%), cN2 (89.5%) : SLN  ALND (n=643) • SN H&E results SNALND • 40% node negative • 60% node positive • SN negative 56 patients (14%)

  22. SENTINA • 4-arm prospective multicenter cohort study • SLN detection rate prior and after NACT • FNR if cN1 downgraded to cN0 • cN1: clinic and all had US • Negative (cN0) • Suspicious or unclear (cN1) • FNAC/ CNB recommended but not mandatory • Cortex asymmetry • Hilum displacement or loss

  23. cN+ definition FNAC/CNB Not Mandatory

  24. ↔ cN0: SLN after NACT: Accurate/ Feasible Less Axill Clearance

  25. Sentinel Lymph Node Prior to NACT (~local and systemic R/) Our preference (FNR & DR) After NACT cN0ycN0: Excellent DR cN0 & SN(+)Repeat SLN = Unacceptable DR cN1 ycN0 DR is 80.1% = Low FNR = Too High?

  26. 35th SABCS 2012 Loco-Regional Therapy • Atypical lesions on core biopsyWLE? • Upgrade to malignant lesions (frequency, nomogram) • WLE for DCIS • Re-excise if + margins (predictors residual DCIS) • Predictors relapse (subtype, gene expression profile) • WLE for IBC • Tumor localisation, 2nd WLE • Sentinel lymph node • Value in post-neoadjuvant setting • Radiotherapy • START (hypofractionation) • APBI – IORT(TARGIT- ELIOT)

  27. Best of SABCS 2012Radiation Oncology Normal a total dose 50Gy in 25 small daily fractions (5 weeks) Content Hypofractionation (= less than 25 fractions) • [S4-1] The UK START (Standardisation of Breast Radiotherapy) Trials: 10-Year Follow-Up Results APBI: Single Fraction RT • [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 ELIOT Local control if metastatic breast cancer • [P4-16-06] RT to Primary Tumor ~ Improved Survival in Stage IV Breast Cancer (Canadia, SEER, 768 cases EBRT vs 2761 no EBRT)

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

  29. START B: Physicians’ assessment of cosmesis Findings

  30. Clinical Practice Changing

  31. APBI ELIOT Photon Radiosurgery System TARGIT • Single fraction IORT • S 4-2 TARGIT for early stage breast cancer • TARGIT vs WB-XRT • TARGIT “ideal” pt age ≥ 45; T preferably ≤ 3.5 cm; MRI no need • TARGIT 20 Gy at surface, 5 Gy at 10 mm • 2000-2012: 3451 pts randomized, 1222 patients median f/u 5 yrs • If “high risk” add WB-XRT to single-fraction IORT (~ 15%)

  32. APBI TARGIT 0.5% LRR/YR “EXPERIMENTAL”

  33. 35th SABCS 2012 Loco-Regional Therapy • Atypical lesions on core biopsyWLE? • Upgrade to malignant lesions (frequency, nomogram) • WLE for DCIS • Re-excise if + margins (predictors residual DCIS) • Predictors relapse (subtype, gene expression profile) • WLE for IBC • Tumor localisation, 2nd WLE • Sentinel lymph node • Value in post-neoadjuvant setting • Radiotherapy • TARGIT (hypofractionation) • APBI - IORT • Local relapse: Secondary adjuvant chemotherapy Clinical Practice Changing ↓ →

  34. Ipsilateral recurrence: Value of Secundary Adj CT Power calculation : needed to include: n= 1000 …results from a RCT that stopped early: poor recruitement The researchers closed the trial with 162 patients Followed patients for more than 5 years. Stratified by ER

  35. Summary 35th SABCS-2012 LOCO-REGIONAL THERAPY • Atypical lesions : WLE • Biological markers for re-excision, LRR and adjuvant local / endocrine therapies for DCIS (not only IBC) • SNB after NACT if cN+ needs further research • (too?) high FNR • repeat SNB alone to be avoided if cN+ • Hypofractionation: new standard if BCS (10 yrs safe) • SF-IORT = WB-XRT (selected patients? but higher recurrence rates. Longer f/u required! • Secondary WLE in previously radiated breast • Secondary adjuvant chemotherapy is important

More Related