NABON-BOOG symposium 10 april Paula Elkhuizen, radiotherapeut-oncoloog Antoni van Leeuwenhoek Ziekenhuis NABOB-BOOG

Transcriptie

1 NABON-BOOG symposium 10 april 2018 Paula Elkhuizen, radiotherapeut-oncoloog Antoni van Leeuwenhoek Ziekenhuis NABOB-BOOG

2 Geen (potentiële) belangenverstengeling Disclosure Belangen Spreker Voor bijeenkomst mogelijk relevante relaties: Sponsoring of onderzoeksgeld geen Honorarium of andere (financiële ) vergoedingen Bedrijfsnamen: geen Aandeelhouder geen Andere relatie, namelijk: geen

3 Ontwikkelingen RT I. Minder waar kan Geen RT Partial breast RT Preoperatieve RT II. Selectie van pt LR risico postnac III. Meer waar kan oligom+ ptn

4 I. Minder waar kan Geen RT ; LORD study TOP studies Partial breast RT Preoperatieve RT

5 Radiation defined Tumor volumes GTV Gross Tumor Volume CTV Clinical Target Volume GTV PTV Plannings Target Volume Treatment Volume

6 Borstsparende behandeling Van gehele borstbestraling naar Partial Breast Irradiation (PBI) RT mamma en boost (5-15%) RT PBI (100%)

7 dia invoegen IORT en EBRT

8 Meta-analysis LR of IDC after electron intraoperative RT Harness et al Cleveland 13 publicaties identified Pooled monthly recurrence rate of 0.02% per person-month for studies < and 0.03 for studies >= 5 yrs FU Predicted 5 years recurrence rate is 2.7% (95% CI 1,9-3,7%) Support the ASTRO guidelines for use of electron IORT in low risk patients

9 Low risk Intermediate risk

10 Dia targit patietn selectie toevoegen

11 Why preoperative Partial Breast RT? Better tumor delineation pre vs postoperative tumor with marker in situ Better radiotherapy tumor coverage CTV tumor + 2 cm Post-operative vd Leij et al R&O 2013 Smaller volumes pre vs postoperative RT Pre-operative Translational studies High dose RT volume is excised!!

12 Preoperative RT Partial Breast (PAPBI -I and PAPBI II) Neo RT (whole breast RT + HT 5 mo; surgery) PRADA studie (RT gevolgd door DIEP) PROBI (whole breast + boost; immediate surgery)

13 Fibrosis in tumor area 90 % of patients none-mild fibrosis Fibrosis is noted in a limited volume (1-2 cm) Fibrosis tumor area 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1 (n=93) 2 (n=81) 3 (n =60) 4 (n=33) Years severe moderate mild none

14 Cosmesis (scored by physician) Good-excellent score >90% Global cosmetic outcome 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0.5 (n=85) 1 (n=74) 2 (n=73) 3 (n=37) 4 (n=29) Years poor fair good excellent

15 Before RT Patient A no complications 6 months after RT

16 12 months after RT Patient A no complications 24 months after RT

17 before RT Patient B postoperative woundinfection; AB 6 mnd after RT

18 24 mo after RT Patient B postoperative woundinfection; AB

19 PAPBI-2 TRIAL MULTICENTER Pre-op APBI Breast conserving surgery Females 51 yrs ct1-2n0 ( 3 cm) Grade I or II 5 x 5.7 Gy Breast conserving surgery Post-op APBI n = 500 Primary endpoint: Cosmetic outcome 5 x 5.7 Gy a.scholten@nki.nl

20 PROBI TRIAL NKI-AVL ct1-2n0 and 50 yrs or grade III or LAI Pre-op whole breast RT Breast conserving surgery n = 94 Primary endpoint: Postoperative surgical comlpications

21 Neo RT study Charlotte Coles UK Hormone positive Neu negative tumors Phase I study; feasibility n=34 Preoperatieve whole breast RT Neoadjuvant HT (letrozol/tam) 20 wk interval Surgery Translational studies

22 PRADA: Pre-op RT whole breast + DIEP Fiona McNeill Inclusion: - NAC patients - Loco (-regional) fractionated RT - Primary ablative - BCS without clear margins Followed by Mastectomy and DIEP Preliminary results; acceptable acute and late toxicity

23 II.Selectie van Patienten Selectie van ptn met hoog risico op Locaal recidief MINDACT Young Boost: high boost? Selectie van RT ptn na NAC

24 Very low risk of locoregional breast cancer recurrence in the EORTC 10041/BIG MINDACT trial: Analysis of risk factors including the 70-gene signature. E. Rutgers, K. Aalders, C. Poncet, F. Cardoso, J. Bogaerts, S. Delaloge, A. Thompson, K. Tryfonidis, L.J. van t Veer, M. Piccart, I.T. Rubio for the MINDACT Investigators EBCC-11, Barcelona, Spain 23 March 2018

25 MINDACT Study Design Cardoso F. et al, NEJM 2016; 375:

26 MINDACT Endpoints and events (first event analysis) & DMFI Distant relapses Deaths (breast cancer) Piccart M. AACR Podium Presentation, April 18 th, 2016.

27 Cumulative incidence of loco-regional recurrence in the MINDACT population Overall population 5-year Cumulative Incidence of LRR Patient at risk at beginning of Year 5 Cumulative numbers of LRR Cumulative Incidence (95%CI) (1.82; 2.57) (years) O N Number of patients at risk : All pts Clinical cut-off date: 16 March 2016; Median follow-up: 5 years

28 Cumulative incidence of loco-regional recurrence by subtype in patients treated with BCS year Cumulative Incidence of LRR Patient at risk at beginning of Year 5 Cumulative numbers of LRR Cumulative Incidence (95%CI) Luminal HER (1.28; 2.10) Luminal HER (0.19; 2.81) HER2+ (non luminal) (0.08; 9.71) Triple negative (3.77; 7.95) Total (1.72; 2.55) 0 (years) O N Number of patients at risk : Subtype (local lab) Luminal HER Luminal HER HER2+ (non lum.) Triple negative

29 Cumulative incidence of loco-regional recurrence by genomic risk in patient treated with mastectomy year Cumulative Incidence of LRR Patient at risk at beginning of Year 5 Cumulative numbers of LRR Cumulative Incidence (95%CI) Low risk (0.09; 1.37) High risk (2.95; 6.92) Total (1.56; 3.37) (years) O N Number of patients at risk : G-risk Low risk High risk

30 Univariate analysis in BCS patient (n=5280)

31 Multivariate analysis in BCS patients (n=5280) The 70-gene is no longer independently associated with LRR

32 Clinical implications LRR and DM have different biology Local relapse is low; overtreatment? The role of high boost dose? Young boost data

33 Dia toevoegen cosmetische data YBT

34 II. Selectie van Patienten Locaal recidief RT na NAC; Mamounas et J Clin Oncol 2012 Higher rates of LRR with tumor > 5 cm or ypn+ after BCT and Mastectomy Low LRR in pcr with negative nides irrespective of tumor size or nodal status

35 Japanese Breast Cancer registry; role of PMRT after NAC (n= ) ct1-4n0-2 breast cancer pts LRR; DDFS and OS ( 5 years FU) PMRT vs no PMRT ypn0 (n=1299) ypn1 (n=1036) ypn2 (n=879) PMRT Univariate Multivariate 14.2% % % LRR, DDFS, OS LRR and OS Conclusion: PMRT might only be benificial for ypn2-3 breast cancer patients

36 The Good, the Bad and the Ugly LR OS Good Bad ypn0 ypn1 RT instead of surgery Ugly ypn2-3 5 yrs 10 yrs?

37 II. Selection of patients Less aggressive therapy in pcr Veilig weglaten van chirurgie bij ptn met goede respons op NAC Rol van radiotherapie Is RT nodig? Low/high risk Wat is de optimale fractionering? Rol van boost (locaal e/o regionaal)

38

39

40 III. Meer waar kan Conventional Radiation Therapy volume definition

41 PTV Plannings Target Volume Very high dose! 1-5 fractions only! Fixation of utmost importance Target necessary; not for microscopic disease

42 Stereotaxie: No margin; GTV = CTV Extremely high dose Fixation very important 1 x 24 Gy ; EQD2 156 Gy 1 x 18 Gy ; EQD2 90 Gy 3 x 10 Gy ; EQD2 90 Gy Vergelijk RT mamma EQD Gy

43 Oligometastasen Radiotherapie met curatieve intentie Stereotaxie belangrijke rol ipv chirurgie; minder bijwerkingen Kortdurend behandeltraject Weinig/ minder bijwerkingen ivm alternatief bv chirurgie hersenmetastasen Levermetastasen Para-aortale klieren Ip macroscopische tumor: TARGET NODIG

44

45

46

47

48 Body Stx Oligo-metastasen curable setting!! MRI pre- en postnac Sacrum links: 3x14 Gy, 2 fr/w Lever-long laesie niet mogelijk indien geen target

49 Spine 1 x 24 Gy

50 Oligometastasen Radiotherapie met curatieve intentie Stereotaxie belangrijke rol ipv chirurgie; minder bijwerkingen Kortdurend behandeltraject Weinig/ minder bijwerkingen ivm alternatief bv chirurgie hersenmetastasen Levermetastasen Para-aortale klieren Ip macroscopische tumor: TARGET NODIG