BETYDNINGEN AF FRIE RESEKTIONSRANDE VED BRYSTBEVARENDE OPERATIONER

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1 BETYDNINGEN AF FRIE RESEKTIONSRANDE VED BRYSTBEVARENDE OPERATIONER Anne Bodilsen

2 Verdenskort hvor marginern står??

3 - 21 studier (n: ) - 14,571 patienter European Journal of Cancer 46 (2010)

4 - 33 studier (n: ) - I alt 28,162 patienter - Alle modtager strålebehandling, 96% også boost

5 METAANALYSENS KONKLUSION Adoption of wider margins, relative to narrower widths, for declaring negative margins is unlikely to have a substantial additional benefit for long-term local control Houssami et al. Ann Surg Oncol 2014;21:717 30

6 DBCG STUDIE - INKLUSIONS KRITERIER Kvinder Alder: Brystbevarende behandling Invasiv cancer Unilateral Ingen tidligere cancersygdomme Behandlet i henhold til DBCG guidelines I alt 11,900 patienter

7 BETYDNINGEN AF MARGINS STØRRELSE

8 IBTR,% BETYDNINGEN AF MARGINS STØRRELSE Overall risiko for IBTR: 5 år: 2.4% 9 år: 5.9% 5 års LR: 2.4% Time since BCS, years 0mm 2-4mm >0-1mm >=5mm Cumulative incidence of IBTR by margin width in 11,900 women

9 0 5 IBTR,% 10 BETYDNINGEN AF MARGINS STØRRELSE Time since BCS, years 0mm 2-4mm >0-1mm >=5mm Cumulative incidence of IBTR by margin width in 11,900 women

10 BETYDNINGEN AF MARGINS STØRRELSE HR 95% CI p value Age < Histology/grade 0.06 Ductal NST, grade I-II 1 Ductal NST, grade III Special subtypes Unknown Lymph node status Negative positive positive >10 positive HR 95% CI p value Re-excisions No 1 Yes Chemotherapy <0.001 No 1 Yes Boost 0.08 No 1 Yes Unknown ER status/treatment <0.001 ER negative 1 ER pos, no endocrine ER pos, endocrine Adjusted risk of IBTR as first event

11 BETYDNINGEN AF MARGINS STØRRELSE HR 95% CI p value Age < Histology/grade 0.06 Ductal NST, grade I-II 1 Ductal NST, grade III Special subtypes Unknown Lymph node status Negative positive positive >10 positive HR 95% CI p value Re-excisions No 1 Yes Chemotherapy <0.001 No 1 Yes Boost 0.08 No 1 Yes Unknown ER status/treatment <0.001 ER negative 1 ER pos, no endocrine ER pos, endocrine Adjusted risk of IBTR as first event

12 BETYDNINGEN AF MARGINS STØRRELSE HR 95% CI p value Age < Histology/grade 0.06 Ductal NST, grade I-II 1 Ductal NST, grade III Special subtypes Unknown Lymph node status Negative positive positive >10 positive HR 95% CI p value Re-excisions No 1 Yes Chemotherapy <0.001 No 1 Yes Boost 0.08 No 1 Yes Unknown ER status/treatment <0.001 ER negative 1 ER pos, no endocrine ER pos, endocrine Adjusted risk of IBTR as first event

13 BETYDNINGEN AF MARGINS STØRRELSE HR 95% CI p value Age < Histology/grade 0.06 Ductal NST, grade I-II 1 Ductal NST, grade III Special subtypes Unknown Lymph node status Negative positive positive >10 positive HR 95% CI p value Re-excisions No 1 Yes Chemotherapy <0.001 No 1 Yes Boost 0.08 No 1 Yes Unknown ER status/treatment <0.001 ER negative 1 ER pos, no endocrine ER pos, endocrine Adjusted risk of IBTR as first event

14 BETYDNINGEN AF MARGINS STØRRELSE HR 95% CI p value Age < Histology/grade 0.06 Ductal NST, grade I-II 1 Ductal NST, grade III Special subtypes Unknown Lymph node status Negative positive positive >10 positive HR 95% CI p value Re-excisions No 1 Yes Chemotherapy <0.001 No 1 Yes Boost 0.08 No 1 Yes Unknown ER status/treatment <0.001 ER negative 1 ER pos, no endocrine ER pos, endocrine Adjusted risk of IBTR as first event

15 SÅ HVAD VED VI - øget risiko for IBTR ved positiv margin - ingen forbedring af lokal kontrol med bredere margin, MEN. - fortsat begrænset viden om helt smalle marginer (>0-1mm)

16 BETYDNING AF MARGIN FOR FJERNMETASTASER

17 BETYDNING AF MARGIN FOR FJERNMETASTASER DBCG Patobank Journal Total IBTR+RR DM Total

18 BETYDNING AF MARGIN FOR FJERNMETASTASER Cause-specific recurrence Risiko ved 5 vs 9 år: IBTR/RR: 2.4% vs 5.7% DM: 6.5% vs 12.6% Contralateral: 2.0% vs 4.0% Time since lumpectomy DM contralateral IBTR/RR Cumulative risk of DM, loco-regional recurrence, and contralateral

19 BETYDNING AF MARGIN FOR FJERNMETASTASER HR 95% CI p-value Final margin mm >0-1mm mm >=5mm 1 Tumour size <0.001 <=20 mm 1 >20 mm Lymph node status <0.001 Negative 1 Positive Vascular invasion No 1 Yes Adjusted risk of DM as first event

20 BETYDNING AF MARGIN FOR FJERNMETASTASER HR 95% CI p-value Final margin mm >0-1mm mm >=5mm 1 Tumour size <0.001 <=20 mm 1 >20 mm Lymph node status <0.001 Negative 1 Positive Vascular invasion No 1 Yes Adjusted risk of DM as first event

21 RE-RESEKTION - inkluderede alle med primær brystbevarende operation - i alt 12,656

22 Number of initial BCS per year RE-RESEKTION Year Re-excision Mastectomy Development in use of repeat surgery over time

23 RE-RESEKTION 20% havde resttumour ved re-resektion 23% invasivt carcinom 63% DCIS 14% DCIS+invasivt carcinom

24 0 5 IBTR,% 10 RE-RESEKTION Time since BCS No reexcision Reexcision, residual Reexcision, no residual Cumulative incidence of IBTR after final BCS by surgery and residual finding

25 0 5 IBTR,% 10 RE-RESEKTION Cumulative incidence IBTR Time since BCS No reexcision Reexcision, inv+/-in situ Reexcision, no residual Reexcision, dcis Cumulative incidence of IBTR after final BCS by surgery and residual finding

26 RE-RESEKTION Cumulative incidence of IBTR after final BCS by surgery and residual finding

27 RE-RESEKTION Time since BCS No re-excision Mastectomy, residual tumour Mastectomy, no residual tumour Re-excision, no residual tumour Re-exision, residual tumour Overall survival by surgical procedure and residual finding

28 RE-RESEKTION 11% re-reseseres, 6% fortsætter til mastektomi. Faldende over tid Øget risiko for lokalt recidiv associeret med resttumour ved reresektion Overlevelse er ikke påvirket

29 KONKLUSION Fordoblet risiko for lokalt recidiv ved positiv margin Ingen forbedring i lokal kontrol med bredere margin Formentligt samme billede for fjernmetastaser Resttumor øger risiko for recidiv og selvom der er negative marginer til slut

30 Spørgsmål/kommentarer

31 BOOST Bartelink et al. JCO 2007;25:

32 BOOST - SSO/ASTRO guidelines anbefaler ikke brug af boost på baggrund af margin status - Boost vs no boost trial kun negativ margin randomiseret. Forskellig dosis til positiv margin men ingen forskel -Andre studier med lignende resultater - Ikke muligt at undersøge i DBCG data

33 MARGIN HOS PATIENTER MED ANDRE DÅRLIGE PROGNOSTIKA Margins wider than no ink on tumour are not indicated based on biologic subtype There is no evidence that increased margin width nullifies the increased risk of IBTR in young patients There is no evidence of an association between increased risk of IBTR [and DCIS outside invasive tumour] when margins are negative Moran et al. Ann Surg Oncol 2014;88:553-64

34 MARGIN HOS PATIENTER MED ANDRE DÅRLIGE PROGNOSTIKA Margins wider than no ink on tumour are not indicated based on biologic subtype

35 MARGIN HOS PATIENTER MED ANDRE DÅRLIGE PROGNOSTIKA There is no evidence that increased margin width nullifies the increased risk of IBTR in young patients Hollansk studie med patienter 40 år: - 5 års risiko for lokalt recidiv positiv (on ink) vs negativ (not on ink) margin: 36.9% vs 8.4% Jobsen et al. Int J Radiat Oncol 2003;57:724-31

36 MARGIN HOS PATIENTER MED ANDRE DÅRLIGE PROGNOSTIKA There is no evidence of an association between increased risk of IBTR [and DCIS outside invasive tumour] when margins are negative

37 DEVELOPMENT IN THE USE OF ADJUVANT SYSTEMIC THERAPY % year No adjuvant systemic Adjuvant systemic

38 DEVELOPMENT IN THE USE OF ADJUVANT SYSTEMIC THERAPY % year No adjuvant systemic Adjuvant systemic

39 0 Re-excision % CANDIDATES OF RE-EXCISION year 0 mm >0-2 mm >2-4 mm >=5 mm Percentage receiving re-excision by margin group

40 Slide med poortman graf Poortmans et al. Seminars in Radiation Oncology, 2012, 22 (1), 29-39

41 0 5 IBTR,% 10 RE-RESEKTION OG BOOST Time since BCS no reex, no boost reex, res, no boost reex, res, boost reex, no res, no boost reex, no res, boost no reex, boost

42 0 5 IBTR,% 10 RE-RESEKTION OG BOOST Time since BCS no reex reex, res, boost reex, res, no boost Risk of IBTR after BCT by residual finding and receipt of boost