MAASTRO- CLINIC More than just an institute for radiotherapy Patientcare research training & education

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1 MAASTRO- CLINIC More than just an institute for radiotherapy Patientcare research training & education Breast reconstruction: Before or after post mastectomy radiotherapy? Prof. dr. Liesbeth Boersma May 2017, Aarhus

2 Contents Introduction Pros and cons of PMRT first or reconstruction first Implant Autologous Shared decision making Further developments Take Home Messages

3 Introduction Breast reconstructions Both autologous techniques & implants In USA mainly implant reconstruction 1 Literature 2 is clear: PMRT increases complication rate of a reconstruction, however Sometimes both is required and/ or wanted! 1 Chetta et al, 2016; 2 e.g. Sbitany et al, 2014

4 4 choices Immediate Implant Immediate Autologous Delayed Implant Delayed Autologous

5 PMRT and reconstruction Immediate vs. delayed General Pros and Cons Immediate Delayed Period w/o a breast Need for 2 nd /3 rd surgery Thinking time Re-excision possibilities Complication rate?? Failure rate?? Cosmetic outcome?? Technical RT challenges?? Delay in starting RT??

6 PMRT and reconstruction Immediate vs. delayed General Pros and Cons Immediate Delayed Period w/o a breast Need for 2 nd /3 rd surgery Thinking time Re-excision possibilities Complication rate Failure rate Cosmetic outcome Technical RT challenges Delay in starting RT What are the data on implant reconstruction?

7 Problems with delayed implant reconstruction, i.e. after RT Problems with expanding pectoral muscle, skin Tissue expanders placed subpectoral, filled with 25 ml / week up to 355 ml, and then replaced by a permanent implant Tuinder et al, 2009

8 Problems with delayed implant reconstruction, i.e. after RT Displacement of the ribs and decreased AP diameter left thoracic wall! Patient: pain, no other discomfort Tuinder et al, 2009

9 Problems with delayed implant reconstruction, i.e. after RT Patient satisfied with cosmetic result; surgeon adviced some additional lipofilling Tuinder et al, 2009

10 Problems with PMRT after immediate reconstruction with bilateral implant Courtesy of Philip Poortmans Jethwa et al, Breast Cancer Research & Treatment 2017, in press

11 Delay in start PMRT after immediate implant reconstruction? Recent retrospective analysis (small series): 60 mastectomy alone, 56 immediate reconstructi0n: No difference in time to PMRT, however: Time to RT: 8 weeks (compared to < 5 weeks in NL) Higher complication rate after IBR compared to no IBR reported in literature à higher risk on delay My conclusion: Risk on delay is higher, but probably no significant impact on oncological outcome. Jethwa et al, Breast Cancer Research & Treatment 2017, in press

12 Complications PMRT & implant reconstruction: immediate vs. delayed No RCTs; large variation in: complication rates ( %) acceptable cosmetic outcome ( %)

13 Implant: before or after PMRT? Literature review Definition of before or after RT: (TE ) Implant RT: Implant before RT TE RT Implant: RT TE Implant: Implant after RT Definition implant: Implant combined with LD flap à categorized as autologous reconstruction. Berbers et al, 2014

14 Weighted mean complication rate after implant reconstruction Berbers et al, 2014 PMRT first or on TE Fibrosis, capsular contraction 20.8% 39.8% Implant problems ( e.g. leakage, deflation, dislocation) 10.9% 3.6% Implant failure 20.3% 15.2% Revision surgery 42.4% 8.5% Total complication rate 48.7% 19.6% Patient satisfaction 61.7% 81.7% Physician satisfaction 73.5% 72.1% PMRT on implant

15 Less implant failures in case of RT on implant vs RT on TE Delayed Favours Immediate Berbers et al, 2014

16 6 new studies included, still no RCTs! Less implant failures in case of RT on implant compared to RT on TE (NS)

17 Conclusions: Immediate implant/rt on implant (compared to RT on TE): Lower reconstruction failures and less major complications (however: non significant difference) More frequent severe capsular contracture (p < 0.001) Lee et al, 2017

18 Analysis insurance databases USA N = 3846 Immediate implant reconstruction RT on implant: Lowest failure rate (NS), lowest complication rate (p = 0.005) Chetta et al, 2016

19 Summary PMRT & implant reconstruction 1. PMRT (- TE ) Implant: Worst sequence! 2. TE- PMRT- Implant: Lower risk on capsular contracture, but more complications, higher failure rate Both strategies acceptable 3. (TE-) Implant - PMRT: Lower complication rate, lower failure rate but higher risk on capsular contracture

20 PMRT and reconstruction Immediate vs. delayed General Pros and Cons Immediate Delayed Period w/o a breast Need for 2 nd surgery Thinking time Re-excision possibilities Complication rate Failure rate Cosmetic outcome Technical RT challenges Delay in starting RT What are the data on autologous reconstruction?

21 Complications PMRT & autologous reconstruction: immediate vs. delayed No RCTs; large variation in: complication rates ( %) acceptable cosmetic outcome ( %)

22 Weighted mean complication rate after autologous reconstr. PMRT first Fibrosis 2.7% 36% Fat necrosis 8.9% 18.7% Flap problems ((partial) necrosis) 9.5% 11.2 Reconstruction first Flap failure 6.3% 1.9%?? Revision surgery 11.5% 23.6% Total complication rate 36% 36.8% Patient satisfaction 69.2% 81.7% Physician satisfaction 51.3% 72.1% Berbers et al, 2014

23 Only 2 studies with direct comparison of total complication rate autologous reconstruction before/after PMRT Delayed Favours Immediate Berbers et al, 2014

24 Only 1 study with direct comparison in satisfaction rate for autologous reconstruction before/ after PMRT Patient Physician No difference or maybe somewhat better in case of delayed reconstruction / RT first? Berbers et al, 2014

25 Analysis insurance databases USA N = 935 Complication rate after autologous reconstruction: no clear differences in timing Chetta et al, 2016

26 Mastectomy Reconstruction Outcomes MROC Prospective multicenter cohort study 57 plastic surgeons, 11 centers 175 patients with autologous reconstruction + RT: F-TRAM - flaps DIEP- flaps SIEA flaps Endpoints: Complications PRO s measured using Breast-Q at baseline, 1 and 2 yr Billig et al, Plastic & Reconstructive Surgery, 2017, in press

27 MROC study: patient characteristics Laterality Unilateral Bilateral Overall N = (73.7%) 46 (26.2%) Immediate N = 108 (61.7%) 71 (65.7%) 37 (34.3%) Delayed N = 67 (38.3%) 58 (86.6%) 9 (13.4%) P-value Reconstruction type F-TRAM DIEP SIEA Mixed ( in case of bilateral) Chemotherapy After reconstruction Not after reconstruction 21 (12%) 115 (65.7%) 29 (16.6%) 10 (5.7%) 83 (47.4%) 92 (52.6%) 1 (0.9%) 76 (0.4%) 24 (22.2%) 7 (6.5%) 81 (75%) 27 (25%) 20 (29.9%) 39 (58.2%) 5 (7.5%) 3 (4.5%) 2 (3%) 65 (97%) < < Billig et al, Plastic & Reconstructive Surgery, 2017, in press

28 MROC study: postoperative complications Billig et al, Plastic & Reconstructive Surgery, 2017, in press

29 Which factors play a role in complication rate after autologous reconstruction? Multivariate analysis No difference in complication rate at 1 and 2 yrs between Immediate vs delayed! Similar for: Type of reconstruction Uni vs bilateral Chemotherapy after reconstruction yes/no Age Smoking yes/no (!) Race Educational level Marital status Only significant factor at 1 yr: BMI <> 30. Billig et al, Plastic & Reconstructive Surgery, 2017, in press

30 MROC study: Results of Breast Q Tendency for somewhat higher scores in delayed group at 2 years (only significant for physical well being) However: Pre-operative: worse results in delayed group à much larger improvement in delayed group Billig et al, Plastic & Reconstructive Surgery, 2017, in press

31 Summary PMRT & autologous reconstruction 1) Complication rate immediate vs delayed: No difference Both strategies acceptable 2) Failure rate immediate vs delayed: No difference 3) Cosmetic outcome / physical well being immediate vs delayed: Probably somewhat better in case of delayed reconstruction

32 MROC - SABCS 2016 Reshma Jagsi Comparison autologous vs. implant 2014 patients with reconstruction (autologous or implant), , 11 centra 553 patients PMRT 1461 patients no PMRT Average age 49 yr Endpoints: Complications Failure PROMs measured using Breast-Q

33 MROC SABCS 2016 Reshma Jagsi After 2 yr at least 1 complication 33.4% in patients with PMRT vs. 23.5% w/o PMRT

34 MROC SABCS 2016 Reshma Jagsi After 2 yr, reconstruction failure 19.7 % in irradiated patients 6.1 % in non irradiated patients No difference for autologous reconstruction!

35 Shared decision making 4 choices Immediate implant, i.e. (TE -) Implant RT Immediate Autologous Delayed implant, i.e. TE - RT Implant Delayed Autologous

36 Issues Period w/o a breast Need for 2 nd (or 3 rd ) surgery Thinking time Re-excision possibilities Complication and failure rate Fibrosis: capsular contracture cosmetic outcome Technical RT challenges Delay in starting RT Immediate RT on implant Implant: Autologous: Implant: Autologous: Implant: Autologous: Delayed TE-RT-Implant

37 2 special situations Also to overcome mentioned problems? 1. Only implant reconstruction possible/ wanted 2. Only delayed reconstruction possible, due to logistics, required thinking time etc; no decision yet on type of reconstruction TE or implant should be placed immediately Later: if wanted followed by implant and/ or autologous reconstruction

38 Further developments to overcome problems Issues Implant Delayed RT - TE-RT-Implant autologous Period w/o a breast Need for 2 nd (or 3 rd ) surgery Thinking time Re-excision possibilities Complication and failure rate Fibrosis: capsular contracture cosmetic outcome Technical RT challenges Delay in starting RT Implant: Autologous: Implant: Autologous: Implant: Autologous:

39 Further developments to overcome problems Pre-operative RT: Best of both worlds? Same advantages as after Primary Systemic Treatment Less interobserver variation in delineating the tumor, instead of the tumorbed Facilitating immediate autologous breast reconstruction? Thinking time during RT No period w/o a breast No impaired cosmetic outcome due to RT-induced fibrosis No need for 2 nd surgery However, still limited possibilities for re-excision

40 PRADA- pilot N = 18, treated in 2013 Conclusions: 3-4 weeks Chemotherapy Radiotherapy Gy Failed Breast Conservation Skin sparing mastectomy with DIEP after chemotherapy 1-6 weeks and radiotherapy is feasible with low Mastectomy complication rate Translational protocols in development Immediate Reconstruction DIEP Thiruchelvam et al, SABCS 2016

41 Ongoing trials preoperative whole breast RT Title Country Study design & patient group Target (N) Investigated intervention Primary Endpoint PRADA UK Phase 2 Intermediate risk 20 Preop WBRT, followed by mastectomy with DIEP Open wound, 4 wks after DIEP PROBI 1 NL, NKI Phase 1-2 Intermediate risk 94 Preop WBRT with boost followed by surgery Surgical complications PAPBI-2 NL, NKI Phase 3 RCT Low risk 500 Pre vs postop APBI, surgery after 6 weeks Cosmetic outcome NeoRT UK Phase 1 Intermediate risk 43 Preop WBRT followed by 6 months HT, then surgery % patients completing Rx

42 Take home messages No RCTs available!! From the limited data in literature: 1. Implant: First TE and/or implant, then PMRT RT on implant: more capsular fibrosis, less failures RT on TE: more failures, less capsular fibrosis 2. Autologous reconstruction: Immediate vs delayed similar complication rate Delayed seems to yield better PROs 3. Autologous yields better PROs, and less influence of PMRT and its timing than implant 4. Future studies: RCTs required; preoperative RT? Multidisciplinary teamwork & Shared decision making essential!

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