1. Breast Reconstruction with Implants and Radiation Therapy: Patient and Timing Selection Dr. Khaled Abulkhair, PhD Medical Oncology SCE, Royal College, UK Ass. Professor of Clinical Oncology Mansoura University, Egypt

2. Reconstruction plus Radiation Therapy Myths? If implants ; better not to give RT. Higher recurrence!!! Autologous Tissues show better results after RT. Once irradiated your implant will rupture. Will muscle flap tolerate high doses of RT. Put the implant after RT! It is always the fault of the radiation oncologist!!!

3. To or not to reconstruct? MastectomyNipple areola full reconstruction A Woman’s right… should be discussed thoroughly with every breast cancer patient.

4. A Higher Recurrence? Once believed that there was a delay in detection of local recurrence in patients with immediate reconstruction. Recent evidence suggests that there is NO DELAY in detecting local recurrence in reconstructed breasts 1. Nedumpara et al. (2011) reported on a series of 691 consecutive patients undergoing mastectomy, of whom 136 (20%) underwent immediate breast reconstruction (either with latissimus dorsi flap or subpectoral implant). The median follow-up was 55 months. For the whole group or within prognostic categories, they found no differences in local recurrence, distant metastases or survival. No significant difference in survival between reconstructed and non-reconstructed breasts 1

5. Tell me about Radiation Therapy!

6. Basics Breast Surgery Mastectomy or EqualBCS/ Any residual breast tissue RT is A MUST RT +/-

7. Progress of (PMRT) Over time What we did prior to the 1970’s? Many patients received PMRT post surgery, RM or MRM. NSABP B-02 randomized patients after RM to receive regional radiation. No difference in overall survival but decrease in regional recurrence. Initiated in 1971, NSABP B-04 randomized patients after RM, TM, or TM + XRT if N0 and if N+ to RM or TM +XRT. Ten year results showed no difference DFS or OS among the groups. Radiation arms did show decrease in local recurrences.

8. What happened in the 80’s? By the mid-80’s, an excess of cardiac mortality seen in patients followed for 10 years. Meta-analysis of 7 randomized trials of PMRT initiated before 1975 showed an increase in cardiac-related deaths in those receiving RT that was almost balanced by a reduction in the deaths due to breast cancer. The excess cardiac mortality was largely due to the increase in cardiac dose from radiation to the internal mammary nodes.

9. Paradigm shift to Alternate hypothesis Breast cancer is both a local and systemic problem at presentation. Trials started examining less extensive surgeries. More extensive local treatment will not improve survival. Wrong Assumption

10. Who did we treat in the 1990’s? Due to Toxicity; indications for PMRT were limited to include only those patients with more advanced disease: T3/4, more than 4 positive nodes. The rationale for choosing these patients is the high recurrence rate 30% which radiation could reduce by half. The treatment volume typically included the chest wall, supraclavicular nodes, and axillary nodes and much less often, the internal mammary nodes. The goal of treatment was only to reduce local and regional recurrence and not to improve overall survival. Wrong Assumption

11. What did we learn in 1997? Two articles published in the NEJM 10/97 showed improvement in survival with PMRT in premenopausal women, all of whom also received chemotherapy (CMF). Patients enrolled in these trials were (generally) node + with the majority having only 1-3 positive nodes and the majority having tumors < 5 cm in size. Fields treated included chest wall and all regional nodes. Similar results seen in postmenopausal stage II/III women treated with Tamoxifen and PMRT, improvement in DFS and OS.

12. Where did we go in 2000? Many people began recommending treatment for any node positive patient following mastectomy. Intergroup study attempted to address role of PMRT in women with 1-3 positive nodes but closed in June 2003 secondary to lack of accrual. Many discussions regarding the value of treating clinically uninvolved nodes and how that may impact overall survival.

13. British Columbia Trial: 20 year results…. significant survival Benefit Breast Cancer Specific Survival Overall Survival

14. What is the downside of PMRT? Greater risk for lymphedema of breast and arm. Increased amount of lung that is fibrosed by radiation, primarily from treatment of either the supraclavicular nodes or internal mammary nodes. May expose contralateral breast to radiation. Decrease in the quality of the cosmetic outcome following reconstruction, especially with implants.

15. Who needs PMRT in 2008? – T3/T4 disease at presentation. – Pathologic involvement of 4 or more nodes. 3 – What about involvement of 1-3 L.N? – What about positive margins?

16. When positive margins are the only risk factor Hard to demonstrate the value of PMRT in patients where positive margins is the only risk factor for local recurrence. Retrospective reviews have found L.R rates of <15% without XRT. Retrospective multivariate analysis of large group in Canada found a L.R rate of >20% in those patients with positive margins who also had T2 tumor, <51 years old, grade 3, or LVSI.

17. Current Recommendations

18. Use of PMRT with Implants …Myths? Any patient irradiated with implant reconstruction will not look as good as a patient who does not receive PMRT…tissue loss, Capsular rupture and skin wrinkles? Autologous reconstruction appear to “tolerate” PMRT better, with better cosmesis. How confident we are about these statements?

19. Silicone Implant is a Mastectomy Procedure?

20. Importance of 3D Planning

21. RTOG …Definition of Target Area

22. Complications…Changing Overtime Chawla et al. (2002) reported on a series of 48 patients who were treated with RT and reconstruction. The two year complication rate was much higher in the implant reconstruction group (53%) compared to the TRAM (transverse rectus abdominis musculocutaneous) reconstruction group (12%). First impression…implants are bad and getting worse after RT… Is this true? How much bad?

23. Complications…Changing Overtime Cordeiro et al. (2004), 70% of 687 patients received RT, with a mean follow-up of 34 months and they were compared to 75 un- irradiated patients. 68% of the irradiated patients developed capsular contracture, compared to 40% in the un-irradiated group. Most complications were in the first 2 years!!! 80% of the irradiated group had acceptable (good to excellent) aesthetic results, compared to 88% of the un-irradiated group,

24. Complications…Changing Overtime Kronowitz & Robb (2009) have performed an extensive literature review of RT and breast reconstruction. For immediate reconstruction with an implant, they concluded that RT is associated with a 40% complication rate and capsular contracture and 15% extrusion rate of the implant. Also reconstructions with autologous tissue were found to have an increased rate of fibrosis and contracture if RT is delivered to the reconstruction site after the reconstruction.

25. Before 2011…Conclusion were There is some evidence that an immediate breast reconstruction is to be preferred to a delayed reconstruction, and that this is safe from an oncologic perspective. However, most guidelines caution the use of immediate breast reconstruction if RT is scheduled, or if there is a high chance of an indication for RT. (breast cancer treatment guidance: UK NICE guidelines 2009; Dutch national guidelines 2011). Unfortunately, the RT indication is not always certain pre-operatively.

26. Recent Advances: MSKCC recently published their algorithm for PMRT with implant reconstruction. They recommend placement of permanent implant after expansion during chemotherapy and before start of PMRT. If SSM i.e. no need for expansion, do it before PMRT. Dosimetry studies around metallic ports of expanders have shown no significant impact on dose or complications.

27. Reconstruction: before or after PMRT? A systematic review of the literature. Eur J Cancer 2014 Nov 26;50(16):2752-62. Meta-analysis..Level 1 evidence 37 eligible studies complications and cosmetic outcome 4 different subgroups: -Autologous reconstruction after radiotherapy. -Definite implant reconstruction after radiotherapy. -Autologous reconstruction before radiotherapy. -Definite implant reconstruction before radiotherapy

28. What did they find? A large variation in complication rates (8.7–70.0%). Acceptable cosmetic outcome (41.4–93.3%) The first analysis showed more complications and a higher revision rate if an implant reconstruction was performed after radiotherapy; for autologous reconstruction fibrosis occurred more often if reconstruction was applied first. The second analysis showed no significant differences in total complication rate. Only implant failure occurred more often if applied after radiotherapy (odds ratio (OR) 3.03 [1.59–5.77]). Concluded that A definite implant reconstruction placed before radiotherapy limits the rate of complications.

29. Conclusion Breast reconstruction doesn’t result in a ‘perfect’ breast, but there can be many benefits; restoring her confidence, improving her image and no external prostheses to wear. You’ll also need to think about timing. Immediate reconstruction often leaves fewer scars, but delayed reconstruction will avoid un-expected complications. Remember, there is no upper time limit for having breast reconstruction. It’s always available – even years after mastectomy.

30. PMRT following MRM, SSM, NAC-SM with reconstruction including Implants should all follow the same principles. Immediate reconstruction is contraindicated in IBC. SSM is not yet considered safe in IBC due to the need to excise all previously involved skin making no advantages for immediate reconstruction. NAC sparing is contraindicated if Paget’s and or bloody nipple discharge. Be cautious using NAC sparing dealing with breast cancer and better to avoid if Hormone negative, Her-2+++, L-V invasion and large primaries with less than 2 cm from NAC.

31. If implant reconstruction is planned for those requiring mastectomy and PMRT; a staged approach is preferred starting with tissue expanders with permanent implant to be put before Radiation therapy. If SSM you can go for immediate implants. Tissue expanders of irradiated skin carries a significantly higher risk for capsular contractures, malposition and poor cosmesis. Complications happen, implant has around 30% complication rate post RT. Let the patient knows.

32. It is not always the fault of the radiation oncologist

34. 1.Malata, McIntosh & Purushotham.(2000). Immediate breast reconstruction after mastectomy for cancer. British Journal of Surgery, 87, 1455-1472. 2.Barreau-Pouhaer, Le, et al (1992). Risk factors for failure of immediate breast reconstruction with prosthesis after mastectomy. Eur J Surg Oncol, 18, 119-23. 3.Schechter, Strom, Perkins, et al. (2005). Immediate breast reconstruction can impact postmastectomy irradiation. American Journal of Clinical Oncology, 28(5), 485-494. 4.Judith Berbers, Angela van Baardwijk, Ruud Houben, Esther Heuts, Marjolein Smidt, Kristien Keymeulen, Maud Bessems, Stefania Tuinder, Liesbeth J Boersma. 'Reconstruction: before or after postmastectomy radiotherapy?' A systematic review of the literature. Eur J Cancer 2014 Nov 26;50(16):2752-62. Epub 2014 Aug 26.Judith BerbersAngela van BaardwijkRuud HoubenEsther HeutsMarjolein SmidtKristien KeymeulenMaud BessemsStefania TuinderLiesbeth J Boersma 'Reconstruction: before or after postmastectomy radiotherapy?' A systematic review of the literature.