Predictors and Timing for Successful Radiated Breast Reconstruction Mark W. Clemens, MD FACS Associate Professor MD Anderson Cancer Center None Disclosure Kaiser Permanente 2018 Plastic Surgery Symposium February 10, 2018 Radiation Sequelae MD Anderson TE Experience Overall Complications Injurious effects of radiation therapy Increased complications Lower patient satisfaction with reconstruction By BREAST-Q Level I Evidence Double major complication rate to non-radiated reconstruction No radiation 24.4% 1 PMRT 45.4% 1 Overall N= 564 Drain time: 22.6 days Complication: 45.3% Infection: 12.4% Explantation: 9% Univariate BMI, p=0.005 Comorbidity, p=0.02 Diabetes, p=0.13 Hypertension, p=0.03 CAD, p=0.08 Postop XRT, p=0.003 CA vs. Proph, p=0.08 In situ vs. invasive, p=0.07 Duct vs Lob, p=0.004 Bra>700cc, p=0.003 Multivariate NSM, p=0.06 Postop XRT, p=0.01 Bra volume, p=0.002 Lobular, p=0.008 Berry T, Brooks S, Sydow N, Djohan R, Nutter B, Lyons J, Dietz J. Complication rates of radiation on tissue expander and autologous tissue breast reconstruction. Ann Surg Oncol. 2010 Oct;17(Suppl 3):202 10. Selber JC, Wren JH, Garvey PB, Zhang H, Erickson C, Clemens MW, Butler CE. Critical Evaluation of Risk Factors and Early Complications in 564 Consecutive Two Stage Implant Based Breast Reconstructions Using ADM at a Single Center. Accepted, in press.2014 TE Experience Infection Immediate DIEP flap after XRT Univariate BMI, p=0.04 Age>52, p=0.005 Comorbidity, p=0.02 NSM, p=0.06 CA vs. Proph, p=0.08 Duct vs Lob, p=0.004 Multivariate Postop XRT, p=0.02 2.3x SLNBx, p=0.009 2.45x 42 year old female Previous left breast IDC, lumpectomy Mastopexy reconstruction Left breast XRT SNLBx, p=0.04 High Intraop fill, p=0.08 Bra>700cc, p=0.003 High drain time, p=0.003 100cc of fill volume, p=0.0001 5x Selber JC, Wren JH, Garvey PB, Zhang H, Erickson C, Clemens MW, Butler CE. Critical Evaluation of Risk Factors and Early Complications in 564 Consecutive Two Stage Implant Based Breast Reconstructions Using ADM at a Single Center. Accepted, in press.2014 1
Preop CT Angio Intraop Dissection Immediate DIEP flap after XRT Postop Preop Algorithm Chemotherapy Changing Radiation Delayed Autologous reconstruction Comorbidities? 75% 2 Stage Tissue Expander/ Autologous 25% 2 Stage Tissue Expander/ Implant Node Positive >5cm Multifocal Invasive? No Radiation Breast cancer Immediate Autologous reconstruction DCIS? Node Negative <5cm Unifocal 2 Stage Tissue Expander/Impl ant Neoadjuvant is standard of care All patients with >2cm breast cancer and LN involvement Substantially improves BCT rates Converts unresectable to operable Allows observation of chemo responders May obviate need for XRT and surgery Level I Evidence Schwartz GF. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast. Hum Pathol. 2004 Jul;35(7):781-4. Kaufman M. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol. 2012 May;19(5):1508-16. Not All Tissue Is Equal C509-T Variant Predicts PMRT Fibrosis Parsa 2009: Level II Evidence Severe skin changes: 75% poor aesthetic outcomes Induration: 100% poor aesthetic outcomes Patients may be stratified as an acceptable prosthetic candidate based upon skin response C509-T Variant in TGF-B promoter allele: 50% of the population, 4x fibrosis after radiation Parsa AA, Jackowe DJ, Johnson EW, Lye KD, Iwahira Y, Huynh TV, Pedro P, Pang J, Parsa FD. Selection criteria for expander/implant breast reconstruction following radiation therapy. Hawaii Med J. 2009 Apr;68(3):66 8. 2
Not All Radiation is Equal Two-angled (Tangential): Technically easiest for reconstructed shapes. Whole breast: Two phases, 50.4 Gy plus 10 Gy boost Multifield Approach (3-dimensional): More adaptable to varying anatomy. Always treats IMNs with less heart and less lung. Technically challenging. Requires flat anatomy or deflated expander. Intensity-modulated radiation therapy (IMRT) 6 field technique. Most uniform dose. Whole thorax dose is 10-20% including contralateral lung and contralateral breast. Complicated, timeintensive and costly Incidence of IM Disease 1200 cases of Stage III Breast Cancer treated 1996-2006 at MDACC 865 had regional lymphatic involvement beyond the axilla: Infraclav, Supraclav, IMC 37% had clinically evident disease beyond the low axilla: Infraclav: 32% Supraclav: 16% IMC: 11% Iyengar SABCS 2008 Benchmark Studies IM Radiation MA-20: Nodal radiation benefits local recurrence in early stage breast cancer Improved survival hormone receptor negative disease disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group DBCG: Danish cohort on IM radiation in early stage node positive breast cancer Improved survival: 75.9% with IMNI versus 72.2% without IMNI Wharten T. Regional Nodal Irradiation in Early Stage Breast Cancer. NEJM, 2015. Jellesmark Thorsen. DBCG-IMN: A population-based cohort study on the effect of internal mammary. JCO, 2015 ADM as Radiation Protector? Higher complications Delayed integration Capsular contracture protective? BCT vs PMRT Implants vs. Autologous reconstruction Left: No radiation Right: Post radiation Clemens MW, Kronowitz SJ. Acellular Dermal Matrix in Irradiated Tissue Expander/Implant-Based Breast Reconstruction: Evidence-Based Review. Plast Reconstr Surg 130(5 Suppl 2):27S-34S, 11/2012. Timing of Complications ADM Protective for Explantation 3 postoperative phases Pre/XRT/Post Majority of complications occur perioperatively Equal rates during and post radiation Explantation Rate No PMRT PMRT Non ADM ADM Non ADM ADM 5.9% 9.5% 20.4% 11.4% Non-ADM patients are significantly impacted by onset of PMRT, experiencing more explantations. OR= 3.19, p =0.002 ADM patients are not impacted by PMRT, and may play a protective role. OR = 0.38, p = 0.04 3
DTI in NSM Prosthetic Reconstruction Previous RT Three week postop 64yo Preop after XRT DTI in NSM Prosthetic Reconstruction Previous RT 2 years postop Fat Grafting the Radiated Breast Case Example: Prosthetic Reconstruction Radiated Breast Hyperpigmentation, ulceration, and dermal thickness all improve in a radiation animal model 1 Attenuates inflammation and slows progression of fibrosis 1 Oncologically safe 2 Recurrence rate 5.3% compared to 4.7% control May require 10-40% overcorrection Preop 41-year-Old Female: Invasive Ductal Carcinoma of the Left Breast 1. Sultan SM. Human fat grafting alleviates radiation skin damage in a murine model. Plast Reconstr Surg. 2011 Aug;128(2):363-72. 2. Agha R. Use of autologous fat grafting for breast reconstruction: A systematic review with meta-analysis of oncological outcomes. JPRAS, 68:143-161, 2015. 18 months postop Case Example: Prosthetic Reconstruction Radiated Breast Case Example: Prosthetic Reconstruction Radiated Breast Chest wall mass and axillary node recurrence Requires ALND, partial pec excision, PMRT ALND 9 months post XRT R Breast Scar 1 month L Breast Scar 1 month Fat grafting at exchange 200cc Left 100cc Right 600cc round bilaterally 9 months post XRT 2 years postoperative 4
PrePectoral TE Placement Prepectoral TE Placement Less postoperative pain No muscle distortion Temporary air filled TE May alter radiation plans Potentially higher doses to chest wall Postpec Modelling Prepectoral Modelling Delayed-Immediate to Prosthetic Timing of Exchange Nava et al. 2011 Level II Evidence 50 patients TE-XRT-Implant 109 patients TE-Implant-XRT Control: 98 Non-XRT All patients chemo postop Nava M et al. Plast Reconstr Surg. 2011 Subpectoral Tissue Expander VS Exchange to Implant TE XRT Imp XRT Failure rates 40% 6.4% P<0.01 Cap con rates 53.3% 57.8% P<0.01 Good results 30.8% 58.7% P<0.01 Exchange to Implant Timing of Radiation: Effect of PMRT Cordeiro 2015 2 : TE-XRT versus implant-xrt BREAST-Q were same Impact of recurrence free survival? If preop chemo, radiate the expander TE XRT Imp XRT Failure rates 18.1% 12.4% P<0.01 Cap con rates 1.2% 6.3% P<0.01 Aesthetic results 75% 67.6% P<0.01 Subpectoral Tissue Expander Expansion 10-14 days postop Chemotherapy Exchange to Implant 1 month 1 month 1. Gross E, Hannoun-Levi JM, Rouanet P, Houvenaeghel G, Teissier E, Ellis S, Resbeut M, Tallet A, Vaini Cowen V, Azria D, Cowen D. [Evaluation of immediate breast reconstruction and radiotherapy: factors associated with complications]. Cancer Radiother. 2010 Dec;14(8):704 10. 2. Cordeiro PG. What is the Optimum Timing of Post-mastectomy Radiotherapy in Two-stage Prosthetic Reconstruction: Radiation to the Tissue Expander or Permanent Implant? Plast Reconstr Surg. 2015 Feb 27. Procedures Timing of Radiation: Effect of PMRT Cordeiro 2015 2 : TE-XRT versus implant-xrt 100 90 80 70 60 50 40 30 20 10 0 Implant XRT TE XRT 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 Year Subpectoral Tissue Expander Expansion 10-14 days postop Chemotherapy Exchange to Implant 1 month 1 month 1. Gross E, Hannoun-Levi JM, Rouanet P, Houvenaeghel G, Teissier E, Ellis S, Resbeut M, Tallet A, Vaini Cowen V, Azria D, Cowen D. [Evaluation of immediate breast reconstruction and radiotherapy: factors associated with complications]. Cancer Radiother. 2010 Dec;14(8):704 10. 2. Cordeiro PG. What is the Optimum Timing of Post-mastectomy Radiotherapy in Two-stage Prosthetic Reconstruction: Radiation to the Tissue Expander or Permanent Implant? Plast Reconstr Surg. 2015 Feb 27. Delayed-Immediate: Radiating Expander Delayed immediate to autologous reconstruction Implant for the select patient To preserve the footprint of the breast and skin envelope Final reconstruction delayed 6 months following RT Higher expander loss rate in DM, smokers, obese Multidisciplinary Breast Consultation Neoadjuvant chemotherapy Prepectoral Tissue Expander 1 2 weeks Partial Deflation of Tissue Expander 5 6 weeks 10 weeks Re-Inflation of Tissue Expander CPM and AFG 3 months 3 months Stage 2: Autologous reconstruction Select Prosthetic reconstruction Kronowitz SJ. Delayed-immediate breast reconstruction: Technical and timing considerations. Plast Reconstr Surg. 2010;125:463 474. 5
Case Example: Delayed-Immediate TE to LD + Implant 42 year old female with IDC of the right breast, Node+ BMI 19 Requires 3-beam radiation therapy with IM Subpectoral Tissue Expander Partial Deflation of Tissue Expander Example Case: Delayed-Immediate 5 months post radiation Re-Inflation of Tissue Expander Stage 2: Abdominally-Based Free flap Latissimus Dorsi Flap with Permanent Implant Robotic Assisted Latissimus Harvest Begin in a lateral decubitus position on a beanbag Use previous mastectomy and/or axillary dissection scar Dissect out pedicle and lateral border of latissimus 30% of superficial dissection As much as possible deep dissection Robotic Assisted Latissimus Harvest Marionette sutures One 12 mm port for camera Two 8 mm ports: Monopolar Maryland retractor dissector Electrocautery scissors 6cm 6cm Clemens MW, Kronowitz SK, Selber JC.. Robotic Assisted Latissimus Dorsi Harvest in Delayed-Immediate Breast Reconstruction. Semin Plast Surg, 2014. Robotic Assisted Latissimus Harvest 6
Technique: Conversion to Autologous Example Case: Delayed-Immediate Inset of muscle over intended implant and/or sizer Total muscle coverage Shaped, high cohesive implants One year postoperative Example Case: Delayed-Immediate Case 2 Two year postoperative 36 month postop Fat Grafting with Robotic LD and Implant Pathway to Adding Robot Skills to Your Practice 1. MD Anderson Visitor 2. Attend International Training Course - RAMSES 3. Engage Urology, Oncology, ENT for preceptorship Delayed-immediate XRT protocol ADM with tissue expander Robotic latissimus dorsi Fat grafting Two year postoperative 7
Predictors and Timing of Radiated Breast Reconstruction Conclusions Thank you Blood test C509-T Variant of TGF-B predicts fibrosis and reconstructive outcomes Prosthetic reconstruction of the radiated breast is more challenging, results in lower patient satisfaction, and is heavily dependent radiation type and timing Improved aesthetic outcomes are possible combining technique advancements, ADM, fat grafting, and conversion to autologous when appropriate mwclemens@mdanderson.org Twitter: @clemensmd 8