�esensko strokovno srečanje "Združenja senologijo 19.11.2015 Hotel Plaza Ljubljana Predavatelji: Prof. dr. Janez Žgajnar, dr. med., Oddelek za onkološko kirurgijo, Onkološki inštitut Ljubljana Prof. dr. Uroš Ahčan, dr.med., Klinični oddelek za plastično kirurgijo in opekline, UKC Ljubljana Dr. Tanja Marinko, dr.med., Oddelek za radioterapijo, Onkološki inštitut Ljubljana Dr. Simona Borštnar, dr. med., Oddelek za internistično onkologijo, Onkološki inštitut Ljubljana Urednica zbornika: Simona Borštnar Organizator in izdrajatelj: Združenje za senologijo pri SZD Strokovno srečanje sta finančno omogočili podjetji AstraZeneca in Roche Ljubljana, november 2015 16.00-16.30 Prihod udeležencev 16.30-16.50 Kdaj ohranitvena operacija raka dojk ni možna? Janez Žgajnar, Oddelek za onkološko kirurgijo, Onkološki inštitut Ljubljana 16.50-17.1 O Kako danes rekonstruiramo dojko? Uroš Ahčan, Klinični oddelek za plastično kirurgijo in opekline, UKC Ljubljana 17.10-17.30 Rekonstrukcija dojke in obsevanje Tanja Marinko, Oddelek za radioterapijo, Onkološki inštitut Ljubljana 17.30-17.50 Novosti v predoperativnem zdravljenju raka dojk Simona Borštnar, Oddelek za internistično onkologijo, Onkološki inštitut Ljubljana 17.50-18.15 Razprava 18.15 Večerja Kdaj ohranitev dojke ni mogoča? R:eview Article Janez Žgajnar 01 Magnetic Resonance lmaging in Patients With Newly Diagnosed Breast Cancer A Review of lhe Literature Me-lls:sa Pilewskie. MO:and Ta:rl A. King, MD Th& LS• ol rnagnetlc f1!!SONll1Ce lrnaging (MRO in petlltnts wlth nowl� � bnMsl � renv,UU. ccntroyg"S:1,!11.. Hefe - mvlew lne cu,re,,t llSllt of bre.Kt MRI arQ tha fflp&Ct ot MRI on J:l'IDrt-tmm Al,gical OMtcomas .arld rat6S 01 local, reo.trnUICII In addlt.101'\, - addraa the UH of MRI n speafic l)5tlelit popuDtiOl'IS. :such 1111 t"°"" w!th CU:tzil c:artinana tn Situ, tnVaSlve k>bula!' c.CS'loma. and OC,Qjt S)l'ffla,y brQ.Mt a!inatf. a,rd dlScusS th& l)Ol�lal rtff ot Mfa tor ass.nsng N!Aporise to �t cr.1Mtl\erltpy. Atl'lou,gh HRI l1a:,, � MMitJllo'IQI' � """""co,w,,w,UO,W ilt\:IQ,l,O. l.'-'. ,._,l l'Wlt. 11.w,� 11'1!:0 � Mllrblanft � �• C0mlD OI' long-1:1!:Jm potSenl benefit. SlJ'Ch es �Ooll!d locat 0Dr1.ro6,,, SU'V'I\Jal. In arry pat;ent pop,.Q.clon. MRI 1s,... impo,t.,r,t dlagnc,s­ t:lc ttst n the � ot pa.tialts pn15Qnthg w�h ccOJII.: prtnwwy 01'9ast C'JlnCW and nas sP'Dwn p,ornl59 In rnot'lllornQ rlt'q)Oftm to neooojw11n1: dwmothenlpy; �- thedata do N>l Sl4)port U'I& l'OlaiM W'8 of�pe-Mitt MA, In i:,otief1:sw1th 1\-'Y � �stc:anr:a � CMrar2D14;1Z0:2090-9.02Dl4��Soc::4t(y. G'fWOROI,; ���Q(-��n..c.�-94")',kk.ail,..CU� Kaj so razlogi za tak naslov? • Delež mastektomij še vedno visok • Delež mastektomij celo raste - Uporaba MRI - Boljše tehnike in dostopnost rekonstrukcij dojk - Porast kontralateralnih profilaktičnih mastektomij BCT je varna Milan I trial 1.0 0.8 ·;; 0.6 0.4 0.2 o.o o Veronesi, NEJM, 2002 - Radical mastactomy - Breast-eonserving therapy 5 10 Years 15 20 Effect of ra diotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials .. " Lanc«l'Oll;371l:l70r16 �Ot!«tOta:b lO-r-'Jiffl15•7'J,(S(I-O; �0-52(95%00-S� • lD1J" ·inl-.2p5=.1�2BI •Dlffutetr pol[tM palbolDgl,: 11111p11111 •W.0.-wkhttnOWIIOfsut.p-.igallltlCl'�-..... - �lkylm\la„lfEnUedfllkofJpt;llaltlll�-are&lldnlltnlbl..aCIIICKwll!l�Dlaraii, •Pn:iphJlldlcbllldarw�fDrrl:lklMIEl:KIIIN'jll9--.., �- '"ierM7 -PA•ct:v: ..- trr: ..,....., 1:::.i� -���------_,..,..--1 - ---· - ■�:::_� _.- NCCN Guick!!lines Verslon 3.2015 �,...- Ouctal Carcinoma in S1tu �-,tQl!b�l'i..,.......,.,.,Cfo__,..pClll(llloG1c:........,lnDCIS. �MtM9outd11,,t�c,1 IHdlM--ll�lht--f:l..,.,.,,,,..._�-�-alllht-111a.......,_ ��----lacto,wlnDCfJ 111�,ar-llWIIO""" ... -if'�""�•Jl:,cal--•- -.�-� ...walnoj<1llffll!M.IMMlrog-.WDOUndlryr>flllo-lrnwlMl0t•lnl110�ot-1.11,vll:,ll,.....c....._�1.11-�-,1r1111cWot1 r.,,MgN,f - d""'" ...tlalio,i ID'lho lrN_ I_.,..,., o1!9lmt.l101Y29) 1-.::.-=--.::--=--•··-----·- JoURNAL OF CLiNICAL ONCOLOGY S PS:C IA l. Af? I I Society of Surgical Oncology -Ameri can Society 1 or Radiation Onco logy Consensus Guideline on M, rgins for Breast-Conserving Surgery With Whole-Breast l:Tadiation in Stages I and II lnvasive Breast Cancer Mana S. Mora11.,. Stwrl f. Sdmif1, Al'fflanAo E. Ci,,!ia„o, Jay R. Jlarns, S..mia A.. Khcin, rincr /larlion. Su;;a,n.1e Klim/>ag . M"riDna C/u,w:•Mm:Gr�. Ga ry, Fncdman, Ndrmul Hvm.sumi. Pc, -gy L fobn10n. anrlMvnicaMorru,.• Annals of Oncology Actvanc.o Ac::coss put>lisnec:11 May 4� 2015 Tailoring therapies - impr-ovlng the managemen t" of earty breast cancer: St Gartenlnternational Expert Consensus on the P rfmary Therapy of Earty Breas� Cancer 2015. surgery of the primaty 1he Pa nel strongly endorsed recent findings that the minimal acceptable surg)cal margin was 1 no ink on invasive tumour or oas· . Thi s conclusion ap pl ies r-egardless of tumollf" charac teristics such as lobu lar hist ology, extensive intrad u ctal component,. young age� multifoca lity or multicentricity and unfavourable biological su btype [7]. A cle ar m ajo rity of the Pane l agreed th at multifoca l and mu lticentric tumour s co u ld be treated with breast conservation, provided the above margin dearance was obtained and whoJe breast radtOtherapy was p lanned. Following neoadjuvant chemo therapy, the Panel di d not consider it nec:ess:ary to resect the entire area of the original primary jf down--staging had occurred . Wh:irl'csttl9msoltr.61naaaM1onr:stdl8'ffi wil:h.iDOSittw�Cantheusea1 � boost. systWnC TNQpy. or �UfllJl'tllill7,rt�lrns ,crea,edli!lt? Oo,na,gr,·.w;th:;.Wldel"�roa\ko:-.!U'TEI" c:t!lls�mBristct:aTil7 l\ftll„aeaNcDct�«� =►r::r:��� roeerwlllQll1YS'Y518miclnlffl'nllnttmm wic»rm21Qt1WIClltts1 ShOu'.d ti� biologtc wotypos (!;Udl z ITipl�tlvo.iruslcancersJ reqtnrn wioor �lfls!th.linno1nko11ttnncrP Sto.Jld flWOt' � b6 ICNf'I no� ��w:;;rr-OIIMr), - l<; 1hP Pltl$M\CII' t,t LCIS .rt 1TI<} !TQ.'Qn :m ,ndiQt'ol[Of19-,i:o-cis,or,]Do� lotll.li.r Cill'e1nom::1!; raqurm a wider m;,rg,r, !l'Nll IIO lflt' l1fl IUTVY'P Wh;i( IS� sig,,i h ana.•ol�phic LCISiltN! _, ��rTl3",ll(lwrdlhs!M1erttt.ll'lllO li'lt ctl-1unor) b8 cmsdlHQd for \IOOr'IQ catl8NS(;iga<40yv.n1? 'Mlal131he�ional�:rnEIC„ffl91l.,nor �ll".dhowdoo�lhel)Ql1iinto 'fW911\�) ...........,,. .... f'l::a:llillt �dtlrw;t&sik:1.S1mrd.ou� Of DClS, Me�ifdset:o1Gn'datal'70ffl n�tM:t���lftWilt''Dla- Pf�ll'a s N.-v� �rlstnlJTR1Stotllllli1ia:lt7f.c»1Neryffla $A011!6 boost. dviwvr, ot syswmic � MldDctne 'hlr.vt, �-b::,ogic�,or�bioirog\' ��n,onkfY'��JD'T11.widl!r Me�alr.ii!;;mdrv� r.ar;pt ---�.,.,,..._Mr'Ei:"h> .-..ru"9"!: ��ts.'Cf;Olt.WOtoNlll;.ttw lftll!O'l -.dh;. � Ol'!\Dl>Ol'•�rotincl(7..-d � .. .,,._no;,,QIOYtlih .. a1:1eat� ��tn;ils:rd� �fl N�� d -'obilr(.� :� �����'ttlll9Bl'.!OIMIIDl!'m �ngltvtn:agirl:iwdlw91Zlnori:mtumol"are �- �w,dv.-th:lnno!!'ll(on!IJl'l'IOrllr9no1,ndic;;itl)db2sed Mu�r��srudlos Of'IDiologlc:!.!Otv;x, OlolQI gf wtJQIQ-Oaast Qdiz;on tlll�V!lfY�. RetlOiSpllClMI :.ludies �andboos;da(.o�l'IOI�� onmerglnwidl!I Wdl!-r ��:tul" no nk:o,, �:im oo:: Re1� sllJtdsi011; ;!'KI '.;1gmOC;mc:1> or �IC l OS �1 ltll.> � r.- Ycui!il „ l.:; 40 V� c .1SXICa!IKI wri:tl batPI � � d3t.l from prOSpUl:W9 :Slll�t.urBCT:111.,..'Qln�kalr�onlha �trlZ!iffldrg� d'lllslw.llaf\vl�omv;,nde.a!somcm� �takl5 �wittl�!::idoglc�palhalogicfmuns; !hml ero��\ �ma,ginWdtl rll6fiQs tt18�ml�IBTR��� EJCiClomJ1185�tswt,omay tg,,JQabtglJ IDSldu;il OCIS Rmlo5peaMI sruc!1i.>S burdm fflUf un:ci�-,.; tMro 1$ �o 8lliaorlC& C: an :iss=�tl9twQwr, �"'51:dll:ITR...,._, m.il'glll5.lf9119'iP".T./9 AD01'� SCT brQiST-o:n:.w:vmo ther.lDY: DCIS. � QroJlClmil n �; EIC. �SZ\18 � com:l00l!nC 16:R � O!li8'ST ?.JIT'IO( rGCl.llftM"ICli: LCIS, 11:o.ibt e;r?'.ll'lfflT' ri snu; WBRT, wl\ae.brQ=: r.icbtJOrt � •••••••I The Breast � ELSEVU:::.R journnlhomep•go:..,_.,lsnvior.comlbru Ong,n,11 ,ll"[l<:le Firsr intemational consensus guidelines for breast cancer in young women (BCY1) An,11 H.l"'aiti .... 1 . 0N� .,.• • """• n,..1 · 0 1 n.t11h.l!rAllullt h.ai ,.. . �l. .; .t n � "' . kt'dbn C' Am;u� ', H4frm A. AlUTl }I, '- , Alt:11:0.tlU ("1\Ll f f , .SWc-flt:"1.\-1.1\utt(:'', C,1.;,,1o1 1-'n>ihch l . Or�iC" IMvrck Ci:1 1 L1 lli U � . M.1di.a H..t;1bcd: '• c.n.ti c:r itlll:' M. J.14.il!, "" . SllPJtk· � 11• . On:H'M .,. J row- •. �ro l'l:(t.J1atflu •. �ILI l (:.11 .1 f r' n:1 11m � . F�11U C'Mder.,-,u...,_ Table4 Early breast cancer locoregional treatment. Guide line statement LoE 8. Surgical treatment oryoung palients with EBC-while being I B tailored to the individual palient - shoukl in general not dilfer I B rrom that or older palients. Although.in general. young age is an independentrisk lacror ror increased loca l rerurrence ali:er BCS and RT. it is alsoa risk fucto r for increased regional recurrence ali:er mastectomy as well as systemic recurrence. thus conservative treatment does notseem tD a ITect OS and the im pact or s ide elfects or more invasive loco­ regiooal treatrnents is often higher. �le11Menn.i 2015: A Briaf Sumnaary of the Consensus Disclmtion Surgery of 1be Primary Tumor �IW ln:silmml � w� itpIIJ .i. � F topu: oCt hR }"CU'�SL GallenNiennaCoo.se:nms.:Despite�disarssioos,. u-"""' no m,p d!uts« •• oxhnJal .2lp«l" of prinruJ' '"""" resed:ion, but i.l am be noled. t.be •� :issue' .appean; oow to be ra;olved and that onu,pb,,lc te;;hn;qo,s bsve foond lheir role the fieldofbreast--consenriDi; ""o"')'.Also, bre"'�'IIIll"T was egain conf m:oed as i.ntended standam of CE!n!:, also in ases of multifocal (72,1; y.., J-4'!(, No, 14% Ab.wn) or m ulticmtric �'II, Yes, 2 1'11, No) oald,!q,hould bc gre,w,,wben age i>les, lhan40 years (JOO'J(, No),should be i;c ea1ec fo,lobular blrity of p=clin> fclt thai ms,gms should not be gmu,, in th, presence of exten:siW? intradnctal compoomt (80% No. 2Mli Yes) and great:er for pure dnctal caicinoma m mu t:han for invasive dis­ ..., (80'Jl, No, 2()'11, Yes) M,cr downs00odju=i1 omothU1f':O.lrl) - ...... Oiltlw -j-:""c:•= ...... =�-=;�'-aa;-, .... =;;--,'-=-" .... ==- �•a;a• ::; --- ;:a; -,,2;-� •·'= ... _5, 1!!>2.,.__ .- ·-- 1 ru X. • aa H�lll,,:3 , �:in t2 * " m � � :t �- 'P) 1� n W ._,'- 1:,,..,-.,:_1 .--. ffl,., ll; fl!:mfl. ..... �'Ml • § tt 'IJ � D.&S�� Ylllflm=0.51J �--+-----< Iti ... � 1D 100 .. _ �.._...,, .. .,,.,.,..,_,...,. ... _III __ ,..___,,..,, .. .., __ _ _____ ..., Zaključek • Delež mastektomij bi lahko/morali znižati • K manj mastektomijam lahko pripomore - Nova spoznanja in smernice - Uvedba tehnik onkoplastične kirurgije - Več argumentiranega pogovora z bolnicami Multidisciplinary team approach and onco-plastic surgery 1n Breast cancer treatment Prof. Uroš Ahčan, MD, PhD Consultant plastic, reconstructive and aesthetic surgeon Department of Plastic Surgery & Burns University Medical Center Ljubljana Breast Cancer realities • 45% of BC patients are facing a mastectomy4 • ONLY "'20% reconstruction rate 5 • Very low level of awareness/information about breast cancer and reconstruction options 2 (70% of women who are eligible forthe procedure are not well informed about their reconstructive) Sources: 1 GLOBOCAN 2008 (lnternational Agency for Research on Cani:er) Web Site 17ttp:llqlobocan.iart:.frl • Lee C, Belkora J, Chang Y, Moy B, Partridge A, Sepucha K, Are Patients Making High-Quality Oeeisions about Breast Reconstrud:ion after Mastectomy? Plasbc: and Reconstructive Surgery, January 2011 'EUPHIX European Union Publie Hearth lnforrnalion System Breast cancer occurrenc:e, w·a,,w,,,,sd:efl!eFiea �•:PrJlQ t1 !::Ff 4 Euromt , C'fTEllleM:f>fFH'ts:!9'7e: � healthldatBbas e �lntemal market assessment; Mentor Reconstruction Summit Breast Cancer realities • More than 350.000 breast cancer cases per year (EU) 1 • One in 10 women in the EU-27 will develop breast cancer • Most frequent cancer type among women(~30%) 1 • The incidence of breast cancer has been increasing for many years in economically developed countries. • Over the thirty year period 1979-2008 the annual number of new cases of breast cancer in women almost doubled. Sources: , GLOBOCAN 2008 (lntemational Agency for Research on Cancer) Web Site http://globocan.iarc.frl � Lee C, Belkora J, Chang Y, Moy B, Partridge A, Sepucha K, Are Patients Making High-Quality Deelsions about Breast Reeonstruction after Mastedomy? Plastic ancl Reconstructive Surgery, January 2011 'EUPHIX European Union Public Health li;ifonnation System Breast eancer oecurrenee. �,iu;nlw.ll[Mllli,rg i9iY!'1'5:! •,-. r>' "°""" '"""" "' """<'d!'O<\ (.l,-,'(.>1,-....-, .... 11� ,m.tl�,,.,.,(",l'\'J'....., ')lrtw-t>fr,l'!',,1.,., 11'1 ... M•t(''!:'t<'tT-.,r['f,;-O<'>\.,'."""•f11'!>us- 2 �+M�stop sS + derm. al flap ADM 011coplaslic ai tologous 2 5! .+-� Teamwork forms the basis for modem breast cancer treatment and personaliz ed approach ... oncoplastic surgery, breast reconstruction with implants, autologous tissue (flaps, lipografting), or combination of different methods Reconstructive options Oncoplastic surgery Autolgous reconstruction lmplants based reconstruction Combination Reconstructive options Oncoplastic surgery Autolgous reconstruction lmplants based reconstruction Combination Autologous recoristruction Delayed Autolgous reconstruction Reconstructive options Oncoplastic surgery Autolgous reconstruction lmplants based reconstruction Combination Preoperative measurements & appropriate implant selection In comparison to breast augmentation (b), bigger implant with greater projection on the lower pole of the breast should be considered in IBBR (d). Mentor CPG'" lmplant 323, 495 CC 323, 495 CC appropriate implant selection in bilateral 2-stage IBBR appropriate implant selection in bilateral 2-stage IBBR Mentor CPG- lmplant 323, 495 CC 323, 495 CC Even with implants we can recreate breasts of different sizes and shapes, even ptotic breasts with shorter post-operative recovery tirne, shorter hospital stay, no additional scaring and donor site morbidity. New trends • in the last decade the number of women with breast cancer having bilateral mastectomy doubled and more than tripled among women without breast cancer but with BRCAl/2 mutation or a high family risk (high risk women). • 1 n USA rising trend in CPM (contralateral prophylactic mastectomy) ., • .,o,,,•--"-.-.tw-1 ..... Y-N, 111 _,,....�,.-,t.,._i.....,,.�,-� ,_ ...... _�.-..---.. �-.•4 • ""'·"''' -·--.... •-.-­ --.>. ..... �-""'- .11, i;,.-•- "'Cl..-.1.,, · -, ,, t...,1-,"'""• ............ _,,_._..,._ • .., ,.1,,b-,-4-•__... --•-'-• .,_._ -- -•-• �-.-...,-., .... _.,_,,,., ... il .... ..._,.,.., IMPLANTS based BREAST RECONSTRUCTION IBBR is not just a "variation of breast augmentation". With an experienced surgeon, breast augmentation is a simple and straightforward surgical procedure of a short duration and minimal complication rates. However, Tebbetts et al. described and categorised 53 variables - that can influence the final result of every breast augmentation - in clinical, tissue and surgeons' factors Studies showed that the average woman's age undergoing bilateral prophylactic mastectomies, varies from 38.1- 40. 7 years (younger, fit patient, less invasive surgery, IBBR) The main factor that needs to be taken into consideration in IBBR is the absence of breast tissue after SS or NS mastectomy "soft tissue envelope" "skin envelope" Comparison of soft tissue coverage between breast augmentation (a) and breast reconstruction with imp/ants (b), where breast tissue is absent, thus irregular, thin skin envelope . . . appropriate implant selection in bilateral ls IBBR CPG "' CPG "' Gel Breast lmplant Result in 37 years old patient after bilateral NSM and single-stage reconstruo:ion using anatomically shaped silicone implants {Mentor CPG"' lmplant 333, 610 ml) & ADM. appropriate implant selection in unilateral ls IBBR The removed tissue is simply replaced with an anatomical implant of similar shape and volume Reconstructive options Oncoplastic surgery Autolgous reconstruction lmplants based reconstruction Combination lmmediate reconstruction with DIEP flap 28 years old patient, left breast: invasive ductal CA Breast surgeon: mastectomy, lymph node surgery, (SLB, axillary LND) SSM & ms TRAM/DIEP breast reconstruction • Min 175 min (2,9 h) • Max 435 min (7,25 h in billateral} • Average 250 min (4,1 h) Benefit from 2-Team approach even in the OR 1 st team 2 nd team UMC LJ in 2010, 2011, 2012 105 DIEPs S revision = 4, 7% 2 flaps last = 1,9% 98% successful rate 147 DIEPs 6 revisian = 4,1% 1 flaps lost = 0,7% 99,3% successful rate 2013. 2014 100% successful rate 156 DIEPs 6 revisian = 3,8 % 1 flaps last= 0,6 % 99,4% successful rate Comecut,ve series of 293 DIEP flaps w,thout a flap fallure Treating Breast Cancer patients: 1s a "project" which should involve several parties­ the patient herself, her husband & family and a group of medical professionals being her advisors. lf all of these parties work in a coordinated way and act with dedication and professionalism, the treatment can represent nothing more than an unpleasant transitional period from patient back to woman ... Breast Reconstruction lnt�Ji11 partofbn�asl CUlC:l!1' tro.tm�nt 'Jfll11111zat1c,11 ol autoloyou� rJ1easl I·eco ns1rucl"J'1 Ljubljana MC oan 1 ms TRAM/DIEP flap breast reconstruction • Two team approach • the use of reverse engineering technology - Additional team members - mechanical engineer ms TRAM/DIEP breast reconstruction optimization of autologous 2nd breast reconst ruction in Ljubljana MC In order to achievEi better breast symmetry in seco 1dary breast recontruction where the footprint, conus, and skin envelope have been damaged dramatically, reverse engineeri11g technology is used. New te chnique 3D image of the remaining breast i:; taken according to the instruction from ti" e plastic surgeon w th 3D scanner by mechanical enginEier. Faculty of mechanical engino, ering New technique (healthy breast replica and a mold) The mold has negative geometry of the contralateral breast and is used for tissue shaping during surgery. Positioning of the flap according to KSP (4+4) is done in few minutes with staples - - - - f- - - -r -�--,. Problem outline 1 1-3 pozitivne bezgavke • Odprto vprašanje: RT res potrebna pri vseh starostih in pri vseh bioloških podtipih? Pri vseh (enaka) dobrobiti • Čakamo objavo napovedane an alize, zaenkrat 1,e odločamo individualno glede na starost bolnic •� in biološke lastnosti tumorJa Č e je načrtovana RD z lastnim tkivom in RT PriporntilJO odloženo ,ekonstrukciJo 1po RT} ali pa takois;nio RD � tkiv,1im 1azsi1Jevalce111 in po ohsevanJu RD z lastnim tl:1vom Č e je načrtovan vsadek in RT: Priporočajo takojš1110 RD s tkivnim razširjevalcem in po obsevanJu (lahko pa tudi pred niim) trajni vsadek. Tako1š11ja vstavitev tra1nega vsadka n, priporočljiva, če je. predvidena RT (več zapletov) 2. Najprimernejši način rekonstrukcije • NCCN smernice (verzija 3. 2015): pri predhodno obsevanih bolnicah je uporaba tkivnih razši1 jevalcev /vsadkov relati ,no kontrai nd icirana zaradi slabšega estetskega izida (vecja možnost kapsularne kontrakture, malpoziciJe, .. ) Priporoča Jo rek011strukciJO z lastnim tkivom. Tako)",n;a rekonstrukciJa Je kcntraindicirana pri vnetnem ra�u doike- fr11pre1šn1e obsevanie 1 ,.....i.,,. -��RG,!ffiP.�: ... lmmediate Reconstruction of the Radiated Breast: Recent Trend, Contrary to Traditional Standards �II ,\c:anoul- !'11D 1 • Kc-Dey M. K�NL Fba-2. \aran .... � \1D 1 , Jrff'n,- IL Kozlmo. MD, u�•� Krota C. (.,.1111� MD. MS 1 , ud ,\d ".' h,o O, Manmh. :'\1D 1 1 .sc,,..-.,..., uf PL,,.,1� Su lJ rr:,. l'kJ,;anmr:ni „rs...r,:,c,-,,. l'rn•O"NI')' o(M..:hltJfl Mnl;.,;al S..:hnul, ,\1111 Al'N•. Ml: '��nm..111 ,,f H,.,.,;at, Nlld-tlh-q,Admlabdmlm ea,ar.rDni:i:[nl-■"""-"'-"rc•(CDml VL IMPLEMENTATlON OFTifE GUWANCE Sincc therclease oflhe draft version oflhis guidance in May 2012. lhc FDA !ms participaled m puhlic d15eussioos �ing lhis plll.hway for drug dcvelopmcnt In Mmdi 2013 � lbc FDA and Uttl Araem:an Socidy oJCl1nical.Onwlogye&SpOr1SOn:d a pubJic neoudJimml bnast� ===-�����c::=:����� R ba-;cd uponanalysisor.:i. full irueot-M>-ltt31 popul:won was.re3SQmlhly l�ly topredictdirucal bcndiLand lha1 th: pou:mial ad\lUDl:tgeS ofgr:mungaca!lerall!dapproval based uponpCR 1mm a neoadjuvam r.mdonuzcd COlllrollcd tnal genm]iy OUlweigbed conci:ms. Tbc panel cnphasrz.ed lha.Lsuch trials should bclunilC:d to high-nsk paaicnts.and lhal.aconfinnatol)' uial sbould be ongoing al lhc timc: ofllCCcleraled applOval . Povezava med tpCR ter EFS in OS t,.,mt,,,,ormi: f'•LoobjiClll� 6169 """'pjou,r�nso . . ,.,..,...-.:c.....:iom ... tioo, J'<3".,) s,; "' l�7◄ 1523 SJS HR036(95-..(IQ.3l-0-44/ . , �.-�- �- .� . -� .- �- ~Q T.,., .. nco••i>d<>ml1,,11Jontyc,:u>,j tp CR= odsotnost invazivnega raka v dojki in pazdušnih bezgavkah po predoperativni KT EFS= čas brez napredovanja bolezni (izhodišče opazovanja je randomizacija, dogodek je lokalno napredovanje bolezni ali oddaljeni zasevki ali smrt iz kateregakoli razloga OS= celotno preživetje (izhodišče je randomizacija, dogodek je smrt) Cortazar Pet al. Lancet 2014; 384: 164--72 Združena analiza 12 kliničnih raziskav predoperativne KT (N=11955) Namen raziskave: ► ugotoviti povezavo med patološkim popolnim odgovorom in časom brez ponovitve bolezni ter celotnim preživetjem, ► razpoznati ustrezno definicijo patološkega popolnega odgovora, ki najbo l jše korelira z izhodom bolezni, ► razpoznati podtipe, pri katerih patološkim popolnim odgovorom najboljše korelira z izhodom bolezni in ► ugotoviti ali večji delež patološkim popolnim odgovorom napoveduje izbo l jšanje preživetja brez napredovanja bolezni (EFS) in celotnega preživetja (OS) N•'733 Prime,javs dveh neosdjuvsntnih KTshem 3 NSABP B-27 N=2411 Neosdjuvanlna KT vs. adjuvantna KT' NSABP B-18 N = 1523 Neoedjuvantns KT vs. sdjuvsntns KP 1 Unteh M e/al, JC/m On<:e/2009 27:293a-29<15 2 von M1�kwatzG . 1t1a/. JC/mOncoi 2005; 232676-2685 3 Unteh M . er;i/ , Ann Onr:Q/2011; 22"1999-2006 4 Boonefo1 H . •tal. Lan<»/ Onco/2011; 12527 - 539 5 vonM1nckwrtzG,ltla/ AnnOnco/2005, 1656-63 6 vonMmckw11ZG,"1a/.JNaUCallCB'lns/2008 100552-562 7.BearHD , ataJ.JC/,nOnco/2006,242019-2027 S WolmarkN tilal.JNaUCaflC9'/n,;/ Monog-2001: �96-102 9 G1an111 L ela/. JC/mOnco/2009, 272474-2481 10, Gianm L . e/a/ Lan"tlt Onco/201◄ 15640-647. 11 UolCh M, Iti;,/ JC/m Onco/2011 293351-33.57 12 ven M1nciOj)lalin/pakfilaksel , Roka C 'PlacebO+ pl�cebo/paldi1aksel . AC na28ll3 tedne x 4 � Veliparib: 2x 50mg po 12 tednov: karboplatin: AUC 6 iv a 3 tedne x 4: paklitaksel 80mglm 2 tedensko x 12 AC:doksorubicin 60 mg/m 2 /ciklofosfamid 600 mg/m 2 p E R ,A C J A Povezava med mutacijo BRCA in odgovorom na predoperativno KT s cisplatinom Byrski BRCA1 mutacija KT brez soli platine 90 14(16%) BRCA 1 mutacija Cisplatin75 mg/m2 x 4 107 65(61%) Silver brez BRCA mutacije Cisplatin75 mg/m2 x 4 26 4(15%) BRCA 1 mutacija Cisplatin 7 5 mg/m2 x 4 2 2 (100%) Ryan Brez BRCA mutacije Cisplatin75 mg/m2 x 4 + 51 8(16%) Bevacizumab 15 mg/kg x3 �� /o��:�/J�� � ���� : ;�� 379; Byrskj T, et al. Breast Cacer Res Treat 2014; 147 (2):401-5; Silver DF, et al JCO 2010; 28(7):1145-53, Trenutna priporočila izbora predoperativne KT za HER2 negativne rake ►Kemoterapija z antraciklini in taksani v sosledju (npr): , FEC na 3 tedne 3-4x-+ DOCE 100 na 3 tedne 3-4x ► FA(E)C na 3 tedne 3x -+ Paklitaksel 60 tedensko x 12 , AC 00 x 4 na 2 tedna 4x-+ Paklitaksel 60 tedensko x 12 , AC 00 x 4 na 2 tedna 4x-+ Paklitaksel 175 na 2 tedna x 4 ►Soli platine (še) niso vključene v trenutna priporočila ; KT NAJ BO-ZAKLJUČENA PRED OPERACIJO! NeoALTTO: rezultati ► Večji delež pCR pri dvojni anti HER2 terapiji (46.8% vs 27.6%, 20.0% z samo enim anti- zdravilom) ► EFS in OS nista različna med skupinami EFS 100 80 - Lapatinib + trastuzumab i 60 -Lapatinib - Trastuzumab 3-YrEFS,Y. LL 40 w EvNits.n (95%0) HR(95%Clj Lupeli!,lb• 30 84(77-.e9) 078(047- 128) 20 •�tuz:umab �,ijb ,. 78( 70-&4) 106(066-169) T""""""b .,, 76 ""'2) o o 2 3 PV..., " 4 os 100 � 80 �:a- 3-YrEFS,% Evfflls,n {95%CI) HR(!W'I. :IJ PVa1ut- l..lpali11ib„ 13 95(90-68) 0.62(030- 2S) 1i 20 ---- � Lapali11ib 18 93(87-96) D86(045- 53) 6S 0 +- T - - - - • � • _ ,, __ '° _ ' ... �"-'------, O 2 3 4 �----- - -- ------ - -- - - ---- - - - - d _ e _ A.. _ a m _ b _ u ;.. j a _ E _ , _ • t _ a _ l . _ La ,cet Oncol. 2014;15:1137-1146 NeoALTTO/BIG 1-06: Predoperativna terapija s lapatinibom in/ali trastuzumabom ► Randomizirana, multicentrična, odprta klinična raziskava faze III HER2+ rak dojk; ECOG PS0-1 (N = 455) teden 6 l teden 18 teden 52 l i Lapatinib Trastuzumab Operacija+ FEC x 3 adjuvantno •1apatinib 1500 mg/dan; trastuzumab 4 mg/kg, nato 2 m�/kg tedensko; .. lapatinib 1000 mg/dan, znižan odmerek na 750 mg/dan s paclitakselom, paclitaksel 8C· mg/m 2 /teden . NeoSphere: načrt in cilji raziskave Bolniki zo perabllnlm ali lokalno napredovalfm/vnetnim• HER2 pozitivnim rakom dojk Kernc-naivni, primarni tumorji >2 c:m (N::417) Umik prejemanja: na 3 tedne x4 o p E R A C A Baselga J, et al. Lancet 2012 ;379:633-640, • Primarni cilji: Primerjava deležev bpCR TDvs PTD TDvs PT PTD vs PD • Sekundami cilji: PFS DFS Varnost • Druge analize: PFS glede n;.1 status hormonskih receptorjev Povezava med PFS i tpCR Giarmi L, e/ a/. Larrcet OnCQ/ 2012: 13:25-32 NeoSphere: načrt in rezultati pCR Bolniki z operabilnim ali lokalno napredovalim/vnetnim* HER2 pozitivnim rakom dojk Kerna-naivni, primarni tumorji >2 cm (N=417) -- u,nOc pt(ljem>U'lj.a: o, 3 tedne x p R A C A p:0 . 0198 60 U 50 � 40 +I 30 �20 'a 10 TD PTD PT PD 80 U 7 0 "" 60 g: 50 � 40 � JO f5 20 .8' 10 o TD PTD PT PD HR,hormonskireceplorji; HR•pozilivni=estroger,skilnlaliprog81;leronskireceptorjipozilivni: �Wli„OW,;,.=lciill.�r9�� Gl-aMI.L.�._L.1,11,WGilci:lf2Q-l�t� NeoSphere: rezultati PFS 100 � . . ..: ... :, 90 80 70 ';i/. 60. "' so 40 30 20 TD n=107 PTD n=107 -- , --L-.. •• , • .••.• . N,l�I' , / PT n=107 PD ••••• TD PTD PT n=96 - PD lO , � .. s-� " le_tn� i �P�FS�.�%� ( 9�5�%- 8 _ 1 _ ( 7 - 1-8 - 7 ) _ 86 _ ( 77 _ --9 _ 1 _ ) _ 7 _ 3 _ ( 6 - .... - , - J - 7 _ 3 _ ( 6 _ 3-8 _ 1 _ ) o+""'---�--..:.....--''--..:...--'�..:....--'�,',-----'-� o 12 24 36 48 60 meseci n atdsk TD 107 101 89 83 78 58 PTD 107 99 94 88 86 63 PT 107 93 86 ao 7 7 55 PD 96 as 76 72 69 57 PFS=čas brez nacredovanja botezn1 (Izhodišče opazovanja f e random:izacqa} NeoSphere: dopolnilna sistemska terapija Bolniki z operabilnim ali lokalno napredovalim/vnetnim" HER2 pozitivnim rakom dojk Kemo-naivni, primarni tumorji >2 cm (N=417) Umik prejemanja: na 3 tedne x NeoSphere: rezultati DFS 100 ,., , ,, 90 80 70 ';i/. 60 "' so :s 40 30 20 TD PTD n "' 107 n•107 10 - ✓-.1 PT PD nc107 n=96 o 5-letni DFS, % (95% CI) 81 (72--ee) 84 (72-91) 60 (70-86) 75 (64-83) o 12 24 36 48 meseci n atrlsk TD 103 92 as 79 n PTD 101 96 92 88 as PT 96 91 87 81 75 PD 92 81 76 72 66 DFS=čas brez napredovanja bolezni (izhodišče opazovanja je operacija) ·= ••••• TD PTD PT PD 60 12 17 10 29 Trenutna priporočila predoperativne sistemske terapije za HER2 pozitivne rake ►Kemoterapija v sosledju antraciklinov in taksanov+ trastuzumab +/- pertuzumab (npr): ► FEC na 3 tedne 3x- DOCE1 00 na 3 tedne 3x + trastuzumab +/­ pertuzumab na 3 tedne ►AC na 3 tedne x 4 - DOCE 100 na 3 tedne 4x + trastuzumat +/­ pertuzumab na 3 tedne KT Zlll