Benefit of Adjuvant Radiotherapy After Breast-Conserving ...
Adjuvant Radiotherapy in Endometrial cancer
Transcript of Adjuvant Radiotherapy in Endometrial cancer
Adjuvant Radiotherapy in Endometrial cancer
February 27th, 2016
FERAH YILDIZ
What we have known in theadjuvant setting
Uterine confined disease:
• EPRT improves LCRs in patients withintermediate risk EC
• No OS benefitPORTEC I, GOG 99
What we have known in theadjuvant setting-II
For patients with dx outside the uterus
• ERT improves pelvic control
• CT improves systemic and abdominalcontrol
Cochrane metaanalysis, 2012
What has changed in Uterusconfined dx?
– Long term results of PORTEC 1 published
– GOG 99 supported the PORTEC results
– Mature results of PORTEC-II changed thetx policy
• 1990-1997, 714 pts• Int risk or HIR• HIR: 2/3 risk factor
– Gr3, ≥60y, >%50 MITAH+BSO , then NFT or EPRTHIR %51 %52
70% recurrence when NFT located in vaginaNSD in secondary cancer risk
EBRT after TAH-BSO-LND
GOG 99• 448 pts: Int risk or HIR• Fup: 69 m• TAH/BSO+LND
EPRT vs NFTRR 3% 12%OS NSD
Keys HM et al, Gynecol Oncol, 2004
YUN5
Slayt 7
YUN5 Burada özl le HIR de pelvik ve vajinal nuls izlem kolunda fazla ama bu GS a yansımıyor. Yazarlar sadece HIR de EPRT juygulanmalı diyorYour User Name; 29.01.2016
EPRT in Int risk EC
– İmproves LC– NSD in OS
– Why?• 70-75% of recurrences are located in vagina
and salvage rates are high
No need for EBRT
YUN6
Slayt 8
YUN6 Özellikle HIR de LOk kontrol avantajı belirginYour User Name; 29.01.2016
ERT vs BRT
Can we use vaginal BRT instead of EBRT?
• Phase III trialsPORTEC2, 2010Sorbe B et al, 2012
PORTEC 2
• 427 pts, HIR
gr 1-2, ≥ 50% MI, age>60ygr 3Cervical glandulary inv
Nout RA ve ark, Lancet 2010
YUN8
Slayt 11
YUN8 Merkezi Pat değerlendirmesi yapılan 316 hastada ise LBRR %2,4 vs %4.8 ve p:0.42
Pelvik nüks : %0.6 vs %3.3 ve p: 0.06
Your User Name; 30.01.2016
PORTEC 2
TAH+BSO then EPRT vs BRTfup 45 m
4y LRR: %2.1 vs %5.1 p: 0.17Pelvic rec %0.5 vs %3.8 p: 0.02
Nout RA ve ark, Lancet 2010
YUN7
Slayt 12
YUN7 Merkezi Pat değerlendirmesi yapılan 316 hastada ise LBRR %2,4 vs %4.8 ve p:0.42
Pelvik nüks : %0.6 vs %3.3 ve p: 0.06
Your User Name; 30.01.2016
• Surgery then BRT vs EPRT+BRT• fup: 62 m
• 5yLRR %5 vs %1.5• OS NSD• İncrease in toxicity with EBRT
Recent developments in EC
Risk groups
• Low risk
• Intermediate risk
• High-Intermediate risk: HIR
• High risk
Low risk
• USAStg I +Grade1-2<%50 MIendometrioidno LVSINo cervical inv
No residual dx after D&C<60y
• EuropeStgI +Grade 1-2<%50 MIendometrioidNo LVSI
Low risk EC
SurgeryTAH+BSO
Recurrence Risk <%5No need for adjuvant treatment
ESMO-ESGO-ESTRO, 2016ASTRO 2014ASCO 2015
Ingtermediate Risk/HIR
• ASTRO-ASCO
Limited to uterus+ risk factor
≥%50 MIhigh grade>60yLVSICervical inv.
ESMO-ESGO-ESTRO
• Orta Risk • HIR
Stg IA+grad 3Stg I gr1-2+LVSI
• IntermediateStg I +grade1-2≥%50 MIendometrioidno LVSI
Intermediate Risk EC
Is there a need foradjuvant RT?
If so, How?EPRT?BRT?
ASTRO-ASCO recommendation
• ≥50% MI+g1-2• < 50% MI+g3
After surgical stagingBRT alone is an effective adjuvant Tx.
ESMO-ESGO-ESTRO
• Stg IB, g1-2, no LVSI
– Adjuvant BRT is recommended todecrease vaginal recurrence
(Level of evidence I)
– No adjuvant tx is an option for pts aged<60y
(Level of evidence II)
HIR Endometrial cancerBRT?
EBRT?NFT?
HIR: g3, LVSI
– PORTEC 15y LRR : 20% vs 5%
– GOG 995y LRR: 26 % vs 6%
HIR: ASTRO recommendation
• ≥ 50% MI+ g3 or cervical stromal inv. EPRT is recommended to reduce pelvic
recurrence
However: ≥ 50% MI, g1-2 + >60y or LVSI…may alsobenefit from EBRT
ESMO-ESO-ESTRO
• Stg IA + gr 3• Stg IB, gr1-2 +LVSI
No LN met after surgical stagingAdj BRT (LOE III, Strength of Rec B)
NFT (LOE III, Strength of Rec C)
ESMO-ESO-ESTRO
• Stg IA + gr 3• Stg IB, gr1-2 and LVSI
No surgical nodal stagingEPRT to decrease PRR when LVSI (+)BRT alone for gr 3 and LVSI(-)Sys CT is of uncertain benefit
High Risk EC
High Risk EC
• ≥50% MI+g3………..stgIII
• Stg IVA?
ESMO-ESGO-ESTRO
High Risk• Stg IB-g3• Stg II• Nonendometrioid• Stg III, RO
resection
Advanced• Stg III, R1 res.
• Stg IVA
Stg III, RO resection
TAH,BSO, Surgical staging5y DFS: %58, OS: %64RR: %41
pelvic: %32DM: %46 LRR: %54pelvic+DM: %22
Ayhan A et al, Eur J Gynecol Oncol, 2002
Prognostic factor- Recurrence pattern
• >50%MIgrade 3
• Cervical stromal invLN met
• (+)cytologySPK, Clear cell hist
• Hematogen
• Lymphatic
Pelvic side wall
• Whole abdominalcavity
Mariani et al, 2004, Randal et al, 1994, Greven et al1993
Adjuvan RT how?
• Whole abdominal RT(TART)?
• Tumor directed RT : EPRT, PART?
• BRT only with CT?
WART
• Whole peritonealcavity: 30 Gy/20f
• +15 Gy pelvic ± PA RT
WART vs CTGOG 122• 388 stg III-IV patients• WART vs 8 cycles CDDP-ADR• fup: 74 m
– PFS: %38 vs %42– OS: %42 vs %53– % recurrence: %54 vs %50
Randall ME ve ark, JCO 2006.
GOG 122
• RecurrencePelvik(%) Abd(%) DM(%)
WART 13 16 22CT 18 14 18
GOG 122
• No optimal surgery<2 cm rezidue !!!!!!, LND optional
• RT inadequate and toxic30 Gy WART+15 Gy pelvic RTPART when there is no PALND.
Can we limit RT todisease spesific sites?
CT vs EPRT/phase III trials
– İtalian GICOG: stg ICG3-III• 5 cyles CA vs 45-50 Gy EPRT
– JGOG 2033: EICG3-III• 3CAP vs 45-50 Gy EPRT
GICOG
J GOG 2033
• 385 pts, stgIC-III+>50 % MI• TAH+BSO+LND--- RO resection• 45-50 Gy EPRT vs ≥3 cycles CAP• fup: 60 m
PFS: %83.5 vs %81.8 NSDOS: %83.5 vs %86.7 NSD
Susumu N ve ark, Gynecol Oncol , 2008
Cochrane Metaanalysis 2012• After optimal surgery• CT vs RT
– Risk of death (HR): 0.86 NSD– CT decreases systemic and abdominal RR– RT decreases PRR
Can we use both CT and RT?
• Purpose: – Efficient control in reducing recurrence
inside and outside the pelvis
• BUT WITHOUT : – İncreasing the toxicity…..
How to combine CT and RT?
GICOG, J GOGRT vs CT
• Compliance to tx– RT: 88-98% KT: 75-97%
• Complication type– RT: bowel– CT: bone marrow
EPRT vs EPRT+CT• NSGO ve EORTC 55991
– 382 pts %81-90 Stg I– EPRT±BRT vs EPRT+4 cycles CT
• MaNGO- ILIADE III – 157 pts, Stg II-III, fav histology– EPRT±BRT vs RT+3 cycles CT
• Finland– 156 pts, Stg IG3-III– EPRT vs RT+3 cycles CT
• GOG 34– 181 pts, Stg IC-III– ERT vs ERT+ADR
Metaanaliz 2012
Cochrane Collaboration, 2012
The absolute difference with CT: %6 in OS
RT katkısı ne?>%50 MI+G3
ERT offers 10% survivaladvantage
RT vs CT-RT
RTOG 9708phase II, 46 ptsStg IC-II, g2-3, Stg IIIA-C145 Gy EPRT+BRT, CDDP in 1.-28. days
+ 4 cycles CDDP-Paclitaxel
Greven K ve ark, Gynecol Oncol, 2006
RTOG 9708
• fup: 4.3 y– 4y OS: 85 %– Stg III : 77%
• Tx compliance >90%• G3-4 compl: 16%-5%
What we are waiting for?
• PORTEC 3Conc CRT vs EBRT
• GOG 258CRT vs CT
• EORTC 55102CT vs izlem
YUN4
Slayt 49
YUN4 PORTEC 3 ve GOG 258 sonlandı. EORTC devam ediyor. Burada LN negatif, Yüksek riskli hastalar alındıYour User Name; 30.01.2016
EPRT vs CT + BRT
• GOG 0249• phase III, 601 high risk pts• EPRT vs 3 T/KP+BRT
2y OS : NSDSignificant increase in hem toxicity with CT
Mc Meekin et al, SGO annualmeeting, 2014, Abst LBA1
ASTRO recommendation• High risk EC
– EBRT standard of care
– EBRT +BRT when there is high risk of vaginal recurrence
ESMO-ESGO-ESTRO
• After surgical stg, stg IB g3
EPRT to decrease LRR (LOE I)
BRT may be considered as an alternative todecrease vaginal RR (LOE III)
Systemic CT: under investigation
ESMO-ESGO-ESTRO• No surg staging, Stg IB g3
EPRT generally recommended for pelviccontrol and RFS (LOE III)
seq CT-RT may be considered in to improvePFS and CSS (LOE II)
There is more evidence to support giving CT and EBRT in combination rather than either txalone (LOE II)
ESMO-ESGO-ESTROStg II dx
Surgical Stg
g1-2, LVSI(-)BRT (LOE III)
g3, LVSI (+)EPRT (LOE III)
+BRT: (LOE IV)
CT: under investigation
No surgical Stg
EPRT standard of care
Consider BRT boost
G3, LVSI(+): Seq adj CT
ESMO-ESGO-ESTROStg III - RO resection
EBRT to decrease PRR (LOE I) to increase PFS (LOE I) to increase OS (LOE IV)
CT to increase PFS and CSS (LOE II)
ESMO-ESGO-ESTRONonendometrioid
Serous, clear cell
CTLOE III
Stg IA, LVSI (-)Only BRT : LOE IV
≥Stg IB, esp in LN + dxEBRT+CT: LOE III
Carcinosarcoma, Undiff
CT LOE II
EPRTLOE III
Optimal Timing of CT-RT
RTOG 9708, phase II trial• Stg I, >50% MI+ g3- stg III• EPRT+conc CDDP—4 cycles of adj
Taxane-Platin
• 4y OS: 85%• 4y DFS: 81%• 4y PRR: 2 %
Greven K et al, 2004
ASTRO recommendation
• Concomittant CRT-----adj CT
• However sequential combinations arealso welcome.
In conclusion…..• Uterine confined EC
– Low risk: No role of adj RT
– Intermediate risk: Vaginal BRT only
– HIR: EBRT, BRT only in certain pts
• High Risk, advanced EC: EBRT