Ioert To The Tumor Bed

ISIORT Europe

IOERT to the tumor bed, followed by whole breast irradiation:Update of the Pooled Analysis on the

BIO-Boost

Sedlmayer F, Fastner G, Merz F, Reitsamer R, Menzel C Salzburg / ACiabattoni A, Petrucci A Rom SGF Neri / IHagen E Klagenfurt / A Willich N, Schuck A, Brinkmann M Münster / DOrecchia R Mailand /IValentini V Rom UC Gemelli/I

BIO-Boost: Linac-based IORT with Electrons

9-10 Gy IORT Boost +

50 Gy Whole-Breast

Patients ISIORT BIO-Boost Pooled Analysis

„Best Selection“: T1-2 N0 G1-2, >50a: 331 Patients (30%)N-positive and/or G3 and/or T3 and/or Age<45a. 716 Pat. (60%)

T N Grading

Dcis 8 N0 611 T0 5 N1 343 G1 143T1 695 N2 32 G2 538T2 295 N3 7 G3 284T3 7 Nx 9 Gx 3

n.st. 21 29 62

Age: 57,3 a (22,5 – 89,9)

Methods

• Energies 4-12 MeV (6/8 MeV);

• IOERT prescription dose: med. 9,7 Gy (5-17)

• Postoperative WBRT: 50/51Gy (998 pts.)

• Time gap to XRT : 5 wks. (HT) – 28 wks. (ChT)

ISIORT BIO-Boost PA

Analysis 5/08 ISIORT BIO-Boost PA

• 1200 Pat; IORT 10/98 – 12/05

– 60 Pats.: secondary mastectomy– 9 Pat. : refused WBRT– 10 pats. lost to FU– Remaining: 1121 Patients

• Med FU: 59,6 mths. (1 – 114)

Analysis 5/08 ISIORT BIO-Boost PA

• 8 In-Breast Recurrences

• In-Breast Tumor Control Rate: 99,3 %• 93 patients developed metastases • DFS (7a): 87,7 %• DSS 94,5 %• OS 90,2 %

In-Breast Recurrences NN age T/N Stage Grade

HR-Status Location Margins DCIS

GAP IORT/RT (weeks)

Time to Recurr. (mths)

MA 59 pT1c/N0 G3 neg true LR inv.: min. 1,5 mm pos 31,6 12is.: 3,5 mm

JG 54 pT1c(m)/pN0 G3 postrue LR ( DCIS ) R1 neg 3,2 25

TM 68 pT2/N0(i+) G3 neg true LR inv.: min 1 mm pos 6,1 29,3is.: min 1 mm

AS 77 pT2 (m) pN0 G2 pos Out

Quadr. R1 (in situ) pos 4 83

SA 46 G2 pos Out

Quadr. inv.: 4 mm pos 6,7 34

36715 50 pT2/pN0 G1/2 neg Out

Quadr. R0 neg 7 n.s.

PB 52 pT1c/N0/L1 G3 neg Out

Quadr. inv.: R1 pektoral pos 5 30is.: min. 3,5 mm

RR 72 pT2(m)/N0/L1 G2 pos Out

Quadr. Inv.: min. 5 mm pos 8,6 17is.: n.s.

pT1c(m)pN0(sn) L1

In-Breast Recurrences - Summary

• 3 True Local Recurrences– All G3, – close margin status / R1,– time to recurrence: 12 – 29,3 months (med 22)

• 5 Out-Quadrant Recurences– 3/5 multicentric– time to recurrence: 17 – 83 months (med. 41)

• All NO• Prominent DCIS in 6/8• No time gap Influence IORT/XRT

ISIORT Europe BIO-Boost Analysis 5/08:

Disease Free Survival (7a):

N0: 93,2 %N1: 82,9 % N2: 69,1%

T1 : 91,7 %T2 : 85 %

Kaplan-Meier - disease free survival (all data)

65,0

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Survival time [months]Pe

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Kaplan-Meier - disease free survival (all data)

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0 20 40 60 80 100 120

Survival time [months]

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T2

Follow-up 2/08: Disease Specific Survival (7a)

Kaplan-Meier - disease specific survival (all data)

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Kaplan-Meier - Disease-specific survival (all data)

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0 20 40 60 80 100 120


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Kaplan-Meier - disease specific survival (all data)

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T2

7 a: 94,8% (all)

Follow-up 4/07: Overall Survival (7a) 5 a: 95,6%

Kaplan-Meier - overall survival (all data)

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7 a: 91,5% (all)


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T1

T2

Boost-RT for everybody ?

Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882Antonini N, …. Bartelink HRadiotherapy and Oncology 82 (2007) 265–271

Boost (16 Gy) versus No-Boost following WBRT with 50 Gy

n = 5.318 Pat.

Re-Analysis at 77,5 Mo med FU:Boost-advantage for all age groups

Spline Kurve for age and risk for developement of a local recurrenceLN-Transformation function in terms of Hazard Risk ratios (5-a-steps)

1. Age-independent boost effect: halfened LR-Rates2. Reduced absolute LR-Risk with growing age3. Highest absolute gain at ages < 45 a

IOERT with 10 Gy has an iso-effect of at least 17 Gy in standard fractionation

IOERT vs. postop. Boost Int J Cancer 2006

In-Breast Tumor Recurrence

after 5 a:

4,3 vs. 0 % P < 0,01

Why BIO-Boost 10 Gy and not Single Modality (ELIOT) 22 Gy ?

• No “low risk” selection, normal case mix• LQ model not tested for doses > 20 Gy for

equal tumor effects, but predicts significant more normal tissue reaction (fibrosis / necrosis).

• Different Surgical techniques : Tumorectomy ≠ (modified) Quadrantectomy

Bio-Boost Milano/ELIOT

Veronesi, Orecchia et al Ann Surg 2005

Why Boost and not Single Modality?

• Incidence of out-quadrant tumor foci ?– unclear, 30- 80% in pathologic series,

MRI,– 50 Gy WB-RT usually controls out-

quadrant low tumor burden – Distant quadrant IBTR occur later than

true LRs !

In-Breast Recurrence : changing topography with time I

• Freedman et al, IJROBP 2005: 1190 Pat. following WBRT • „True“ Local Recurrence 2%, 5%, and 7% after 5, 10, and 15 a,• Recurrence „elsewhere“ :

1%, 2%, and 6 % nach 5, 10, and 15 a

• Krauss et al. IJROBP 2004 : – 1448 Pat. > 60 Gy, med. FU 8.5 a

• 79 In-Breast Recurrences :– 59 IBR (74.7%) “true” LR / Marginal misses,– 20 (25.3%) Out-Quadrant

• Occurence of “distant-quadrant” recurrences: 39% (5-10 y), und 27% (10-15 y)

In-Breast Recurrence : changing topography with time II

Statement 24a of the S3 guidelines of the German Cancer Society

“ Accelerated partial breast irradiation as a sole intraoperative or postoperative radiotherapy instead of whole breast radiotherapy is an experimental method and should not be performed except in studies (LoE 3, GR A)”

Ioert To The Tumor Bed

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