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Jm.nogaret

LAUSANNE 13.09.12

IORT screening

minimalist treatments

MAXIMUM TOLERABLE TREATMENT

MINIMAL EFFICACE TREATMENT

SCREENING

SCREENING STAGE

D.C.I.S. 25 %

T < 2 cm 50 %

T > 2 cm 25 %

CONTROVERSIES

• Halsted

• Radiotherapy

• Modified mastectomy

• Adjuvant chemotherapy

• Conservative surgery

• Adjuvant hormonotherapy

• Sentinel node

• Neoadjuvant systemical treatment

• IORT

1900

2012

RADIATION AFTER CONSERVATIVE

SURGERY

• discussions none…

– local recurrences 10 years

– 25 - 30% without RT

– 6 -11% with RT

radiation is indispensable

n

TRUE LOCAL RECURRENCES

• 85% in the tumor bed Van Limbergen ’87, Fourquet ’80, Veronesi ‘2000…

• the % remaining tumor cells decrease from the area where the primary carcinoma exised

Holland ’85 et ‘90

IORT

very selective technique to intensify the local treatment:

a high single dose as exlusive or boost treatment

IORT in Europe

1905 first procedure

C. Comas

(1905, Barcelone)

PARTIAL BREAST RADIATION PBI

• INTRAOPERATIVE

IO(E)RT (NOVAC-7 MOBETRON) INTRABEAM (RX)

• POSTOPERATIVE

MAMMOSITE NEEDLES Ir 192 EXTERNAL RXT 3D OR IMRT

INTRA BEAM

RX 50 KV :

20 Gy contact

10 Gy 5 mm

5 Gy 10 mm

20-30 min

Raggi X 50 Kv

Xoft

Ir-192

! only 20-25 % patients

Pawlik et al. Cancer 2004; 100:490-8

MAMMOSITE

IRIDIUM

Ir-192

IOERT

mobile linear accelerator

can enter into the surgical theatre

Novac7, Hitesys Mobetron, Intraop

0

20

40

60

80

100

120

0 20 40 60

Depth (mm)

Rel

ativ

e d

ose

(%

)

X-ray source 50kVp (higher RBE)

DOSE DISTRIBUTION

QUESTIONS

• Local recurrences ?

• Side effects ?

IORT, a single fraction of radiation, giving a high dose

as

Sole Treatment

Or Boost

IOERT boost

– 6 Institutions ISIORT-Europe – Oct ’98 till May ’05 – 1031 patients – Median FU : 52 months – LR : 5/1031

• DFS : 99.4%

Félix Sedlmayer, Strahlenther Onkol 2007; 183(2):32-34

IOERT boost

• Résults ( Salzburg ) – 378 patients stade I-II – 1996-2001 – Group 1 51-56 Gy + 12 Gy ( external boost )

Group 2 IORT 9 Gy ( boost ) + 51-56 Gy

R.Reitsamer,F.Sedlmayer et all. Int.J.Cancer 2006 jun 1; 118(11):2882-7)

Group 1 Group 2

local reccurences 5 y 4.3% 0%

Survival without recurrences 5y 90.9 % 95.8%

IORT boost

• Jules Bordet experience – 258 patients – 1988-2003 – FU 18 - 206 months – T0, T1, T2<3cm – 15 Gy 192 Ir + 50 Gy ERT

Philippson, Nogaret, Simon et al, Cancer Radiothérapie, 9 (2005) 501)

LR 3.5%

28 Institutions in 9 Countries

2,232 patients enrolled (started March 2000, closed May 2008 )

Age 45 years old or more, with IDC suitable for wide local excision

- IORT (20 Gy at the surface) vs conventional WBRT (40-56 Gy, w/w-out Boost)

- Each center could decide that patients randomized to IORT with

certain pathological finding (lobular, EIC+…) receive WBRT in

addition

Vaidya JS et al, Lancet, July 2010

TARGeted Intraoperative radioTherapy

(TARGIT)

Median age 63 years,

Tumor size < 1 cm in 36%,

50% between 1-2 cm

G3 tumors in 15%,

N+ in 17%

66% hormone therapy

12% chemotherapy

Vaidya JS et al, Lancet, July 2010

-No statistical difference in complication rate (11.5 in Targit arm vs 10.6% in EBRT arm)

TARGeted Intraoperative radioTherapy (TARGIT)

TARGeted Intraoperative radioTherapy (TARGIT)

At 4 years, 6 LR in the TARGIT group (1.2%), 5 in the EBRT group (0.95%)

Milan ELIOT out-trial on 1822 patients

Breast Cancer Res Treat, August 2010

< 1 cm: 613 patients (33.5%)



Negative node: 1301 patients (71.4%)



Grade 1: 467 patients (25.6%)



Absent: 1528 patients (83.9%)



Luminal A: 648 patients (35.6%)

Luminal B: 977 patients (53.6%)

Cerb +++ : 53 patients (2.9%)

Basal: 137 patients (7.5%)

Veronesi & Orecchia, Breast Cancer Res Treat, August 2010

ELIOT

1822 patients • Tumor < 25mm • Jan 2000-Dec 2008 • 21 Gy • médian FU : 36.1 mois

U.Veronesi et al Breast Cancer Res Treat (2010) 121: 141-151

LR 2.3%

Free survival 5 years

Free survival 10 years

97.4%

89.7%

severe fibrosis

mild fibrosis 0.1%

1.8%

ASTRO

suitable

ESTRO

low risk

ASTRO

cautionary

ESTRO

Intermediate

risk

ASTRO

unsuitable

ESTRO

contraindic

ation

Age ≥ 60 y > 50 y 50-59 y 40-50 y < 50 y ≤ 40 y

BRCA 1,2 mut Not present Present

Tumor size ≤ 2 cm ≤3 cm 2.1-3 cm > 3 cm

T stage T1 pT1-2 T2 T3-T4

Margins ≥ 2 mm ≥ 2 mm < 2 mm < 2 mm Positive Positive

Grade Any Any Any

LVSI No Not allowed Focal Not allowed Extensive Present

ER status Positive Any Negative Any

Multicentricity Unicentric only Pluricentric

Multifocality Clinically

unifocal ≤2cm

Clinically

unifocal 2.1-3cm

Multifocal >3cm

Histology Invasive ductal Invasive

ductal

Invasive

lobular

Invasive

lobular

Pure DCIS Not allowed Not allowed ≤3cm Allowed If > 3 cm

EIC Not allowed ≤3cm If > 3 cm

Associated LCIS Allowed Allowed Allowed

Nodal status pN0 (i-,i+) pN0 pN1mi, pN1a pN1, pN2, pN3 pNX, pN2a

Neoadj therapy Not allowed Not allowed Not allowed If used If used

Tableau 1

“Suitable”

1.5% at 5-y

R. Orecchia, Genève, sept 2011

“Good”

1.9% at 5-y

R. Orecchia, Genève, sept 2011

MOBETRON OUR STUDY

INCLUSION CRITERIA

More than 40 years old

Ductal invasive carcinoma (preoperative biopsy)

pT less than 20 mm (peroperative analysis)

Free margins (peroperative analysis)

Unicentric (MRI)

Unifocal (MRI)

All HR

All grade

pN0 (peroperative analysis)

No EIC or LVI (preop biopsy)

MOBETRON

Mobile linear accelerator self

shielded and ‘light’ (1,2 T)

Operate with 9 GHz instead of 3

Accelerated electrons beam

of 4, 6, 9 and 12 MeV

Dose rate: 10 Gy/min

Mobetron

Aluminium applicators of

3 to 10 cm diameter

Flat or beveled (15° et 30°)

boluses of 5 or 10 mm for every applicator

SURGICAL TECHNIC

tumor resection till the muscle detachment of the gland shield positioning on the muscle

suture of the tumor bed applicator positionning

muscle pectoral

face Profil

cône en place-protection de la peau

February 2010 till February 2012

286 selected patients

60 excluded: 226 evaluable

200 exclusive (21 Gy)

26 boost (9 Gy)

FU: 4 to 26 months (mean 13)

Review of our 200 first patients

September 2012 290 patients ( 261 exclusive )

AGE


Age distribution for treated patients

9%

37%54%

40-49

50-60

>60

STAGE


T1a T1b T1c Total

Nb 3 81 120 204

% 1.5 39.7 58.8 100

Review of our 200 first patients Collimator distribution for all patients

Collimator size (dia in mm) distribution for

PBI

45 mm

17,6%

50 mm

36,8%

55 mm

28,4%

60 mm

15,2%

40 mm

0,0%

35 mm

0,5%65 mm

1,5%


ENERGY DISTRIBUTION for PBI

0% 9%

48%

43% 4 MeV6 MeV 9 MeV 12 MeV

Energy distribution

HISTOLOGY


pN0 pN1mic pN1a Total

Nb 190 8 6 204

% 93.1 3.9 2.9 100

AP ductal lobular mixt mucinus Total

Nb 192 7 1 4 204

% 94.1 3.4 0.5 2.0 100

HISTOLOGY: MOLECULAR SUB-TYPE


Nb %

Luminal A 151 74

Luminal B 32 16

Basal like 10 5

HER2neu +++ 11 5

TOTAL 204 100

COMPLICATIONS


Nb %

None 194 95

Hematoma 3 1.5

Infection 3 1.5

Scar rupture 2 1

inflamation 1 0.5

Infection + scar rupture 1 0.5

TOTAL 204 100

COSMESIS


59

32

9

00

10

20

30

40

50

60

%

Cosmesis for PBI Treatments

Very Good

Good

Fair

Bad

CONCLUSIONS (2)


► Importance of preoperative diagnosis

► Follow-up to short in most of the studies and

the risk of local relapse continue after 5 years

CONCLUSIONS (3)


► Complications rate very low

► Side effects moderated

► Maximal protection of the normal tissues

► Gain in quality of life

CONCLUSIONS

obvious progress

MORE EFFICINCY LESS MORBIDITY MORE COMFORT

IORT

YESTERDAY

TODAY

RT post Chimio néo adj+chir

Sein d, A.L, 3 mois

RT post op Co-60

Sein g, 6 mois

Rec bilat post RT bilat

pour multicentrique

TOMORROW

postoperative:

• 3 - 6 weeks

intraoperative:

1 day….

More effective !

RECURRENCES AND SURVIVAL

20% LR 5 years

5% mortality 15 years

EBCTCG, Lancet, 366-déc 2006

Toute vérité franchit trois étapes. D’abord elle est ridiculisée. Ensuite, elle subit un forte opposition. Puis, elle est considérée

comme ayant toujours été une évidence….

ARTHUR SCHOPENHAUER

IORT - Accueilmeeting-com.ch/.../Senologie_septembre_2012/J.-M._Nogaret_-_IORT...• iort 1900 2012...

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