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KONTROVERSEN IN DER RADIOTHERAPIE DES MAMMAKARZINOMS. GUENTHER GRUBER Institut für Radio-Onkologie Klinik Hirslanden, Zuerich guenther.gruber @ hirslanden.ch. KONTROVERSEN - RT. INDIKATION VOLUMINA RT - PLANUNG RT – APPLIKATION. KONTROVERSEN – RT BRUSTERHALTUNG.

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slide1

KONTROVERSEN IN DER RADIOTHERAPIE DES MAMMAKARZINOMS

GUENTHER GRUBER

Institut für Radio-Onkologie

Klinik Hirslanden, Zuerich

guenther.gruber @ hirslanden.ch

slide2

KONTROVERSEN - RT

  • INDIKATION
  • VOLUMINA
  • RT - PLANUNG
  • RT – APPLIKATION
slide3

KONTROVERSEN – RT

BRUSTERHALTUNG

Bei welchen Pat. kann auf eine RT nach

Brusterhaltung verzichtet werden?

slide4

BREAST CONSERVATION

EBCTCG 2000 RT metaanalysis, Lancet 12/05

N0 N+/N?

n=6097 n=1214

%

p<0.00001p=0.006 p<0.00001 p<0.01

slide6

BREAST CONSERVATION

CONCLUSION

  • BC surgery: No omission of RT !
slide7

BREAST CONSERVATION

INVASIVE CANCER

  • Omission of RT in ‚low risk‘ ?
slide8

BREAST CONSERVATION

BC surgery +/- RT

Swedish Breast Cancer Group, EJC 2003

median tu-size: 12mm; n=1187;

median F-up: 8J

14%

4%

slide9

BREAST CONSERVATION

BC surgery +/- RT, pT1a/pT1b pN0

16.5

9.3

p<0.0001

p=0.01

2.8

NSABP B-21, n=1009; JCO 2002

slide10

BREAST CONSERVATION

Local relapse rates, pT1a/pT1b pN0

Age 70+ ?

Therapy,-ies n LR

TAM 43 3 (7%)

RT 59 5 (8%)

TAM+RT 57 0

RT vs. TAM => HR 1.06 (0.25-4.46) !

NSABP B-21, n=1009

JCO, 2002

slide11

BREAST CONSERVATION

… in T1, N0, R0, ER+ (in 97%), >70yrs

CALGB, RTOG, ECOG (Hughes et al. NEJM, 9/2004)

n=636 (75+ years: 55%)

median F-up: 5J

LOCAL RELAPSE

with tamoxifen 4%

with tamoxifen and RT 1%

p<0.001

slide12

BREAST CONSERVATION

T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)

5yrs LR

-2cm, R0, HR+ n=611

Tam 3.2%

Tam + WB-RT 0.4% (p<0.001)

-1cm, R0, HR+ n=263

Tam 2.6%

Tam + WB-RT 0% (p=0.02)

Files et al., NEJM 2004

slide13

BREAST CONSERVATION

T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)

5yrs LR 8yrs LR

-2cm, R0, HR+ n=611

Tam 3.2% 15.2%

Tam + WB-RT 0.4% (p<0.001)3.6%

-1cm, R0, HR+ n=263

Tam 2.6%

Tam + WB-RT 0% (p=0.02)

+ 3J

x 5 !

Files et al., NEJM 2004

slide14

BREAST CONSERVATION

T1/T2, >50yrs: 769 randomised (of 1572 ‚eligible‘ pts.)

5yrs LR 8yrs LR

-2cm, R0, HR+ n=611 (B21)

Tam 3.2% 15.2%(16.5%)

Tam + WB-RT 0.4% (p<0.001)3.6%( 2.8%)

-1cm, R0, HR+ n=263

Tam 2.6%

Tam + WB-RT 0% (p=0.02)

+ 3J

x 5 !

Files et al., NEJM 2004

slide15

BREAST CONSERVATION

postmenop., T <3cm, N0, ER+ and/or PR+

ABCSG 8 (8A) (Pötter et al. ASTRO, OEGRO, ECCO 13, 11/2005)

n=826 (60+ years: about two thirds)

median F-up: 42 mo

LOCAL RELAPSE 5yrs

with Tamoxifen/AI 4.5%

with Tamoxifen/AI and RT 0.6%

p=0.001

slide16

BREAST CONSERVATION

„low risk“ – studies

summary

Follow up still too short !

No subgroup of pts.

which does not profit from RT!

IMPORTANT: Trade-offs !

If overall survival > 5yrs: RT !

slide17

BREAST CONSERVATION

CONCLUSION

  • BC surgery: No omission of RT !
  • No omission of RT in ‚low risk‘ !
slide18

BREAST CONSERVATION

INVASIVE CANCER

  • Breast conserving surgery: Omission of RT ?
  • Omission of RT in ‚low risk‘ ?
  • PBI for ‚low risk‘ ?
slide19

BREAST CONSERVATION

CONCLUSION

  • BCT + Mastectomy equivalent !
  • BC surgery: No omission of RT !
  • No omission of RT in ‚low risk‘ !
  • The target is the whole breast !
slide20

BREAST CONSERVATION

INVASIVE CANCER

  • BCT vs mastectomy ?
  • Breast conserving surgery: Omission of RT ?
  • Omission of RT in ‚low risk‘ ?
  • PBI for ‚low risk‘ ?
  • Altered fractionation?
slide21

BREAST CONSERVATION

altered fractionation

Stage I/II

n=1234

R

42.5Gy/2.65Gy

22 days

n=622

50Gy/2Gy

35 days

n=612

median f-up : 69 months

Whelan et al., JNCI 94, 2002

slide22

BREAST CONSERVATION

altered fractionation

LRFS DFS

100%

95%

Whelan et al., JNCI 94, 2002

slide23

BREAST CONSERVATION

altered fractionation

T1-3 N0-1

n=1410

R

39Gy/3Gy

5 wks

n=474

42.9Gy/3.3Gy

5 wks

n=466

50Gy/2Gy

5 wks

n=470

median f-up : 9.7 years

Owen et al., Lancet Oncol, 2006

slide24

BREAST CONSERVATION

altered fractionation

Owen et al., Lancet Oncol, 2006

slide25

BREAST CONSERVATION

CONCLUSION

  • BC surgery: No omission of RT !
  • No omission of RT in ‚low risk‘ !
  • The target is the whole breast !
  • There are equivalent schedules !
slide26

BREAST CONSERVATION

INVASIVE CANCER

  • Breast conserving surgery: Omission of RT ?
  • Omission of RT in ‚low risk‘ ?
  • PBI for ‚low risk‘ ?
  • Altered fractionation?
  • Increase of dose (boost) ?
slide27

BREAST CONSERVATION

Local recurrences after BCS + RT BOOST versus NO BOOST

no boost boost H.R.

  • Lyon 5 y 4.5 % 3.6 % (10 Gy) 0.80 p = 0.044

n = 1024

  • French M.C. 5 y 6.8 % 3.6 % (16Gy) 0.53 p = 0.13

n = 664

  • EORTC 10801 5 y 6.8 % 3.4 % (15Gy) 0.59 p = 0.0001

n = 5569

slide28

BREAST CONSERVATION

BREAST-RT +/- BOOST

- 40J (n=449)

41-50J (n=1334)

p=0.02

p=0.002

51-60J (n=1803)

> 60J (n=1732)

p=0.07

p=0.11

Bartelink et al., NEJM 2001

slide29

BREAST CONSERVATION

CONCLUSION

  • BCT + Mastectomy equivalent !
  • BC surgery: No omission of RT !
  • No omission of RT in ‚low risk‘ !
  • The target is the whole breast !
  • There are equivalent schedules !
  • Boost efficient (! <50yrs !)
slide30

RT – BREAST CANCER

‚TIMING‘

RT – Tamoxifen: simultaneous vs sequential

Journal of Clinical Oncology, Vol 23, No 1, 2005

* 3 (small) retrospective studies

z.B. Ahn et al, 2005

OS

LRFS

slide31

RT – BREAST CANCER

‚TIMING‘

RT – Tamoxifen: simultaneous vs sequential

Lokalrezidiv

Bentzen, S. M. et al. JCO; 23:6266-6267 2005

slide32

RT – BREAST CANCER

‚TIMING‘

RT – 6xCMF: ‚RT first‘ vs ,CMF first‘

Breast conservation; n=244

DFS

No significant difference!

Bellon, J. R. et al. JCO; 23:1934-1940; 2005

slide33

RT – BREAST CANCER

‚TIMING‘

RT – 6xCMF: ‚RT first‘ vs ,CMF first‘

Breast conservation; n=244

DFS

DMFS

No significant difference!

Bellon, J. R. et al. JCO; 23:1934-1940; 2005

slide34

RT – BREAST CANCER

‚TIMING‘

RT – 6xCMF: ‚RT first‘ vs ,CMF first‘

Breast conservation; n=244

DFS

DMFS

OS

No significant difference!

Bellon, J. R. et al. JCO; 23:1934-1940; 2005

slide35

RT – BREAST CANCER

‚TIMING‘

‚ChT => RT‘ vs ,simChT/RT‘

ChT= mitoxantrone, 5-FU, cyclophosphamide; 6 cycles

RT= 50Gy/2Gy; +/- boost

ARCOSEIN III trial (n=214 for late toxicity)

! No difference in acute toxicity !

(skin, esophagus, infections, neutropenia)

! No statistical difference in grade 2 or higher

breast edema, lymphedema, pain !

! simChT/RT: Significant more breast atrophy,

subcutaneous fibrosis, teleangiectasia, skin pigmentation !

Toledano et al.; Int J Radiat Oncol Biol Phys; 2006

slide36

RT – BREAST CANCER

‚TIMING‘

RT – Herceptin ®

N9831: AC->T->H vs AC->TH->H

RT (after BCS or Mx4+LN sim to H allowed)

1460 available for adverse events analyses

median f-up: 1.5yrs

  • Skin reaction (p=0.78); pneumonitis (p=0.78), dyspnea (p=0.87)
  • Cough (p=0.54); dysphagea (p=0.26); neutropenia (p=0.16)
  • Concurrent H-RT is not associated with acute RT adverse events
  • Further follow up is needed for late adverse events

Halyard MY et al. ASCO; 2006

slide37

RT – BREAST CANCER

‚TIMING‘

How to combine RT with systemic therapies ?

Individual

HT:

simultaneous possible

ChT

:

In most centers: ChT -> RT

simultaneous RChT possible

but more side effects!

=> Not recommended

Herc: simultaneous possible (heart!)

slide38

BREAST CONSERVATION

TECHNIQUE / RT APPLICATION

slide40

BREAST CONSERVATION

Hurkmans et al., 2001

Lung

HEART

42 mm

slide42

BREAST CONSERVATION

IMRT

„Open“ homogeneous beam (OB)

Intensity modulatedbeam (IMB)

slide44

BREAST CONSERVATION

IMRT

n=306

R

Standard 2D 3D IMRT

5yrs – Differences in breast appearence (Photos)

60% 48%

p=0.06

(QoL no difference)

Yarnold et al., ECCO 13; 2005

slide45

BREAST CONSERVATION

6MV + 12e

Protons

IMRT

IMRT

Lomax et al.

IJROBP 2003

slide46

TARGET VOLUME ?

SCHLUSSFOLGERUNG

slide47

TARGET VOLUME ?

MAMMARIA INTERNA – RT: SFRO trial

PATIENTS / METHODS RESULTS

n=1281 (1/91 – 12/97); MI-RT+ MI-RT

Median f-up: 65mo Death 19% 19%

Mastectomy Cancer 11% 11%

LR 4% 3%

Meta 17% 20%

CW+Supra CW+Supra+MI

R

slide48

RT – BREAST CANCER

RE-IRRADIATION