hypofractionated whole breast radiotherapy (rt) an useful technique for the future ? bruno cutuli md...
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HYPOFRACTIONATED WHOLE BREAST
RADIOTHERAPY (RT)AN USEFUL TECHNIQUE FOR THE FUTURE ?
Bruno CUTULI MDRadiation Oncology Department
Polyclinique de Courlancy – REIMSCORS MEETING
JUAN LES PINS 27-06-2009
Altough whole breast RT after conservative surgery is a well established standard, it is still underused, especially in elderly people (20-25% in U.S)
On the other hand, in several countries, RT resources are quite limited and / or very restricted to large cities inducing long delays for RT treatment
Thus, since 1986, several « alternative » RT schemes have been used in order to « simplify » treatment modalities and offer a wider access to patients
In 1995, a preliminary study was published by the Institut Curie team (MAHER M. et al IJRBOP 1995, 31 : 783-789)70 women of 81-year median age were treated between 1988 and 1994 by hypofractionated RT and Tamoxifen (5x6.5 Gy to whole breast + 2 x 6.5 Gy to tumor bed once a week)There were 38 T1T2 and 32 T3T4 (with 28 N1-N2)
RESULTS AT 36 MONTHS
Local control : 86%
Disease specific survival : 88%
…This study demonstrates that very high rates of loco-regional control are achievable using Tamoxifen and high dose per fraction once- weekly RT
ROYAL MARSDEN HOSPITAL STUDYOWEN JR LANCET 2006, 7 : 467-471
1410 PATIENTS INCLUDED FROM 1986 TO 1998
BCS +/- AD (60%) - Median age : 55 y (< 70 y)T1T2 : 94% - pN+ : 37% (out of 60%)Tamoxifen : 64% - CT : 14%
5 WeeksRT (Randomization)
50 Gy / 25 fr. 49.9 Gy / 13 fr. 39 Gy / 13 fr.
RMH / GOC STUDY LOCAL CONTROL – F.U : 9.7 y – 1410
PTS
Courtesy of Y. KIROVA
RMH / GOC STUDY LATE TOXICITY
Courtesy of Y. KIROVA
START A TRIALTHE START TRIALIST’S GROUP
2236 PTS INCLUDED IN 17 UK CENTERS FROM 1998 TO 2002
BCS (85%) or Mastectomy : 15%pN+ : 29% Tamoxifen : 78% - CT : 36%LN irradiation depends of centers
RT (Randomization)
50 Gy / 25 fr.2 Gy / f
41.6 Gy / 13 fr.3.2 Gy / f
39 Gy / 13 fr.3 Gy / f
NB : 61% 10 Gy Boost (e-) Lancet Oncol 2008, 331-341
LANCET ONCOL 2008, 9 : 331-341
START A TRIAL
LANCET ONCOL 2008, 9 : 331-341
START A TRIAL
LANCET ONCOL 2008, 9 : 331-341
START A TRIAL
LANCET ONCOL 2008, 9 : 331-341
INCIDENCE OF ISCHAEMIC HEART DISEASE SYMPTOMATIC RIB FRACTURE AND SYMPTOMATIC LUNG FIBROSIS ACCORDING TO FRACTIONATION
SCHEDULE
START B TRIALTHE START TRIALIST’S GROUP Lancet Oncol 2008, 371 : 1098-1107
2215 PTS INCLUDED IN 23 CENTERS FROM 1999 TO 2001
BCS : 92% or Mastectomy : 8%pN+ : 23% Tamoxifen : 86% - CT : 22%LN irradiation depends of centers
RT (Randomization)
50 Gy / 25 fr – 5 W2 Gy / f
40 Gy / 15 fr – 3 W2.67 Gy / f
NB : 43% 10 Gy Boost
START B 2225 PTS FU : 6 YEARS. LOCAL
RECURRENCES :
3.3% 50 Gy
2% 40 Gy
START B 923 PTS SUB GROUPBREAST CONSERVING SURGERY AND RT :
ESTHETIC RESULTS
INCIDENCE OF ISCHAEMIC HEART DISEASE SYMPTOMATIC RIB FRACTURE AND SYMPTOMATIC LUNG
FIBROSIS ACCORDING TO FRACTIONATION SCHEDULE
LANCET ONCOL 2008, 371 : 1104
CANADIAN TRIALT. WHELAN et al JNCI 2002, 94 : 1143-5
SABCS 2007 : Abs 6
1234 women treated from 1993 to 1996
50 Gy/25f / 35 days
(Long arm = SWBI)pT1T2N0 : BCS + RT
42.5 Gy/16f / 22 days(Short arm = AHWBI)
BASELINE CHARACTERISTICS
SWBI(612)
AHWBI(622)
AGE > 50Y 76% 75%
T1 67% 69%
TAMOXIFEN 41% 41%
CT 11% 11%
RESULTSLOCAL RECURRENCES RATES
5 YEARS 12 YEARS
SWBI 3.2% 6.7%
AHWBI 2.8% 6.2%
ESSAI CANADIEN
Récidive localeRécidive locale
SABCS 2007 - D’après Whelan T et al., abstract 21 actualisé.
0,1
0,08
0,06
0,04
0,02
0
6,2 %
Années depuis randomisation0 2 4 6 8 10 12
6,7 %
Ré
cid
ive
(%
)
1 3 5 7 9 11
612
622
578
592
550
548
499
500
470
447
410
406
218
214
597
609
592
569
553
524
485
472
449
430
317
330
SWBI
AHWBI
Résultats à long terme de la radiothérapie accélérée hypofractionnée
ESSAI CANADIEN
SABCS 2007 - D’après Whelan T et al., abstract 21 actualisé.
Survie globale : 84.5%Survie globale : 84.5%0,1
0,08
0,06
0,04
0,02
0
Années depuis randomisation0 2 4 6 8 10 12
Su
rvie
(%
)
1 3 5 7 9 11
612
622
594
605
573
576
535
539
505
495
453
455
242
241
606
617
583
592
559
562
519
517
487
482
355
369
SWBI
AHWBI
À risque
Résultats à long terme de la radiothérapie accélérée hypofractionnée
ADJUVANT HYPOFRACTIONATED RADIATION THERAPY FOR BREAST CANCER AFTER
CONSERVING SURGERYLIVI L et al Clinical Oncology 2007, 19 : 120-124
Florence University experience539 pts treated between 1997 and 2003 pT1s (9%), pT1 (79%) or pT2 (12%) Median age : 59 yearsMedian FU : 4.3 yearspN+ : 20% CT : 26% TAM : 73%Delivered breast RT dose : 44 Gy/16 f. (2.75/f)48% : 10 Gy boost
RESULTSLocal relapse : 10 / 539 1.8%
negative : 1.7%Margins
(p=0.05)positive : 7%
40 y : 11%Age (p=0.04)
> 40 y : 1.5%
Yes : 0.5%Tamoxifen (p=0.0001)
No : 5.3%
Grade 2 : 21%Fibrosis
Grade 3 : 2.5%(No correlation with CT and / or breast volume)
LIVI Clin Oncol 2007, 19 : 120- 4
FRENCH RIVIERA EXPERIENCE (1) Long term results of adjuvant
hypofractionated radiotherapy for breast cancer in elderly patients
ORTHOLAN C et al IJROBP 2005, 61 : 154-162
150 pts (median age : 78 years) treated between 1987 and 1999 by surgery (BCS : 72%, mastectomy : 28%) and hypofractionated RT (5x6.5 Gy once a week)Boost : 33%Tam : 76%Median FU : 65 months
RESULTS
Local recurrence : 2.3%
DFS : 5y 80% 10y 71%
OS : 5y 72% 10y 46%
DSS : 5y 89% 10y 77%
ORTHOLAN C et al IJROBP 2005, 61 : 154-162
SIDE EFFECTS
ACUTE(Erythema)
LATE(Fibrosis)
G1 19% 30%
G2 9% 19%
G3 - 5%
FRENCH RIVIERA EXPERIENCE (2) Long term results of a hypofractionated
radiotherapy and hormonal therapy without surgery for breast cancer
in elderly patientsCOURDI A. et al Radiother Oncol 2006, 79 : 156-161
115 pts (median age : 83 years) with 124 BC treated between 1987 AND 1999 by HFRT and TamoxifenThe main reasons for adopting this schedule were patient refusal of surgery, very old age, locally advanced case, and/or comorbid diseaseRT was delivered as once-a-week, 6.5 Gy for total dose of 32.5 Gy in 5 fractions, followed with 1-3 fractions of 6.5 Gy to the tumor site
RESULTS
Median FU : 41 months
Local failure : 19 cases : 15%
5-year local progression-free rate : 78%
Breast cancer deaths : 26%
COURDI RADIOTH ONCO 2006, 79 : 156-161
COURDI RADIOTH ONCO 2006, 79 : 156-161
FRANCO-ITALIAN EXPERIENCE
910 women (with 927 treated breast) older than 70 years treated from 1983 to 2000 in three French Centers (TOULOUSE, STRASBOURG, NANCY) and two Italian Centers (BRESCIA, PERUGIA) for a pT1T2 BC by BCS + RTMedian age : 74 years
Lumpectomy : 31%Sugery : AD : 94%Quadrantectomy : 69%
Standard : 87%Whole Breast RTHypofractionated (Toulouse) : 13%
pN+ : 30.6%
Tamoxifen : 56%
CT : 50%
RESULTS
Median FU : 65 months
Local recurrences : 28 / 927 3%
Nodal recurrences : 9 / 927 0.7%
Metastases : 26 / 910 3%
Contralateral BC :51 / 910 5.6%
LOCAL RECURRENCE RATES
Classical RT (50 Gy/25 f +/- 10 Gy Boost) : 2.7%
NSHypofractionated RT (32.5 Gy/6 f) : 3.7%
METASTATIC RISK FACTOR
CUTULI B. ONCOL HEMATOL 2009, 71 : 79-88
CURIE INSTITUTE EXPERIENCE
Breast-conserving treatment in the elderly : long-term results of
adjuvant hypofractionated and normofractionated radiotherapy
KIROVA Y IJROBP 2009Analysis of 367 women older than 70 years treated at CI by BCS + RT for T1T2 BC, between 1995 and 1999317 (median age : 73 y) : NF-RT (50Gy/25 f, classical) +/- boost50 (median age : 80 y) : HF-RT (32.5 Gy/6 f), no boostMedian FU : 93 months
LOCAL RECURRENCE RATES
5 Y 7 Y
NF – RT (317)
5% 7%
HF – RT (50) 6% 9%
KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009
KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009
DISEASE SPECIFIC SURVIVAL RATES
5 Y 7 Y
NF – RT (317)
96% 93%
HF – RT (50) 95% 87%
KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009
KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009
KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009
La Radiothérapie mammaire hypofractionnée en 13
séancesParfaite tolérance ou réaction
cutanée décalée ?
***Etude prospective de l’Institut
CurieBOTTI M. et al
Cancer Radiothérapie, in press
METHODE :Recueil prospectif entre 02/2006 et 03/2007 de toutes les patientes recevant à l’IC une RT mammaire adjuvante de 42,9 Gy en 13 fractions (3.3 Gy/f – 3 sem.) et 5 semaines
POPULATION :- 81 patientes de 40 à 83 ans (age médian : 70 a)- T0 : 53 - T2 : 5- T1 : 21 - T3T4 : 2- Pas de CT ou HT concomitante- 17 TTS en DD et 64 en D2
REACTIONS CUTANEES
GRADE SEM. 3SEM 5
(FIN RT)
0 47 15
I 34 59
II 0 7
Les auteurs ont noté dans ¼ des cas des réactions cutanées de G II 15 jours après la fin de la RT et préconisent une consultation de surveillance pour ces patientesNB : Aucune réaction de grade III-IV n’a été notée
CONCLUSION
La radiothérapie hypofractionnée, en particulier à doses modérées (2.7 – 3.3 Gy/f) semble une alternative de traitement intéressante tout spécialement pour les patientes âgées, permettant soit une réduction de la durée globale du traitement, soit un espacement des séancesLa tolérance immédiate est satisfaisante et les résultats carcinologiques sont équivalents à ceux du traitement classique.La toxicité à long terme semble également acceptable, surtout avec l’optimisation des techniques. Des études complémentaires sont nécessaires.
COMPARISON TOXICITY
0
5
10
15
20
25
30
35
40
45
50
50 42.9 39 50 41.6 39 50 40
% R
écid
ives
locale
s
RMH / GOC START A START B
Courtesy of Y. KIROVA