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HYPOFRACTIONATED WHOLE BREAST RADIOTHERAPY (RT) AN USEFUL TECHNIQUE FOR THE FUTURE ? Bruno CUTULI MD Radiation Oncology Department Polyclinique de Courlancy.

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Présentation au sujet: "HYPOFRACTIONATED WHOLE BREAST RADIOTHERAPY (RT) AN USEFUL TECHNIQUE FOR THE FUTURE ? Bruno CUTULI MD Radiation Oncology Department Polyclinique de Courlancy."— Transcription de la présentation:

1 HYPOFRACTIONATED WHOLE BREAST RADIOTHERAPY (RT) AN USEFUL TECHNIQUE FOR THE FUTURE ? Bruno CUTULI MD Radiation Oncology Department Polyclinique de Courlancy – REIMS CORS MEETING JUAN LES PINS

2 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

3 Thus, since 1986, several « alternative » RT schemes have been used in order to « simplify » treatment modalities and offer a wider access to patients

4 In 1995, a preliminary study was published by the Institut Curie team (MAHER M. et al IJRBOP 1995, 31 : ) 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)

5 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

6 ROYAL MARSDEN HOSPITAL STUDY OWEN JR LANCET 2006, 7 : 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 Weeks RT (Randomization) 50 Gy / 25 fr.49.9 Gy / 13 fr.39 Gy / 13 fr.

7 RMH / GOC STUDY LOCAL CONTROL – F.U : 9.7 y – 1410 PTS Courtesy of Y. KIROVA

8 RMH / GOC STUDY LATE TOXICITY Courtesy of Y. KIROVA

9 START A TRIAL THE START TRIALISTS 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,

10 LANCET ONCOL 2008, 9 : START A TRIAL

11 LANCET ONCOL 2008, 9 : START A TRIAL

12 LANCET ONCOL 2008, 9 : START A TRIAL

13 LANCET ONCOL 2008, 9 : INCIDENCE OF ISCHAEMIC HEART DISEASE SYMPTOMATIC RIB FRACTURE AND SYMPTOMATIC LUNG FIBROSIS ACCORDING TO FRACTIONATION SCHEDULE

14 START B TRIAL THE START TRIALISTS GROUP Lancet Oncol 2008, 371 : 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 W 2 Gy / f 40 Gy / 15 fr – 3 W 2.67 Gy / f NB : 43% 10 Gy Boost

15 START B 2225 PTS FU : 6 YEARS. LOCAL RECURRENCES : 3.3% 50 Gy 2% 40 Gy

16 START B 923 PTS SUB GROUP BREAST CONSERVING SURGERY AND RT : ESTHETIC RESULTS

17 INCIDENCE OF ISCHAEMIC HEART DISEASE SYMPTOMATIC RIB FRACTURE AND SYMPTOMATIC LUNG FIBROSIS ACCORDING TO FRACTIONATION SCHEDULE LANCET ONCOL 2008, 371 : 1104

18 Comparison among UK trials : - Local control - Toxicity (Breast change and / or fibrosis)

19 COMPARISON LOCAL CONTROL % local control RMH / GOC START A START B Courtesy of Y. KIROVA

20 CANADIAN TRIAL T. WHELAN et al JNCI 2002, 94 : SABCS 2007 : Abs women treated from 1993 to Gy/25f / 35 days (Long arm = SWBI) pT1T2N0 : BCS + RT 42.5 Gy/16f / 22 days (Short arm = AHWBI)

21 BASELINE CHARACTERISTICS SWBI (612) AHWBI (622) AGE > 50Y76%75% T167%69% TAMOXIFEN41% CT11%

22 RESULTS LOCAL RECURRENCES RATES 5 YEARS12 YEARS SWBI3.2%6.7% AHWBI2.8%6.2%

23 ESSAI CANADIEN Récidive locale SABCS Daprès Whelan T et al., abstract 21 actualisé. 0,1 0,08 0,06 0,04 0,02 0 6,2 % Années depuis randomisation ,7 % Récidive (%) SWBI AHWBI Résultats à long terme de la radiothérapie accélérée hypofractionnée

24 ESSAI CANADIEN SABCS Daprès Whelan T et al., abstract 21 actualisé. Survie globale : 84.5% 0,1 0,08 0,06 0,04 0,02 0 Années depuis randomisation Survie (%) SWBI AHWBI À risque Résultats à long terme de la radiothérapie accélérée hypofractionnée

25 ADJUVANT HYPOFRACTIONATED RADIATION THERAPY FOR BREAST CANCER AFTER CONSERVING SURGERY LIVI L et al Clinical Oncology 2007, 19 : Florence University experience 539 pts treated between 1997 and 2003 pT1s (9%), pT1 (79%) or pT2 (12%) Median age : 59 years Median FU : 4.3 years pN+ : 20%CT : 26% TAM : 73% Delivered breast RT dose : 44 Gy/16 f. (2.75/f) 48% : 10 Gy boost

26 RESULTS Local relapse : 10 / % 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 :

27 FRENCH RIVIERA EXPERIENCE (1) Long term results of adjuvant hypofractionated radiotherapy for breast cancer in elderly patients ORTHOLAN C et al IJROBP 2005, 61 : 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

28 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 :

29 SIDE EFFECTS ACUTE (Erythema) LATE (Fibrosis) G119%30% G29%19% G3-5%

30 FRENCH RIVIERA EXPERIENCE (2) Long term results of a hypofractionated radiotherapy and hormonal therapy without surgery for breast cancer in elderly patients COURDI A. et al Radiother Oncol 2006, 79 : pts (median age : 83 years) with 124 BC treated between 1987 AND 1999 by HFRT and Tamoxifen The main reasons for adopting this schedule were patient refusal of surgery, very old age, locally advanced case, and/or comorbid disease RT 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

31 RESULTS Median FU : 41 months Local failure : 19 cases : 15% 5-year local progression-free rate : 78% Breast cancer deaths : 26%

32 COURDI RADIOTH ONCO 2006, 79 :

33

34 FRANCO-ITALIAN EXPERIENCE

35 910 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 + RT Median age : 74 years Lumpectomy : 31% Sugery : AD : 94% Quadrantectomy : 69% Standard : 87% Whole Breast RT Hypofractionated (Toulouse) : 13% pN+ : 30.6% Tamoxifen : 56% CT : 50%

36 RESULTS Median FU : 65 months Local recurrences : 28 / 927 3% Nodal recurrences : 9 / % Metastases : 26 / 910 3% Contralateral BC :51 / %

37 LOCAL RECURRENCE RATES Classical RT (50 Gy/25 f +/- 10 Gy Boost) : 2.7% NS Hypofractionated RT (32.5 Gy/6 f) : 3.7%

38 METASTATIC RISK FACTOR CUTULI B. ONCOL HEMATOL 2009, 71 : 79-88

39 CURIE INSTITUTE EXPERIENCE Breast-conserving treatment in the elderly : long- term results of adjuvant hypofractionated and normofractionated radiotherapy KIROVA Y IJROBP 2009 Analysis of 367 women older than 70 years treated at CI by BCS + RT for T1T2 BC, between 1995 and (median age : 73 y) : NF-RT (50Gy/25 f, classical) +/- boost 50 (median age : 80 y) : HF-RT (32.5 Gy/6 f), no boost Median FU : 93 months

40 LOCAL RECURRENCE RATES 5 Y7 Y NF – RT (317)5%7% HF – RT (50)6%9% KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009

41

42 DISEASE SPECIFIC SURVIVAL RATES 5 Y7 Y NF – RT (317)96%93% HF – RT (50)95%87% KIROVA INT J RADIAT ONCOL BIOL PHYS. 2009

43

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45 La Radiothérapie mammaire hypofractionnée en 13 séances Parfaite tolérance ou réaction cutanée décalée ? *** Etude prospective de lInstitut Curie BOTTI M. et al Cancer Radiothérapie, in press

46 METHODE : Recueil prospectif entre 02/2006 et 03/2007 de toutes les patientes recevant à lIC 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

47 REACTIONS CUTANEES GRADE SEM. 3 SEM 5 (FIN RT) I3459 II07 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 patientes NB : Aucune réaction de grade III-IV na été notée

48 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 séances La 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 loptimisation des techniques. Des études complémentaires sont nécessaires.

49

50 COMPARISON TOXICITY % Récidives locales RMH / GOC START A START B Courtesy of Y. KIROVA


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