La radiothérapie stéréotaxique. en cancérologie digestive

Transcription

1 La radiothérapie stéréotaxique en cancérologie digestive Marseille 22 novembre 2012 PY Bondiau PhD. MD. Centre Antoine Lacassagne. Nice. France High Precision Radiotherapy Unit Cyclotron / Cyberknife 1

2 Clinical indications Head/neck Re irradiation Boost Brain. shwanoma. meningioma. glia. l Pancreas Kidney Breast Neoadj Boost Lung boost IIIB Liver HK Mets Spine Lung Mets Chondrosarcoma T1-2 N0 Mets Bladder 2 Prostate

3 High Precision Treatment Site in Nice MEDICYC CYCLOTRON FLUOR 18 PRODUCTION (20MeV) PROTON TREATMENT ROOM (65MeV) CYBERKNIFE 3

4 Cyberknife : new treatment and number of fractions (December 2011) Year New T Nb Fr Fr/T

5 Patients Lille Caen Paris inhabitants Bordeaux Nancy C A L 3 0 % Te a c h H ospi t a l 3 7 % Other French areas 12% Bordeaux Lyon Marseille Toulon Cannes Monaco Gap C H G 10 % C l i ni c s 2 3 % Nice 39% PACA 49% Provence Alpes-Côte d Azurd PACA: inhabitants 5

6 Evolution N patient/localization Other Liver HandN Breas t Spine Skull Brain Lung

7 Defining Radio Surgery [1] Lars Leksell Gammaknife Radiosurgery (1 fraction) 1967 Stockholm Karolinska Institut High precision RT >100 converging mini-beam Target : 3 cm max 1-3 Loc (5?) Millimetric accuracy Image matching PET/MRI and CT Mechanical accuracy => only intra cranial Volume is spherical 7

8 Patient Positioning Robotic couch 3 rotations 3 translations 0.3 mm Numeric X Rays 2 sources of X Rays with 2 flat panels at 90 Automatic. Discontinued 41 * 41 cm 1024 *1024 pxl Pxl : 0.4 mm² 0.4 mm 8

9 70? Conventional RT Radiosurgery CyberKnife Accuracy < cm multiple fractions 9 Accuracy < mm unique fraction Accuracy < mm multiple fractions

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16 Radiosurgery Varian Electa Vero 16

17 Defining Accuracy Traditional Definition: Mechanical Accuracy New Definition: Total Clinical Accuracy 5 Tumor motion Patient Positioning 2 - Patient movement Total Clinical Accuracy 3 - Imaging quality (CT. MRI. ) 6 - Beam delivery 4 - Treatment planning

18 Comparison of Hybrid Gantry and CyberKnife SBRT Hybrid Gantry SBRT CyberKnife SBRT GTV: Gross Tumor Volume TUMOR TUMOR Subclinical Disease Subclinical Disease Healthy Tissue CTV: Clinical Target Volume PTV: Planning Target Volume Video courtesy of MD Anderson 18

19 Patient: Flowchart (cont.) Radiologist / Lung specialist Consultation +/- PET Fiducial insertion (1-4) + histology (8 cases) 1 week Dosimetric CT scan Treatment 19

20 Mvt thorax/tumor Diods thorax Fiducials X Y Z 20

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27 Clinical indications Head/neck Re irradiation Boost Brain. shwanoma. meningioma. glia. l Pancreas Kidney Breast Neoadj Boost Lung boost IIIB Liver HK Mets Spine Lung Mets Chondrosarcoma T1-2 N0 Mets Bladder Prostate 27

28 Liver is difficult to treat Liver moves with respiration and deforms 28 Its motion (translation and rotation) depends on the patient breathing pattern and needs to be tracked in real time.

29 Fiducials SOLVES THE EQUATION Based on fiducial tracking Fiducial implantation allows to : - localize the region to be treated (difficult in a uniform-density organ like liver) - assess for the target motion in 6D (translation + rotation) - assess for the target deformation during treatment 29

30 Oligométastases : Radiothérapie des métastases hépatiques à visée curative? Dr Xavier Mirabel Département Universitaire de Radiothérapie Centre Oscar Lambret Lille - France x-mirabel@o-lambret.fr

31 Traitement «curatif» des métastases hépatiques Résection complète de métas pulmonaires ou hépatiques de CCR Survie à 1/3/5/10 ans 85/50/40/20 % Mortalité opératoire 1 à 3 % Timmermann ; CA Cancer J Clin 2009 Survie récidive locale récidive hépatique récidive à distance Quel critère pour évaluer un tt local? Contrôle local 31

32 Lille Patients 42 Métas 62 Technique cyber Dose 3 x 15 Gy Contrôle local 1 an 90 % 2 ans 86 % Vautravers-Dewas ; IJROBP

33 Author Patients/Mets Dose (Gy) / fractionation Median follow-up (months) Actuarial LC 1 year % Actuarial LC 2 years % Actuarial survival 1 year % Actuarial survival 2 years % OS median Herfarth 2001 Heidelberg / / Wulf 2006 Wurtzburg, Bern / / Mendez Romero 2006 Rotterdam / / (mets) (mets) Hoyer 2006 Aarhus /97 45/ Katz 2007 Cleveland 0/174 48/ (10 months) 37 (20 months) 14.5 Milano 2008 Rochester / Rusthoven 2009 USA Multicentri c 47/63 60/ Lee 2009 Toronto 68/ / (18 months) 17.6 Ambrosini 2009 Vicenza 27/ 25-60/ Vautravers-Dewas 2010 Lille 42/ / Chang 2011 USA Multicentri c 65/102 variable/

34 Facteurs pronostiques facteurs pronostiques défavorables contrôle local survie sans maladie survie sexe masculin + Hoyer 2006 métas synchrones Hoyer 2006 lésions extra-hépatiques ++ Chang 2011 nombre de cibles hépatiques ++ taille cible hépatique ++ + Hoyer 2006 ; Chang nombres de lignes de traitement dose ++ Dewas 2010 ; Chang 2011

35 Toxicité Author Patient s/mets Herfarth 2001 Heidelberg /46 Wulf 2006 Wurtzburg, Bern /39 Mendez Romero 2006 Rotterdam /34 Dose (Gy) / fractio nation 14-26/ / /3 Media n followup (mont hs) Actuar ial LC 1 year % Actuar ial LC 2 years % Toxicités G3/ (mets) 4/34 12 % Hoyer 2006 Aarhus /97 45/ dc RILD, 3 ulcérations digestives Katz 2007 Cleveland 0/174 48/ Milano 2008 Rochester / Rusthoven 2009 USA Multicentric 47/63 60/ /47 2 % Lee 2009 Toronto 68/143 Ambrosini 2009 Vicenza 27/ Vautravers-Dewas 2010 Lille 42/ / / / /63 10 % /42 2 % Chang 2011 USA Multicentric 65/102 variabl e/ % 35

36 CRC liver mets N = 51 Local control dose p < 0,05 p < 0,05 Survival tumor size p < 0,05 p < 0,05 36

37 Phase II : liver metastases from colorectal cancer 1 to 3 metastases Cumulative size < 10 cm No extra-hepatic disease 72 patients Multicentric international 3 x 15 Gy 37 Primary objective = local control

38 3 études ouvertes en Europe France multicentric Ph II Condition Intervention Sponsor Liver mets CRC Conformal or SRT 4 X 10 Centre René Gauducheau PHRC International Ph II Liver mets CRC Robotic SRT 3 x 15 Gy Accuray International Ph III Liver mets CRC RTS vs RFA U of Aarhus 38 ClinicalTrials.gov

39 Hepatocellular carcinoma Surgery can be a curative options nevertheless only 15-35% of the patients are surgically resectable Some typical causes of inoperability are the diffusion of the illness the liver functional status and the tumor position 39 For those patients not suitable for resection, there are possible loco-regional techniques Radiofrequency Percutaneous alcoholization Chemoembolization Cryotherapy

40 Radiotherapy is efficient for HCC nb HCC Blomgren dose volume median followup median local control 1y local control 2y survival 1y survival 2y remarks 30 Gy2 or 3f 22 cm % retrospective Mendez ,5 Gy 22 cm % 75% 75% 40% Ph I/II Tse f 73 cm % 48% Ph I Choi f 25 cm % 81% retrospective Cardenes f 34 cm % 75% 60% Ph I Mirabel Gy 3 f 73 cm % 90.50% 72% 42% retrospective 40

41 Robotic stereotactic radiotherapy for 153 liver tumors HCC 48 Metastases 99 Cholangio Relapse free survival 153 targets Relapse free survival 153 targets Local control 1 year 84 % (CI 95% : %) Probability Probability years 74.6 % (CI 95% : %) Months Months 41

42 Local control : 120 patients n LC1y LC2y Metastases HCC Relapse free survival Relapse free survival Probability Probability Months Months Liver Metastases HCC ICC Liver Metastases HCC ICC 42

43 Local control is size-related Diameter < 5 cm p = 0,019 local control 1 year 2 years < 5 cm 88 % 79 % 43 > 5 cm 75 % 63 %

44 Local control is dose-related Dose = 45 Gy p = Local control 1 year 92 % 2 years 72 % 44

45 Conclusion La radiothérapie est un traitement curatif des métastases hépatiques Les techniques évoluent rapidement. C est dorénavant un traitement de routine Inclure dans des études de Phase II pour consolider les résultats Aujourd hui traitement de recours, son positionnement dans la stratégie thérapeutique va évoluer 45

46 Stereotactic radiotherapy indications for liver tumors HCC 1 (or 2) lesions N0 M0 Cirrhosis Child A or (B7-8) Liver metastases 1 to 3 lesions no other possibility of local treatment resistance to chemotherapy or toxicity 46 Possibility to implant and visualize the fiducials

47 Limites de la RTS hépatique Fonction hépatique précaire Taille > 8-10 cm Nombre de lésions > 3 Obésité Lésions volumineuses à proximité de l estomac / duodénum 47 Contre-indication à la pose des fiduciels Ascite Dilatation des voies biliaires

48 Ne sont pas des limites Taille > 3-4 cm Proximité des vaisseaux ou des voies biliaires Thrombose porte Antécédents de chirurgie, de radiofréquence, de chimioembolisation 48

49 2 atouts de la RTS Simplicité de mise en œuvre Traitement ambulatoire Fiduciels +scan dosi + IRM + 3 séances Coût 49

50 50 Thank you for your attention G. ANGELLIER (PhD) K. BENEZERY (MD) J. THARIAT (MD) G. PALAMINI (radiotherapist) L. MILAN (Secretary) B. GRANIER (Secretary) M. MAURIN (ACR) P.Y. BONDIAU (MD. PhD)