Métastases hépatiques du cancer colorectal : Point de vue du radiothérapeute 26ème Congrès de la SMC Tanger 28.04.2018.

Présentation au sujet: "Métastases hépatiques du cancer colorectal : Point de vue du radiothérapeute 26ème Congrès de la SMC Tanger 28.04.2018."— Transcription de la présentation:

1 Métastases hépatiques du cancer colorectal : Point de vue du radiothérapeute
26ème Congrès de la SMC Tanger

2 INTRODUCTION Amélioration du pronostique du CCR M+
Survie médiane 2 ans Amélioration des thérapies systémiques+++ Réponse complète rx = >80% de rechutes locales Benoist JCO 2006 Chirurgie des M+ hépatique améliore le pronostique (Survie à 5 ans = 30-40%) Mets non résécables dans 80-90% des cas Small R, Isr Med Assoc 2007 CT = 10 à 30% deviennent résécables Kemeny N, Oncology 2006

3 Radiosensitivity of liver mets based on primary
Radiosensitive Radioresistant Ahmed KA, IJROBP 2016

4 SBRT vs RFA 161 pts 282 CCR liver mets (112 RFA vs 170 SBRT)
Primitif CCR : 40% (RFA) / 20% (SBRT) Median FU : 24.6 mos Tox G3+ 4SBRT vs 3 RFA (NS) SBRT meilleure si T>2cm Jackson WC, IJROBP 2018

5 Schémas 50Gy / 10fx (43%) BED10= 75 Gy 60Gy/3fx (19%) BED10= 180 Gy
99.5% PTV = IDL 80% (75-85) Minimum PTV dose 90% BED10= 75 Gy BED10= 180 Gy BED10= Gy BED10= Gy BED10= Gy Jackson WC, IJROBP 2018

6 Résultats de la SBRT hépatique
Mahadevan 25-427 Majorité CCR 14 à 75Gy 1 à 6 séances 0-3% G3 0 G4+ Suivi 1 à 2 ans CL>70%

7 Single dose Heidelberg Stanford Phase I Phase I/II
N= 26 (19 w/ liver mets) 18 to 30Gy Med FU = 18 mos No DLT (1 acute G2 = duodenal ulcer and 2 late duodenal ulcer) 1-y LC 77% 1-y and 2-y OS = 62 and 49% Phase I/II N= 37 Liver mets = 55 14 to 26Gy / 1fx 1-y LC 67% 22-26Gy (80%) 14-20Gy (0%) Herfarth KK, JCO 2001 Goodman KA, IJROBP 2010

8 Fractionated SBRT Liver mets 45Gy/3fx (BED10= 112.5Gy) 2-y LC = 79%
1 death (hepatic failure), 1 colonic perforation, 2 duodenal ulcers No tracking/gating (Large PTV margins) Hoyer M, Acta Oncol 2006

9 University of Colorado
Phase I N= 18 1-3 Liver mets <6cm 36 to 60Gy / 3Fx No DLT Phase II N= 47 (63 liver mets) 38 had 60Gy/3fx Med FU 16 mos 1-y / 2-y in-field LC = 95% /92% 100% if <3cm 1G3+ (2%) / No G4+ Schefter TE, IJROBP 2005 Rusthoven KE, JCO 2009

10 University of Colorado (Phase I/II)
Favorable histology = 15CRC/23 (65%) Rusthoven KE, JCO 2009

11 University of Texas southwestern
Phase I dose escalation 30Gy/3fx - 2-y LC 56% (NoG3+) 50Gy/5fx – 2-y LC 89% (No G4+ - 1G3 liver enzyme) 60Gy/5fx – 2-y LC 100% (No G3+) Dose-response relationship betwwen 30Gy and 60Gy (p=0.009) Rule W, Timmerman R, Ann Surg Oncol 2011

12 Ultra high dose (University of Milan, Italy)
76 liver mets 75Gy/ 3fx (BED10=262.5Gy) Med FU = 12 mos LC = 95%, 2-y OS 70% Scorsetti M, IJROBP 2013

13 CRC Liver Mets : Prognosticators on LC
3 institutions 1 to 4 liver mets N= 65 (102 lesions = 100% CRC) 72% ≥ 1 CT before SBRT, 42% had ≥2 CT regimen Predictors of LC on MVA: Total dose (> vs < 42Gy) Dose /fx BED (< vs >75Gy) LC> 90% if 46-52Gy/3fx Recommendation = 48+Gy /3fx N of chemo regimen (NS) 90% LC BED 117Gy Chang DT, Cancer 2011

14 CRC Liver Mets: Prognosticators on OS
Active non-liver disease (p=0.046) Local failure (p=0.06) N of chemo regimen (NS) Chang DT, Cancer 2011

15 CRC & Liver Mets : Phases I + II
N= 60 82% previous CT, 23% previous liver tx, 38% extrahepatic disease Median n of GTV = 1 (1-6) Median target size= 6cm (4.5-21) Median min GTV dose = 37.6 ( ) / 6 fx over 2w median FU= 28.1 mos 1-y and 4-y LC = 49.8% and 26.2% 1-y and 4-y LC = 65.0% and 49.8% if BED>75Gy (>45Gy/6fx) McPartlin A, IJROBP 2017

16 CRC & Liver Mets : PMH Experience
McPartlin A, IJROBP 2017

17 The international multi-institutional RSSearch® Patient Registry
427 pts 568 liver Mets 25 academic and community-based Median FU 14 mos n Median OS (mos) 1-y OS CRC 189 27 76.4% Breast 42 21 66.4% Gynae 26 25 81.3% Lung 52 10 50% Other GI 33 61% Pancreas 20 6 18% Other 65 Mahadevan A, Radiat Oncol 2018

18 Effet dose/volume <40cm3 ≥40cm3 Mahadevan A, Radiat Oncol 2018

19 CRC & Liver Mets : LC predicts OS!!
McPartlin A, IJROBP 2017

20 CONCLUSIONS Option thérapeutique ablative et conservatrice pour les M+ non résécables Contrôle local en SBRT >80% et relié à la survie Modélisation de l’effet dose/volume permet d’établir les schémas thérapeutiques efficaces T>3cm efficacité >RFA mais BED >117Gy Toxicités minimes+++ Intérêt de combiner thérapies systémiques?