Role of SBRT in the management of lung and liver metastases. Ronan TANGUY, M.D. Radiation Oncologist

Transcription

1 Role of SBRT in the management of lung and liver metastases Ronan TANGUY, M.D. Radiation Oncologist

2 Oligometastatic RCC mrcc: Lung, Bone, Liver, Brain (Schlesinger-Raab, EJC2008) Targeted therapies Objective response: 20-40% patients Complete Response: 1-3% patients (Motzer, JCO 2009) Median OS: 9-40 months (Heng DY,Lancet Oncol 2013) Oligometastatic disease 25% metachronous mrcc / 10% synchronous mrcc (Alt, Cancer2011; Oddsson,Scand Journ Surg 2012) Clinical benefit to local control of metastatic sites

3 Liver metastases Colo-Rectal cancer Liver resection 5-yr OS: >35% vs 11% (all mcrc) Morbidity rates: 20-45% Mortality rates: 1-3% Better results nb M+, no extra hepatic M+, R0, response to systemic ttt Limitations Operability; Resectability : minimum size of future liver with adequate vascular function For non CRC primitives (Hatzaras, HBP 2012) Lo, Nat Rev Clin Oncol 2011; Dabestani, Lancet Oncol 2014

4 SBRT Dose escalation: High dose per fraction Different radiobiology: no differential effect Millimeter precision Moving target tracking fiducials Sharp dose gradient Isodose prescription and Multiple non-opposing and noncoplanar beams

5 Patients Child-Pugh < C, 1 3 lesions, Size < 6 cm, > 700cc liver spared Dose 48Gy / 3 fractions on 70-80%, at least > 36 Gy / 3 (Mc Cammon, IJROBP 2009) Results 2-yr LC: 60%-90%; 2-yr OS: 30-83%; Median OS: months Hoyer, IJROBP 2012 Lo, NRCO 2011

6 Toxicity Liver SBRT Radiation Induced Liver Disease: Veino-occlusive disease Anicteric ascites and hepatomegaly higher elevated liver enzymes, thrombocytopenia 2 patients with grade 3 +/- 1 grade 5 on early studies Child-Pugh ++, functional liver volume Gastro-duodenal ulceration: 4 patients with Grade 3 hemorrhagic ulcerations Dosimetric constraints Hoyer, IJROBP 2012 Lo, NRCO 2011

7 Liver SBRT for mrcc Author/d ate Svedman, 2006 Wersall, 2005 Liver target / total Average marginal dose (Gy) Median follow-up (months) Crude/1y LC (%) Median OS (months) Toxicity 3 / 77 40Gy / / No RILD 2 /154 45Gy / /99 NR 23/58 GI-II 1 GV Ranck, / 39 50y / % NR No RILD G.Kothari, Acta Oncol 2015

8 Liver SBRT for mrcc Unsuitable for Surgery Unsuitable for ablative therapy Size > 3-5 cm Vascular / major biliary structure closeness Suitable for SBRT Child-Pugh<C, >700cc liver spared

9 Lung SBRT Medically inoperable stage I NSCLC (Chi,RO 2010) 5-yr local control : 85% +/- 15% 5-yr CSS : 60% +/- 17% 5-yr OS: 47% +/-20% Toxicity < 10% G3

10 Lo, Nat.Rev.Clin.Oncol 2011 Lung SBRT

11 Lung SBRT for mrcc Author/d ate Svedman, 2006 Patient (target) Location Average marginal dose (Gy) Median followup Crude/ 1y LC /Gen LC (%) 26 (77) 63 lung 40Gy / /100/ 79% Median OS Toxicity 32 52% GI-II 0 G>2 Wersall, (154) 117 lung 32Gy-40Gy / 4 45Gy/ /99 NR 40% GI-II G.Kothari, Acta Oncol 2015

12 Prospects Association with targeted therapies? Pre-clinical: RT / SBRT (Zeng, Lancet Oncol 2014; El Kaffas, Angiogenesis 2013) Clinical: oligometastatic disease (J.Kao, Target Oncol 2014)

13 Conclusion Major advance in mrcc: Targeted therapies Oligometastatic state Lung and Liver metastases SBRT is a reliable and safe alternative for patients unsuitable for surgery Spine and Brain metastases SBRT: central treatment modality

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