Radioembolization: technical aspects

Transcription

1 Radioembolization: technical aspects Rita Golfieri Unità Operativa Radiologia Malpighi Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola - Malpighi

2 La sottoscritta dichiara di non aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione non contiene discussione di farmaci in studio o ad uso off-label

3 TARE (Radioembolization) theoretical assumptions: Yttrium-90 microspheres are μm particles that emit β- radiation: max penetration in soft tissue 10 mm (Ø 2.5 mm). Delivered via the hepatic arterial route: treatment algorithm analogous to that followed with TACE.

4 Dose (Gy) TARE (Radioembolization) theoretical assumptions: HEPATIC STRUCTURAL TARGETING Distance (cm)

5 TARE (Radioembolization) theoretical assumptions: Conventional TACE Ø >1 mm DEB-TACE Ø μm TAE Ø μm TARE Ø μm

6 TheraSphere MDS Nordion, Canada SIR-Spheres Sirtex Medical, Australia Glass matrix Resin surface 1-8 million microspheres low number Microscopic embolization (mainy radiation dose effect) Half-life 64.2 h Particle Ø μm Time to near complete decay 13 days 1,2-8 mil. spheres per dose 2500 Bq per sphere 6 Doses: 3-20 GBq/pts Embolic effect: mild Shunt hep/polm <10% No dose variation with tumor volume million microspheres high number Macroscopic embolization (ischemia + radiation dose effect) Half-life 64.2 h Particle Ø μm Time to near complete decay 13 days mil. sphere per dose 50 Bq per sphere 1 Dose: 3 GBq/pts Embolic effect: moderate Shunt hep/polm <20% Dose variation with tumor volume CE Mark 2006 for liver tumors CE Mark 2002 for liver tumors

7 Median Survival (months) Clinical Outcomes of HCC Patients Treated with 90 Y Glass or Resin Microspheres 48 Glass (n=291) Resin (n=325) 95% Confidence Interval BCLC A BCLC B BCLC C Child A no PVT Child A + PVT Child B no PVT Child B + PVT Salem R et al. Gastroenterology 2010; 138: Sangro B et al. Hepatology 2011; 54:

8 Multidisciplinary team discussion Patient selection and treatment planning Surgical oncologist Tumor board (LOM) Interventional radiologist Hepatologist Transplant surgeon Medical oncologist Medical physics 90 Y patient Medical radiation oncology Radiation safety Nuclear medicine

9 1 st : Patient selection HCC - Indications to TARE MAIN Pts poor candidate to TACE large tumors (>5cm), bilobar disease or > 5 nodules Infiltrative & hypovascular tumors Pts who failed TACE/sorafenib Pts who are contraindicated for TACE (e.g. HCC + PVT) ADDITIONAL Elderly Bridging to transplant (tumor control in the waiting list) Bridging to resection (radiation-induced segmentectomy/lobectomy + contralateral hypertrophy)

10 2 nd : TARE planning dictated by tumour burden and presence/severity of any underlying concomitant disorders such as cirrhosis, and can also be influenced by intent, i.e. radiation segmentectomy. whole-liver Bilobar/sequential Whole-remnant right lobe left lobe sub/segmental

11 29/04/2014 TC

12 16/12/2014: TAE Embozene ( 2 vials 40 μm, 2 vials 75 μm, 2 vials 100 μm)

13 23/01/2015 TC

14 Absolute: Contraindications for TARE Reflux into the arteries supplying the gastroduodenal region: inability to prevent the deployment of microspheres into the GI tract Prior external irradiation to the liver Liver cirrhosis (high risk of severe complications) Child-Pugh score >8 or score 7 with ascites (serum bilirubin >2mg/dL) Impaired renal function (serum creatinine >2mg/dl, glomerular filtration rate <30 ml/min Relative: Intense, non-correctable hepato-pulmonary shunt (>20%) HCC (futility of procedure): massive tumors involving both lobes Bile duct occlusion or incompetent papilla due to stent or surgery Potential Morbidity Gastric/Duodenal ulcerations Radiation-induced Liver damage (RILD) Veno-occlusive disease (VOD) Radiation hepatitis (chronic ascites) Pulmonary (radiation pneumonia)

15 Overview of TARE Procedure Typically a 2-stage process 1. Work-up procedure: Trans-femoral catheter access to hepatic artery vasculature and identify tumor feeding vessels Prophylactic occlusion of extra-hepatic vessels (GDA, right gastric etc) Injection of 99mTc-MAA / gamma camera study to assess lung-shunt and spheres distribution CT volumetry (lesion/treated area/whole liver) 2. Treatment procedure: 1 3 weeks later Reassessment of vascular occlusion Injection of 90Y microspheres dose Optional PET/CT study to confirm implantation Sequential lobar approach if necessary for patient safety

16 Overview of TARE Procedure Typically a 2-stage process 1. Work-up procedure: Trans-femoral catheter access to hepatic artery vasculature and identify tumor feeding vessels Prophylactic occlusion of extra-hepatic vessels (GDA, right gastric etc) Injection of 99mTc-MAA / gamma camera study to assess lung-shunt and spheres distribution CT volumetry (lesion/treated area/whole liver) 2. Treatment procedure: 1 3 weeks later Reassessment of vascular occlusion Injection of 90Y microspheres dose Optional PET/CT study to confirm implantation Sequential lobar approach if necessary for patient safety

17 Therapy planning: initial work-up (1) Pre-treatment angiography and embolization of the extrahepatic arteries leading to the gastroduodenal region (i.e. the gastroduodenal artery and right gastric artery) to ensure delivery of the microspheres to the target Anatomic variants

18 Replaced RHA from SMA Replaced LHA from LGA

19 Therapy planning: initial work-up (1) Pre-treatment angiogram to check extrahepatic flow: Prophylactic coil embolization: right gastric artery + GDA Left hepatic artery embolization GDA embolization

20 Therapy planning: initial work-up (1) Pre-treatment angiogram to check extrahepatic flow: Prophylactic coil embolization: Retroduodenal artery from right hepatic artery.

21 Overview of TARE Procedure Typically a 2-stage process 1. Work-up procedure: Trans-femoral catheter access to hepatic artery vasculature and identify tumor feeding vessels Prophylactic occlusion of extra-hepatic vessels (GDA, right gastric etc) Injection of 99m Tc-MAA / SPECT study to assess lung-shunt and spheres distribution CT volumetry (lesion/treated area/whole liver) 2. Treatment procedure: 1 3 weeks later Reassessment of vascular occlusion Injection of 90Y microspheres dose Optional PET/CT study to confirm implantation Sequential lobar approach if necessary for patient safety

22 Therapy planning: initial work-up (2) Scintigraphy: 150 MBq of 99m Tc-MAA as a microsphere surrogate into the hepatic arterial territory, to calculate lung and extra-hepatic shunts and to perform lesion and whole liver dosimetry using the MIRD formalism. Dangerous Shunt 99m Tc- MAA > 20% Up to 30 Gy to the lungs could be tolerated in a single injection, and an up to 50 Gy cumulative lung dose in multiple treatments Leung TW et al. Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys 1995;33:

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24 Therapy planning: initial work-up (2) Extrahepatic flow Confirmation of the exclusion of gastrointestinal flow: use of the combined information obtained from meticulous hepatic angiography, 3D CT angiography, and SPECT imaging Fusion of CT and 99m Tc-MAA SPECT images to identify extrahepatic flow or non-target infusion Hamami ME, et al. J Nucl Med. 2009;50:

25 Therapy planning: initial work-up (2) Liver (RILD) Individualize the risk Avoiding significant radiation exposure for non-target tissues correlate MAA activity with MRI or CT images

26 Therapy planning: initial work-up (2) Avoiding significant radiation exposure for non-target tissues failure to target the tumor; MAA SPECT MRI fusion

27 Therapy planning: initial work-up (2) Gallbladder (cystic artery) Individualize the risk Avoiding significant radiation exposure for non-target tissues Inject from beyond the cystic artery double injection (but watch for tumor irrigation by the cystic artery)

28 case#1: 63 year old male, first diagnosis of HCV-related liver cirrhosis, AFP ng/ml HCC nodule in segment VI near the gallbladder (recurring after RF); partial PVT 2 feeding vessels to the tumor: one is the cystic artery and the second the VI segment branch (Ø 3.5x3.4 cm)

29 TACE of the branch originating from the cystic artery Final control after TACE TACE is less risky for development of acute cholecystitis: radiation >> chemical/ischemic post-tace cholecystitis

30 Planning of superselective TARE in the VI segmental branch

31 End treatment control Arterial phase 1 month follow-up CT Portal venous phase

32 Case # 2: colorectal metastases, bilateral involvement Planned whole liver treatment Angiogram preliminary to TARE: right gastric artery + GDA coil embolization

33 Case # 2: colorectal metastases, bilateral involvement Planned whole liver treatment 99m Tc-MAA SPECT Shunt 99m Tc-MAA =2%

34 Case # 2: colorectal metastases, bilateral involvement Planned whole liver treatment Repeated pre-tare angiogram falciform artery microcoils embolization

35 Case # 2: colorectal metastases, bilateral involvement Planned whole liver treatment Repeated 99m Tc-MAA SPECT Radioembolization: whole liver treatment

36 If shunt - patient enrolled. Catheter removal and schedule for TARE treatment after 90 Y dose calculation and order If shunt + alternative intrarterial treatment (TAE, TACE) or catheter removal

37 Overview of TARE Procedure Typically a 2-stage process 1. Work-up procedure: Trans-femoral catheter access to hepatic artery vasculature and identify tumor feeding vessels Prophylactic occlusion of extra-hepatic vessels (GDA, right gastric etc) Injection of 99mTc-MAA / gamma camera study to assess lung-shunt and spheres distribution CT volumetry (lesion/treated area/whole liver) 2. Treatment procedure: 1 3 weeks later Reassessment of vascular occlusion Injection of 90Y microspheres dose Optional PET/CT study to confirm implantation Sequential lobar approach if necessary for patient safety

38 Therapy planning: initial work-up (3) Volume calculation 1. Tumor volume 2. Whole liver volume Dosimetry calculations based on: 3. Volume of vascular bed supplied by the artery to be catheterized

39 Therapy planning: initial work-up (3) Dose calculation Modulated based on tumor and normal liver doses: normal liver maximal dose: 30 Gy more than 200 Gy on treated lesion had a better tumor response and a longer survival Tumor dose evaluation based on 99 mtc-maa SPECT/CT -40% if between 15% and 20%..

40 Therapy planning: initial work-up (3) Modulated based on tumor and normal liver doses: normal liver maximal dose: 30 Gy more than 200 Gy on treated lesion had a better tumor response and a longer survival Tumor dose evaluation based on 99 mtc-maa SPECT/CT BSA formula Activity (GBq) reduced by: Dose calculation A(GBq) = BSA vol tum -20% if hepato-pulmonary shunt between 10 and 15% -40% if hepato-pulmonary shunt between 15% and 20%. Treatment exclusion for hepato-pulmonary shunt >20%. vol lobo

41 Therapy planning: initial work-up (3) Dose calculation

42 Overview of TARE Procedure Typically a 2-stage process 1. Work-up procedure: Trans-femoral catheter access to hepatic artery vasculature and identify tumor feeding vessels Prophylactic occlusion of extra-hepatic vessels (GDA, right gastric etc) Injection of 99mTc-MAA / gamma camera study to assess lung-shunt and spheres distribution CT volumetry (lesion/treated area/whole liver) 2. Treatment procedure: 1 3 weeks later Reassessment of vascular occlusion Injection of 90Y microspheres dose Optional PET/CT study to confirm implantation Sequential lobar approach if necessary for patient safety

43 Ready for Assembly

44 Treatment process 90 Y microspheres resin

45 Treatment process 90 Y microspheres glass

46 Infusion through a microcatheter

47 Case #3: double treatment of TARE - double feeding arteries: splitting the dose 1992: HCV infection interferon August 2009: US detection of multiple liver lesions. October 2009: MDCT multifocal HCC with bilobar distribution. Larger lesion 8 cm VII-VI e VIII segments Wedge Resection of HCC II segment + TARE to the larger lesion in VII-VIII segment. Sorafenib for 2 years Previous wedge resection II segment HCC VII-VIII segment

48 February 2012: 2 years follow up New lesion + PR - mrecist of the previously treated lesion in VII-VIII segment

49 Planned second Y 90 TARE, splitting the dose: 2\3 for the new lesion in VIII S and 1\3 for the residual in VII-VIII S Two different feeding arteries

50 Post-Tx Imaging: PET/CT 1 hour after treatment to verify the exclusive uptake in liver tumor area To detect suspected extrahepatic deposition PET\CT after 2 TARE To elucidate the distribution of microspheres in the liver

51 CT: Assessing treatment outcome Imaging findings 1 month: peripheral hypervascularity of the treated areas due to oedema, congestion e microinfarcts 2-3 months: vascularity and size reduction (mrecist) Baseline

52 Radioembolization: Volume Reduction Peripheral hypervascularity due to fibrosis 1 month /06 4 months 7 months 02/07

53 Infiltrative HCC + PVT: baseline CT Bisegmental TARE V-VIII

54 1 month F-U CT: Volume Reduction segmental hypervascularity due to fibrosis

55 9 months 3 months 6 months

56 1 year RADIATION SEGMENTECTOMY

57 Pre-treatment CT RADIATION LOBECTOMY CT: 6 months FU

58 The current systematic review showed hypertrophy of 26 47% at time intervals of from 44 days to 9 months after unilobar SIRT with Y90. PVE has been reported to give rise to FLR hypertrophy of 10 46% after 2 8 weeks.

59 Expanding the room for hepatic resection Radio-embolization as conversion therapy M.P. male 72 y. Chronic hepatitis C. HCC of the caudate lobe in between the right and the left hepatic veins with neoplastic infiltration of the left portal vein. CTP A, no comorbidities, HVPG = 13mmHg but biased from tumor compression on the hepatic veins.

60 Expanding the room for hepatic resection Radio-embolization as conversion therapy 3 month control: OBJECTIVE RESPONSE. INTERVENTION: LEFT HEPATECTOMY WITH VENO-VENOUS BY-PASS AND VASCULAR RECONSTRUCTIONS

61 Thanks for the attention Rita Golfieri Unità Operativa Radiologia Malpighi Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola - Malpighi rita.golfieri@aosp.bo.it