EC916
Drug Eluting Bead: Clinical
Updates and Histological Data
Eva Gallardo, MD
Medical Manager, Biocompatibles UK
EC916
DC Bead: Clinical Programme
Primary Liver Cancer
Very Early/Early Stage
Prior to resection
Bridge to transplant
RFA + PRECISION TACE
Intermediate Stage
Precision I
Precision II
Precision V
Advanced Stage
Doxorubicin Bead
Breast
Melanoma
Gastric
Irinotecan Bead
Other Primary Cancers
Neuroendocrine
Early CT Lines
Late Stage
Sorafenib + PRECISION TACE
Secondary Liver Cancer
Renal
Colorectal Metastases
Cholangiocarcinoma
Sarcoma
EC916
PRECISION TACE in treatment of
Colorectal Metastases
Investigators: Camillo Aliberti, MD
Giammaria Fiorentini, MD
Department of Diagnostic and Interventional Radiology,
Delta Hospital AUSL Ferrara, Ferrara Italy
Department of Oncology, General Hospital San Giuseppe,
Empoli, Florence, Italy
EC916
Irinotecan Bead in Advanced
Colorectal Cancer: Patient
Selection
• 62 patients (M/F = 42/20), median aged 64.6 (range 42-85)
• Not operable and pretreated at least two lines of chemo
(range 2-6)
• Maximum dose 4 ml (2ml of 100-300mm and 2ml of 300500mm) with 200mg of Irinotecan
• 2-3 TACE 4 weeks
EC916
Irinotecan Bead in Advanced
Colorectal Cancer: Toxicity
Postembolization-syndrome
RUQP (G2-G3)
Pain
100%
Vomiting
Fever
Asthenia
40
90%
Nausea and Vomiting (G2G3)
100%
Increased Transaminases
(G2-G3)
80%
30
25
20
15
10
5
ee
k
2
w
ee
k
w
1
da
y
2
da
y
1
1
ho
ur
6
ho
ur
s
12
ho
ur
s
18
ho
ur
s
0
0
Fever (G2)
Procedures
35
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Irinotecan Bead in Advanced
Colorectal Cancer: Response to
Treatment
• The median follow-up was 15.4 months
• 1 month CT scan showed reduction of metastatic CE
85%, range 75-100% in all patients
• RECIST at 3 months: 78%
• 55/62 pts (90%) declared a general improvement of
QoL lasting 6.5 months, range 3-12
EC916
Irinotecan Bead in Advanced
Colorectal Cancer: Survival
• Median survival not reached
at 22 months
100
90
80
• Median Free Time from
symptoms 5.3 (5-20
months)
survival (%)
70
60
50
40
30
20
• Median Time to further
chemoteraphy 6.3 (5-22
months )
10
0
0
2
4
6
8
10
12
time months
14
16
18
20
22
EC916
Irinotecan Bead in Advanced
Colorectal Cancer: Cases
18 months after TACE
EC916
Irinotecan Bead in Advanced
Colorectal Cancer: Cases
02.2005
09.2005
6 months after TACE
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Neuroendocrine Metastasis
Principal Investigator: Thierry De Baere, MD
Chief of Interventional Radiology Department
Institut de Cancérologie Gustave Roussy - Villejuif France
EC916
Doxorubicin Bead in NET:
Materials and Methods
• 20 patients with liver metastases from low-grade GEP
tumour
• Progressive liver disease on two subsequent imaging
studies according to RECIST criteria
• Disease predominant to the liver
• Up to 4ml DC Bead 500-700mm loaded with up to
100mg doxorubicin
• Concomitant treatment with long-acting ST analog
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Doxorubicin Bead in NET:
Results
• 34 sessions (6 unilobar, 14 bilobar)
– 16/20 (80%) partial response
– 3/20 (10%) stable disease
– 1/20 (15%) progressive disease
• After a median follow-up of 15 months
(6-24), disease remained controlled
without tumour progression in 45%
Progression rate
• RECIST 3M:
Progression
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
At 12 months :
47% (95%CI = 23% - 72%)
0
Patients at risk
20
6
12
18
24
Months since treatment
15
6
1
• 1 patient become resectable
Median Time to Progression: 15 months
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Doxorubicin Bead in NET:
Toxicity
• Post-embolisation syndrome:
– < 7 days in 67% sessions
– > 7 days in 22% sessions
– No symptoms in 11% sessions
• Hypodense subsegmental peripheral areas (TACEinduced necrotic liver tissue?) in 5 patients at 1 month
CTscan
• 1 death: resected patient due to postoperative septic
complications
EC916
Doxorubicin Bead in NET:
Cases
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Doxorubicin Bead in NET:
Cases
EC916
Combined PRECISION TACE/RFA:
Results and Outcome
Principal Investigator: Riccardo Lencioni, MD
Associate Professor of Diagnostic and Interventional
Radiology
Department of Oncology, Transplants, and Advanced
Technologies in Medicine – Pisa University, Italy
EC916
RFA: Inherent Limitations
50 °C
Sub-lethal heating
(45-50 °C)
Vessel
EC916
DEB-Enhanced RFA of HCC: A Pilot Study
Design / Enrollment Criteria
20 pts (mean age, 70 ± 6 ) with residual viable tumour at CT /
MRI 1-2 hrs after RFA
- Tumour diameter 3.3-7.0 cm (mean, 5.0 cm ± 1.4)
- Child-Pugh class A, ECOG 0
- PT ratio > 50%, platelets > 50,000/mm3
Excl: - Eligibility for liver resection or transplantation
- Vascular invasion / extrahepatic disease
- Any previous treatment for HCC
EC916
DEB-Enhanced RFA of HCC: A Pilot Study
Materials and Methods
DC Bead (Biocompatibles) injection < 24 hrs of RFA
- 50 mg doxorubicin in 2 ml of 100-300 μm beads
- Additional loads (100-300 / 300-500 µm) if needed
Follow-up period 6-20 months (mean, 12 months ± 5)
Tumour response: RECIST criteria - EASL amendment
- CR: absence of enhancement at 1-month CT / MRI
- Confirmed CR: CR lasting no less than 6 months
- OR: confirmed CR target lesion, no new lesions
EC916
DEB-Enhanced RFA of HCC: A Pilot Study
Results – Change in Ablation Volume
Ablation Volume (mm3)
180,000
160,000
140,000
120,000
+ 61%
100,000
80,000
60,000
40,000
20,000
0,000
Standard RFA
DEB-Enhanced RFA
EC916
DEB-Enhanced RFA of HCC: A Pilot Study
Results – Clinical Case # 2
6 cm
Pre-treatment CT
Post-RFA
Post-TACE
EC916
DEB-Enhanced RFA of HCC: A Pilot Study
Results – Overall Response
Table. Overall Response at the End of Follow-Up
Overall response
Target lesions
New lesions
No. (%)
CR
CR
No
10 (50%)
PR
PR
No
5 (25%)
PD
CR / PR
Yes
3 (15%)
PD
Yes / No
2 (10%)
Note: Numbers are numbers of patients. Overall
number of patients: 20.
EC916
DEB-Enhanced RFA of HCC: A Pilot Study
Results – Overall Survival
100%
92%
100
80
60
40
20
0
DEB-enhanced RFA (n = 20)
0
6
12
18
months
24
30
EC916
Doxorubicin Bead prior to liver transplant
EC916
TACE Prior to Transplant
• Major issue = Dropout rate (30-40%)
• Role of TACE:
• Patients within Milan criteria (maintain in waiting list)
• Patients outside Milan criteria (for downstaging to fullfil
Milan criteria)
• Induce high hystological tumour response rate
• Decrease recurrence rates?
EC916
Dr Citron –Atlanta, US
• Retrospective study
• 9 listed patients (>Child A-B, single nodules, mean
tumour size 2cm (0.3-5.1)
• 1-3 treatments prior to transplant
• 100-300 and/or 300-500mm DC Bead with up
150mg doxorubicin
• Liver transplant (1-281 days post-treatment)
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Results
• CTscan:
– Complete necrosis 88% patients
• Histology:
– Complete necrosis 77% patients
– 2 non-complete necrosis:
• Patient transplanted 8 hours after TACE with no necrosis
• Patient with residual 0.5cm viable tumour within 7.5cm
necrotic tumour
EC916
Dr Nicolini - Italy
• Retrospective study Doxorubicin Bead vs TAE
• 16 patients (15 waiting list/ 1 outside Milan)
DC Bead
TAE
HCV
HDV + HBV
Others
3
3
2
4
0
4
Child-Pugh A
Child-Pugh B
5
3
6
2
3.0
3.4
7
1
5
3
Mean tumour size (cm)
Single
2 nodules
•1-4 treatments until complete RX response
•DC Bead arm: 100-300mm DC Bead with 50mg epirubicin
•TAE:100-300mm Embosphere
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Tumour Response
CTscan Response*
Complete Necrosis
Partial Necrosis (>70%)
Histological Response*
Complete Necrosis
Necrosis >70%
Necrosis <50%
DC Bead
TAE
88
12
45
55
78
22
0
P=0.04
27
54
19
* % Tumour response by tumours
• 62.5% DC Bead achieved complete RX response after one treatment vs
12.5% in TAE
• 15 patients alive with no recurrence
EC916
Prof Goffette - Belgium
• 16 patients:
– 9 within the Milan criteria for LT
– 7 outside the Milan criteria for LT
• Diameter > 5 cm
4
• More than 3 tumours 3
• Mean tumour size 5.4 cm (2.3-7.8) , 2 portal vein thrombosis
• Standardized DC Beads doses and sizes:
– 4ml (2 vials) of 300-500 µm particles loaded with 25mg/ml
doxorubicin:100 mg Doxo/session
• Additional unloaded particles (300-500,500-700µ) if persitent
flow
• Sequential treatment every 3 months (Max 4)
• Alternate treatment if bi-lobar lesions
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Procedural Results
• Mean number of sessions
4pts:1, 6pts:2, 7pts:3, 1pt:4
• Serious adverse event
Cholecystitis
• 30-day mortality
• Post-embol syndrome
• Transient impaired liver function
2.7
1
0
15
12
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Clinical Results
• Transplanted patients
•
10
Delay: 6.5 months (2-15)
• Biliary complications:
3
• Follow-up: 7.5 months
– 1 recurrence at 5 m (40% necrosis)
• Patients on waiting list
4
• Deaths
• Pneumonia
2
• Terminal liver failure
• Significant downstaging in 6/7 patients
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Results Imaging (EASL)
• Complete
• Partial
–
–
Residual peripheral enhancement
Persistent enhanced nodules
• Stable Disease
• Progressive Disease
• Objective Response
4(25%)
11(69%)
9
4
1
0
15(94%)
EC916
Histological Response
All
patients
(n=12)
Vascular
permeation
Portal
thrombosis
Recurrence
After OLT
(n=10)
Complete
tumor necrosis
5 (42%)
0
0/5 (0%)
Partial
tumor necrosis
≥75%
and <99%
6 (50%)
2
0/4 (0%)
Incomplete
tumor necrosis <
50%
1 (8%)
1
1/1 (100%)
PATHOLOGIC ASSESSMENT
RESPONSE
NO RESPONSE
EC916
Surgical Complications
• Complicated arterial anastomosis
– Co/proper Hep. Art. occlusion
– Pedicular inflammation
– Early arterial occlusion…redo-OLT in 1
• Difficult biliary anastomosis
• Severe chronic cholecystitis
7
4
3
3
4
EC916
46 yr old male: Bilobar HCC ( >7cm seg IV)
Downstaging before LT
First TACE session left lobe
EC916
46 yr old male: Bilobar HCC ( >7cm seg IV)
Downstaging before LT
Repeated controls CT after first session
Second TACE (right lobe) and control CT……waiting list