+ Radioembolization for ColoRectal Cancer Metastatic to the Liver Alain Hendlisz, Institut Jules Bordet Oct 4 th 2017 1 st International Course on THERANOSTICS & MOLECULAR RADIOTHERAPY
+ Radioembolization
for ColoRectal Cancer
Metastatic to the Liver
Alain Hendlisz, Institut Jules Bordet
Oct 4th 2017
1st International Course on
THERANOSTICS & MOLECULAR RADIOTHERAPY
Indication and Rationale
EMEA : Y90 resin microspheres are indicated for the treatment of patients with non-operable liver cancer.
90Y-Radioembolization
35μ diameter resin microspheres
Yttrium90-loaded (beta-emitter 0.93 MeV)
Half-life: 2.67 days
Penetration 2cm max
Radioembolization : randomized data in CRC
Trials Line Treatments N RR (%)
TTP (mo)
TTLP (mo)
OS (mo)
Gray et al Ann Oncol 2001
1
RE+ HAC
HAC
36
34
44
18
p=0.004
nr
nr
15.9
9.7
NS
39
29
NS
Van Hazel et al J Surg Oncol 2004
1 RE+ 5FU/LV
5FU/LV
11
10
90.1
0
18.6
3.6
nr
nr
29.4
12.8
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
p=0.0012
10.3
11.0
NS
12.6
20.5
p=0.002
23.3
22.6
NS
SIRFLOX, FOXFIRE & FOXFIRE global
Wasan Lancet Oncol 2017
SIRFLOX, FOXFIRE & FOXFIRE global
Wasan Lancet Oncol 2017
SIRFLOX, FOXFIRE & FOXFIRE global
Wasan Lancet Oncol 2017
SIRFLOX, FOXFIRE & FOXFIRE global
Wasan Lancet Oncol 2017
Radiological progression within the liver Non-liver progression
SIRFLOX, FOXFIRE & FOXFIRE global
Wasan Lancet Oncol 2017
SIRFLOX Progression-Free Survival
van Hazel J Clin Oncol 2016
1.5% 4.5% 1.9% 6.0%
66.5% 71.9% 66.9% 72.7%
0%
10%
20%
30%
40%
50%
60%
70%
80%
68.1% CR + PR: p=0.113
Tu
mo
ur
Re
sp
on
se
Ra
te
78.7% 68.8%
FOLFOX + SIRT
(n = 267)
FOLFOX
(n = 263)
CR: Complete Response; PR: Partial Response.
p=0.054
ORR at Any Site ORR in the Liver
p=0.042
p=0.020
FOLFOX + SIRT
(n = 267)
FOLFOX
(n = 263)
76.4%
CR: CR: CR: CR:
PR: PR: PR: PR:
Hepatic Resection
FOLFOX + SIRT
(n = 267)
FOLFOX
(n = 263)
He
pa
tic
Re
se
cti
on
Ra
te
0%
10%
20%
30%
40%
50%
60%
70%
80%
p=0.857 13.7% 14.2%
Radioembolization : randomized data in CRC
Trials Line Treatments N RR (%)
TTP (mo)
TTLP (mo)
OS (mo)
Gray et al Ann Oncol 2001
1
RE+ HAC
HAC
36
34
44
18
p=0.004
nr
nr
15.9
9.7
NS
39
29
NS
Van Hazel et al J Surg Oncol 2004
1 RE+ 5FU/LV
5FU/LV
11
10
90.1
0
18.6
3.6
nr
nr
29.4
12.8
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
p=0.0012
10.3
11.0
NS
12.6
20.5
p=0.002
23.3
22.6
NS
Radioembolization : randomized data in CRC
Trials Line Treatments N RR (%)
TTP (mo)
TTLP (mo)
OS (mo)
Gray et al Ann Oncol 2001
1
RE+ HAC
HAC
36
34
44
18
p=0.004
nr
nr
15.9
9.7
NS
39
29
NS
Van Hazel et al J Surg Oncol 2004
1 RE+ 5FU/LV
5FU/LV
11
10
90.1
0
18.6
3.6
nr
nr
29.4
12.8
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
p=0.0012
10.3
11.0
NS
12.6
20.5
p=0.002
23.3
22.6
NS
Hendlisz et al JCO 2010
3 RE+ protracted 5FU
protracted 5FU
21
23
0 *
0
4.6
2.1
p=0.03
5.5
2.1
p=0.003
9.9
7.4
NS
Radioembolization improves PFS of CRC metastatic to the liver
Chemorefractory liver only mCRC
44 patients R
5FU 300mg/m² D1-14 qw 3weeks
5FU 300mg/m² D1-14 qw 3weeks
+ Radioembolization
Radioembolization
at progression ( )
Hendlisz et al JCO 2010
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
10.3
11.0
12.6
20.5
23.3
22.6
Hendlisz et al JCO 2010
3 RE+ protracted 5FU
protracted 5FU
21
23
0 *
0
5.5
2.1
4.6
2.1
9.9
7.4
To Radioembolize or not to Radioembolize?
Main differences: • Liver-limited versus Liver-only no difference in pts with LOmCRC
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
10.3
11.0
12.6
20.5
23.3
22.6
Hendlisz et al JCO 2010
3 RE+ protracted 5FU
protracted 5FU
21
23
0 *
0
5.5
2.1
4.6
2.1
9.9
7.4
To Radioembolize or not to Radioembolize?
Main differences: • Liver-limited versus Liver-only
• Different Backbone Chemotherapy
no difference in pts with LOmCRC
FOLFOX+Beva > protracted 5FU
Role of « adj » CT in LOmCRC unclear
Effect of CT + surgery in LOmCRC
Nordlinger Lancet Oncol 2013
No effect of CT on PFS nor OS after locoregional treatment
Effect of loco-regional Treatment in LOmCRC
Tomlinson JCO 2007
Radiological progression within the liver
25%
25%
Survival after curative-intent surgery
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
10.3
11.0
12.6
20.5
23.3
22.6
Hendlisz et al JCO 2010
3 RE+ protracted 5FU
protracted 5FU
21
23
0 *
0
5.5
2.1
4.6
2.1
9.9
7.4
To Radioembolize or not to Radioembolize?
Main differences: • Liver-limited versus Liver-only
• Different Backbone Chemotherapy
• Different diseases
no difference in pts with LOmCRC
FOLFOX+Beva > protracted 5FU
Role of « adj » CT in LOmCRC unclear
BETTER SELECTION OF PATIENTS
• Different study design SIRT after 1st course CT
Wasan et al
Lancet Oncol 2017
1 FOLFOX(+Beva)
FOLFOX(+Beva)+SIRT
549
554
63
72
10.3
11.0
12.6
20.5
23.3
22.6
Hendlisz et al JCO 2010
3 RE+ protracted 5FU
protracted 5FU
21
23
0 *
0
5.5
2.1
4.6
2.1
9.9
7.4
To Radioembolize or not to Radioembolize?
Main differences: • Liver-limited versus Liver-only
• Different Backbone Chemotherapy
• Different diseases
no difference in pts with LOmCRC
FOLFOX+Beva > protracted 5FU
Role of « adj » CT in LOmCRC unclear
BETTER SELECTION OF PATIENTS
• Different study design SIRT after 1st course CT
In Other Words …
Undoubtedly efficient but …
as for surgery, need for patients selection (biomarkers)
+
Perspectives
1) Taking in account Tumoral Heterogeneity 2) Multimodal locoregional Approach
SIRT in Multimodality approach… Intralesional Heterogeneity
Pre SIRT PET-CT
Post SIRT PET-CT
Pre SIRT MAA simulation SPECT-CT
Post SIRT Y90- PET/CT
R
NR
NR
SIRT in Multimodality approach… Interlesional Heterogeneity
Radiation Segmentectomy
Gulec et al. WJSO 2009
Baseline 4 weeks post first SIRT
3 months post second SIRT
Garlipp ASCO 2017 abs 3532
Downstaging potential of SIRT
CONCLUSIONS
Radioembolization effective & safe for liver mets
Indicated as salvage for chemorefractory LOmCRC
Alternative to Surgery (unresectable LOmCRC)
Multimodal Therapy Liver hypertrophy presurgery
Liver OligoResistant diseases
Combined Ablative Modalities
...
Should improve patients selection (Tumor Biology)
…as for any other locoregional approach
!
+ Thank you
Life is full of misery, loneliness, and suffering … and it's all over much
too soon. Woody Allen