Radioembolization for ColoRectal Cancer€¦ · Radioembolization for ColoRectal Cancer Metastatic to the Liver Alain Hendlisz, Institut Jules Bordet Oct 4th 2017 1st International

+ 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







Radiological progression within the liver Non-liver progression



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%



TTP (mo)

TTLP (mo)

OS (mo)


1

RE+ HAC

HAC

36

34

44

18

p=0.004

nr

nr

15.9

9.7

NS

39

29

NS


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



TTP (mo)

TTLP (mo)

OS (mo)


1

RE+ HAC

HAC

36

34

44

18

p=0.004

nr

nr

15.9

9.7

NS

39

29

NS


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 ( )


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



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



protracted 5FU

21

23

0 *

0

5.5

2.1

4.6

2.1

9.9

7.4


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



protracted 5FU

21

23

0 *

0

5.5

2.1

4.6

2.1

9.9

7.4




• Different diseases




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



protracted 5FU

21

23

0 *

0

5.5

2.1

4.6

2.1

9.9

7.4




• Different diseases




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

Documents

Radioembolization for ColoRectal Cancer€¦ · Radioembolization for ColoRectal Cancer Metastatic to the Liver Alain Hendlisz, Institut Jules Bordet Oct 4th 2017 1st International