T h e Role of Interventional

Radiology in the Treatment of NET

Jonathan Kessler, MD

Assistant Clinical Professor

Division of Interventional Radiology

City of Hope Comprehensive Cancer Center

D is c lo s u r e s

N o r e le v a n t d is c lo s u r e s

R o le o f In t e r v e n t io n a l R a d io lo g y

W h a t r o le d o e s IR p la y in t h e t r e a tm e n t o f m e t a s t a t ic N ET ? I d o n ’t k n o w M o re t h a n w e a r e c u r r e n t ly d o in g

R o le o f In t e r v e n t io n a l R a d io lo g y

W h a t r o le d o e s IR p la y in t h e t r e a tm e n t o f m e t a s t a t ic N ET ? R e v ie w t h e e v o lv in g d a t a f o r t r e a tm e n t o f N ET

liv e r m e t a s t a s e s J u s t if y e x p a n d in g t r e a tm e n t s t o m o r e p a t ie n t s

w it h N ET liv e r m e t a s t a s e s

N ET M e t a s t a s e s

N ET in c id e n c e 8 / 10 0 ,0 0 0 D is t a n t m e t a s t a s e s 4 4 - 7 3 % a t d ia g n o s is

S m a ll b o w e l 8 0 - 9 0 % P a n c r e a s 6 0 - 7 0 %

Liv e r t u m o r in v o lv e m e n t s t r o n g p ro g n o s t ic in d ic a t o r

Pavel et al ENETS Consensus Guidleines for the Management of Patients with Liver and

Other Distant Metasases from Neuroendocrine Neoplasms. Neuroendocirnology 2012

M e t a s t a t ic N ETN C C N v 1.2 0 15

Tr e a t m e n t O p t io n sC o n s id e r o c t re o t id e o r la n re o t id e• Ev e ro lim u s o r• S u n it in ib o r• Cy t o t o x ic c h e m o t h e ra p y o r• H e p a t ic re g io n a l t h e ra p y o r• Cy t o re d u c t iv e s u rg e r y / a b la t iv e

In d ic a t io n sS y m p t o m a t ic o rC lin ic a lly s ig n if ic a n to rC lin ic a lly s ig n if ic a n t d is e a s e

M e t a s t a t ic N ET EN ET S

W h a t a r e w e d o in g ?

2 1%

15 %

2 7 %

17 %5 %

15 %2 0 %

S u p p o r t iv e C a r e

C h e m o t h e r a p y

R e s e c t io n o f P r im a r yT u m o rL iv e r R e s e c t io n

S u r g ic a l R e s e c t io n +T r a n s a r t e r ia l T h e r a p yT ra n s a r t e r ia l T h e r a p y

California Cancer Registry 2005-2012

Treatments of Hepatic Metastases

N = 8 2 4

T r a n s a r t e r ia l T h e r a p y f o r L iv e r M e t a s t a s e s

T ra n s a r t e r ia l T h e r a p y

12 .5 % 17 .8 % 10 .7 % 16 .5 % 2 0 .0 %

S t o m a c h P a n c r e a s M id g u t C o lo r e c t a l U n k n o w n

T r a n s a r t e r ia l T h e r a p y + S u r g e r y

T r a n s a r t e r ia l T h e r a p y in N o n - S u r g ic a l P a t ie n t s

N ET M e t a s t a s e s 5 y r S u r v iv a l

Pavel et al ENETS Consensus Guidleines for the Management of Patients with Liver and

Other Distant Metasases from Neuroendocrine Neoplasms. Neuroendocirnology 2012

0 %

10 %

2 0 %

3 0 %

4 0 %

5 0 %

6 0 %

7 0 %

8 0 %

9 0 %

S EER N ET C e n t e r s

p N ETS m a ll B o w e l

IR T r e a t m e n t s o f M e t a s t a t ic N ET

W h o P a t ie n t s e le c t io n

W h e n In d ic a t io n s a n d t im in g o f

t h e r a p y

W h a t T A C E v s T A E v s Y 9 0

L im it e d M e t a s t a t ic D is e a s e

P e r c u t a n e o u s A b la t io n

R e s e c t io n v s A b la t io n Le s io n s < 3 c m

N o d if f e r e n c e in s u r v iv a l o r r e c u r r e n c e f r e e s u r v iv a l

P ro c e d u r e t im e , le n g t h o f s t a y a n d b lo o d lo s s w e r e a ll lo w e r in a b la t io n g ro u p

Feng J Hepatol. 2012 Oct;57(4):794-802.

Chen Ann Surg 2006; 243:321–328

P e r c u t a n e o u s A b la t io n

P e r c u t a n e o u s L iv e r A b la t io n G u id e lin e s ≤ 3 lesions

≤ 3 cm in size

Location amenable to ablation

No ablation modality proven to be better

RFA/Microwave/Cryo…

P e r c u t a n e o u s A b la t io n

P e r c u t a n e o u s L iv e r A b la t io n G u id e lin e s ≤ 3 lesions 5 lesions

≤ 3 cm in size 5 cm in size

Location amenable to ablation

No ablation modality proven to be better

RFA/Microwave/Cryo…

L im it e d M e t a s t a t ic D is e a s e

E x t e n s iv e M e t a s t a t ic D is e a s e

T h e r a p y o p t io n s

C h a m b e r la in e t a l N o d if f e r e n c e in p a in o r

h o rm o n a l s y m p t o m r e lie f w it h e it h e r s u rg e r y o r e m b o liz a t io n w h e n n o t w it h c u r a t iv e in t e n t

Chamberlain et al. JCAS 2000 Apr; 190

T h e r a p y o p t io n s

M a y o e t a l R e t ro s p e c t iv e IA T v s S u rg e ry

7 5 3 p t s a t 9 c e n t e r s• Ex t r a h e p a t ic d is e a s e

• 4 0 .6 % v s 16 .2 %• > 5 0 % liv e r in v o lv e m e n t

• 6 5 % v s 2 6 %

N o d if f e r e n c e in s u r v iv a l f o r a s y m p t o m a t ic p t s w it h > 2 5 % t u m o r b u rd e n

Mayo et al Annals of Surg Onc 2011

W h o s h o u ld g e t t r a n s a r t e r ia l t h e r a p y

U n re s e c t a b le o r R e c u r r e n t d is e a s e S y m p t o m c o n t ro l L im it p ro g r e s s io n

T e c h n ic a lly R e s e c t a b le A s y m p t o m a t ic , n o n - b u lk y d is e a s e ? Ex t r a h e p a t ic d is e a s e ?

W h e n s h o u ld p a t ie n t s g e t LD T

E a r ly / T im e o f D ia g n o s is RC T a lp h a in t e f e r o n + / - e m b o liz a t io n a t t im e o f

d ia g n o s is N o e m b o : 3 8 % RR , 4 0 % O S a t 5 y r Em b o : 6 0 % RR , 7 5 % O S a t 5 y r

La t e R e t r o s p e c t iv e r e v ie w 12 3 p t s t r e a t e d w it h

e m b o liz a t io n R a n g e o f d u r a t io n o f liv e r d is e a s e 1- 14 4 m o n t h s 8 0 % o v e r a ll R R D u ra t io n o f d is e a s e h a d n o e f f e c t o n RR , O S , P F S

Hanssen et al Acta Oncol. 1991;30(4):523-7

Gupta Cancer. 2005 Oct 15;104(8):1590-602

R e p e a t T r e a t m e n t

S w a rd e t a l 10 7 p t s w it h m id g u t

c a r c in o id 1- 4 t r e a tm e n t s

M e d ia n s u r v iv a l f r o m t x5 6 m o n t h s

Sward et al Br J Surg. 2009 May;96(5):517-21.

A r t e r ia l T h e r a p ie s

B la n d e m b o liz a t io n

C h e m o e m b o liz a t io n

R a d io e m b o liz a t io n

D o e s r e g io n a l c h e m o t h e r a p y a d d b e n e f i t ?

T A E B la n d r e g im e n

G e lf o a m P V A p a r t ic le s C y a n o a c ry la t e g lu e T r is a c r y l g e la t in

m ic ro s p h e r e s• 4 0 - 7 0 0 m ic r o n

T A C E C h e m o r e g im e n

c is p la t in , v in b lis t in e S t r e p t o z o c in , 5 - f u S t r e p t o z o c in D o x o ru b ic in C is p la t in , d o x o ru b ic in ,

m it o m y c in

Madoff et al. J Vas Interv Radiol 2006 Aug;17(8):1235-49

T A C E / T A E

S t u d y N M e t h o d R e s p o n s e % S u r v iv a l( m o n t h s )

D o n g e t a l 12 3 TA C E 6 2 3 9

D e B a e re e t a l 2 0 TA C E 8 0 N R

V o g l e t a l 4 8 TA C Em / TA C Eg m 11/ 2 3 3 8 / 5 7

Lo e w e e t a l 2 3 TA E 7 3 6 9

E r ik s s o n e t a l 4 1 TA E 5 0 8 0

T A C E / T A E

S t u d y N M e t h o d To x ic i t y R e s p o n s e % S u r v iv a l( m o n t h s )

P it t e t a l 10 0 TA E / TA C E TA E : 6 .6TA C E : 2 .4N S

N R 2 5 .5 / 2 5 .7 N S

Ru u t ia n ie n e t 6 7 TA E / TA C E TA E : 2 2 %TA C E : 2 5 %

3 8 / 2 2 3 9 / 4 4N S

G u p t a e t a l 4 9 TA E / TA C E TA E : 12 %TA C E 2 0 %

2 5 / 5 0 C a rc in o id : p N ET : 18 / 3 3 *

M a ire e t a l * 2 6 TA E / TA C E TA C E : 3TA E : 2

9 2 / 10 0 2 y r : 10 0 % / 8 0 %N S

DEB - TACE

DEB vs cTACE in HCC (PRECISION V Trial)

Reduced liver toxicity and side effects

SAE: 30.6% vs 20.4%

Alopecia: 19.4% vs 2.2%

Max transaminase change 50% less

Lammer et al. CVIR 2010 33:41-52.

DEB- TACE

Drug eluting bead TACE

Phase II 13 pts treated with doxorubicin beads

ORR 78%

54% biloma formation

4 required drainage

Bhagat et al CVIR 2013

Radioembolization

Yttrium 90 Pure beta-emitter with a

half-life of 64.2 hours.

Tissue penetration of the emissions is 2.5 to 11 mm

Available in two forms Glass (HDE for HCC) and Resin (FDA for CRC)

Delivered via transarterial catheter and emits local high dose of radiation to tumor.

Y t t r iu m 9 0 m ic r o s p h e r e s

P r o s C o n s B e t t e r s h o r t t e rm

t o le r a b ilit y

O u t p a t ie n t p r o c e d u r e

Le a v e a r t e r ie s p a t e n t f o r a d d it io n a l t h e r a p y

P o t e n t ia l in c r e a s e d G I a n d p u lm o n a r y t o x ic it y

C u m u la t iv e h e p a t ic r a d ia t io n t o x ic it y

R a d io e m b o l iz a t io n

K e n n e d y e t a l R e t r o s p e c t iv e r e v ie w 14 8

p t s 10 c e n t e r s 6 7 % s m a ll b o w e l 19 % p a n c r e a s

G ra d e 3 / 4 t o x ic it y F a t ig u e 6 .5 % N a u s e a 3 .2 % P a in 2 .7 % A s c it e s 0 .5 %

R e s p o n s e R a t eC R - 2 .7 %P R - 6 0 .5 %S D - 2 2 .7 %P D - 4 .9 %

Kennedy et al Am J Clin Onc June 2008

Radioembolization

S t u d y N R e s p o n s e S u r v iv a l( m e d ia n m o n t h s )

R h e e e t a l 4 2 5 0 2 8Ke n n e d y e t a l 14 8 6 3 7 0K in g e t a l 5 8 3 9 3 6S a x e n a e t a l 4 8 5 4 3 5C a o e t a l 5 8 3 9 3 6P a p ro t t k a e t a l 4 2 5 5 N R ( 9 5 % a t 16 M e m o n e t a l 4 0 6 4 % W H O

7 1% EA S L3 4

T A C E v s T A R E

P o o le d a n a ly s is o f 3 7 a r t ic le s w it h 15 0 0 p t s T A C E

O RR 5 8 % M e d ia n s u r v iv a l 3 5 m o n t h s

T A RE O RR 6 3 % M e d ia n s u r v iv a l 2 8 m o n t h s

C o n c lu s io n “T r e a tm e n t s t r a t e g ie s m u s t b e t a ilo r e d in d iv id u a lly f o r

p a t ie n t s a c c o rd in g t o t h e ir d is e a s e , m e d ic a l s t a t u s , p r e f e r e n c e a n d q u a lit y o f lif e c o n s id e r a t io n s ”

Yang et al Surgical Oncology 2012

W h a t is t h e r o le o f In t e r v e n t io n a l R a d io lo g y ?

2 1%

15 %

2 7 %

17 %5 %

15 %2 0 %

S u p p o r t iv e C a r e

C h e m o t h e r a p y

R e s e c t io n o f P r im a r yT u m o r

L iv e r R e s e c t io n

S u r g ic a l R e s e c t io n +Em b o liz a t io n

Em b o liz a t io n

W h a t is t h e r o le o f In t e r v e n t io n a l R a d io lo g y ?

19 %

3 4 %

2 2 %6 %

19 %2 5 %

C h e m o t h e r a p y

R e s e c t io n o f P r im a r yT u m o r

L iv e r R e s e c t io n

S u rg ic a l R e s e c t io n +Em b o liz a t io n

Em b o liz a t io n

Liv e r R e s e c t io n

A b la t io n

Em b o liz a t io nP r im a r y

R e s e c t io n

C h e m o t h e ra p y