y menu how to monitor hcc treatment jfim hani 2015

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Yves Menu Hôpital Saint Antoine – Paris [email protected] 1905 2015

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Yves Menu Hôpital Saint Antoine – Paris

[email protected]

1905 2015

Some facts about the population

�  500 - 700 000 deaths per year (worldwide) �  15% are detected at a « curative » stage �  Less than 50 % of countries in the world

are equiped for relevant curative treatment �  5-7 % have the benefit of the curative

treatment

Rationale for targeted therapies

� Overexpression of VEGF is one of the major features of HCC (Chow 1997) and is associated with a poor prognosis (Poon 2004)

� Microvascular density is a factor for recurrence after resection (Poon 2002)

There is a price for that

�  Medical price : �  Hand foot syndrome +++ �  Diarrhoea �  Asthenia

�  Economical price (per month) �  China 7 300 $ �  USA 5 400 $ �  Brasil 5 000 $ �  France 4 800 $

Patent for Nexavar will expire in 2020 (EU) and 2022 (USA)

Good candidates

� Excellent performance status � Expected survival > 6 month � Normal or moderately abnormal liver

tests � Not eligible for transplantation,

resection, ablation or TACE

Other perspectives

� Adjuvant (STORM) � Neo-adjuvant (Hoffmann, 2015,

negative) � Combined therapies (+TACE, unclear) � Other drugs

à Under evaluation

Benefit (economic) of Sorafenib related to HCC

Some practical conclusions for the oncologist �  Sorafenib is mostly given to patients who

will not have a curative treatment �  There is no recommendation for a second

line �  Tolerance is good to excellent à No reason to prompt PD, as there is nothing else than BSC after failure of Sorafenib, excepting trials. PD if « symptomatic ».

Some practical conclusions for the Radiologist � No need to detect as early as possible

progression or recurrence � No necessity to develop complicated

algorithms for evaluation � Only call PD when absolutely

unequivocal

CT or MRI?

� MRI clearly superior � Adds a bonus of 20% for Se and Sp

However… 1.  Early detection is not the main issue 2.  CT is by far superior for evaluation of extra

hepatic disease 3.  If MRI is performed, a plain CT should be

associated 4.  Reproducibility is better with CT 5.  Radiation dose is not a relevant issue in this

population

Therefore

� CT is today the work horse of evaluation � Combination CT/MRI is relevant in

patients included in a protocol � Cross-over from CT to MR is

unacceptable

07-2012

07-2012

11-2012

What are the standards? Response RECIST 1.1 mRECIST CHOI mCHOI CR 0 0 0 0

PR -30% SOD -30% SOD (viable)

Size < 10% OR

Tumour density < 15%

Size < 10% AND

Tumour density < 15%

PD +20% SOD +20% SO (Viable)

Tumour size + 10% AND

No « Density PR)

Tumour size + 10% AND

No « Density PR)

Recist 1.1

� Universally rejected for the evaluation of HCC, due to inability to evaluate the viable compartment

� Remains a « Plan B » for hypovascular lesions

mRECIST

� Adopted as THE reference standard

mRECIST

Sep 2009 97 mm

Sept 2010 32 mm

25/07/2014 12/01/2015

arterial

portal

CHOI and mCHOI � Advantages

�  Simple exploration of viability �  Portal phase à less dependent on the

quality of arterial acquisition � Good predictor of survival (Ronot 2014)

� Pitfalls � Dedicated to CT � mCHOI may not be relevant (Weng, 2013) �  Interobserver agreement suboptimal (Ronot,

2014)

Arterial Phase

Portal Phase

25/07/2014 12/01/2015

arterial

portal

80 HU 15 HU

CHOI and mCHOI � Advantages

�  Simple exploration of viability �  Portal phase à less dependent on the

quality of arterial acquisition � Good predictor of survival (Ronot 2014)

� Pitfalls � Dedicated to CT � mCHOI may not be relevant (Weng, 2013) �  Interobserver agreement suboptimal (Ronot,

2014)

� EASL (European Association for the Study of the Liver) �  Powerful, but time

consuming �  Not a « fast tool »

03/14 07/14

10/14

03-2011

11-2011 01-2014

RECIST

mRECIST

mor

phol

ogy

enha

ncem

ent

EASL/CHOI

WHO

1D 2D 3D

vRECIST

vEASL

Volume of enhancement Parameters of enhancement

Enhancement curve Histogram Texture

Endovascular treatments

§  TACE

§  DC Beads

§  Radio embolisation: RE Y90

TACE: MR>>CT (lipiodol)

TACE Evaluation of response?

Post Pre

cTACE

mRECIST: PR

Ablation

§  mRECIST and RECIST non applicable

§  MRI superior to CT

The right area?? 1.  Same place

2.  Ablation > initial tumour

If no margin à high recurrence rate

11/2011

01/2012, J0 post RF

11/2011

01/2012, J0 post RF

11/2011

05/2012 02/2012

Recurrence? Difficult procedure, several accesses.

Seeding

Take Home Points

§  For the evaluation of systemic therapy,

mRECIST is the standard. No need to develop

sophisticated tools for the moment

§  Concerning endovascular treatment, the

situation is more complicated. Value of

parametric images and MRI

Jun 2009 Sep 2009