How to monitor HCC treatment

1. Yves MenuHôpital Saint Antoine – Paris
yves.menu@aphp.fr
1905 2015

2. Some facts about the population
ž 500 - 700 000 deaths per year (worldwide)
ž 15% are detected at a « curative » stage
ž Less than 50 % of countries in the world
are equiped for relevant curative treatment
ž 5-7 % have the benefit of the curative
treatment

3. Rationale for targeted therapies
ž Overexpression of VEGF is one of the
major features of HCC (Chow 1997) and
is associated with a poor prognosis
(Poon 2004)
ž Microvascular density is a factor for
recurrence after resection (Poon 2002)

5. There is a price for that
ž Medical price :
— Hand foot syndrome +++
— Diarrhoea
— Asthenia
ž 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)

6. Good candidates
ž Excellent performance status
ž Expected survival > 6 month
ž Normal or moderately abnormal liver
tests
ž Not eligible for transplantation,
resection, ablation or TACE

7. Other perspectives
ž Adjuvant (STORM)
ž Neo-adjuvant (Hoffmann, 2015,
negative)
ž Combined therapies (+TACE, unclear)
ž Other drugs
à Under evaluation

8. Benefit (economic) of Sorafenib
related to HCC

9. Some practical conclusions for
the oncologist
ž Sorafenib is mostly given to patients who
will not have a curative treatment
ž There is no recommendation for a second
line
ž 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 ».

10. Some practical conclusions for
the Radiologist
ž No need to detect as early as possible
progression or recurrence
ž No necessity to develop complicated
algorithms for evaluation
ž Only call PD when absolutely
unequivocal

11. CT or MRI?
ž MRI clearly superior
ž Adds a bonus of 20% for Se and Sp

13. 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

14. Therefore
ž CT is today the work horse of evaluation
ž Combination CT/MRI is relevant in
patients included in a protocol
ž Cross-over from CT to MR is
unacceptable

15. 07-2012

16. 07-2012
11-2012

17. 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)

18. Recist 1.1
ž Universally rejected for the evaluation of
HCC, due to inability to evaluate the
viable compartment
ž Remains a « Plan B » for hypovascular
lesions

19. mRECIST
ž Adopted as THE reference standard

20. mRECIST
Sep 2009
97 mm
Sept 2010
32 mm

21. 25/07/2014 12/01/2015
arterial
portal

22. CHOI and mCHOI
ž Advantages
— Simple exploration of viability
— Portal phase à less dependent on the
quality of arterial acquisition
— Good predictor of survival (Ronot 2014)
ž Pitfalls
— Dedicated to CT
— mCHOI may not be relevant (Weng, 2013)
— Interobserver agreement suboptimal (Ronot,
2014)

23. Arterial Phase
Portal Phase

24. 25/07/2014 12/01/2015
arterial
portal
80 HU 15 HU

25. CHOI and mCHOI
ž Advantages
— Simple exploration of viability
— Portal phase à less dependent on the
quality of arterial acquisition
— Good predictor of survival (Ronot 2014)
ž Pitfalls
— Dedicated to CT
— mCHOI may not be relevant (Weng, 2013)
— Interobserver agreement suboptimal (Ronot,
2014)

26. ž EASL (European
Association for the
Study of the Liver)
— Powerful, but time
consuming
— Not a « fast tool »
03/14 07/14
10/14

27. 03-2011

28. 11-2011 01-2014

29. RECIST
mRECIST
morphologyenhancement
EASL/CHOI
WHO
1D 2D 3D
vRECIST
vEASL

30. Volume of enhancement Parameters of enhancement

31. Enhancement curve HistogramTexture

33. Endovascular treatments
§ TACE
§ DC Beads
§ Radio embolisation: RE Y90

34. TACE:
MR>>CT
(lipiodol)

35. TACE
Evaluation of response?
PostPre

36. cTACE
mRECIST: PR

37. Ablation
§ mRECIST and RECIST non applicable
§ MRI superior to CT

38. The right area??
1. Same place
2. Ablation > initial tumour
If no margin à high recurrence rate

39. 11/2011
01/2012, J0 post RF

40. 11/2011
01/2012, J0 post RF

41. 11/2011
05/201202/2012

42. Recurrence?
Difficult procedure, several accesses.
Seeding

43. 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

44. Jun 2009 Sep 2009