1. COLORECTAL LIVER METASTASES:
To resect the unresectable: which imaging after treatment ?
Raffaella Basilico
Chieti, 19 Ottobre 2017
Dipartimento di Neuroscienze e Imaging
Sezione di Imaging Integrato e
Terapie Radiologiche
CHIETI

2. BEFORE AND AFTER TREATMENT Volumetric assessment
PREOPERATIVE IMAGING
Number
Distribution
(Unilobar Bilobar)
BEFORE AND AFTER TREATMENT
Volumetric assessment
Vessels relationship
Future liver remnant

3. Preoperative imaging
BEFORE TREATMENT

4. Sensitivity CT 81,2% CT 74,4% MR 93,4% MR 80,3% FDG-PET 94 %
Preoperative imaging
BEFORE TREATMENT
Sensitivity
Lesion per lesion basis >10 mm
Patient per patient basis
CT ,2%
MR ,4%
FDG-PET 94 %
CT ,4%
MR ,3%
FDG-PET 81,4%
< 10 mm
MR > CT (p=.006)

5. MR FDG-PET/CT * FDG-PET FDG-PET/CT First line modality
Preoperative imaging
BEFORE TREATMENT MR
First line modality
FDG-PET/CT *
FDG-PET
Second line modality
extrahepatic disease
FDG-PET/CT
Small number of studies
*Georgakopoulos A et al Clin Imaging Oct 2012

6. 2000-2015 DWI-MRI HOW TO PERFORM MRI ? Preoperative imaging
BEFORE TREATMENT
HOW TO PERFORM MRI ?
DWI-MRI
It is an unenhanced MRI method of supplying information of molecular diffusion of water in biologic tissues

7. DWI-MRI alone DWI -MRI+ CE- MRI Sensitivity 87,1% 95,5%
Preoperative imaging
BEFORE TREATMENT
DWI-MRI alone
DWI -MRI+ CE- MRI
Sensitivity
87,1%
95,5%

8. Colorectal liver metastases
Preoperative imaging
WHAT HAPPENS AFTER TREATMENT?
Colorectal liver metastases
- Radiofrequency ablation
Neoadjuvant Chemotherapy
- Radiotherapy
- y 90 Radioembolization
Immunotherapy
- Chemoembolization

9. Colorectal metastases
NEOADJUVANT CHEMOTHERAPY
Imaging modalities limitations
Chemotherapy-associated hepatic parenchymal injury
Steatosis
Steatohepatitis
Sinusoidal dilatation
Imaging sensitivity and specificity
Hôpital Beaujon - Paris
Focal fatty sparing or
liver metastasis?

10. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
SENSITIVITY
FDG-PET/CT < MDCT*
Immediate resection
33 lesions
Neoadjuvant chemotherapy
122 lesions
FDG-PET/CT 93,3%
MDCT ,5%
FDG-PET/CT 49%
MDCT ,3%
*Lubezky N et al J Gastroint Surg 2007; 11: 472

11. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
SENSITIVITY
FDG-PET/CT < MDCT*
Bevacizumab -
Bevacizumab +
FDG-PET/CT 59%
MDCT %
FDG-PET/CT 39%
MDCT %
*Lubezky N et al J Gastroint Surg 2007; 11: 472

12. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
Colorectal metastases
FDG-PET/CT < MDCT
WHY ?
- Size of the lesion
decrease in size of the lesion
following CHT
- Reduction of FDG uptake altered tumor glucose
metabolism induced by chemotherapy
- Heterogeneous FDG uptake
central necrosis
(Bevacizumab!)
- Lesion uptake only slightly greater than relatively high FDG uptake in normal liver

13. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
Normalization of FDG uptake
not usually related to complete pathologic response
Tan M. et al J Gastroint Surgery 2007;

14. FDG-PET/CT 34 lesions = complete metabolic response 5 lesions
Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
FDG-PET/CT
34 lesions = complete metabolic response
5 lesions
29 lesions
complete tumor destruction
at pathology
viable tumor at pathology
Contrast–enhanced FDG PET/CT ?
Eur J Radiol Feb 2013

15. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
SENSITIVITY
MDCT*
Neoadjuvant chemotherapy
60 pts
NO neoadjuvant chemotherapy
32 pts
Lesion per lesion basis
71%
76%
Patient per patient basis
54%
69%
*Angiviel B et al Ann Surg Oncol 2009; 16 (5): 1247

16. Colorectal metastases MORFOLOGIC ASSESSMENT vs RECIST CRITERIA*
POST NEOADJUVANT
CHEMOTHERAPY
MDCT
MORFOLOGIC ASSESSMENT vs RECIST CRITERIA*
(Bevacizumab)
RECIST-stable disease and morphological optimal response
* Chun S et al Jama 2009; 302 (21): 2338

17. Colorectal metastases MORFOLOGIC ASSESSMENT vs RECIST CRITERIA*
POST NEOADJUVANT
CHEMOTHERAPY
MDCT
MORFOLOGIC ASSESSMENT vs RECIST CRITERIA*
(Bevacizumab)
RECIST-stable disease and morphological incomplete response
* Chun S et al Jama 2009; 302 (21): 2338

18. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
MDCT
Steatosis: a big issue
63 year old male
2009 colon carcinoma diagnosis
Subtotal colectomy
T3 Mo Nx G Adjuvant chemotherapy
Sept CT liver metastases segment III and IV
3 cycles chemotherapy
Jan 2013 CT preoperative staging

19. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
MDCT
Steatosis: a big issue
PRE
POST

20. 9 mm metastasis from colon carcinoma G2
Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
Histopathology
III
9 mm metastasis from colon carcinoma G2
III IV IV
1.1 cm fibronecrotic nodule from previous colorectal metastasis

21. Colorectal metastases
POST NEOADJUVANT
CHEMOTHERAPY
3.0 T MRI vs 64 row MDCT
( IOUS and histopathology as standard of reference)
3.0 T MRI
64 row MDCT
66/68 lesions 97%
49/68 lesions 72%
p < 0.001
Lesions < 1 cm
p < 0.001
29/31 lesions 93%
13/31 lesions 42%
*Berger-Kulemann et al Eur J Surg Oncol 2012; 38(8): 670
** Macera A et al Eur Radiol 2013; 23: 739 (DWI+Gd-EOB-DTPA MRI)

22. Preoperative imaging
POST NEOADJUVANT
CHEMOTHERAPY
MR > CT

23. Preoperative imaging
POST NEOADJUVANT
CHEMOTHERAPY
MR > CT

24. WHAT ABOUT US ? Liver metastases DETECTION US Sensitivity 57%-82%
< 1 cm 20%
Kinkel K Radiology 2002; 224:748
CEUS
Sensitivity %
Specificity % e 100% > 2 cm
Quaia E Eur Radiology 2006; 16:1599

25. CEUS for all oncologic patients during follow up?
Liver metastases
WHAT ABOUT US ?
CEUS for all oncologic patients during follow up?
…”CEUS seems to be promising in the detection of liver metastases; however, there have not been enough studies to conduct meta-analysis. Further studies are required before this promising method can be widely used”.
Baseline
CEUS

26. Hepatic metastasis of GIST
Contrast Tissue Discriminator CTD
Hepatic metastasis of GIST
Before Tt
After 2 weeks
Before treatment : 90% of contraste uptake
After 14 days : total necrosis of lesions
Courtesy of Dr. N. Lassau

27. RESULTS Lesion enhancement pattern 10 20 40 6 34 6 5 23 6 4 4 5 4 3 2
Basilico R et al RSNA 2008
Lesion enhancement pattern
Diffuse enh.
Rim enh.
Neoplasm
CEUS
MDCT
CEUS
MDCT 10 20 GI 40 6
Breast 34 6 5 23
Lung 6 4 4 5
Pancreas 4 3 2 2
Carcinoid 3 3
Melanoma, kidney, lymphoma 4 3 1
Prostate, bladder, ovary, uterus, sclerosing fibros. 4 1 3 6

28. RESULTS
Arterial phase
Timing issues
Basilico R et al RSNA 2008

29. Colorectal metastases
CEUS
FOLFOX + BEVACIZUMAB
PRE
15 days POST

30. Colorectal metastases
CEUS
Early response to treatment
Perfusion parameters of 3D-CEUS (PE and AUC) significantly decreased respectively by up to 69% and 77% in responsive tumors within 1 day after antiangiogenetic treatment
BUT
Not in non responsive tumors

31. Colorectal metastases
CEUS
Before neoadjuvant chemotherapy

32. Colorectal metastases
CEUS
2 months post FOLFOX + BEVACIZUMAB
Fibrotic nodule

33. Disappearing of liver colo-rectal metastases at
POST NEOADJUVANT
CHEMOTHERAPY
IMAGING
Disappearing of liver colo-rectal metastases at
cross-sectional imaging
SERIAL IMAGING
To avoid a complete radiological response when possible
GOAL = resectability rather than waiting
for maximum response
COMPLETE RESPONSE ?
Low rate of true complete response + high rate of
intrahepatic recurrences in surgically untreated patients *
complete surgical treatment
of all original sites
*Van Vledder M et al J Gastroint Surg 2010; 14: 1691

34. CT vs EOB MRI POST NEOADJUVANT CHEMOTHERAPY
Disappearing colorectal liver
metastases after chemotherapy

35. EOB MRI > CT POST NEOADJUVANT CHEMOTHERAPY
Prediction of pathologic absence of tumor and lack
of lesion recurrence in disappearing CRM after
chemotherapy

36. Initial delay in response to treatment
POST IMMUNOTHERAPY
Initial delay in response to treatment
Slow decrease in tumor size
Enlarging tumors
immediately after treatment
Appearance of
new lesion
Follow up imaging studies should be performed at least 4 weeks after completion of treatment
Kwak J et al Radiographics 2015: 35:424

37. MRI First line modality US contrast agents Perfusion CT/MRI
Preoperative imaging
AFTER TREATMENT
MRI
First line modality
US contrast agents
Perfusion CT/MRI
Diffusion MRI
Early evaluation of treatment
response

38. Before and After treatment
Preoperative imaging
LIVER METASTASES
Before and After treatment
MULTIDISCIPLINARY
TEAM
Oncology
Pathology
Imaging
Surgery