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

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

Preoperative imaging BEFORE TREATMENT 1990-2010

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 81,2% MR 93,4% FDG-PET 94 % CT 74,4% MR 80,3% FDG-PET 81,4% < 10 mm MR > CT (p=.006)

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

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

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%

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

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?

Colorectal metastases POST NEOADJUVANT CHEMOTHERAPY SENSITIVITY FDG-PET/CT < MDCT* Immediate resection 33 lesions Neoadjuvant chemotherapy 122 lesions FDG-PET/CT 93,3% MDCT 87,5% FDG-PET/CT 49% MDCT 65,3% *Lubezky N et al J Gastroint Surg 2007; 11: 472

Colorectal metastases POST NEOADJUVANT CHEMOTHERAPY SENSITIVITY FDG-PET/CT < MDCT* Bevacizumab - Bevacizumab + FDG-PET/CT 59% MDCT 67% FDG-PET/CT 39% MDCT 63% *Lubezky N et al J Gastroint Surg 2007; 11: 472

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

Colorectal metastases POST NEOADJUVANT CHEMOTHERAPY Normalization of FDG uptake not usually related to complete pathologic response Tan M. et al J Gastroint Surgery 2007; 11. 1112

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

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

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

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

Colorectal metastases POST NEOADJUVANT CHEMOTHERAPY MDCT Steatosis: a big issue 63 year old male 2009 colon carcinoma diagnosis Subtotal colectomy T3 Mo Nx G2 Adjuvant chemotherapy Sept 2012 CT liver metastases segment III and IV 3 cycles chemotherapy Jan 2013 CT preoperative staging

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

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

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)

Preoperative imaging POST NEOADJUVANT CHEMOTHERAPY MR > CT

Preoperative imaging POST NEOADJUVANT CHEMOTHERAPY MR > CT

WHAT ABOUT US ? Liver metastases DETECTION US Sensitivity 57%-82% < 1 cm 20% Kinkel K Radiology 2002; 224:748 CEUS Sensitivity 80-98% Specificity 66-98% e 100% > 2 cm Quaia E Eur Radiology 2006; 16:1599

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

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

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

RESULTS Arterial phase Timing issues Basilico R et al RSNA 2008

Colorectal metastases CEUS FOLFOX + BEVACIZUMAB PRE 15 days POST

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

Colorectal metastases CEUS Before neoadjuvant chemotherapy

Colorectal metastases CEUS 2 months post FOLFOX + BEVACIZUMAB Fibrotic nodule

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

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

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

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

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

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