Functional imaging in liver tumours

Ronot, Maxime; Clift, Ashley Kieran; Vilgrain, Valérie; Frilling, Andrea

doi:10.1016/j.jhep.2016.06.024

Cited by 46 publications

(37 citation statements)

References 151 publications

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“…The development of novel radiotracers (beyond 18 F-FDG) for PET imaging could bridge the findings from proteomics and metabolomics analyses to imaging and thus add useful and important information on tissue distribution to these data. Today, molecular imaging for primary liver tumors is still limited by e.g ., lack of specific tracer uptake into malignant cells[ 57 ].…”

Section: Proteomics Glycomics and Imagingmentioning

confidence: 99%

Biomarkers for hepatocellular carcinoma: What’s new on the horizon?

Ocker¹

2018

WJG

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Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids (DNA, RNA or miRNA-containing exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.

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Section: Proteomics Glycomics and Imagingmentioning

confidence: 99%

Biomarkers for hepatocellular carcinoma: What’s new on the horizon?

Ocker¹

2018

WJG

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“…Hepatocellular carcinoma (HCC) is the fourth most common cancer worldwide [ 19 ]. Although a spectrum of methods has been developed for the early detection of different cancer types in order to allow early therapeutic interventions, early detection of HCC is difficult because the symptoms often do not appear until the late developmental stages, leading to a poor survival rate of HCC patients [ 20 , 21 ]. Additionally, since liver is a major metabolic organ, this represents an additional challenge for the development of molecular probes for HCC imaging.…”

Section: Introductionmentioning

confidence: 99%

Heptamethine carbocyanine DZ-1 dye for near-infrared fluorescence imaging of hepatocellular carcinoma

Zhao

Zhang

et al. 2017

Oncotarget

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Near-infrared fluorescence (NIRF) dyes have recently emerged as promising tools for non-invasive imaging of different types of cancers. Here, we explored the potential utility of a NIRF DZ-1 dye, with dual imaging and tumour targeting functions, in hepatocellular carcinoma (HCC). We showed the preferential uptake of DZ-1 by HCC cells in vitro and in derived subcutaneous/orthotopic tumour xenografts, accompanied by a minimal effect on normal cells. DZ-1 simplified tumour growth profiling as well, since we were able to correlate NIRF signals with tumour volume and/or tumour-emitting luminescence in mice. Using both orthotopic tumour transplantation and cirrhosis models in parallel, we demonstrated the ability of DZ-1 to differentiate liver tumour from cirrhosis. DZ-1 showed superiority in HCC imaging over indocyanine green by demonstrating significantly enhanced tumour-targeting specificity. At the cellular level, DZ-1 was mainly retained in mitochondria and lysosomes. Additionally, DZ-1 fluorescence spectroscopy has been used for the intraoperative navigation of rabbit liver cancer, to determine surgical margins. We showed that tumor hypoxia and select organic anion-transporting polypeptide genes mediate NIRF dye uptake in HCC, which was supported by clinical evidence. All these findings represent the first evidence that DZ-1 is an effective molecular probe for tumour-specific imaging in HCC, and provide insights into the development of a new generation of imaging agents for intraoperative guidance of cancer surgery.

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“…Other imaging features have been proposed as surrogate biomarkers of response and survival in patients treated by antiangiogenic therapies, including perfusion CT,21 contrast-enhanced ultrasound,22 and diffusion-perfusion MRI 23. However, these techniques have failed widespread implementation primarily because of lack of reproducibility.…”

Section: Introductionmentioning

confidence: 99%

Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab

Dohan

Gallix

Guiu

et al. 2019

Gut

111

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PurposeThe objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders.MethodsThis study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial.ResultsIn the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10–7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p<0·001). Patients with a SPECTRA Score >0·02 had a lower OS in the training cohort (p<0·0001), in the validation cohort (p<0·0008) and in the external validation cohort (p=0·0027). SPECTRA Score at 2 months had the same prognostic value as RECIST at 6 months, while non-response according to RECIST1·1 at 2 months was not associated with a lower OS in the validation cohort (p=0·238). Morphological response was not associated with OS (p=0·41).ConclusionA radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies.Trial registrationClinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.

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Functional imaging in liver tumours

Cited by 46 publications

References 151 publications

Biomarkers for hepatocellular carcinoma: What’s new on the horizon?

Biomarkers for hepatocellular carcinoma: What’s new on the horizon?

Heptamethine carbocyanine DZ-1 dye for near-infrared fluorescence imaging of hepatocellular carcinoma

Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab

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