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. 2022 Sep 16;11(18):5451.
doi: 10.3390/jcm11185451.

Functional Investigation of the Tumoural Heterogeneity of Intrahepatic Cholangiocarcinoma by In Vivo PET-CT Navigation: A Proof-of-Concept Study

Luca Viganò  1   2 , Egesta Lopci  3 , Luca Di Tommaso  2   4 , Annarita Destro  4 , Alessio Aghemo  2   5 , Lorenza Rimassa  2   6 , Luigi Solbiati  2   7 , Arturo Chiti  2   3 , Guido Torzilli  2   8 , Francesco Fiz  3   9
Affiliations

Functional Investigation of the Tumoural Heterogeneity of Intrahepatic Cholangiocarcinoma by In Vivo PET-CT Navigation: A Proof-of-Concept Study

Luca Viganò et al. J Clin Med. .

Abstract

Intra-tumoural heterogeneity (IH) is a major determinant of resistance to therapy and outcomes but remains poorly translated into clinical practice. Intrahepatic cholangiocarcinoma (ICC) often presents as large heterogeneous masses at imaging. The present study proposed an innovative in vivo technique to functionally assess the IH of ICC. Preoperative 18F-FDG PET-CT and intraoperative ultrasonography were merged to perform the intraoperative navigation of functional tumour heterogeneity. The tumour areas with the highest and the lowest metabolism (SUV) at PET-CT were selected, identified during surgery, and sampled. Three consecutive patients underwent the procedure. The areas with the highest uptake at PET-CT had higher proliferation index (KI67) values and higher immune infiltration compared to areas with the lowest uptake. One of the patients showed a heterogeneous presence of FGFR2 translocation within the samples. Tumour heterogeneity at PET-CT may drive biopsy to sample the most informative ICC areas. Even more relevant, these preliminary data show the possibility of achieving a non-invasive evaluation of IH in ICC, paving the way for an imaging-based precision-medicine approach.

Keywords: FGFR2 translocation; imaging fusion; immunology; intra-tumoural heterogeneity; intrahepatic cholangiocarcinoma; navigation technology; positron emission tomography–computed tomography.

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Conflict of interest statement

The authors declare no conflict of interest pertinent to the present manuscript. Considering the conflicts of interest in general, we state that: (1) L.V. received speaker’s honoraria from Johnson & Johnson. (2) A.C. received speaker’s honoraria from Advanced Accelerator Applications, General Electric Healthcare, Sirtex Medical Europe and AmGen Europe; received travel grants form General Electric Healthcare and Sirtex Medical Europe; he is a member of Blue Earth Diagnostics’ and Advanced Accelerator Applications’ advisory boards; received scientific support, in terms of a three-year Ph.D. fellowship, from the Sanofi Genzyme. (3) L.R. reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. All other authors have no relevant disclosures.

Figures

Figure 1
Figure 1
Navigation technology with the intraoperative fusion of preoperative PET-CT and IOUS. The tumour areas having different uptake at PET-CT are identified in vivo during surgery. (a) PET axial view of ICC; (b) Intraoperative fusion of PET-CT and IOUS images.
Figure 2
Figure 2
IOUS-guided biopsy of the tumour areas having different uptake at PET-CT.
See this image and copyright information in PMC

References

    1. Gerlinger M., Rowan A.J., Horswell S., Math M., Larkin J., Endesfelder D., Gronroos E., Martinez P., Matthews N., Stewart A., et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 2012;366:883–892. doi: 10.1056/NEJMoa1113205. - DOI - PMC - PubMed
    1. Kreso A., O’Brien C.A., van Galen P., Gan O.I., Notta F., Brown A.M., Ng K., Ma J., Wienholds E., Dunant C., et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 2013;339:543–548. doi: 10.1126/science.1227670. - DOI - PMC - PubMed
    1. Laurent-Puig P., Pekin D., Normand C., Kotsopoulos S.K., Nizard P., Perez-Toralla K., Rowell R., Olson J., Srinivasan P., Le Corre D., et al. Clinical relevance of KRAS-mutated subclones detected with picodroplet digital PCR in advanced colorectal cancer treated with anti-EGFR therapy. Clin. Cancer Res. 2015;21:1087–1097. doi: 10.1158/1078-0432.CCR-14-0983. - DOI - PubMed
    1. Haberkorn U., Ziegler S.I., Oberdorfer F., Trojan H., Haag D., Peschke P., Berger M.R., Altmann A., van Kaick G. FDG uptake, tumor proliferation and expression of glycolysis associated genes in animal tumor models. Nucl. Med. Biol. 1994;21:827–834. doi: 10.1016/0969-8051(94)90162-7. - DOI - PubMed
    1. Paudyal B., Oriuchi N., Paudyal P., Higuchi T., Nakajima T., Endo K. Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]-2-fluro-2-deoxy-D-glucose positron emission tomography. Cancer Sci. 2008;99:260–266. doi: 10.1111/j.1349-7006.2007.00683.x. - DOI - PMC - PubMed

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