Partner: Georg Dimcevski |
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Recent publications
1. | Dimcevski G.♦, Kotopoulis S.♦, Bjånes T.♦, Hoem D.♦, Schjøt J.♦, Gjertsen B.T.♦, Biermann M.♦, Molven A.♦, Sorbye H.♦, McCormack E.♦, Postema M., Gilja O.H.♦, A human clinical trial using ultrasound and microbubbles to enhance gemcitabine treatment of inoperable pancreatic cancer, Journal of Controlled Release, ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2016.10.007, Vol.243, pp.172-181, 2016 Abstract: Background: Ultrasound, Microbubbles, Sonoporation, Pancreatic cancer, Image-guided therapy, Clinical trial Affiliations:
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2. | Kotopoulis S.♦, Dimcevski G.♦, McCormack E.♦, Postema M.♦, Gjertsen B.T.♦, Gilja O.H.♦, Ultrasound and microbubble-enhanced chemotherapy for treating pancreatic cancer: a phase I clinical trial, JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA, ISSN: 0001-4966, DOI: 10.1121/1.4950209, Vol.139, No.4, abstract, pp.2092, 2016 Abstract: Experimental research of ultrasound to induce or improve delivery has snowballed in the past decade. In our work, we investigate the use of low-intensity ultrasound in combination with clinically approved microbubbles to enhance the therapeutic efficacy of chemotherapy. Ten voluntary patients with locally advanced or metastatic pancreatic adenocarcinoma were consecutively recruited. Following standard chemotherapy protocol (intravenous infusion of gemcitabine over 30 min), a clinical ultrasoundscanner was targeted at the largest slice of the tumour using modified non-linear contrastimaging settings (1.9 MHz center frequency, 0.27 MPa peak-negative pressure), and SonoVue® was injected intravenously. Ultrasound and microbubble treatment duration was 31.5 min. The combined therapy did not induce any additional toxicity or increase side effect frequency when compared to chemotherapy alone. Combination treated patients were able to tolerate an increased amount treatment cycles when compare historical controls (n = 63); average of 8.3±6.0 cycles, versus 13.8±5.6 cycles. The median survival also increased from 7.0 months to 17.6 months (p = 0.0044). In addition, five patients showed a primary tumor diameter decrease. Combined treatment of ultrasound,microbubbles, and gemcitabine does not increase side effects and may have the potential to increase the therapeutic efficacy of chemotherapy in patients with pancreatic adenocarcinoma. Affiliations:
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3. | Kotopoulis S.♦, Delalande A.♦, Popa M.♦, Mamaeva V.♦, Dimcevski G.♦, Gilja O.H.♦, Postema M.♦, Gjertsen B.T.♦, McCormack E.♦, Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft, Molecular Imaging and Biology, ISSN: 1536-1632, DOI: 10.1007/s11307-013-0672-5, Vol.16, pp.53-62, 2014 Abstract: Purpose Sonoporation, Pancreatic cancer, Ultrasound, Chemotherapy, 3D ultrasound, Bioluminescence Affiliations:
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4. | Kotopoulis S.♦, Dimcevski G.♦, Gilja O.H.♦, Hoem D.♦, Postema M.♦, Treatment of human pancreatic cancer using combined ultrasound, microbubbles, and gemcitabine: A clinical case study, Medical Physics, ISSN: 0094-2405, DOI: 10.1118/1.4808149, Vol.40, No.7, pp.072902-1-9, 2013 Abstract: Purpose: Ultrasound, Microbubbles, Sonoporation, Chemotherapy Affiliations:
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Conference papers
1. | Kotopoulis S.♦, Dimcevski G.♦, Gjertsen B.T.♦, Gilja O.H.♦, McCormack E.♦, Postema M.♦, Sonoporation: From the lab to human clinical trials, IUS 2014, IEEE International Ultrasonics Symposium, 2014-09-03/09-06, Chicago (US), DOI: 10.1109/ULTSYM.2014.0208, Vol.1, pp.846-849, 2014 Abstract: Therapeutic ultrasound has been in use for over 70 years but has primarily been a thermal modality. Sonoporation, the use of ultrasound and stable gas microbubbles in the size range of 2-10 μm to form transient pores in cell membranes, has been of great interest in the past 15 years. This technique could be used to improve the delivery of current drugs in very localised regions. There are several phenomena behind sonoporation that all occur non-exclusively: push, pull, jetting, inertial cavitation, shear and, translation. Pre-clinical work has shown that sonoporation can be used to reduce primary tumour burden and inhibit metastatic development. Our clinical trial showed that ultrasound in combination with microbubbles and chemotherapy can effectively double the number of chemotherapy cycles patients can undergo, meaning that the patients were healthier for a longer period of time. Nevertheless, sonoporation is still in its infancy and there is vast room for improvement in both the areas of microbubbles and ultrasound. Keywords:Sonoporation Affiliations:
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Conference abstracts
1. | Dimcevski G.G.♦, Kotopoulis S.♦, Bjåne T.♦, Hoem D.♦, Schjött J.♦, Gjertsen B.T.♦, Biermann M.♦, Molven A.♦, Sorbye H.♦, McCormack E.♦, Postema M.♦, Gilja O.H.♦, Ultrasound and microbubble enhanced treatment of inoperable pancreatic adeonocarcinoma, ASCO Annual Meeting, 2016-06-03/06-07, Chicago (US), Vol.34, No.suppl; abstr e15703, pp.1, 2016 Abstract: Background: Pancreatic Adenocarcinoma (PDAC) represents one of the most lethal human cancers. Surgery is often unfeasible, and the tumors respond poorly to radiation or chemotherapeutic drugs. Consequently, pancreatic cancer represents a huge burden to society and the need for new therapeutic options is evident. Experimental research using ultrasound to improve therapeutic delivery has soared in the past decade. We aimed toevaluate the safety and potential toxicity of gemcitabine combined with microbubbles under sonication in inoperable pancreatic cancer patients. The secondary goal was to develop a novel image-guided microbubble-based therapy, based on commercially available technology, towards improving chemotherapeutic efficacy, preserving patient performance grade, and prolongation of survival. Methods: Ten patients were enrolled and treated in this Phase I clinical trial. Gemcitabine was infused intravenously over 30 min. Subsequently patients were treated using a commercial clinical ultrasound scanner for 31.5 min. SonoVue was injected intravenously (0.5 ml followed by 5 ml saline every 3.5 min) during the ultrasound treatment with the aim of enhancing therapeutic efficacy. Results: The combined therapeutic regimen did not induce any additional toxicity or increase side effect frequency when compared to gemcitabine chemotherapy alone (historical controls). Combination treated patients (n = 10) tolerated an increased number of gemcitabine cycles compared with historical controls (n = 63 patients; average of 8.3±6.0 cycles, versus 13.8±5.6 cycles). In five patients, the maximum tumor diameter was decreased during treatment. The median survival in our patients was also increased from 7.0 months to 17.6 months (p = 0.0044). Conclusions: We perform the first-in-human study evaluating the toxicity and efficacy of ultrasound and microbubble enhanced chemotherapy. It is possible to combine ultrasound, microbubbles, and chemotherapy in a clinical setting with no additional toxicity. This combined treatment may improve the clinical efficacy of chemotherapeutic agents, prolong the quality of life, and extend survival in patients with PDAC. Clinical trial information: NCT01674556. Affiliations:
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2. | Kotopoulis S.♦, Dimcevski G.♦, Hoem D.♦, Postema M.♦, Gilja O.H.♦, Ultrasound sonoporation in pancreatic adenocarcinoma, AIUM 2015, Ultrasound in Medicine and Biology Annual Convention, 2015-03-21/03-25, Lake Buena Vista (US), Vol.41, No.4, Supplement, pp.S94, 2015 | |||||||||||||||||||||||||||||||||||||
3. | Kotopoulis S.♦, Delalande A.♦, Popa M.♦, Dimcevski G.♦, Gilja O.H.♦, Postema M.♦, Gjertsen B.T.♦, McCormack E.♦, Ultrasound and microbubble enhanced therapy of orthotopic human pancreatic cancer in mice, MedViz Conference 2013, 2013/, Bergen (NO), pp.45-47, 2013 | |||||||||||||||||||||||||||||||||||||
4. | Dimcevski G.♦, Kotopoulis S.♦, Hoem D.♦, Postema M.♦, Gjertsen B.T.♦, Bjåne T.K.♦, Biermann M.♦, McCormack E.♦, Sorbye H.♦, Molven A.♦, Gilja O.H.♦, Ultrasound-assisted treatment of an inoperable pancreatic cancer, MedViz Conference 2013, 2013/, Bergen (NO), pp.49-52, 2013 |