A Novel Strategy to Improve Radiotherapy Effectiveness: First-in-Human MR-guided Focused Ultrasound-Stimulated Microbubbles (MRgFUS+MB) Radiation Enhancement Treatment

Author:

Daniel Moore-Palhares,Murtuza Saifuddin,Ling Ho,Lin Lu,Archya Dasgupta,Martin Smoragiewicz,Irene Karam,Andrew Bayley,Arjun Sahgal,Ian Poon,Gregory J Czarnota

Abstract

Background and aim: Preclinical in vitro and in vivo experiments suggest that radiation-induced tumour cell death can be enhanced 10- to 40-fold when combined with focused-ultrasound (FUS)-stimulated microbubbles (MB). The acoustic exposure of MB in the tumour volume causes vasculature perturbation, activation of the acid sphingomyelinase (ASMase) ceramide pathway, and resultant endothelial cell apoptosis. When the tumour is subsequently treated with radiation, there is increased endothelial cell death and anoxic tumour killing. Here we describe a first-in-human experience treating patients with magnetic resonance (MR)-guided FUS-stimulated MB (MRgFUS+MB) radiation enhancement. Case presentation: A head and neck cancer patient with recurrent disease underwent radiotherapy for 5 separate sites of locoregional disease followed by systemic therapy. The first consisted of a course of 45 Gy in 5 fractions alone, the second of 30 Gy in 5 fractions with hyperthermia, and the three others of 20-30 Gy in 5 fractions along with MRgFUS+MB treatment. The treatment methodology used an MR-coupled FUS-device operating at 500 KHz and 540 kPa peak negative pressure with an insonification time of 750 ms spread over 5 minutes to stimulate intravenously administered MB within tumour target. All sites treated with stimulated MB had a complete radiological response, and subsequently, the patient’s other cutaneous metastatic disease disappeared. The patient has been under surveillance for over two years without active treatment or disease progression. Discussion: MRgFUS+MB was well-tolerated with no reported treatment-related adverse events, which can be attributed to the capability of FUS to selectively stimulate MB within the tumour volume while sparing the surrounding normal tissue. Sustained local control at all target sites aligns with earlier preclinical findings suggesting the radiation enhancement potential of FUS+MB. Conclusion: MRgFUS+MB represents a novel and promising therapy for enhancing radiation efficacy and improving therapeutic index with potential improvements in disease control.

Publisher

Heighten Science Publications Corporation

Subject

General Earth and Planetary Sciences,General Engineering,General Environmental Science

Reference15 articles.

1. 1. Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, Burtness B, Ghi MG, Cohen EEW, Grau C, Wolf G, Hitt R, Corvò R, Budach V, Kumar S, Laskar SG, Mazeron JJ, Zhong LP, Dobrowsky W, Ghadjar P, Fallai C, Zakotnik B, Sharma A, Bensadoun RJ, Ruo Redda MG, Racadot S, Fountzilas G, Brizel D, Rovea P, Argiris A, Nagy ZT, Lee JW, Fortpied C, Harris J, Bourhis J, Aupérin A, Blanchard P, Pignon JP; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol. 2021 Mar;156:281-293. doi: 10.1016/j.radonc.2021.01.013. Epub 2021 Jan 27. PMID: 33515668; PMCID: PMC8386522.

2. 2. Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V; EHNS Executive Board. Electronic address: secretariat@ehns.org; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org; ESTRO Executive Board. Electronic address: info@estro.org. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31(11):1462-1475. doi: 10.1016/j.annonc.2020.07.011. Epub 2020 Oct 23. PMID: 33239190.

3. 3. Bollen H, van der Veen J, Laenen A, Nuyts S. Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer. Front Oncol. 2021 Sep 16;11:720052. doi: 10.3389/fonc.2021.720052. PMID: 34604056; PMCID: PMC8483718.

4. 4. Czarnota GJ. Ultrasound-stimulated microbubble enhancement of radiation response. Biol Chem. 2015 Jun;396(6-7):645-57. doi: 10.1515/hsz-2014-0297. PMID: 25741736.

5. 5. El Kaffas A, Al-Mahrouki A, Hashim A, Law N, Giles A, Czarnota GJ. Role of Acid Sphingomyelinase and Ceramide in Mechano-Acoustic Enhancement of Tumor Radiation Responses. J Natl Cancer Inst. 2018 Sep 1;110(9):1009-1018. doi: 10.1093/jnci/djy011. PMID: 29506145; PMCID: PMC6136928.

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