Focused Ultrasound Therapy
Focused ultrasound is a noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with melanoma. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the body without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces precise ablation (thermal destruction of tissue). This destruction can be done to completely destroy the target or to partially treat it, and partial treatment is believed to stimulate the patient’s immune response, which may have a broader impact. There is also the combination of lower intensity focused ultrasound that can be used with or without microbubbles and in combination with other therapeutic modalities, such as radiotherapy for a combined benefit.
Advantages
The primary options for treatment of melanoma include invasive surgery.
For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications – such as surgical wound healing or infection – at a lower cost. It can reach the desired target without damaging surrounding tissue and is repeatable, if necessary. Focused ultrasound also enables a enhanced chemotherapy dose for the target, with less impact to the rest of the patient.
Clinical Trials
There is a clinical trial in Ontario Canada, where they are using the combination of low intensity focused ultrasound with microbubbles and radiotherapy in the treatment of patients with melanoma.
Regulatory Approval and Reimbursement
Focused ultrasound treatment for melanoma is not yet approved by regulatory bodies or covered by medical insurance companies.
Notable Papers
Thim EA, Kitelinger LE, Rivera-Escalera F, Mathew AS, Elliott MR, Bullock TNJ, Price RJ. Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation. Theranostics. 2024 Feb 11;14(4):1647-1661. doi: 10.7150/thno.92089. eCollection 2024. PMID: 38389838
Curley CT, Stevens AD, Mathew AS, Stasiak K, Garrison WJ, Miller GW, Sheybani ND, Engelhard VH, Bullock TNJ, Price RJ. Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound. Theranostics. 2020 Jul 11;10(19):8821-8833. doi: 10.7150/thno.47983. eCollection 2020.
Sethuraman SN, Singh MP, Patil G, Li S, Fiering S, Hoopes PJ, Guha C, Malayer J, Ranjan A. Novel calreticulin-nanoparticle in combination with focused ultrasound induces immunogenic cell death in melanoma to enhance antitumor immunity. Theranostics. 2020 Feb 10;10(8):3397-3412. doi: 10.7150/thno.42243. eCollection 2020.
Singh MP, Sethuraman SN, Ritchey J, Fiering S, Guha C, Malayer J, Ranjan A. In-situ vaccination using focused ultrasound heating and anti-CD-40 agonistic antibody enhances T-cell mediated local and abscopal effects in murine melanoma. Int J Hyperthermia. 2019 Nov;36(sup1):64-73. doi: 10.1080/02656736.2019.1663280.
Galanzha EI, Menyaev YA, Yadem AC, Sarimollaoglu M, Juratli MA, Nedosekin DA, Foster SR, Jamshidi-Parsian A, Siegel ER, Makhoul I, Hutchins LF, Suen JY, Zharov VP. In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma. Sci Transl Med. 2019 Jun 12;11(496). pii: eaat5857. doi: 10.1126/scitranslmed.aat5857. PMID: 31189720
Baghirov H, Snipstad S, Sulheim E, Berg S, Hansen R, Thorsen F, Mørch Y, Davies CL, Åslund AKO. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model. PLoS One. 2018 Jan 16;13(1):e0191102. doi: 10.1371/journal.pone.0191102. eCollection 2018.
Hoogenboom M, Eikelenboom DC, van den Bijgaart RJE, Heerschap A, Wesseling P, den Brok MH, Fütterer JJ, Adema GJ. Impact of MR-guided boiling histotripsy in distinct murine tumor models. Ultrason Sonochem. 2017 Sep;38:1-8. doi: 10.1016/j.ultsonch.2017.02.035. Epub 2017 Feb 28.
Li H, Yuan SM, Yang M, Zha H, Li XR, Sun H, Duan L, Gu Y, Li AF, Weng YG, Luo JY, He TC, Wang Y, Li CY, Li FQ, Wang ZB, Zhou L. High intensity focused ultrasound inhibits melanoma cell migration and metastasis through attenuating microRNA-21-mediated PTEN suppression. Oncotarget. 2016 Aug 2;7(31):50450-50460. doi: 10.18632/oncotarget.10433.
Bandyopadhyay S, Quinn TJ, Scandiuzzi L, Basu I, Partanen A, Tomé WA, Macian F, Guha C. Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape. J Immunol. 2016 Feb 15;196(4):1964-76. doi: 10.4049/jimmunol.1500541. Epub 2016 Jan 11.
Yuan SM, Li H, Yang M, Zha H, Sun H, Li XR, Li AF, Gu Y, Duan L, Luo JY, Li CY, Wang Y, Wang ZB, He TC, Zhou L. High intensity focused ultrasound enhances anti-tumor immunity by inhibiting the negative regulatory effect of miR-134 on CD86 in a murine melanoma model. Oncotarget. 2015 Nov 10;6(35):37626-37. doi: 10.18632/oncotarget.5285.
Li H, Yuan S, Yang M, Duan L, Wang H, Zha H, Li X, Sun H, Weng Y, Luo J, He T, Li C, Wang Y, Li F, Wang Z, Zhou L. [High-intensity focused ultrasound inhibits tumor metastasis in a melanoma-bearing mouse model]. Nan Fang Yi Ke Da Xue Xue Bao. 2015 Feb;35(2):223-8. Chinese.
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