High-frequency (20 MHz) high-intensity focused ultrasound: New Treatment of actinic keratosis, basal cell carcinoma, and Kaposi sarcoma. An open-label exploratory study

Jørgen Serup, Torsten Bove, Tomasz Zawada, Alexander Jessen, Mattia Poli, Jørgen Serup, Torsten Bove, Tomasz Zawada, Alexander Jessen, Mattia Poli

Abstract

Background: Skin cancer is common, growing, challenging, and in need of progress in early-stage treatment. 20 MHz high-intensity focused ultrasound (HIFU) is new and applied to actinic keratosis (AK) and skin cancers for the first time. HIFU of lower frequency is already used in the treatment of internal cancers.

Materials and methods: Eight patients with 201 AK lesions, one patient with 7 basal cell carcinomas (reoccurrences after PDT), and one patient with 7 Kaposi sarcoma lesions (4 treated with radiotherapy in the past) were given 1-3 HIFU treatments. Twenty megahertz HIFU was dosed as 150 ms at 0.6-1.2 J/shot applied to target lesions. Probes with different target depths were available. The preferred shot energy and focal depth in AK were 0.9 J and 1.3 mm. A "Sandwich" strategy with HIFU applied in two depths were tried in cancers. The follow-up period was 3-6 months.

Results: All AK cleared except 5, giving a cure rate of 97%. Post-treatment lesion healed in 1-2 weeks with no scar. VAS pain was from 1 to 8, and in any case less than experienced with previous PDT. In both basal cell carcinoma (BCC) and sarcoma, healing was confirmed by histological verification.

Discussion/conclusion: 20 MHz HIFU was an effective and safe treatment of AK. This new treatment, applicable to any anatomical site, has promising advantages relative to PDT and has the potential to replace or supplement PDT in future. Case-observations indicated that HIFU can be useful in skin cancers as well.

Keywords: cure rate; guidance; high-intensity focused ultrasound; pain; photodynamic therapy; premalignant; scar; sequelae; skin cancer; verruca.

Conflict of interest statement

This study has been funded by TOOsonix A/S, Denmark.

© 2020 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Schematic illustration of high‐intensity focused ultrasound (HIFU) and skin. The transducer is a focused piezoelectric element constructed to deliver non‐invasive acoustic energy of a high intensity into a confined focal zone below the skin surface. In the focal zone and the adjacent part of the skin above the focal point heating, the ultrasound energy is absorbed and transduced into a temperature insult. In contrast, the energy attenuates abruptly below the focal point. The increase in temperature depends on the power and duration of the ultrasound beam
Figure 2
Figure 2
TOOsonix System ONE with a close‐up photograph of the dermascope picture of a suggested target lesion filmed real time through the probe. The red cross indicates the horizontal location of a high‐intensity focused ultrasound (HIFU) shot by activation of the foot switch
Figure 3
Figure 3
Case 1. A, before high‐intensity focused ultrasound (HIFU); B, follow‐up after 3 wk, inflammation of end‐stage healing; C, 3 mo after HIFU, AKs cleared
Figure 4
Figure 4
Case 2. High‐intensity focused ultrasound (HIFU) treatment of actinic keratosis (AK) on the neck. A, before HIFU treatment; B, 6 mo after HIFU. There was no scar and no dyspigmentation
Figure 5
Figure 5
Case 3. A, before high‐intensity focused ultrasound (HIFU) treatment; B, immediately after HIFU, with treatment inducing minor wheal and flare reaction. C, 2 wk after HIFU treatment; some post‐treatment inflammation, however, without subjective complaints. At follow‐up after 3 mo, the actinic keratosis (AK) was flattened and healed, and patient felt satisfied. No recurrence as observed at a 6‐mo follow‐up visit
Figure 6
Figure 6
Case 4. A, before high‐intensity focused ultrasound (HIFU), presenting two larger recurrences encircled with a blue pen. B, after 2 wk; treated lesions were in late healing phase. On this occasion, 5 minor lesions were treated with HIFU. C, after 2 mo. Subsequent follow‐up after 6 mo showed no reoccurrence. Follow‐up biopsy from one initial lesion, see A, taken after 6 mo showed no basal cell carcinoma
Figure 7
Figure 7
Case 5. A, Kaposi sarcoma prior to high‐intensity focused ultrasound (HIFU) treatment. B, treated site 10 wk later. A thick crust of keratotic material and debris had developed, however, easily removed. C, same after 10 mo. Histology showed no sarcoma, but the esthetic outcome was less satisfactory with remnant iron stain and some inflammation. The cosmetic result may improve over time. The illustrated lesion shown was a worst case; the other 6 lesions healed without complications and no special crustation, and some remnant iron stain

References

    1. Focused Ultrasound Foundation . State of the Field 2019. . Accessed March 10, 2020.
    1. Ellens NPK, Partanen A. Preclinical MRI‐guided focused ultrasound: a review of systems and current practices. IEEE Trans Ultrason Ferroelectr Freq Control. 2017;64(1):291‐305.
    1. Stephanie G, Peters M, Arya M, et al. A multicentre study of 5‐year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer. Eur Urol. 2018;74:422‐429.
    1. Quinn SD, Gedroyc WM. Thermal ablative treatment of uterine fibroids. Int J Hyperth. 2015;31(3):272‐279.
    1. Barile A, Arrigoni F, Zugaro L, et al. Minimally invasive treatments of painful bone lesions: state of the art. Med Oncol. 2017;34(53):1‐11.
    1. Kim M, Jung NY, Park CK, et al. Comparative evaluation of magnetic resonance‐guided focused ultrasound surgery for essential tremor. Stereotact Funct Neurosurg. 2017;95:279‐286.
    1. Lamsam L, Johnson E, Connolly ID, Wintermark M, Hayden Gephart M. A review of potential applications of MR‐guided focused ultrasound for targeting brain tumor therapy. Neurosurg Focus. 2018;44(2):1‐7.
    1. Peek MCL, Wu F. High‐intensity focused ultrasound in the treatment of breast tumours. Ecancer. 2018;12(794):1‐10.
    1. Lang BH, Wu ALH. High Intensity Focused Ultrasound (HIFU) ablation of benign thyroid nodules—a systematic review. J Therapeutic Ultrasound. 2017;5(11):1‐9.
    1. Bove T, Zawada T, Serup J, Jessen A, Poli M. High‐frequency (20‐MHz) high‐intensity focused ultrasound (HIFU) system for dermal intervention: preclinical evaluation in skin equivalents. Skin Res Technol. 2019;25(2):217‐228.
    1. Soegaard S, Aarup V, Serup J, et al. High frequency (20 MHz) High Intensity Focused Ultrasound (HIFU) system for dermal intervention: a 12 week local tolerance study in minipigs. Skin Res Technol. 2020;26(2):241‐254.
    1. Saaki GH, Tevez A. Clinical safety and focused‐image ultrasonography: a 2‐year experience. Aesthet Surg J. 2012;32(5):601‐612.
    1. Day D. Microfocused ultrasound for facial rejuvenation: current perspectives. Res Rep Focus Ultrasound. 2014;2:13‐17.
    1. White MW, Makin IRS, Barthe PG, et al. Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy. Arch Facial Plast Surg. 2007;9:22‐29.
    1. White MW, Makin IRS, Slayton MH, Barthe PG, Gliklich R. Selective transcutaneous delivery of energy to porcine soft tissues using Intense Ultrasound (IUS). Lasers Surg Med. 2008;40:67‐75.
    1. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (Keratinocyte Carcinomas) in the US population, 2012. JAMA Dermatol. 2015;151(10):1081‐1086.
    1. Health Europa . Non‐Melanoma Skin Cancer: The Hidden Epidemic Faced By Outdoor Workers. 2019 April. . Accessed January 5, 2020.
    1. Zawada T, Bove T. Acoustic Device for Skin Treatment and Methods of Using the Same. Patent application WO 2018/158355 A1.
    1. TOOsonix System ONE‐R system description. Available from . Accessed January 5, 2020.
    1. Goldenberg G. Treatment considerations in actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31:12‐16.
    1. James WD, Berger TG, Elston DM, eds. Andrews Diseases of the Skin (12th ed.). Philadelphia, PA: Elsevier; 2015.
    1. Morton CA, Szeimies R‐M, Basset‐Seguin N, et al. European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications – actinic keratosis, Bowen's disease and basal cell carcinomas. J Eur Acad Dermatol Venereol. 2019;33:2225‐2238.
    1. Stockfleth E. The importance of treating the field in actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31:8‐11.

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