High-intensity focused ultrasound in breast pathology:

non-invasive treatment of benign and malignant* lesions B. Cavallo Marincola, F. Pediconi, M. Anzidei, E.Miglio, L. Di Mare, M. Telesca,M. Mancini,

G. D’Amati, M. Monti, C. Catalano and A. Napoli; Expert Rev. Med. Devices; 2014

Methods

Results

10 patients diagnosed with one or multiple fibroadenomas (12 FA treated in 10 sessions) were treated

with ultrasound-guided high intensity focused ultrasound (i.e. echotherapy)

Maximum diameter range : 19mm – 44mm (Median: 26.5)

Mean patient age: 26y [18-34]

Treatment on an outpatient basis and under local anesthesia and mild sedation

Rationale

Breast tumors, either benign of malignant, are commonly diagnosed during screening imaging

procedures.

Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable.

High-intensity focused ultrasound (HIFU) is already established as a valid non-invasive technique that

ensures tumor ablation in various organs. The publication reports the use of echotherapy (ultrasound-

guided HIFU) for the ablation of fibroadenomas.

Mean treatment duration: 57.2 min [40-100]

No adverse events but mild swelling and hardness

of the treated area

None of the patients reported pain

Before After

Mean volume reduction over time (% vs. months)

US images of a breast fibroadenoma before and 3 months after echotherapy

Conclusion

Echotherapy has a strong potential role for the ablation of benign breast tumors in order to provide a

valid noninvasive alternative treatment for breast conservative surgery.

50%

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20

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60

80

100

Baseline 3

Me

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%)

20-mm fibroadenoma 10-mm fibroadenoma

THERACLION SA - THC 901682-A * The technology developed by Theraclion (i.e. Echotherapy) is only indicated to treat benign breast lesions like fibroadenomas.

Months

Ultrasound-guided high-intensity focused ultrasound treatment

of breast fibroadenoma - a multicenter experience R. Kovatcheva, JN. Guglielmina, M. Abehsera, L. Boulanger, N. Laurent and E. Poncelet;

Journal of Therapeutic Ultrasound; 2015

Methods

Results

Multicenter, open label and prospective study

42 patients diagnosed with one or multiple fibroadenoma (51 FA treated among which 8 treated twice)

were treated with ultrasound-guided high intensity focused ultrasound (i.e. echotherapy)

Treatment performed on an outpatient basis under conscious sedation

Mean patient age: 32y [16-52]

Mean FA volume at baseline: 3.89ml [0.34 – 19.66]

Rationale

Breast fibroadenoma (FA) is the most common benign lesion, affecting women in about 10% during

their lifetime, usually occurring under the age of 30.

As a consequence of breast imaging development, benign epithelial diseases represent a growing

percentage of breast pathology diagnoses.

Before After

2.96 ml FA

Before After

8.14 ml FA

Volume reduction of 62.3% 12mo after echotherapy

Volume reduction of 73.5% 12mo after echotherapy

Mean volume reduction over time (% vs. months)

US images of two breast fibroadenomas before and 12 months after echotherapy

Conclusion

Echotherapy is effective in reducing the volume and clinical symptoms of fibroadenomas without

serious side effects. Echotherapy may become a noninvasive alternative to surgery.

0

-73% -81,3

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00 4 8 12 16 20 24 28 32 36

Unpublished data of patients

having reached the resp. f/u Me

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%)

Months

Complete disappearance of discomfort

after 12 months in all patients

Complete disappearance of FA-related pain

after 12 months in all patients

Treatment well tolerated by all the patients

No serious adverse event

Mean total procedure duration: 118min [60 – 255]

THERACLION SA - THC 901683-A

Benign Solid Thyroid Nodules: US-guided High-Intensity Focused

Ultrasound Ablation — Initial Clinical Outcomes

R. D. Kovatcheva, J. D. Vlahov, J. I. Stoinov, K. Zaletel; Radiology; 2015

Methods

Results

20 euthyroid patients diagnosed with a benign solitary or dominant thyroid nodule were treated in one

session with ultrasound-guided high intensity focused ultrasound (i.e. echotherapy)

Mean thyroid volume at baseline: 4.96 ml ± 2.79

Mean patient age: 44.5y [24-65]

Treatment on an outpatient basis and under conscious sedation

Rationale

The prevalence of thyroid nodules found by means of palpation is approximately 5%, but an estimated

50% of unselected populations have nodules that can be discovered at ultrasonography. 95% of all

thyroid nodules are benign.

Even if surgery is the treatment of choice, risks of complications lead to the development of various

non-surgical, minimally invasive techniques.

Mean procedure duration: 86.8min [37-152]

Treatment well tolerated by all the patients

No serious adverse event

Before echotherapy 1 month after

Mean volume reduction over time (% vs. months)

Color Doppler US images of longitudinal scan in a 42yo woman

Conclusion

Echotherapy is an effective and safe non-invasive treatment method for benign solid thyroid nodules.

Months

65.3% volume reduction 86.5% volume reduction 92.9% volume reduction

3 months after 6 months after

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(%

)

Unpublished data of patients

having reached the resp. f/u

THERACLION SA - THC 901684-A

9 patients diagnosed with a single thyroid nodule (6 cold – 3 hot nodules) were treated in one session

with ultrasound-guided high intensity focused ultrasound (i.e. echotherapy)

Median thyroid volume at baseline: 3.5mL [0.8-7.7]

Median patient age: 52y [36-80]

Treatment on an outpatient basis and under local anesthesia

Volume reduction of benign thyroid nodules 3 months after a

single treatment with high-intensity focused ultrasound (HIFU) H. Korkusuz, N. Fehre, M. Sennert, C. Happel and F. Grünwald; Journal of Therapeutic Ultrasound; 2015

Methods

Results

Rationale

Thyroid nodules are common in western population, most being of a benign nature.

For many years, surgery and radioiodine therapy were the only options. Both procedures are costly and

the former is not without risk. Additional techniques that have been widely discussed. High-intensity

focused ultrasound (HIFU) (i.e. echotherapy) is a promising, non-invasive technique in treating benign

thyroid nodules (TNs). The aim of this study was to evaluate the efficacy of echotherapy.

Median volume reduction: 48,8% [11,4-75]

Very good acceptance of the treatment

No major complications

Median procedure duration: 62min [42-96]

Before echotherapy 3 month after

Median volume reduction over time (% vs. months)

Sonographical volume measurement of an exemplary thyroidal nodule

Conclusion

Echotherapy appears to be safe and effective for inducing nodular shrinkage.

Me

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%)

64.7% volume reduction

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Baseline 3 months

Patient 1 Patient 2

Patient 3 Patient 4

Patient 5 Patient 6

Patient 7 Patient 8

Patient 9

Before echotherapy 3 month after

THERACLION SA - THC 901685-A

3 Months

12 patients diagnosed with a single thyroid nodule were treated in one session with ultrasound-guided

high intensity focused ultrasound (i.e. echotherapy)

Mean thyroid volume at baseline: 3.4mL [0.6-5.0]

Mean patient age: 56.9y [37-81]

Treatment on an outpatient basis and under local anesthesia

Localized thyroid tissue ablation by HIFU: Volume reduction,

effect on thyroid function and immune response H. Korkusuz, M. Sennert, N. Fehre, C. Happel and F. Grünwald; Röfo; 2015

Methods

Results

Rationale

Initial demonstration of thyroid nodule volume reduction by high intensity focused ultrasound has been

done.

The goal of this study is to assess the effectiveness of the treatment in reducing the volume while

preserving thyroid function as measured by immunological response.

Complete thyroid hormone status pre ablation, 24h and

3m post ablation showed no significant change in thyroid

function.

Antibodies measurement pre ablation, 24h and 3m post

ablation showed no clinically meaningful induced

immune response.

Preserved thyroid function and absence of immune response at 24 h and 3 months follow up

Conclusion

Echotherapy is safe, effective and easy to use for the treatment of benign thyroid nodules. The

procedure preserves thyroid function and there is no indication of related autoimmune diseases or

thyrotoxicosis. Volume reduction is significant and in most cases sufficient.

Thyroglobulin evaluation pre ablation, 24h and 3 months

post ablation demonstrate the efficacy of thyroid tissue

ablation

Efficacy of tissue ablation assessed

hTg serum levels

Parameter Baseline 24 hours after HIFU 3 months after HIFU

T3 [nmol/L] 1.7 (1.4 – 2.3) 1.7 (0.9 – 2.7) 1.5 (1 – 2.2)

T4 [nmol/L] 84 (69 - 144) 92 (74 – 146) 87 (60 – 164)

TSH [nE/L] 0.9 (0.5 – 5.6) 0.7 (0.1 – 3.0) 1.2 (0.1 – 1.8)

hTg [ng/mL] 29.6 (0.1 – 459) 72.01 (28.9 – 3431.0) 15.3 (0.09 – 155)

TPOAbs [nmol/L] 10 (6 – 1119) 12 (6 – 986) 7 (3 – 791)

TABs [U/mL] 9 (5 – 110) 7 (5 – 63) 9 (3 – 108)

TRAbs [IU/L] 0.02 (0 – 0.92) 0.30 ( 0 – 0.74) 0.3 ( 0 – 0;74)

THERACLION SA - THC 901686-A

2 groups of patients diagnosed with a benign solitary or dominant thyroid nodule were treated with

ultrasound-guided high intensity focused ultrasound (i.e. echotherapy) (group 1-12 pts) and with

moving-beam echotherapy (BEAMOTION - CE-pending) (group 2-11 pts)

Treatment has been performed on an outpatient basis and under conscious sedation.

Comparison of thyroid nodules treatment duration with

US-guided HIFU vs US-guided moving-beam HIFU (BEAMOTION)

Unpublished data – Originated from R. Kovatcheva clinical trials

Methods

Results

Rationale

Thyroid nodules are common in western population, most being of a benign nature.

However, various non-surgical thermoablation techniques have been developed to reduce the size of

thyroid nodules, among which high-intensity focused ultrasound (i.e. echotherapy). The latter is the first

and only non-invasive thermoablative method.

Previous procedure: 83 min [36– 144]

vs

BEAMOTION: 17 min [10-27]

Mean treatment duration

Conclusion

Several studies demonstrate that echotherapy is a safe and effective treatment for benign thyroid

nodules.

Echotherapy treatment with BEAMOTION reduces up to 5 times the treatment duration as compared

with traditional US-guided HIFU.

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THERACLION SA - THC 901687-A