High intensity focused ultrasound in clinical tumor ablation

Table 1 Summary of most popular high-intensity focused ultrasound system for clinical use

Model	Manufacturer	Size (mm)	Focal length (mm)	Frequency (MHz)	Focusing method	Imaging guidance	Clinical applications
FEP-BY02	Beijing Yuande Biomedical Engineering Inc, China	OD = 370 ID = 120	255	1	251 elements driven in phase	GE Logiq series ultrasound system	Liver, kidney, breast, pancreatic, bone tumor and uterine fibroid
Model-JC	Chongqing Haifu Tech Ltd, China	D = 120 or 150	90, 130, 160	0.8, 1.6, 3.2	Flat ceramics with acoustic lens	AU3 ultrasound imaging system	Liver, kidney, breast, pancreatic, bone tumor and uterine fibroid
ExAblate 2000	InSightec Ltd, Israel	120	150	0.9, 1.3	Phased array 208 hexagonal elements, 3 cavitation detector	GE Signa 1.5/3.0T MR imaging system	Uterine fibroids, breast tumor, liver cancer, bone metastases, neurosurgery, prostate cancer
Sonalleve	Philips, USA	N/A	N/A	1.2, 1.4	Phased array	Philips Achieva 1.5/3.0T MR imaging system	Uterine fibroids
Sonablate 500	Focus Surgery Inc., USA	30 × 22	30 and 40 or 45/50	4	2 elements mounted back-to-back	Element for both therapy and imaging	Prostate cancer
Ablatherm	Edap-Technomed, France	40 × 22 ID = 8	45	3	Single concave element	7.5 MHz integrated ultrasound imaging	Prostate cancer
TH-One	Theraclion, France	56	38	3	Single concave element	B-K Medical ultrasound imaging system	Hyperparathyroidism

N/A: Not available; GE: General electronics; MR: Magnetic resonance.

Table 2 Summary of high-intensity focused ultrasound clinical outcomes

Cases	Authors	HIFU system	Patients	Outcomes
BPH	Sullivan et al[32]	Sonablate	25 patients (mean age 67 years, range 47-84)	5 patients with large glands were withdrawn; the remaining 20 patients had improvements in the AUA symptom score (20.25 to 9.56), Qmax (9.2 to 13.7 mL/s) and QOL score (4.75 to 2.50)
	Uchida et al[34]	Sonablate	35 patients mean age 68.5 ± 7.7 (52-84) treated by Sonablate; 22 patients mean age 68 ± 6.8 (57-81) treated by Sonablate 200	IPSS and QOL scores showed significant improvement at 3, 6, and 12 mo follow-up (P < 0.001-0.01); maximum flow rate (8.9-15.5 mL/s, P < 0.001) and prostatic volume (32.2-22.8 mL, P < 0.01) were significantly improved at 12 moths follow-up treated by Sonablate 200
		Sonablate 200
Prostate cancer	Chaussy et al[36]	Ablatherm	271 patients were selected: 96 in the HIFU group and 175 in the TURP + HIFU group	A significant impact was observed on catheter time (40.0 d vs 7.0 d), incontinence (15.4% vs 6.9%), urinary infection (47.9% vs 11.4%), and the evolution of the post-treatment IPSS (8.91 vs 3.37) in favor of TURP + HIFU group; no significant changes were observed regarding efficacy during short-term follow-up, 25% and 4% retreatment rate in the HIFU and TURP + HIFU group, respectively
	Gelet et al[37]	Ablatherm	14 patients (mean age 72.5 years) with clinical stage T1 (3) and T2 (11) prostatic cancers	Early complications occurred in 6 (rectal burns 3, urinary retention 2, transient incontinence 1) and late complications in 5 (incontinence 2, bladder neck stenosis 3) patients; the PSA nadir value (1.79 ± 2.35 ng/mL) was achieved at 6 mo and the final PSA value was 2.94 ± 3.27 ng/mL (mean follow-up 380 d); No residual cancer was observed in 7 patients; Residual cancer was found in 7 patients: 4 required complementary treatment (orchidectomy 2, external beam radiation therapy 2)
	Gelet et al[40]	Ablatherm	82 patients (mean age 71 ± 5.7 years) with biopsy-proven localized (stage T1-T2) cancer	62% of patients exhibited no disease progression at 60 mo follow-up; the disease-free rate was 68% for the moderate-risk group of 50 patients (PSA < 15.0 ng/mL, Gleason sum < 8, prostate volume < 40 cm3, and number of positive biopsies < 5); for the low-risk group of 32 patients (PSA < 10 ng/mL and Gleason sum < 7), the disease-free survival rate was 83%
	Chaussy et al[41]	Ablatherm	184 patients (mean age of 72 years, range 59-81)	Cancer free in 80% of patients and the tumor mass was reduced more than 90% in the residual cancer; the nadir value of PSA was < 4 ng/mL in 97%, including 61% who had values < 0.5 ng/mL; no severe side effects (fistula, grade 2 or 3 incontinence, rectal mucosal burn) were seen
	Uchida et al[41]	Sonablate-500	181 patients (median age of 70 years, range 44-88) and pretreatment PSA was 9.76 ng/mL (range 3.39-89.60)	The disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively; the disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P < 0.0001)
	Blana et al[42]	Ablatherm	223 patients with age of 68.2 ± 6.8 years, PSA 11.3 ± 10 ng/mL (range 0.5-81.2), Gleason score 5.3 ± 1.5 and a prostate volume of 23.5 ± 10.7 cm3 (range 3-62.5)	The complications rates were: urinary tract infection 0.4%, chronic pelvic pain 0.9%, infravesical obstruction 19.7%, stressincontinence 7.6%, impotence 49.8%; among the 49 patients who received a second HIFU therapy, the cumulative incontinence rate (12.2%, P = 0.024) and cumulative impotence rate (55%, P < 0.001) were significantly increased
	Blana et al[43]	Ablatherm	146 patients with a mean age of 66.9 ± 6.7 years, mean PSA of 7.6 ± 3.4 ng/mL, mean Gleason score of 5 ± 1.2, and prostate volume of 23 ± 7.7 cm3	The median PSA nadir 3 mo after treatment was 0.07 ng/mL (0-5.67); The median PSA at 22 mo follow-up was 0.15 ng/mL (0-12.11), and 87% of patients had constant PSA < 1 ng/mL; 93.4% of patients had negative control biopsies; Of all the patients, 12% underwent transurethral resection because of obstruction with no severe stress incontinence (grade 2-3)
	Vallancien et al[45]	Ablatherm	30 patients with a mean age of 72 years, a median prostate volume of 30 cc, a median Gleason score of 6, a median PSA of 7 ng/mL	At a mean of 20 mo of follow-up 86% of patients had negative biopsies after HIFU; Median PSA was 0.9 ng/mL; At 1 year of follow-up the mean International Prostate Symptom Score was 8; Regarding sexual function, 73% of previously potent patients reported preserved sexual activity
	Lee et al[45]	Ablatherm	62 patients with clinical stage T1-2, PSA value < 30 ng/mL	After HIFU treatment, 78% of patients had a decreased PSA level to < 0.5 ng/mL within 3 mo; the median value of the last PSA was 0.6 ng/mL and the median nadir PSA was 0.2 ng/mL; The success rates of HIFU were 85, 77 and 47% in low-, intermediate- and high-risk groups, respectively
	Thüroff et al[39]	Ablatherm	402 patients with localized (stage T1-2N0-xM0) prostate cancer at 6 sites, mean age of 69.3 ± 7.1 years, mean prostate volume 28.0 ± 13.8 cc, mean PSA 10.9 ± 8.7 ng/mL	Negative biopsy rate in T1-2 primary cancer population was 87.2%, 92.1% in low-risk patients
Breast cancer	Wu et al[50]	JC	22 patients (4 in TNM stage I, 9 in stage IIA, 8 in stage IIB, and 1 in stage); Tumor size ranged from 2 to 4.8 cm in diameter (mean 3.4 cm)	After a median follow-up of 54.8 mo, 1 patient died, 1 was lost, and 20 were still alive; 2 of 22 patients developed local recurrence; 5-year disease-free survival and recurrence-free survival were 95% and 89%, respectively; cosmetic result was judged as good to excellent in 94% of patients
	Furusawa et a[49]	ExAblate 2000	21 cases median age is 54 years (range 34-72), median diameter of tumor is 15 mm (range 5-50)	1 case of recurrence of pure mucinous carcinoma; 2 cases of skin burns
Uterine fibroids	LeBlang et al[52]	ExAblate 2000	147 symptomatic leiomyomas in 80 women (average age: 46, range: 34-55) with average fibroids volume of 175 ± 201 cm3	The average nonperfused volume ratio was 55% ± 25% immediately after treatment; 6 mo after treatment, the average volume of treated fibroids had decreased to 112 ± 141 cm3 (n = 81) (P < 0.0001) with an average volume reduction of 31% ± 28%
	Funaki et al[54]	ExAblate 2000	91 Japanese women (45 of Type 1-2 and 46 of Type 3)	The mean volume change ratios of Type 1-2 myomas were -36.5% and -39.5% at 6 and 24 mo follow-up, respectively; SSS value for patients with Type 1-2 myomas before MRgFUS was 35.1 ± 21.0, and the values diminished significantly during the 24-mo follow-up period to a mean value of ~15.0; Type 3 myomas did not decrease in size 6 mo after MRgFUS; The reintervention rates were 14.0% for Type 1-2 patients and 21.6% for Type 3 patients at 24 mo follow-up, respectively
Liver cancer	Li et al[65]	JC	100 patients (80 male, 20 female, mean age of 56, ranging 30-74 years) including 62 primary and 38 metastatic liver cancers	Clinical symptoms were relieved in 86.6% (71/82) of patients; the ascites disappeared in 6 patients; ALT (95 ± 44) U/L and AST (114 ± 58) U/L were reduced to normal in 83.3% (30/36) and 72.9% (35/48) patients after HIFU, respectively; AFP was lowered by more than 50% in 65.3% (32/49) patients
	Wu et al[66]	JC	50 patients with stage IVA HCC (T4N0-1M0) The tumors were 4-14 cm in diameter (mean, 10.5 cm)	The 6-mo and 1-year survival rate was 80.4%-85.4%, and 42.9%, respectively; median reductions in tumor volume at 1, 3, 6, and 12 mo after treatment were 28.6%, 35.0%, 50.0%, and 50.0%, respectively
Renal cancer	Wu et al[70]	JC	12 patients with advanced stage renal cell carcinoma and 1 patient with colon cancer metastasized to kidney	After HIFU hematuria disappeared in 7 of 8 patients and flank pain of presumed malignant origin disappeared in 9 of 10 patients; it showed decrease in or absence of tumor blood supply and significant shrinkage of the ablated tumor; 7 patients died (median survival 14.1 mo, range 2-27) and 6 were alive with median follow-up of 18.5 mo (range 10-27)
Pancreatic cancer	Wu et al[73]	JC	8 patients mean of 62 years range 48 to 86 years	No complications were observed, and preexisting severe back pain disappeared after intervention; Follow-up images revealed an absence of tumor blood supply and shrinkage of the ablated tumor; a median survival time was 11.25 mo
	He et al[72]	FEP-BY02	251 (147 men and 104 women) patients in 25 hospitals with mean age of 59, range 39-82, 3-12 cm tumor diameter; TNM grade II 7%, III 34%, IV 59%; Concurrent jaundice 18.7% and pain 68%; Head 183, body 53, 14 trail	21.5% cases exhibited a remarkable effect, 64% exhibited a general effect; survival time is 12.5 mo; 6 patients survived more than 3 years; no complications, such as skin burn, gastrointestinal perforation and pancreatic fistula were observed
Bone metastases	Liberman et al[81]	ExAblate 2000	31 patients in 3 medical centers	25 patients underwent the planned treatment and were available at 3 mo follow-up; 72% of the patients reported significant pain improvement; average VAS score was reduced from 5.9 to 1.8 at 3 mo follow-up; 67% of patients reported a reduction in their opioid usage

HIFU: High intensity focused ultrasound; BPH: Benign prostate hyperplasia; AUA: American Urology Association; QOL: Quality of life; PSA: Prostate specific antigen; AFP: α-fetoprotein; MRgFUS: Magnetic resonance-guided focused US surgery.