High intensity focused ultrasound in clinical tumor ablation

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BPH	Sullivan et al[32]	Sonablate	25 patients (mean age 67 years, range 47-84)	5 patients with large glands were withdrawn; the remaining 20 patients had improvements in the AUA symptom score (20.25 to 9.56), Qmax (9.2 to 13.7 mL/s) and QOL score (4.75 to 2.50)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.