High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

Table 1 Studies of continuous-wave high intensity focused ultrasound treatment for patients with advanced pancreatic cancer

Study	n	Patients	Treatment method	HIFU Device	Outcome and survival	Complications
Wu et al[21]	8	A phase I-II study of HIFU for advanced pancreatic cancer, unresectable. Average tumor size 5.89 cm (4.5-8 cm)	One-session HIFU monotherapy	Continuous HIFU irradiation, Model-JC HIFU System	Pain relief: 8/8 (100%); Median survival: 11.25 mo (2-17 mo)	None
Orsi et al[22]	6	Late-stage pancreatic cancer, unresectable. Average tumor size 4.6 ± 1.4 cm	One-session HIFU monotherapy	Continuous HIFU irradiation, Model-JC HIFU System	Pain relief: 6/6 (100%); Median survival: 7 mo; Overall survival: 42.9% at 12 mo and 21.4% at 24 mo	Portal vein thrombosis: 1/6 (16%)
Wang et al[24]	40	Advanced pancreatic cancer, unresectable. Average tumor size 4.3 cm (2-10 cm)	One-session HIFU monotherapy	Continuous HIFU irradiation, Model-JC HIFU System	Pain relief: 35/40 (87.5%)Median survival: 8 mo (stage III: 10 mo; stage IV: 6 mo); Overall survival: 58.8% at 6 mo and 30.1% at 12 mo	None
Sung et al[25]	46	Advanced pancreatic cancer, unresectable. Average tumor size 4.2 ± 1.4 cm (1.6-9.3 cm)	One-session HIFU monotherapy	Continuous HIFU irradiation, Model-JC HIFU System	A significant reduction of pain score (P < 0.001); Median survival: 12.4 mo; Overall survival: 52.2% at 6 mo, 30.4% at 12 mo, and 21.79% at 18 mo	Mild abdominal pain: 16/46 (34%); severe abdominal pain with vomiting: 2/46 (4%); transient fever: 3/46 (6%); 2nd-3rd skin burns: 2/46 (4%); pancreaticoduodenal fistula: 1/46 (2%),; gastric bleeding due to ulcer: 1/46 (2%)
Wang et al[26]	224	Advanced Pancreatic cancer	One-session HIFU monotherapy	Continuous HIFU irradiation, Model-JC HIFU System	Pain relief and survival data not reported	Abdominal distension, anorexia and nausea: 10/224 (4%); asymptomatic vertebral injury: 2/224 (1%); obstructive jaundice: 1/224 (1%)
Gao et al[27]	39	Locally advanced pancreatic cancer, unresectable. Tumor size unclear	One-session HIFU alone: 14 pts; HIFU + gemcitabine: 25 pts	Continuous HIFU irradiation, Model-JC HIFU System	Pain relief: 31/39 (79.5%) Median survival: 11 mo; Overall survival: 82.1% at 6 mo, and 39.5% at 12 mo	None
Zhao et al[28]	37	A phase II study of HIFU + gemcitabine for locally advanced pancreatic cancer, average tumor size 3.4 cm (1.7-8.5 cm).	Gemcitabine on days 1, 8 and 15, and multiple HIFU sessions on days 1, 3 and 5. The combined treatment repeated every 28 d	Continuous HIFU irradiation, HIFUNIT-9000 HIFU System	Overall survival: 12.6 mo (95%CI: 10.2-15.0); Pain relief: 29/37 (78%)	Fever: 26/37(70%); neutropenia: 6/37 (16%); thrombocytopenia 2/37 (5%); nausea and vomiting 3/37 (8%); diarrhea 2/37 (5%)

HIFU: High intensity focused ultrasound; pts: Patients.

Table 2 Studies of pulsed-wave high intensity focused ultrasound treatment for patients with advanced pancreatic cancer

Study	n	Patients	Treatment Method	HIFU Device	Outcome and Survival	Complications
Wang et al[29]	15	Late-stage pancreatic cancer, unresectable, average tumor size 5.6 cm (2.2-8 cm)	Multiple-session HIFU monotherapy, average sessions 8.1 (2-12)	Pulsed HIFU irradiation, FEB-BY HIFU System	Pain relief: 13/13 (100%)No survival data available	Mild abdominal pain: 2/15 (13%)
Li et al[30]	25	Advanced pancreatic cancer, unresectable, average tumor size unclear	One-session HIFU: 19 pts; 2-session HIFU: 6 pts; average sessions 1.2	Pulsed HIFU irradiation, FEB-BY HIFU System	Performance statue and pain improvement: 23/25 (92%); median overall survival: 10 mo; 1-year survival: 42%	First-degree skin burn: 3/25 (12%)
Ge et al[31]	20	A retrospective study for unresectable pancreatic cancer, average tumor size (4.5 ± 1.2) × (3.5 ± 1.0) cm	Multiple-session HIFU monotherapy; average HIFU session 9.3 ± 4.1	Pulsed HIFU irradiation, FEB-BY HIFU System	Pain relief and survival data not reported	Mild abdominal pain: 5/25 (25%); subcutaneous fat callus: 4/25 (20%); 2nd-degree skin burn: 1/25 (5%); pancreatic effusion: 1/25 (5%)
Xiong et al[32]	89	A retrospective study for unresectable pancreatic cancer. Tumor size not reported	Multiple-session HIFU monotherapy: 84 pts;HIFU + gemcitabine: 5 pts; HIFU sessions ranging 4-10	Pulsed HIFU irradiation, FEB-BY HIFU System	Pain relief: 54/67(80%), median survival: 26.0 mo (stage II), 11.2 mo (stage III) and 5.4 mo (stage IV)	Superficial skin burns: 3/89 (3%); subcutaneous fat sclerosis: 8/89 (6%); asymptomatic pseudocyst: 1/89 (1%)
Lee et al[33]	12	Advanced pancreatic cancer, unresectable, average tumor size 3.5 cm (2.3-5.3 cm)	Multiple-session HIFU monotherapy: 9 pts; HIFU + gemcitabine: 3 pts; average HIFU sessions: 4.2 (1-18)	Pulsed HIFU irradiation, FEB-BY HIFU System	Median survival for those receiving HIFU alone: 10.3 mo; Overall survival for 3 patients receiving the combined treatment: 26.0, 21.6 and 10.8 mo, respectively	Pancreatitis: 1/12 (8%); skin burn: 5/12 (41%); subcutaneous fat sclerosis: 2/12 (16%)

HIFU: High intensity focused ultrasound; pts: Patients.

Table 3 Technical and therapeutic differences in continuous high intensity focused ultrasound and pulsed focused ultrasound therapy

	US wave	US intensity	Treatment session	Change in US image during procedure	Treatment mechanism	Treatment use	Required anesthesia	Appearances in follow-up images
Continuous HIFU therapy	Continuous	5-20kW/cm2	One session	Real-time hyperechoic change in the focus during each shot	Thermal ablation for coagulation necrosis	Monotherapy, used alone	Sedation or general anesthesia	No contrast enhancement in tumor on MRI/CT; negative uptake on PET/CT
Pulsed focused ultrasound therapy	Pulsed	< 3 kW/cm2	Multiple sessions	No real-time US image change during each shot	Hyperthermia for enhancing sensitive to chemotherapeutic agents	Need to be combined with chemotherapy	Sedation or none	Tumor shrinkage on MRI/CT; negative uptake on PET/CT

HIFU: High intensity focused ultrasound; US: Ultrasound.