A Retrospective Case Series Of High-Intensity Focused Ultrasound (HIFU) In Combination With Gemcitabine And Oxaliplatin (Gemox) On Treating Elderly Middle And Advanced Pancreatic Cancer

Figures & data

Table 1 Patient Baseline Characteristics

Characteristics	Characteristics	No. Of Patients (%/Range)
Gender	Male	21 (55.3%)
	Female	17 (44.7%)
Age	Median (range), years	69 (60–78)
KPS	Mean±SD	72.63±10.27
	≥ 80	17 (44.7%)
	< 80	21 (55.3%)
VAS	Mean±SD	5.86±2.13
	≥ 4	29 (76.3%)
	<4	9 (23.7%)
Tumor location	Head	16 (41.2%)
	Body	13 (33.3%)
	Tail	9 (23.7%)
UICC-Stage	Stage II	4 (10.5%)
	Stage III	15 (39.5%)
	Stage IV	19 (50.0%)
Tumor size*	Mean±SD, cm	4.2±1.6
	≥ 3cm	22 (57.9%)
	< 3cm	16 (42.1%)
CA 19-9	Mean±SD, U/mL	247.9±68.6
	Positive	32 (84.2%)
	Negative	6 (15.8%)
HIFU sessions	Median (range)	8 (5–16)

Notes: *Tumor size at baseline was measured by CT and MRI imaging in 30 and 14 cases, respectively. Within six patients who evaluated by both imaging modalities, the results from MRI were adopted.

Abbreviations: CT, computed tomography; HIFU, high-intensity focused ultrasound; MRI, magnetic resonance imaging; VAS, visual analogue scale; UICC, Union for International Cancer Control; DCR, disease control rate; KPS, Karnofsky Performance Status.

Table 2 Toxic Effects Of HIFU Combined With Chemotherapy In The Treatment Of Advanced Pancreatic Cancer

Toxic Effects	Grade				III–IV(%)	Rate (%)
	I	II	III	IV
Leukopenia	16	9	4	3	18.4	84.2
Thrombocytopenia	12	7	3	1	10.5	60.5
Hemoglobin reduction	25	4	1	0	2.6	78.9
Hepatic dysfunction	9	2	1	1	5.2	34.2
Renal dysfunction	8	2	0	0	0	26.3
Nausea and vomiting	16	5	1	0	2.6	57.8
Peripheral nerve toxicity	11	3	0	0	0	36.8

Figure 1 Treatment process and CT imaging of a 65-year-old male patient with pancreatic cancer who received HIFU treatment.

Notes: (A) This patient was receiving HIFU ablation in a supine position. (B) Before treatment, a space-occupying lesion with a diameter of about 2 cm could be seen in the pancreatic uncinate process, without pancreatic duct dilated. The CA 19–9 level was tested to be 4370 U/mL. (C) Six months after HIFU treatment, the size and morphology of the pancreas returned to normal, and no visible space-occupying lesions were found in the uncinate process. The CA 19–9 level reduced to 362 U/mL.

Abbreviations: CT, computed tomography; HIFU, high-intensity focused ultrasound.

Table 3 Best Overall Response And CA 19–9 Response Of Patients

Response	Total (N=38) n (%)	Stage II (n=4) n (%)	Stage III (n=15) n (%)	Stage IV (n=19) n (%)
Best overall response*
CR	1 (2.6%)	0	1 (6.7%)	0
PR	6 (15.8%)	1 (25.0%)	2 (13.4%)	3 (15.8%)
SD	22 (57.9%)	2 (50.0%)	9 (60.0%)	11 (57.9%)
PD	9 (23.7%)	1 (25.0%)	3 (20.0%)	5 (26.3%)
ORR (CR+PR)	7 (18.4%)	1 (25.0)	3 (20.0%)	3 (15.8%)
DCR (CR+PR+SD)	29 (76.3%)	3 (75.0%)	12 (80.0%)	14 (73.7%)
CA 19–9 Decrease
>20%	26 (68.4%)	3 (75.0%)	10 (66.7%)	13 (68.4%)
>50%	17 (53.1%)	2 (50.0%)	7 (46.7%)	8 (42.1%)
>90%	11 (34.4%)	1 (25.0%)	4 (26.7%)	6 (31.6%)

Notes: *Response evaluation was performed at one month and three months after HIFU and then 3-month intervals during the first years and 6-month intervals during the remainder of the follow-up phase. Here, the best overall response was reported. In the results of the best overall response, 3 cases were evaluated by both CT and MRI.

Abbreviations: CT, computed tomography; HIFU, high-intensity focused ultrasound; MRI, magnetic resonance imaging; CR, complete response; PR, partial response; SD, stable disease; PD, progression disease; ORR, objective response rate; DCR, disease control rate.

Figure 2 Survival outcome of patients treated with HIFU and Gemox.

Notes: (A) OS of the overall cohort; (B) PFS of the overall cohort; (C) Subgroup analysis of OS by UICC Stage; No significant difference was detected between cases in different stages (Log-rank p = 0.95); (D) Subgroup analysis of PFS by UICC Stage; No significant difference was detected between cases in various stages (Log-rank p = 0.95).

Abbreviations: OS, overall survival; PFS, progression-free survival; HIFU, high-intensity focused ultrasound; CI, confidence interval; UICC, Union for International Cancer Control.

Table 4 CBR Evaluation Of HIFU Combined With Chemotherapy In The Treatment Of Advanced Pancreatic Cancer

CBR	Total, n (%)	Stage II, n (%)	Stage III, n (%)	Stage IV, n (%)
Valid	26 (68.4%)	2 (50.0%)	11 (73.3%)	13 (68.4%)
Pain relief*	27 (90%)	1 (50.0%)	12 (92.3%)	13 (86.7%)
Analgesic reduction*	23 (76.6%)	2 (100.0%)	10 (76.9%)	11 (73.3%)
KPS improvement*	19 (63.3%)	1 (50.0%)	9 (69.2%)	9 (60.0%)
Weight Gain*	17 (56.6%)	1 (50.0%)	7 (53.8%)	9 (60.0%)
Invalid	12 (31.6%)	2 (50.0%)	4 (26.7%)	6 (32.6%)

Notes: *These items were evaluated in 30 patients by excluding eight cases without any pain, analgesic, KPS reduction, or weight loss.

Abbreviations: CBR, clinical benefit rate; HIFU, high-intensity focused ultrasound; KPS, Karnofsky Performance Status.

Table 5 Survival Outcome And Subgroup Analyses By The UICC Stage Of Patients Treated With HIFU And Gemox

Survival	Overall (n=38)	Stage II (n=4)	Stage III (n=15)	Stage IV (n=19)	Log-rank p-values
Median OS, months (95% CI)	12.5 (10.3–13.9)	11.5 (5.7-NE)	12.5 (4.8-NE)	12.2 (7.5–14.2)	0.95
6-month OS rate, % (95% CI)	82.13 (64.45–91.56)	75.00 (12.79–96.05)	76.92 (44.21–91.91)	87.50 (58.60–96.72)	-
1-year OS rate, % (95% CI)	59.34 (38.93–47.92)	37.50 (1.10–80.80)	65.93 (31.54–86.04)	59.58 (30.84–79.62)	-
Median PFS months (95% CI)	6.7 (5.1–9.7)	6.2 (4.8-NE)	6.9 (1.7–10.8)	5.7 (3.7–10.4)	0.81
6-month PFS rate, % (95% CI)	53.91 (36.65–68.36)	75.00 (12.79–96.05)	53.33 (26.32–74.38)	48.63 (24.29–69.27)
1-year PFS rate, % (95% CI)	16.39 (6.14–30.98)	0 (NE-NE)	23.33 (5.92–47.27)	14.19 (2.42–35.88)

Abbreviations: OS, overall survival; PFS, progression-free survival; HIFU, high-intensity focused ultrasound; CI, confidence interval; UICC, Union for International Cancer Control; NE, not evaluable.