Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer

Table 1 Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
Radiologic confirmation of locally advanced pancreatic cancer	Resectable pancreatic adenocarcinoma
Histological or cytological confirmation of pancreatic adenocarcinoma	Chemotherapy or radiotherapy prior to the procedure
Tumor diameter ≤ 5 cm	Allergy to contrast media
Age ≥ 18 yr	History of epilepsy
Adequate bone marrow, liver, renal, and coagulation function: Hemoglobin level ≥ 115 g/L; platelet count ≥ 100 × 109/L; neutrophil count ≥ 2 × 109/L; white blood cell count ≥ 4 × 109/L	History of cardiac disease: Congestive heart failure > NYHA classification 2; cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker
PS 0-2	Uncontrolled hypertension
Written informed consent	Any implanted metal stent/device within the area of ablation that cannot be removed

NYHA: New York Heart Association.

Table 2 Demographics and tumor parameters of eligible patients

Characteristic	GEM + IRE group (n = 33)	GEM group (n = 35)	P value
Age, yr
Median	63	65
Range	45-86	39-81
Sex
Female	18 (54.5)	19 (54.3)	0.983
Male	15 (45.5)	16 (45.7)
Pathology
Adenocarcinoma	26	23
Lesion size (cm)	4.1 (3.0-5.0)	3.9 (3.0-5.0)
Tumor location
Head and neck	23 (23.3)	21 (26.7)	0.686
Body and tail	5 (40.0)	6 (50.0)
Previous surgical therapy			0.479
Gastrojejunostomy	3 (9.1)	4 (11.4)
Hepaticojejunostomy	1 (3.0)	2 (5.7)
Double bypass	2 (6.1)	0 (0.0)
Plastic retrievable endoprosthesis	1 (3.0)	1 (2.9)
Performance status			0.757
0	12 (36.3)	14 (40.0)
1	21 (63.7)	21 (60.0)
Accepted treatment			0.681
Biliary bypass and gastrojejunostomy	2 (6.1)	1 (2.9)
Cholecystectomy	1 (3.0)	0 (0.0)
Gastroenterostomy	2 (6.1)	2 (5.7)
Herb therapy	2 (6.1)	3 (8.6)
Immunotherapy	1 (3.0)	0 (0.0)

IRE: Irreversible electroporation; GEM: Gemcitabine.

Table 3 Univariate and multivariate analyses of overall survival in patients

Characteristic		GEM + IRE group (n = 33)			GEM group (n = 35)
		Univariate analysis			Multivariate analysis
		HR	95%CI	P value	HR	95%CI	P value
Age (yr)	≤ 60/> 60	1.632	0.763-3.325	0.121
Gender	Female/male	2.321	1.202-4.047	0.215
Tumor site	Head/body/tail	0.952	0.676-1.524	0.832
Tumor volume (cm3)	≤ 37/> 37	2.386	1.312-4.415	0.008	2.913	1.181-6.381	0.023
WBC (× 109)	≤ 10/> 10	1.128	0.343-2.872	0.988
HGB (g/L)	≤ 120/> 120	0.586	0.254-1.693	0.383
PLT (× 109)	≤ 300/> 300	1.218	0.526-2.867	0.672
ALT (U/L)	≤ 40/> 40	0.778	0.368-1.686	0.514
AST (U/L)	≤ 40/> 40	0.427	0.275-1.406	0.209
ALP (U/L)	≤ 100/> 100	0.895	0.506-1.824	0.793
CEA (ng/mL)	≤ 5/> 5	1.381	1.027-2.741	0.474
CA19-9 level	≤ 35/> 35	1.350	0.618-3.572	0.245
CA19-9 decrease 3 mo after treatment	≤ 50%/>50%	2.659	1.096-6.532	0.032	3.084	1.304-7.854	0.011
GEM	With/without IRE	0.389	0.178-0.952	0.045	0.422	0.157-0.958	0.047

IRE: Irreversible electroporation; GEM: Gemcitabine; HR: Hazard ratio; WBC: White blood cell count; HGB: Hemoglobin; PLT: Platelet count; ALT: Alanine transaminase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9.

Table 4 Univariate and multivariate analyses of progression free survival in patients

Characteristic		GEM + IRE group (n = 33)			GEM group (n = 35)
		Univariate analysis			Multivariate analysis
		HR	95%CI	P value	HR	95%CI	P value
Age (yr)	≤ 60/> 60	1.167	0.669-2.203	0.554
Gender	Female/male	1.602	0.942-2.802	0.097
Tumor size (cm)	≤ 4/> 4	0.787	0.489-1.280	0.334
Tumor site	Head/body/tail	0.942	0.623-1.410	0.750
Tumor volume (cm3)	≤ 37/> 37	2.386	1.298-4.406	0.012	2.856	1.180-6.420	0.025
WBC (× 109)	≤ 10/> 10	1.149	0.468-2.575	0.697
HGB (g/L)	≤ 120/> 120	0.587	0.298-1.513	0.285
PLT (× 109)	≤ 300/> 300	0.653	0.274-1.752	0.342
ALT (U/L)	≤ 40/> 40	0.542	0.433-1.533	0.341
AST (U/L)	≤ 40/> 40	0.636	0.347-1.521	0.304
ALP (U/L)	≤ 100/> 100	0.726	0.521-1.367	0.572
CEA (ng/mL)	≤ 5/> 5	1.322	0.715-2.602	0.162
CA19-9 (U/ml)	≤ 35/> 35	2.056	1.009-3.019	0.052
CA19-9 decrease 3 mo after IRE	≤ 50%/> 50%	2.258	0.895-6.428	0.032
GEM	With/without IRE	0.557	0.308-1.210	0.046	0.582	0.322-1.050	0.042

IRE: Irreversible electroporation; GEM: Gemcitabine; HR: Hazard ratio; WBC: White blood cell count; HGB: Hemoglobin; PLT: Platelet count; ALT: Alanine transaminase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9.

Table 5 Adverse reactions after treatment

Adverse event	GEM + IRE group (n = 33)			GEM group (n = 35)
Grade	I/II	III	IV	I/II	III	IV
Toxicity
Hypoalbuminemia	5	0	0	3	0	0
Lymphopenia	2	0	0	1	0	0
Hemoglobin reduction	3	0	0	2	0	0
Neutropenia	1	0	0	0	0	0
Thrombocytopenia	2	0	0	3	0	0
Vomiting	2	0	0	3	0	0
Hypokalemia	1	0	0	1	0	0
Diarrhea	2	0	0	1	0	0
Complications
Pancreatitis	0	2	0	0	0	0
Ascites	2	0	0	4	0	0
Bleeding from duodenal ulcer	0	1	0	0	0	0
Portal vein thrombosis	1	0	0	3	0	0
Loss of appetite	2		0	1	0	0
Gastroparesis	1	0	0	1	0	0
Abdominal pain	2	0	0	2	2	0

IRE: Irreversible electroporation; GEM: Gemcitabine.