Comparison of efficacy between adjuvant chemotherapy and chemoradiation therapy for pancreatic cancer: AJCC stage-based approach

Table 1 Baseline characteristics

Variables	n = 335
Age	63.5 ± 9.1
Female/male	143 (42.7)/192 (57.3)
ECOG
0	275 (82.1)
1	60 (17.9)
Charlson's comorbidity index	4.6 ± 1.3
Tumor location, n (%)
Head/uncinate	215 (64.2)
Body	54 (16.1)
Tail	54 (16.1)
Overlapping	12 (3.6)
Surgery type, n (%)
Pancreaticoduodenectomy	222 (66.3)
Distal pancreatectomy	102 (30.4)
Total pancreatectomy	7 (2.1)
Subtotal pancreatectomy	4 (1.2)
Differentiation, n (%)
WD	24 (7.2)
MD	268 (80.0)
PD	29 (8.7)
UD	3 (0.9)
Unknown	11 (3.3)
AJCC stage, n (%)
IA	46 (13.7)
IB	90 (26.9)
IIA	12 (3.6)
IIB	128 (38.2)
III	59 (17.6)
Lymphovascular invasion, n (%)	196 (58.9)
Perineural invasion, n (%)	280 (83.6)
Preoperative laboratory findings
WBC as × 103 cells/µL	6.1 ± 1.8
Hb in g/dL	12.9 ± 1.5
AST in IU/L	43.4 ± 49.6
ALT in IU/L	66.4 ± 93.7
ALP in IU/L	159.3 ± 165.1
Albumin in mg/dL	4.2 ± 3.5
Total bilirubin in mg/dL	2.2 ± 3.6
Creatinine in mg/dL	0.8 ± 0.2
CA 19-9 in U/mL	623.2 ± 1491.9
CEA in ng/mL	22.4 ± 307.2
Duration to initial adjuvant treatment in d	47.5 ± 17.7
Follow-up duration in mo	32.2 ± 28.6

AJCC: American Joint Committee on Cancer; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CA 19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; ECOG: Eastern Cooperative Oncology Group; Hb: Hemoglobin; MD: Moderately differentiated; PD: Poorly differentiated; UD: Undifferentiated; WBC: White blood cell; WD: Well differentiated.

Table 2 Cox proportional hazard regression analysis predicting overall survival

	Number of patients, n = 335	Median OS, mo (95%CI)	Univariable		Multivariable
			HR (95%CI)	P value	HR (95%CI)	P value
Age ≥ 70				0.145		0.218
No	237	35.1 (28.5-44.4)	1.00		1.00
Yes	98	26.9 (22.2-39.2)	1.24 (0.91-1.70)		1.29 (0.84-1.99)
Sex				0.226		0.394
Female	143	33.3 (27.1-46.1)	1.00		1.00
Male	192	32.3 (25.7-39.8)	1.21 (0.90-1.62)		1.14 (0.83-1.55)
ECOG				0.469		0.731
0	275	34.2 (27.8-42.4)	1.00		1.00
1	60	27.4 (19.1-39.8)	1.16 (0.79-1.69)		1.11 (0.74-1.65)
Charlson’s index ≥ 6				0.222		0.876
No	257	34.0 (28.5-39.8)	1.00		1.00
Yes	78	26.0 (22.2-50.8)	1.21 (0.87-1.68)		1.07 (0.68-1.67)
Safety margin ≤ 0.1 cm				0.032		0.345
No	209	35.9 (30.7-47.0)	1.00		1.00
Yes	126	26.9 (22.3-34.8)	1.41 (1.04-1.91)		1.18 (0.86-1.62)
Histology				0.077		0.038
WD/MD	292	33.9 (27.8-39.6)	1.00		1.00
PD/UD	32	18.0 (16.2-NA)	1.50 (0.94-2.40)		1.71 (1.04-2.82)
Lymphovascular invasion				< 0.001		< 0.001
No	137	60.9 (44.4-89.6)	1.00		1.00
Yes	196	25.3 (21.5-28.5)	2.14 (1.61-2.85)		1.91 (1.36-2.69)
Perineural invasion				< 0.001		0.590
No	55	59.3 (42.4-114.6)	1.00		1.00
Yes	280	30.6 (26.0-35.7)	1.73 (1.16-2.59)		1.17 (0.75-1.82)
AJCC stage
I	136	59.3 (39.6-82.1)	1.00	< 0.001		0.003
II	140	27.6 (23.0-34.8)	1.83 (1.32-2.54)		1.36 (0.96-1.94)
III	59	22.0 (16.3-27.4)	2.84 (1.93-4.18)		1.97 (1.29-3.01)
CA19-9 ≥ 100 U/mL				< 0.001		0.002
No	159	47.0 (34.0-90.6)	1.00		1.00
Yes	175	26.9 (22.5-33.6)	1.74 (1.30-2.33)		1.67 (1.21-2.30)

AJCC: American Joint Committee on Cancer; CA 19-9: Carbohydrate antigen 19-9; ECOG: Eastern Cooperative Oncology Group; MD: Moderately differentiated; NA: Not available; PD: Poorly differentiated; UD: Undifferentiated; WD: Well differentiated.

Table 3 Differences in baseline characteristics between chemotherapy, chemoradiation therapy and chemotherapy plus chemoradiation therapy groups

Variables	Group A, n = 65	Group B, n = 62	Group C, n = 208	P value
Female, n (%)	23 (35.4)	27 (43.5)	93 (44.7)	0.410
Age ≥ 70, n (%)	24 (36.9)	26 (41.9)	48 (23.1)	0.005
ECOG, n (%)				0.009
0	47 (72.3)	47 (75.8)	181 (87.0)
1	18 (27.7)	15 (24.2)	27 (13.0)
Histology, n (%)				0.160
WD/MD	52 (80.0)	55 (88.7)	185 (88.9)
PD/UD	10 (15.4)	7 (11.3)	15 (7.2)
Unknown	3 (4.6)	0 (0.0)	8 (3.8)
Charlson's index ≥ 6, n (%)	17 (26.2)	20 (32.3)	41 (19.7)	0.101
Safety margin ≤ 0.1 cm, n (%)	26 (40.0)	32 (51.6)	68 (32.7)	0.024
CA19-9 ≥ 100 U/mL, n (%)	26 (40.0)	36 (58.1)	113 (54.6)	0.074
Lymphovascular invasion, n (%)	27 (41.5)	34 (54.8)	87 (42.0)	0.435
Perineural invasion, n (%)	54 (83.1)	56 (90.3)	170 (81.7)	0.275
Surgery type, n (%)				0.388
Pancreaticoduodenectomy	42 (64.6)	38 (61.3)	142 (68.3)
Distal pancreatectomy	19 (29.2)	24 (38.7)	59 (28.4)
Subtotal pancreatectomy	1 (1.5)	0 (0.0)	3 (1.4)
Total pancreatectomy	3 (4.6)	0 (0.0)	4 (1.9)
AJCC stage, n (%)				0.080
IA/IB	19 (29.2)	28 (45.2)	89 (42.8)
IIA/IIB	37 (56.9)	21 (33.9)	82 (39.4)
III	9 (13.8)	13 (21.0)	37 (17.8)
Duration to initial adjuvant treatment in d	46.8 ± 15.3	43.9 ± 18.4	48.8 ± 18.0	0.223
Treatment duration	39.8 ± 9.9	143.2 ± 47.5	194.8 ± 48.2	< 0.001

Group A: Chemoradiation therapy; Group B: Chemotherapy, Group C: Chemotherapy plus chemoradiation therapy. AJCC: American Joint Committee on Cancer; CA 19-9: Carbohydrate antigen 19-9; ECOG: Eastern Cooperative Oncology Group; MD: Moderately differentiated; PD: Poorly differentiated; UD: Undifferentiated; WD: Well differentiated.

Table 4 Recurrence pattern between chemotherapy, chemoradiation therapy, and chemotherapy plus chemoradiation therapy groups, n (%)

Recurrence site	Group A, n = 65	Group B, n = 62	Group C, n = 208	P value
Remnant pancreas	2 (3.1)	2 (3.2)	8 (3.8)	0.945
Operation bed	16 (24.6)	17 (27.4)	47 (22.5)	0.728
Liver	24 (36.9)	13 (21.0)	53 (25.4)	0.089
Peritoneum	9 (13.8)	3 (4.8)	29 (13.9)	0.144
Lung	8 (12.3)	4 (6.5)	19 (9.1)	0.521
Lymph node	3 (4.6)	8 (12.9)	17 (8.1)	0.238
Local only	9 (19.1)	12 (36.4)	29 (22.0)	0.158
Distant	38 (80.9)	21 (63.6)	100 (75.8)	0.205
Multiple site	13 (20.0)	11 (17.7)	36 (17.3)	0.884

Group A: Chemoradiation therapy; Group B: Chemotherapy; Group C: Chemotherapy plus chemoradiation therapy.

Table 5 Differences in adverse events between chemoradiation therapy, chemotherapy and chemotherapy plus chemoradiation therapy groups, n (%)

Complications	Group A, n = 65			Group B, n = 62			Group C, n = 208			P value
	Grade 2	Grade 3	Grade 4	Grade 2	Grade 3	Grade 4	Grade 2	Grade 3	Grade 4
Febrile neutropenia	-	-	-	-	-	-	-	1 (0.5)	-	0.736
Neutropenia	15 (23.1)	3 (4.6)	5 (7.7)	15 (24.2)	15 (24.2)	6 (9.7)	63 (30.3)	68 (32.7)	21 (10.1)	< 0.001
Anemia	14 (21.5)	1 (1.5)	1 (1.5)	19 (30.6)	2 (3.2)	1 (1.6)	84 (40.4)	17 (8.2)	1 (0.5)	0.001
Thrombocytopenia	-	1 (1.5)	-	5 (8.1)	2 (3.2)	1 (1.6)	16 (7.7)	7 (3.4)	2 (1.0)	0.037
Hypertransaminasemia	3 (4.6)	1 (1.5)	-	3 (4.8)	1 (1.6)	-	24 (11.5)	12 (5.8)	3 (1.4)	0.006
N/V	4 (6.2)	-	-	5 (8.1)	2 (3.2)	-	10 (4.8)	4 (1.9)	-	0.441
Diarrhea	4 (6.2)	-	-	3 (4.8)	1 (1.6)	-	16 (7.7)	2 (1.0)	-	0.735
Anorexia	5 (7.7)	1 (1.5)	-	4 (6.5)	-	-	14 (6.7)	-	-	0.770
Abdominal pain	3 (4.6)	-	-	3 (4.8)	-	-	10 (4.8)	1 (0.5)	-	0.973
GERD	4 (6.2)	-	-	1 (1.6)	-	-	7 (3.4)	-	-	0.374
Fatigue	5 (7.7)	2 (3.1)	-	2 (3.2)	1 (1.6)	-	19 (9.1)	2 (1.0)	-	0.408
Mucositis	1 (1.5)	-	-	2 (3.2)	1 (1.6)	-	5 (2.4)	1 (0.5)	-	0.545
Peripheral neuropathy	-	-	-	-	1 (1.6)	-	-	3 (1.4)	-	0.611

Group A: Chemoradiation therapy; Group B: Chemotherapy, Group C: Chemotherapy plus chemoradiation therapy. GERD: Gastroesophageal reflux disease; N/V: Nausea and vomiting.