Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

Table 1 Clinicopathological characteristics of patients with surgically treated ampulla of Vater carcinoma according to the adjuvant treatment, n (%)

Variables	Total (n = 104)	AC (n = 52)	Surgery alone (n = 52)	P value
Age, median (range)	64 (49-83)	69 (62-83)	64 (49-83)	0.924
Gender
Male	58 (55.8)	33 (56.9)	25 (43.1)	0.114
Female	46 (44.2)	19 (41.3)	27 (58.7)
Tumor size (cm), mean ± SD	2.5 ± 1.1	2.6 ± 1.3	2.4 ± 1.0	0.314
Resection status
R0	102 (98.0)	50 (49.0)	52 (51.0)	0.495
R1	2 (2.0)	2 (100)	0
Histologic grading
Grade 1/2	94 (90.3)	45 (47.9)	49 (52.1)	0.319
Grade 3	10 (9.7)	7 (70.0)	3 (30.0)
Tumor stage
T1-2	56 (53.8)	23 (41.1)	33 (58.9)	0.049
T3-4	48 (46.2)	29 (60.4)	19 (39.6)
Node stage
N0	45 (43.3)	14 (31.1)	31 (68.9)	0.001
N1-2	59 (56.7)	38 (64.4)	21 (35.6)
TNM stage1
Stage IB	30 (28.8)	8 (26.7)	22 (73.3)	0.002
Stage II	15 (14.4)	6 (40.0)	9 (60.0)
Stage III	59 (56.8)	38 (64.4)	21 (35.6)
Lymphatic invasion
No	42 (40.4)	13 (31.0)	29 (69.0)	0.001
Yes	62 (59.6)	39 (62.9)	23 (37.1)
Vascular invasion
No	81 (77.9)	34 (42.0)	47 (58.0)	0.002
Yes	23 (22.1)	18 (78.3)	5 (21.7)
Perineural invasion
No	74 (71.2)	32 (43.2)	42 (56.8)	0.030
Yes	30 (28.8)	20 (66.7)	10 (33.3)
Preoperative CA19-9 level
Within normal (< 40 U/mL)	45 (43.3)	22 (48.9)	23 (51.1)	0.516
Above normal (≥ 40 U/mL)	43 (41.3)	24 (55.8)	19 (44.2)
Missig data	16 (15.4)

¹According to American Joint Committee on Cancer 8^th edition. AC: Adjuvant chemotherapy; TNM: Tumor, node, metastasis; CA 19-9: Carbohydrate antigen 19-9.

Table 2 Univariate and multivariate analyses of the clinicopathologic findings and adjuvant chemotherapy for disease-free survival in patients with ampulla of Vater carcinoma

Variables	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age ≥ 70 yr (vs < 70 yr)	1.57 (0.91-2.70)	0.102
Histologic grade 3 (vs grade 1-2)	2.66 (0.98-7.18)	0.054	2.24 (1.02-4.95)	0.046
Tumor stage 3 or 4 (vs stage 1 or 2)	1.99 (1.21-3.28)	0.007	1.85 (1.06-3.22)	0.030
Nodal metastasis (vs none)	1.24 (0.76-2.03)	0.390	1.10 (0.63-1.95)	0.736
Lymphatic invasion (vs none)	1.76 (1.07-2.90)	0.025	1.49 (0.80-2.80)	0.212
Vascular invasion (vs none)	2.98 (1.53-5.80)	0.001	2.14 (1.20-3.79)	0.010
Perineural invasion (vs none)	1.47 (0.85-2.55)	0.164	0.97 (0.55-1.71)	0.901
Received AC (vs none)	0.85 (0.52-1.40)	0.536	0.50 (0.29-0.88)	0.015

HR: Hazard ratio; AC: Adjuvant chemotherapy.

Table 3 Univariate and multivariate analyses of the clinicopathologic findings and adjuvant chemotherapy for overall survival in patients with ampulla of Vater carcinoma

Variables	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age ≥ 70 yr (vs < 70 yr)	2.66 (1.40-5.07)	0.003	2.16 (1.18-3.98)	0.013
Histologic grade 3 (vs grade 1-2)	1.91 (0.67-5.49)	0.228	1.93 (0.77-4.81)	0.159
Tumor stage 3 or 4 (vs stage 1 or 2)	2.32 (1.31-4.11)	0.004	2.50 (1.31-4.80)	0.006
Nodal metastasis (vs none)	1.36 (0.77-2.39)	0.284	1.09 (0.58-2.04)	0.799
Lymphatic invasion (vs none)	1.50 (0.84-2.65)	0.168	1.23 (0.62-2.45)	0.553
Vascular invasion (vs none)	2.89 (1.35-6.20)	0.006	1.93 (0.96-3.88)	0.064
Perineural invasion (vs none)	2.17 (1.13-4.17)	0.020	1.27 (0.66-2.45)	0.477
Received AC (vs none)	1.04 (0.59-1.82)	0.018	0.58 (0.30-1.11)	0.098

HR: Hazard ratio; AC: Adjuvant chemotherapy.

Table 4 Relative dose intensity and dose modification of the adjuvant chemotherapy

	FL (n = 30)	FP (n = 22)
Duration of treatment, weeks, median (range)	24.1 (7.9-29.0)	24.1 (7.7-29.6)
Cycles of drug administration, median (range)	6 (2-6)	6 (2-6)
Relative dose intensity, mean (range)	0.83 (0.27-1.00)	0.85 (0.33-1.00)
Received all cycles of chemotherapy, n (%)	20 (66.7)	16 (72.7)
Dose reduction or interruption, n (%)	10 (33.3)	10 (45.5)
Discontinued adjuvant chemotherapy, n (%)	10 (33.3)	6 (27.3)
Relapse	5 (16.7)	2 (9.0)
Intolerance	5 (16.7)	4 (18.3)

FL: Fluorouracil/leucovorin; FP: Fluorouracil/cisplatin.

Table 5 Adverse events during treatment

Adverse event	FL (n = 30)		FP (n = 22)		P value1
	Grade 1-2	Grade 3-4	Grade 1-2	Grade 3-4
Stomatitis	11 (36.7)	0	3 (13.6)	0	0.112
Nausea	6 (20.0)	0	19 (86.4)	0	< 0.001
Vomiting	1 (3.3)	0	4 (18.2)	0	0.149
Diarrhea	2 (6.6)	1 (3.3)	0	0	0.253
Fatigue	8 (26.7)	1 (3.3)	19 (86.4)	0	< 0.001
Neutropenia	3 (10.0)	0	10 (45.5)	4 (18.2)	< 0.001
Febrile neutropenia	0	0	0	2 (9.0)	0.174
Anemia	8 (26.7)	0	10 (45.5)	1 (4.5)	0.084
Thrombocytopenia	2 (6.6)	0	8 (36.4)	0	0.012
Increased AST/ALT level	4 (13.3)	0	0	0	0.128

¹Comparison of the proportion of all grades of adverse events. FL: Fluorouracil/leucovorin; FP: Fluorouracil/cisplatin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.