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Clinical Implications of Naples Prognostic Score in Patients with Resected Pancreatic Cancer

Nakagawa, Nobuhiko Yamada, Suguru Sonohara, Fuminori Takami, Hideki Hayashi, Masamichi Kanda, Mitsuro Kobayashi, Daisuke Tanaka, Chie Nakayama, Goro Koike, Masahiko Fujiwara, Michitaka Kodera, Yasuhiro 名古屋大学

2020.03

概要

Background: Nutritional and immunological statuses are attracting increasing attention for their ability to predict surgical outcomes in various cancers. The Naples prognostic score (NPS) consists of the serum albumin level, total cholesterol level, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio and could be useful for predicting survival. Patients and Methods: We retrospectively analyzed 196 patients with pancreatic cancer who underwent curative R0/R1 resection with a surgery-first strategy between June 2003 and August 2016. The NPS of the patients was calculated from preoperative data, and the patients were then divided into three groups based on their NPS. Clinicopathological characteristics, surgical outcomes, and long-term survival were compared, and multivariate analysis of overall survival was conducted. Results: Of a total of 196 patients, 22 were classified into group 0 (NPS 0), 113 into group 1 (NPS 1 or 2), and 61 into group 2 (NPS 3 or 4). Median survival time was 103.4 months in group 0, 33.3 months in group 1, and 21.3 months in group 2. Significant survival differences were observed among the 3 groups (group 1 vs. 2, group 0 vs. 2, P = 0.0380, P = 0.0022, respectively). On multivariate analysis, NPS was identified as an independent prognostic factor [hazard ratio (HR) = 1.78; P = 0.0131]; however, there were no significant differences in the incidence of postoperative morbidity among the NPS groups. Conclusions: The NPS could be an easy scoring system and an independent preoperative predictor of survival.

関連論文

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27

FIGURE LEGENDS

Figure 1.

A, Kaplan-Maier curves of overall survival for each NPS group. B, Kaplan-Maier

curves of recurrence-free survival for each NPS group.

Supplementary Figure 1.

Calculation of the Naples prognostic score.

Supplementary Figure 2.

10

Kaplan-Maier curves of overall survival and recurrence-free survival in patients

without adjuvant chemotherapy.

Supplementary Figure 3.

Kaplan-Maier curves of overall survival and recurrence-free survival in patients

15

with adjuvant chemotherapy.

Supplementary Figure 4.

28

Receiver operating characteristic curves of the prognostic indicators.

29

TABLE 1. Patient Characteristics

Variables

64.2 ± 10.3

Age, mean ± SD (years)

Sex

Male

126 (64.3%)

Female

70 (35.7%)

21.6 ± 3.17

Body mass index, mean ± SD

Tumor location

Head

147 (75.0%)

Body or tail

49 (25.0%)

Operative procedure

PD

60 (30.6%)

PPPD

15 (7.7%)

SSPPD

63 (32.2%)

DP

45 (22.9%)

TP

11 (5.6%)

Others

2 (1.0%)

UICC stage

IA

6 (3.1%)

IB

2 (1.0%)

IIA

57 (29.1%)

IIB

108 (55.1%)

III

2 (1.0%)

IV

21 (10.7%)

72 (36.7%)

Adjuvant chemotherapy

S-1

38 (19.4%)

GEM

18 (9.2%)

GS

4 (2.0%)

Others

12 (6.1%)

Naples prognostic score

Group 0

22 (11.2%)

Group 1

113 (57.7%)

30

61 (31.1%)

Group 2

PD; Pancreaticoduodenectomy, PPPD; Pylorus-preserving pancreaticoduodenectomy,

SSPPD;

Subtotal

stomach-preserving

pancreaticoduodenectomy,

DP;

Distal

pancreatectomy, TP; Total pancreatectomy, GEM; Gemcitabine, GS; Gemcitabine + S-1

31

TABLE 2. Association of Naples Prognostic Score and Clinicopathological Characteristics in 196

Patients with Resected Pancreatic Cancer

Variables

Age, years

Group 0

Group 1

Group 2

(n = 22)

(n = 113)

(n = 61)

61.1 ± 9.8

64.6 ± 10.1

64.6 ± 10.7

0.3281

0.0168*

Sex

Male

8 (36.4)

75 (67.6)

41 (67.2)

Female

14 (63.6)

36 (32.4)

20 (32.8)

20.4 ± 0.96

21.5 ± 0.41

20.7 ± 0.63

Body mass index

P value

0.4034

0.0022*

Tumor Location

Head

13 (59.1)

77 (69.4)

55 (90.2)

Body or tail

9 (40.9)

34 (30.6)

6 (9.8)

0.1302

CA19-9

≤ 37 IU/ml

10 (45.5)

29 (25.7)

46 (75.4)

> 37 IU/ml

12 (54.5)

84 (74.3)

15 (24.6)

0.6825

Tumor Size

≤ 20 mm

7 (31.8)

31 (27.4)

14 (22.9)

> 20 mm

15 (68.2)

82 (72.6)

47 (77.1)

0.0121*

Serosa invasion

(+)

13 (59.1)

90 (79.7)

54 (88.5)

(-)

9 (40.9)

23 (20.3)

7 (11.5)

0.0608

Retroperitoneum invasion

(+)

19 (86.4)

99 (87.6)

45 (73.8)

(-)

3 (13.6)

14 (12.4)

16 (26.2)

<.0001*

Bile duct invasion

(+)

7 (31.8)

46 (40.7)

44 (72.1)

(-)

15 (68.2)

67 (59.3)

17 (27.9)

<.0001*

Duodenum invasion

(+)

6 (27.3)

36 (31.9)

40 (65.6)

(-)

16 (72.7)

77 (68.1)

21 (34.4)

0.3431

Portal venous system invasion

(+)

8 (36.4)

46 (40.7)

18 (29.5)

(-)

14 (63.6)

67 (59.3)

43 (70.5)

0.7926

Regional artery invasion

(+)

2 (9.1)

13 (11.5)

5 (8.3)

(-)

20 (90.1)

100 (88.5)

55 (91.7)

32

0.6995

Nerve plexus invasion

(+)

3 (13.6)

20 (17.7)

13 (21.3)

(-)

19 (86.4)

93 (82.3)

48 (78.7)

0.7959

Lymphatic invasion

(+)

19 (90.5)

90 (84.9)

44 (86.3)

(-)

2 (9.5)

16 (15.1)

7 (13.7)

0.9006

Venous invasion

(+)

12 (57.1)

64 (60.4)

29 (56.9)

(-)

9 (42.9)

42 (39.6)

22 (43.1)

0.1349

Perineural invasion

(+)

17 (80.9)

88 (83.0)

48 (94.1)

(-)

4 (19.1)

18 (17.0)

3 (5.9)

0.099

Lymph node metastasis

(+)

11 (50.0)

79 (71.2)

45 (73.8)

(-)

11 (50.0)

32 (28.8)

16 (26.2)

0.3743

Peritoneal cytology

(+)

3 (13.6)

17 (15.0)

14 (22.9)

(-)

19 (86.4)

96 (85.0)

47 (77.1)

0.8913

UICC stage

I or II

III or IV

20 (90.9)

99 (87.6)

54 (88.5)

2 (9.1)

14 (12.4)

7 (11.5)

0.0989

Residual tumor

R1

2 (9.1)

30 (27.3)

20 (32.8)

R0

20 (90.9)

80 (72.7)

41 (67.2)

8 (36.3)

30 (26.5)

18 (29.5)

Adjuvant chemotherapy

CA19-9; Carbohydrate antigen 19-9, *; Statistically significant

33

0.6353

TABLE 3. Univariate and Multivariate Cox Proportional-hazard Regression Analysis of Overall Survival of Patients

Univariate analysis

Variables

Multivariate analysis

HR (95% CI)

P value

HR (95% CI)

P value

Age (≥ 70 years vs. < 70 years)

1.21 (0.79-1.83)

0.3667

Sex (male vs. female)

0.78 (0.52-1.16)

0.2166

Tumor location (head vs. body or tail)

1.23 (0.80-1.95)

0.3552

Tumor size (≤ 20 mm vs. > 20 mm)

0.48 (1.31-3.52)

0.0014

1.12 (0.66-1.96)

0.6795

Serosa invasion (+ vs. -)

1.13 (0.72-1.83)

0.5969

Retroperitoneum invasion (+ vs. -)

0.91 (0.57-1.52)

0.7024

Bile duct invasion (+ vs. -)

1.55 (1.05-2.30)

0.0261

1.03 (0.65-1.64)

0.9076

Duodenum invasion (+ vs. -)

1.41 (0.95-2.07)

0.0891

Portal venous system invasion (+ vs. -)

2.24 (1.52-3.31)

<.0001

1.94 (1.23-3.08)

0.0046*

Regional artery invasion (+ vs. -)

1.97 (1.05-3.41)

0.0359

0.78 (0.39-1.46)

0.4504

Nerve plexus invasion (+ vs. -)

2.04 (1.26-3.20)

0.0047

1.26 (0.70-2.20)

0.4335

Lymphatic invasion (+ vs. -)

3.39 (1.68-8.09)

0.0002

1.75 (0.77-4.55)

0.1883

Venous invasion (+ vs. -)

1.86 (1.25-2.84)

0.0023

0.96 (0.60-1.57)

0.8820

Perineural invasion (+ vs. -)

3.64 (1.73-9.36)

0.0002

1.58 (0.67-4.37)

0.3112

Lymph node metastasis (+ vs. -)

2.71 (1.68-4.60)

<.0001

1.99 (1.18-3.53)

0.0096*

Peritoneal cytology (+ vs. -)

1.93 (1.15-3.09)

0.0146

1.83 (1.06-3.05)

0.0305*

UICC stage (III or IV vs. I or II)

2.75 (1.61-4.46)

0.0004

1.39 (0.76-2.44)

0.2786

Residual tumor (R1 vs. R0)

2.14 (1.37-3.26)

0.0011

1.55 (0.93-2.53)

0.0942

CA19-9 (≥ 37 IU/ml vs. < 37 IU/ml)

1.37 (0.88-2.19)

0.1690

34

Adjuvant chemotherapy (- vs. +)

2.66 (1.75-4.16)

<.0001

2.71 (1.75-4.29)

<.0001*

NPS (Grade 2 vs. Grade 0/1)

1.73 (1.14-2.59)

0.0109

1.82 (1.15-2.84)

0.0104*

CA19-9; Carbohydrate antigen 19-9; NPS; Naples prognostic score, *; Statistically significant

35

TABLE 4. Association of Naples Prognostic Score and Surgical Outcome

Grade 0

Grade 1

Grade 2

(n = 22)

(n = 113)

(n = 61)

Operative time (min)

384.7 ± 28.9

423.8 ± 12.9

457.9 ± 17.4

Estimated blood loss (ml)

822.4 ± 200.1 1009.4 ± 89.1 1159.9 ± 120.2

P value

0.0755

0.3201

Postoperative complications (CD ≥ Ⅲ)

8 (38.1)

43 (40.6)

17 (33.3)

0.6828

ISGPF grade ≥ B

6 (28.6)

25 (23.6)

8 (15.7)

0.5167

Bile leakage

0 (0)

1 (0.9)

3 (5.8)

0.1124

Intra-abdominal bleeding

0 (0)

3 (2.8)

1 (1.9)

0.7168

Delayed gastric emptying

1 (4.8)

12 (11.3)

7 (13.7)

0.5488

Infectious complications

1 (4.8)

11 (10.4)

8 (15.7)

0.3728

Portal vein thrombosis

1 (4.8)

3 (2.8)

1 (1.9)

0.8074

34.8 ± 5.5

37.8 ± 2.5

37.4 ± 3.5

0.8806

Postoperative hospital stay (day)

CD; Clavien-Dindo grade, ISGPF; International Study Group for Pancreatic Fistula

...

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