Ann Surg Oncol DOI 10.1245/s10434-015-4518-z
ORIGINAL ARTICLE – GASTROINTESTINAL ONCOLOGY
The Platelet-to-Lymphocyte Ratio Versus Neutrophil-toLymphocyte Ratio: Which is Better as a Prognostic Factor in Gastric Cancer? Eun Young Kim, MD, Jin Won Lee, MD, Han Mo Yoo, MD, Cho Hyun Park, MD, and Kyo Young Song, MD Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
ABSTRACT Background. As indicators of the systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed to predict the clinical outcome in some cancers. The purpose of this study was to investigate the impact of NLR and PLR on the prognosis of gastric cancer. Methods. From 2000 to 2009, 1986 consecutive patients who underwent curative surgery for gastric cancer were enrolled. The optimal cutoff value of PLR and NLR was determined according to receiver operating characteristic analysis. We categorized the patients into the high or low PLR and NLR group based on the cutoff value, and the clinical features of these two groups were comparatively analyzed. Results. The high NLR and PLR groups were significantly associated with poor prognosis. The NLR was an independent prognostic factor for overall survival [hazard ratio (HR) = 1.403; p = 0.023]; however, the PLR was not (p = 0.788). Conclusions. Although both the PLR and NLR can reflect the prognosis, the NLR is more predictive of overall survival than the PLR.
Currently, the major issue in treating gastric cancer is how best to individualize therapy based on tumor characteristics as well as patient factors. For example, to improve the quality of life as well as achieve an early recovery,
Ó Society of Surgical Oncology 2015 First Received: 30 January 2015 K. Y. Song, MD e-mail: [email protected]
minimally invasive treatments, such as laparoscopic gastrectomy, have been proposed as a suitable alternative to conventional open surgery in patients with early gastric cancer (EGC). Meanwhile, radical surgery with extended lymph node dissection is a standard approach for advanced gastric cancer. The ability to predict the precise prognosis of a patient is critical for selecting the optimal treatment plan and followup strategies. Although the only reliable prognosticator is the tumor, node, metastasis (TNM) stage, even within the same tumor stage, heterogeneous clinical courses are frequently observed. Therefore, further studies should be performed to provide a more reliable prognostic factor. Recently, the systemic inflammatory response has been found to be an independent marker of prognosis in several types of cancer. Investigations have shown a significant relationship between leukocytosis, thrombocytosis, an elevated neutrophil-to-lymphocyte ratio (NLR) or plateletto-lymphocyte ratio (PLR), and poor survival in various cancers.1–6 However, in only a few studies were these inflammation-based scores associated with the prognosis of gastric cancer. Therefore, the purpose of this study was to confirm that the PLR and NLR are associated with the prognosis of gastric cancer and to compare the clinical usefulness of these two factors based on a large volume of data concerning gastric cancer after curative surgery. PATIENTS AND METHODS The prospectively collected data on 2494 patients with gastric adenocarcinoma who underwent gastrectomy at Seoul St. Mary’s Hospital between 2000 and 2009 were reviewed. Of these 2494 patients, 1986 who underwent curative-intent surgery for gastric cancer were enrolled in this study. The exclusion criteria for this study were as
E. Y. Kim et al.
follows: remnant gastric cancer, neoadjuvant chemotherapy, synchronous and metachronous malignancies, emergency surgery, liver cirrhosis, evidence of a severe inflammatory condition, presence of coexisting hematological malignancies or disorders, autoimmune disorders and recent steroid therapy, and incomplete/inaccurate medical records. Institutional review board approval was obtained. Blood Sample Analysis Blood samples were obtained preoperatively for the measurement of the white blood cell count, and neutrophil, lymphocyte and platelet counts.
were 0.574 and 0.554. When the PLRs were 126 and 200, the Youden index was maximal. Therefore, the cutoff values of the PLR for survival and recurrence were set at 126 and 200, respectively (Fig. 1). Next, patients with a PLR greater than the cutoff value were defined as high PLR (HPLR), and others were defined as low PLR (LPLR). The NLR was defined as the neutrophil count divided by the lymphocyte count. Similar to the PLR, the cutoff values were analyzed, and those of the NLR for survival and recurrence were set at 2 and 3, respectively (Fig. 1). Additionally, the patients were divided into two groups according to the level of the NLR; i.e., high NLR (HNLR) and low NLR (LNLR). Statistical Analysis
Definition and Detection of the Optimum Cutoffs of the PLR and NLR The PLR was defined as the platelet count divided by the lymphocyte count. Using the overall survival and recurrence, respectively, as end points, the areas under the receiver operating characteristic (ROC) curve for the NLR
PLR (Survival, Total F/up)
(a)
PLR (Recurrence, Total F/up)
(b)
80
80
Sensitivity
100
Sensitivity
100
60
40
20
60
40
Criterion: >200,49 AUC=0.55, P value=0.008
20
Criterion: >126,19 AUC=0.57, P value=1.99 AUC=0.55, P value=0.002
80
100
60
40 Criterion:>2.99 AUC=0.53, P value=0.103
20
0
60 40 100-Specificity
NLR (Recurrence, Total F/up)
100
20
20
(d)
100
Sensitivity
FIG. 1 ROC curves for the PLR and NLR. a Overall survival (cutoff value of PLR: 126; sensitivity: 50.27 %; specificity: 60.30 %). b Overall recurrence (cutoff value of PLR: 200; sensitivity: 21.25 %, specificity: 91.37 %). c Overall survival (cutoff value of NLR: 2; sensitivity: 48.40 %; specificity: 63.23 %). d Overall recurrence (cutoff value of NLR: 3; sensitivity: 23.75 %; specificity: 84.75 %)
To evaluate the sensitivity and specificity for the 5-year overall survival (OS), the ROC was calculated, and the Youden index was estimated, to determine the optimal NLR and PLR cutoff values. Comparison of categorical variables was performed using a Chi squared test. Kaplan– Meier curves were used for OS and disease-free survival
0 0
20
40 60 100-Specificity
80
100
0
20
40 60 100-Specificity
80
100
PLR and NLR in gastric cancer TABLE 1 Association of the patients’ characteristics with the platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios Factors
Total N = 1,986 (%)
PLR Low PLR n = 1,178 (%)
High PLR n = 808 (%)
58.2 ± 11.7
57.8 ± 11.3
58.8 ± 12.2
Male
1,317 (66.31)
836 (71.97)
481 (59.53)
Female
669 (33.69)
342 (29.03)
327 (40.47)
Age (year) (mean ± SD)
p value
NLR Low NLR n = 1,247 (%)
0.0497 57.6 ± 11.4
p value High NLR n = 739 (%) 59.2 ± 12.1
\0.0001
Gender
Approach method
0.0001 788 (63.19)
529 (71.58)
459 (36.81)
210 (28.42)
1028 (82.44)
639 (86.47)
219 (17.56)
100 (13.53)
0.002
Open
1,667 (83.94)
964 (81.83)
703 (87.0)
Laparoscopy
319 (16.06)
214 (18.17)
105 (13.0)
Extent of resection
0.0181
0.0367
0.846
Partial gastrectomy
1,476 (74.32)
899 (76.32)
577 (71.41)
933 (74.82)
543 (73.48)
Total gastrectomy
510 (25.68)
279 (23.68)
231 (28.59)
314 (25.18)
196 (26.52)
Histologic type
0.3338
0.4189
Differentiated
906 (45.85)
546 (46.63)
360 (44.72)
558 (45.0)
348 (47.28)
Undifferentiated
1,064 (53.85)
620 (52.95)
444 (55.16)
677 (54.6)
387 (52.58)
6 (0.30)
5 (0.43)
1 (0.12)
5 (0.40)
1 (0.14)
Other Depth of invasiona
\0.0001
\0.0001
T1
1,109 (55.84)
710 (60.27)
399 (49.38)
738 (59.18)
371 (50.20)
T2
240 (12.08)
147 (12.48)
93 (11.51)
147 (11.79)
93 (12.58)
T3
356 (17.93)
197 (16.72)
159 (19.68)
226 (18.12)
130 (17.59)
T4
281 (14.15)
124 (10.53)
157 (19.43)
136 (10.91)
145 (19.62)
N0
1,291 (65.04)
814 (69.16)
477 (59.03)
850 (68.22)
441 (59.68)
N1
262 (13.20)
147 (12.49)
115 (14.23)
162 (13.0)
100 (13.53)
N2
178 (8.97)
96 (8.16)
82 (10.15)
99 (7.95)
79 (10.69)
254 (12.80)
120 (10.20)
134 (16.58)
135 (10.83)
119 (16.10)
I
1,208 (60.82)
772 (65.53)
436 (53.96)
799 (64.07)
409 (55.35)
II
373 (18.78)
215 (18.25)
158 (19.55)
234 (18.77)
139 (18.81)
III
405 (20.40)
191 (16.21)
214 (26.49)
214 (17.16)
WBC counts (9109/L)b
6.20 (2.19– 77.10)
6.37 (2.30–77.10)
5.96 (2.19–20.21) \0.0001 5.80 (2.19–77.10)
Lymphocyte counts (9109/L)b
1.96 (0.39– 26.21)
2.27 (0.45–26.21)
1.51 (0.39–3.42)
Neutrophil counts (9109/L)b
3.39 (0.71– 42.48)
3.26 (0.80–42.48)
3.64 (0.71–17.73) \0.0001 2.90 (0.71–42.48)
Platelet counts (9109/L)b
226 (30–726)
213 (30–438)
253 (95–726)
NLRb
1.70 (0.30– 29.50)
PLRb
116.10 (9– 559.80)
Node status
a
N3 Stage
\0.0001
a
0.0048
0.0002
\0.0001
\0.0001
\0.0001 2.19 (0.69–26.21)
\0.0001 224 (30–508)
191 (25.85) 6.86 (3.26–20.21) \0.0001 1.52 (0.39–3.74)
\0.0001
4.53 (1.58–17.73) \0.0001 232 (35–726)
0.0246
SD standard deviation, WBC white blood cell, NLR neutrophil-to-lymphocyte ratio, PLR platelet-to-lymphocyte ratio a
According to the 7th edition of AJCC TNM classification
b
Median (range)
(DFS) to compare patients with each score, and differences in the survival rate between the groups were compared using the log-rank test. Cox regression model was used to
identify variables that influence OS and DFS. Multivariate analysis was performed using variables that had a significant independent relationship with OS and DFS.
E. Y. Kim et al.
Significance was defined as a p \ 0.05. All statistical analyses were performed using SPSS version 18.0 (SPSS, Inc., Chicago, IL, USA). RESULTS
respectively. The numbers of low NLR and high NLR patients were 1247 and 739, respectively (Table 1). Older age, an open approach, higher T or N stage, and advanced stage were significantly associated with the high PLR and NLR groups.
Clinicopathologic Characteristics
Prognostic Factors for OS and DFS
Of 1986 patients, 1317 (66.31 %) were male, and the median age was 59 years (range 23–88 years; Table 1). Overall, 1470 patients (74.02 %) underwent subtotal gastrectomy, and most of the patients presented with stage I disease (n = 1208; 60.83 %). The median values of the preoperative neutrophil, lymphocyte, and platelet counts were 3.39 9 109/L, 1.96 9 109/L, and 226 9 109/L, respectively. The median values of the NLR and PLR were 1.7 and 116.1, respectively.
The 5-year OS rates of the LPLR and LNLR groups were significantly higher than those of the HPLR and HNLR groups. Similarly, the 5-year DFS rates of the LPLR and LNLR groups were significantly higher than those of the HPLR and HNLR groups (Fig. 2). In terms of OS, older age, an open approach, higher T or N stage, advanced stage, and HNLR were identified as significant independent risk factors (Table 2). However, HPLR was not an independent risk factor.
Relationship Between Clinicopathologic Characteristics and Inflammation-Based Score
Overall Survival Rates Based on Stage According to the PLR and NLR
When OS was used as an end point, the numbers of low PLR and high PLR patients were 1178 and 808,
When the 5-year OS rates of the patients were stratified according to stage, high NLR and PLR were shown to be
(a)
(b) 100 Overall recurrence probability (%)
Overall survival probability (%)
100
80
60
p=0.0002
40
20
LNLR HR(95%Cl):1 HNLR HR(95%Cl):1.59(1.29-1.94)
80
60
p
ORIGINAL ARTICLE – GASTROINTESTINAL ONCOLOGY
The Platelet-to-Lymphocyte Ratio Versus Neutrophil-toLymphocyte Ratio: Which is Better as a Prognostic Factor in Gastric Cancer? Eun Young Kim, MD, Jin Won Lee, MD, Han Mo Yoo, MD, Cho Hyun Park, MD, and Kyo Young Song, MD Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
ABSTRACT Background. As indicators of the systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed to predict the clinical outcome in some cancers. The purpose of this study was to investigate the impact of NLR and PLR on the prognosis of gastric cancer. Methods. From 2000 to 2009, 1986 consecutive patients who underwent curative surgery for gastric cancer were enrolled. The optimal cutoff value of PLR and NLR was determined according to receiver operating characteristic analysis. We categorized the patients into the high or low PLR and NLR group based on the cutoff value, and the clinical features of these two groups were comparatively analyzed. Results. The high NLR and PLR groups were significantly associated with poor prognosis. The NLR was an independent prognostic factor for overall survival [hazard ratio (HR) = 1.403; p = 0.023]; however, the PLR was not (p = 0.788). Conclusions. Although both the PLR and NLR can reflect the prognosis, the NLR is more predictive of overall survival than the PLR.
Currently, the major issue in treating gastric cancer is how best to individualize therapy based on tumor characteristics as well as patient factors. For example, to improve the quality of life as well as achieve an early recovery,
Ó Society of Surgical Oncology 2015 First Received: 30 January 2015 K. Y. Song, MD e-mail: [email protected]
minimally invasive treatments, such as laparoscopic gastrectomy, have been proposed as a suitable alternative to conventional open surgery in patients with early gastric cancer (EGC). Meanwhile, radical surgery with extended lymph node dissection is a standard approach for advanced gastric cancer. The ability to predict the precise prognosis of a patient is critical for selecting the optimal treatment plan and followup strategies. Although the only reliable prognosticator is the tumor, node, metastasis (TNM) stage, even within the same tumor stage, heterogeneous clinical courses are frequently observed. Therefore, further studies should be performed to provide a more reliable prognostic factor. Recently, the systemic inflammatory response has been found to be an independent marker of prognosis in several types of cancer. Investigations have shown a significant relationship between leukocytosis, thrombocytosis, an elevated neutrophil-to-lymphocyte ratio (NLR) or plateletto-lymphocyte ratio (PLR), and poor survival in various cancers.1–6 However, in only a few studies were these inflammation-based scores associated with the prognosis of gastric cancer. Therefore, the purpose of this study was to confirm that the PLR and NLR are associated with the prognosis of gastric cancer and to compare the clinical usefulness of these two factors based on a large volume of data concerning gastric cancer after curative surgery. PATIENTS AND METHODS The prospectively collected data on 2494 patients with gastric adenocarcinoma who underwent gastrectomy at Seoul St. Mary’s Hospital between 2000 and 2009 were reviewed. Of these 2494 patients, 1986 who underwent curative-intent surgery for gastric cancer were enrolled in this study. The exclusion criteria for this study were as
E. Y. Kim et al.
follows: remnant gastric cancer, neoadjuvant chemotherapy, synchronous and metachronous malignancies, emergency surgery, liver cirrhosis, evidence of a severe inflammatory condition, presence of coexisting hematological malignancies or disorders, autoimmune disorders and recent steroid therapy, and incomplete/inaccurate medical records. Institutional review board approval was obtained. Blood Sample Analysis Blood samples were obtained preoperatively for the measurement of the white blood cell count, and neutrophil, lymphocyte and platelet counts.
were 0.574 and 0.554. When the PLRs were 126 and 200, the Youden index was maximal. Therefore, the cutoff values of the PLR for survival and recurrence were set at 126 and 200, respectively (Fig. 1). Next, patients with a PLR greater than the cutoff value were defined as high PLR (HPLR), and others were defined as low PLR (LPLR). The NLR was defined as the neutrophil count divided by the lymphocyte count. Similar to the PLR, the cutoff values were analyzed, and those of the NLR for survival and recurrence were set at 2 and 3, respectively (Fig. 1). Additionally, the patients were divided into two groups according to the level of the NLR; i.e., high NLR (HNLR) and low NLR (LNLR). Statistical Analysis
Definition and Detection of the Optimum Cutoffs of the PLR and NLR The PLR was defined as the platelet count divided by the lymphocyte count. Using the overall survival and recurrence, respectively, as end points, the areas under the receiver operating characteristic (ROC) curve for the NLR
PLR (Survival, Total F/up)
(a)
PLR (Recurrence, Total F/up)
(b)
80
80
Sensitivity
100
Sensitivity
100
60
40
20
60
40
Criterion: >200,49 AUC=0.55, P value=0.008
20
Criterion: >126,19 AUC=0.57, P value=1.99 AUC=0.55, P value=0.002
80
100
60
40 Criterion:>2.99 AUC=0.53, P value=0.103
20
0
60 40 100-Specificity
NLR (Recurrence, Total F/up)
100
20
20
(d)
100
Sensitivity
FIG. 1 ROC curves for the PLR and NLR. a Overall survival (cutoff value of PLR: 126; sensitivity: 50.27 %; specificity: 60.30 %). b Overall recurrence (cutoff value of PLR: 200; sensitivity: 21.25 %, specificity: 91.37 %). c Overall survival (cutoff value of NLR: 2; sensitivity: 48.40 %; specificity: 63.23 %). d Overall recurrence (cutoff value of NLR: 3; sensitivity: 23.75 %; specificity: 84.75 %)
To evaluate the sensitivity and specificity for the 5-year overall survival (OS), the ROC was calculated, and the Youden index was estimated, to determine the optimal NLR and PLR cutoff values. Comparison of categorical variables was performed using a Chi squared test. Kaplan– Meier curves were used for OS and disease-free survival
0 0
20
40 60 100-Specificity
80
100
0
20
40 60 100-Specificity
80
100
PLR and NLR in gastric cancer TABLE 1 Association of the patients’ characteristics with the platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios Factors
Total N = 1,986 (%)
PLR Low PLR n = 1,178 (%)
High PLR n = 808 (%)
58.2 ± 11.7
57.8 ± 11.3
58.8 ± 12.2
Male
1,317 (66.31)
836 (71.97)
481 (59.53)
Female
669 (33.69)
342 (29.03)
327 (40.47)
Age (year) (mean ± SD)
p value
NLR Low NLR n = 1,247 (%)
0.0497 57.6 ± 11.4
p value High NLR n = 739 (%) 59.2 ± 12.1
\0.0001
Gender
Approach method
0.0001 788 (63.19)
529 (71.58)
459 (36.81)
210 (28.42)
1028 (82.44)
639 (86.47)
219 (17.56)
100 (13.53)
0.002
Open
1,667 (83.94)
964 (81.83)
703 (87.0)
Laparoscopy
319 (16.06)
214 (18.17)
105 (13.0)
Extent of resection
0.0181
0.0367
0.846
Partial gastrectomy
1,476 (74.32)
899 (76.32)
577 (71.41)
933 (74.82)
543 (73.48)
Total gastrectomy
510 (25.68)
279 (23.68)
231 (28.59)
314 (25.18)
196 (26.52)
Histologic type
0.3338
0.4189
Differentiated
906 (45.85)
546 (46.63)
360 (44.72)
558 (45.0)
348 (47.28)
Undifferentiated
1,064 (53.85)
620 (52.95)
444 (55.16)
677 (54.6)
387 (52.58)
6 (0.30)
5 (0.43)
1 (0.12)
5 (0.40)
1 (0.14)
Other Depth of invasiona
\0.0001
\0.0001
T1
1,109 (55.84)
710 (60.27)
399 (49.38)
738 (59.18)
371 (50.20)
T2
240 (12.08)
147 (12.48)
93 (11.51)
147 (11.79)
93 (12.58)
T3
356 (17.93)
197 (16.72)
159 (19.68)
226 (18.12)
130 (17.59)
T4
281 (14.15)
124 (10.53)
157 (19.43)
136 (10.91)
145 (19.62)
N0
1,291 (65.04)
814 (69.16)
477 (59.03)
850 (68.22)
441 (59.68)
N1
262 (13.20)
147 (12.49)
115 (14.23)
162 (13.0)
100 (13.53)
N2
178 (8.97)
96 (8.16)
82 (10.15)
99 (7.95)
79 (10.69)
254 (12.80)
120 (10.20)
134 (16.58)
135 (10.83)
119 (16.10)
I
1,208 (60.82)
772 (65.53)
436 (53.96)
799 (64.07)
409 (55.35)
II
373 (18.78)
215 (18.25)
158 (19.55)
234 (18.77)
139 (18.81)
III
405 (20.40)
191 (16.21)
214 (26.49)
214 (17.16)
WBC counts (9109/L)b
6.20 (2.19– 77.10)
6.37 (2.30–77.10)
5.96 (2.19–20.21) \0.0001 5.80 (2.19–77.10)
Lymphocyte counts (9109/L)b
1.96 (0.39– 26.21)
2.27 (0.45–26.21)
1.51 (0.39–3.42)
Neutrophil counts (9109/L)b
3.39 (0.71– 42.48)
3.26 (0.80–42.48)
3.64 (0.71–17.73) \0.0001 2.90 (0.71–42.48)
Platelet counts (9109/L)b
226 (30–726)
213 (30–438)
253 (95–726)
NLRb
1.70 (0.30– 29.50)
PLRb
116.10 (9– 559.80)
Node status
a
N3 Stage
\0.0001
a
0.0048
0.0002
\0.0001
\0.0001
\0.0001 2.19 (0.69–26.21)
\0.0001 224 (30–508)
191 (25.85) 6.86 (3.26–20.21) \0.0001 1.52 (0.39–3.74)
\0.0001
4.53 (1.58–17.73) \0.0001 232 (35–726)
0.0246
SD standard deviation, WBC white blood cell, NLR neutrophil-to-lymphocyte ratio, PLR platelet-to-lymphocyte ratio a
According to the 7th edition of AJCC TNM classification
b
Median (range)
(DFS) to compare patients with each score, and differences in the survival rate between the groups were compared using the log-rank test. Cox regression model was used to
identify variables that influence OS and DFS. Multivariate analysis was performed using variables that had a significant independent relationship with OS and DFS.
E. Y. Kim et al.
Significance was defined as a p \ 0.05. All statistical analyses were performed using SPSS version 18.0 (SPSS, Inc., Chicago, IL, USA). RESULTS
respectively. The numbers of low NLR and high NLR patients were 1247 and 739, respectively (Table 1). Older age, an open approach, higher T or N stage, and advanced stage were significantly associated with the high PLR and NLR groups.
Clinicopathologic Characteristics
Prognostic Factors for OS and DFS
Of 1986 patients, 1317 (66.31 %) were male, and the median age was 59 years (range 23–88 years; Table 1). Overall, 1470 patients (74.02 %) underwent subtotal gastrectomy, and most of the patients presented with stage I disease (n = 1208; 60.83 %). The median values of the preoperative neutrophil, lymphocyte, and platelet counts were 3.39 9 109/L, 1.96 9 109/L, and 226 9 109/L, respectively. The median values of the NLR and PLR were 1.7 and 116.1, respectively.
The 5-year OS rates of the LPLR and LNLR groups were significantly higher than those of the HPLR and HNLR groups. Similarly, the 5-year DFS rates of the LPLR and LNLR groups were significantly higher than those of the HPLR and HNLR groups (Fig. 2). In terms of OS, older age, an open approach, higher T or N stage, advanced stage, and HNLR were identified as significant independent risk factors (Table 2). However, HPLR was not an independent risk factor.
Relationship Between Clinicopathologic Characteristics and Inflammation-Based Score
Overall Survival Rates Based on Stage According to the PLR and NLR
When OS was used as an end point, the numbers of low PLR and high PLR patients were 1178 and 808,
When the 5-year OS rates of the patients were stratified according to stage, high NLR and PLR were shown to be
(a)
(b) 100 Overall recurrence probability (%)
Overall survival probability (%)
100
80
60
p=0.0002
40
20
LNLR HR(95%Cl):1 HNLR HR(95%Cl):1.59(1.29-1.94)
80
60
p
