The Prognostic Significance of Novel Pancreas Cancer Prognostic Index in Unresectable Locally Advanced Pancreas Cancers Treated with Definitive Concurrent Chemoradiotherapy

Figures & data

Table 1 Pretreatment Patient and Disease Characteristics

Characteristics	All Patients (N=152)	PCPI-1 (N=36)	PCPI-2 (N=78)	PCPI-3 (N=38)	P-value
Median age, years (range)	52 (27–79)	62 (36–78)	57 (27–79)	60 (33–77)	0.74
Age group
< 70	118 (77.6)	28 (77.8)	59 (75.6)	31 (81.6)	0.79
≥ 70	34 (22.4)	8 (22.2)	19 (24.4)	7 (18.4)
Gender, N (%)
Female	33 (21.7)	7 (19.4)	21 (26.9)	5 (13.2)	0.26
Male	119 (78.3)	29 (80.6)	57 (73.1)	33 (86.8)
ECOG performance, N (%)
0	58 (38.2)	16 (44.4)	27 (34.6)	15 (39.5)	0.53
1	94 (51.8)	20 (55.6)	51 (65.4)	23 (60.5)
Median BMI, kg/m^2	21.9 (20.1–26.8)	24.6 (20.7–26.8)	22.4 (20.3–25.7)	20.8 (20.1–22.3)	0.012
Weight loss, N (%)
˂ 5%	66 (43.4)	23 (63.9)	32 (41.0)	11 (28.9)	< 0.001
≥ 5%	86 (56.6)	13 (36.1)	46 (59.0)	27 (71.1)
Tumor Location, N (%)
Head	123 (80.9)	29 (80.5)	63 (80.7)	31 (81.6)	0.72
Body/Tail	29 (19.1)	7 (19.5)	15 (19.3)	7 (18.4)
N-stage, N (%)
0	78 (53.2)	26 (72.2)	40 (51.3)	12 (31.6)	0.007
1	74 (46.8)	10 (27.8)	38 (48.7)	26 (68.4)
Median CA 19–9, U/mL (range)	91.8 (19.4–785.2)	46.2 (19.4–86.8)	96.4 (39.7–141.3)	171.6 (91.4–785.2)	<0.001
Median SIRI	1.82 (1.21–3.84)	1.46 (1.23–1.81)	1.97 (1.32–3.54)	2.53 (1.89–3.84)	< 0.001

Abbreviations: PCPI, pancreas cancer prognostic index; ECOG, Eastern Cooperative Oncology Group; BMI, body mass index; N-stage, nodal stage; CA 19–9, cancer antigen 19–9; BMI, body mass index; M/L, monocyte/lymphocyte; SIRI, systemic inflammation response index.

Figure 1 Receiver operating characteristic curve analyses outcomes per pretreatment CA 19-9 and systemic inflammation response index measures: (A) CA 19-9 and progression-free survival, (B) CA 19-9 and overall survival, (C) Systemic inflammation response index and progression-free survival, and (D) Systemic inflammation response index and overall survival.

Table 2 Definition of Blended CA 19–9 and Systemic Inflammation Response Index Groups, and Pancreas Cancer Prognostic Index

Characteristic	Definition
Blended CA 19-9 and SIRI Groups
Group 1	CA 19-9 < 90 U/m/L and SIRI < 1.8
Group 2	CA 19-9 < 90 U/m/L but SIRI ≥ 1.8
Group 3	CA 19-9 ≥ 90 U/m/L but SIRI < 1.8
Group 4	CA 19-9 ≥ 90 U/m/L and SIRI ≥1.8
PCPI Groups
PCPI-1	CA 19-9 < 90 U/m/L and SIRI < 1.8
PCPI-2	CA 19-9 < 90 U/m/L but SIRI ≥ 1.8, or CA 19-9 ≥ 90 U/m/L but SIRI < 1.8
PCPI-3	CA 19-9 ≥ 90 U/m/L and SIRI ≥1.8

Abbreviations: CA 19-9, cancer antigen 19-9; SIRI, systemic inflammation response index; PCPI, pancreas cancer prognostic index.

Table 3 Survival Outcomes per Blended CA 19-9 and Systemic Inflammation Response Index Groups

Blended CA 19–9 and SIRI Groups	Patients (n)	Median PFS mo. (95% CI)	P-value	Median OS, mo. (95% CI)	P-value
Group 1	36	17.0 (8.8–25.2)	<0.001	26.1 (15.7–36.5)	<0.001
Group 2	37	7.7 (5.5–9.9)		15.0 (11.4–18.6)
Group 3	41	7.3 (5.0–9.6)		14.5 (11.9–17.1)
Group 4	38	4.4 (2.8–6.0)		7.4 (4.3–10.5)

Notes: Significant Bonferroni corrected P <0.0083. PFS: Group 1 versus 2; P<0.001, Group 1 versus 3; P<0.001, Group 1 versus 4; P<0.001, Group 2 versus 3; P= 0.79, Group 2 versus 4; P<0.001, Group 3 versus 4; P<0.001; and OS: Group 1 versus 2; P<0.001, Group 1 versus 3; P<0.001, Group 1 versus 4; P<0.001, Group 2 versus 3; P= 0.86, Group 2 versus 4; P<0.001, Group 3 versus 4; P<0.001.

Abbreviations: CA 19-9, cancer antigen 19-9; SIRI, systemic inflammation response index; mo., months; CI, confidence interval; PFS, progression-free survival; OS, overall survival.

Table 4 Survival Outcomes per Pancreatic Cancer Prognostic Index Groups

Endpoint	All Patients (N=152)	PCPI-1 (N=36)	PCPI-2 (N=78)	PCPI-3 (N=38)	P-value
Progression-free survival
Median, mo. (95% CI)	7.5 (6.1–8.9)	17.0 (8.8–25.2)	7.5 (4.7–10.3)	4.4 (2.8–6.0)	<0.001
5-year (%)	10.3	25.4	13.3	0
Overall survival
Median	14.8 (11.9–17.7)	26.1 (15.7–36.5)	15.1(10.7–19.5)	7.4 (4.3–10.5)	<0.001
5-year	16.5	38.2	22.1	0

Notes: Significant Bonferroni corrected P < 0.0017. PCPI-1 versus 2; P<0.001, PCPI-1 versus 3; P<0.001, PCPI-2 versus 3: P<0.001.

Abbreviations: PCPI, pancreatic cancer prognostic index; mo., months; CI, confidence interval.

Figure 2 Survival outcomes per pancreas cancer prognostic index (PCPI) groups: (A) Progression-free survival, and (B) Overall survival (Red line: PCPI-1; Dark blue line: PCPI-2; and Dark green line: PCPI-3).

Table 5 Results of Uni- and Multivariate Analyses

Factor	Overall Survival			Progression-Free Survival
	Univariate	Multivariate	HR (95% CI)	Univariate	Multivariate	HR (95% CI)
	P-value	P-value		P-value	P-value
Age group (<70 vs ≥70 y)	0.77	-	-	0.73	-	-
Gender (Female vs male)	0.83	-	-	0.86	-	-
ECOG (0 vs 1)	0.92	-	-	0.87	-	-
BMI (< 21.9 vs ≥ 21.9 kg/m^2)	0.17	-	-	0.19	-	-
Weight loss (< 5% vs ≥ 5%)	0.006	0.009	2.14 (1.89–2.39)	0.007	0.008	2.27 (2.01–2.53)
Tumor location (H vs B/T)	0.83	-	-	0.86	-	-
N-stage (0 vs 1)	0.008	0.014	1.79 (1.63–1.95)	0.01	0.012	1.97 (1.79–2.15)
Pre-C-CRT CA 19–9 (<90 vs ≥ 90 U/m/L)	0.009	0.016	1.62 (1.44–1.80)	0.006	0.010	1.89 (1.69–2.09)
Median post C-CRT CA 19–9 (<64.6 vs ≥ 64.6 U/m/L)	0.18	-	-	0.22	-	-
Adjuvant chemotherapy cycles (≤4 vs >4)	0.27	-	-	0.32	-	-
SIRI (< 1.8 vs ≥1.8)	<0.001	<0.001	2.86 (2.65–3.07)	<0.001	<0.001	3.46 (3.19–3.73)
PCPI group (1 vs 2 vs 3)	<0.001	<0.001	5.38 (4.96–5.80)	<0.001	<0.001	5.67 (5.19–6.15)

Abbreviations: HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; BMI, body mass index; H, head; B/T, body/tail; N-stage, nodal stage; CA 19–9, cancer antigen 19–9; C-CRT, concurrent chemoradiotherapy; SIRI, systemic inflammation response index; PCPI, pancreas cancer prognostic index.

Table 6 Survival Outcomes per Factors Showing Independent Prognostic Significance in Multivariate Analyses

Factor	Progression-Free Survival			Overall Survival
	Median (mo.)	5-Year (%)	P-value	Median (mo.)	5-Year (%)	P-value
Weight loss
< 5%	9.9 (7.4–12.4)	15.6	0.006	22.1 (17.0–27.2)	23.6	0.007
≥ 5%	5.8 (4.1–7.5)	6.4		9.7 (6.9–12.5)	9.3
N-stage
0	9.4 (8.6–11.2)	14.7	0.008	19.4 (16.2–22.6)	21.8	0.01
1	6.6 (5.0–8.2)	7.2		11.3 (8.4–14.2)	10.9
PCPI group
1	17.0 (8.8–25.2)	25.4	<0.001	26.1 (15.7–36.5)	38.2	<0.001
2	7.5 (4.7–10.3)	13.3		15.1(10.7–19.5)	22.1
3	4.4 (2.8–6.0)	0		7.4 (4.3–10.5)	0

Abbreviations: mo., months; N, nodal stage; CA 19-9, cancer antigen 19-9; SIRI, systemic inflammation response index; PCPI, pancreas cancer prognostic index.