Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial

Figures & data

Figure 1 Flow chart of the study.

Abbreviation: ALRI, aspartate aminotransferase-lymphocyte ratio index.

Table 1 Patient characteristics (n=284)

Patient characteristics	ALRI		p-values
	<14	≥14
	n (%)	n (%)
Median age, years (range)	66 (34–83)	65 (33–81)	0.771
Gender			0.904
Male	86 (60.6)	84 (59.2)
Female	56 (39.4)	58 (40.8)
Performance status ECOG			0.005
0	123 (86.6)	103 (72.5)
1–2	19 (13.4)	39 (27.5)
Tumor localization			0.893
Rectum	37 (26.1)	38 (26.8)
Colon	105 (73.9)	104 (73.2)
Stage at diagnosis			0.646
I–III	35 (25.9)	31 (22.8)
IV	100 (74.1)	105 (77.2)
CT regimen			0.028
FOLFOX4	97 (68.3)	78 (54.9)
FOLFIRI	45 (31.7)	64 (45.1)
KRAS statusa			0.387
Wild type	95 (66.9)	87 (61.3)
Mutated	47 (33.1)	55 (38.7)
ITACa treatment			0.812
CT+B	67 (47.2)	70 (49.3)
CT	75 (52.8)	72 (50.7)

Note:

a Mandatory as consequence of amendment no 1 of May 3, 2009.

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; B, bevaci zumab; CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; ITACa, Italian Trial in Advanced Colorectal Cancer; n, number.

Table 2 Comparison of median values of ALRI, AST and lymphocytes as a function of toxicity

	Number of patients	ALRI median value (range)	p-values	AST median value (range)	p-values	Lymphocyte median value (range)	p-values
Nausea			0.623		0.970		0.733
G0	153	14.9 (1.3–172.3)		21 (9–193)		1.55 (0.43–10.40)
G1+G2	124	13.2 (3.2–141.0)		21 (8–100)		1.64 (0.58–10.51)
G3+G4	7	15.0 (9.3–28.6)		24 (14–28)		1.57 (0.98–2.07)
Vomiting			0.852		0.929		0.687
G0	217	14.0 (2.1–172.3)		21 (9–193)		1.63 (0.43–5.85)
G1+G2	60	13.8 (1.4–82.6)		20 (8–100)		1.50 (0.87–10.51)
G3+G4	7	15.0 (9.2–29.7)		24 (16–35)		1.60 (0.82–2.07)
Diarrhea			0.032		0.194		0.540
G0	150	14.9 (3.0–172.3)		22 (9–193)		1.57 (0.43–10.51)
G1+G2	117	13.9 (1.3–141.0)		21 (10–88)		1.57 (0.61–10.40)
G3+G4	17	11.4 (4.3–33.3)		20 (8–43)		1.93 (0.72–3.75)
Stomatitis			0.230		0.073		0.468
G0	220	14.0 (1.3–172.3)		20 (8–193)		1.55 (0.43–10.51)
G1+G2	57	13.8 (4.8–102.3)		23 (11–96)		1.64 (0.77–4.75)
G3+G4	7	21.0 (12.6–31.0)		30 (17–83)		1.57 (1.25–2.68)
Fatigue			0.010		0.0004		0.220
G0	159	13.2 (2.1–169.8)		20 (8–117)		1.54 (0.43–5.85)
G1+G2	106	14.4 (1.3–141.0)		22 (9–142)		1.64 (0.56–10.51)
G3+G4	19	20.1 (5.1–172.3)		28 (11–193)		1.46 (0.86–2.44)
Anemia			0.221		0.187		0.857
G0	224	13.8 (1.3–172.3)		21 (8–193)		1.60 (0.43–10.51)
G1+G2	54	17.1 (3.5–102.3)		23 (10–96)		1.53 (0.72–3.75)
G3+G4	6	11.4 (4.2–55.4)		16 (12–51)		1.63 (0.92–2.87)
Neutropenia			0.791		0.683		0.182
G0	101	14.8 (3.0–172.3)		20 (9–193)		1.51 (0.43–3.50)
G1+G2	58	12.5 (3.5–70.5)		20 (10–117)		1.67 (0.58–3.75)
G3+G4	124	14.7 (1.3–102.3)		22 (8–100)		1.57 (0.72–10.51)
Thrombocytopenia			0.595		0.367		0.691
G0	219	14.1 (1.3–172.3)		21 (8–193)		1.60 (0.43–10.51)
G1+G2	59	13.2 (6.3–102.3)		23 (12–88)		1.60 (0.86–3.98)
G3+G4	6	19.3 (6.3–33.3)		24 (17–33)		1.47 (0.72–3.15)
Febrile neutropenia			0.515		0.820		0.202
G0	278	14.1 (1.3–172.3)		21 (8–193)		1.57 (0.43–10.51)
G1+G2	2	10.3 (3.5–17.0)		20 (10–30)		2.32 (1.76–2.89)
G3+G4	4	11.5 (8.7–17.2)		23 (18–28)		1.90 (1.57–2.36)
Hemorrhage			0.863		0.713		0.596
G0	249	13.9 (1.3–172.3)		21 (8–193)		1.57 (0.43–10.51)
G1+G2	35	15.6 (4.3–74.7)		22 (9–142)		1.68 (0.97–3.75)
G3+G4	0	–		–		–
Hypertension			0.096		0.429		0.077
G0	226	14.7 (1.3–172.3)		21 (8–193)		1.57 (0.43–10.40)
G1+G2	51	11.2 (2.0–82.6)		20 (10–100)		1.69 (0.77–10.51)
G3+G4	7	17.1 (6.4–102.3)		25 (16–88)		1.46 (0.86–2.97)
Thrombosis			0.379		0.335		0.361
G0	232	14.1 (1.3–172.3)		21 (8–193)		1.57 (0.43–10.51)
G1+G2	19	14.6 (4.8–82.6)		21 (12–100)		1.31 (0.56–2.55)
G3+G4	33	11.9 (3.0–50.0)		20 (9–73)		1.73 (0.72–3.50)
Proteinuria			0.001		0.005		0.514
G0	221	13.2 (1.4–169.8)		20 (8–117)		1.60 (0.43–10.51)
G1+G2	63	16.9 (4.2–172.3)		25 (11–193)		1.60 (0.61–3.50)
G3+G4	0	–		–		–
Neurologic system			0.028		0.168		0.044
G0	183	15.0 (1.3–172.3)		22 (8–193)		1.58 (0.43–10.40)
G1+G2	83	13.9 (3.2–102.3)		20 (10–88)		1.55 (0.58–10.51)
G3+G4	18	9.8 (3.5–50.0)		18 (10.83)		1.88 (1.17–4.75)

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; AST, aspartate aminotransferase.

Figure 2 Kaplan–Meier curves of PFS (A), OS (B).

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; PFS, progression-free survival; OS, overall survival.

Table 3 Multivariate analysis of PFS and OS

	PFS		OS
	HR (95% CI)	p-values	HR (95% CI)	p-values
ALRI (≥14 vs <14)	1.35 (1.02–1.79)	0.034	1.35 (1.01–1.83)	0.048
Age (continuous variable)	1.00 (0.98–1.01)	0.818	0.99 (0.98–1.01)	0.222
Gender (male vs female)	0.81 (0.62–1.07)	0.139	0.87 (0.65–1.16)	0.349
ECOG PS (1–2 vs 0)	1.33 (0.94–1.88)	0.109	2.18 (1.50–3.18)	<0.0001
Tumor localization (colon vs rectum)	0.98 (0.72–1.34)	0.908	1.09 (0.79–1.51)	0.585
CT regimen (FOLFIRI vs FOLFOX4)	1.27 (0.95–1.70)	0.104	1.07 (0.79–1.44)	0.659
KRAS status (mutated vs wild type)	0.98 (0.75–1.30)	0.910	1.17 (0.87–1.56)	0.296
ITACa treatment (CT+B vs CT)	0.84 (0.64–1.11)	0.230	1.19 (0.89–1.59)	0.228
LDH (>UNL vs ≤UNL)	1.20 (0.90–1.60)	0.202	1.30 (0.96–1.76)	0.095
Liver metastasis
Only 1 lesion <5 cm vs no liver mts	0.55 (0.28–1.06)	0.076	0.62 (0.30–1.27)	0.191
Multiple liver lesions or 1 liver lesion ≥5 cm vs no liver mts	1.09 (0.78–1.52)	0.624	1.15 (0.81–1.64)	0.437

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; CT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; ITACa, Italian Trial in Advanced Colorectal Cancer; LDH, lactate dehydrogenase; PFS, progression-free survival; OS, overall survival; UNL, upper normal limit.

Figure 3 Kaplan–Meier curves of PFS (A) and OS (B) of patients treated with CT+B, Kaplan–Meier curves of PFS (C) and OS (D) in patients treated with CT.

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; B, bevacizumab; CT, chemotherapy; OS, overall survival; PFS, progression-free survival.

Figure 4 Kaplan–Meier curves of PFS of patients treated with CT+B and CT on the basis of ALRI levels.

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; B, bevacizumab; CT, chemotherapy; PFS, progression-free survival.

Table 4 Liver disease and median value of AST

	Number of patients	AST median value (range)	p-values	Lymphocyte median value (range)	p-values	ALRI median value (range)	p-values
Overall			<0.0001		0.229		0.003
No liver disease +1 single liver lesion <5 cm	81	17 (9–117)		1.51 (0.56–10.40)		12.70 (1.35–80.15)
Multiple lesions (including 1 liver) or 1 single hepatic lesion ≥5 cm	203	23 (8–193)		1.62 (0.43–10.51)		15.20 (2.05–172.32)

Abbreviations: ALRI, aspartate aminotransferase-lymphocyte ratio index; AST, aspartate aminotransferase.