Prognostic value of ferritin, neuron-specific enolase, lactate dehydrogenase, and urinary and plasmatic catecholamine metabolites in children with neuroblastoma

Figures & data

Table 1 Demographic, biological and clinical features of the study patients stratified by stage, and comparison with the whole NB population diagnosed during the study period

Study patients	Stage						NB patients	P
	1	2	3	4	4S	Total	Total
N	109	39	92	217	48	505	1717
Sex
Female	42	21	49	87	21	220 (43.6%)	764 (44.5%)	NS
Male	67	18	43	130	27	285 (56.4%)	953 (55.5%)
Age
≤18 months	57	25	48	56	48	234 (46.3%)	855 (49.8%)	NS
MYCN status
Normal	48	23	33	28	37	169 (72.2%)	606 (70.9%)	NS
Amplified	2	1	12	18	5	38 (16.2%)	90 (10.5%)	NS
Not known	7	1	3	10	6	27 (11.6%)	159 (18.6%)	<0.01
5 years EFS	96.7%	100%	88.5%	45.9%	75.0%	76.9%	77.8%	NS
5 years OS	98.2%	100%	92.5%	56.1%	81.3%	82.9%	85.2%	NS
>18 months	52	14	44	161	–	271 (53.7%)	862 (50.2%)	NS
MYCN status					–
Normal	27	10	16	86	–	139 (51.3%)	433 (50.2%)	NS
Amplified	2	2	15	31	–	50 (18.4%)	123 (14.3%)	<0.05
Not known	23	2	13	44	–	82 (30.3%)	306 (35.5%)	NS
5 years EFS	100%	83.3%	63.6%	22.5%	–	38.2%	37.6%	NS
5 years OS	100%	92.9%	75.2%	30.1%	–	50.6%	50.8%	NS

Abbreviations: NB, neuroblastoma; NS, not significant; EFS, event-free survival; OS, overall survival.

Table 2 Concentration of each analyte in the entire cohort of study patients (N = 505) and in patients with localized disease (N = 288)

N	VMA/creatinine (μg/mg)	HVA/creatinine (μg/mg)	Plasma VMA (ng/mL)	Plasma HVA (ng/mL)	Ferritin (ng/mL)	NSE (ng/mL)	LDH (IU/mL)
Study patients (N = 505)
Valid	411	402	174	174	272	233	279
Missing	94	103	331	331	233	272	226
Mean	167.5	195.1	318.9	1265.9	262.7	130.2	1653.3
Median	53.0	73.6	98.0	553.5	119.5	56.6	912.0
Standard deviation	320.5	542.2	792.9	2434.1	407.9	175.5	2104.9
Percentiles
25	14.4	25.2	39.0	205.0	47.25	23.1	579.0
50	53.0	73.6	98.0	553.5	119.5	56.6	912.0
75	180.6	209.6	295.4	1367.7	280.2	169.2	1727.0
Patients with localized disease (N = 288)
Valid	227	226	93	93	155	132	159
Missing	61	62	195	195	133	156	129
Mean	144.6	125.9	278.1	795.5	150.4	80.7	1259.8
Median	30.7	41.2	64.0	269.0	69.0	30.2	687.0
Standard deviation	319.0	204.1	793.7	1321.8	214.7	115.3	1637.6
Percentiles
25	10.4	19.3	33.5	154.7	26.0	17.1	513.0
50	30.7	41.2	64.0	269.0	69.0	30.3	687.0
75	100.7	128.1	172.3	880.8	193.0	93.7	1334.0

Abbreviations: HVA, homovanillic acid; LDH, lactate dehydrogenase; NSE, neuron-specific enolase; VMA, vanillylmandelic acid.

Figure 1 Kaplan–Meier plots of event-free survival of (A) patients with localized NB stratified by urinary VMA/HVA cut-off value; (B) patients with localized disease stratified by plasma VMA/HVA cut-off value; (C) the entire cohort of study patients stratified by ferritin cut-off value; (D) patients with stage 4 disease stratified by NSE cut-off value; (E) patients with localized disease stratified by LDH cut-off value; and (F) patients with stage 4 disease stratified by LDH cut-off value.

Note: For each marker the cut-off value corresponded to the first quartile of the marker distribution in that group of patients.
Abbreviations: HVA, homovanillic acid; LDH, lactate dehydrogenase; NB, neuroblastoma; NSE, neuron-specific enolase; VMA, vanillylmandelic acid.

Table 3 Prognostic value of each marker in the different groups of neuroblastoma patients

MYCN	Patients with localized NB				Patients with metastatic NB				Cut-off value
	≤18 months		>18 months		≤18 months		>18 months
	NA	A	NA	A	NA	A	NA	A
Urinary VMA/HVA ratio									0.50
N total	111	13	41	10	22	14	66	26
Mean	1.28	0.55	0.76	0.57	1.32	0.30	1.09	0.71
N (%) over cut-off	14 (12.6)	8 (61.5)	14 (34.1)	6 (60.0)	5 (22.7)	11 (78.6)	15 (22.7)	17 (65.4)
Association with outcome	Y	N	Y	N	N	N	N	N
P	0.017				NS
Plasma VMA/HVA ratio									0.15
N total	46	6	25	4	5	7	50	9
Mean	0.59	0.13	0.29	0.09	0.24	0.11	0.34	0.11
N (%) over cut-off	5 (10.9)	5 (83.3)	6 (24.0)	4 (100.0)	3 (60.0)	6 (85.7)	19 (38.0)	8 (88.9)
Association with outcome	Y	N	Y	–	–	N	N	N
P	0.017				NS
Ferritin (ng/mL)									119.5
N total	73	14	31	11	11	13	56	15
Mean	151.4	182.4	64.0	394.7	179.1	351.3	372.2	802.2
N (%) over cut-off	4 (6.1)	3 (27.3)	4 (12.9)	8 (72.7)	5 (45.5)	10 (76.9)	37 (66.1)	14 (93.3)
Association with outcome	N	N	N	N	–	N	N	N
P	NS				NS
NSE (ng/mL)									200.0
N total	66	11	28	7	10	12	51	12
Mean	69.9	158.1	65.8	152.7	99.0	366.2	165.2	243.2
N (%) over cut-off	4 (6.1)	3 (27.3)	2 (7.1)	2 (28.6)	0 (0.0)	6 (50.0)	10 (19.6)	5 (41.7)
Association with outcome	N	N	N	N	–	N	Y	N
P	NS				0.01
LDH (IU/Ml)									1300/2500a
N total	75	14	32	11	12	14	56	16
Mean	782.4	2495.2	882.4	3449.1	1020.8	5121.3	1367.0	4059.2
N (%) over cut-off	7 (9.3)	11 (78.6)	7 (21.9)	9 (81.8)	3 (25.0)	12 (85.7)	20 (37.5)	14 (87.5)
Association with outcome	Y	N	Y	N	–	N	Y	N
P	0.0001				0.0001

Note:

a For localized/metastatic group.

Abbreviations: A, amplified; HVA, homovanillic acid; LDH, lactate dehydrogenase; N, no, as determined by multivariate analysis; NA, not amplified; NB, neuroblastoma; NS, not significant; NSE, neuron-specific enolase; VMA, vanillylmandelic acid; Y, yes, as determined by multivariate analysis.