Elevated levels of pre-treatment lactate dehydrogenase are an unfavorable predictor factor in patients with EML4-ALK rearrangement non-small cell lung cancer treated with crizotinib

Figures & data

Table 1 Log-rank test analysis of clinical pathological characteristics and PFS in 212 ALK-positive NSCLC patients

Variables	No. (%)	PFS
		Median (months)	95% CI (months)	P-value (log-rank)
Gender
Male	101 (47.6%)	12.8	10.2–15.4	0.440
Female	111 (52.4%)	14.6	10.4–18.7
Age
Median (range)	49.5 (22–82)
≤50 years old	115 (54.2%)	15.0	11.7–18.4	0.407
>50 years old	97 (45.8%)	12.6	9.7–15.5
Smoking history
Never	153 (72.2%)	13.3	9.9–16.7	0.940
Ever	59 (27.8%)	14.6	10.5–18.7
Pathology
Non-squamous	210 (99.18%)	13.4	10.6–16.3	0.552
Squamous	2 (0.9%)	9.9	–
Stage
IIIb	28 (13.2%)	16.8	11.8–21.7	0.300
IV	184 (86.8%)	13.0	10.6–15.4
EGFR status
Wild type	190 (89.6%)	13.4	10.2–16.7	0.640
Mutant type	12 (5.7%)	12.2	0.0–30.7
Unknown	10 (4.7%)	–	–
ALK evaluation method
FISH	124 (58.5%)	15.3	11.1–19.6	0.636
IHC (D5F3)	103 (48.6%)	14.1	9.9–18.3
NGS	10 (4.7%)	20.7	8.5–33.0
Previous treatment
Never	138 (65.1%)	16.5	14.1–19.0	0.148
Ever	74 (34.9%)	11.5	9.5–13.6
Lung metastases
Yes	80 (37.7%)	14.6	9.2–20.0	0.694
No	132 (62.3%)	13.3	9.6–17.0
Brain metastases
Yes	43 (20.3%)	16.5	10.3–22.7	0.961
No	169 (79.7%)	13.0	10.5–15.5
Liver metastases
Yes	29 (13.7%)	10.9	7.3–14.6	0.032
No	183 (86.3%)	15.0	12.1–18.0
Bone metastases
Yes	71 (33.5%)	10.9	8.8–13.1	0.052
No	141 (66.5%)	16.5	13.7–19.3
Pleural metastases
Yes	75 (35.4%)	13.4	9.0–17.9	0.698
No	137 (64.6%)	13.0	9.2–16.8
Adrenal metastases
Yes	11 (5.2%)	5.0	2.0–8.0	0.001
No	201 (94.8%)	14.3	11.5–17.1
Pre-treatment LDH level
≤250 U/L	100 (47.2%)	14.1	10.3–18.0	0.004
>250 U/L	29 (13.7%)	7.9	5.7–10.0
Post-treatment mean-LDH level
≤250 U/L	64 (30.2%)	14.3	10.9–17.7	0.970
>250 U/L	129 (60.8%)	13.3	9.2–17.4

Abbreviations: LDH, lactate dehydrogenase; PFS, progression-free survival; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; NGS, next-generation sequence; ALK, anaplastic lymphoma kinase; NSCLC, non-small cell lung cancer.

Table 2 Chi-square test analysis of LDH level and clinical pathological characteristics

Variables	Pre-treatment LDH level			Post-treatment mean-LDH level
	≤250 U/L	>250 U/L	P-value (Fisher)	≤250 U/L	>250 U/L	P-value (Fisher)
Gender
Male	53	15	1.000	36	54	0.067
Female	47	14		28	75
Age
Median (range)
≤50 years old	55	14	0.534	41	66	0.094
>50 years old	45	15		23	63
Smoking history
Never	67	20	0.819	44	95	0.499
Ever	33	8		20	34
Pathology
Non-squamous	99	29	1.000	62	124	1.000
Squamous	1	0		2	5
Stage
IIIb	10	3	1.000	8	17	1.000
IV	90	26		56	112
EGFR status
Wild type	92	24	1.000	60	115	0.312
Mutant type	7	2		1	9
Unknown	1	3		3	5
Previous treatment
Never	65	14	0.131	47	78	0.081
Ever	35	15		17	51
Lung metastases
Yes	39	7	0.187	23	52	0.639
No	61	22		41	77
Brain metastases
Yes	20	8	0.444	13	26	1.000
No	80	21		51	103
Liver metastases
Yes	12	8	0.076	7	19	0.512
No	88	21		57	110
Bone metastases
Yes	31	15	0.051	22	44	1.000
No	69	14		42	85
Pleural metastases
Yes	40	8	0.277	24	44	0.749
No	77	21		40	85
Adrenal metastases
Yes	4	4	0.075	0	8	0.054
No	96	25		64	121

Abbreviation: LDH, lactate dehydrogenase.

Table 3 Evaluation of post-treatment LDH levels in every month

Months	No. of patients with LDH evaluated	No. of patients with LDH elevated	No. of patients with LDH elevated for the first-time	Mean value of LDH level
1	119	68	68	289
2	86	39	25	248
3	115	64	21	266
4	75	37	11	256
5	107	66	9	281
6	79	44	6	262
7	93	59	3	280
8	77	39	3	267
9	74	44	3	277
10	69	37	0	262
>10	310	195	16	276

Abbreviation: LDH, lactate dehydrogenase.

Table 4 Logistic regression analysis of elevated post-treatment LDH levels

Variables	B	SE	Wals	Sig	Exp (B)	95% CI
ALT	−0.329	0.398	0.684	0.408	0.720	0.330–1.569
AST	0.300	0.502	0.358	0.550	1.350	0.505–3.613
CK	1.904	0.348	29.960	<0.001	6.712	3.395–13.273
CKMB	1.840	0.386	22.679	<0.001	6.297	2.953–13.427
Cr	−0.271	0.314	0.742	0.389	0.763	0.412–1.412
HGB	1.426	0.445	10.277	<0.001	4.163	1.741–9.956

Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; Cr, creatinine; CK, creatine kinase; CKMB, creatine kinase isoenzyme; HGB, hemoglobin; LDH, lactate dehydrogenase.

Figure 1 Kaplan-Meier progression-free survival curve according to pre-treatment LDH levels.

Figure 2 Kaplan-Meier progression-free survival curve according to post-treatment mean-LDH levels.