The prognostic significance of serum lactate dehydrogenase for patients with small cell lung cancer treated first-line therapy: a retrospective analysis of 163 consecutive cases

doi:10.21203/rs.3.rs-2620618/v1

Purpose: To investigate the association between lactate dehydrogenase (LDH) and the prognosis of first-line therapy in patients with small cell lung cancer (SCLC).

Methods: 163 small cell lung cancer patients were consecutively included from January 2011 to June 2020 as initial therapy in Fujian Medical University Union Hospital. A retrospective analysis of the clinical data were conducted to explore the association between LDH, the progression free survival (PFS) and overall survival (OS). PFS and OS were calculated using the Kaplan-Meier method and compared with the log-rank test.

Results: 163 patients were divided into 90 patients in the high LDH group (pre-treatment LDH≥202 IU/L) and 73 patients in the low LDH group (pre-treatment LDH <202 IU/L). The low LDH group has a longer PFS than the high LDH group (6.23±0.28 months vs. 5.24±0.21 months; P=0.002). In the subgroup analysis of extensive stage (ES), the low LDH group has a longer PFS than the high LDH group (6.67±0.35 months vs. 5.02±0.23months; P=0.000). In the high LDH group, patients have a significantly longer PFS when treated with the cisplatin-etoposide (EP) regimen compared to those treated with the carboplatin-etoposide (EC) regimen(5.72±0.29 months vs. 4.72±0.28 months; P=0.029). Among the high-LDH group, the PFS of EP regimen in the LS subgroup was longer than that of EC regimen, with a statistical difference (6.39±0.58 months vs. 4.71±0.45 months; P=0.018). After 2 cycles of first-line treatment, the OS in the group with LDH-significant-decrease group was longer (10.44±0.77 months vs. 14.79±1.67 months; P=0.009), compared with LDH-non-significant-decrease group. In the subgroup analysis of ES patients, OS in the LDH-significant-decrease group was longer than that in the LDH-no-significant-decrease group(13.96±2.25 months vs. 9.49±0.81 months; P=0.027). In the subgroups using EP regimen, OS in the LDH-significant-decrease group was longer than that in the LDH-no-significant-decrease group (16.67±2.33 months vs. 10.20±1.03 months; P=0.004).

Conclusion: LDH is of certain significance to the efficacy of first-line chemotherapy of small cell lung cancer. Higher LDH is a biomarker of poor clinical prognosis. The decrease of LDH after 2 cycles of first-line treatment may suggest longer PFS and OS for patients with SCLC. Patients with high pretreatment-LDH choosing EP treatment may have a longer PFS.

small cell lung cancer

serum lactate dehydrogenase

chemotherapy

prognosis

survival

Lung cancer is one of the most common malignant tumors that threaten human health at present. Accounting for about 15% of lung cancer, small cell lung cancer(SCLC) are characterized as an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. [1-3]Clinical progress in SCLC treatment has been notoriously slow in decades[1] and chemotherapy is still the main treatment in patients with limited stage(LS) SCLC and extensive stage(ES) SCLC. The standard first-line chemotherapy regimen in patients with SCLC is cisplatin–etoposide(EP) or carboplatin–etoposide(EC). [1,4,5] Despite that there is no obvious difference in the efficacy in EP and EC, the toxicity profiles of EP and EC is different. [6-8].

Pathological examination is the golden standard for diagnosing SCLC[9]. Although the tumor's response to chemotherapy can be judged by the degree of necrosis of tumor tissue, it is not easy to achieve real-time pathological monitoring in clinical practice. At present, it seems that clinical biomarker is limited in the real-time monitoring of the progression of SCLC and the evaluation of the chemotherapy efficacy and prognosis.

It has been shown that inflammation promotes a favorable microenvironment for cancer cell growth and spread, and activates carcinogenic signaling pathways[10]. LDH is one of the inflammation-related peripheral blood parameters. As a routine hematological test, LDH is clinically convenient and practically noninvasive. Additionally, it has been identified that LDH plays an important role in predicting prognosis in different types of tumors, such as breast cancer, pancreatic sarcoma, prostate cancer[11-13]. However, the association between serum LDH and prognosis of SCLC is controversial according to results from many researches. Abnormal expression in serum of patients with small cell lung cancer and its association with small cell lung cancer are worthy of further study.

Thisstudy retrospectively analyzed the association between LDH, the progression free survival (PFS) and overall survival (OS) in 163 consecutive patients with small cell lung cancer to investigate the prognostic significance of LDH in first-line treatment.

Patients

The clinical data of 163 small cell lung cancer patients were consecutively included from January 2011 to June 2020 as initial therapy in Fujian Medical University Union Hospital(Fuzhou, China). This study was approved by the Institutional Review Board (IRB) of Fujian Medical University Union Hospital (IRB no. 2017KY084) and informed consent was obtained from the patients.

All the patients were confirmed with SCLC by pathological examination (the histopathological examination of lung tumor confirmed as small-cell carcinoma, and the immunohistochemical examination confirmed as small-cell lung cancer). Exclusion criteria were as follows :I) second primary tumor; II) diseases that may cause hematologic changes (including lymphoma, leukemia and myelodysplasia syndrome); III) chronic diseases (including cardiovascular diseases, diabetes, asthma and COPD); IV) histologically mixed tumors with adenocarcinoma and other histological types (such as lung squamous cell carcinoma, alveolar carcinoma, mesenchymal sarcoma, and large cell carcinoma); V) No prophylactic craniocerebral exposure. All the patients received first-line treatment EP or EC. [4]

Treatment

Patients with LS SCLC treated with at least 4 cycles of EP (cisplatin 25 mg/m² iv days 1 to 3 and etoposide 100 mg/m² iv days 1 to 3 every 21d) or EC (carboplatin AUC 4–5 iv day 1 and etoposide 100 mg/m² iv days 1 to 3 every 21d) plus concurrent or sequential radiotherapy were then identified, along with all the patients with ES SCLC and treated with at least 4 cycles of EP (cisplatin 25 mg/m² iv days 1 to 3 and etoposide 100 mg/m² iv days 1 to 3 every 21d) or EC (carboplatin AUC 4–5 iv day 1 and etoposide 100 mg/m² iv days 1 to 3 every 21d).[4]

Clinical Data

The electronic medical records and registration database of all patients were reviewed, and data were collected according to demographic and clinical characteristics, including patient age, sex, smoking, stage(LS or ES), Eastern Cooperative Oncology Group(ECOG) performance status, brain metastases, lung metastases, bone metastases, pleural metastases, LDH before treatment and after 2 cycles of first-line treatment.

Lactate dehydrogenase test data were collected at the first visit and 2 cycles after the first-line treatment for each patient. The progression free survival (PFS) and overall survival time (OS) were obtained from inpatient and outpatient medical records and telephone follow-up. PFS was calculated from the date of initial diagnosis to disease progression (according to RECIST 1.1 solid tumor efficacy evaluation criteria[14]). OS time was determined as the date from diagnosis to the date of death or last follow-up.

Research Methods

By calculating the receiver operating characteristic (ROC) curve of Yoden’s index, the cut-off value of pre-treatment LDH is selected as 202 IU/L. Patients were then divided into two groups: low LDH group (pre-treatment LDH < 202 IU/L) and high LDH group (pre-treatment LDH ≥ 202 IU/L). SCLC patients were further divided into the LS group and the ES group, according to the staging method of the Veterans Administration Lung Study Group of the United States[15]. Statistical methods were used to analyze the association between LDH, options of first-line chemotherapy, PFS and OS time.

Statistical analysis

Clinical data were presented as mean ± standard deviation or median and range. All analyses were conducted by using SPSS19.0 software (IBM Corp., Armonk, NY, USA). ROC curve analysis is used to determine the cut-off value of LDH. Chi-square test was used to compare the different clinical characteristics of each group, t-test or rank-sum test was used to compare the LDH between the groups, and paired t-test was used to compare the LDH before and after chemotherapy. Kaplan-Meier method was used to analyze the difference in survival time between the high and low LDH groups and the groups with significant decrease in LDH and those without significant decrease. Log-rank test was used to compare the difference in survival time between the groups. Patients with LS and ES were stratified to compare the prognosis of different chemotherapy regimens. P < 0.05 was considered statistically significant. All P values are two-tailed.

1. Clinical characteristics of the patients

The clinical characteristics and pretreatment LDH characteristics of the patients before treatment were summarized in Table 1. The 163 SCLC patients were between the range of 38-88 years old, with an average age of 61.65 years, including 152 males (93.3%, 39-88 years old) and 11 females (6.7%, 38-76 years old). (Figure 1) Among 163 patients with small cell lung cancer 75 cases(46.0%) were in the limited stage and 88 cases(54.0%) were in the extensive stage.(Figure 2)

2. The association between LDH and clinical characteristics before and after 2 cycles of therapy

163 SCLC patients were divided into high LDH group (n=90, 55.20%) and low LDH group (n=73, 44.80%) before treatment. (Figure 3) Stratified by gender, smoking status, brain metastasis and other clinical characteristics, there was no statistically significant difference in LDH between the groups (P>0.05, as shown in Table 2). Stratified by age, stage, ECOG PS score, lung metastasis, bone metastasis, pleural metastasis and other clinical characteristics, LDH differences among the groups were statistically significant (P<0.05, as shown in Table 2).

A total of 115 of the 163 patients who completed 2 cycles of chemotherapy without death or loss to follow-up were divided into the high LDH group (n=44) and the low LDH group (n=71). Stratified by age, gender, smoking status, brain metastasis, stage, ECOG PS score, brain metastasis, pleural metastasis and other clinical characteristics, LDH difference among groups was not statistically significant (P>0.05, as shown in Table 3). Stratified according to the clinical characteristics of lung metastasis and bone metastasis, LDH differences among the groups were statistically significant (P<0.05, as shown in Table 3).

LDH after chemotherapy decreased significantly compared with that before chemotherapy, and the difference was statistically significant (288.23±296.02 vs. 209.22±203.20, P=0.002). After 2 cycles of treatment, LDH in the female group, non-smoking group, LS group, brain metastasis group, non-lung metastasis group, non-bone metastasis group and pleural metastasis group showed no significant decrease compared with that before treatment, and the difference was not statistically significant (P>0.05, as shown in Table 4). LDH in each age group, male group, smoking group, extensive stage group, ECOG PS evaluation group, no brain metastasis group, lung metastasis group, bone metastasis group and no pleural metastasis group decreased significantly after 2 cycles of treatment, with statistically significant differences (P< 0.05, Table 4).

3. Association between LDH and PFS and OS before treatment

Compared with the high LDH group (n=90), the low LDH group (n=73) had longer PFS (6.23±0.28 months vs. 5.24±0.21 months, P=0.002, as shown in Figure 4A). In the subgroup analysis of LS patients, there was no statistical difference in PFS between the low LDH group (n=43) and the high LDH group (n=32) (5.93±0.42 months vs. 5.66±0.41 months, P=0.516, as shown in Figure 4B). In the subgroup analysis of ES patients, the PFS of the low LDH group (n=30) was longer than that of the LDH group (n=58), with a statistically significant difference (6.67±0.35 months vs. 5.02±0.23 months, P=0.000, as shown in Figure 4C). There was no significant difference in OS time between the high LDH group (n=26) and the low LDH group (n=34) (13.73±1.87 vs. 13.22±2.18 months, P =0.785, Figure 4D). In the ES and LS subgroups, there was no significant difference in OS time between the high LDH group and the low LDH group (Figure 4E, 4F).

4. Association between LDH, PFS and OS in EC/EP regimens

PFS of patients treated with EP (n=91) was 5.91±0.26 months, and PFS of patients treated with EC (n=72) was 5.40±0.22 months, with no statistically significant difference in PFS (P=0.083 as shown in Figure 5A).

PFS of EP group (n=44) and EC group (n=29) in the low LDH group were similar, with no statistical significance (6.11±0.44 vs. 6.41±0.26 months, P=0.812, as shown in Figure 5B). However, in the high LDH group, the PFS of EP regimen (n=47) was significantly longer than that of EC regimen (n=43) (5.72±0.29 vs. 4.72±0.28 months, P=0.029, Figure 5C). In the subgroup with high LDH, PFS of EP regimen (n=18) in LS group was longer than that of EC regimen (n=14), with statistical difference (6.39±0.58 months vs. 4.71±0.45 months, P=0.018, as shown in Figure 5D). However, in the ES group there was no significant difference in PFS between using EP regimen (n=29) and EC regimen (n=29) (5.31±0.28 months, 4.72±0.36 months for EC therapy, P=0.458, as shown in Figure 5E).

Among all the patients who reached the study end point at OS time, 91 cases were treated with EP regimen and 72 cases with EC regimen. There were no statistically significant differences in OS (EP 11.56±1.07 months, EC 9.96±0.73 months, P=0.340, Figure 5F). The OS of EP and EC regiments were similar in both the low and the high LDH group, and the difference was not statistically significant (low LDH group 11.36±1.46 vs. 10.41±1.15 months, P=0.687, Figure 5G; high LDH group 11.75±1.57 vs. 9.65±0.96 months, P=0.368, Figure 5H).

5. Association between LDH, PFS and OS after 2 cycles of first-line treatment

Patients (n=115) who completed 2 cycles of first-line treatment without death or loss to follow-up were divided into the LDH-significant-decrease group (n=34) and the LDH-no-significant-decrease group (n=81), according to the LDH decreased by 30% or not. There was no statistically significant difference in PFS between the two groups (6.00±0.24 months vs. 5.91±0.41 months, p=0.998, as shown in Figure 6A). In the ES and LS subgroups, there was no significant difference in PFS between the LDH-significant-decrease group and the LDH-no-significant-decrease group (p>0.05, Figure 6B, Figure 6C). Compared with the LDH-no-significant-decrease group (n=81), the LDH-significant-decrease group (n=34) had longer OS (10.44±0.77 months vs. 14.79±1.67 months, P=0.009, as shown in Figure 6D). In the subgroup analysis of LS patients, there was no statistically significant difference in OS between the LDH-significant-decrease group (n=11) and the LDH-no-significant-decrease group (n=42) (16.54±2.17 months vs. 11.33±1.26 months, P=0.117, as shown in Figure 6E). In the subgroup analysis of ES patients, OS of the group with significant LDH decrease (n=23) was longer than that of the group with no significant LDH decrease (n=39), with statistically significant difference (13.96±2.25 months vs. 9.49±0.81 months, P=0.027, as shown in Figure 6F).

There was no significant difference in PFS between the LDH-significant-decrease group and the LDH-no-significant-decrease group treated with EP regimen or EC regimen (P>0.05, Figure 6G, Figure 6H). Among the subgroups using EP regimen, OS in the LDH-significant-decrease group was significantly longer than that in the LDH-no-significant-decrease group, showing a statistically significant difference (16.67±2.33 months vs. 10.20±1.03 months, P=0.004, as shown in Figure 6I). Among the subgroups using EC regimen, there was no significant difference in OS between the LDH-significant-decrease group and the LDH-no-significant-decrease group (11.77±2.06 months vs. 10.81±1.14 months, P=0.665, as shown in Figure 6J).

In recent years, with the vigorous development of medicine, NSCLC has developed rapidly from the molecular mechanism to the clinical application. All kinds of genetic drivers drugs are emerging, and immune checkpoint blockades are in the limelight, which has greatly improved survival time and life quality of patients with NSCLC, especially with lung adenocarcinoma. However, at the same time, there is limited clinical progress in SCLC treatment. The standard chemotherapy regimen in patients with SCLC is cisplatin–etoposide or carboplatin–etoposide, which has not been changed for the past three decades. The currently attempted clinical application of immune checkpoint blockade has brought new hope to the patients with SCLC, such as durvalumab and atezolizumab, but the clinical survival benefits are still considered to be limited.[16,17] Meanwhile, effective predictive prognosis biomarker is greatly needed for initial treatment.

The change from oxidative phosphorylation to glycolysis of glucose utilization in tumor cells, so- called Warburg effect, which is one of the characteristics of tumor.[18] LDH is one of the important metabolic enzymes and common biochemical biomarkers involved in glycolysis and gluconeogenesis. It is a tetramer composed of A and B subunits. Among them, LDHA gene expression is regulated by Hypoxia inducible factes-1 (HIF.1A)[19,20]LDHA was identified as the direct target gene of carcinogenic transcription factors of C-MYC[20,21]Anne Le's study shows that LDHA is required for tumor molecules and that targeting cancer metabolism is attractive to control tumor growth.[22] PDE4 expression in lung cancer with HIF signal crosstalk and promote the progression of lung cancer findings suggest that PDE4 is expressed in lung cancer, crosstalks with HIF signaling and promotes lung cancer progression.[23] LDH produced by rapidly growing tumors and therefore reflects the tumor burden. Lung cancer cells grow rapidly, accompanied by different degrees of metastasis. The body could not provide sufficient oxygen and nutrients for this rapid growth, and glucose is in the anaerobic state for fermentation in LDH catalyzed into lactic acid, so that the serum LDH concentration increased.[24]

In this study, the PFS is longer in the low LDH group than in high LDH group, indicating that the increase of serum LDH in patients with small cell lung cancer may be positively correlated with tumor growth and negatively correlated with the efficacy of drug therapy. In the analysis of treatment efficacy, EP regimen and EC regimen have no statistical difference on overall survival, while treatment efficacy of EP is superior to the EC high in patients with high LDH group, which is probably because higher LDH may mean higher tumor malignant degree, and choosing more intense EP regimen can lead to better survival benefit to patients.

LDH before therapy could not predict the OS of the patients, however, we found that the OS of the groups with a decrease of more than 30% in LDH after 2 cycles of first-line chemotherapy was significantly prolonged, with a statistical difference. On one hand, this is consistent with the correlation between LDH and tumor prognosis found in previous studies; on the other hand, it shows that LDH may serve as an effective biomarker to predict the efficacy in the early stage of chemotherapy, providing an important reference for the subsequent chemotherapy plans.

SCLC is very sensitive to chemotherapy and radiotherapy. Until today, EP regimen of etoposide combined with cisplatin is still the recommended classical regimen for the treatment of small-cell lung cancer[4]. It seems to have similar efficacy, but less side effects and better tolerability than cisplatin. Therefore, carboplatin is often used to replace cisplatin in clinical treatment. How to choose between carboplatin with less side effects and cisplatin with higher efficacy? It has become a problem in SCLC therapy research, which many previous studies are also constantly exploring.[25]In this study, EP regimen and EC regimen were compared in High-LDH patients, and the EP scheme containing cisplatin is better from the perspective of PFS and OS.

For the prognosis of patients with small-cell lung cancer, the role of tumor staging is unquestionable. SCLC patients using first-line treatment with limited stage have longer progression-free survival time and better prognosis than with limited stage. In addition to staging, according to the results of our study, we found that LDH level may be another biomarker to predict PFS in SCLC patients, which is negatively correlated with the prognosis of SCLC patients. The change in LDH after 2 cycles of treatment may also be a predictor of efficacy and OS. And therefore the decision to use EP or EC as the first-line treatment for SCLC patients may be based on pre-treatment LDH levels, besides individual patient factors and the toxicity profile of the regimens. Before treatment, SCLC patients with low LDH were treated with EC regimen as well as EP regimen with less side effects. SCLC Patients with high LDH before treatment may have a longer PFS to be treated with EP regimen than with EC Regimen, as the general situation permits. The shorter PFS of EC regimen compared with EP regimen in small-cell Carcinoma patients with high LDH levels before treatment may be associated with higher malignancy or insensitivity to Carboplatin agents in their tumors, which needs further investigation.

As an inflammation-related peripheral blood marker, the degree of serum LDH decrease before therapy and after 2 cycles of first-line chemotherapy is of certain significance to the evaluation of clinical prognosis and the selection of first-line chemotherapy for initially diagnosed patients with SCLC. Higher LDH predicts poor clinical prognosis. The decreasing of LDH after 2 cycles of first-line treatment may suggest longer PFS and OS for patients with SCLC. Patients with high pretreatment-LDH choosing EP treatment may have a longer PFS. Since this study is a retrospective study, further research is warranted.

Ethics approval and consent to participate All of the protocols were reviewed and approved by the Institutional Review Board of Fujian Medical University Union Hospital, Fuzhou, China (Institutional Review Board No. 2017KY084). Informed consent was obtained from patients included in the study. No animals were used in this study. The reported experiments were performed in accordance with the ethical standards of the committee responsible for human experimentation (institutional and national), and with the Helsinki Declaration of 1975, as revised in 2013 (http://ethics.iit.edu/ecodes/node/3931).
Consent for publication Not applicable.
Availability of data and materials All data generated or analyzed during this study are included in this article.
Competing interests The authors declared that they have no potential conflicts of interest regarding research, authorship, and/or publication of this article.
Funding This study was sponsored by Fujian provincial health technology project(Grant No. 2019-1-28) and Startup Fund for scientific research, Fujian Medical University(Grant No. 2020QH1097, 2020QH1100) .
Authors' contributions M. LZ and ZP conception, design, data analysis, and editing the manuscript. Dr. HW, CS, XL, and YC contributed to data acquisition, statistical analysis, and interpretation of the data. Dr. CS and YC contributed to the revision of the manuscript.
Acknowledgements The authors gratefully acknowledge the support of all the patients included.

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Table 1. The clinical characteristics and pre-treatment LDH of patients with SCLC

Variables	Median	Range
Age (years)	61.65	38-88
PFS (months)	5.72	1-16
OS (months)	10.82	1-63
Pre-treatment LDH (IU/L)	280.90	99-2101
SCLC, small-cell lung cancer; LDH, lactate dehydrogenase

Table 2. Association between LDH and clinical characteristics of patients with SCLC before therapy

LDH before therapy

t

p

n

High LDH

Low LDH

χ²

p

Age at diagnosis

<60

≥60

239.13±124.29

310.04±324.47

-1.70

0.009

67

96

35

55

32

41

0.407

0.523

Gender

Male

Female

274.51±235.14

193.00*

Z(-0.404)**

0.687

152

11

86

4

66

7

1.695

0.976

Smoking

NO

YES

269.42±260.75

284.38±264.84

-0.306

0.820

38

125

19

71

19

54

0.545

0.460

Stage

LS-SCLC

ES-SCLC

238.23±207.87

317.26±298.83

-1.927

0.046

75

88

32

58

43

30

8.846

0.003

ECOG performance status

1 Point

2 Point

242.82±127.60

214.00*

-3.462

0.000

125

38

69

17

56

21

0.000

0.995

Brain metastases

no

yes

283.87±274.34

228.50*

0.385

0.438

143

20

78

12

65

8

0.211

0.646

Lung metastases

no

yes

243.27±174.25

365.94±385.90

-2.802

0.006

113

50

56

34

57

16

4.768

0.029

Bone metastases

no

yes

247.23±237.27

340.24±296.39

-2.194

0.036

104

59

45

59

14

16.580

0.000

Pleural metastasis

no

yes

265.34±223.44

257.00*

Z(-2.481)**

0.013

152

11

81

9

71

2

3.376

0.066

LDH, lactate dehydrogenase; SCLC, small-cell lung cancer; LS-SCLC, limited stage small-cell lung cancer; ES-SCLC, extensive stage small-cell lung cancer; ECOG, Eastern Cooperative Oncology Group;

* Due to the small number of patients, the median value is used to illustrate the central tendency of the sample

** Due to the small number of patients, LDH presents a skewed distribution, so the rank sum test was used to analyze the data

Table 3. Association between LDH and clinical characteristics of patients with SCLC after 2 circles of first-line therapy

LDH after 2 circles of first-line therapy

t

p

n

High LDH

Low LDH

χ²

p

Age at diagnosis

<60

≥60

190.04±78.23

223.97±117.38

-1.76

0.519

50

65

15

29

35

36

2.556

0.110

Gender

Male

Female

210.41±105.36

170.00*

Z(-0.526)**

0.599

106

9

42

2

64

7

1.063

0.302

Smoking

NO

YES

179.04±45.48

218.48±113.88

3.898

0.051

27

88

7

37

20

51

2.273

0.132

Stage

LS-SCLC

ES-SCLC

200.15±83.32

216.97±117.70

3.367

0.069

53

62

20

24

33

38

0.011

0.915

ECOG performance status

1 Point

2 Point

197.80±91.82

210.00*

3.477

0.065

88

27

29

15

59

12

4.468

0.035

Brain metastases

no

yes

214.59±107.96

157.00*

2.961

0.088

102

13

43

1

59

12

5.798

0.016

Lung metastases

no

yes

195.73±80.53

230.98±129.99

5.344

0.023

71

44

26

18

45

26

0.212

0.646

Bone metastases

no

yes

196.52±81.24

229.70±129.60

4.696

0.032

71

44

25

19

46

25

0.731

0.393

Pleural metastasis

no

yes

204.21±98.17

240.00*

Z(-1.182)**

0.237

107

8

40

4

67

4

0.502

0.479

LDH, lactate dehydrogenase; SCLC, small-cell lung cancer; LS-SCLC, limited stage small-cell lung cancer; ES-SCLC, extensive stage small-cell lung cancer; ECOG, Eastern Cooperative Oncology Group;

* Due to the small number of patients, the median value is used to illustrate the central tendency of the sample

** Due to the small number of patients, LDH presents a skewed distribution, so the rank sum test was used to analyze the data

Table 4. The differences of LDH before and after 2 cycles of treatment

LDH ( before therapy)

LDH ( after 2 circle therapy)

t

p

n

Age at diagnosis

<60

≥60

239.13±124.29

310.04±324.47

190.04±78.23

223.97±117.38

2.499

2.643

0.016

0.010

50

65

Gender

Male

Female

274.51±235.14

369.18±527.14

210.41±105.36

195.22±76.43

3.080

1.101

0.003

0.303

106

9

Smoking

NO

YES

276.26±260.75

284.38±264.84

179.04±45.48

218.48±113.88

1.747

2.630

0.092

0.010

27

88

Stage

LS-SCLC

ES-SCLC

238.23±207.87

317.26±298.83

200.15±83.32

216.97±117.70

1.526

2.806

0.133

0.007

53

62

ECOG performance status

1 Point

2 Point

242.82±127.60

406.13±477.13

197.80±91.82

246.44±128.87

3.827

2.190

0.000

0.038

88

27

Brain metastases

no

yes

283.87±274.34

259.6±165.76

214.59±107.96

167.08±30.15

3.049

1.761

0.003

0.104

102

13

Lung metastases

no

yes

243.27±174.25

365.94±385.90

195.73±80.53

230.98±129.99

1.825

2.631

0.072

0.012

71

44

Bone metastases

no

yes

247.23±237.27

340.24±296.39

196.52±81.24

229.70±129.60

1.922

2.729

0.059

0.009

71

44

Pleural metastasis

no

yes

265.34±223.44

495.82±559.99

204.21±98.17

276.13±148.41

2.994

1.148

0.003

0.289

107

8

LDH, lactate dehydrogenase; SCLC, small-cell lung cancer; LS-SCLC, limited stage small-cell lung cancer; ES-SCLC, extensive stage small-cell lung cancer; ECOG, Eastern Cooperative Oncology Group;

No competing interests reported.

The prognostic significance of serum lactate dehydrogenase for patients with small cell lung cancer treated first-line therapy: a retrospective analysis of 163 consecutive cases

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Abstract

Figures

Introduction

Materials And Methods

Patients

Treatment

Clinical Data

Research Methods

Statistical analysis

Results

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

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