Prognostic significance of serum LDH in small cell lung cancer: A systematic review with meta-analysis

Zhang, Xiuxiu; Guo, Mengfei; Fan, Jinshuo; Lv, Zhi; Huang, Qi; Han, Jiapeng; Xu, Jing; Jin, Yang

doi:10.3233/cbm-160580

Cited by 81 publications

(87 citation statements)

References 40 publications

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“…As an important prognostic factor for SCLC patients, many researches have revealed the association between elevated LDH levels at baseline and poor survival (9,12). In the present study, patients who had an abnormally elevated baseline LDH were observed to have a 1.92-fold risk of death than those with normal LDH (95% CI, 1.29-2.86).…”

Section: Discussionmentioning

confidence: 48%

“…Therefore, measurements of serum LDH levels can reflect the intensity of tumor activities and thus can be used as a prognostic biomarker. Zhang et al (9) conducted a metaanalysis involving 4,785 SCLC patients from 28 studies to investigate the prognostic value of baseline LDH for SCLC patients. Their results indicated that patients with an abnormal elevation of serum LDH at baseline would have a 1.45 times higher risk of death than those with normal LDH level (HR =1.45; 95% confidence interval (CI), 1.27-1.66).…”

Section: Original Articlementioning

confidence: 99%

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Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

et al. 2018

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Background: Elevated pretreatment lactate dehydrogenase (LDH) has been reported to be associated with poor survival in small cell lung cancer (SCLC). The present study aimed to investigate the continuous relationship between baseline LDH level and survival in patients with extensive-disease SCLC (ED-SCLC). Results: A total of 132 eligible ED-SCLC patients were analyzed. Elevated LDH at baseline was associated with poor survival (HR =1.92; 95% CI,). An increment of LDH would still raise the risk of death even in abnormal range. Among patients with elevated LDH, those who had relatively higher LDH levels (>370 U/L) would have a poorer prognosis than those with moderately elevated LDH levels (245-370 U/L; median survival time, 114 vs. 274 days; P value of log rank test, 0.007).Conclusions: LDH is a significant prognostic biomarker for ED-SCLC patients. The interpretation of continuous relationship between LDH and patients' survival can provide more accurate information for clinical practice. In recent decades, novel approaches of immunotherapy have brought light to cancer treatment (4,5). And trials for investigating the efficacy and safety of immunotherapy with or without chemotherapy in SCLC patients are ongoing (6,7).Predicting prognostic risks of SCLC patients through reliable biomarkers can provide information for disease monitoring and treatment evaluation, which will contribute to the exploration of novel treatments. Lactate dehydrogenase (LDH) is the key enzyme in glycolytic pathway, which is the main source of energy in activities of rapid proliferation and distant metastases for tumor cells. When tissue damage occurs because of tumor activities, LDH will be released from intracellular microenvironment and then lead to an abnormal elevation of serum LDH (8). Therefore, measurements of serum LDH levels can reflect the intensity of tumor activities and thus can be used as a prognostic biomarker. Zhang et al. (9) conducted a metaanalysis involving 4,785 SCLC patients from 28 studies to investigate the prognostic value of baseline LDH for SCLC patients. Their results indicated that patients with an abnormal elevation of serum LDH at baseline would have a 1.45 times higher risk of death than those with normal LDH level (HR =1.45; 95% confidence interval (CI), 1.27-1.66).However, measurements of LDH were all treated as binary outcomes in above studies with a cutoff value at the upper limit of normal range. In that way, it would be impossible to explore the continuous relationship between baseline LDH and survival; namely, different LDH levels within the same group would be regarded as to have the same risk of death.Modeling the relationship between exposure of risk factors and disease outcomes can provide more accurate information for clinical practice. Zhou et al. (10) found nonlinear associations between biomarkers and prognosis in resectable pancreatic ductal adenocarcinoma (PDAC) patients. Their results suggested that a preoperative Carbohydrate antigen 19-9 (CA19-9) level of 100 U/mL and a carcinoembryoni...

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Section: Discussionmentioning

confidence: 48%

Section: Original Articlementioning

confidence: 99%

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

et al. 2018

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“…These conditions (high consumption of glucose and hypoxic environment) lead to higher LDH levels. More generally, a high LDH level is known to be a factor of poor prognosis in other cancers, such as lung15 and breast cancer16, and two other studies in NEC (pulmonary17 and colorectal12) also reported high LDH serum levels. Among 61 patients with available AST data at diagnosis, 31% had AST ≥ 2 ULN and they were associated with poorer outcome in multivariate analysis.…”

Section: Discussionmentioning

confidence: 91%

Prognostic factors in neuroendocrine carcinoma: biological markers are more useful than histomorphological markers

Freis

Graillot

Rousset

et al. 2017

Sci Rep

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Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are a very aggressive type of cancer, for which prognostic factors are lacking. We analysed clinical and histomorphological prognostic markers of overall survival (OS), completed with a record of biological and haematological data of patients diagnosed between December 2002 and December 2015. The median OS was 16 months (95% CI 13.9–18.1). After univariate analysis, performance status (PS) ≥ 2 and stage IV were associated with a worse outcome (9 months and 14 months, respectively), as well as patients with lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels ≥ 2 ULN (9 months and 8 months, respectively). After multivariate analysis, LDH and AST levels were the only factors that remained significantly associated with better survival: HR 0.36 (p = 0.04) and 0.31 (p = 0.03), respectively. When patients had elevated LDH and AST levels, OS was 20 months, when they had high LDH or AST levels, 13 months and 8 months in the group with low LDH and AST levels (p < 0.001). Therefore, biological data appeared to be more relevant prognostic factors than usual factors described in other studies (PS, stage, and Ki-67). Considering LDH and AST levels at diagnosis could help physicians to predict survival and to stratify patients for clinical trials.

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“…Several studies have already identified pretherapeutic prognostic markers and scores to predict outcome in SCLC patients [7,8,9,10,11,12,13,14]. A recent study also demonstrated that pretreatment mGPS and PNI are independent predictors of OS in patients with advanced SCLC [14].…”

Section: Discussionmentioning

confidence: 99%

“…For about 30 years, lactate dehydrogenase (LDH) and serum albumin have been described to predict OS in SCLC [7,8,9]. Different markers and scores for acute inflammation, i.e., the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) levels, the modified Glasgow prognostic score (mGPS), the prognostic nutritional index (PNI), and the systemic immune-inflammation index (SII) have been associated with poor outcome in SCLC [10,11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Pretherapeutic Inflammation Predicts Febrile Neutropenia and Reduced Progression-Free Survival after First-Line Chemotherapy in SCLC

Kauffmann-Guerrero¹,

Kahnert²,

Syunyaeva³

et al. 2018

Oncol Res Treat

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Background: Despite initial response to chemotherapy, the prognosis of small cell lung cancer (SCLC) patients is limited. Following first-line therapy, the strongest predictor of durable progression-free survival (PFS) is remission quality. Febrile neutropenia (FN) is a frequent complication after chemotherapy, and its prevention could improve treatment density and degree of remission. Patients and Methods: We retrospectively analyzed 39 SCLC patients treated at a German tertiary care lung cancer center between 2013 and 2016. We extracted data sets from electronic records and analyzed anthropometric data, pretherapeutic blood values, and prognostic scores. Discriminant analysis was performed to predict FN. Results: PFS after first-line chemotherapy was significantly shorter in patients with FN (p = 0.003). Pretherapeutic albumin (p = 0.019), C-reactive protein (CRP; p < 0.001), lactate dehydrogenase (p = 0.041), neutrophil-to-lymphocyte ratio (p = 0.009), prognostic nutritional index (p = 0.018), and Glasgow prognostic score (p < 0.001) were significantly associated with FN. CRP in combination with absolute neutrophil count is a strong predictor of FN (positive predictive value 79.8%). Conclusion: SCLC patients with FN after chemotherapy showed significantly reduced PFS. Prevention of FN may improve treatment results. We identified pretherapeutic markers which can predict FN risk. This simple and cost-effective method could serve to identify the need for preventive measures against FN (e.g., prophylactic antibiotic treatment or granulocyte colony stimulating factor administration).

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Prognostic significance of serum LDH in small cell lung cancer: A systematic review with meta-analysis

Cited by 81 publications

References 40 publications

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

Prognostic factors in neuroendocrine carcinoma: biological markers are more useful than histomorphological markers

Pretherapeutic Inflammation Predicts Febrile Neutropenia and Reduced Progression-Free Survival after First-Line Chemotherapy in SCLC

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