Pretreatment Serum Lactate Dehydrogenase Research Articles

Elevated pretreatment lactate dehydrogenase and albumin-to-alkaline phosphatase ratio predict poor prognosis and early treatment discontinuation in head and neck cancer patients with preexistent diabetes mellitus.

Increased serum lactate dehydrogenase (LDH) activity is considered as amarker of cellular necrosis and serves as ametabolomic diagnostic marker in several types of cancer including head and neck squamous cell carcinoma (HNSCC). LDH, an enzyme involved in the glycolytic cycle, is correlated not only with the activation of oncogenes such as HIF-α and Myc, but also with effects such as tumor proliferation and metastasis. Serum alkaline phosphatase (ALP) is amarker of cell differentiation and tumor induction. Albumin-to-alkaline phosphatase ratio (AAPR) could be an advantageous biomarker due to its easily accessible dynamics and cost-effectiveness. Elevated values of AAPR could be associated with longer overall survival (OS) in cases with solid tumors. Diabetes mellitus (DM) could influence the outcome of patients with HNSCC by contributing to insulin resistance and chronic inflammation, and by being involved in various aspects of carcinogenesis, disease progression and metastasis. However, the use of antihyperglycemic medications (metformin) can have beneficial effects by inhibiting tumor metabolic pathways. The biomarker role of LDH and AAPR in HNSCC patients with DM has been less evaluated. The purpose of the study was to assess the prognostic value of pretreatment serum lactate dehydrogenase (LDH) and albumin-to-alkaline phosphatase ratio (AAPR) in predicting the duration of non-surgical oncological treatment and glycemic control in cases of head and neck cancers patients with DM, including cases selected from the database of the oncology clinic and oncology outpatient clinic of the Craiova County Hospital. Both LDH and AAPR can be used as pre-treatment biomarkers predictive of treatment response, or prognostic tools included in complex multi-parametric models in HNC associated with DM. However, given the impact of short-term glycemic control on the LDH level, it is necessary to evaluate these biomarkers after assessing and controlling for DM, and with the recommended cut-off value set around 0.5. Due to the limited number of cases, it is necessary to validate the results in multicentric trials with alarger number of patients (Tab. 5, Ref. 50). Keywords: diabetes mellitus, HNC, LDH, AAPR, biomarkers, predictive, head and neck cancers, lactate dehydrogenase, albumin-to-alkaline phosphatase ratio.

Evaluating Prognostic Value of Dynamics of Circulating Lactate Dehydrogenase in Colorectal Cancer Using Modeling and Machine Learning.

Pretreatment serum lactate dehydrogenase (LDH) levels have been associated with poor prognosis in several types of cancer, including metastatic colorectal cancer (mCRC). However, very few models link survival to longitudinal LDH measured repeatedly over time during treatment. We investigated the prognostic value of on-treatment LDH dynamics in mCRC. Using data from two large phase III studies (2L and 3L+ mCRC settings, n = 824 and 210, respectively), we found that integrating longitudinal LDH data with baseline risk factors significantly improved survival prediction. Current LDH values performed best, enhancing discrimination ability (area under the receiver operating characteristic curve) by 4.5~15.4% and prediction accuracy (Brier score) by 3.9~15.0% compared with baseline variables. Combining all longitudinal LDH markers further improved predictive performance. After controlling for baseline covariates and other longitudinal LDH indicators, current LDH levels remained a significant risk factor in mCRC, increasing mortality risk by over 90% (P < 0.001) in 2L patients and 60-70% (P < 0.01) in 3L+ patients per unit increment in current log (LDH). Machine-learning techniques, like functional principal component analysis (FPCA), extracted informative features from longitudinal LDH data, capturing over 99% of variability and allowing prediction of survival. Unsupervised clustering based on the extracted FPCA features stratified patients into three groups with distinct LDH dynamics and survival outcomes. Hence, our approaches offer a valuable and cost-effective way for risk stratification and improves survival prediction in mCRC using LDH trajectories.

Prognostic Impact of Pretreatment Serum Lactate Dehydrogenase Levels in Adult Patients with Acute Myeloid Leukemia: Single Center Experience

prognostic Impact of Pretreatment Serum Lactate Dehydrogenase Levels in Adult Patients with Acute Myeloid Leukemia: Single Center Experience

Anomogram to predict the cumulative risk for brain metastases in patients with limited-stage small cell lung cancer without prophylactic cranial irradiation.

Patients with small cell lung cancer (SCLC) have ahigh risk of developing brain metastases (BM). Prophylactic cranial irradiation (PCI) is astandard therapy for limited-stage SCLC (LS-SCLC) patients who achieved complete or partial response after thoracic chemoradiotherapy (Chemo-RT). Recent studies have indicated that asubgroup of patients with alower risk of BM can avoid PCI, and the present study therefore tries to construct anomogram to predict the cumulative risk of development of BM in LS-SCLC patients without PCI. After screening of 2298 SCLC patients who were treated at the Zhejiang Cancer Hospital from December 2009 to April 2016, atotal of 167consecutive patients with LS-SCLC who received thoracic Chemo-RT without PCI were retrospectively analyzed. The paper analyzed clinical and laboratory factors that may be correlated with BM, such as response to treatment, pretreatment serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, and TNM stage. Thereafter, anomogram was constructed to predict 3‑ and 5‑year intracranial progression-free survival (IPFS). Of 167patients with LS-SCLC, 50developed subsequent BM. Univariate analysis showed that pretreatment LDH (pre-LDH) ≥ 200 IU/L, an incomplete response to initial chemoradiation, and UICC stageIII were positively correlated to ahigher risk of BM (p < 0.05). Multivariate analysis identified pretreatment LDH level (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.08-3.34, p = 0.026), response to chemoradiation (HR 1.87, 95% CI 1.04-3.34, p = 0.035), and UICC stage (HR 6.67, 95% CI 1.03-49.15, p = 0.043) as independent predictors for the development of BM. Anomogram model was then established, and areas under the curve of 3‑year and 5‑year IPFS were 0.72 and 0.67, respectively. The present study has developed an innovative tool that is able to predict the individual cumulative risk for development of BM in LS-SCLC patients without PCI, which is beneficial for providing personalized risk estimates and facilitating the decision to perform PCI.

Pretreatment Serum Lactate Dehydrogenase and Metastases Numbers as Potential Determinants of Anti-PD-1 Therapy Outcome in Nasopharyngeal Carcinoma.

We aimed to investigate the determinant factors of anti-PD-1 therapy outcome in nasopharyngeal carcinoma (NPC). In this retrospective study, we included 64 patients with recurrent/metastatic NPC. The association of patients' characteristics, C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) with survival benefit of anti-PD-1 therapy were analyzed using Cox regression models and Kaplan-Meier analyses. Patients were divided based on the median value of CRP, NLR or LDH into different subgroups. At a median follow-up time of 11.4months (range: 1-28months), median progression-free survival (PFS) and overall survival (OS) were 1.9months (95% CI, .18-3.6) and 15months (95% CI, 10.9-19.1) months, respectively. Pretreatment metastases numbers was significant predictor of PFS (HR = 1.99; 95% CI 1.10-3.63; P = .024) and OS (HR = 2.77; 95% CI 1.36-5.61; P = .005). Baseline LDH level was independent predictor of OS (HR = 7.01; 95% CI 3.09-15.88; P < .001). Patients with LDH level >435U/L at the baseline had significantly shorter PFS and OS compared to patients with LDH level ≤435U/L (median PFS: 1.7 vs 3.5months, P = .040; median OS: 3.7 vs 18.5months, P < .001). Patients with non-durable clinical benefit (NDB) had significantly higher LDH level at the baseline compared to patients who achieved durable clinical benefit (DCB) (P = .025). Post-treatment levels of CRP, LDH, and NLR were decreased compared to baseline in patients with DCB (P = .030, P = .088, and P = .066, respectively), whereas, there was a significant increase in post-treatment level of LDH compared with baseline in patients with NDB (P = .024). LDH level at the baseline was an independent predictor of OS and pretreatment metastases numbers was a significant predictor of PFS and OS.

Serum lactate dehydrogenase predicts brain metastasis and survival in limited-stage small cell lung cancer patients treated with thoracic radiotherapy and prophylactic cranial irradiation.

Small cell lung cancer (SCLC) is characterized by ahigh risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI). This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan-Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival. Of the total patients, 28had higher pretreatment LDH levels and mLDH levels were increased in 95patients during treatment. In patients in the normal and elevated mLDH groups, the 1‑, 2‑, and 5‑year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had ahigher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73-8.63; P < 0.01) and worse overall survival (HR 2.59; 95%CI 1.67-4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95%CI 1.57-7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95%CI 1.22-4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95%CI 1.56-3.86; P < 0.001), IIIB stage (HR 1.75; 95%CI 1.06-2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95%CI 1.04-2.65; P = 0.034). The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification.

Value of pretreatment serum lactate dehydrogenase as a prognostic and predictive factor for small-cell lung cancer patients treated with first-line platinum-containing chemotherapy.

BackgroundThe current study aimed to evaluate the serum pretreatment lactate dehydrogenase (LDH) and overall survival (OS) in small cell lung cancer (SCLC) patients who received first‐line platinum‐containing chemotherapy.MethodsA total of 234 SCLC patients, who received first‐line platinum‐based chemotherapy between 2013 and 2018, were retrospectively analyzed. The data of hematological characteristics, age, gender, ECOG score, staging, metastatic site, smoking history, chemotherapy cycle, thoracic radiotherapy and hyponatremia were collected. Overall survival was calculated using the Kaplan‐Meier method. The statistically significant factors in the univariate analysis were selected for the multivariate COX model analysis.ResultsAge, ECOG score, stage, thoracic radiotherapy, hyponatremia, liver metastasis, brain metastasis, bone metastasis, LDH, NSE and neutrophil‐to‐lymphocyte ratio (NLR) were closely correlated to OS in the univariate analysis. Furthermore, the multivariate analysis revealed that age (<65 years), ECOG score (<2 points), limited‐stage (LD), thoracic radiotherapy and LDH <215.70 U/L were the independent prognostic factors for survival. The median OS time was worse for patients with LDH ≥215.70 U/L. In the subgroup analysis, LDH ≥215.70 U/L was significant for survival in both limited and extensive disease. Patients who achieved CR + PR in the first‐line treatment had lower initial LDH levels. It was found that the pretreatment LDH increased the incidence of patients with liver metastasis.ConclusionsPositive independent prognostic factors for SCLC patients were age < 65 years old, ECOG score < 2 points, LD‐SCLC, and pretreatment LDH <215.70 U/L. These factors may be useful for stratifying patients with SCLC for treatment approaches.Key pointsSignificant findings of the studyAge < 65 years old, ECOG score < 2 points, LD‐SCLC, and pretreatment LDH <215.70 U/L are the positive independent prognostic factors for SCLC patients.What this study addsThe current study provided more references for SCLC diagnosis and treatment and determined more factors for stratifying patients with SCLC for treatment approaches.

Induction Chemotherapy Combined With Intensity-Modulated Radiotherapy for 129 Nasopharyngeal Carcinoma Patients With Synchronous Metastases: A Retrospective Study.

ObjectiveTo analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT).MethodsA total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS).ResultsA total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) >180U/L, chemotherapy cycles<4, and M1 stage subdivision (M1b, single hepatic metastasis and/or multiple metastases excluding the liver; and M1c, multiple hepatic metastases). The 5-year OS rates for M1a, M1b and M1c were 62.6%,40.4% and 0%, respectively.ConclusionPlatinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.

Lactate Dehydrogenase Prior to Transarterial Hepatic Chemoperfusion Predicts Survival and Time to Progression inPatients with Uveal Melanoma Liver Metastases.

To assess serum lactate dehydrogenase (LDH) as a pretreatment prognostic factor in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion (THC). 56 patients (48 % male, median age: 63.5 years) underwent a median of 4 THC sessions. Kaplan-Meier for median overall survival (OS) and time to hepatic progression (TTP; 95 %CI) in months and Cox proportional hazards model for uni- (UVA) & multivariate analyses (MVA) for hazard ratio (HR) evaluation were calculated. The median OS was 9.4 months. The pretreatment LDH value before 1st THC was the strongest OS predictor with 19.8 months for normal (≦ 280 units per liter (U/L)), 9.7for intermediate (> 280-< 1000 U/L), and 3.84 months for high (≧ 1000 U/L) LDH. LDH significantly predicted a median TTP with 8 months, 4 months, and 1 month for normal, intermediate, and high LDH, respectively. UVA revealed intermediate (16.5) and high (77.3) LDH, bilirubin > the upper limit of normal (ULN) (2.89), alkaline phosphatase > 1.5 ULN (6.8), leukocytes > ULN (4.2), gamma-glutamyl transferase (GGT) > ULN (7), extrahepatic metastases (1.8) and liver lesions ≥ 5 cm (3.6) as significant predictors for worse OS. MVA confirmed intermediate (5) and high (27.1) LDH, bilirubin (5.7), GGT (2.9), and tumor size ≥ 5 cm (3.7) as significant independent predictors for worse OS. Patients with decreasing vs. increasing LDH > 10 % between 1st and 2nd THC (median: 38 days) survived longer (14.6 vs. 4.3 months) and progressed later (7 months vs. 1 month). Elevated pretreatment serum LDH is an essential and robust OS and TTP predictor, potentially allowing for the identification of patients benefiting most from transarterial hepatic chemoperfusion. · Pretherapeutic LDH is the most reliable prognosticator for OS and TTP. · Therapy-related LDH decrease > 10 % between 1st and 2nd THC had prolonged OS and TTP. · Lower Values of LDH, bilirubin, gamma-glutamyl transferase, and tumor size are independent pretherapeutic predictors for longer OS. · Extrahepatic metastases do not have an independent influence on overall survival. · Ludwig J, Haubold J, Heusner T et al. Lactate Dehydrogenase Prior to Transarterial Hepatic Chemoperfusion Predicts Survival and Time to Progression in Patients with Uveal Melanoma Liver Metastases. Fortschr Röntgenstr 2021; 193: 683 - 691.

The Predictive Value of Lactate Dehydrogenase in Patients with Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Increasing evidence has indicated that higher levels of lactate dehydrogenase (LDH) is associated with poor prognosis in various malignancies; however, the correlation between LDH levels and clinical outcomes in esophageal squamous cell carcinoma (ESCC) has been poorly studied. The objective of this study was to assess whether LDH has prognostic value in patients with ESCC undergoing chemoradiotherapy. A total of 614 ESCC patients were enrolled in this retrospective study from January 1, 2012 to December 31, 2016.The optimal cutoff points for LDH were determined by X-tile software. we analyzed the association between the levels of LDH and clinicopathological characteristics, as well as the relationship between LDH levels and responses. Kaplan-Meier method with log-rank test was used to explore the prognostic value for overall survival (OS) and progression-free survival (PFS). And then We examined the prognostic value for OS and PFS by univariate and multivariate Cox regression models. A 1:3 propensity score matching was used to compensate for differences in baseline characteristics. The optimal cutoff points of LDH was 134U/L. The median OS in the high LDH group was 31.3 months, and more than 50% of patients with low LDH were still survive to the last follow-up (P = 0.020).The median PFS of low LDH and high LDH were 40.1 and 18.0 months, respectively (P = 0.010).Gender,Cyfra21-1,tumor length, cN/M stage, treatment options and LDH were independent prognostic indicators for OS. Gender, Cyfra21-1, tumor length, cN/M stage, treatment options, chemotherapy cycles, and LDH were independent prognostic indicators for PFS. Unfortunately, there was no significant difference for OS and PFS by Kaplan–Meier method after matching, but the survival curve showed a tendency to separate between the two groups. The present study revealed the existence of a significant association between the pretreatment serum LDH level and OS in patients with ESCC receiving treatment with chemoradiotherapy as well as a significant association with PFS. It implied that the management of patients with high LDH levels should be changed. However, it is worth noting that this conclusion was not certified after matching. Although the consistent conclusions were not obtained in predicting the prognosis of ESCC patients with LDH before and after matching, a multicenter, large-sample prospective study is needed to further verify the conclusions of this study before this method can be applied to conventional clinical studies.

Pretreatment age and serum lactate dehydrogenase as predictors of synchronous second primary cancer in patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common cancer and is treated primarily by chemotherapy and radiotherapy. However, NPC with synchronous second primary cancer (SSPC) is very rare and its risk factors, treatment and prognosis remain unclear. In this study, we aimed to analyze patients with NPC and SSPC, and attempt to find potential predictors for these patients. We retrospectively collected 681 patients with NPC from 2006 to 2018. Patients in this study were divided into two groups: those patients with SSPC and those without SSPC. We then analyzed the demographic data and survival of these two groups. Independent predictors of SSPC were determined by multivariate regression analysis. A comprehensive review of the literature was also performed. We identified 17 NPC patients with SSPC in our case series and 13 cases in the literatures, and the most common SSPC is lung (16.1%). In univariate analysis, NPC patients with SSPC had older age (P<0.001) and higher serum lactate dehydrogenase (LDH) (P=0.008), compared with those without SSPC. In multivariate analysis, old age (P=0.001) and high serum LDH (P=0.023) remained independent predictors of SSPC, and a predictive equation model was established. NPC patients with SSPC had a significantly lower 5-year disease-specific survival rate compared with patients without SSPC (34.0% vs. 77.6%, P<0.001) CONCLUSION: This study demonstrated that pretreatment age and serum LDH were independent predictors for SSPC in NPC patients. These independent factors can be used for early detection, and better facilitate the design of more appropriate treatment by medical professionals.

Prognostic role of pretreatment lactate dehydrogenase in patients with metastatic renal cell carcinoma: A systematic review and meta-analysis.

To date, there remain uncertainties over the prognostic role of serum lactate dehydrogenase (LDH) in patients with metastatic renal cell carcinoma (mRCC). A systematic review and meta-analysis was performed. Eligible studies were retrieved from PubMed, Embase, Cochrane Library and Web of Science databases up to October 2019. The endpoints included overall survival (OS) and progression-free survival (PFS). Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate each endpoint. Thirty observational studies of low to moderate risk of bias embracing 6754 patients with mRCC were included. The results showed that patients with a high pretreatment serum LDH had an inferior OS (HR: 2.15, 95% CI: 1.85-2.51; P<0.001) and PFS (HR: 1.76, 95% CI: 1.49-2.10; P<0.001). Subgroup analyses according to year of publication, study design, patient population, geographic region, sample size and NOS score did not alter the direction of results. There was significant publication bias for OS, but not for PFS. Sensitivity analyses further confirmed the robustness of the results. Our findings indicated that a high level of pretreatment serum LDH was associated with an inferior OS and DFS in patients with mRCC. Methodological limitations should be considered while interpreting these results.

Multimodal Approach to Outcome Prediction in Metastatic Castration-Resistant Prostate Cancer by Integrating Functional Imaging and Plasma DNA Analysis.

Biomarkers for treatment personalization in metastatic castration-resistant prostate cancer (mCRPC) could help improve patient outcomes. Multiple tests on blood have reported associations with poorer outcome, including serum lactate dehydrogenase (LDH), chromogranin A (CGA), neutrophil:lymphocyte ratio (NLR), and, recently, copy number (CN) of androgen receptor (AR) in plasma DNA. Biologic data suggest an association between choline uptake and AR signaling. We aimed to integrate 18F-fluorocholine (FCH) uptake on positron emission tomography/computed tomography (PET/CT) scanning with plasma AR CN and other routinely obtained circulating biomarkers to evaluate their association with outcome. We determined plasma AR CN by digital droplet polymerase chain reaction from 105 mCRPC samples collected before abiraterone (n = 65) or enzalutamide (n = 40) therapy in the before (n = 26) and after (n = 79) chemotherapy settings. Pretreatment serum LDH, CGA, and NLR were also measured. FCH-PET/CT scan was performed at baseline, and maximum standardized uptake value (SUVmax), total lesion activity (TLA), and metabolic tumor volume (MTV) were calculated. Main end points were the correlation of FCH-PET/CT parameters with circulating biomarkers and their impact on outcome. Plasma AR CN gain was observed in 27 patients (25.7%), and it correlated significantly with higher median SUVmax, TLA, and MTV values (P < .001). Kaplan-Meier curves showed significantly worse progression-free survival and overall survival in patients with plasma AR gain and higher SUVmax, TLA, and MTV values (P < .001 in each prognostic group). Conversely, no association was reported for prostate-specific antigen response. On multivariable analysis of overall survival, we showed as independent factors AR gain (hazard ratio [HR], 1.92; 95% CI, 1.07 to 3.47; P = .029), presence of visceral metastasis (HR, 3.04; 95% CI, 1.66 to 5.58; P = < .001), LDH (HR, 2.95; 95% CI, 1.72 to 5.05; P < .001), NLR (HR, 3.51; 95% CI, 2.14 to 5.74; P < .001), serum CGA (HR, 3.36; 95% CI, 1.99 to 5.67; P < .001), and MTV (HR, 2.09; 95% CI, 1.25 to 3.50; P = .005). Our results indicate the potential usefulness of integrating functional imaging with plasma DNA analysis and other noninvasive biomarkers as a tool to improve treatment selection for CRPC. A larger prospective evaluation is warranted.

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.

BackgroundTargeted therapy is an important treatment for advanced non-small cell lung cancer (NSCLC) patients with specific genetic mutations, crizotinib can prolong survival in advanced NSCLC patients with echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) rearrangement. We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with EML4-ALK rearrangement NSCLC receiving treatment with crizotinib.MethodsAdvanced (stage IIIb–IV) NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled between January 2007 and January 2016 at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences.ResultsOverall, 212 patients were enrolled. Kaplan–Meier univariate analysis showed that elevated pre-treatment LDH level (7.9 vs 14.1 months, HR =1.251, CI: 1.008–1.553, P=0.004) was significantly associated with shorter PFS, while the post-treatment mean-LDH level (13.3 vs 14.3 months, HR=1.439, 95% CI: 0.994–2.082, P=0.970) was not significantly associated with PFS. Cox proportional hazards model also identified that pre-treatment LDH level (HR=2.085, 95% CI: 1.150–3.781, P=0.016) was associated with the PFS. Logistic regression analysis showed that post-treatment LDH level was associated with creatine kinase (OR=6.712, 95% CI 3.395–13.273, P<0.01), creatine kinase isoenzyme (OR=6.297, 95% CI 2.953–13.427, P<0.01), and hemoglobin (OR=4.163, 1.741–9.956, P<0.001).ConclusionAn elevated pre-treatment serum LDH level (>250 U/L) was significantly associated with shorter PFS in patients with EML4-ALK rearrangement NSCLC. Post-treatment elevated serum LDH level was not significantly associated with PFS, which related to adverse events including muscle damage and anemia.

Application value of serum LDH in advanced non-small cell lung cancer patients treated with EGFR-TKI

Objective To investigate the value of serum lactate dehydrogenase (LDH) in advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). Methods Pretreatment LDH level, pathological characteristic, tumor staging and treatment situation of 190 advanced NSCLC patients with EGFR sensitive mutation confirmed by pathology were retrospectively collected in Zhuhai People′s Hospital of Guangdong Provice from July 2011 to July 2015. All the patients were divided into LDH normal group (LDH≤252 U/L, n=78) and elevated group (LDH>252 U/L, n=112) according to pretreatment LDH level. Imaging evaluations of the patients were performed regularly, and the progression-free survival (PFS) and overall survival (OS) were recorded. The survival curves were plotted by Kaplan-Meier method and survival difference between patients with different LDH level was compared by log-rank test. Cox regression analysis was used to analyze prognostic factors for mortality. Results The objective response rate of the LDH normal group was 76.9% (60/78), and the elevated group was 71.4% (80/112), with no statistically significant difference (χ2=0.716, P=0.398). The disease control rate of the LDH normal group was 89.7% (70/78), and the elevated group was 85.7% (96/112), with no statistically significant difference (χ2=0.676, P=0.411). The median PFS of the LDH normal group was 11.5 months, and the elevated group was 9.7 months (χ2=5.92, P=0.015). The median OS was 31.0 months in the LDH normal group, and 26.1 months in the elevated LDH group (χ2=4.79, P=0.029). Both PFS and OS of patients with elevated LDH were shorter than those of patients with normal LDH. Cox multivariate regression analysis showed that tumor staging (HR=1.652, 95%CI: 1.386-2.259, P=0.018), PS score (HR=2.248, 95%CI: 1.507-3.846, P<0.001), carcino-embryonic antigen (CEA) level (HR=1.250, 95%CI: 1.066-1.703, P=0.037) and LDH level (HR=1.771, 95%CI: 1.324-1.947, P=0.015) were independent prognostic factors in patients with advanced NSCLC. Conclusion Pretreatment serum LDH can not affect the objective response rate and disease control rate of EGFR-TKI in the treatment of advanced NSCLC, but can affect the PFS and OS of patients. Pretreatment serum LDH is an independent prognostic factor. Key words: Lactate dehydrogenase; Carcinoma, non-small cell lung; Epidermal growth factor receptor-tyrosine kinase inhibitors; Prognosis

Association of PFS with levels of pretreatment lactate dehydrogenase in patients with EML4-ALK rearrangement non-small cell lung cancer treated with ALK tyrosine kinase inhibitor.

e20513 Background: We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with echinoderm microtubule-associated protein-like 4-anaplasticlymphoma kinase (EML4-ALK) rearrangement non-small cell lung cancer (NSCLC) receiving treatment with crizotinib. Methods: Advanced NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences between January 2007 and January 2016. Pre-treatment or post-treatment serum LDH levels were analyzed with progression-free survival (PFS) and patients’ clinical parameters. Results: Overall, 212 patients were studied. Kaplan-Meier univariate analysis showed that elevated pre-treatment LDH level (7.9 vs. 14.1 months, P = 0.004) were associated with PFS, while the mean value of post-treatment LDH level (14.3 vs. 13.3 months, P = 0.970) were not associated with PFS. Coxproportional hazards model also identified that pre-treatment LDH level (hazard ratio [HR] = 1.841, 95% confidence interval [CI] 1.062-3.190, P = 0.030) was associated with the PFS. Logistic regression analysis showed that post-treatment LDH level was associated with creatine kinase(OR = 6.712, 95% CI 3.395-13.273, P &lt; 0.01), CKMB (OR = 6.297, 95% CI 2.953-13.427, P &lt; 0.01), and hemoglobin(OR = 4.163, 1.741-9.956, P = 0.001). Conclusions: An elevated pre-treatment serum LDH level ( &gt; 250U/L) is significantly associated with shorter PFS in patients with EML4-ALK rearrangement NSCLC. Post-treatment elevated serum LDH level is associated with multiple factors including muscle damage and anemia, rather than PFS.

18F-Fludeoxyglucose PET/CT in SCLC: Analysis of the CONVERT Randomized Controlled Trial

IntroductionWe used phase-3 CONVERT trial data to investigate the impact of fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in SCLC. MethodsCONVERT randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) chemoradiotherapy. Patients were divided into two groups in this unplanned analysis: those staged with conventional imaging (contrast-enhanced thorax and abdomen CT and brain imaging with or without bone scintigraphy) and those staged with 18F-FDG PET/CT in addition. ResultsData on a total of 540 patients were analyzed. Compared with patients who underwent conventional imaging (n = 231), patients also staged with 18F-FDG PET/CT (n = 309) had a smaller gross tumor volume (p = 0.003), were less likely to have an increased pretreatment serum lactate dehydrogenase level (p = 0.035), and received more chemotherapy (p = 0.026). There were no significant differences in overall (hazard ratio = 0.87, 95% confidence interval: 0.70–1.08, p = 0.192) and progression-free survival (hazard ratio = 0.87, 95% confidence interval: 0.71–1.07], p = 0.198) between patients staged with or without 18F-FDG PET/CT. In the conventional imaging group, we found no survival difference between patients staged with or without bone scintigraphy. Although there were no differences in delivered radiotherapy dose, 18F-FDG PET/CT–staged patients received lower normal tissue (lung, heart, and esophagus) radiation doses. Apart from a higher incidence of late esophagitis in patients staged with conventional imaging (for grade ≥1, 19% versus 11%; [p = 0.012]), the incidence of acute and late radiotherapy-related toxicities was not different between the two groups. ConclusionIn CONVERT, survival outcomes were not significantly different in patients staged with or without 18F-FDG PET/CT. However, this analysis cannot support the use or omission of 18F-FDG PET/CT owing to study limitations.

Pre-treatment Serum Lactate Dehydrogenase Predicts Distant Metastasis and Poor Survival in Nasopharyngeal Carcinoma.

Background: Pre-treatment serum lactate dehydrogenase (LDH) has emerged as prognostic factor for many cancers. In this study, we evaluated the value of LDH in predicting distant metastasis and poor survival for patients with nasopharyngeal carcinoma (NPC).Methods: Clinical data from 172 non-metastatic NPC patients were retrospectively collected and serum LDH levels were routinely measured before treatment. The independent-samples t test was used to calculate differences between serum LDH levels from the various patient groups. Receiver-operating characteristic (ROC) curve analysis was performed to select the optimal cutoff points. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the distant metastasis free survival (DMFS) and overall survival (OS) rates. The Cox proportional hazards model was used to carry out univariate and multivariate analyses.Results: NPC patients progressed with distant metastasis often have higher pre-treatment serum LDH levels than those did not develop distant metastasis (mean LDH level was 237.1U/L and 108.8U/L, respectively, p=0.001). Elevated LDH level was identified as an independent prognostic factor for poor DMFS (hazard ratio (HR), 8.31; 95% confidence interval (CI), 2.44-28.32; p=0.001) and OS (HR, 4.45; 95% CI, 1.77-11.21; p=0.002). Moreover, subgroup analyses revealed significant associations between serum LDH level and worse survival in advanced stage patients.Conclusions: Pre-treatment serum LDH level can predict distant metastasis and associate with the poor survival in patients with NPC.

Prognostic value of pretreatment serum lactate dehydrogenase level in pancreatic cancer patients: A meta-analysis of 18 observational studies.

Background:Several studies were conducted to investigate the prognostic value of pretreatment serum lactate dehydrogenase (LDH) level in pancreatic cancer (PC), but the results were inconsistent. This study aims to comprehensively assess the prognostic value of pretreatment serum LDH level in PC patients by combining the data of the published literatures on this topic.Methods:Embase, PubMed, and Web of Science were completely retrieved until June, 2018. The observational studies focusing on the prognostic value of pretreatment serum LDH level in PC patients were eligible. STATA version 12.0 was used to undertake the statistical analysis.Results:Eighteen studies with a total of 3345 patients were included in this meta-analysis. The meta-analysis was conducted to generate pooled hazard ratios (HRs) and 95% confidence interval (CI) for overall survival (OS). Our analysis results suggested that high serum LDH level predicted worse OS (HR 1.57, 95% CI 1.30–1.90, P < .001) in PC patients. Moreover, for patients with advanced PC, the prognostic relevance of pretreatment serum LDH level not only existed in those receiving palliative chemotherapy (HR 1.72, 95% CI 1.35–2.18, P < .001), but also in those who were precluded from chemotherapy (HR 1.91, 95% CI 1.4219–2.58, P < .001).Conclusion:The meta-analysis results demonstrated that pretreatment serum LDH level is closely associated with OS, and it may be a useful biomarker for assessing the prognosis of PC patients.

767P - Predictive factors of outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy

Background: Gemcitabine plus cisplatin (GC) is acknowledged as standard chemotherapy for advanced biliary tract cancer (BTC). Few studies have been conducted to identify the prognostic factors in patients receiving this therapy. The purpose of this study was to identify and validate predictive factors of outcome in patients with advanced BTC receiving GC therapy. Methods: The data of 307 patients with advanced BTC who received GC as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. All patients were randomly assigned to the investigation and validation datasets at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors in the investigation dataset (n = 205) and the patients were classified, according to the prognostic factors, into three risk groups, that is, groups with a good, intermediate and poor prognosis. This classification was then applied to the validation dataset (n = 102). Results: The median overall survival (OS) and 1-year survival rate in the investigation dataset were 13.0 months (95% confidence interval, 11.0-13.9) and 54.7% respectively. Multivariate analysis identified the performance status, pretreatment serum lactate dehydrogenase level and pretreatment neutrophil-to-lymphocyte ratio as independent predictive factors of the OS. The patients were classified into three groups according to the identified prognostic factors, and the outcomes were found to differ significantly among the three groups (p < 0.01). When this classification was applied to the validation dataset, the OS was found to differ significantly among the three risk groups (p < 0.05). Conclusions: This study identified three predictive factors of outcome, which allowed patients of advanced BTC receiving GC therapy to be classified into three risk groups. Legal entity responsible for the study: Principal Investigator: Masafumi Ikeda, M.D. Funding: Has not received any funding. Disclosure: H. Takahashi: Research funding: Bayer Pharmaceutical, Bristol-Myers Squibb; Honoraria: Taiho Pharmaceutical. I. Ohno: Honoraria: Taiho Pharmaceutical, Merck Serono. M. Ikeda: Research fundings: Bayer Yakuhin, Kyowa Hakko Kirin, Yakult, Taiho Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Eisai, AstraZeneca, Zeria Pharmaceutical, Baxter, Chugai Pharmaceutical, Bristol Myers Sqiibb, Merck Serono, Kowa, Nano Carrier, ASLAN Pharmaceuticals; Honoraria: Novartis Pharma, Bayer Yakuhin, Bristol-Myers Squibb, Abbott Japan, Eisai, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi-Sankyo, Yakult, Otsuka Pharmaceutical, and Nobelpharma. All other authors have declared no conflicts of interest.