Pretreatment Lactate Dehydrogenase Levels Research Articles

Peripheral blood biomarkers in immune checkpoint inhibition therapy in metastatic melanoma.

e21543 Background: Immune checkpoint inhibitors are extensively employed in the management of various solid cancers. Our study aims to assess the potential prognostic and predictive value of peripheral blood biomarkers, as well as their correlation with adverse events. Methods: In this study, we conducted a retrospective analysis of data retrieved from a cohort of 23 patients diagnosed with metastatic melanoma at a single institution between 2015 and 2019. Specifically, we focused on analyzing the neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil+monocyte-to-absolute lymphocyte+eosinophil ratio (ANMC/ALEC) from complete blood count (CBC), and lactate dehydrogenase (LDH) level from peripheral blood to assess their correlation with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs). Results: Our findings revealed that NLR values less than 0.34 and ANMC/ALEC ratio less than 3.45 were associated with improved PFS and OS, as well as a lower incidence of immune-related adverse events, which supports our initial hypothesis. However, these results were not statistically significant due to the low power of our study. On the other hand, high NLR values were significantly associated with higher pre-treatment LDH levels (P-value = 0.037), which is a well-established adverse prognostic factor in melanoma. Additionally, high ANMC/ALEC ratios were also found to be associated with high LDH levels, although this relationship was not statistically significant (P-value = 0.133). Conclusions: The results of our study suggest that patients with lower pre-treatment NLR and ANMC/ALEC ratios have better PFS and OS, as well as lower incidence of irAEs. Conversely, those with high NLR and high ANMC/ALEC ratios exhibited lower PFS and OS, as well as higher incidence of irAEs. High NLR and ANMC/ALEC ratios were also found to be associated with higher pre-treatment LDH levels, which have previously been demonstrated to be an adverse prognostic factor in melanoma. [Table: see text]

Long-term complete remission and peripheral biomarkers in Hodgkin lymphoma patients after decitabine-plus-camrelizumab epi-immunotherapy and treatment cessation.

Patients with relapsed/refractory classical Hodgkin lymphoma (cHL) achieve complete response (CR) after decitabine-plus-camrelizumab therapy, while long-term outcome especially after treatment discontinuation remains unclear. We present a retrospective analysis of 87 relapsed/refractory cHL patients who acquired CR after decitabine-plus-camrelizumab. Patients were divided into two groups and received consolidation treatment every 3-4 or 6-12weeks, and 1-year of continuous CR was guaranteed for treatment cessation. At a median follow-up of 5.3 years, the median relapse-free survival (RFS) after achieving CR with decitabine-plus-camrelizumab therapy was 4.5 years, and patients underwent consolidation per 3-4weeks might have longer RFS. The baseline percentage of peripheral central memory T cells was not associated with RFS, while patients with higher pretreatment serum levels of interleukin-6 (IL-6) and lactate dehydrogenase (LDH) had significantly shorter RFS and increased risk for disease recurrence. Fifty-seven patients completed and discontinued decitabine-plus-camrelizumab, and their median RFS had not been reached. The 2-year RFS rate after treatment cessation was 78% (95% CI, 67-90%). Patients in the high-risk subgroup with higher pretreatment IL-6 and LDH levels showed poor treatment-free remission. Moreover, decitabine-plus-camrelizumab therapy was safe and cost-effective. In conclusion, patients who obtained CR with decitabine-plus-camrelizumab and received consolidation per 3-4weeks can achieve long-term remission after treatment discontinuation.

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 Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy.

Background Immune checkpoint inhibitors have considerably changed the treatment paradigm for metastatic cervical cancer; nonetheless, only a proportion of patients achieve a durable response. Therefore, exploring the predictive biomarkers of immunotherapy response is of crucial importance. This study aimed to evaluate the predictive and prognostic value of hematological parameters in patients with metastatic cervical cancer treated with combination immunotherapy. Methods Clinical data of patients with metastatic cervical cancer treated with combination immunotherapy between June 2019 and April 2021 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the cut-off values of continuous variables, and binary logistic analysis was conducted to compare the treatment response between groups. The Kaplan–Meier method was applied for survival analysis. A Cox proportional hazards regression model was used to identify factors associated with progression-free survival (PFS). Results Seventy patients were included in this study. The cut-off values for the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) were 5.33 and 195.00 U/L, respectively. High pretreatment NLR (≥5.33) was correlated with decreased objective response rate (53.19% vs. 78.26%, p = 0.048). The survival analysis revealed that high pretreatment NLR (hazard ratio [HR] = 2.401, 95% confidence interval [CI]: 1.151–5.009, p = 0.020) and LDH level (HR = 1.987, 95% CI: 1.029–3.835, p = 0.041) were independent prognostic factors associated with short PFS. Conclusions Our study suggested that high pretreatment NLR and LDH values were independently correlated with poor survival in patients with metastatic cervical cancer treated with combination immunotherapy. Pretreatment NLR and LDH values could serve as potential biomarkers that may aid in the selection of patients who would benefit from combination immunotherapy. Further prospective studies investigating the prognostic value of NLR and LDH are warranted. Trial registration number: UHCT22008.

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.

Serum parameters as prognostic biomarkers in a real world cancer patient population treated with anti PD-1/PD-L1 therapy

Background Immune checkpoint inhibitors (ICI) are regarded as a standard of care in multiple malignancies. We hypothesized that serum parameters are of prognostic value in ICI treated patients suffering from solid tumours. Methods Data from 114 patients treated with ICIs for solid malignancies from 2015 to 2019 at the Medical University of Vienna were collected retrospectively. Data included baseline characteristics, cancer type, serum parameters such as lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (Alb) and lymphocyte counts as well as overall survival (OS) and progression free survival. Additionally, the Gustave Roussy Immune Score (GRIm score) and the Glasgow prognostic score (GPS) were calculated. Cox regression models including time-dependent effects and strata for tumour type were used. Prognostic factors were pre-selected using a relaxed LASSO approach. Results The majority of patients were male (64.9%). The most common cancer types were non-small cell lung cancer (30.7%) and renal cell carcinoma (21.9%). Increased LDH and CRP were associated with poor 6-month OS (Hazard ratios (HR)=1.16 and 1.06 per 20% LDH/CRP increase; 95% CI 1.07–1.26 and 95% CI 1.03–1.09, respectively; p < .001). Both GRIm Score and GPS had a significant influence on OS (GRIm: HR = 2.84, 95% CI 1.72–4.69; p < .001 for high vs. low; GPS HR 3.57, 95% CI 1.76–7.25; p < .001 for poor vs. good). The proportion of explained variation (PEV) of our full multivariable model was significantly higher compared to the GRIm and GPS (PEV = 29.5% vs. 14.8% and 14.65%). When grouped into quartiles according to the individual 8-weeks change, both increased LDH and CRP correlated with poor OS (LDH (p=.001) and CRP (p < .001)). Conclusion The results of this analysis suggest that serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type. Key messages In this retrospective analysis, 114 patients with solid tumours were included. The results of this analysis point out that pre-treatment LDH, CRP and albumin levels are strongly prognostic for a poor 6-month OS. In addition to that, a high GRIm-score and poor GPS were associated with a worse OS (GRIm: HR = 2.84, 95% CI 1.72–4.69; p < .001 for high vs. low; GPS HR = 3.57, 95% CI 1.76–7.25; p < .001 for poor vs. good). Pre-treatment serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type.

Clinicopathological Features and Prognostic Factors of Sinonasal Rhabdomyosarcoma.

Sinonasal rhabdomyosarcoma (RMS) is a rare soft tissue malignancy. Due to the limited cases, the clinicopathological features and prognostic factors are still not well understood. This retrospective review included eight patients with sinonasal RMS at our institution between 2004 and 2020. Patient demographics, tumor features, Intergroup Rhabdomyosarcoma Study Group (IRSG) stage and clinical group, treatment strategy, and survival rates were evaluated. Kaplan-Meier analysis and log-rank tests were performed to analyze the possible prognostic factors. We observed a predominance of male sex and alveolar-type tumor in sinonasal RMS. Nasal obstructions and neck masses were the most common symptoms. Patients with pretreatment lactate dehydrogenase (LDH) levels >400 U/l and negative immunohistochemical staining for desmin or MyoD1 had lower survival rates. In patients with sinonasal RMS, pretreatment LDH levels >400 U/l and negative immunohistochemical staining for desmin or MyoD1 may suggest a poor prognosis. These factors can not only contribute to the prediction of prognosis in patients with sinonasal RMS but also facilitate the design of more appropriate treatment strategies.

Prognostic value of lactate dehydrogenase for melanoma patients receiving anti-PD-1/PD-L1 therapy: A meta-analysis.

Background:Several studies indicate the level of pretreatment lactate dehydrogenase (LDH) may be associated with the prognosis of patients receiving immune checkpoint inhibitors targeting programmed death receptor-1 (PD-1)/programmed death ligand 1 (PD-L1) which had been reported to dramatically improve the survival of patients with advanced or metastatic melanoma; however, no consensus has been reached because the presence of controversial conclusions. This study was to perform a meta-analysis to comprehensively explore the prognostic values of LDH for melanoma patients receiving anti-PD1/PD-L1 monotherapy.Methods:A systematic electronic search in the databases of PubMed, EMBASE and the Cochrane library was performed to identify all related articles up to April, 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained to assess the prognostic values of pretreatment LDH in blood for overall survival (OS) and progression-free survival (PFS).Results:A total of 22 eligible studies involving 2745 patients were included. Of them, 19 studies with 20 results assessed the OS and the pooled analysis showed that an elevated pretreatment LDH level was significantly associated with a worse OS (HR = 2.44; 95% CI: 1.95–3.04, P < .001). Thirteen studies reported PFS and meta-analysis also revealed that a higher pretreatment LDH level predicted a significantly shorter PFS (HR, 1.61; 95% CI, 1.34–1.92; P < .001). Although heterogeneity existed among these studies, the same results were acquired in subgroup analyses based on sample size, country, study design, cut-off of LDH, type of PD-1/PD-L1 inhibitors and statistics for HRs (all HRs > 1 and P < .05).Conclusion:This meta-analysis suggests LDH may serve as a potential biomarker to identify patients who can benefit from anti-PD-1/PD-L1 and then schedule treatments.

Association between serum biomarkers CEA and LDH and response in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

BackgroundIn addition to radiological evaluation, biomarkers may be useful in providing early information on the response to treatment, and supporting clinical decision‐making. The objective of this study was to investigate carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) as biomarkers for early assessment of response in patients with advanced non‐small cell lung cancer (NSCLC) treated with platinum‐based chemotherapy.MethodsA retrospective follow‐up study was conducted from 2012 to 2017 among 593 consecutive patients with advanced NSCLC treated with first‐line platinum‐based chemotherapy in a large teaching hospital in the Netherlands. Pretreatment biomarker levels and changes from pretreatment levels were studied for association with radiologic response (partial response [PR] or complete response [CR], according to RECIST 1.1) using multivariate logistic regression, and with overall survival using COX proportional hazard modeling. Patient and disease characteristics such as age and disease stage were taken into account as potential confounding factors.ResultsDecreases in CEA and LDH (≥ 20%), particularly early in treatment, were significantly associated with better radiological response. Increases in these biomarkers (≥ 20%) and high pretreatment LDH levels (≥ 247 U/L) were significantly associated with lower overall survival.ConclusionsOur results support determination of CEA and LDH levels for earlier assessment of response to platinum‐based chemotherapy in patients with advanced NSCLC. Hence, routine determination and evaluation of CEA and LDH levels, prior to each cycle of platinum‐based chemotherapy in advanced NSCLC, should be considered as part of daily clinical practice.Key pointsSignificant findings of the study Serum biomarkers in monitoring of treatment in advanced NSCLC would be useful.CEA and LDH decrease (≥ 20%) is favorable for achieving radiological response.High LDH levels and CEA/LDH increase (≥ 20%) is associated with reduced survival. What this study adds Monitoring of CEA seems to be particularly relevant in early stage of treatment.CEA and LDH determination should be considered as part of daily clinical practice.

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.

Pretreatment lactate dehydrogenase may predict outcome of advanced non small-cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

The main aim of this study is to investigate whether baseline lactate dehydrogenase (LDH) is associated with the clinical outcome of non small‐cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). We searched Pubmed, the Cochrane Central library and Embase for peripheral blood biomarker of LDH in advanced NSCLC patients treated with ICIs. We extracted the hazard ratio (HR) with 95% confidence interval (CI) for the progression free survival (PFS) and overall survival (OS) and performed meta‐analysis of HR. Pooled estimates of treatment outcomes were calculated by stata 15.1. Six studies with 1136 patients were included in this study. The pooled results of univariate analysis suggested that an elevated pretreatment LDH level was correlated with significant shorter PFS (HR = 1.53, 95% CI 1.27‐1.83, P < 0.001) and OS (HR = 2.11, 95% CI 1.43‐3.11, P < 0.001). The association remained significant in the multivariate analysis that elevated pretreatment LDH level was associated with poor PFS (HR = 1.62, 95% CI 1.26‐2.08, P < 0.001) and OS (HR = 2.38, 95% CI 1.37‐4.12, P = 0.002). A high pretreatment LDH level was significantly correlated with shorter PFS and OS. Pretreatment LDH may serve as a predictive biomarker for advanced NSCLC patients treated with ICIs.

Prognostic Values of Systemic Inflammation Response (SIR) Parameters in Resectable Cervical Cancer.

Background:Cervical carcinoma is the leading cause of cancer mortality in women. C-reactive protein (CRP), albumin (ALB), globulin (GLB), lactate dehydrogenase (LDH), and albumin-to-globulin ratio (AGR) are indicators of systemic inflammation response correlated with tumor outcomes.Methods:This study recruited 110 patients with cervical cancer. The patients were divided into 2 groups according to pretreatment median values of CRP, ALB, GLB, LDH, and AGR. The post/preradiotherapy or post/pretreatment ratios were defined as rates of pretreatment CRP, ALB, GLB, LDH, and AGR values and the corresponding ones obtained after radiotherapy or whole treatment.Results:Higher pretreatment CRP or LDH levels were correlated with worse progression-free survival (PFS) and overall survival (OS). Increased post/preradiotherapy CRP ratio was correlated with worse PFS and OS, increased post/preradiotherapy LDH ratio was correlated with worse PFS. Increased post/pretreatment CRP ratio was correlated with worse PFS and OS, not-increased post/pretreatment AGR ratio was correlated with worse OS. Cox regression analysis model indicated that, moderately or poorly of differentiation, higher pretreatment CRP or LDH levels were independently associated with worse PFS, higher pretreatment CRP or LDH levels and increased post/pretreatment CRP ratio were independently associated with worse OS.Conclusion:CRP, LDH, or AGR are correlated with outcomes of resectable cervical cancer.

Correlation between the clinicopathological features and prognosis in patients with extranodal natural killer/T cell lymphoma

ObjectiveTo investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). MethodsOne hundred and four patients diagnosed with ENKTCL at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China from November 1991 to September 2011 were included in the study. The clinicopathological features and their correlations with disease prognosis were evaluated in these patients. ResultsThe number of effective follow-up cases was 56 (53.8%) by the end of last follow-up in October 2015. Univariate survival analysis showed that granzyme B, perforin, and Bcl-2 expression was significantly associated with a poor prognosis in ENKTCL (P = 0.033, 0.004, and 0.034, respectively), whereas platelet-derived growth factor receptor-alpha (PDGFRA) expression was significantly associated with a better prognosis (P = 0.034). Ki-67 overexpression (≥50%) was significantly associated with a poor prognosis (P = 0.017). Different treatment approaches were also associated with prognosis (P = 0.014); specifically, the efficacies of combination treatments including chemotherapy and radiotherapy, and autologous hematopoietic stem cell transplantation were significantly better than those involving radiotherapy and chemotherapy alone. Patient gender, age, tumor location, staging, the presence of B symptoms, pretreatment lactate dehydrogenase levels, and β2-microglobulin levels were not associated with the prognosis of ENKTCL (P > 0.05). However, multivariate analyses showed that the treatment approach and all the immune markers were not independent prognostic factors for ENKTCL. ConclusionGranzyme B, perforin, and Bcl-2 expression and Ki-67 overexpression (≥50%) might be adverse prognostic factors for ENKTCL, whereas PDGFRA-positivity suggested a better disease prognosis. In addition, different treatment approaches might be closely related to patient prognosis.

Effect of pretreatment serum LDH and ALP levels on the prognosis of patients with nasopharyngeal carcinoma

Objective:To investigate the effects of serum lactate dehydrogenase (LDH) and serum alkaline phosphatase (ALP) levels on the prognosis of patients with nasopharyngeal carcinoma (NPC) before treatment.Method:Three hundred and thirty nine NPC cases, who were firstly treated in our hospital from April 2006 to October 2008, were enrolled in our study. Association of overall survival (OS) rate and disease-free survival (DFS) rate with clinical characteristics (age, gender, Tclassification, Nclassification, clinicalstage, radio therapy methods, radio therapy dose, the levels of pretreatment serum LDH) were evaluated using univariate and multivariate analysis methods.Result:Univariate analysis showed that age, clinical stage, pretreatment LDH level were significantly associated with OS and DFS of NPC. And multivariate analysis revealed that age, clinical stage and pretreatment LDH level were independent factors for OS and DFS.Conclusion:Age, clinical stage and the levels of pretreatment LDH level may be independent prognostic factorsto predict recurrence and death of NPC.

Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis.

Background:Lactate dehydrogenase (LDH) as a hypoxia-regulator plays a vital role in alternative metabolic pathways of cancer cells. Numerous studies have assessed the prognostic value of elevated pretreatment LDH in malignant mesothelioma (MM). However, the results have been largely inconsistent. Hence, the aim of current study was to investigate the prognostic value of pretreatment LDH levels in patients with MM by performing a meta-analysis of relevant studies.Methods:A literature search for English language studies, which investigated the association of LDH levels with overall survival (OS) in malignant mesothelioma, was performed in the electronic databases, PubMed, Medline, Embase, and Web of Science. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated. Heterogeneity was assessed using Cochran Q and I2 statistics. Sensitivity analysis, meta-regression model, and subgroup analysis were performed to trace the source of heterogeneity, if applicable.Results:A total of 9 studies with a combined study population of 1977 patients came within the purview of this meta analysis. Pooled HR for OS in patients with high LDH level was 1.68 (95% CI = 1.36–2.00). Significant heterogeneity was observed in the included studies (I2 = 54.1%, P = 0.026). Sensitivity analysis after sequential exclusion of 1 study at a time, and meta-regression with inclusion of 6 confounding factors failed to identify the source of heterogeneity. However, in the subgroup analysis, it was found that the publication of Nojiri et al was the origin of heterogeneity. When omitted the publication of Nojiri et al, the pooled HR of the rest 8 studies was 1.83 (95% CI = 1.45–2.20, I2 = 0.0%, P = 0.723). Egger test and funnel plots excluded the possibility of publication bias affecting the results of the current meta-analysis.Conclusion:A negative association was observed between high LDH levels and poor overall survival in the current study. Our findings suggest that pretreatment LDH level could serve as a useful predictor of prognosis in patients with malignant mesothelioma.

The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis

Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis. Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment. Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH. We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.

Impact of Pre-Treatment Lactate Dehydrogenase Levels on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.

BackgroundTo investigate the impact of pre-treatment lactate dehydrogenase (LDH) levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial.MethodsThree hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX) plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS), overall survival (OS) and objective response rate.ResultsInformation on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073), whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001). In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081) and to a prolonged PFS (p= 0.028).ConclusionA high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.Trial Registration NCT01878422 ClinicalTrials.gov

560P - Impact of Pre-Treatment Lactate Dehydrogenase (Ldh) Levels on Prognosis and Bevacizumab Efficacy in Advanced Colorectal Cancer Patients

ABSTRACT Aim: As LDH and pro-angiogenesis factors are regulated by the same HIF1a-driven pathway, high lactate dehydrogenase (LDH) levels are associated with abnormal activation of the VEGF pathway. We assessed the impact of pretreatment LDH levels on the prognosis of advanced colorectal cancer (ACC) patients treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase 3 randomized trial (NCT01878422). Methods: The relationship between pre-treatment LDH and progression free (PFS) and overall survival (OS) was assessed in 376 patients randomized to receive FOLFOX4 or FOLFIRI with or without bevacizumab. PFS, OS and their 95% confidence intervals (95% CI) were calculated by the Kaplan-Meier method. Results: Information on pre-treatment LDH levels was available for 344 ACC patients; 119 had normal LDH values and 225 had an LDH above the upper limit of the normal range (abnormal LDH). At a median follow up of 36 months (range 1-65), abnormal LDH levels were predictive of a lower median PFS (8.3 months, 95% CI 7.1-8.9 versus 9.8 months, 95% CI 9.1-10.9, p= 0.003) and median OS (19.2 months, 95% CI 16.3-21.1 versus 28.0 months, 95% CI 21.4-36.6, p= 0.0003). In the bevacizumab arm, median PFS was 9.1 (95% CI 7.8-10.2) and 9.7 (95% CI 7.4-12.2) months in patients with abnormal LDH and normal LDH, respectively (p = 0.308), whereas in the chemotherapy-only arm median PFS was 7.2 (95% CI 6.5-8.5) and 9.8 (95% CI 8.9-11.5) months, respectively (p = 0.002). Median OS was significantly associated with LDH levels in both treatment arms. Chemotherapy + bevacizumab Chemotherapy Pre-treatment LDH No. of patients No. of events Median PFS (95% CI) No. of patients No. of events Median PFS (95% CI) p LDH 62 53 9.7 (7.4-12.2) 57 51 9.8 (8.9-11.5) 0.522 LDH ≥ ULN 101 98 9.1 (7.8-10.2) 124 118 7.2 (6.5-8.5) 0.108 p 0.308 0.002 Pre-treatment LDH No. of patients No. of events Median OS (95% CI) No. of patients No. of events Median OS (95% CI) p LDH 62 36 28.0 (17.8-37.6) 57 35 28.6 (21.3-38.7) 0.444 LDH ≥ ULN 101 85 15.8 (13.1-21.1) 124 101 20.2 (17.9-23.2) 0.282 p 0.015 0.007 ULN, upper limit of normal Conclusions: In our study abnormal LDH values were correlated with worse prognosis. Bevacizumab appeared to improve the PFS of this population, but not the OS. Disclosure: All authors have declared no conflicts of interest.