Baseline Serum Lactate Dehydrogenase Research Articles

Cardiac biomarkers are associated with increased risks of adverse clinical outcomes after ischemic stroke.

Impaired cardiac function was suggested to be implicated in the functional recovery after ischemic stroke, but the prognostic value of cardiac biomarkers among ischemic stroke patients remains unclear. We aimed to prospectively explore the associations of serum lactate dehydrogenase (LDH), plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), and plasma high-sensitivity cardiac troponin T (hs-cTnT) with adverse clinical outcomes after ischemic stroke in a large-scale cohort study. We measured serum LDH, plasma NT-proBNP, and plasma hs-cTnT levels at baseline among 5056 ischemic stroke patients from the Minhang Stroke Cohort study. All patients were followed up at 3months after ischemic stroke onset. The primary outcome was composite outcome of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3months after stroke onset, and secondary outcomes included death and ordered 7-level categorical score of the mRS. During 3months of follow-up, 1584 patients developed the primary outcome. Baseline serum LDH, plasma NT-proBNP, and plasma hs-cTnT were positively associated with the risk of adverse outcomes after ischemic stroke. The multivariable-adjusted odds ratios of primary outcome for the highest versus lowest quartile of LDH, NT-proBNP, and hs-cTnT were 1.37 (95% CI 1.13-1.66; Ptrend = 0.001), 2.51 (95% CI, 2.00-3.16; Ptrend < 0.001), and 2.24 (95% CI 1.77-2.83; Ptrend < 0.001), respectively. Each SD increase of log-transformed cardiac biomarker score was associated with a 49% (95% CI 37-62%; P < 0.001) increased risk of primary outcome. Multivariable-adjusted spline regression analyses showed linear relationships between cardiac biomarkers and the risk of primary outcome (all P for linearity < 0.001). Moreover, adding LDH, NT-proBNP, hs-cTnT, or cardiac biomarker score to conventional risk factors significantly improved the risk reclassification of primary outcome after ischemic stroke (all P < 0.05). High LDH, NT-proBNP, hs-cTnT, and cardiac biomarker score were independently associated with increased risks of adverse clinical outcomes among ischemic stroke patients, suggesting that cardiac biomarkers might be potential prognostic biomarkers for ischemic stroke.

Efficacy of first-line chemotherapy based on primary site of tumor versus etoposide-platinum in advanced gastroenteropancreatic neuroendocrine carcinoma.

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) constitute a rare and aggressive group of malignancies usually with widespread disease. There are limited studies on GEP-NECs, and therefore, we aim to acquire more information on the clinical features, treatment regimens, and prognosis. Data from advanced GEP-NECs patients who had not previously received systemic treatment for advanced disease at The First Affiliated Hospital of Nanjing Medical University from 2010 to 2022 were retrospectively collected. Relationships between clinical-pathological features, treatment regimens, and prognosis were investigated using Kaplan-Meier curves and cox regression models. A total of fifty-four patients were enrolled in the study. The median age was 65.5 years and 79.6% were male. At diagnosis, 51.9% and 3.7% of patients developed liver and brain metastasis respectively. Sixteen (29.6%) patients received chemotherapy according to primary site of tumor (PST), while thirty-eight (70.4%) were treated with etoposide-platinum (EP) regimen, which based on the first-line treatment of advanced small cell lung cancer (SCLC). No significant differences on progression-free survival (PFS) and response rate were observed between these two groups. Univariate survival analysis showed that liver metastasis, elevated baseline serum carcinoembryonic antigen, elevated baseline serum neuron-specific enolase, elevated baseline serum lactate dehydrogenase, and elevated baseline serum neutrophil-to-lymphocyte ratio (NLR) were associated with shorter PFS. After multivariate analysis, elevated NLR was the only factor that remained significantly associated with shorter PFS (P=0.01). GEP-NECs are aggressive neoplasms, of which elevated NLR is proven to be an independent negative predictor. Treatment regimens based on PST are not inferior to regiments based on SCLC (EP) for GEP-NECs patients. Large-scale, prospective randomized controlled trials are required to establish the standard of care.

Clinical significance of serum lactate dehydrogenase combined with a multivariate model for predicting the near-term outcome of primary nasopharyngeal carcinoma

Background and objectivesThis investigation explores the clinical significance of integrating serum lactate dehydrogenase (LDH) with a multivariate model for assessing the short-term prognosis of primary nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) quantification is a crucial prognostic indicator in NPC cases, but not all patients with NPC test positive for EBV. Furthermore, widespread adoption of EBV-DNA quantification remains challenging due to its high cost. Consequently, it is imperative to incorporate additional convenient and cost-effective prognostic markers to comprehensively evaluate patient outcomes. MethodsThis retrospective analysis included 203 newly diagnosed NPC cases treated at the Affiliated Qingyuan Hospital of Guangzhou Medical University between January 2018 and March 2022. The dataset included personal information and clinical data, and the treatment protocols followed the CSCO guidelines. Efficacy assessments were based on the RECIST 1.1 criteria and were conducted after induction chemotherapy and one week and three months after radiotherapy. ResultsA noteworthy correlation emerged between baseline serum LDH levels and treatment efficacy at one week after radiotherapy (P = 0.03) and at three months after radiotherapy (P < 0.01). Additionally, a prognostic model that incorporates age (P = 0.010), LDH (P < 0.001), C-reactive protein (P = 0.010), and alkaline phosphatase (P = 0.005) demonstrated robust predictive accuracy and clinical applicability. ConclusionThis investigation substantiates the significant correlation between baseline serum LDH levels and NPC outcomes. Furthermore, we introduce a refined prognostic model that holds promise for informing personalized treatment strategies, thereby contributing to the advancement of the diagnosis of NPC.

A Clinical Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25-8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12-17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

High serum lactate dehydrogenase as a predictor of cardiac insufficiency at follow-up in elderly patients with acute myocardial infarction

BackgroundImpairment of cardiac function progresses after acute myocardial infarction (AMI). Lactate dehydrogenase (LDH), a marker of cardiac injury and an enzyme in anaerobic glycolysis, is suggested as a risk factor for patient mortality in inflammatory diseases. MethodsIn this study, 448 older and 445 younger AMI patients were recruited and followed up. The effect of baseline serum LDH on post-infarction cardiac function was assessed at follow-up. ResultsElderly patients in the high baseline LDH group had a high risk of being diagnosed with cardiac insufficiency during follow-up (adjusted hazard ratio: 3.643, P = 0.007), and the follow-up left ventricular ejection fraction of the quartile subgroup tended to decrease with increasing in baseline serum LDH (adjusted odds ratio: 1.301, P = 0.001) for each 100 U/L increase. The LVDd and LVVd of elderly patients in the high LDH group were not significantly different from those of patients in the normal LDH group at baseline but were further increased in the high LDH group at follow-up. In younger patients, the effect of LDH on post-infarction cardiac structure and function was similar to that in older patients, but unlike older patients, Cox regression analysis showed that LDH was not the predominant influence. ConclusionLongitudinal changes in cardiac function were independently associated with high baseline serum LDH levels in patients with AMI. Baseline LDH levels are superior to other myocardial injury markers and may be a useful parameter in predicting future cardiac dysfunction after AMI, especially in the elderly.

Risk Factors for and Outcomes of Follicular Lymphoma Histological Transformation at First Progression in the GALLIUM Study.

Although advanced‑stage follicular lymphoma (FL) is considered incurable, survival has improved with the introduction of the anti-CD20 antibodies, rituximab (R) and obinutuzumab (G). However, FL can undergo histological transformation (HT) to a more aggressive disease, and a validated model for predicting HT risk is not yet available. We assessed HT incidence, risk factors and outcomes in the phase III, GALLIUM study evaluating R- or G-chemotherapy in patients with previously untreated, advanced-stage FL (ClinicalTrials.gov NCT01332968). HT rates were assessed by repeat tumour biopsy at disease progression or relapse, at the investigator's discretion. Of 1202 patients enrolled, 315 (26.2%) experienced progressive disease; 46 (14.6%) had a biopsy at first progression, 40 of whom had biopsy-confirmed HT. HT risk factors were male sex (subdistribution hazard ratio [sHR], 2.21; 95% confidence interval [CI], 1.16-4.20), elevated baseline serum lactate dehydrogenase (sHR, 3.97; 95% CI, 2.03-7.76), and elevated baseline serum β2-microglobulin (sHR, 1.96; 95% CI, 1.02-3.79). Patients with HT at first progression had poorer post-progression survival than those with relapsed FL (2-year rate: 55.9% vs. 83.1%). Relapse with HT occurred earlier than FL relapse (median time from randomisation: 0.8 vs. 2.3 years). HT was a low-frequency event associated with poor survival outcomes in the GALLIUM study. Male sex and elevated baseline levels of serum LDH and B2M were significant risk factors for HT. Further research is required to develop validated prognostic indices for HT risk and guide treatment decisions.

Evaluation of lactate dehydrogenase (LDH) in predicting the severity of lung involvement and pneumomediastinum in hospitalized COVID-19

BackgroundCOVID-19 is a health crisis that triggered the need to find a rapid and sensitive tool to screen populations with a high risk of complications. Lactate dehydrogenase (LDH) is an enzyme found in almost all body cells, particularly pneumocytes, and appears to be associated with worst outcome. Pneumomediastinum (PM), which results from ruptured alveoli, can occur in non-ventilated patients. Acute pneumocytes injury induces the release of serum LDH. ObjectiveThis study evaluates the role of baseline serum LDH levels in predicting COVID-19 lung necrosis. MethodsThis retrospective study was conducted among 524 COVID-19 patients admitted to Hôtel-Dieu de France university hospital, Lebanon, between March 2020 and March 2021. Baseline serum LDH was retrieved from patients’ medical records. Radiological severity outcomes were assessed at admission and during follow-up by non-contrast computed tomography (NCCT) of the chest. ResultsThe mean age of participants was 63 ± 16 years, with 359 males (68.5%) and median (IQR) LDH levels upon admission of 328 (248–430). LDH was correlated with lobar involvement at both admission and NCCT follow-up (Spearman’s rho 0.527 and 0.264, respectively) and the development of a PM (p = 0.035) in 3% of the patients. Using ROC analysis, a baseline LDH value higher than 395 U/L was associated with the presence of a PM on admission and follow-up chest CT, with a sensitivity of 75% and a specificity of 60.1%. ConclusionBaseline LDH levels could serve as a tool for early diagnosis of severe pulmonary injury with poor radiological outcomes in hospitalized COVID-19 patients.

Serum lactate dehydrogenase in the prognostic assessment of patients with oral squamous cell carcinoma.

Lactate dehydrogenase (LDH) has been proven to be a diagnostic marker in oral squamous cell carcinoma (OSCC). However, the prognostic value of serum LDH in OSCC is yet to be explored. The purpose of this study is to correlate the level of serum LDH with the degree of OSCC and to evaluate the role of serum LDH as a prognostic marker in OSCC. The investigators designed and implemented a prospective cohort study composed of patients with OSCC (n = 66) sub-grouped as follows: 2A-well-differentiated (n = 22), 2B-moderately differentiated (n = 22), 2C-poorly differentiated OSCC (n = 22), and normal healthy controls (n = 40). The primary outcome variable was the serum LDH measured at baseline (pre-treatment) and 2 and 12 months post-treatment in OSCC patients. The statistical analysis was performed using the student t-test and analysis of variance, and the P value was set at 0.05. The habit of alcohol consumption alone as a single habit was found only in males (17.5%) (P = 0.3343), whereas betel quid chewing was more common among females (P = 0.0182). A significant difference was observed in the mean serum LDH between OSCC subjects (pre-treatment) (831.56 ± 93.43 IU/L) and controls (188.82 ± 25.53 IU/L), P < 0.00001. The baseline serum LDH was significantly higher in subgroup 2C (933.41 ± 46.1969 IU/L) than in the 2A (742.59 ± 46.5676 IU/L) and 2B (818.68 ± 58.1643 IU/L) subgroups (P = 0). There was a significant decline in the serum LDH within 2 months after treatment, and a further decrement was observed during a 12-month follow-up among the survivors of all three subgroups; P < 0.00001. Serum LDH can play a dual role as a reliable indicator of the degree of OSCC for decision-making in treatment modalities and as a prognostic marker of response to therapy.

Pembrolizumab monotherapy or combination therapy for bone metastases in advanced non-small cell lung cancer: a real-world retrospective study.

BackgroundThe incidence of bone metastases in non-small cell lung cancer (NSCLC) patients is about 30–40% and bone-related events can seriously affect quality of life. Immune checkpoint inhibitor (ICI) therapy has become the standard treatment for advanced NSCLC patients. However, the specific efficacy of ICIs in NSCLC patients with bone metastases remains unclear. The aim of the present study was to explore the prognosis of immunotherapy in this population and to find potential biomarkers.MethodsIn this retrospective study, a total of 110 advanced NSCLC patients with bone metastases who received pembrolizumab therapy were enrolled. Patient characteristics; palliative bone radiotherapy or bone-targeted therapy; serum levels of lactate dehydrogenase (LDH), and the neutrophil-to-lymphocyte ratio (NLR) at baseline were assessed. The correlation of these factors with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) was analyzed.ResultsThe ORR of the total population was 29.1%, and PFS and OS were 7.0 and 14.8 months, respectively. Fifty-eight patients (52.7%) received pembrolizumab treatment as first-line therapy, and 52 patients (47.3%) as second-line therapy or beyond [ORR: 41.4% vs. 15.4%, P=0.011; PFS: 9.0 vs. 4.0 months, P=0.004; OS: not reached (NR) vs. 11.5 months, P<0.0001]. Bone therapy, including palliative bone radiotherapy and bone-targeted therapy, increased the ORR (34.9% vs. 11.1%, P<0.0001) and prolonged PFS (8.5 vs. 2.0 months, P=0.002). Eastern Cooperative Oncology Group performance status score of 0–1 [OS: hazard ratio (HR) =0.117, P<0.0001] and first-line pembrolizumab therapy (OS: HR =0.372, P=0.004) were independent predictors of OS. Patients whose baseline serum LDH level was ≤240.5 IU/L (NR vs. 10.0 months, P<0.0001) or NLR ≤5.55 (NR vs. 18.0 months, P=0.039) showed longer OS.ConclusionsThe efficacy of Pembrolizumab therapy is confirmed in advanced NSCLC patients with bone metastases, particularly when palliative bone radiotherapy or bone-targeted therapy is delivered. Baseline serum LDH level ≤240.5 IU/L and NLR ≤5.55 might predict the prognosis of patients with bone metastases from advanced NSCLC treated with immunotherapy.

Effects of Eculizumab Treatment on the Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated in Japan

Introduction: PNH is a hematopoietic stem cell disorder with the expansion of a PIGA mutated clone(s). PNH clones are deficient in the membrane expression of GPI-anchored proteins including CD55 and CD59, which leave erythrocytes susceptible to complement attack, resulting in intravascular hemolysis. Many symptoms experienced by PNH patients such as fatigue, dyspnea, and stomachache have been found to be associated with serum free hemoglobin (Hb) released from erythrocytes by intravascular hemolysis (JAMA. 2005;293(13):1653-1662). Eculizumab (Soliris®), a humanized monoclonal antibody against Complement Factor C5, has shown dramatic effect in blocking intravascular hemolysis. Previous reports have revealed that eculizumab has not only improved anemia but also patients' quality of life (QoL) (N Engl J Med. 2006; 355: 1233-1243, Blood. 2008; 111: 1840-1847, Int J Hematol. 2011; 93: 36-46). However, factors which may be associated with improvement of QoL have yet to be fully understood. To clarify the clinical significance of QoL improvement in PNH patients treated with eculizumab, we analyzed the change in QoL in 54 PNH patients treated with eculizumab based on the data from the post-marketing surveillance (PMS) of eculizumab in Japan.Methods: All PNH patients treated with eculizumab have been registered in PMS based on the revised Pharmaceutical Affairs Law in Japan since June 2010. Of 491 patients registered as at March 2017, QoL questionnaires were obtained from 225 patients. 54 patients who received both baseline and one-year assessment of QoL were analyzed in this study. QoL was assessed using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) instruments. Summary statistics were obtained from the figures of QoL scoring systems and the lab values, and paired Student's t-test was used for the change of the values in one year from the baseline. Canonical correlation analysis was performed among QoL variates (consisted of 16 items) and lab data variates (LDH, Hb, and platelets).Results: There was no bias in the baseline characteristics between the total (491) and the analyzed (54) patients. One-year administration of eculizumab improved serum LDH level (mean: from 1435.3 to 289.5 U/L), Hb level (mean: from 8.22 to 9.46 g/dL), and QoL in most of their items in comparison with the baseline. In particular, significant improvement of EORTC QLQ-C30 was shown in the items of fatigue, dyspnea, physical function, and global health status. Canonical correlation analysis revealed a high correlation between QoL variates and lab data variates (Canonical R=0.8393, p=0.004). Of the lab data variates, LDH (Canonical correlation coefficient: -0.91) and Hb (0.76) showed strong correlations with QoL improvement as expected. Interestingly, QoL improvement was independent of patient's baseline characteristics such as the coexistence of aplastic anemia and/or myelodysplastic syndrome and the degree of lactate dehydrogenase (LDH) (Fig. 1, 2).Conclusion: In this study, QoL improvement following treatment with eculizumab was statistically strongly correlated to the degree of hemolysis, which is consistent with the previous reports. Herein we also demonstrated, for the first time, that the degree of improvement was independent of the baseline serum LDH level before eculizumab treatment and of the presence or absence of bone marrow failure. Those PNH patients without eculizumab treatment due to mild hemolysis might benefit from eculizumab treatment regardless of the presence of bone marrow failure syndromes. [Display omitted] DisclosuresUeda:Alexion Pharma GK: Honoraria, Research Funding. Obara:Alexion Pharma GK: Honoraria, Research Funding. Yonemura:Alexion Pharma GK: Honoraria, Research Funding. Noji:Alexion Pharma GK: Honoraria, Research Funding. Matsuda:Alexion Pharma G.K.: Employment. Akiyama:Alexion Pharma G.K.: Employment. Chiba:Nippon Shinyaku: Honoraria, Research Funding. Kawaguchi:Alexion Pharma G.K.: Honoraria; Novartis,Pfizer: Consultancy, Honoraria. Shichishima:Alexion Pharma GK: Honoraria. Okamoto:Bristol-Myers K.K: Honoraria; Pfizer Japan: Speakers Bureau; Alexion Pharma G.K.: Honoraria; Astellas: Honoraria; Pfizer: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Novartis: Research Funding; Bristol-Myers K.K: Research Funding. Nishimura:Alexion Pharma GK: Honoraria, Research Funding. Kanakura:Fujimotoseiyaku: Research Funding; Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding; Kyowa Hakko Kirin: Research Funding; Astellas: Research Funding; Eisai: Research Funding; Shionogi: Research Funding; Chugai Pharmaceutical: Research Funding; Nippon Shinyaku: Research Funding; Pfizer: Research Funding; Bristol Myers: Research Funding; Toyama Chemical: Research Funding. Ninomiya:Alexion Pharma GK: Honoraria.

Real Clinical Practice Data of Monthly Dupilumab Therapy in Adult Patients With Moderate-to-Severe Atopic Dermatitis: Clinical Efficacy and Predictive Markers for a Favorable Clinical Response.

PurposeDupilumab is recommended to be administered biweekly to treat adult patients with moderate-to-severe atopic dermatitis (AD). Real clinical practice data on the clinical efficacy of monthly dupilumab therapy are limited. We analyzed real clinical practice data on the clinical efficacy of monthly dupilumab therapy and predictive markers for favorable clinical responses to the therapy.MethodsMedical records of 57 adult patients with moderate-to-severe AD who received dupilumab therapy every 4 weeks for 16 weeks were analyzed retrospectively. Eczema Area and Severity Index (EASI) were recorded at baseline and week 16. Clinical responses to monthly dupilumab therapy were defined as the proportion of patients with decreased EASI scores of at least 50% or 75% from baseline at week 16 (EASI-50 or EASI-75). Blood eosinophil counts and serum lactate dehydrogenase (LDH) levels were measured at baseline and week 16.ResultsMonthly dupilumab therapy showed EASI-50 and EASI-75 clinical responses in 48 (84.2%) and 27 (47.4%) of 57 patients at week 16, respectively. The percentage decrease in EASI scores from baseline at week 16 was significantly inversely correlated with baseline blood eosinophil count (correlation coefficient [r] = −0.405, P = 0.002) and baseline serum LDH level (r = −0.466, P < 0.001). The EASI-75 response rate was higher in patients with low (< 500/µL, 73.3%) than in those with high (≥ 500/µL, 37.5%) baseline blood eosinophil counts (P = 0.032), and was higher in patients with low (< 400 U/L, 55.6%) than those with high (≥ 400 U/L, 10.0%) baseline serum LDH levels (P = 0.013).ConclusionsMonthly dupilumab therapy was clinically effective in adult patients with moderate-to-severe AD in real clinical practice. Baseline blood eosinophil count and serum LDH level could be predictive markers for clinical response to dupilumab therapy.

Integrative assessment of clinicopathological parameters and the expression of PD-L1, PD-L2 and PD-1 in tumor cells of retroperitoneal sarcoma.

Evidence is limited regarding the immunologic profile and immune microenvironment of soft tissue sarcoma subtypes. The aim of the present study was to describe the clinical significance and prognostic implications of PD-L1, PD-L2, and PD-1 in patients with retroperitoneal sarcoma (RSar). In this retrospective, multicenter, collaborative study, medical charts were reviewed and the immunohistochemical staining results of resected tissue specimens from 51 patients with RSar were examined. Immunohistochemical staining was performed with primary antibodies against PD-L1, PD-L2, PD-1, and Ki-67. The correlations between the baseline clinical parameters and expression levels of the four molecules in sarcoma cells were evaluated, and their prognostic values after tumor resection were assessed. Dedifferentiated liposarcoma (41%), leiomyosarcoma (20%), and undifferentiated pleomorphic sarcoma (16%) were the three major types identified. Dedifferentiated liposarcoma and leiomyosarcoma showed higher levels of PD-L1 expression than did other sarcomas. The Spearman correlation analysis revealed that baseline serum lactate dehydrogenase levels were moderately and positively correlated with PD-L1 (P=0.02, r=0.41) and PD-L2 (P=0.006, r=0.47) expression. The median recurrence-free and disease-specific survival was 58 and 16 months, respectively, during the 29-month median follow-up after surgery. On univariate analysis, a higher expression level of PD-1 was associated with a higher risk of recurrence, whereas multivariate analyses revealed that independent predictors of recurrence-free and disease-specific survival indicated a high expression of Ki-67 (P=0.03; hazard ratio, 2.29 vs. low expression) and prognostic stage IIIB (P=0.04; hazard ratio, 5.11 vs. stage I–II), respectively. Findings of the current study provide novel insights about the prognostic value of PD-L1, PD-L2, and PD-1 expression in RSar. Serum lactate dehydrogenase levels constitute a potential predictor of PD-L1 and PD-L2 expression levels in RSar. Further investigations are needed to determine the immunologic landscape of RSar and provide a foundation for therapeutic intervention using immune checkpoint inhibitors.

P-266 LDH levels as predictors of efficacy in second-line treatment for metastatic gastric cancer: The LINE study

Serum lactate dehydrogenase (LDH) levels are recognized as an indirect biomarker of tumor hypoxia and angiogenesis for several solid tumors. Ramucirumab represents the first molecularly targeted agent proven to be effective in second-line therapy for advanced gastric or gastro-oesophageal junction adenocarcinoma, alone or in combination with chemotherapy. However, little is known so far about potential predictive factors of benefit from antiangiogenic treatment. Thus, we conducted an observational retrospective study aimed at evaluating the possible differential prognostic impact of baseline serum LDH levels in advanced gastric cancer (GC) patients treated or not with ramucirumab in the second-line setting.

Higher baseline serum lactate dehydrogenase level is associated with poor effectiveness of dupilumab in the long term in patients with atopic dermatitis.

Dupilumab shows high efficacy and tolerable safety for the treatment of atopic dermatitis (AD). However, the extent of its effectiveness varies in individual patients. To date, practical predictors of later effectiveness of dupilumab in AD patients have not been reported. To explore practical predictors of later effectiveness of dupilumab in AD, we retrospectively investigated the correlation of baseline demographics and baseline laboratory results with the percentage reduction in Eczema Area and Severity Index (EASI) scores at 1, 3, 6 and 12months after initiating dupilumab. Furthermore, multiple regression analyses were conducted. Data were collected from patients' charts. Data on 54 Japanese adult patients (43 men and 11 women) with moderate to severe AD were analyzed. Baseline serum lactate dehydrogenase (LDH) level was negatively correlated with the percentage reduction in EASI score at 3, 6 and 12months after initiating dupilumab but not at 1month. Multiple regression analyses also revealed that effectiveness of dupilumab at 3 and 6months was associated with lower baseline serum LDH level. AD patients with allergic diseases tended to have lower percentage reduction in EASI at 1month, but had higher percentage reduction in EASI in the long term than patients without allergic diseases. In conclusion, higher baseline serum LDH level was associated with poor effectiveness of dupilumab in the long term in patients with AD. Furthermore, it tended to take a longer time for AD patients with allergic diseases to respond to dupilumab, and these patients responded better to dupilumab in the long term than patients without allergic diseases.

Can autologous stem cell transplantation abrogate the poor prognosis associated with high LDH in myeloma patients?

e19524 Background: Multiple myeloma (MM) is a plasma cell neoplasia characterized by a diffuse clonal plasma cell infiltration of the bone marrow. Serum lactate dehydrogenase (LDH) is a relevant biomarker in MM and in the era of novel agents, LDH confirmed its negative impact on survival in newly diagnosed setting (Bal et al., presented at ASH2018). Methods: This single center retrospective study included 208 patients with a diagnosis of MM who underwent ASCT at our center between January 2008 - Mart 2018 were prospectively analyzed. We identified patients with baseline serum LDH values (ULN = 247 U/L). We compare baseline characteristics and outcomes of ASCT according to LDH values. Results: All clinical data were available in 208 cases (High LDH: 92 (44.2%), Normal LDH: 116 (55.8%)) There were 87 (41.8 %) female and 87 (41.8 %) male patients. The median age at diagnosis of MM was 63 years (range, 37-77 years). The median time of follow-up was 48 months (range, 2.8-197.5 months). Of the 92 patients with high LDH who underwent ASCT, median age was 65 years and ECOG performance status was 1 and 58.6 % were male. There was no statistically differences in performance status, induction treatment regimens and the number of treatment line prior to ASCT. Induction therapy consisted of 3 drugs in 91.3% and 2 drugs in 8.7 % in high LDH group (p = NS). Forty-eight (53.3%) patients with high LDH received a bortezomib-based induction and 35 patients (40.2 %) achieved ³ very good partial remission (VGPR) after the induction therapy. During follow up, 45 relapses were occurred and all relapsed patients died. According to the long-rank test, estimated 5-year OS was not significantly different between normal and high LDH categories (63.3 %±0.6 % vs. 64.6 %±0.5 %; p = 0.99). Median PFS was 101.4 months (95% CI: 73.7-129) in high LDH group and 92.1 months (95% CI: 71.1-113.1) in normal LDH group (p = 0.99). Conclusions: Elevated LDH was confirmed as a poor prognostic factor in previous reports. In our transplanted patients with high LDH cohort, clinical outcomes are favorable and similar those have normal LDH. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant LDH levels on ASCT outcomes.

Baseline serum lactate dehydrogenase level predicts survival benefit in patients with metastatic colorectal cancer receiving bevacizumab as first-line chemotherapy: a systematic review and meta-analysis of 7 studies and 1,219 patients.

Bevacizumab, a humanized monoclonal antibody against vascular epithelial growth factor, plays a significant role in first-line, second-line, beyond-progression, and maintenance treatment of patients with metastatic colorectal carcinoma (mCRC). Nevertheless, there are currently no biomarkers available to predict patient response or resistance to bevacizumab, which would be useful in clinical trials. Using PRISMA guidelines, we conducted a systematic review and meta-analysis of the association between serum lactate dehydrogenase (LDH) level and progression-free survival (PFS), overall survival (OS), and objective response rate in mCRC patients treated with bevacizumab-based first-line chemotherapy. A comprehensive, computerized literature search of PubMed, the Web of Science, Scopus, Ovid, and the gray literature was performed. Only studies conforming to specific eligibility criteria were included. Pooled hazard ratios (HRs) were estimated using random-effects or fixed-effects models according to heterogeneity between studies. Sensitivity analysis was conducted to evaluate the stability of the results by removing each individual study from the meta-analysis. Seven eligible studies of 1,219 total patients were included in the analysis. Meta-analysis of all studies revealed that high serum LDH level is associated with shorter PFS (HR: 1.43, 95% CI: 1.05-1.94; P=0.023) and OS (HR: 1.667, 95% CI: 1.230-2.259; P=0.001) times in mCRC patients treated with bevacizumab-based first-line chemotherapy. However, there was no significant association between serum LDH and objective response rate. High serum LDH level is significantly associated with shorter PFS and OS time and may have utility as a prognostic factor for mCRC patients receiving bevacizumab as first-line chemotherapy and as a predictive factor for those receiving bevacizumab-based therapy at other times.

An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system

BackgroundThe oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. Patients and methodsIn this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). ResultsBetween March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. ConclusionsFinal results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work.

Mapping heterogeneity in glucose uptake in metastatic melanoma using quantitative 18F-FDG PET/CT analysis

BackgroundMetastatic melanoma patients can have durable responses to systemic therapy and even long-term survival. However, a large subgroup of patients does not benefit. Tumour metabolic alterations may well be involved in the efficacy of both targeted and immunotherapy. Knowledge on in vivo tumour glucose uptake and its heterogeneity in metastatic melanoma may aid in upfront patient selection for novel (concomitant) metabolically targeted therapies. The aim of this retrospective study was to provide insight into quantitative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters and corresponding intra- and inter-patient heterogeneity in tumour 18F-FDG uptake among metastatic melanoma patients. Consecutive, newly diagnosed stage IV melanoma patients with a baseline 18F-FDG PET/CT scan performed between May 2014 and December 2015 and scheduled to start first-line systemic treatment were included. Volume of interests (VOIs) of all visible tumour lesions were delineated using a gradient-based contour method, and standardized uptake values (SUVs), metabolically active tumour volume (MATV) and total lesion glycolysis (TLG) were determined on a per-lesion and per-patient basis. Differences in quantitative PET parameters were explored between patient categories stratified by BRAFV600 and RAS mutational status, baseline serum lactate dehydrogenase (LDH) levels and tumour programmed death-ligand 1 (PD-L1) expression.ResultsIn 64 patients, 1143 lesions ≥ 1 ml were delineated. Median number of lesions ≥ 1 ml was 6 (range 0–168), median maximum SUVpeak 9.5 (range 0–58), median total MATV 29 ml (range 0–2212) and median total TLG 209 (range 0–16,740). Per-patient analysis revealed considerable intra- and inter-patient heterogeneity. Maximum SUVs, MATV, number of lesions and TLG per patient did not differ when stratifying between BRAFV600 or RAS mutational status or PD-L1 expression status, but were higher in the patient group with elevated LDH levels (> 250 U/l) compared to the group with normal LDH levels (P < 0.001). A subset of patients with normal LDH levels also showed above median tumour 18F-FDG uptake.ConclusionsBaseline tumour 18F-FDG uptake in stage IV melanoma is heterogeneous, independent of mutational status and cannot be fully explained by LDH levels. Further investigation of the prognostic and predictive value of quantitative 18F-FDG PET parameters is of interest.

Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.

Ipilimumab was the first immunotherapy approved for metastatic melanoma in decades and is currently registered as a second-line treatment. However, new immunotherapies, in combination with ipilimumab, offer even better clinical outcomes for patients compared with single-agent treatments, at the expense of improved toxicity. The aim of this study was to evaluate the feasibility of ipilimumab outside the clinical trials and to identify survival predictors for treatment benefit. Data were collected on 47 advanced melanoma patients treated with ipilimumab between 2010 and 2015 at a single center. Association of clinical characteristics (including primary tumor characteristics), serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil, lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte ratio with toxicity and clinical outcome were assessed using univariate and multivariate analysis. Median progression-free survival at a median follow-up of 10months was 2.7months and median overall survival was 9.8months. Objective response was observed in 17% of patients and the disease control rate at week 24 was 40%. The 1- and 2-year survival rates documented were 40 and 28%, respectively. Significant association between high LDH level (>1.5× upper limit of normal) and decreased overall survival was demonstrated in uni- and multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p = 0.019). Neither biomarkers nor clinical outcome were associated with toxicity. Using baseline serum LDH to identify patients most likely to benefit from ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical outcome.

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

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). Data were retrospectively collected from Shanghai Health Information Network. Patients primarily diagnosed as ED-SCLC from April 2011 to August 2014 were eligible for our study. Patients' survival status was checked in March 2016. A multivariate Cox proportional hazard model was used to detect the association between baseline serum LDH and overall survival. The corresponding continuous relationship was analyzed by using natural spline functions in the Cox model. A total of 132 eligible ED-SCLC patients were analyzed. Elevated LDH at baseline was associated with poor survival (HR =1.92; 95% CI, 1.29-2.86). 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). 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.