Prognostic value of pretreatment serum lactate dehydrogenase level in pancreatic cancer patients

Gan, Jing; Wen-hu, Wang; Yang, Zengxi; Pan, Jiebin; Zheng, Liang; Yin, Lanning

doi:10.1097/md.0000000000013151

Cited by 27 publications

(24 citation statements)

References 43 publications

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“…Actually, serum level of LDH signi cantly increases in hypoxic condition, and serves as an indirect marker of tumor hypoxia [25]. For these reasons, the results of our study, consistent with previous reports, also suggested that an elevated serum LDH level might be associated with a poor prognosis [25,28].…”

Section: Discussionsupporting

confidence: 90%

Prognostic Nomogram for Patients With Unresectable Pancreatic Cancer Treated With Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX: Real-world Results From a Multicenter Retrospective Study (NAPOLEON study).

Shibuki

Mizuta²,

Shimokawa

et al. 2020

Preprint

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Background No reliable nomogram has been developed until date for predicting the survival in patients with unresectable pancreatic cancer undergoing treatment with gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FFX).Methods This analysis was conducted using clinical data of patients with unresectable pancreatic cancer undergoing GnP or FFX treatment obtained from a multicenter study (NAPOLEON study). A Cox proportional hazards model was used to identify the independent prognostic factors. A nomogram to predict 6-, 12-, and 18-month survival probabilities was generated, validated by using the concordance index (C-index), and calibrated by the bootstrapping method. And then, we attempted risk stratification for survival by classifying the patients according to the sum of the scores on the nomogram (total nomogram points; TNP).Results A total of 318 patients were enrolled. A prognostic nomogram was generated using data on the Eastern Cooperative Oncology Group performance status, liver metastasis, serum LDH, serum CRP, and serum CA19-9. The C-indexes of the nomogram were 0.77, 0.72 and 0.70 for 6-, 12-, and 18-month survival, respectively. The calibration plot showed optimal agreement at all points. Risk stratification based on tertiles of the TNP yielded clear separations of the survival curves. The median survival times in the low-, moderate-, and high-risk groups were 15.8, 12.8 and 7.8 months (P<0.05), respectively.Conclusions: Our nomogram is a convenient and inexpensive tool to accurately predict survival in patients with unresectable pancreatic cancer undergoing treatment with GnP or FFX, and will help clinicians in selecting appropriate therapeutic strategies for individualized management.

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Section: Discussionsupporting

confidence: 90%

Prognostic Nomogram for Patients With Unresectable Pancreatic Cancer Treated With Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX: Real-world Results From a Multicenter Retrospective Study (NAPOLEON study).

Shibuki

Mizuta²,

Shimokawa

et al. 2020

Preprint

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“…[ 58 ] Moreover, a recent meta‐analysis has shown a negative correlation between serum LDH levels in pancreatic cancer patients and overall survival, highlighting the prognostic role of this enzyme. [ 59 ] The pleiotropic effects of lactate in the TME are associated with tumor aggressiveness and include fueling tumor cells proliferation, inhibiting antitumor immunity, facilitating invasion, and promoting drug resistance. [ 60 ] In pancreatic cancer, excessive lactate production by hypoxic cancer cells has been shown to support the growth of lactate‐catabolizing normoxic cells and to favor tumor progression.…”

Section: Resultsmentioning

confidence: 99%

Stratified 3D Microtumors as Organotypic Testing Platforms for Screening Pancreatic Cancer Therapies

et al. 2021

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Cancer‐associated pancreatic stellate cells installed in periacinar/periductal regions are master players in generating the characteristic biophysical shield found in pancreatic ductal adenocarcinoma (PDAC). Recreating this unique PDAC stromal architecture and its desmoplastic microenvironment in vitro is key to discover innovative treatments. However, this still remains highly challenging to realize. Herein, organotypic 3D microtumors that recapitulate PDAC‐stroma spatial bioarchitecture, as well as its biomolecular, metabolic, and desmoplastic signatures, are bioengineered. Such newly engineered platforms, termed stratified microenvironment spheroid models – STAMS – mimic the spatial stratification of cancer‐stromal cells, exhibit a reproducible morphology and sub‐millimeter size. In culture, 3D STAMS secrete the key molecular biomarkers found in human pancreatic cancer, namely TGF‐β, FGF‐2, IL‐1β, and MMP‐9, among others. This is accompanied by an extensive desmoplastic reaction where collagen and glycosaminoglycans (GAGs) de novo deposition is observed. These stratified models also recapitulate the resistance to various chemotherapeutics when compared to standard cancer–stroma random 3D models. Therapeutics resistance is further evidenced upon STAMS inclusion in a tumor extracellular matrix (ECM)‐mimetic hydrogel matrix, reinforcing the importance of mimicking PDAC‐stroma bioarchitectural features in vitro. The 3D STAMS technology represents a next generation of biomimetic testing platforms with improved potential for advancing high‐throughput screening and preclinical validation of innovative pancreatic cancer therapies.

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“…Although there were several meta-analyses to investigate the prognostic values of pretreatment LDH level for cancer patients, [ 45 – 48 ] only 2 focused on the patients treated with ICIs: one was for non-small-cell lung cancer [ 18 ] and the other was for melanoma. [ 49 ] Also, in the study of Petrelli et al, [ 49 ] the literatures involving all ICIs (including anti-PD-1/PD-L1 monotherapy, anti-CTLA4 monotherapy and combined therapy) were integrated together for meta-analyses.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of lactate dehydrogenase for melanoma patients receiving anti-PD-1/PD-L1 therapy

Xu¹,

Zhao

Wang

et al. 2021

Medicine

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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.

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Prognostic value of pretreatment serum lactate dehydrogenase level in pancreatic cancer patients

Cited by 27 publications

References 43 publications

Prognostic Nomogram for Patients With Unresectable Pancreatic Cancer Treated With Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX: Real-world Results From a Multicenter Retrospective Study (NAPOLEON study).

Prognostic Nomogram for Patients With Unresectable Pancreatic Cancer Treated With Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX: Real-world Results From a Multicenter Retrospective Study (NAPOLEON study).

Stratified 3D Microtumors as Organotypic Testing Platforms for Screening Pancreatic Cancer Therapies

Prognostic value of lactate dehydrogenase for melanoma patients receiving anti-PD-1/PD-L1 therapy

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