scholarly journals Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors

2021 ◽  
Vol 9 (6) ◽  
pp. e002344
Author(s):  
Daan P. Hurkmans ◽  
Sebastiaan D.T. Sassen ◽  
Karlijn de Joode ◽  
Lisanne Putter ◽  
Edwin A. Basak ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Real World ◽  
Cell Cancer ◽  
Drug Clearance ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Serum Samples ◽  
Factors Affecting ◽  
Serial Sampling ◽  
Advanced Stage Cancer

BackgroundDosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I–III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.MethodsAdvanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. A PK model was generated, covariate effects assessed and internally validated by a bootstrap procedure. PK parameters were related to overall survival (OS) and the occurrence of immune-related adverse events (irAEs).Results588 serum samples derived from 122 patients with (non-)small-cell lung cancer ([N]SCLC), malignant pleural mesothelioma (MPM), melanoma and urothelial cell cancer (UCC) were analyzed. Median follow-up was 2.2 years. A one-compartment PK model was generated: body surface area (BSA) and serum albumin had a significant effect on drug clearance (CL; covariate estimate 1.46 and −1.43, respectively), and serum lactate dehydrogenase (LDH) on the distribution volume(Vd; 0.34). A significant inverse CL–OS relationship was determined for NSCLC (HR:1.69; 95%CI1.07–2.68; p=0.024) and MPM (HR: 3.29; 95% CI 1.08 to 10.09; p=0.037), after correction for prognostic factors, which could not confirmed for melanoma (p=0.22) or UCC (p=0.34). No relationship could be determined between CL and grade >3 irAEs (p=0.70).ConclusionsHigh interpatient variability of pembrolizumab PK is determined by BSA and serum albumin (on CL) and LDH (on Vd). A strong inverse CL–OS relationship was demonstrated for NSCLC and MPM, which could not be observed for melanoma and UCC. The findings suggest that personalized dosing should be prospectively explored.

scholarly journals Commutable Calibrator with Value Assigned by the IFCC Reference Procedure to Harmonize Serum Lactate Dehydrogenase Activity Results Measured by 2 Different Methods

2008 ◽  
Vol 54 (8) ◽  
pp. 1349-1355 ◽  
Author(s):  
Giampaolo Cattozzo ◽  
Elena Guerra ◽  
Ferruccio Ceriotti ◽  
Carlo Franzini ◽  
Keyword(s):  
Total Error ◽  
Systematic Difference ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Serum Samples ◽  
Lactate Dehydrogenase Activity ◽  
Reference Procedure ◽  
Reference Limit ◽  
Quality Specifications ◽  
Upper Reference Limit

Abstract Background: The availability of commutable calibrator materials may ease considerably the task of harmonizing assay results and ensuring their traceability to reference procedures. We sought to verify the commutability of potential calibrator materials and evaluate their effectiveness in harmonizing LDH results by 2 measurement methods. Methods: We measured LDH in 109 serum samples and 31 materials, including frozen serum pools (with either normal or abnormal isoenzyme patterns), commercial stabilized materials, and the ERM-AD453/IFCC reference material. We assayed LDH activity with the IFCC reference procedure and with 2 commercial methods, 1 using the lactate-to-pyruvate (LP) reaction, and the other the pyruvate-to-lactate (PL) reaction. We selected a commutable material, with LDH value assigned by the reference procedure, as a calibrator for recalculating the results for patient sera by both LP and PL, thereby making them traceable to the IFCC reference procedure. Results: Original values for patient sera (n = 109) by the 2 commercial methods showed a mean (SD) PL/LP ratio of 1.97 (0.03); this ratio changed to 1.06 (0.02) after recalculation of results. Linear regression of PL vs LP recalibrated values gave y = 1.108x – 9.7. At the clinically important concentration of 250 U/L (upper reference limit), the systematic difference between methods was 6.8%, which met our proposed quality specifications for inaccuracy and total error. Conclusions: By properly selecting the calibrator, the results of serum LDH measurement by 2 different methods may be harmonized and made traceable to the selected highest (reference) metrological level.

scholarly journals TREATMENT OUTCOMES AND CLINICAL RELEVANCE IN PATIENTS WITH DOUBLE EXPRESSOR DLBCL

2021 ◽  
Vol 13 (1) ◽  
pp. e2021063
Author(s):  
PIMJAI NIPARUCK
Keyword(s):  
Treatment Outcomes ◽  
Clinical Presentation ◽  
Serum Lactate ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Ki 67 ◽  
Factors Affecting ◽  
Immunohistochemistry Staining ◽  
Germinal Center B Cell ◽  
High Incidence

Background: Double-expressor lymphoma (DEL) was found accounting for 20- 30% of DLBCL. We conducted this study to analyze the survival, the clinical presentation and the factors associated with treatment outcomes in DEL-DLBCL. Methods:  A retrospective study of 291 patients diagnosed with DLBCL during January 2015 - December 2018. Results: Of the 291 patients, median age was 63 years, germinal center B cell like DLBCL (GCB) and non-GCB subtypes were found in 32% and 68%, respectively. DEL was found in 46% of 264 patients with available immunohistochemistry staining for MYC protein. Patients with DEL was significantly more common in elderly patients (p= 0.017) and non-GCB subtype (p= 0.006). High serum lactate dehydrogenase (LDH) levels and high Ki-67 index were significantly found in DEL patients than those in non-DEL patients (p= 0.024 and p= 0.04, respectively).  3y-OS and 3y-DFS in DEL patients were shorter than those in non-DEL group, 58.7% versus 78.9% (p=0.026) and 58.4% versus 67.7% (p=0.343), respectively. Independent factors affecting both OS and DFS in DEL patients were ECOG 3-4, high LDH level, extranodal involvement> 1 site, DHL, high IPI and stage III-IV. Conclusions: High incidence of DEL was observed in this study, especially in patients aged 60 years or older and non-GCB subtype. Patients with DEL showed dismal DFS and OS.

Interconverting measurements of human lactate dehydrogenase activities in three buffers.

1977 ◽  
Vol 23 (2) ◽  
pp. 200-204 ◽  
Author(s):  
S N Buhl ◽  
A H Richards ◽  
K Y Jackson ◽  
R Lubinski ◽  
R E Vanderlinde
Keyword(s):  
Lactate Dehydrogenase ◽  
Analytical Method ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Normal Range ◽  
Serum Samples ◽  
Reaction Conditions ◽  
Clinical Laboratories ◽  
Wide Range ◽  
The Matrix

Abstract The lactate-to-pyruvate reaction for serum lactate dehydrogenase (LD) is most frequently assayed in one of three buffers, pyrophosphate (PPi), tris(hydroxymethyl)amino-methane (Tris), or 2-amino-2-methyl-1-propanol (AMP). We described interconverting results for serum samples and for highly purified LD isoenzymes I (dissolved in one of these matrixes) assayed in these buffers under optimized reaction conditions. The equation for converting results obtained for sera in Tris (x) to those in PPi(y) (both at 30 degrees C) is y = 0.74x+10 (n = 98). Since AMP is used extensively in Technicon procedures, we determined the LD activity of sera with an SMA 12/60, at 37 degrees C. The equation for convering these AMP results to results obtained in PPi at 30 degrees C is y = 0.45x-16 (n = 90). Very different equations were obtained with highly purified LD isoenzyme I maintained in two different matrixes and with both isoenzymes assayed in the same matrix. The matrix in which LD is dissolved and the proportion of various LD isoenzymes affect the magnitude of difference in observed LD activity under various conditions. Therefore, in clinical laboratories that use more than one analytical method or when conversion equations are used in the comparison of interlaboratory results, it is important to define the LD source, isoenzyme content, and the matrix, as well as the reaction conditions, and to use many samples with a wide range of activities when determining the conversion equations. For any changes in reagent source, substrate concentration, or alteration in procedure, a new normal range and new conversion equations should be determined.

Continuous-flow serum albumin determination by reaction with picrate ions, with use of a flow-through picrate ion electrode.

1981 ◽  
Vol 27 (3) ◽  
pp. 427-430 ◽  
Author(s):  
E P Diamandis ◽  
D S Papastathopoulos ◽  
T P Hadjiioannou
Keyword(s):  
Serum Albumin ◽  
Continuous Flow ◽  
Peak Height ◽  
Ion Concentration ◽  
Screening Tests ◽  
Albumin Concentration ◽  
Serum Samples ◽  
Factors Affecting ◽  
Analytical Recovery ◽  
Flow Through

Abstract An automated potentiometric method for serum albumin determination by use of the picrate/albumin reaction is described. A continuous-flow system and a specially designed flow-through picrate ion electrode were used in making the measurements. Various factors affecting the reaction, such as pH, picrate ion concentration, and reaction time, were studied. Peak height in millivolts and albumin concentration were linearly related in the range 10-70 g/L. Both within-run and day-to-day, the CV for the method was about 2%. Analytical recovery of albumin added to serum samples ranged from 97.0 to 110.3%, averaging 102.2%. Results compare favorably with those by the established bromcresol green method. The proposed method is suitable for routine use and for screening tests.

Stage III follicular lymphoma: durable remissions with a combined chemotherapy-radiotherapy regimen.

1987 ◽  
Vol 5 (6) ◽  
pp. 867-874 ◽  
Author(s):  
P McLaughlin ◽  
L M Fuller ◽  
W S Velasquez ◽  
J J Butler ◽  
F B Hagemeister ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Elevated Serum ◽  
Large Cell ◽  
Cell Types ◽  
Serum Lactate ◽  
Stage Iii ◽  
Serum Lactate Dehydrogenase ◽  
Factors Affecting ◽  
Combined Modality ◽  
Abdominal Disease

From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.

Serum Lactate Dehydrogenase Isoenzyme 1 and Relapse in Patients with Nonseminomatous Testicular Germ Cell Tumors Clinical Stage I

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Germ Cell ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Serum Lactate ◽  
Stage I ◽  
Serum Lactate Dehydrogenase ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dehydrogenase Isoenzyme

An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the ‘Pamerit’ study

2020 ◽  
Author(s):  
Alessandra Mosca ◽  
Ugo De Giorgi ◽  
Giuseppe Procopio ◽  
Umberto Basso ◽  
Giacomo Cartenì ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Renal Cell Cancer ◽  
Real World ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Metastatic Renal Cell Cancer ◽  
Metastatic Rcc

Abstract Objective Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Methods Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan–Meier curves, log-rank test and multivariable Cox’s models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Results Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium’s good prognosis (P < 0.001), ECOG PS 0 (P < 0.001), age (<75 years, P = 0.005), surgery (P < 0.001) and response to pazopanib (P < 0.001). After 3 months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium’s favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. Conclusions In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium’s favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium’s good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

scholarly journals The incremental value of computed tomography of COVID-19 pneumonia in predicting ICU admission

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maurizio Bartolucci ◽  
Matteo Benelli ◽  
Margherita Betti ◽  
Sara Bicchi ◽  
Luca Fedeli ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Confidence Interval ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Receiver Operating Characteristic Curves ◽  
Icu Admission ◽  
Reactive Protein ◽  
Incremental Value ◽  
Validation Set ◽  
Radiological Model

AbstractTriage is crucial for patient’s management and estimation of the required intensive care unit (ICU) beds is fundamental for health systems during the COVID-19 pandemic. We assessed whether chest computed tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient’s admission to ICU. We performed volumetric and texture analysis of the areas of the affected lung in CT of 115 outpatients with COVID-19 infection presenting to the emergency room with dyspnea and unresponsive hypoxyemia. Admission blood laboratory including lymphocyte count, serum lactate dehydrogenase, D-dimer and C-reactive protein and the ratio between the arterial partial pressure of oxygen and inspired oxygen were collected. By calculating the areas under the receiver-operating characteristic curves (AUC), we compared the performance of blood laboratory-arterial gas analyses features alone and combined with the CT features in two hybrid models (Hybrid radiological and Hybrid radiomics)for predicting ICU admission. Following a machine learning approach, 63 patients were allocated to the training and 52 to the validation set. Twenty-nine (25%) of patients were admitted to ICU. The Hybrid radiological model comprising the lung %consolidation performed significantly (p = 0.04) better in predicting ICU admission in the validation (AUC = 0.82; 95% confidence interval 0.73–0.97) set than the blood laboratory-arterial gas analyses features alone (AUC = 0.71; 95% confidence interval 0.56–0.86). A risk calculator for ICU admission was derived and is available at: https://github.com/cgplab/covidapp. The volume of the consolidated lung in CT of patients with COVID-19 pneumonia has a mild but significant incremental value in predicting ICU admission.

scholarly journals Outcomes of Adult Ewing Sarcoma Treated with Multimodality Therapy: A Single-Institute Experience

2020 ◽  
Vol 09 (04) ◽  
pp. 191-194
Author(s):  
Ravi Chandran ◽  
Siva Prasad Kuruva ◽  
Rachana Chennamaneni ◽  
Stalin Bala ◽  
Meher Lakshmi Konatam ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Ewing Sarcoma ◽  
Univariate Analysis ◽  
Lactate Dehydrogenase Level ◽  
Serum Lactate ◽  
Normal Serum ◽  
Multimodality Therapy ◽  
Serum Lactate Dehydrogenase ◽  
Common Symptom ◽  
Localized Disease

Abstract Introduction Ewing sarcoma (ES) is more common in children and relatively rare in adults. Adult ES has poor prognosis than children. Treatment approaches for adults have been extrapolated from pediatric experience. Data on adult ES are very few because of its rarity in adults. The present study was done to analyze the clinical profile and outcome of adult ES. Aims The aim was to study the clinical and pathological treatment and outcomes in adult ES. Subjects and Methods Between 2010 and 2017, a total of 73 ES patients with age more than 18 years were retrospectively analyzed. Survival analysis was done by plotting Kaplan–Meier curves. Results A total of 73 patients were diagnosed with ES during 2010 to 2017. Among them, 43 (58.9%) had localized disease with a median age of 24.5 years. Males were 44 (60.3%) and females were 29 (39.7). Pain (75.3%) was the most common symptom at presentation. Nine patients had incomplete details and were excluded from the analysis. Among 21 (28.8%) patients, the lung (61.9%) was the most common site of metastasis followed by the bone, bone marrow, and brain. The median number of chemotherapy cycles in the localized disease was 14 (range 1–17), and in metastatic disease, it was 4 (range 1–7). Univariate analysis was done with respect to age (< 25 vs. ≥25), gender, elevated or normal serum lactate dehydrogenase level, tumor size (< 8 cm versus ≥8 cm), site (axial versus extremity), and neoadjuvant chemotherapy (NACT) given or not. NACT had a significant impact on overall survival (OS) and the rest had no effect. At a median follow-up of 40 months, the 3-year OS in localized disease was 87.4%. In metastatic disease, the median OS was 13 months with 3-year OS of 26%. Conclusions Outcomes with multimodality therapy in adult ES patients with localized disease are comparable to that of a pediatric cohort. However, metastatic disease has poor survival.

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