S100-Beta, Melanoma-Inhibiting Activity, and Lactate Dehydrogenase Discriminate Progressive From Nonprogressive American Joint Committee on Cancer Stage IV Melanoma

1999 ◽  
Vol 17 (6) ◽  
pp. 1891-1891 ◽  
Author(s):  
Martin Deichmann ◽  
Axel Benner ◽  
Michael Bock ◽  
Andreas Jäckel ◽  
Karen Uhl ◽  
...  

PURPOSE: Monitoring advanced malignant melanoma, serum levels of S100-beta (S100β) and melanoma-inhibiting activity (MIA) were assessed for the ability to discriminate progressive from nonprogressive disease. S100β and MIA were supposed to be superior to conventional variables, such as lactate dehydrogenase (LDH) level.PATIENTS AND METHODS: Seventy-one patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer (AJCC) were included in the study. Results of restaging examinations were used as an independent reference standard for diagnosing progressive disease, and S100β, MIA, LDH level, and erythrocyte sedimentation rate (ESR) were determined in venous blood just before restaging. Sensitivities and specificities of the parameters were calculated by logistic regression analysis. Discrimination ability was assessed by Somers' Dxyrank correlation and the area under the receiver-operating characteristic curve (ROC-AUC).RESULTS: All tested serum parameters were significantly elevated in patients with progressive disease. The highest sensitivities according to the established thresholds were found for S100β and MIA (91% and 88%, respectively). LDH had the highest specificity (92%). ESR was dropped from the analysis because of low specificity. In calculating Somers' Dxyand ROC-AUC values, S100β, MIA, and LDH showed high discrimination ability. By multiple logistic regression, LDH was identified to be the only statistically significant marker for progressive disease. S100β and MIA did not provide additional significant information because of their high correlation with LDH with respect to clinical outcome.CONCLUSION: Elevated serum levels of S100β, MIA, and LDH indicate current disease progression in AJCC stage IV melanoma. LDH was the most relevant overall parameter.

2009 ◽  
Vol 19 (5) ◽  
pp. 316-320 ◽  
Author(s):  
Pierre Vereecken ◽  
Ahmad Awada ◽  
Stefan Suciu ◽  
Gilberto Castro ◽  
Renato Morandini ◽  
...  

2016 ◽  
Vol 174 (4) ◽  
pp. 823-830 ◽  
Author(s):  
A.L. Frauchiger ◽  
J. Mangana ◽  
M. Rechsteiner ◽  
H. Moch ◽  
B. Seifert ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Simona Simone ◽  
Francesca Cianciotta ◽  
Fabio Sallustio ◽  
Francesco Pesce ◽  
Giuseppe Grandaliano ◽  
...  

Abstract Background and Aims Several studies suggested an independent association between elevated Lipoprotein (a) [Lp(a)] levels and the incidence of CV events in the normal population. Lp(a) levels start to rise with decreasing glomerular filtration rate. Whether high Lp(a) serum levels may contribute to the pathogenesis of atherosclerosis or thrombosis in CKD and, particularly, in transplanted (Tx) patients is largely unclear. Furthermore, it is still uncertain to which extent very high Lp(a) levels might influence CV events in this population. Aims: 1. To evaluate Lp(a) serum concentrations and lipid profile in CKD, dialysis and Tx patients. 2. To investigate the relationship between Lp(a) serum levels and atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, coronary revascularization, cerebrovascular accident, carotid endarterectomy, peripheral revascularization, gangrene, or limb amputation. 3. To assess whether Lp(a) may have a role in thrombotic events (failure of vascular access in HD or early renal allograft thrombosis after transplantation) in these patients. Method Serum Lp(a) levels and lipid profile were assessed in 295 patients (M 172, F 123; mean age 57.3, range 19-85 years): 23 with CKD stage I-III, 76 with CKD stage IV-V, 128 on dialysis (68 hemodialysis (HD), 60 peritoneal dialysis) and 68 were kidney Tx recipients (eGFR>30 ml/min). In the latter group, Lp(a) values were assayed before and after transplantation. Lp(a) levels were determined using the Macra® Lp(a) ELISA kit (Trinity Biotech, USA). Values are expressed as median and interquartile range. Logistic regression analysis was used to determine whether Lp(a) is a risk factor for CV and thrombosis disease. The cut-off value was identified according to maximum Youden index by receiver operating characteristic (ROC) curve. Results Increased mean serum levels of LDL-C (93.85 mg/d; normal values=<70 mg/dl) were observed in all groups of patients, while HDL-C and triglycerides serum levels were in the normal range. Serum Lp(a) levels (nv=14-31 mg/dl) were significantly (p<0.001) increased in advanced CKD group (stage IV-V) (45.5, 1.5-216.5 mg/dl) and, mostly, in patients on dialysis treatment (63.2, 2.0-216.6 mg/dl, p=0.001) compared to mild-moderate CKD group (stage I-III) (32, 1.3-149 mg/dl). Lp(a) serum levels correlated significantly with age (r=0.11, p<0.05) and, inversely, with eGFR only in advanced CKD group (r=-0.21 p<0.05). A significant (-56%; p<0.001) decrease of serum Lp(a) was observed after renal Tx, while staying in HD for another year resulted in an increase in serum Lp (a) levels of about 23.7% (p<0.003). No significant relationship was found between Lp(a) values and gender, inflammation (as assessed by serum C-reactive protein levels), or diabetes. By logistic regression analysis, Lp(a) values were found to be a risk factors for ASCVD in the whole population (No events 246 pts: Lp(a) 47.8 mg/dl; Yes events 49 pts: Lp(a) 53.8 mg/dl; p=0.049) and for thrombotic events in HD group (vascular access thrombosis: 4 events) and Tx patients (early acute renal vein thrombosis after Tx: 4 events) (p=0.028). The ROC curve (AUC 0.7829, 95% CI 0.5751-0.9907) allowed us to define the cut-off value for serum Lp(a) (82.45 mg/dl) (sensitivity of 87%; specificity of 73%) as a thrombotic risk factor in HD and Tx patients. Conclusion The study confirms the relevance of Lp(a) as non-traditional CV risk factor in CKD and Tx patients predicting both, the development of ASCVD and thrombosis. Serum Lp(a) levels higher than 82.45 mg/dl are potential thrombotic risk factors for vascular access failure in HD patients or early acute renal allograft thrombosis in Tx patients, suggesting more aggressive strategies to lower Lp(a) serum levels in this patient setting.


2020 ◽  
pp. 20-31 ◽  
Author(s):  
Jan Braune ◽  
Laura Keller ◽  
Florian Schiller ◽  
Erika Graf ◽  
David Rafei-Shamsabadi ◽  
...  

PURPOSE We evaluated circulating tumor DNA (ctDNA) for detecting tumor burden in melanoma and examined whether early changes in the number of ctDNA copies predict response to treatment. PATIENTS AND METHODS We included 12 patients with stage III and 50 patients with stage IV melanoma with BRAF exon 15 or NRAS exon 3 mutations in tumor tissue. We used droplet digital polymerase chain reaction to retrospectively analyze serial plasma samples for mutation-positive ctDNA. RESULTS Matched plasma and serum samples were positive for ctDNA, lactate dehydrogenase, and S100 in 113 (45.8%), 108 (43.7%; not significant), and 58 (23.5%; P < .0001) of 247 samples from 50 patients with stage IV melanoma, and in 17 (63%), eight (29.6%; P = .014), and five (18.5%; P < .0001) of 27 samples from 12 patients with stage III melanoma. The number of mutant ctDNA copies correlated with concentrations of lactate dehydrogenase ( r = 0.50) and S100 ( r = 0.64), tumor volume ( r2 = 0.58), and tumor metabolic activity ( r2 = 0.83). Within 30 days before surgery, initiation of treatment, or change in treatment, ctDNA, LDH, and S100 were positive in 76.8%, 53.6% ( P = .01), and 46.4% ( P < .001) of patients, respectively. In patients with stage III or IV melanoma, early changes in ctDNA within 1 month after initiation of treatment correctly predicted RECIST response categories in 19 of 20 patients. Detectable ctDNA within 30 days after surgery or initiation of systemic treatment predicted inferior progression-free survival in patients with stage III disease ( P = .018). In patients with stage IV disease, 10 or more copies of ctDNA per mL at first follow-up indicated shorter progression-free survival (3.8 v 9 months; hazard ratio, 4.05; 95% CI, 1.56 to 10.53). CONCLUSION ctDNA indicated active tumor and was an adverse prognostic marker for tumor progression. Dynamic changes in ctDNA allowed prediction of response early after initiation of treatment. These data support the use of ctDNA to guide treatment in melanoma.


2016 ◽  
Vol 136 (12) ◽  
pp. 2444-2452 ◽  
Author(s):  
Benjamin Weide ◽  
Tina Schäfer ◽  
Alexander Martens ◽  
Anastasia Kuzkina ◽  
Laura Uder ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3361
Author(s):  
Matias A. Bustos ◽  
Rebecca Gross ◽  
Negin Rahimzadeh ◽  
Hunter Cole ◽  
Linh T. Tran ◽  
...  

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients’ disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients’ responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients’ and 73 normal donors’ plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors’ plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII.


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