Prognostic Marker For Survival Research Articles

Efficacy of the Nutritional Risk Index, Geriatric Nutritional Risk Index, BMI, and GLIM-Defined Malnutrition in Predicting Survival of Patients with Head and Neck Cancer Patients Qualified for Home Enteral Nutrition.

Malnutrition is a poor prognostic factor in cancer disease. In case of head and neck cancer, there are multiple disease symptoms and side effects of treatment that increase the risk of malnutrition. The aim of the study is to assess the association between nutritional status at the time of qualification for home enteral nutrition (HEN) and overall survival of patients with head and neck cancer (HNC), and assessment usefulness of selected nutritional indices as prognostic factors. The retrospective survival analysis involved 157 patients with HNC referred to HEN between January 2018 and October 2021. The nutritional status assessment was performed at the qualification for HEN visit. We have analyzed results of body mass index (BMI), Nutritional Risk Index (NRI) for patients <65 years, Geriatric Nutritional Risk Index (GNRI) for patients ≥65 years and malnutrition defined by Global Leadership Initiative on Malnutrition (GLIM). The mean patient survival was 44.7 weeks and the median was 23.9 weeks. Patients with low NRI and GNRI score had a higher risk of death (NRI: p = 0.0229; GNRI: p = 0.371). NRI, GNRI, and malnutrition defined by GLIM were superior to BMI as prognostic markers for survival. Results suggest that the use of NRI, GNRI, and GLIM criteria could provide useful prognostic information. The longer survival since the qualifying visit for home enteral nutrition suggests that nutritional management could be initiated earlier.

Correlation between leukocyte phenotypes and prognosis of amyotrophic lateral sclerosis.

The prognostic role of immune cells in amyotrophic lateral sclerosis (ALS) remains undetermined. Therefore, we conducted a longitudinal cohort study including 288 ALS patients with up to 5-year follow-up during 2015-2020 recruited at the only tertiary referral center for ALS in Stockholm, Sweden, and measured the levels of differential leukocytes and lymphocyte subpopulations. The primary outcome was risk of death after diagnosis of ALS and the secondary outcomes included functional status and disease progression rate. Cox model was used to evaluate the associations between leukocytes and risk of death. Generalized estimating equation model was used to assess the correlation between leukocytes and functional status and disease progression rate. We found that leukocytes, neutrophils, and monocytes increased gradually over time since diagnosis and were negatively correlated with functional status, but not associated with risk of death or disease progression rate. For lymphocyte subpopulations, NK cells (HR= 0.61, 95% CI = [0.42-0.88] per SD increase) and Th2-diffrentiated CD4+ central memory T cells (HR= 0.64, 95% CI = [0.48-0.85] per SD increase) were negatively associated with risk of death, while CD4+ effector memory cells re-expressing CD45RA (EMRA) T cells (HR= 1.39, 95% CI = [1.01-1.92] per SD increase) and CD8+ T cells (HR= 1.38, 95% CI = [1.03-1.86] per SD increase) were positively associated with risk of death. None of the lymphocyte subpopulations was correlated with functional status or disease progression rate. Our findings suggest a dual role of immune cells in ALS prognosis, where neutrophils and monocytes primarily reflect functional status whereas NK cells and different T lymphocyte populations act as prognostic markers for survival.

CT-defined low-skeletal muscle mass as a prognostic marker for survival in prostate cancer: A systematic review and meta-analysis.

Low-skeletal muscle mass (LSMM) is defined as progressive skeletal muscle loss, which can be assessed by imaging modalities. It was shown that this parameter is predictive and prognostic of several clinically relevant factors in several tumor entities. Our aim was to establish the effect of LSMM on overall survival (OS) in prostate cancer patients based on a large patient sample. MEDLINE library, EMBASE and SCOPUS databases were screened for the associations between LSMM and mortality in prostate cancer patients up to April 2021. The primary endpoint of the systematic review was the hazard ratio of LSMM on OS. In total, five studies were suitable for the analysis and included into the present study. The included studies comprised over all 1221 patients. The identified frequency of LSMM was 61.02%. The pooled hazard ratio for the effect of LSMM on OS was 1.4 [95% CI 0.7-2.5] in univariate analysis and was 1.6 [95% CI 1.2-2.1] in multivariate analysis. CT-defined LSMM has a frequency of 61% in patients with PC and shows a positive association with the overall survival with a hazard ratio of 1.4. LSMM assessment should therefore be included into clinical routine as a relevant prognostic biomarker.

CCL5 as a Prognostic Marker for Survival and an Indicator for Immune Checkpoint Therapies in Small Cell Lung Cancer.

The standard treatment for small cell lung cancer (SCLC) has not changed in decades. Recently, important advances have been made in immunotherapy. However, analysis of these trials suggests that only a small proportion of patients benefit from immune checkpoint blockade (ICB). Identifying these patients is a clinical challenge. In this study, we applied the ESTIMATE calculation to calculate immune scores in 159 cases of SCLC from two published cohorts. COX regression analysis was used to analyze the differentially expressed genes (DEGs) with high and low immune score. We found that CCL5 expression was positively correlated with survival in SCLC patients. In addition, we verified the effect of CCL5 on survival and response to treatment in another cohort that received immunotherapy. Meanwhile, Gene set enrichment analysis (GSEA) showed that genes with high expression of CCL5 were mainly enriched in immune-related activities. The result of Tumor Immune Dysfunction and Exclusion (TIDE) demonstrated that CCL5 was a potential biomarker to predict response to ICB for SCLC, which is correspondent with the result in verified cohort. These results suggest that CCL5 may be the reason for TME to maintain its immune dominance, making it a favorable factor for ICB. Therefore, CCL5 levels may help to outline the prognosis of patients with SCLC.

Is the presence of tumor-infiltrating lymphocytes predictive of outcomes in patients with melanoma?

The significance of tumor-infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs. The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma-specific survival (MSS). Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P < .05). The median follow-up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P < .001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values < .05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.95; P = .0154). TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered.

PLK2 Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding.

Chromosomal instability is a hallmark of gastric cancer (GC). It can be driven by single nucleotide variants (SNVs) in cell cycle genes. We investigated the associations between SNVs in candidate genes, PLK2, PLK3, and ATM, and GC risk and clinicopathological features. The genotyping study included 542 patients with GC and healthy controls. Generalized linear models were used for the risk and clinicopathological association analyses. Survival analysis was performed using the Kaplan-Meier method. The binding of candidate miRs was analyzed using a luciferase reporter assay. The PLK2 Crs15009-Crs963615 haplotype was under-represented in the GC group compared to that in the control group (Pcorr=0.050). Male patients with the PLK2 rs963615 CT genotype had a lower risk of GC, whereas female patients had a higher risk (P=0.023; P=0.026). The PLK2 rs963615 CT genotype was associated with the absence of vascular invasion (P=0.012). The PLK3 rs12404160 AA genotype was associated with a higher risk of GC in the male population (P=0.015). The ATM Trs228589-Ars189037-Grs4585 haplotype was associated with a higher risk of GC (P<0.001). The ATM rs228589, rs189037, and rs4585 genotypes TA+AA, AG+GG, and TG+GG were associated with the absence of perineural invasion (P=0.034). In vitro analysis showed that the cancer-associated miR-23b-5p mimic specifically bound to the PLK2 rs15009 G allele (P=0.0097). Moreover, low miR-23b expression predicted longer 10-year survival (P=0.0066) in patients with GC. PLK2, PLK3, and ATM SNVs could potentially be helpful for the prediction of GC risk and clinicopathological features. PLK2 rs15009 affects the binding of miR-23b-5p. MiR-23b-5p expression status could serve as a prognostic marker for survival in patients with GC.

Clinical significance of circulating tumor cells after chemotherapy in unresectable pancreatic ductal adenocarcinoma

Circulating tumor cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). A total of 52 patients with PDAC were prospectively enrolled in this study. Peripheral blood samples were serially collected at the time of diagnosis and after chemotherapy with clinical assessments. CTCs were isolated through a centrifugal microfluidic disc, enumerated with immunostaining against Epithelial cell adhesion molecule (EpCAM), Cytokeratin (CK), Plectin-1 and CD45, and identified by an automated imaging system. One or more CTCs were detected in 84.62% patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumor sizes, location and metastatic sites. The absolute number of CTCs after chemotherapy was inversely related to overall survival (OS), and the decreased number of CTCs after chemotherapy was significantly associated with longer OS in patients with PDAC. Identifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survival in patients with unresectable PDACs.

Prognostic Markers of Survival among Japanese Patients with Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer Receiving First-Line Alectinib.

The prognoses of patients with non-small-cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangement have dramatically improved with the use of ALK tyrosine kinase inhibitors. Although immunological and nutritional markers have been investigated to predict outcomes in patients with several cancers, their usefulness in targeted therapies is scarce, and their significance has never been reported in patients receiving first-line treatment with alectinib. Meanwhile, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (PLR) has been investigated during crizotinib treatment. This multicenter retrospective study evaluated 42 consecutive Japanese patients with ALK-positive NSCLC who received first-line treatment with alectinib. Immunological and nutritional markers were evaluated at baseline and 3 weeks after alectinib introduction, and their significance in predicting progression-free survival (PFS) was explored. PFS duration was significantly associated with baseline PLR (hazard ratio (HR): 2.49, p = 0.0473), systemic immune-inflammation index (SII; HR: 2.65, p = 0.0337), prognostic nutrition index (PNI; HR: 4.15, p = 0.00185), and the 3-week values for SII (HR: 2.85, p = 0.0473) and PNI (HR: 3.04, p = 0.0125). Immunological and nutritional markers could be useful in predicting the outcomes of first-line treatment with alectinib. Since PLR and SII consist of platelet counts, platelet count could be an important constituent of these markers.

Pretransplant Elevated Serum D-Dimer Level May Be A Prognostic Marker For Survival in Patients Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation

Pretransplant Elevated Serum D-Dimer Level May Be A Prognostic Marker For Survival in Patients Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation

Do diurnal changes in blood pressure affect myocardial work indices?

Do diurnal changes in blood pressure affect myocardial work indices?

Heart rate: Activity mismatch as a prognostic marker of survival in metastatic non-small cell lung cancer (NSCLC).

190 Background: Performance status (PS) is the foundation for clinical trial eligibility criteria and the basis for treatment decisions in the treatment of NSCLC, but it is limited by subjectivity and potential miscommunication between patient, physician, and family. Activity trackers use is widespread and offers the potential to collect a broad range of patient generated data (steps, activity, heart rate, calories, sleep, etc.) to supplement the assessment of PS while minimizing subjectivity. Here we evaluated a clinical observation that elevated heart rate at rest is prognostic of survival. Methods: Patients with metastatic NSCLC were asked to participate in a prospective, observational study of potential prognostic survival factors that included wearing a FitBit tracker with a goal to measure HR-Activity mismatch measured by 2 parameters: 1) Heart Rate-Activity Mismatch (HAM) by percent of time when HR is high and activity is moderate or low over a day; 2) inappropriate HR (iHR) is the ratio of time with elevated HR/sedentary minutes average over a week. Correlation and regression analyses were performed for the initial 55 patients enrolled prior to COVID restrictions using data limited to the average of 7 days with wear &gt; 500 minutes closest to date of consent. Results: We enrolled 55 patients with metastatic NSCLC. There were 35 females and 20 males with a median age of 67 years. A majority of patients were never (38%, n = 21) or former smokers (40%, n = 22); adenocarcinoma (83%, n = 83%) was the most common histology. 30% (n = 17) patients were on 2nd or greater line of therapy. 52 were included for survival analysis and 21 expired with median survival 226 days (149, NA). As average daily steps increased by 1000, the hazard of death decreased by a factor of 0.65 (95% CI: 0.45, 0.93, p = 0.018). As daily average distance increased by 1 mile, the hazard of death decreased by 0.55 (95% CI: 0.33, 0.91, p = 0.019). For HAM, the risk of death increased by 1.14 (95% CI: 1, 1.13, p = 0.046) for every 10% increase in HAM. For iHR &lt; 1 (i.e. high HR when sedentary), the risk of death was 2.84 (95% CI: 1.05, 7.67, p = 0.04) compared those with iHR &gt; 1. Steps, Distance, HAM and iHR were not statistically different by gender. Conclusions: Tracker-based measures of steps/distance and HR-Activity are prognostic of survival in NSCLC and may be useful to supplement evaluation of PS in clinical trials and practice.

Duration of Reduced CA19-9 Levels Is a Better Prognostic Factor Than Its Rate of Reduction for Unresectable Locally Advanced Pancreatic Cancer.

Simple SummaryUpon diagnosis, about 35% of patients have initially unresectable locally advanced pancreatic cancer. The prognosis of these patients is still poor. Chemotherapy alone has been generally accepted as a standard therapeutic approach. However, clinical decision-making processes have not been established for aggressive treatments such as surgery and chemoradiotherapy in patients with a response and stable case of initially unresectable locally advanced pancreatic cancer. In the current study, we evaluated the reduction rate and duration of carbohydrate antigen (CA) 19-9 within 6 months as long-term survival. Cases of over 44% CA 19-9 reduction only one month from the baseline after treatment were not significantly associated with overall survival. On the other hand, more than 3 months of over 44% CA 19-9 reduction was significantly associated with prognosis, which is the same as the occurrence of distant metastasis. Multidisciplinary treatment focus on local treatment is expected in these selected patients.A decrease in carbohydrate antigen (CA) 19-9 levels has been proposed as a prognostic marker for survival and recurrence in patients with pancreatic cancer. We evaluated the association between duration of reduced CA 19-9 levels during 6 months after treatment and long-term survival for 79 patients with unresectable locally advanced pancreatic cancer (LAPC). We calculated the differences between pretreatment and monthly CA19-9 levels. We categorized 71 patients with decreases in CA19-9 levels into three groups based on the duration of these reduced levels (>2, >3, and >4 months). The cut-off level for long-term (more than 2 years) survival was identified as a 44% reduction from the baseline, using a ROC curve. A reduction duration >2 months was not associated with overall survival (p = 0.1), while >3 months was significantly associated with survival (p =.04). In multivariate analysis, a reduction duration >3 months predicted a good long-term prognosis (odds ratio = 5.75; 95% confidence interval = 1.47–22.36; p < 0.01). In patients with unresectable LAPC, the duration of reduced CA19-9 levels for more than 3 months, rather than the rate of reduction in CA19-9 levels, during 6 months after treatment was significantly associated with good prognosis.

Programmed cell death ligand-1 expression and survival in a cohort of patients with non-small cell lung cancer receiving first-line through third-line therapy in Denmark

BackgroundPD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status. MethodsDanish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included. Data were extracted from population-based medical registries. Tumor samples from pathology archives were tested for biomarkers. High PD-L1 expression was defined as expression on ≥25 % of TCs or ICs based on first diagnostic biopsy or surgical resection. KRAS and EGFR mutation status were tested using PCR-based assays. Cox regression analysis was used to compute adjusted HRs and associated 95 % CIs. ResultsPD-L1 TC and IC ≥ 25 % were observed in 24.3 %–31.0 % and 11.7–14.7 % of patients, respectively. EGFR and KRAS mutations were detected in 4.7 %–8.8 % and 26.5 %–30.7 % of patients, respectively. PD-L1 TC ≥ 25 % was not associated with survival advantage in first- (HR = 0.96, 95 % CI: 0.75–1.22), second- (1.08, 0.81–1.42), or third-line (0.94, 0.74–1.20) therapy. PD-L1 IC ≥ 25 % was associated with survival advantage in second-line (HR = 0.56, 95 % CI: 0.36–0.86) and third-line (0.69, 0.49–0.97) but not first-line (1.00, 0.70–1.41) therapy. ConclusionNo association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.

Epidermal growth factor as a potential prognostic and predictive biomarker of response to platinum-based chemotherapy.

In this study, we investigated serum epidermal growth factor (EGF) in an oncological population of head- and neck and pulmonary neoplasms and whether serum EGF could serve as a prognostic marker of survival and as a predictive marker for treatment response to platinum-based chemotherapy. A total of 59 oncological patients and a control group of age- and sex-matched healthy volunteers were included in this study. Pre-treatment serum EGF from both groups was determined. Patient’s and tumour characteristics and mortality were recorded during a 5-year follow up period. Baseline serum EGF significantly differed between the oncological patients and the healthy volunteers (p<0.001). Serum EGF was associated with lymph node metastasis (p = 0.004) but not with sex (p = 0.753), age (p = 1.00), TNM stage (p = 0.191) or tumour size (p = 0.077). Neither serum EGF (p = 0.81) nor age (p = 0.55) showed an effect on the patient’s survival. Tumour location was significantly associated with overall 5-year survival (p = 0.003). The predictive capacity of serum EGF of response to chemotherapy was limited (AUC = 0.606), a sensitivity of 80% and a specificity of 56% was observed resulting in a likelihood ratio of a positive and negative test equal to 1.81 and 0.36, respectively. In conclusion, serum EGF levels are 5.5 times higher in an oncological population compared to a control group. Within the oncological population, low serum EGF values are associated with the presence of lymph node metastasis. Further investigation is necessary to determine if the serum EGF levels could serve as a diagnostic biomarker.

The Efficacy of Hemoglobin, Albumin, Lymphocytes, and Platelets as a Prognostic Marker for Survival in Octogenarians and Nonagenarians Undergoing Colorectal Cancer Surgery.

Objectives: With the aging population worldwide, the octogenarians are becoming a substantial group and since cancer incidence increases by age, this group of patients is becoming more affected. However, no distinct treatment algorithm has been established for elderly patients with cancer. The present study aimed to determine the prognostic value of several inflammatory parameters by comparing octogenarian patients treated surgically for colorectal cancer with their younger counterparts, as well as to predict and prevent age-related complications in this frail group of patients. Methods: The demographic and clinical data were collected from octogenarians and older people as case group (51 patients) and from a nonelderly control group of patients 65 years old or younger (88 patients). Results: The results showed that Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) values were statistically different between case and control groups. Based on the results of the receiver operating characteristic analysis performed, there was a positive correlation between HALP and survival. HALP had a significant discrimination power at the good level [AUC = 0.775 (0.696-0.854); p < 0.001]. The multivariate model showed that age groups and HALP scores were significant factors for patient survival. Conclusions: HALP biomarker was associated with the prognosis of patients treated surgically for colorectal cancer with curative intent. Furthermore, HALP score was significantly different in octogenarians compared to their younger counterparts. The newly formulated Hemoglobin, Albumin, Lymphocytes, Platelets, and Age (HALPA) appeared to be a promising biomarker of survival for elderly patients scheduled for colorectal cancer surgery.

Clinical presentation and outcome of patients with AL amyloidosis requiring salvage therapy.

e20043 Background: The diagnosis and upfront management of immunoglobulin light chain (AL) amyloidosis have greatly improved in recent years. However, little is known about the presentation, treatment, and outcome of these patients at first relapse/progression (R/P). Methods: All patients with AL amyloidosis who received salvage therapy for first R/P disease at Moffitt Cancer Center between 2008 and 2020 were included in this retrospective review. Definitions of hematologic and organ R/P were based on 2012 consensus. Overall survival was measured from the time of salvage to last follow up/death. Survival was assessed by Kaplan-Meier with log-rank comparison. Results: Sixty-nine patients were included. The median age at diagnosis was 62 years and 61% were male. Upfront therapy included high dose melphalan with autologous transplant in 36% and bortezomib in 52%. At salvage, 19% had disease refractory to upfront therapy and 40% had not achieved an organ response. The median time from upfront to salvage therapy was 22 months. Salvage regimens included proteasome inhibitors, daratumumab and immunomodulatory drugs in 55%, 13% and 22%, respectively. At least a very good partial response and organ response were achieved in 35% (22/62) and 39% (21/54) with measurable disease. The median overall survival was 60 months. Based on salvage indication, patients were classified into hematologic (n = 29) and organ R/P (n = 40), and the latter showed more frequent lambda-light chain disease (59% vs. 83%, p = 0.028) and low difference of involved-uninvolved free light chain at diagnosis (&lt; 50 mg/L, 8% vs. 44%, p = 0.002). Negative prognostic markers for survival included bone marrow plasma cells ≥20% at diagnosis (median 17 months vs. not reached; p &lt; 0.001) and organ, particularly cardiac R/P (median, 31 months vs. not reached; p = 0.003). Salvage ( p = 0.48) or prior regimens ( p = 0.11) did not impact post-salvage survival. Conclusions: Our study highlights the unmet need of salvage in R/P AL amyloidosis in a real-world setting, given the low rate of deep responses regardless of current salvage options. Patients with bone marrow plasma cells ≥20% at diagnosis and organ R/P at salvage had inferior survival, supporting use of intensive upfront regimens for the former and adjustment of therapy if deep response is not achieved.[Table: see text]

Elevated platelet count as a possible prognostic marker of survival in patients with head and neck tumours

The association between cancer-related thrombocytosis and worse survival has been described with a variety of solid neoplasms. However, only limited data are available on the prognostic significance of elevated platelet count in head and neck tumours. We aimed to investigate the correlation between the survival of patients with head and neck cancer and thrombocytosis. We conducted an analysis of the data from 312 patients with head and neck squamous cell carcinoma of various stages and locations. Preoperative platelet counts were analysed; elevated platelet count was defined as 300 G/l or higher. The influence of platelet count on survival was calculated with the Kaplan-Meier method as well as with multivariate Cox regression. In patients with excessive thrombocytosis, survival was significantly worse (overall survival: p = 0.007, disease-free survival: p = 0.192). This association remained significant even after adjusting the multivariate analysis for age, gender as well as tumour stage, grade, location, red and white blood cell count (overall survival: p = 0.027). The magnitude of thrombocytosis differed among tumours of different anatomical locations (hypopharynx: 43.6%, sub- and supraglottis: 35.8%, oral cavity: 35.7%, vocal cord: 22.5%, oropharynx: 19%, multiple: 50%), but this did not affect survival significantly (p = 0.603). Elevated platelet count may be related to a worse prognosis in head and neck squamous cell carcinoma patients. The impact of thrombocytosis does not vary with the anatomical location of the tumour. Orv Hetil. 2021; 162(17): 676-682.

Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study

IntroductionAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials.ObjectiveThis study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort.MethodsThe ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS’) was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS’ was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis.Results and conclusionsBoth ΔFS’ and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS’, is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by immune-mediated destruction of intrahepatic bile ducts and the presence of specific antibodies. The aim of the study was to examine the diagnostic significance of antibodies against promyelocytic leukemia nuclear body (PML NB) components such as Sp100, Sp140, and PML in a cohort of PBC patients and compare the results with biochemical and histological parameters. Serum samples were collected from 93 PBC patients. Anti-Sp100 and anti-PML antibodies were assessed using commercially available kits, anti-Sp140 using developed “in-house” ELISA test. Anti-Sp140, anti-Sp100, and anti-PML antibodies were present in 25 (27%), 37 (40%), and 29 (31%) PBC patients, respectively. Anti-PML NB positive patients also showed increased concentration of bilirubin and alkaline phosphatase (p < 0.05). In the group with the presence of at least two types of these antibodies, more frequent deaths or transplantations were observed. A correlation between the presence of antibodies and histological grade (OR = 2.55 p = 0.039) was established. Patients with bilirubin > 1.1 mg/dL at the time of diagnosis had a significantly shorter time of survival than patients with bilirubin ≤ 1.1 mg/dL (HR 5.7; 95% C.I., 2.7, 12.3; p < 0.001). Our data confirm very high specificity of anti-PML NB antibodies, which can expand the laboratory diagnostic capabilities of PBC. We found an association between positive reactivity of autoantibodies directed against components of PML nuclear bodies and higher concentrations of bilirubin and alkaline phosphatase, but the main prognostic marker of survival remains serum bilirubin.

Detection of Circulating Tumor Cells in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Evaluation as a Prognostic Marker.

Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.