Pre-chemotherapy Levels Research Articles

Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer.

Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation. This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples. An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007). This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).

Analysis of prognostic factors for borderline resectable pancreatic cancer after neoadjuvant chemotherapy: the importance of CA19-9 decrease in patients with elevated pre-chemotherapy CA19-9 levels

BackgroundNeoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel. MethodsFrom 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors. ResultsEighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)]. ConclusionIn patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.

Relationship between PLR and Clinicopathological Characteristics of Patients with Advanced NSCLC and Its Predictive Value for the Efficacy of Chemotherapy and Prognosis.

Objective To investigate the relationship between blood platelet-to-lymphocyte ratio (PLR) and clinicopathological characteristics of patients with advanced non-small cell lung cancer (NSCLC) and evaluate the value of PLR for predicting the efficacy of chemotherapy and prognosis. Methods The clinical data of 175 patients with advanced NSCLC diagnosed from March 2017 to December 2018 in our hospital were retrospectively analyzed, and the data of 175 healthy subjects from our hospital physical examinations were included. The platelet was detected by using a blood cell analyzer to calculate PLR. According to the average PLR value (197) before chemotherapy, 175 patients were divided into the low PLR group (=78) and the high PLR group (=97). The relationship between the expression levels of PLR and clinicopathologic features was analyzed, and the Kaplan–Meier survival curve was used to analyze the relationship between the expression levels of PLR and prognosis. Results The results showed that prechemotherapy PLR levels were significantly higher in NSCLC compared with the healthy subjects (P < 0.05). After 4 cycles of chemotherapy, the PLR levels were significantly lower than those during prechemotherapy (P < 0.05). The proportion of TNM (IV) stage cases in the low PLR group was lower than that in the high PLR group (P < 0.05). The total effective rate of the first-line chemotherapy was 46.9% (82/175). The effective rate of IIIb staging was higher than that in IV staging (P < 0.05), and the effective rate of the low PLR group was higher than that in the high PLR group (P < 0.05). Multivariate logistic analysis showed that TNM stage 4 and high PLR level were the independent risk factors for the efficacy of the first-line chemotherapy in patients with advanced NSCLC (P < 0.05), and the high PLR level was an independent risk factor affecting the prognosis of patients with advanced NSCLC. The median overall survival (OS) of patients with the low PLR group was 20.8 months, higher than the 12.0 months of patients with the high PLR group (P < 0.05). Conclusion PLR might have a certain clinical significance for predicting the TNM staging of NSCLC and can provide important diagnostic and prognostic results for patients.

Assessment of clinical utility and predictive potential of pre-chemotherapy soluble urokinase plasminogen activator receptor: Observational single center study.

Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a prerequisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and therelevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3 - 5.11). In univariate Cox regression, suPAR was predictive of shortened progression-free survival (PFS) (hazard ratio 1.065, 95% confidence interval 1.002 - 1.13; p = 0.041). There was a trend towards shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state.

Abstract LB515: Cardiovascular risk assessed by aptamer-based proteomics is increased in early breast cancer

Abstract Background: Cancer patients with a high risk for cardiovascular (CV) disease may be susceptible to cardiotoxic injury during cancer therapy. Accordingly, CV risk assessment may help in identifying candidates for preventive cardioprotective treatment. Since existing CV risk scores may lack the sensitivity and granularity to reflect the changes in CV risk that is associated with early cancer, we hypothesized that a CV risk score based on aptamer-based proteomics would permit discrimination of CV risk between patients with early breast cancer and age-, sex- and risk factor-matched healthy subjects. Moreover, we hypothesized that CV risk as assessed by aptamer-based proteomics first increases during and subsequently decreases after anthracycline-containing chemotherapy. Methods: We included 120 women with early breast cancer participating in the 2x2 factorial, randomized, placebo-controlled Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA) trial who were assigned to candesartan vs placebo and metoprolol vs placebo. Blood samples were obtained serially at: Visit 1 (ie, post-surgery but prior to epirubicin), following the first cycle of epirubicin (Visit 2), after the completion of epirubicin therapy (Visit 3), following adjuvant therapy (Visit 4), and 1-2 years after completion of adjuvant and blinded therapy (Visit 5). Age-, sex-, and risk factor-matched subjects (n = 500) from the Fenland study served as controls. We used highly multiplexed modified aptamer-based proteomics to measure ~5000 plasma proteins. A validated 27-protein CV risk model (CVD) that provides information on absolute risk of myocardial infarction, stroke, heart failure or mortality over a 4-year period was used as the dependent variable. Results: The CVD risk probability was significantly higher at Visit 1 than in the age-, sex- and risk-factor matched control group (p &amp;lt; 0.001). The CVD risk probability increased significantly from baseline to completion of epirubicin therapy (p &amp;lt; 0.001) and dropped below baseline levels for subsequent timepoints after the completion of epirubicin treatment. The mean CVD risk increased from 15.9% at Visit 2 to 24.6% at Visit 3, resulting in the percentage of subjects in the medium-high risk bin increasing from 9% at Visit 2 to 28% at Visit 3. The CVD risk distribution at the end of study was similar to the initial distribution at baseline and Visit 2. Conclusion: Using a novel CVD risk proteomics model, we observed that (1) The CVD risk of patients with early breast cancer is increased compared to age-, sex- and risk factor-matched individuals from the general population; (2) CVD risk increases during adjuvant epirubicin-containing chemotherapy, and (3) after completed adjuvant cancer therapy CVD risk returns to pre-chemotherapy level. Use of the CVD risk score may represent a novel tool to identify and monitor cancer patients who may benefit from preventive cardioprotective therapy. Citation Format: Torbjørn Omland, Jessica Chadwick, Ragnhild Røysland, Geeta Gulati, David Astling, Siri L. Heck, Victoria Vinje, Rachel Ostroff, Peter Ganz, Jürgen Geisler, Steve Williams. Cardiovascular risk assessed by aptamer-based proteomics is increased in early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB515.

A novel approach to assessing the effects of smoking on treatment response rate in muscle-invasive bladder cancer.

e16554 Background: Cigarette smoking is the strongest modifiable risk factor for bladder cancer and has been implicated in mechanisms of chemotherapy resistance. Prior studies examining tobacco exposure on chemotherapy response were limited by use of retrospective design and self-report assessment of smoking status, potentially under-estimating the association and risking bias towards the null. Cotinine is the central metabolite of nicotine and can be detected in saliva for up to 4 days after tobacco use. In this prospective cohort study, we tested the association between salivary cotinine level and pathologic response to neoadjuvant chemotherapy, assessed post-chemotherapy at the time of cystectomy, among patients with muscle-invasive bladder cancer (MIBC). Methods: Thirty-one patients with MIBC were prospectively recruited and surveyed on their smoking habits. Salivary cotinine was measured during chemotherapy using NicAlert test strips with cotinine concentration &gt; 10ng/mL indicating active smoking (cotinine = 1) and cotinine concentration &lt; 10ng/mL indicating no evidence of active tobacco use (cotinine = 0). Primary outcome was pathologic response at cystectomy, defined as complete response (pT0) or residual disease (pT1-4 or node+). For patients with prior history of tobacco use, the association between pre-chemotherapy cotinine level and post-chemotherapy response at cystectomy was assessed using a chi-squared test and an odds ratio with a 95% confidence interval (CI) using the Baptista-Pike method. Results: Thirty-one patients had cotinine levels measured during chemotherapy and 25 reported prior history of smoking. Of these 25 patients, 17 patients denied active smoking, 2 of whom had cotinine levels = 1 during chemotherapy. Response to chemotherapy by cotinine level among patients with prior history of tobacco use are shown in table 1. One patient declined cystectomy and was excluded from the analysis. The odds ratio of a complete response at cystectomy for patients with cotinine = 0 vs. cotinine = 1 was 3.86 (95% CI: 0.54-22.05) (p = 0.148). The odds ratio of residual disease with cotinine = 0 vs. cotinine = 1 was 0.26 (95% CI: 0.045-1.86) (p = 0.148). Conclusions: Prior smokers with no evidence of active tobacco use during curative chemotherapy were more than three-times as likely to demonstrate a complete response at the time of cystectomy compared to those with evidence of current tobacco use based on salivary cotinine levels. While this study was limited by a small sample size, it highlights a novel approach to tobacco use monitoring and the importance of continued smoking cessation counseling in patients with bladder cancer even after the diagnosis of cancer is made.[Table: see text]

Longitudinal Changes in Skeletal Muscle Metabolism, Oxygen Uptake, and Myosteatosis During Cardiotoxic Treatment for Early-Stage Breast Cancer

BackgroundWhile cardiotoxic chemotherapy is known to negatively impact cardiac function and hemoglobin levels, the impact on skeletal muscle has been understudied among patients. The purpose was to longitudinally characterize myosteatosis (muscle fat), skeletal muscle metabolism, and oxygen (O2) consumption during cardiotoxic chemotherapy for breast cancer.Patients and MethodsThirty-four patients with stage I-III breast cancer were enrolled before trastuzumab-containing and/or anthracycline-containing chemotherapy. We used magnetic resonance imaging to non-invasively quantify thigh myosteatosis (fat-water imaging), and lower leg metabolism (31P spectroscopy), O2 consumption (custom techniques), and peak power output during single-leg plantarflexion exercise at pre-, mid-, end-chemotherapy, and 1-year. We also measured pulmonary VO2peak and maximal leg press strength.ResultsDuring chemotherapy, VO2peak and leg press strength decreased while peak plantarflexion power output was maintained. At mid-chemotherapy, hemoglobin decreased (16%) and lower leg blood flow increased (37%) to maintain lower leg O2 delivery; exercise Pi:PCr and myosteatosis increased. Between mid- and end-chemotherapy, lower leg O2 extraction (28%) and O2 consumption (21%) increased, while plantarflexion exercise efficiency (watts/O2 consumed) decreased. At one year, VO2peak and leg press strength returned to pre-chemotherapy levels, but lower leg exercise O2 extraction, consumption and Pi:PCr, and myosteatosis remained elevated.ConclusionLower leg skeletal muscle blood flow and O2 extraction adapt to compensate for chemotherapy-related hemoglobin reduction for small muscle mass exercise but are insufficient to maintain large muscle mass exercise (pulmonary VO2peak, leg press strength). The excess O2 required to perform work, increased Pi:PCr ratio and myosteatosis together suggest suppressed fat oxidation during chemotherapy.

Dwindled serum IgG levels of Rubella, Diphtheria toxin, Hepatitis B virus and Tetanus Toxoid after chemotherapy; a report from Iranian children with malignancy

Backgrounds: Epigenetic regulation such as DNA methylation plays a major role in chromatin organization Background: Chemotherapy suppresses immunoglobulin production as a result of cell toxicity. Decreased immunoglobulin levels can result in the onset of opportunistic infections. The aim of the current study is to compare the immunoglobulin G (IgG) levels of the selected vaccine-preventable disease (VPD) before and six months after chemotherapy in a group of Iranian children with malignancies. Materials and Methods: In this interventional study, serum levels of Rubella, Diphtheria toxin, Hepatitis B virus (HBV), Tetanus Toxoid, Mumps, and Measles IgG were measured in 30 children with malignancy and previously vaccinated for these diseases. Six months after chemotherapy, serum IgG levels were reassessed and compared with their corresponding pre-chemotherapy levels. Results: In this study, 17 (56.7%) male and 13 (43.3%) female were included. The mean age was 7.69±3.09 years. After chemotherapy, Rubella IgG levels dropped from 73.88±85.11 to 56.59±72.84 IU/mL (P&lt;0.05; r= 0.956; 33.4% become serum negative (SN)). Diphtheria toxin IgG was diminished from 0.683±0.454 to 0.174±0.248 IU/mL (P&lt;0.05; r=0.601; 26.7% SN). Anti-HBV IgG showed a reduction from 46.26±101.56 to 25.56±80.49 IU/mL (p&lt;0.05; r= 0.524; 60% SN) and Anti-Tetanus Toxoid IgG fell down from 1.031±0.582 to 0.321±0.408 IU/mL (p&lt;0.05; r= 0.365; 33.4% SN). Anti-Measles and Anti-Mumps IgGs showed no significant change (p&gt;0.05). Conclusion: Pediatric chemotherapy was associated with dropped serum IgG levels of most VPDs. A good correlation was also observed between serum levels of IgG before and six months after chemotherapy. Revaccination of children with malignancies may be necessary upon declined serum IgG titers.

Real time remote symptom monitoring during chemotherapy for cancer: European multicentre randomised controlled trial (eSMART)

ObjectiveTo evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy,...

A novel nomogram based on prognostic factors for predicting venous thrombosis risk in lymphoma patients

Lymphoma-associated venous thromboembolism (VTE) can be a serious complication in lymphoma patients. We designed a nomogram as a guide to estimate the VTE risk in lymphoma patients. We retrospectively analyzed 555 Chinese lymphoma patients who were newly diagnosed at West China Hospital. The nomogram was generated based on multivariate regression coefficients. The multivariate analysis indicated that advanced clinical stage (p < .001*), Hodgkin lymphoma (p = .045*), and prechemotherapy Hb level <115 g/L (p = .01*) were independent risk factors for VTE in lymphoma patients. A calibration plot and the area under the receiver operating characteristic curve were used to validate the novel nomogram. The nomogram displayed a good C-index (0.73), and the calibration plot showed excellent agreement between the predicted and actual probabilities. The AUROC of the nomogram was 0.731, demonstrating a strong discriminatory ability. Notably, the predictive value of the nomogram was better than the Khorana risk score.

Longitudinal Dynamics of Coagulation and Angiogenesis Markers in Cancer Patients During and After Chemotherapy.

Hemostatic parameters have been investigated as molecular determinants of tumor progression. To analyze the dynamics of microparticle-associated tissue factor activity (MPTF), tissue factor antigen (TF-Ag), and angiopоietin-2 (ANG-2) in cancer patients before, during, and after active treatment and to explore their potential as biomarkers for metastatic occurrence and death. Blood for the analysis of MPTF, TF-Ag, ANG-2, and conventional hemostatic tests was sampled in 111 patients with various cancers at 4 consecutive visits: before first chemotherapy cycle, after 3 courses, at the sixth course, and 3 months after chemotherapy cessation. Patients were followed up until metastatic progression/death or the end of the study. MPTF did not change during chemotherapy, but increased significantly after treatment cessation. Total TF-Ag and ANG-2 decreased throughout active treatment. Significant drop of their levels was observed 3 months post therapy cessation. Progressive disease was significantly associated with higher pre-chemotherapy TF-Ag and fibrinogen. Elevated baseline levels of fibrinogen were associated with increased risk of shortened progression free survival. Cessation of chemotherapy is associated with significant change of hemostatic parameters. Pre-chemotherapy levels of TF-Ag and fibrinogen may be informative of disease state and prognosis.

Von Willebrand factor:antigen and ADAMTS-13 level, but not soluble P-selectin, are risk factors for the first asymptomatic deep vein thrombosis in cancer patients undergoing chemotherapy

BackgroundThere is a high incidence of deep vein thrombosis (DVT) among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is characterized by increased plasma levels of von Willebrand factor (vWF) and soluble P-selectin (sP-selectin), leading to the activation of endothelial cells and signaling cascades. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) is to control the activity of vWF and consequently the risk of thrombosis. The objective of this study was to investigate the roles of sP-selectin, vWF, and ADAMTS-13 as risk factors for the first episode of DVT in cancer patients undergoing chemotherapy.MethodsThis prospective cohort study was conducted at Dr. Kariadi Hospital, Indonesia, on 40 cancer patients. Prechemotherapy (baseline) and postchemotherapy sP-selectin, vWF antigen (vWF:Ag), and ADAMTS-13 plasma levels were determined with ELISAs before and 3 months after chemotherapy. The clinical characteristics of the patients, cancer type, cancer stage, chemotherapy regimen, ABO blood type, D-dimer level and Khorana risk score were also analyzed using logistic regression. Patients were observed for the possibility of developing DVT during chemotherapy.ResultsDVT was confirmed in 5 patients (12.5%) after a period of 3 months. In patients with DVT, sP-selectin and vWF were significantly higher while ADAMTS-13 was lower than in their counterparts. The levels of baseline vWF:Ag and ADAMTS-13, with cut-off points ≥ 2.35 IU/mL and ≤ 1.03 IU/mL, respectively, were found to independently predict the incidence of DVT. In the multivariate logistic regression analysis, the relative risk (RR) for DVT in patients with high vWF:Ag was 3.80 (95% CI 1.15–12.48, p = 0.028), and that for patients with low ADAMTS-13 was 2.67 (95% CI 1.22–23.82, p = 0.005). The vWF:Ag/ADAMTS-13 ratio and both vWF:Ag and ADAMTS-13 dynamics during treatment were also able to differentiate those with prospective DVT. However, sP-selectin and other covariates showed no statistical significance.ConclusionWe found that prechemotherapy plasma levels of vWF:Ag ≥ 2.35 IU/mL and ADAMTS-13 ≤ 1.03 IU/mL are independent risk factors for DVT incidence among cancer patients.

Plasma Heat Shock Protein 90 Alpha: A Valuable Predictor of Early Chemotherapy Effectiveness in Advanced Non-Small-Cell Lung Cancer.

BackgroundHeat shock protein-90 alpha (HSP90α) is more abundant in non-small-cell lung cancer (NSCLC) patients than in control individuals. However, whether it can reflect chemotherapy efficacy remains unknown. This study aimed to investigate the association of HSP90α with chemotherapy in advanced NSCLC.Material/MethodsWe retrospectively evaluated data from patients admitted to the Department of Respiratory Medicine, Shaoxing People’s Hospital, from September 2016 to September 2018 with stage IIIB or IV NSCLC and administered 4 cycles of third-generation platinum-based combination chemotherapy (2 drugs simultaneously). Based on the RECIST1.1 criteria, complete remission (CR), partial response (PR), and stable disease (SD) in 60 cases were determined before and after chemotherapy. Before chemotherapy and after 1, 2, and 4 cycles of chemotherapy, plasma HSP90α levels were quantitated by ELISA. Chest CT was performed before and after 2 and 4 cycles of chemotherapy.ResultsAfter 1–4 cycles of chemotherapy, plasma HSP90α levels were significantly lower than pre-chemotherapy levels (P<0.05). The sums of the longest tumor diameters after 2 and 4 cycles of chemotherapy were decreased compared with pre-chemotherapy values (P<0.05). Plasma HSP90α levels and tumor size showed no significant correlation before and after chemotherapy (r=0.244, P=0.06).ConclusionsPlasma HSP90α can be considered a valuable predictor of early chemotherapy effectiveness in advanced NSCLC, and is positively correlated with tumor remission after chemotherapy. However, plasma HSP90α level is not correlated with tumor diameter and pathological type.

Troponin trends during anthracycline chemotherapy and their correlation with cardiovascular risk scores

Abstract Background Anthracycline cardiotoxicity has been known for many years but identifying patients most at risk remains imperfect. Conventionally, standard cardiovascular risk factors including biomarkers are included in assessments. Purpose We investigated serial troponin T (Tn-t) values during anthracycline chemotherapy and correlated these with baseline patient risk factors using a validated cardiovascular risk assessment tool (QRISK3). Methods 52 patients from the ERIC-ONC study had their QRISK3 score calculated using https://qrisk.org/. ERIC-ONC (Effect of Remote Ischaemic Conditioning in ONCology) is an ongoing double-blind randomised sham-controlled study in patients receiving anthracyclines, with high sensitivity Tn-t taken before and after (within 24 hrs) each chemotherapy cycle. Results Mean age was 50±16 (range 22–80) with 42% females. Mean QRISK3 score was 6.9±7.3% (range 0.1–33.4%). 53% were non-smokers and 27% ex-smokers. 77% had no family history of premature coronary disease. 8% had hypertension and 2 patients had diabetes. Mean Tn-t at each cycle (baseline to cycle 6) was 8ng/L (n=51, range &amp;lt;3–45ng/L), 10ng/L (n=50, &amp;lt;3–48ng/L), 12ng/L (n=50, &amp;lt;3–45ng/L), 16ng/L (n=39, &amp;lt;3–64ng/L), 24ng/L (n=35, 5–99ng/L) and 32ng/L (n=33, 3–67ng/L) (Figure). Mean Tn-t at one month post chemotherapy was 39ng/L, (n=40, 5–128ng/L). There was a significant increase in Tn-t by cycle 6 (mean difference 25ng/L compared to baseline, p&amp;lt;0.001) that persisted one month after chemotherapy (mean difference 32ng/L compared to baseline, p&amp;lt;0.001). Tn-t was more commonly positive (i.e.&amp;gt;14ng/L) with each successive cycle (10% at baseline vs 73% at cycle 6). Tn-t remained positive in 75% of cases at one month. There was a moderate positive correlation (ρ=0.464, p=0.001) between QRISK3 and baseline Tn-t that became stronger by cycles 4 and 5 (cycle 4 ρ=0.555, p&amp;lt;0.001, cycle 5 ρ=0.618, p&amp;lt;0.001). At one month follow up, correlation was weaker but still present (ρ=0.513, p=0.001). Correlation of QRISK3 with troponin difference from baseline (ΔTn-t) was moderately positive only in the later cycles (ΔTn-t-cycle-3 ρ=0.25, p=0.09, ΔTn-t-cycle-5 ρ=0.521 p=0.001) and remained positive at one month post chemotherapy (ρ=0.445, p=0.005). Samples taken after each cycle (median=108 minutes for 127 samples) were not significantly different to the pre-chemotherapy levels at each cycle with a mean reduction in Tn-t of 0.82ng/L for cycle 1 (p=0.12), 1.83ng/L for cycle 2 (p=0.001), 2.36ng/L for cycle 3 (p=0.002), 1.58ng/L for cycle 4 (p=0.119), 2.58ng/L for cycle 5 (p=0.001) and 2.35ng/L for cycle 6 (p=0.101). Conclusion Troponin values increase during chemotherapy with anthracyclines and remain elevated one month after chemotherapy. QRISK3 strongly correlates with Tn-t elevations during later chemotherapy cycles and early post chemotherapy, and may be useful to identify patients at risk of cardiotoxicity. Subsequent analysis will reveal if these elevations affect clinical outcomes. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): UCH Charitable Trust Rosetrees Foundation

Can Anti-Müllerian Hormone Be a Reliable Biomarker for Assessing Ovarian Function in Women Postchemotherapy?

PurposeThe predictive value of anti-Müllerian hormone (AMH) for ovarian dysfunction postchemotherapy is controversial. This study aimed to evaluate the value of serum AMH levels clinically and theoretically.Patients, Animals, and MethodsWe detected the serum estradiol, follicular stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels in 144 premenopausal women with breast cancer receiving cyclophosphamide-based chemotherapy. The hormone levels before and postchemotherapy were compared; the correlations among the hormones and amenorrhea and menstrual recovery were analyzed. In addition, the serum AMH levels were detected randomly in 177 normal healthy women and 36 normal female C57BL/6J mice of different ages; meanwhile, the status of ovarian follicles was also examined. Furthermore, 72 Balb/c nude mice with breast cancer were randomly assigned to three groups that received different doses of cyclophosphamide (CTX) (control, 100 mg/kg, and 200 mg/kg), and the alterations in serum AMH levels and ovarian follicles were recorded and analyzed.ResultsChemotherapy-induced amenorrhea was associated with prechemotherapy AMH levels, E2 levels, and FSH levels (P < 0.0001). The recovery of menstruation was associated with prechemotherapy AMH levels (P < 0.0001), but not with E2 and FSH levels (P > 0.05). In patients with breast cancer treated with chemotherapy, the serum AMH levels did not differ significantly between the pre- and post-chemotherapy periods in patients aged <35 years (P > 0.05), whereas a dramatic reduction was detected in patients aged >35 years (P < 0.0001). In healthy women, the serum AMH levels declined sharply after 35 years of age (P < 0.0001) and remained relatively stable at a younger age. Similar results were obtained in experiments using normal mice. The cancer-bearing mice exposed to 200 mg/kg CTX exhibited a significant decline in AMH levels and a remarkable decrease in the number of primordial and growing follicles (P < 0.0001).ConclusionOur results indicate that AMH is an efficient marker for predicting postchemotherapy ovarian function exclusively in premenopausal female patients with breast cancer aged >35 years.

Association between pre-chemotherapy serum levels of vitamin D and clinicopathologic findings in gastric cancer.

Background:To examine the serum levels of vitamin D in newly diagnosed gastric cancer (GC) patients compared with normal subjects and any possible association with prognostic variables.Methods:One-hundred subjects (50 GC and 50 controls) were enrolled and serum vitamin D levels were assessed using ELISA. Based on two definitions, vitamin D was classified as a sufficient level (≥30 ng/dL) and optimal level (25-80 ng/dL). The χ2and unpaired t-test was used for data analysis with a significance level of 0.05.Results:The mean serum levels of vitamin D in patients and controls were 26.86 (±14.6) and 31.72 (±13.4), respectively (P=0.09). The prevalence of vitamin D insufficiency and deficiency was higher in GC cases than controls (P=0.045 if sufficient level ≥30 and P=0.065 if sufficient level ≥25). According to histological grade analysis, grade 3 patients (poorly differentiated) were found with significantly lower vitamin D concentrations in serum than grade 1 and 2 subjects (22.25 vs 33.29 ng/dL, P=0.021). No significant differences were observed between the two groups in pathological tumor-node-metastasis (pTNM) stages, distant metastasis, and location of the tumor.Conclusion:Higher prevalence of vitamin D insufficiency and deficiency in GC patients may reflect its role in malignancy; however, further studies are needed to confirm this relationship and any possible benefits to the patients.

Decrease of Epstein-Barr Virus Anti Early Antigen Imunoglobulin a Levels and Primary Tumor Size in PostCisplatin-Paclitaxel Chemotherapy in Nasopharyngeal Carcinoma Patients

Background: Nasopharyngeal carcinoma (NPC) associated with Epstein-Barr virus (EBV) chronic infection is a common head and neck malignancy in South China and Indonesia. Although radiation and chemotheraphy is the main theraphy, it requires repeated and invasive biopsy for pathological evaluation. Therefore, a marker is required for screening including the level of anti early antigen imunoglobin a serology level. Method: Pre-pots test, longitudinal cohort design. The PTV of 18 samples were examined using CT scan, while their serum EBV anti EA IgA level were examined using pre and post three series-cisplatin-paclitaxel chemotherapy ELISA. Results: Although there was no significant changes in the level of anti EA IgA, however we found a decrease in the mean of pre-chemotherapy anti EA IgA level from 136.49 U/ml to 124.61 U/ml. There was significant changes in the VTP in pre and post-chemotherapy (p&lt;0.05). The mean of VTP in pre-chemotherapy was 66.26 cm3 (SD-38.61 cm3), while in post-chemotherapy was 31.64 cm3 (SD-27.5 cm3). The delta mean of changes in anti EA IgA level was 11.8 U/ml and in VTP was 34.62 cm3. No correlation was found between the changes of anti EA IgA and the changes of VTP in post-chemotheraphy (p&gt;0.05). However, decreases were found in the level of EBV EA IgA and PTV in pre and post NPC patients. Conclusion: There were decreases of serum EBV EA IgA level and PTV in pre and post-chemotherapy NPC patients.

Analysis of pre-chemotherapy WBC, PLT, monocyte, hemoglobin, and MPV levels in acute myeloid leukemia patients with WT1, FLT3, or NPM gene mutations.

Effects of mutations on AML (acute myeloid leukemia) patients have been an area of clinical interest. The aim of this study was to analyze pre-chemotherapy WBC (white blood cell), platelet, monocyte, hemoglobin, and mean platelet volume (MPV) levels in acute myeloid leukemia patients with Wilms tumor 1 (WT1), FMS-like tyrosine kinase 3 (FLT3), or nucleophosmin (NPM) gene mutations, attempting to detect and compare possible differences in these values.The study included 71 patients with acute myeloid leukemia known to have WT1, FLT3, or NPM gene mutations. The patients were divided into 3 groups: FLT3-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 1), NPM-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 2), WT1-mutated AML patients with no other accompanying known mutations at the time of diagnosis (Group 3). We carried out intergroup comparisons of WBC, platelet (PLT), monocyte, hemoglobin, and MPV levels before chemotherapy.There was a statistically significant difference between the groups in terms of WBC parameters (P = .001). There were no statistically significant differences between the groups with respect to hemoglobin, platelet, and monocyte levels.Higher white blood cell counts could be observed in patients with FLT3-mutated AML.

Evaluation of Micro-RNA Levels, Apoptosis and Oxidative Stress Markers in Patients Recieving Chemotherapy.

The primary objective of this study was to compare oxidative DNA damage markers, apoptosis markers and changes in miRNA levels in patients diagnosed with cancer and treated through chemotherapy. Our secondary objective was also to evaluate tumor responses that can be determined after post-chemotherapy clinical evaluations by physical examinations, laboratory results and radiological imagings, and to compare the clinical results to oxidative stress and apoptosis markers and micro RNA levels. To do that we designed a prospective observational cross-sectional study. A total of 34 cancer patients and 27 healthy controls were included in the study from the Harran University School of Medicine Department of Oncology. Newly diagnosed chemotherapy or radiotherapy naive patients without any chronic diseases were included into the study. Patients with a poor performance status (ECOG 2 and 3) and patients who did not meet the inclusion criteria were excluded. The cancer patients received chemotherapy according to their scheduled periods. Blood samples were taken from the patients before the first chemotherapy course and before the second chemotherapy round. Patients were called for toxicity control on the 10th day after the chemotherapy. Pre-chemotherapy, post-chemotherapy and control group miR-29a expression levels, change in apoptosis markers and oxidative DNA damage markers were obtained and compared. We studied 8-hydroxy 2-deoxyguanosine, total oxidant status, total anti-oxidant status, and oxidative status index for oxidative stress markers. We studied M30 and M65 as apoptosis markers. Clinical results of efficiency of the chemotherapy was acquired and compared to biochemical markers based on chemotherapy results. Chemotherapy toxicities were recorded. As a result, we found oxidative DNA damage markers and apoptosis markers were high in the cancer group, demonstrating that oxidative DNA damage and apoptosis might play a direct or indirect role in cancer etiology. However, there were subtle differences between pre-chemotherapy and post-chemotherapy levels. Mir-29a expressions were lower in cancer patients as compared to controls. However, the expression levels were not significantly change in pre- and postchemotherapy status. Moreover, we found no relationship between clinical status of patients (progression and regression) and studied biochemical markers. Thus, checking for DNA damage markers and taking precautions to lower the levels of these markers in individuals with cancer risk may be helpful in preventing cancer.

Is there a seasonal variation of survival after systemic chemotherapy for metastatic castration-resistant prostate cancer in a rural part of North Norway?

ABSTRACT The winter darkness or polar night induces endocrine and metabolic mechanisms, which might reduce the efficacy of cancer treatment and thus contribute to shorter survival. Moreover, season-and weather-related treatment delays and irregularities might also cause reduced efficacy of anti-cancer drugs. Therefore, this study evaluated the prognostic impact of timing of chemotherapy (start during winter darkness or outside of this season), in terms of overall survival, in patients with metastatic castration-resistant prostate cancer (MCRPC) who received oncology care at the Nordland hospital Bodø. The study included 111 patients treated with first-line docetaxel chemotherapy for MCRPC. Twenty patients (18%) started their treatment during winter darkness (arbitrarily defined as ±4 weeks around 21 December). In unadjusted univariate analysis, survival was shorter in this group (median 10.2 vs. 18.9 months, p = 0.055). However, not all baseline parameters were equally distributed between the two groups. In multivariable-adjusted Cox regression analysis accounting for several confounding variables, only one factor was statistically significant: pre-chemotherapy serum lactate dehydrogenase level (a surrogate marker of disease burden). Thus, the present results suggest that seasonal variation is not a major contributor to the diverging survival outcomes observed after docetaxel chemotherapy.