Clinical utility of plasma miR-371a-3p in germ cell tumors

Germ cell tumours predominantly of the testis ((T)GCTs) are remarkably chemotherapy sensitive. However, a small proportion of patients fail to be cured with cisplatin-based combination chemotherapy. miR-371a-3p is a new liquid biopsy biomarker for (T)GCTs. The aim of this study was to evaluate clinical utility of plasma miR-371a-3p level in patients starting systemic chemotherapy. Patients were included before the first cycle (N = 180) and second cycle (N = 101) of systemic first line chemotherapy, treated between July 2010 and May 2017. Plasma miR-371a-3p levels were measured with the ampTSmiR test and compared to disease characteristics and outcome. Pretreatment plasma miR-371a-3p levels were increased in 51.7% of cases and associated with number of metastatic sites, presence of lung, retroperitoneal, and mediastinal lymph node metastases, S – stage, IGCCCG risk group, and response to therapy. Patients with a negative pretreatment plasma level had better progression-free survival (PFS) and overall survival (OS) compared to patients being positive for miR-371a-3p (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.09-0.71, P = 0.02 for PFS and HR = 0.21, 95% CI 0.07-0.67, P = 0.03 for OS, respectively). Patients negative for miR-371a-3p in both samples had a superior PFS (HR = 0.10, 95% CI 0.01-21.49, P = 0.02) and OS (HR = 0.08, 95% CI 0.01-27.81, P = 0.008) compared to patients with miR-371a-3p positive in both samples (multivariate analyses were non-significant). In total 68% of the patients were S0. This study demonstrates clinical value of plasma miR-371a-3p level in chemotherapy naïve (T)GCT patients starting first line of chemotherapy to predict prognosis

Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors

BackgroundSurvivors of testicular germ cell tumors (GCT) may suffer from late cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis.MethodsGCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial translocation and dysbiosis high mobility group box-1 (HMGB-1), lipopolysaccharide, d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6).ResultsGCT survivors with higher sCD14 (above median) had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overall cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and lipopolysaccharide. Survivors treated with ≥ 400mg/m2 vs < 400mg/m2 of cisplatin-based chemotherapy had a higher lipopolysaccharide (567.8 μg/L ± 42.7 vs 462.9 μg/L ± 51.9, (p = 0.03).ConclusionssCD14 is a marker of monocytic activation by lipopolysaccharide and may also serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors within the gut-brain axis

Prognostic value of various subtypes of extracellular DNA in ovarian cancer patients

Abstract Background Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Plasma DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of extracellular DNA in advanced ovarian cancer. Methods This prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and paclitaxel, carboplatin and bevacizumab (42 pts). Thirty-five patients had optimal surgical debulking before chemotherapy. Extracellular DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts). Results Total extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p < 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16, 984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR = 0.35 (0.14–0.86)) and overall survival (HR = 0.18 (0.04–0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis. Conclusions Our data suggest that ecDNA of both, nuclear and mitochondrial origin could be added to prognostic markers in ovarian cancer. Analysis of ecDNA does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Study of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer

Опыт применения сунитиниба при метастатическом почечно-клеточном раке в Центральной и Восточной Европе: субанализ международного исследования расширенного доступа

ISSN (online): 1996-1882; ISSN (print): 1726-977

Changes in CoQ10/Lipids Ratio, Oxidative Stress, and Coenzyme Q10 during First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma (mUC)

Oxidative stress plays an important role in cancer pathogenesis, and thiobarbituric acid-reactive substance level (TBARS)&mdash;a parameter of lipid peroxidation&mdash;has prognostic significance in chemotherapy-naive patients with metastatic urothelial carcinoma (mUC). However, the effect of cisplatin (CDDP)-based chemotherapy on oxidative stress, coenzyme Q10, and antioxidants remains unknown. The objective of this prospective study was to determine possible changes in the CoQ10 (coenzyme Q10)/lipids ratio, antioxidants (&alpha;-tocopherol, &gamma;-tocopherol, &beta;-carotene, CoQ10), total antioxidant status (TAS), and TBARS in plasma at baseline and during first-line chemotherapy based on CDDP in mUC subjects. In this prospective study, 63 consecutive patients were enrolled. The median age was 66 years (range 39&ndash;84), performance status according to the Eastern Cooperative Oncology Group (ECOG) was 2 in 7 subjects (11.1%), and visceral metastases were present in 31 (49.2%) patients. Plasma antioxidants were determined by HPLC and TAS and TBARS spectrophotometrically. After two courses of chemotherapy, we recorded significant enhancements compared to baseline for total cholesterol (p &lt; 0.0216), very low-density lipoprotein (VLDL) cholesterol (p &lt; 0.002), triacylglycerols (p &lt; 0.0083), &alpha;-tocopherol (p &lt; 0.0044), and coenzyme Q10-TOTAL (p &lt; 0.0001). Ratios of CoQ10/total cholesterol, CoQ10/HDL-cholesterol, and CoQ10/LDL-cholesterol increased during chemotherapy vs. baseline (p &lt; 0.0048, p &lt; 0.0101, p &lt; 0.0032, respectively), while plasma TBARS declined (p &lt; 0.0004). The stimulation of antioxidants could be part of the defense mechanism during CDDP treatment. The increased index of CoQ10-TOTAL/lipids could reflect the effect of CDDP protecting lipoproteins from peroxidation

Delays in diagnosis and treatment of breast cancer: a multinational analysis

BACKGROUND: Reducing treatment delay improves outcomes in breast cancer. The aim of this study was to determine factors influencing patient- and system-related delays in commencing breast cancer treatment in different countries. METHODS: A total of 6588 female breast cancer patients from 12 countries were surveyed. Total delay time was determined as the sum of the patient-related delay time (time between onset of the first symptoms and the first medical visit) and system-related delay time (time between the first medical visit and the start of therapy). RESULTS: The average patient-related delay time and total delay time were 4.7 (range: 3.4-6.2) weeks and 14.4 (range: 11.5-29.4) weeks, respectively. Longer patient-related delay times were associated with distrust and disregard, and shorter patient-related delay times were associated with fear of breast cancer, practicing self-examination, higher education level, being employed, having support from friends and family and living in big cities. The average system-related delay time was 11.1 (range: 8.3-24.7) weeks. Cancer diagnosis made by an oncologist versus another physician, higher education level, older age, family history of female cancers and having a breast lump as the first cancer sign were associated with shorter system-related delay times. Longer patient-related delay times and higher levels of distrust and disregard were predictors of longer system-related delay times. CONCLUSIONS: The delay in diagnosis and treatment of breast cancer remains a serious problem. Several psychological and behavioural patient attributes strongly determine both patient-related delay time and system-related delay time, but their strength is different in particular countries