Measurement of HE4 six months after first-line treatment as optimal time in identifying patients at high risk of progression advanced ovarian cancer

Objectives: The objective of the study was to assess the usefulness of determining HE4 and CA125 in ovarian cancer patients, to indicate which of the measurements may be optimal in the prognosis, depending on the treatment scheme. Material end methods: The concentrations of CA125 and HE4 were performed in 70 patients with advanced ovarian cancer during I-line therapy and after treatment. The subjects were divided based on the treatment scheme: group I - primary surgery and adjuvant chemotherapy, II- neoadjuvant therapy, and surgery. Results: Multivariate analysis showed that HE4 levels six months after treatment was significantly higher in patients with disease progression. ROC analysis in the group of patients treated with neoadjuvant therapy showed that the cut-off values indicating relapse for HE4 and CA125 after six months of follow up, were > 90.4 pmol/L, > 25.6 IU/mL, respectively. In the group of patients not treated with neoadjuvant therapy, the cut-off points differentiating patients with progression were: HE4 > 79.1 pmol/L, CA125 > 30.7 IU/mL. We demonstrated significantly higher HE4 and CA125 at both 6- and 12-months follow-up in patients treated with neoadjuvant therapy. In both groups of patients, the cut-off points were lower than those proposed by the manufacturer of the kits. Conclusions: Measurement of HE4 six months after treatment may be useful in identifying patients at high risk of progression, especially when CA125 levels may be non-specifically elevated. The cut-off values indicating relapse for HE4 and CA125 after six months of follow up may be lower than the normal range

Pretreatment neutrophil to lymphocyte and platelet to lymphocyte ratios as predictive factors for the survival of cervical adenocarcinoma patients

Joanna Jonska-Gmyrek,1 Leszek Gmyrek,2 Agnieszka Zolciak-Siwinska,3 Maria Kowalska,4 Malgorzata Fuksiewicz,4 Beata Kotowicz4 1Department of Uro-oncology, Maria Sklodowska-Curie Institute – Oncology Center, Warsaw 02-781, Poland; 2Department of Gynecological Oncology, The Holy Family Hospital, Warsaw 02-544, Poland; 3Department of Brachytherapy, Maria Sklodowska-Curie Institute – Oncology Center, Warsaw 02-781, Poland; 4Laboratory of Tumor Markers, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute – Oncology Center, Warsaw 02-781, Poland Objective: Our study assessed the clinical utility and prognostic value of pretreatment hematological parameters and calculated coefficients including the platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR) in patients with cervical adenocarcinoma (CA).Materials and methods: Among 738 cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA–IV treated at our institution, 96 (13%) presented with CA histology. The blood samples, collected within 10 days before treatment, were analyzed using a Sysmex XN-2000 system. The statistical tests included Mann–Whitney U-tests, log-rank tests, and Cox regression models. The cutoff points for the calculated hematological coefficients (NLR, PLR, and MLR) were determined using the MedCalc statistical program.Results: The prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in CA was clinical stage according to FIGO classification (FIGO IIB–IV vs I–IIA) (P=0.0001; P=0.002). Among patients with FIGO stage IIB–IV treated with radiotherapy/chemoradiotherapy, an elevated PLR was a negative prognostic factor for OS (P=0.017; HR: 2.96; 95% CI: 2.069–3.853). Among all patients, an elevated pretreatment NLR was a poor prognostic factor for OS (P=0.014; HR: 2.85; 95% CI: 2.011–3.685) and RFS (P=0.049; HR: 4.0; 95% CI: 2.612–5.392). The white blood cell count (WBC) before treatment was significantly higher in patients who died during follow-up (P=0.009).Conclusion: Elevated NLR values before treatment may be associated with a shorter time of RFS and OS, while PLR index may have prognostic significance for OS in patients with advanced disease (FIGO IIB–IV). Both indexes and WBC may be a cost-effective biomarker that can be used conveniently for stratification of recurrence risk and death. Keywords: platelet to lymphocyte ratio, cervical cancer, neutrophil to lymphocyte ratio, prognostic factor

Tumour necrosis factor receptor 1 and mortality in a multi-ethnic cohort: the Northern Manhattan Study

Objective: to study the association between soluble tumour necrosis factor receptor 1 (sTNFR1) levels and mortality in the population-based Northern Manhattan Study (NOMAS). Methods: NOMAS is a multi-ethnic, community-based cohort study with mean 8.4 years of follow-up. sTNFR1 was measured using ELISA. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (HR, 95% CI) for the association of sTNFR1 with risk of all-cause mortality after adjusting for relevant confounders. Results: sTNFR1 measurements were available in 1,862 participants (mean age 69.2 ± 10.2 years) with 512 all-cause deaths. Median sTNFR1 was 2.28 ng/ml. Those with sTNFR1 levels in the highest quartile (Q4), compared with those with sTNFR1 in the lowest quartile (Q1), were at an increased risk of all-cause mortality (adjusted HR: 1.8, 95% CI: 1.4–2.4) and non-vascular mortality (adjusted HR: 2.5, 95% CI: 1.5–3.6), but not vascular mortality (adjusted HR: 1.3, 95% CI: 0.9–1.9). There were interactions between sTNFR1 quartiles and medical insurance-status [likelihood ratio test (LRT) with 3 degrees of freedom, P(interaction) = 0.02] and alcohol consumption (LRT with 3 degrees of freedom, P(interaction) < 0.01) for all-cause mortality. In participants with no insurance or Medicaid, those with sTNFR1 in the top quartile had nearly a threefold increased risk of total mortality than the lowest quartile (adjusted HR: 2.9, 95% CI: 1.9–4.4). Conclusion: in this multi-ethnic cohort, sTNFR1 was associated with all-cause and non-vascular mortality, particularly among those of a lower socioeconomic status

Why not treat human cancer with interleukin-1 blockade?

Contains fulltext : 87440.pdf (publisher's version ) (Closed access)The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1beta as an add-on therapy in human metastatic disease. In animal studies for over 20 years, IL-1 has been demonstrated to increase adherence of tumor cells to the endothelium in vitro, and administration of IL-1 to mice increases the number of metastatic colonies and tumor growth. Importantly, reducing endogenous IL-1 activity, particularly IL-1beta, with the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduces both metastasis as well as tumor burden. Inhibition of IL-1 activity prevents in vivo blood vessel formation induced by products released from hypoxic macrophages or vascular endothelial cell growth factor itself. Mice deficient in IL-1beta do not form blood vessels in matrigels embedded with vascular endothelial cell growth factor or containing products of macrophages. Recombinant IL-1Ra (anakinra) has been administered to over 1,000 patients with septic shock resulting in a consistent reduction in all-cause 28-day mortality. Approved for treatment of rheumatoid arthritis, anakinra has a remarkable safety record. Anakinra resulted in decreased blood vessels in the pannus of affected joints in patients with rheumatoid arthritis. Neutralizing monoclonal antibodies to IL-1beta and a soluble receptor to IL-1 are approved for treating chronic inflammatory diseases. Given the availability of three therapeutic agents for limiting IL-1 activity, the safety of blocking IL-1, and the clear benefit of blocking IL-1 activity in animal models of metastasis and angiogenesis, clinical trials of IL-1 blockade should be initiated, particularly as an add-on therapy of patients receiving antiangiogenesis-based therapies.1 juni 201