Renal cancer.

Approximately 1,000 patients are being diagnosed with renal cell carcinoma in Denmark each year, and 20% of these are metastatic at diagnosis. Renal mass biopsies, developing the diagnostic images improve the diagnosis process. Nephron sparing surgery has been the golden standard for the last decade. Robotic/laparoscopic surgery and ablation therapy have shortened the post-hospital stay and led to a faster recovery. Tyrosine kinase inhibitors and immunotherapy has improved overall survival in the last decade. Despite these great advances, more research is needed to achieve further improvement.

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer.

Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in patients with recurrent EOC. DNA was purified from 4 mL plasma and, following bilsulfite conversion, meth-HOXA9 was analyzed using a methylation-specific droplet digital PCR. Detection of meth-HOXA9 was reported as a percentage of total DNA and as a binary variable (detectable and undetectable). Meth-HOXA9 status and its dynamics during palliative treatment were correlated with overall survival (OS) as the primary endpoint. At baseline, meth-HOXA9 was detected in 65.9% (83/126) of the patients. The median OS was 8.9 and 17.9 months in patients with detectable and undetectable meth-HOXA9 at baseline (hazard ratio: 2.04, p = 0.002), which remained significant in the multivariate analysis. Median OS in patients with an increase in meth-HOXA9 after one treatment cycle was 5.3 months compared to 33 months in patients with undetectable meth-HOXA9 (p < 0.001). Meth-HOXA9 was significantly related to poor survival and may serve as a prognostic marker in patients with recurrent EOC. The longitudinal monitoring of meth-HOXA9 is clinically feasible with the perspective of aiding clinical decision making.

Blood natural killer cells during treatment in recurrent ovarian cancer.

OBJECTIVE: Recent research indicated favorable prognostic impact of intratumoral natural killer (NK) cells in ovarian carcinoma (OC). The role of NK cells during chemotherapy in OC is unknown. We investigated impact of NK cells in OC patients treated with palliative chemotherapy. METHODS: Participants receiving palliative chemotherapy for recurrent OC (N = 72) had prospectively blood samples at baseline and before cycle 2. NK cell counts were quantified by flow cytometry. NK cell activity was measured by the NK Vue® assay, estimating interferon-gamma production. Overall survival (OS) was the primary endpoint. Cutoffs were predefined, NK numbers (≥184 × 106 cells/L vs. <184 × 106 cells/L) and NK activity (<200 pg/mL vs. ≥200 pg/mL). RESULTS: Median OS in patients with low vs. high NK cell count at baseline was 7.1 months vs. 15.6 months (p = .028), respectively, and before cycle 2 was 5.7 vs. 17.3 months, p < .001, respectively. The difference in restricted mean survival (ΔRMST) was 5.7 months (95% CI: 3.3-8.0) at cycle 2 vs. 2.5 months (95% CI: -0.6 to 5.6) at baseline, showing a significant difference with no overlap of confidence intervals. In multivariate analyses, low NK cell count remained significant with a hazard ratio (HR)=2.83, 95% CI: 1.53-5.22, p = .001 (baseline) and HR = 3.34, 95% CI: 1.67-6.71, p = .001 (before cycle 2). Patients with both low NK count and NK activity at baseline (N = 20) had median OS 6.5 months vs. 11.5 months in patients with either high activity, high count or both (p = .007). In parallel, patients with both low NK activity and count at cycle 2 (N = 18) had a median survival of 4.0 months vs. 15.4 months (p < .001). CONCLUSIONS: A low blood NK cell count in recurrent metastatic ovarian cancer during chemotherapy is associated with unfavorable prognostic impact. Early increase in survival difference based on NK cell status suggests an association between NK cell count and treatment benefit.

Prognostic significance of baseline T cells, B cells and neutrophil-lymphocyte ratio (NLR) in recurrent ovarian cancer treated with chemotherapy.

PURPOSE: Biomarkers are needed to guide treatment decisions in recurrent ovarian cancer, as a high proportion of patients do not benefit from treatments. Data on immune subsets in patients receiving chemotherapy are scarce. We investigated the impact of T cells, B cells, neutrophils and the neutrophil-lymphocyte ratio (NLR) in ovarian cancer patients receiving palliative chemotherapy. METHODS: Blood samples were collected prospectively at baseline in recurrent ovarian cancer (N = 72) receiving chemotherapy. T cells, B cells, neutrophils, and NLR were analyzed. Primary and secondary endpoints were overall survival (OS) and treatment response, respectively. Cut-offs for T and B cells were predefined. RESULTS: In patients with low vs. high T and B cells counts, OS was 6.1 months vs 12.0 months (P = 0.017) and 6.1 months vs 12.0 months (P = 0.011, respectively. Low T and B cells analyzed as continuous variables were also associated with unfavorable OS, P = 0.011 and P = 0.007, respectively. Neutrophils had no significant prognostic impact. Median NLR was 4.1. High vs. low NLR was associated with poor survival, 7.4 months vs. 15.9 months (P = 0.012). In multivariate analysis including platinum sensitivity, number of prior lines of chemotherapy, and performance status, high NLR remained an independent poor prognostic factor HR: 2.17 (95% CI 1.21-3.88) (P = 0.009). High NLR was also significantly associated with lack of response, OR 0.15 (95% CI: 0.04-0.51) (P = 0.002). CONCLUSION: In recurrent ovarian cancer patients undergoing palliative chemotherapy, low T and B lymphocyte counts had an unfavorable prognostic impact. High NLR was associated with lack of response and a poor prognosis, and the parameter may be used in patient counselling and treatment decisions.

Favorable prognostic impact of Natural Killer cells and T cells in high-grade serous ovarian carcinoma.

Introduction: The aim of the present study was to investigate the prognostic impact of intratumoral cytotoxic T cells, Natural Killer (NK) cells, neutrophils and PD-L1 expression in patients with epithelial ovarian cancer.Methods: All patients diagnosed with high-grade serous carcinoma (HGSC) in Denmark in 2005 were included in the study. Immunohistochemical staining for PD-L1, CD8, CD66b and CD57 was performed on tumor tissue from 283 patients. Cell densities were analyzed using a digital image analysis method. The primary endpoint was overall survival (OS).Results: The median OS for HGSC patients was 30 months. It was 45 months in patients with high level of CD57+ NK cells (≥10 cells/mm2) compared with 29 month in patients with low level (<10 cells/mm2) (p = .0310). The median OS was 37 and 25 months in patients with high vs. low level of CD8+ T cells (cutoff 80 cells/mm2) (p = .0008). In multivariate analysis, high numbers of CD57+ NK cells and CD8+ T cells remained independent markers of favorable OS, adjusted hazard ratio (HR) 0.67; p = .041, and HR 0.72; p = .020, respectively. PD-L1 expression was associated with improved OS (37 months vs. 22 months, p = .0006), but was only borderline significant in the multivariate analysis (HR 0.77, p = .061). CD66b + neutrophils had no association with OS.Conclusions: In patients with HGSC tumor-infiltrating CD57+ NK cells and CD8+ T cells had favorable prognostic impact, while PD-L1 expression had borderline favorable prognostic significance. CD66b + neutrophils had no prognostic association. These findings may influence future immunotherapy development.