Living with Advanced Kidney Cancer and Treatment with Cabozantinib: Through the Eyes of the Patient and the Physician

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b> <a href="https://link.springer.com/article/10.1007/s40487-018-0057-7">https://link.springer.com/article/10.1007/s40487-018-0057-7</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Forrest plots evaluating maximally adjusted association between TAN and clinical outcomes in all cancers.

<p>(A) Forrest plot to assess the overall effect of TAN on OS in all cancer patients. (B) Forrest plot to assess the overall effect of TAN on RFS/DFS in all cancer patients.</p

Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-Analysis

<div><p>Purpose</p><p>Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer.</p><p>Method</p><p>Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed.</p><p>Results</p><p>A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I² = 55.8%, <i>p</i><0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I² = 0%, <i>p</i><0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I² = 70.5%, <i>p</i><0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I² = 67.7%, <i>p</i><0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I² = 45.9%, <i>p</i> = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15.</p><p>Conclusion</p><p>High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival.</p></div

Follow diagram of the meta-analysis.

<p>Follow diagram of the meta-analysis.</p

Sensitivity analysis of subgroups.

<p>(A) Sensitivity analysis of studies evaluated intratumoral neutrophils expression on OS. (B) Sensitivity analysis of studies evaluated intratumoral neutrophils expression on RFS/DFS.</p

Characteristics of included studies.

<p>Abbreviations: Gastric: gastric carcinoma; RCC: renal cell carcinoma; HNC: head and neck carcinoma; HCC: hepatocellular carcinoma; ICC: intrahepatic cholangiocarcinoma; NSCLC: non-small-cell lung cancer; CRC: colorectal carcinomas; CC: cervical cancer; PDC: pancreatic ductal carcinoma; HE: hematoxylin-eosin staining; OS: overall survival; CSS: cancer-specific survival; RFS: recurrence-free survival; DFS: disease-free survival; NM: not mentioned; a: OS; b: CSS; c: RFS; d: DFS; m: months; y: years; DE: data extrapolated; SR: systematic review <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098259#pone.0098259-Donskov3" target="_blank">[36]</a>.</p

Forrest plots evaluating maximally adjusted association between intratumoral neutrophils and clinical outcomes in subgroups.

<p>HRs of HCC patients are reported as (A). HRs of HNC patients are reported as (B). HRs of NSCLC patients are reported as (C). HRs of RCC patients are reported as (D). HRs of Gastric carcinoma patients are reported as (E).</p

Diagnosis of hyponatremia and increased risk of a subsequent cancer diagnosis: results from a nationwide population-based cohort study

<p><b>Background:</b> Hyponatremia has recently been associated with subsequent cancer risk. This population-based nationwide study assessed whether the diagnosis of hyponatremia can predict a cancer diagnosis within most common cancers.</p> <p><b>Material and methods:</b> Using Danish medical registries, we identified 16,220 patients with a first-time diagnosis of hyponatremia, without a cancer diagnosis, from January 2006 through November 2013. We quantified the relative risk of a subsequent cancer diagnosis by standardized incidence ratios (SIRs), comparing observed cancer incidence among patients diagnosed with hyponatremia to that expected, based on national cancer incidence during that period.</p> <p><b>Results:</b> During 40,207 person-years of follow-up, we observed 1546 cancer diagnoses compared to 956 expected (SIR: 1.62; 95% confidence interval (CI), 1.54–1.70). The increase in risk of a cancer diagnosis following a hyponatremia diagnosis was most pronounced within 0–6 months of follow-up (SIR 4.16; 95% CI, 3.85–4.48) and in the younger age group; 0–29 years (SIR 8.71; 95% CI, 2.82–20.28), 30–49 years (SIR 3.16; 95% CI, 2.26–4.31), 50–69 years (SIR 2.29; 95% CI, 2.10–2.48) and 70 + years (SIR 1.35; 95% CI, 1.27–1.44). Within six months after a hyponatremia diagnosis, the SIRs increased 10-fold for cancers of the lung (SIR 17.14; 95% CI, 15.15–19.32), brain (SIR 13.52; 95% CI, 8.90–19.66) and liver (SIR 13.26; 95% CI, 7.57–21.53) and increased 5 to 10-fold for cancers of the pancreas (SIR 8.25; 95% CI, 5.72–11.53), esophagus (SIR 6.59; 95% CI, 3.15–12.12), kidney (SIR 6.36; 95% CI, 3.39–10.88), pharynx (SIR 6.15; 95% CI, 1.27–17.97) and non-Hodgkin lymphoma (SIR 6.10; 95% CI, 4.17–8.61). The rate increased across virtually all types of cancers, except melanoma and basal cell carcinomas.</p> <p><b>Conclusions:</b> A diagnosis of hyponatremia may be a marker of occult neoplasms, especially cancers of the lung, brain, liver, pancreas, esophagus, kidney, pharynx and non-Hodgkin lymphoma. Hyponatremia may aid in early detection of cancer.</p

Additional file 1 of Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial

Additional file 1. Checklist for SPIRIT guidelines

Molecular analysis and favorable clinical outcomes in real-world patients with metastatic renal cell carcinoma

Prior biomarker studies have mainly been restricted to advanced RCC patients treated in clinical trials or have had limited integration of immunotherapy features such as programmed death ligand (PD-L)-1 with gene expression signatures intended to capture other canonical pathways to confirm their prognostic value. PD-L1 and PD-L2 by immunohistochemistry (IHC), PD-L2 messenger RNA (mRNA), and 10 gene expression profile (GEP) signatures targeting immune, angiogenesis and canonical pathways were analyzed in nephrectomy specimens from 227 advanced clear cell RCC (ccRCC) and 42 non-clear cell RCC (nccRCC) patients treated with targeted therapies including VEGF and mTOR inhibitors. Biomarker association with best overall response (BOR), progression-free survival (PFS), and overall survival (OS) were evaluated using multivariable modeling. Except for PD-L1 IHC and angiogenesis, tested with a nominal p-value of .05, multiplicity control was applied with a 0.1 significance level given limited experience in this setting. The strongest biomarker correlations were observed for hypoxia inducible factor (HIF)-2a and angiogenesis signatures (rho = 0.860 [ccRCC], 0.819 [nccRCC]); hypoxia and glycolysis signatures (rho = 0.943 [ccRCC], 0.973 [nccRCC]); PD-L2 mRNA and T-cell-inflamed GEP signatures (rho = 0.764 [ccRCC], 0.897 [nccRCC]); and PD-L2 mRNA and monocytic myeloid-derived suppressor cell signature (rho = 0.787 [ccRCC], 0.815 [nccRCC]). For ccRCC, higher angiogenesis expression was associated with improved BOR (OR:2.85 [95%CI:1.37, 5.93]), longer PFS (HR:0.61 [95%CI:0.45, 0.82]) and OS (HR:0.74 [95%CI:0.54, 1.00]); higher PD-L1 expression with shorter OS (HR:1.44 [95%CI:1.01, 2.07]). For nccRCC, there was more than a two-fold increased risk with longer OS associated with lower angiogenesis (HR:2.43 [95%CI:1.04, 5.68]), glycolysis (HR:7.03 [95%CI:1.51, 32.76]) and hypoxia (HR:8.83 [95%CI:1.69, 46.05]) gene signature expression. Data pointed at PD-L1 IHC and angiogenesis expression in ccRCC and hypoxia, glycolysis, and angiogenesis expression in nccRCC as potential prognostic factors. These findings may have implications for the design and interpretation of advanced RCC trials and to identify potential targets for combination therapy strategies.</p