Multiple tumors in patients are frequently diagnosed, either synchronous or metachronous. The distinction between a second primary and a metastasis is important for treatment. Chromosomal DNA copy ...number aberrations (CNA) patterns are highly unique to specific tumors. The aim of this study was to assess genome-wide CNA-patterns as method to identify clonally related tumors in a prospective cohort of patients with synchronous or metachronous tumors, with at least one intrapulmonary tumor. In total, 139 tumor pairs from 90 patients were examined: 35 synchronous and 104 metachronous pairs. Results of CNA were compared to histological type, clinicopathological methods (Martini-Melamed-classification (MM) and ACCP-2013-criteria), and, if available, EGFR- and KRAS-mutation analysis. CNA-results were clonal in 74 pairs (53%), non-clonal in 33 pairs (24%), and inconclusive in 32 pairs (23%). Histological similarity was found in 130 pairs (94%). Concordance between histology and conclusive CNA-results was 69% (74 of 107 pairs: 72 clonal and two non-clonal). In 31 of 103 pairs with similar histology, genetics revealed non-clonality. In two out of four pairs with non-matching histology, genetics revealed clonality. The subgroups of synchronous and metachronous pairs showed similar outcome for the comparison of histological versus CNA-results. MM-classification and ACCP-2013-criteria, applicable on 34 pairs, and CNA-results were concordant in 50% and 62% respectively. Concordance between mutation matching and conclusive CNA-results was 89% (8 of 9 pairs: six clonal and two non-clonal). Interestingly, in one patient both tumors had the same KRAS mutation, but the CNA result was non-clonal. In conclusion, although some concordance between histological comparison and CNA profiling is present, arguments exist to prefer extensive molecular testing to determine whether a second tumor is a metastasis or a second primary.
Loose tumor cells and tumor cell clusters can be recognized in the lumen of intratumoral pulmonary arteries of resected non-small cell lung cancer specimens. It is unclear whether these should be ...considered tumor-emboli, and as such could predict a worsened prognosis.
To investigate the nature and prognostic impact of pulmonary artery intraluminal tumor cells.
This multicenter study involved an exploratory pilot study and a validation study from 3 institutions. For the exploratory pilot study, a retrospective pulmonary resection cohort of primary adenocarcinomas, diagnosed between November 2007 and November 2010, were scored for the presence of tumor cells, as well as potentially other cells in the intravascular spaces, using hematoxylin-eosin and cytokeratin 7 (CK7) stains. In the validation part, 2 retrospective cohorts of resected pulmonary adenocarcinomas, between January 2011 and December 2016, were included. Recurrence-free survival (RFS) and overall survival (OS) data were collected.
In the pilot study, CK7+ intravascular cells, mainly tumor cells, were present in 23 of 33 patients (69.7%). The 5-year OS for patients with intravascular tumor cells was 61%, compared with 40% for patients without intravascular tumor cells (P = .19). In the validation study, CK7+ intravascular tumor cells were present in 41 of 70 patients (58.6%). The 5-year RFS for patients with intravascular tumor cells was 80.0%, compared with 80.6% in patients without intravascular tumor cells (P = .52). The 5-year OS rates were, respectively, 82.8% and 71.6% (P = .16).
Loose tumor cells in pulmonary arterial lumina were found in most non-small cell lung cancer resection specimens and were not associated with a worse RFS or OS. Therefore, most probably they represent an artifact.
Highlights • EGFR - and KRAS -mutations in lung cancer are relevant for treatment decisions. • Current guidelines do not advise to analyze squamous cell carcinomas. • We examined the fraction of ...mutations that would have been missed in our database. • 2.0% (2/102) of EGFR - and 1.7% (4/237) of KRAS -mutations would not have been tested. • The percentage is slightly higher than the suggested threshold of 1% for EGFR.
The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. Open-label randomized phase II clinical trial investigating ...tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of alpha = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.
In the past decade, major progress has been made toward personalized medical treatment of non–small-cell lung cancer (NSCLC) through the discovery of epithelial growth factor receptor (EGFR) ...mutations. However, mutation analysis takes extra time and additional costs in the diagnostic evaluation of lung cancer patients. It has been hypothesized that EGFR mutations are restricted to terminal respiratory unit -type adenocarcinoma expressing thyroid transcription factor-1 (official symbol NKX2-1) as determined by immunohistochemistry. The aim of the current study is to evaluate the potential of NKX2-1 immunohistochemistry as a prescreening test for EGFR mutation analysis.
From 2004 to December 2010, 810 consecutive NSCLC tumor specimens were tested for EGFR mutations in a routine diagnostic procedure. Immunohistochemistry for NKX2-1 was performed (clone 8G7G3/1 Dako) and the results were compared with tumor EGFR-mutation status and clinicopathological characteristics.
EGFR mutations were detected in 114 specimens (14%). NKX2-1 expression was present in 68%. In the cases with EGFR mutation, NKX2-1 staining was positive in 92%. NKX2-1 immunohistochemical (IHC) staining was significantly associated with the presence of EGFR mutations (p = 5.3×10−10). NKX2-1 increased the negative predictive value in NSCLC to more than 95%.
In case of a negative NKX2-1 IHC staining, and only if clinically urgent, the high negative predictive value of more than 95% for EGFR mutations is a suitable temporary surrogate marker for the choice of starting with chemotherapy. In case of positive NKX2-1 IHC, the best strategy is to wait for the outcome of EGFR-mutation analysis and then choose the appropriate treatment.
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