Conleyovergaard1407

Intracranial progression is considered an important cause of treatment failure in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients. Recent advances in targeted therapy and radiomics have generated considerable interest for the exploration of prognostic imaging biomarkers to predict the clinical course. Here, we developed a magnetic resonance imaging (MRI) radiomic signature that can stratify survival and intracranial progression.

We analyzed 87 brain metastatic lesions in 24 ALK-positive NSCLC patients undergoing ALK-inhibitor ensartinib therapy and divided them into training (n=61) and validation (n=26) sets. Radiomic features were extracted and screened from contrast-enhanced MR images. Combined with these selected features, the Rad-score was calculated with multivariate logistic regression. The predictive model and Rad-score performance were assessed in the training set and validated in the validation set; decision curve analysis was performed with the combined traiC patients with brain metastases undergoing ensartinib treatment, allowing follow-up and treatment to be tailored to the patient's individual risk profile.

We investigated the association of peripheral blood inflammatory markers with overall survival (OS) in pembrolizumab treated advanced non-small cell lung cancer (aNSCLC) patients with programmed death ligand 1 (PD-L1) expression ≥50%. Clinical risk factors for development of immune-related adverse events (irAE) were also explored.

aNSCLC patients with high PD-L1 expression receiving pembrolizumab monotherapy outside of clinical trials were identified retrospectively. All patients were treated at one of six British Columbia Cancer clinics between August 2017 and June 2019. Patients were dichotomized using baseline neutrophil-to-lymphocyte ratio (NLR, </≥6.4) and platelet-to-lymphocyte ratio (PLR, </≥441.8). Factors associated with OS were assessed with Cox proportional hazard models. Logistic regression models were utilized in landmark analysis of risk factors for irAE.

Among 220 patients, median age was 70.0 years, 55.0% were female, 40.5% had baseline Eastern Cooperative Oncology Group performancNLR and PLR were associated with shorter OS in a cohort of patients receiving largely frontline pembrolizumab for aNSCLC in routine practice. ECOG PS 2/3 was associated with higher risk of developing an irAE. Given that NLR and PLR values are easily obtainable, prospective studies are warranted to confirm their prognostic significance in this patient population and explore a predictive utility.

Disease recurrence in localized lung adenocarcinoma is a major obstacle for improving the overall outcome of lung cancer. Thus, better prognostic biomarkers are needed to identify patients at risk. In order to clear cancer, immune detection of tumor cells is of vital importance. DNA-leakage into the cytosol and tumor environment is one important tumor-associated danger signal and cGAS is a pivotal DNA-sensor that detects misplaced DNA and initiates an innate immune response. In this study, we investigate the cGAS-STING-pathway expression in tumor tissue and circulating immune cells from lung adenocarcinoma patients in relation to stage of disease and overall survival (OS).

Gene expression was measured using target specific droplet digital polymerase chain reaction (ddPCR) assays in a cohort of 80 patients with lung adenocarcinoma and 45 patients suspected of lung cancer, but determined to be cancer-free. The expression values were correlated to stage of disease. For further exploration of stage dependent t and high expression is correlated with localized adenocarcinoma. For patients with localized disease, high cGAS, STING and TBK1 expression correlated with improved OS and may be a potential biomarker for this patient subgroup.

Serial profiling of circulating tumor DNA (ctDNA) could reflect dynamic molecular changes in response to treatment and potentially predict impending disease progression (PD). Herein, we investigated the molecular factors and dynamic changes in ctDNA that can serve as predictors of survival outcomes of patients with epidermal growth factor receptor (

)-mutated advanced non-small cell lung cancer (NSCLC) who received osimertinib therapy after progression from prior EGFR inhibitor regimen.

Capture-based targeted sequencing was performed on the baseline and longitudinal plasma samples collected from 72 and 57 patients, respectively, using a 168-gene panel.

Analysis revealed that inferior overall survival (OS) was correlated with various baseline molecular features including high allelic fraction (AF) of

sensitizing mutations (P=0.045), high maximum AF (maxAF, P=0.060), or harboring concurrent genomic alterations such as copy number amplification (CNA) in

(P=0.026) or in other genes (P=0.026), and genes involved in the cell cycle (P=0.004) or TP53 signaling pathway (P=0.032). Moreover, ctDNA clearance at first follow-up after 6 weeks of osimertinib therapy was correlated with significantly longer progression-free survival (PFS) (P=0.022) and OS (P=0.009). Molecular PD, reflected by the emergence of new mutation or increased AF of existing mutations, was detected at an average lead time of 2.5 months prior to radiological PD. Patients with molecular PD were more likely to harbor CNA (P=0.035) and

mutations (P=0.023).

Molecular factors derived from serial ctDNA profiling can serve as predictive and prognostic markers, which could allow early detection of PD, preceding imaging modalities by 2.5 months.

Molecular factors derived from serial ctDNA profiling can serve as predictive and prognostic markers, which could allow early detection of PD, preceding imaging modalities by 2.5 months.

Rearranged during transfection (

) rearrangements occur in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib administered at doses of 300 mg and 600 mg twice daily (BID) is approved for.

rearranged NSCLC in Japan and other countries, respectively. Since alectinib has activity against RET, we conducted a phase (P) 1/2 study of alectinib to determine its activity in Japanese patients with.

rearranged NSCLC.

This study was a single-arm, open-label, multi-institutional P1/2 trial. Previously treated patients with

-rearranged NSCLC, screened by nation-wide network (LC-SCRUM-Japan), were recruited. In P1, alectinib (600 or 450 mg BID) was administered following a 3+3 design and its safety was assessed. During P2, alectinib was administered at the recommended dose (RD) determined in P1. The primary endpoint was the objective response rate (ORR) in RET inhibitor-naïve patients treated with the RD of alectinib.

Thirty-four patients were administered alectinib. selleck kinase inhibitor In cohort 1 (600 mg BID) of P1, we observed 5 dose-limiting toxicities (DLTs), including grade 3 rash and thromboembolic event, in 3 of 6 patients.