Marchetti A, et al -2014 |
To investigate the feasibility of detecting EGFR mutations in circulating tumor cells of patients with non-small cell LC by coupling the CellSearch system with next generation sequencing (NGS) in the 454 GS Junior system (454 Life Sciences, Branford, CT and Roche Applied Sciences, Indianapolis, IN). |
Blood samples were collected from 37 patients participating in the TRIGGER study, a prospective multicenter phase II trial of erlotinib in patients with advanced non-small cell LC with EGFR-activating mutations in tumor tissue. 10 circulating tumor cells (CTC) were prepared from breast cancer patients without EGFR mutations in their primary tumors and 12 samples from healthy subjects were analyzed as negative controls. The CTC preparations, obtained with the VeridexCellSearch System, were subjected to the latest generation ultra-deep sequencing (NGS) in the 454 GS junior platform from Roche. |
The Cell Search system, together with NGS, has been reported to be highly sensitive and specific as a diagnostic tool for the analysis of EGFR mutations in CTC preparations, with potential clinical impact, and may be particularly useful in cases with a very limited amount of biological material or for monitoring the mutational status of the tumor during treatment, with special emphasis on the presence of mutations involved in the acquisition of resistance to TKIs. |
Roche Pharmaceutical Industry |
Sun M, et al - 2014 |
To explore the pattern of SPRY4-IT1 expression in non-small cell LC (NSCLC) tissues and cell lines, and investigate the effects of SPRY4-IT1 expression on NSCLC cell phenotypes both in vitro and in vivo. |
SPRY4-IT1 expression was investigated in 121 paired NSCLC samples and histologically normal adjacent tissues using PCR (qPCR) |
SPRY4-IT1 expression was down-regulated and correlated with a poor prognosis of non-small cell LC. |
National Natural Scientific Foundation of China |
Yamamoto S, et al - 2014 |
To provide a radiogenomic characterization of computed tomography of ALK-rearranged NSCLC (ALK + NSCLC) from data in a multi-institutional cohort. |
In this retrospective study, tomographic studies, ALK status and clinical-pathological data from 172 patients with NSCLC from three institutions were analyzed. Twenty-four CT features plus six clinical-pathological covariates were used to identify a radiogenomic predictor of ALK+ status. This predictor was then validated in an independent cohort (n=113). Test analyses for precision and subsets were performed. A similar analysis was performed to identify a biomarker associated with lower progression-free survival (PFS) after therapy with the ALK inhibitor crizotinib. |
ALK + NSCLC has distinct characteristics in the computed tomography image that, when combined with clinical covariates, discriminate ALK+ from non-ALK tumors and can potentially identify patients with a shorter durable response to crizotinib. |
Not declared. |
Bar J, et al - 2015 |
To evaluate the prognostic and predictive significance of serum levels of angiotensin-converting enzyme (ACE) and aldosterone, regulators of blood pressure, in patients with advanced non-small cell lung cancer (NSCLC) participating in the NCIC Clinical Trial Group Trial BR.24. |
Angiotensin-converting enzyme and aldosterone were retrospectively measured using enzyme-linked immunosorbent assays at the start and during treatment, in serum samples from 226 and 176 of 296 participants, respectively. Cox regression was performed to correlate biomarkers and patient characteristics with overall survival (OS) and progression-free survival (PFS). |
Low initial levels of ACE were predictors of a low total survival rate and predictive of the overall survival benefit of cediranib. An increase in the level of aldosterone with treatment may also be predictive of the overall survival benefit of cediranib. These biomarkers must be validated in additional antiangiogenic assays in NSCLC and other cancers. |
Ottawa Regional Cancer Center and Ottawa Regional Cancer Foundation |
Chen X, et al - 2015 |
To investigate the diagnostic performance of folate- receptor positive circulating tumor cell in distinguishing non-small cell LC (NSCLC) from benign lung disease, a new polymerase chain reaction (PCR) technique targeting ligand detection. |
Circulating tumor cells from 3 mL of blood were enriched by leukocyte immunomagnetic depletion and then labeled with a conjugate of a tumor-specific folic acid and a synthesized oligonucleotide. After washing the free conjugates, the removed ligand conjugates were analyzed by quantitative PCR. |
The ligand-targeted PCR technique was feasible and reliable for detecting folate receptor-positive circulating tumor cells in patients with NSCLC, and circulating tumor cell levels could be used as a useful biomarker for the diagnosis of NSCLC. |
This research was partially supported by the Guide Project of the Science and Technology Commission of Shanghai Municipality (grant 124119a8000); the Forefront and Emerging Technology Projects of Shanghai Shenkang Hospital Development Center (grant SHDC12013102); and the key project supported by Shanghai Science and Technology Commission (grant 13441902200). |
Shimizu T, et al - 2016 |
The aim of this study is to determine whether the number of TYMS gene copies predicts the outcome in patients receiving pemetrexede (PMT). The association between the number of copies of the TYMS gene and the therapeutic efficacy of PMT plus carboplatin (CBDCA) in patients with advanced NSCLC was investigated in a phase II study. |
The participants were patients who had never undergone treatment with chemotherapy, with advanced non-small cell LC, treated with pemetrexed plus carboplatin (CBDCA), a prospective phase II clinical study. TYMS (Thymidylate synthase) expression was assessed in 40 patients by gene copy number and protein expression using FISH and IHC. Therapeutic efficacy was assessed by investigating response rate (RR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). |
The analysis of the number of TYMS gene copies is more adequate than TYMS protein expression for evaluation of TYMS expression. Amplification of the TYMS gene predicts outcomes for patients with NSCLC who receive premetrexede. |
Not declared |
Niemeijer AN, et al - 2018 |
To show that PD-L1 and PD-1 tumor expression can be non-invasively quantified using PET- CT in patients with non-small cell LC. |
Participating patients underwent full body scans for PD- (L) 1 using PET-CT. Thirteen patients were included in this exploratory of an open, single-center, one-arm biomarker study,the firs t in humans. |
PD-L1 and PD-1 tumor expression can be non-invasively quantified using PET-CT in patients with non-small cell LC. Entire body PD-(L) 1 PET-CT reveals significant heterogeneity in the uptake of the tumor tracer both between patients and between different tumor lesions within patients. |
Bristol-Myers Squibb (BMS) |
Villalobos M, et al - 2018 |
The aim of this study was to assess the impact of ERCC1 on the survival of patients with non-squamous NSCLC (NS-NSCLC) stage IIIB / IV participating in the INNOVATIONS trial, treated with erlotinib / bevacizumab (EB) or cisplatin / gemcitabine / bevacizumab (PGB). |
Retrospective analysis of the t umor tissue of 72 patients using immunohistochemistry to evaluateERCC1 expression. The distribution between treatment arms was equal (36 patients in each). Two different H scores were calculated and correlated with survival. |
The findings support the hypothesis that patients whose tumors have low ERCC1 expression benefit from cisplatin-based chemotherapy. In patients treated with erlotinib and bevacizumab, a positive effect on progression free survival was found for ERCC1 positive tumors based on the H score, but not with the modified scoring system. |
Roche Pharmaceutical Industry |