domingo, 19 de noviembre de 2017

The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer. - PubMed - NCBI

The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer. - PubMed - NCBI



 2017 Oct 23;10(1):167. doi: 10.1186/s13045-017-0536-6.

The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer.

Abstract

The treatment paradigm of non-small cell lung cancer (NSCLC) has evolved into oncogene-directed precision medicine. Identifying actionable genomic alterations is the initial step towards precision medicine. An important scientific progress in molecular profiling of NSCLC over the past decade is the shift from the traditional piecemeal fashion to massively parallel sequencing with the use of next-generation sequencing (NGS). Another technical advance is the development of liquid biopsy with great potential in providing a dynamic and comprehensive genomic profiling of NSCLC in a minimally invasive manner. The integration of NGS with liquid biopsy has been demonstrated to play emerging roles in genomic profiling of NSCLC by increasing evidences. This review summarized the potential applications of NGS-based liquid biopsy in the diagnosis and treatment of NSCLC including identifying actionable genomic alterations, tracking spatiotemporal tumor evolution, dynamically monitoring response and resistance to targeted therapies, and diagnostic value in early-stage NSCLC, and discussed emerging challenges to overcome in order to facilitate clinical translation in future.

KEYWORDS:

Liquid biopsy; Next-generation sequencing; ctDNA

PMID:
 
29061113
 
PMCID:
 
PMC5654124
 
DOI:
 
10.1186/s13045-017-0536-6

Implementing an oncology precision medicine clinic in a large community health system. - PubMed - NCBI

Implementing an oncology precision medicine clinic in a large community health system. - PubMed - NCBI

 2017 Aug;23(10 Spec No.):SP425-SP427.

Implementing an oncology precision medicine clinic in a large community health system.


PMID:
 
29087641
Free full text

An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer. - PubMed - NCBI

An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer. - PubMed - NCBI



 2017 Nov 10. pii: S0090-8258(17)31459-2. doi: 10.1016/j.ygyno.2017.10.037. [Epub ahead of print]

An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer.

Abstract

OBJECTIVES:

The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification.

METHODS:

Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods.

RESULTS:

Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status.

CONCLUSIONS:

A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system.

KEYWORDS:

Combined Lynch syndrome screening and molecular classification; Endometrioid endometrial cancer; Molecular classification; Prognosis

PMID:
 
29132872
 
DOI:
 
10.1016/j.ygyno.2017.10.037

A seven-gene prognostic signature for rapid determination of head and neck squamous cell carcinoma survival. - PubMed - NCBI

A seven-gene prognostic signature for rapid determination of head and neck squamous cell carcinoma survival. - PubMed - NCBI



 2017 Dec;38(6):3403-3411. doi: 10.3892/or.2017.6057. Epub 2017 Oct 24.

A seven-gene prognostic signature for rapid determination of head and neck squamous cell carcinoma survival.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and displays divergent clinical outcomes. Prognostic biomarkers might improve risk stratification and survival prediction. We aimed to investigate the prognostic genes associated with overall survival. A two-step gene selection method was used to develop a seven-gene-based prognostic model based on the training set collected from The Cancer Genome Atlas (TCGA). In addition, the prognostic model was validated in an independent testing set from Gene Expression Omnibus (GEO). The score based on the model successfully distinguished HNSCC survival into high-risk and low-risk groups in the training set (HR, 2.79; 95% CI, 1.98-3.92; P=4.05x10-9) and the testing set (HR, 2.05; 95% CI, 1.35-3.11; P=7.98x10-4). In addition, the score could significantly predict 5-year survival by ROC curves (AUCs for training set, 0.73; testing set, 0.66). Combining risk scores with clinical characteristics improved the AUCs beyond using clinical characteristics alone (training set, from 0.57 to 0.75; testing set, from 0.63 to 0.72). A subgroup sensitivity analysis with HPV status and tumor sites revealed that the risk score was significant in all subgroups except oral cavity tumors of the testing set. Furthermore, HPV-positive status improves survival in oropharyngeal HNSCC but not non-oropharyngeal HNSCC. In conclusion, the seven-gene prognostic signature is a reliable and practical prognostic tool for HNSCC. This approach can add prognostic value to clinical characteristics and provides a new possibility for individualized treatment.

PMID:
 
29130107
 
DOI:
 
10.3892/or.2017.6057

Molecular Tumor Boards: Realizing Precision Oncology Therapy. - PubMed - NCBI

Molecular Tumor Boards: Realizing Precision Oncology Therapy. - PubMed - NCBI



 2017 Nov 14. doi: 10.1002/cpt.920. [Epub ahead of print]

Molecular Tumor Boards: Realizing Precision Oncology Therapy.

Abstract

Technological advances in high-throughput next-generation sequencing (NGS) along with advances in computational processes have brought about the dawn of the genomic medicine era. NGS has enabled molecular characterization of malignancies, and facilitated the development and approval of gene- and immune-targeted therapies, both of which impact the mutanome. Clinical implementation of this technology, approval of novel targeted agents, and establishment of molecular tumor boards has enabled precision oncology to become a reality.

PMID:
 
29134641
 
DOI:
 
10.1002/cpt.920

Clinical and translational implications of RET rearrangements in non-small cell lung cancer. - PubMed - NCBI

Clinical and translational implications of RET rearrangements in non-small cell lung cancer. - PubMed - NCBI



 2017 Nov 8. pii: S1556-0864(17)32866-6. doi: 10.1016/j.jtho.2017.10.021. [Epub ahead of print]

Clinical and translational implications of RET rearrangements in non-small cell lung cancer.

Abstract

Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations. To date, several preclinical models, clinical trials, and retrospective studies have investigated multi-target inhibitors with anti-RET activity in RET-rearranged lung cancer patients. In the clinical setting, the benefit in terms of response (16% to 47%) and progression-free survival (2 to 7 months) is clearly not comparable to that seen with other targeted agents in oncogene-addicted NSCLC. Furthermore, multi-kinase agents showed high rates of severe toxicities, leading to frequent dose reduction and drug discontinuation. To date, no definitive conclusions about a potentially different impact of anti-RET therapies according to RET fusion variants have been drawn, due to discordant data, coming mostly from small subgroup analyses. Importantly, the absence of a striking clinical benefit in RET-oncogene-addicted NSCLC underscores the clear need for the development of more selective and potent RET inhibitors and for a better characterization of concomitant genomic alterations and mechanisms of resistance to RET inhibition in lung cancer patients.

KEYWORDS:

KIF5B-RET; NSCLC; RET inhibitors; RET rearrangement; oncogene addiction

PMID:
 
29128428
 
DOI:
 
10.1016/j.jtho.2017.10.021
Free full text

Investigating Uncertainty in Genetic Counseling Encounters: Managing Information About Genetic Cancer Risk. - PubMed - NCBI

Investigating Uncertainty in Genetic Counseling Encounters: Managing Information About Genetic Cancer Risk. - PubMed - NCBI



 2017 Nov;22(11):896-904. doi: 10.1080/10810730.2017.1373875. Epub 2017 Nov 10.

Investigating Uncertainty in Genetic Counseling Encounters: Managing Information About Genetic Cancer Risk.

Abstract

The Theory of Motivated Information Management (TMIM) was used to investigate how individuals at increased risk of developing hereditary cancer seek information from genetic counselors. Results show the TMIM model fit the data well in predicting participants' intentions to seek information from genetic counselors. Participants felt an uncertainty discrepancy that elicited feelings of anxiety, which in turn negatively predicted both outcome expectancies and efficacy assessments. Efficacy assessments, but not anxiety, significantly predicted participants' intentions to seek information from a genetic counselor in the future. Findings showed no significant relationship between outcome expectancies and efficacy assessments. One implication for genetic counselors is the need to more closely monitor emotional response to genetic disease risk-whether that emotional response be positive or negative-as that response may influence information-seeking intentions. Further, genetic counselors might also pay more attention to building efficacy for themselves (making patients feel the counselor is more credible) and their patients (increasing patient ability to communicate effectively about genetic disease risk). Analysis also extends TMIM theory by showing that in a relationship where information exchange is the primary function the model still showed good fit. However, outcome expectancies functioned differently than in previous tests of the model.

PMID:
 
29125386
 
DOI:
 
10.1080/10810730.2017.1373875