Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening–Detected Lung Cancers

Verri, Carla; Borzi, Cristina; Holscher, Todd; Dugo, Matteo; Devecchi, Andrea; Drake, Katherine; Sestini, Stefano; Suatoni, Paola; Romeo, Elisa; Sozzi, Gabriella; Pastorino, Ugo; Boeri, Mattia

doi:10.1016/j.jtho.2017.03.001

Cited by 13 publications

(12 citation statements)

References 40 publications

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“…In terms of survival, HPV-positive oropharyngeal tumours were associated with better prognosis, showing an increased OS and PFS compared to HPV-negative tumours as it was previously defined 26,[43][44][45][46][47] . Secondly, the presence of mutation in the targeted genes was associated with inferior outcome demonstrated by the presence of detrimental OS.…”

Section: Discussionmentioning

confidence: 67%

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

Fernández-Mateos

Pérez-García

Seijas-Tamayo

et al. 2020

Sci Rep

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234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours.

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Section: Discussionmentioning

confidence: 67%

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

Fernández-Mateos

Pérez-García

Seijas-Tamayo

et al. 2020

Sci Rep

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“…The MSC is composed of 24 miRNAs whose reciprocal ratios stratify subjects into three risk levels, with the MSC high-risk patients having worse prognoses than MSC intermediate-or low-risk patients (14). We have also shown that the MSC risk level was independent of tumor histology and mutational burden (15).…”

Section: Introductionmentioning

confidence: 73%

Circulating miRNAs and PD-L1 Tumor Expression Are Associated with Survival in Advanced NSCLC Patients Treated with Immunotherapy: a Prospective Study

Boeri

Milione

Proto

et al. 2019

Clinical Cancer Research

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Purpose: Immune-checkpoint inhibitors (ICI) have improved the survival of patients with non-small cell lung cancer (NSCLC). However, only a subset of patients benefit from ICIs, and the role of PD-L1 as predictive biomarker is still debated. A plasma immune-related miRNA-signature classifier (MSC) was established in lung cancer screening settings to identify the lethal form of the disease in early stages. In this exploratory study, we tested the efficacy of the MSC as prognostic marker in patients with advanced NSCLC treated with ICIs. Experimental Design: The MSC risk level was prospectively assessed in a consecutive series of 140 patients with NSCLC before starting treatment with ICIs. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in strata of PD-L1 and MSC alone or combined were considered as endpoints. Multiple plasma samples to monitor MSC risk level during treatment were also profiled. Results: Adequate tissue and plasma samples were available from 111 (79%) and 104 (75%) patients with NSCLC, respectively. MSC risk level was associated with ORR (P ¼ 0.0009), PFS [multivariate HR ¼ 0.31; 95% confidence interval (CI), 0.17-0.56; P ¼ 0.0001], and OS (multivariate HR ¼ 0.33; 95% CI, 0.18-0.59; P ¼ 0.0002). The combination of MSC and PD-L1 stratified patients into three risk groups having 39%-18%-0% 1-year PFS (P < 0.0001) and 88%-44%-0% 1-year OS (P < 0.0001), according to the presence of 2-1-0 favorable markers. During treatment, MSC risk level decreased or remained low until tumor progression in patients with responsive or stable disease. Conclusions: The plasma MSC test could supplement PD-L1 tumor expression to identify a subgroup of patients with advanced lung cancer with worse ORR, PFS, and OS in immunotherapy regimens.

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“…Specifically, MSC could implement LDCT screening by reducing false-positive results to 3.7%, from 19.7% for LDCT alone 29 . The MSC test has also shown to have a good prognostic performance when considering only lung cancer patients, and could be used as a monitoring tool alone or in combination with other clinical pathological parameters 43 44 . Potentially, the MSC test could enable greater consistency of lung cancer diagnostic algorithms, thus decreasing screening cost-effectiveness.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier (MSC) for Lung Cancer Screening

Mensah

Borzi

Verri

et al. 2017

JoVE

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The development of a minimally invasive test, such as liquid biopsy, for early lung cancer detection in its preclinical phase is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs) are tissue specific, small, non-coding RNAs regulating gene expression, which may act as extracellular messengers of biological signals derived from the cross-talk between the tumor and its surrounding microenvironment. They could thus represent ideal candidates for early detection of lung cancer. In this work, a methodological workflow for the prospective validation of a circulating miRNA test using custom made microfluidic cards and quantitative Real-Time PCR in plasma samples of volunteers enrolled in a lung cancer screening trial is proposed. In addition, since the release of hemolysis-related miRNAs and more general technical issues may affect the analysis, the quality control steps included in the standard operating procedures are also presented. The protocol is reproducible and gives reliable quantitative results; however, when using large clinical series, both pre-analytical and analytical features should be cautiously evaluated.

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Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening–Detected Lung Cancers

Abstract: Tumor mutational status along with a microRNA-based liquid biopsy can provide additional information in planning clinical follow-up in lung cancer LDCT screening programs.

Cited by 13 publications

References 40 publications

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

Circulating miRNAs and PD-L1 Tumor Expression Are Associated with Survival in Advanced NSCLC Patients Treated with Immunotherapy: a Prospective Study

MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier (MSC) for Lung Cancer Screening

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