Comprehensive Review on the Clinical Impact of Next-Generation Sequencing Tests for the Management of Advanced Cancer

Gibbs, Sarah N; Carter, Gebra Cuyún; Palomares, Melanie R.; Thakkar, Snehal Govind; Hall, David W.; Dalglish, Hannah; Campos, Cynthia; Yermilov, Irina

doi:10.1200/po.22.00715

Cited by 8 publications

(5 citation statements)

References 62 publications

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“…Matched targeted therapy with ALK, NTRK, and BRAF inhibitors showed significantly improved progression-free survival (PFS, p = .012) and overall survival (OS, p = .036) in comparison with conventional treatment or no treatment (4). These longer PFS and OS were also found in a comprehensive literature review on the clinical impact of NGS tests for the management of adults with advanced cancer (5).…”

Section: Introductionmentioning

confidence: 73%

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Next-generation sequencing for pediatric CNS tumors: does it add value in a middle-income country setup?

Amayiri,

Al-Hussaini,

Maraqa

et al. 2024

Front. Oncol.

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IntroductionAdvances in molecular diagnostics led to improved targeted interventions in the treatment of pediatric CNS tumors. However, the capacity to test for these is limited in LMICs, and thus their value needs exploration.MethodsWe reviewed our experience with NGS testing (TruSight RNA Pan-Cancer-seq panel) for pediatric CNS tumors at KHCC/Jordan (March/2022–April/2023). Paraffin blocks’ scrolls were shipped to the SickKids laboratory based on the multidisciplinary clinic (MDC) recommendations. We reviewed the patients’ characteristics, the tumor types, and the NGS results’ impact on treatment.ResultsOf 237 patients discussed during the MDC meetings, 32 patients (14%) were included. They were 16 boys and 16 girls; the median age at time of testing was 9.5 years (range, 0.9–21.9 years). There were 21 samples sent at diagnosis and 11 upon tumor progression. The main diagnoses were low-grade-glioma (15), high-grade-glioma (10), and other histologies (7). Reasons to request NGS included searching for a targetable alteration (20) and to better characterize the tumor behavior (12). The median turnaround time from samples’ shipment to receiving the results was 23.5 days (range, 15–49 days) with a median laboratory processing time of 16 days (range, 8–39 days) at a cost of US$1,000/sample. There were 19 (59%) tumors that had targetable alterations (FGFR/MAPK pathway inhibitors (14), checkpoint inhibitors (2), NTRK inhibitors (2), and one with PI3K inhibitor or IDH1 inhibitor). Two rare BRAF mutations were identified (BRAFp.G469A, BRAFp.K601E). One tumor diagnosed initially as undifferentiated round cell sarcoma harbored NAB2::STAT6 fusion and was reclassified as an aggressive metastatic solitary fibrous tumor. Another tumor initially diagnosed as grade 2 astroblastoma grade 2 was reclassified as low-grade-glioma in the absence of MN1 alteration. NGS failed to help characterize a tumor that was diagnosed histologically as small round blue cell tumor. Nine patients received targeted therapy; dabrafenib/trametinib (6), pembrolizumab (2), and entrectinib (1), mostly upon tumor progression (7).ConclusionIn this highly selective cohort, a high percentage of targetable mutations was identified facilitating targeted therapies. Outsourcing of NGS testing was feasible; however, criteria for case selection are needed. In addition, local capacity-building in conducting the test, interpretation of the results, and access to “new drugs” continue to be a challenge in LMICs.

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Section: Introductionmentioning

confidence: 73%

“…LGG (15) Targetable alteraƟon was found (11) Used in treatment (6) Tumor stable/ responded (6) Not used in treatment (5) Stable tumor (4) Family refusal (1) No alteraƟon was found (4) HGG (10) No alteraƟon was found (2) Targetable alteraƟon was found (8) Not used in treatment (…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing for pediatric CNS tumors: does it add value in a middle-income country setup?

Amayiri,

Al-Hussaini,

Maraqa

et al. 2024

Front. Oncol.

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“…Many reports say that the comprehensive profiling of driver gene mutations with multiplex cancer genome panel testing, which can be analyzed using next-generation sequencing (NGS), is useful for the clinical practice of recurrent and metastatic solid cancer [ 10 , 11 , 12 ]. In recent years, two genetic mutation tests have been conducted in general clinical practice to determine the optimal cancer treatment and have been established as a guideline for treatment decision-making in the metastatic setting [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer

Arimura,

Sakai,

Kaneshiro

et al. 2024

Cancers

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Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients’ clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.

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“…3 Nowadays, multimarker tumor panel tests that examine DNA alterations in 200-300 genes are becoming highly used in clinical settings. 4,5 This is due to the growing conviction among clinicians regarding their clinical utility, the development of guidelines recommending their implementation, and the willingness of healthcare payers to provide coverage for the costs associated with these advanced tests. 6,7 However, worldwide accessibility and interpretation of multimarker panel tests remain challenging.…”

Section: Introductionmentioning

confidence: 99%

Fusion Challenges in Solid Tumors: Shaping the Landscape of Cancer Care in Precision Medicine

Ahmed,

Torrado,

Chelariu

et al. 2024

JCO Precis Oncol

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Targeting actionable fusions has emerged as a promising approach to cancer treatment. Next-generation sequencing (NGS)–based techniques have unveiled the landscape of actionable fusions in cancer. However, these approaches remain insufficient to provide optimal treatment options for patients with cancer. This article provides a comprehensive overview of the actionability and clinical development of targeted agents aimed at driver fusions. It also highlights the challenges associated with fusion testing, including the evaluation of patients with cancer who could potentially benefit from testing and devising an effective strategy. The implementation of DNA NGS for all tumor types, combined with RNA sequencing, has the potential to maximize detection while considering cost effectiveness. Herein, we also present a fusion testing strategy aimed at improving outcomes in patients with cancer.

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Comprehensive Review on the Clinical Impact of Next-Generation Sequencing Tests for the Management of Advanced Cancer

Cited by 8 publications

References 62 publications

Next-generation sequencing for pediatric CNS tumors: does it add value in a middle-income country setup?

Next-generation sequencing for pediatric CNS tumors: does it add value in a middle-income country setup?

TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer

Fusion Challenges in Solid Tumors: Shaping the Landscape of Cancer Care in Precision Medicine

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