Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

IF 3.2 Q2 ONCOLOGY

Oncology and Therapy Pub Date : 2024-03-01 Epub Date: 2024-01-11 DOI:10.1007/s40487-023-00252-5

Francesco Pepe, Gianluca Russo, Alessandro Venuta, Claudia Scimone, Mariantonia Nacchio, Pasquale Pisapia, Gaia Goteri, Francesca Barbisan, Caterina Chiappetta, Angelina Pernazza, Domenico Campagna, Marco Giordano, Giuseppe Perrone, Giovanna Sabarese, Annalisa Altimari, Dario de Biase, Giovanni Tallini, Daniele Calistri, Elisa Chiadini, Laura Capelli, Alfredo Santinelli, Anna Elisa Gulini, Elisa Pierpaoli, Manuela Badiali, Stefania Murru, Riccardo Murgia, Elena Guerini Rocco, Konstantinos Venetis, Nicola Fusco, Denise Morotti, Andrea Gianatti, Daniela Furlan, Giulio Rossi, Laura Melocchi, Maria Russo, Caterina De Luca, Lucia Palumbo, Saverio Simonelli, Antonella Maffè, Paola Francia di Celle, Tiziana Venesio, Maria Scatolini, Enrico Grosso, Sara Orecchia, Matteo Fassan, Mariangela Balistreri, Elisabetta Zulato, Daniela Reghellin, Elena Lazzari, Maria Santacatterina, Maria Liliana Piredda, Manuela Riccardi, Licia Laurino, Elena Roz, Domenico Longo, Daniela Petronilla Romeo, Carmine Fazzari, Andrea Moreno-Manuel, Giuseppe Diego Puglia, Andrey D Prjibelski, Daria Shafranskaya, Luisella Righi, Angela Listì, Domenico Vitale, Antonino Iaccarino, Umberto Malapelle, Giancarlo Troncone

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引用次数: 0

Abstract

Introduction: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples.

Methods: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated.

Results: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation.

Conclusions: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

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对参考样本进行非小细胞肺癌检测：意大利多中心经验

简介生物标记物检测是晚期非小细胞肺癌（NSCLC）患者临床治疗的必备条件。目前有无数种技术平台可用于生物标记分析，但它们在复用能力、分析灵敏度和周转时间（TAT）方面存在差异。我们对 24 家具有代表性的意大利机构的诊断工作流程的技术性能进行了评估，这些机构对一系列模拟常规诊断样本的人工参考样本进行了分子检测：方法：向每个参与机构分发了八张切片样本集，这些切片来自携带表皮生长因子受体（EGFR）19外显子p.E746_AT50del、KRAS（Kirsten大鼠肉瘤病毒癌基因同源物）2外显子p.G12C、ROS1（c-ros oncogene 1）-未知基因融合和MET（MET原癌基因，受体酪氨酸激酶）Δ 14外显子缺失的人工参考标本细胞块。两个独立的细胞块标本在运送前由那不勒斯费德里科二世大学（University of Naples Federico II）验证。对参考标本的方法学和分子数据进行了注释：总体而言，通过自动和手动技术程序分别获得了 3.3 ng/µL（范围 0.1-10.0 ng/µL）和 13.4 ng/µL（范围 2.0-45.8 ng/µL）的中位数 DNA 浓度。检测到的 RNA 浓度分别为 5.7 ng/µL（范围 0.2-11.9 ng/µL）和 9.3 ng/µL（范围 0.5-18.0 ng/µL）。在所有检测病例中均发现了KRAS第2外显子p.G12C、表皮生长因子受体第19外显子p.E736_A750del热点突变和ROS1异常转录本，而16个中心中有15个（93.7%）检测到了MET第14外显子跳越突变：结论：优化技术工作流程对 NSCLC 患者的决策策略至关重要。人工参考标本可以优化诊断工作流程，从而在常规临床实践中进行预测性分子分析。

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来源期刊

Oncology and Therapy ONCOLOGY-

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of clinical therapies. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. Digital features and plain language summaries Oncology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case by case basis and should be sent to the journal editor. Copyright Oncology and Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0 Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of £3650/€4500/$5100. The journal will consider fee discounts for developing countries and this is decided on a case by case basis. Open Access All articles published by Oncology and Therapy are published open access Contact For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.