共查询到16条相似文献,搜索用时 15 毫秒
1.
Douglas B. Johnson Kimberly H. Dahlman Jared Knol Jill Gilbert Igor Puzanov Julie Means‐Powell Justin M. Balko Christine M. Lovly Barbara A. Murphy Laura W. Goff Vandana G. Abramson Marta A. Crispens Ingrid A. Mayer Jordan D. Berlin Leora Horn Vicki L. Keedy Nishitha M. Reddy Carlos L. Arteaga Jeffrey A. Sosman William Pao 《The oncologist》2014,19(6):616-622
Background.
Oncogenic genetic alterations “drive” neoplastic cell proliferation. Small molecule inhibitors and antibodies are being developed that target an increasing number of these altered gene products. Next-generation sequencing (NGS) is a powerful tool to identify tumor-specific genetic changes. To determine the clinical impact of extensive genetic analysis, we reviewed our experience using a targeted NGS platform (FoundationOne) in advanced cancer patients.Patients and Methods.
We retrospectively assessed demographics, NGS results, and therapies received for patients undergoing targeted NGS (exonic sequencing of 236 genes and selective intronic sequencing from 19 genes) between April 2012 and August 2013. Coprimary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage who received genotype-directed therapy.Results.
Samples from 103 patients were tested, most frequently breast carcinoma (26%), head and neck cancers (23%), and melanoma (10%). Most patients (83%) were found to harbor potentially actionable genetic alterations, involving cell-cycle regulation (44%), phosphatidylinositol 3-kinase-AKT (31%), and mitogen-activated protein kinase (19%) pathways. With median follow-up of 4.1 months, 21% received genotype-directed treatments, most in clinical trials (61%), leading to significant benefit in several cases. The most common reasons for not receiving genotype-directed therapy were selection of standard therapy (35%) and clinical deterioration (13%).Conclusion.
Mutational profiling using a targeted NGS panel identified potentially actionable alterations in a majority of advanced cancer patients. The assay identified additional therapeutic options and facilitated clinical trial enrollment. As time progresses, NGS results will be used to guide therapy in an increasing proportion of patients. 相似文献2.
Jeffrey S. Ross Kai Wang Laurie Gay Rami Al‐Rohil Janne V. Rand David M. Jones Hwa J. Lee Christine E. Sheehan Geoff A. Otto Gary Palmer Roman Yelensky Doron Lipson Deborah Morosini Matthew Hawryluk Daniel V. T. Catenacci Vincent A. Miller Chaitanya Churi Siraj Ali Philip J. Stephens 《The oncologist》2014,19(3):235-242
Background.
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer that is rarely curable by surgery and is rapidly increasing in incidence. Relapsed ICC has a poor prognosis, and current systemic nontargeted therapies are commonly extrapolated from those used in other gastrointestinal malignancies. We hypothesized that genomic profiling of clinical ICC samples would identify genomic alterations that are linked to targeted therapies and that could facilitate a personalized approach to therapy.Methods.
DNA sequencing of hybridization-captured libraries was performed for 3,320 exons of 182 cancer-related genes and 36 introns of 14 genes frequently rearranged in cancer. Sample DNA was isolated from 40 μm of 28 formalin-fixed paraffin-embedded ICC specimens and sequenced to high coverage.Results.
The most commonly observed alterations were within ARID1A (36%), IDH1/2 (36%), and TP53 (36%) as well as amplification of MCL1 (21%). Twenty cases (71%) harbored at least one potentially actionable alteration, including FGFR2 (14%), KRAS (11%), PTEN (11%), CDKN2A (7%), CDK6 (7%), ERBB3 (7%), MET (7%), NRAS (7%), BRCA1 (4%), BRCA2 (4%), NF1 (4%), PIK3CA (4%), PTCH1 (4%), and TSC1 (4%). Four (14%) of the ICC cases featured novel gene fusions involving the tyrosine kinases FGFR2 and NTRK1 (FGFR2-KIAA1598, FGFR2-BICC1, FGFR2-TACC3, and RABGAP1L-NTRK1).Conclusion.
Two thirds of patients in this study harbored genomic alterations that are associated with targeted therapies and that have the potential to personalize therapy selection for to individual patients. 相似文献3.
Liangxuan Zhang Liangjing Chen Sachin Sah Gary J. Latham Rajesh Patel Qinghua Song Hartmut Koeppen Rachel Tam Erica Schleifman Haider Mashhedi Sreedevi Chalasani Ling Fu Teiko Sumiyoshi Rajiv Raja William Forrest Garret M. Hampton Mark R. Lackner Priti Hegde Shidong Jia 《The oncologist》2014,19(4):336-343
Purpose.
The success of precision oncology relies on accurate and sensitive molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method for next-generation sequencing (NGS) using the Ion Torrent platform, provides a fast, easy, and cost-effective sequencing workflow for detecting genomic “hotspot” regions that are frequently mutated in human cancer genes. Most recently, the U.K. has launched the AmpliSeq sequencing test in its National Health Service. This study aimed to evaluate the clinical application of the AmpliSeq methodology.Methods.
We used 10 ng of genomic DNA from formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46 cancer genes using the AmpliSeq platform. In a validation study, we developed an orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq variant calls.Results.
Validated mutational analyses revealed that AmpliSeq was effective in profiling gene mutations, and that the method correctly pinpointed “true-positive” gene mutations with variant frequency >5% and demonstrated high-level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also produced several recurrent “false-positive” calls in clinically druggable oncogenes such as PIK3CA.Conclusion.
AmpliSeq provided highly sensitive and quantitative mutation detection for most of the genes on its cancer panel using limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those genes with recurrent “false-positive” variant calls, caution should be used in data interpretation, and orthogonal verification of mutations is recommended for clinical decision making. 相似文献4.
Next‐Generation Sequencing of Circulating Tumor DNA Reveals Frequent Alterations in Advanced Hepatocellular Carcinoma 下载免费PDF全文
Sadakatsu Ikeda Igor F. Tsigelny Åge A. Skjevik Yuko Kono Michel Mendler Alexander Kuo Jason K. Sicklick Gregory Heestand Kimberly C. Banks AmirAli Talasaz Richard B. Lanman Scott Lippman Razelle Kurzrock 《The oncologist》2018,23(5):586-593
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6.
Farzad Jamshidi Erin Pleasance Yvonne Li Yaoqing Shen Katayoon Kasaian Richard Corbett Peter Eirew Amy Lum Pawan Pandoh Yongjun Zhao Jacqueline E. Schein Richard A. Moore Rod Rassekh David G. Huntsman Meg Knowling Howard Lim Daniel J. Renouf Steven J.M. Jones Marco A. Marra Torsten O. Nielsen Janessa Laskin Stephen Yip 《The oncologist》2014,19(6):623-630
7.
Clinical Application of Targeted Deep Sequencing in Solid‐Cancer Patients and Utility for Biomarker‐Selected Clinical Trials 下载免费PDF全文
Soomin Ahn Jae‐Won Yun Kyu‐Tae Kim Se Hoon Park Peter J. Park Hee Cheol Kim Tae Sung Sohn Dong Il Choi Jong Ho Cho Jin Seok Heo Wooil Kwon Hyuk Lee Byung‐Hoon Min Sung No Hong Young Suk Park Ho Yeong Lim Won Ki Kang Woong‐Yang Park Jeeyun Lee 《The oncologist》2017,22(10):1169-1177
8.
Implementation of a Multicenter Biobanking Collaboration for Next‐Generation Sequencing‐Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies 下载免费PDF全文
Fleur Weeber Isaac J. Numan Annette H. Bruggink Paul J. van Diest Stefan M. Willems Wouter B. Veldhuis Michel M. van den Heuvel Rob J. de Knegt Marco J. Koudijs Erik van Werkhoven Ron H.J. Mathijssen Edwin Cuppen Stefan Sleijfer Jan H.M. Schellens Emile E. Voest Marlies H.G. Langenberg Maja J.A. de Jonge Neeltje Steeghs Martijn P. Lolkema 《The oncologist》2017,22(1):33-40
9.
Fluorescence In Situ Hybridization,Immunohistochemistry, and Next‐Generation Sequencing for Detection of EML4‐ALK Rearrangement in Lung Cancer 下载免费PDF全文
Marina Pekar‐Zlotin Fred R. Hirsch Lior Soussan‐Gutman Maya Ilouze Addie Dvir Theresa Boyle Murry Wynes Vincent A. Miller Doron Lipson Gary A. Palmer Siraj M. Ali Shlomi Dekel Ronen Brenner Paul A. Bunn Jr. Nir Peled 《The oncologist》2015,20(3):316-322
Background.
The U.S. Food and Drug Administration-approved method for detecting EML4-ALK rearrangement is fluorescence in situ hybridization (FISH); however, data supporting the use of immunohistochemistry (IHC) for that purpose are accumulating. Previous studies that compared FISH and IHC considered FISH the gold standard, but none compared data with the results of next-generation sequencing (NGS) analysis.Materials and Methods.
We studied FISH and IHC (D5F3 antibody) systematically for EML4-ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance.Results.
Of 51 patients, 4 were positive with FISH (7.8%), and 8 were positive with IHC (15.7%). Three were positive with both. NGS confirmed that four of the five patients who were positive with IHC and negative with FISH were positive for ALK. Two were treated by crizotinib, with progression-free survival of 18 and 6 months. Considering NGS as the most accurate test, the sensitivity and specificity were 42.9% and 97.7%, respectively, for FISH and 100% and 97.7%, respectively, for IHC.Conclusion.
The FISH-based method of detecting EML4-ALK rearrangement in lung cancer may miss a significant number of patients who could benefit from targeted ALK therapy. Screening for EML4-ALK rearrangement by IHC should be strongly considered, and NGS is recommended in borderline cases. Two patients who were negative with FISH and positive with IHC were treated with crizotinib and responded to therapy. 相似文献10.
Implementation of a Molecular Tumor Board: The Impact on Treatment Decisions for 35 Patients Evaluated at Dartmouth‐Hitchcock Medical Center 下载免费PDF全文
Laura J. Tafe Ivan P. Gorlov Francine B. de Abreu Joel A. Lefferts Xiaoying Liu Jason R. Pettus Jonathan D. Marotti Kasia J. Bloch Vincent A. Memoli Arief A. Suriawinata Konstantin H. Dragnev Camilo E. Fadul Gary N. Schwartz Clinton R. Morgan Britt M. Holderness Jason D. Peterson Gregory J. Tsongalis Todd W. Miller Mary D. Chamberlin 《The oncologist》2015,20(9):1011-1018
Background.
Although genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients’ tumor genetic profiles and provide treatment recommendations.Patients and Methods.
DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors.Results.
During the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months.Conclusion.
For the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes.Implications for Practice:
Case evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment. 相似文献11.
FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non‐Small Cell Lung Cancers Harboring BRAF V600E Mutations 下载免费PDF全文
Lauretta Odogwu Luckson Mathieu Gideon Blumenthal Erin Larkins Kirsten B. Goldberg Norma Griffin Karen Bijwaard Eunice Y. Lee Reena Philip Xiaoping Jiang Lisa Rodriguez Amy E. McKee Patricia Keegan Richard Pazdur 《The oncologist》2018,23(6):740-745
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Laura Bonanno Alberto Pavan Alessandra Ferro Lorenzo Calvetti Stefano Frega Giulia Pasello Giuseppe Aprile Valentina Guarneri PierFranco Conte Rete Oncologica Veneta 《The oncologist》2020,25(12)
BackgroundTargeted agents have improved the outcome of a subset of non‐small cell lung cancer (NSCLC). Molecular profiling by next‐generation sequencing (NGS) allows screening for multiple genetic alterations both in tissue and in plasma, but limited data are available concerning its feasibility and impact in real‐world clinical practice.MethodsPatients with advanced NSCLC consecutively referring to our Institution for potential eligibility to VISION trial () were prospectively enrolled. They were already screened with standard method, and EGFR/ALK/ROS‐1 positive cases were excluded. NGS was performed in plasma and tissue using the Guardant360 test covering 73 genes and the Oncomine Focus Assay covering 59 genes, respectively.ResultsThe study included 235 patients. NGS was performed in plasma in 209 (88.9%) cases; 78 of these (37.3%) were evaluated also in tissue; tissue only was analyzed in 26 cases (11.1%). Half of the tissue samples were deemed not evaluable. Druggable alterations were detected in 13 (25%) out of 52 evaluable samples and 31 of 209 (14.8%) of plasma samples. Improved outcome was observed for patients with druggable alterations if treated with matched targeted agents: they had a longer median overall survival (not reached) compared with the ones who did not start any targeted therapy (9.1 months; 95% confidence interval, 4.6–13.6; p = .046). The results of NGS testing potentially also affected the outcome of patients treated with immunotherapy.ConclusionSystematic real‐life NGS testing showed the limit of tissue analysis in NSCLC and highlighted the potentiality of genetic characterization in plasma in increasing the number of patients who may benefit from NGS screening, both influencing the clinical decision‐making process and affecting treatment outcome.Implications for PracticeGenetic characterization of cancer has become more important with time, having had positive implications for treatment specificity and efficacy. Such analyses changed the natural history of advanced non‐small cell lung cancer (aNSCLC) with the introduction of drugs targeted to specific gene alterations (e.g., EGFR mutations, ALK and ROS‐1 rearrangements). In the field of cancer molecular characterization, the applicability of the analysis of a wide panel of genes using a high‐throughput sequencing approach, such as next‐generation sequencing (NGS), is still a matter of research. This study used NGS in a real‐world setting to systematically and prospectively profile patients with aNSCLC. The aim was to evaluate its feasibility and reliability, as well as consequent access to targeted agents and impact on clinical outcome whenever a druggable alteration was detected either in tumor tissue samples or through liquid biopsy. NCT02864992相似文献
13.
Clinical sequencing using a next‐generation sequencing‐based multiplex gene assay in patients with advanced solid tumors 下载免费PDF全文
Tadayuki Kou Masashi Kanai Yoshihiro Yamamoto Mayumi Kamada Masahiko Nakatsui Tomohiro Sakuma Hiroaki Mochizuki Akinori Hiroshima Aiko Sugiyama Eijiro Nakamura Hidehiko Miyake Sachiko Minamiguchi Kyoichi Takaori Shigemi Matsumoto Hironori Haga Hiroshi Seno Shinji Kosugi Yasushi Okuno Manabu Muto 《Cancer science》2017,108(7):1440-1446
Advances in next‐generation sequencing (NGS) technologies have enabled physicians to test for genomic alterations in multiple cancer‐related genes at once in daily clinical practice. In April 2015, we introduced clinical sequencing using an NGS‐based multiplex gene assay (OncoPrime) certified by the Clinical Laboratory Improvement Amendment. This assay covers the entire coding regions of 215 genes and the rearrangement of 17 frequently rearranged genes with clinical relevance in human cancers. The principal indications for the assay were cancers of unknown primary site, rare tumors, and any solid tumors that were refractory to standard chemotherapy. A total of 85 patients underwent testing with multiplex gene assay between April 2015 and July 2016. The most common solid tumor types tested were pancreatic (n = 19; 22.4%), followed by biliary tract (n = 14; 16.5%), and tumors of unknown primary site (n = 13; 15.3%). Samples from 80 patients (94.1%) were successfully sequenced. The median turnaround time was 40 days (range, 18–70 days). Potentially actionable mutations were identified in 69 of 80 patients (86.3%) and were most commonly found in TP53 (46.3%), KRAS (23.8%), APC (18.8%), STK11 (7.5%), and ATR (7.5%). Nine patients (13.0%) received a subsequent therapy based on the NGS assay results. Implementation of clinical sequencing using an NGS‐based multiplex gene assay was feasible in the clinical setting and identified potentially actionable mutations in more than 80% of patients. Current challenges are to incorporate this genomic information into better therapeutic decision making. 相似文献
14.
Lung cancer adrenal gland metastasis: Optimal fine‐needle aspirate and touch preparation smear cellularity characteristics for successful theranostic next‐generation sequencing 下载免费PDF全文
Ferga C. Gleeson MD Benjamin R. Kipp PhD Michael J. Levy MD Jesse S. Voss CT Michael B. Campion Douglas M. Minot CT Zheng J. Tu PhD Eric W. Klee PhD Konstantinos N. Lazaridis MD Sarah E. Kerr MD 《Cancer cytopathology》2014,122(11):822-832
15.
Next‐generation sequencing of urine specimens: A novel platform for genomic analysis in patients with non–muscle‐invasive urothelial carcinoma treated with bacille Calmette‐Guérin 下载免费PDF全文
Sasinya N. Scott Irina Ostrovnaya PhD Caroline M. Lin Nancy Bouvier Bernard H. Bochner MD FACS Gopakumar Iyer MD David Solit MD Michael F. Berger PhD Oscar Lin MD PhD 《Cancer cytopathology》2017,125(6):416-426
16.
A Curative‐Intent Trimodality Approach for Isolated Abdominal Nodal Metastases in Metastatic Colorectal Cancer: Update of a Single‐Institutional Experience 下载免费PDF全文
Benny Johnson Zhaohui Jin Michael G. Haddock Christopher L. Hallemeier James A. Martenson Rory L. Smoot David W. Larson Eric J. Dozois David M. Nagorney Axel Grothey 《The oncologist》2018,23(6):679-685