Clinical benefit of next generation sequencing in soft tissue and bone sarcoma: Rush University Medical Center’s experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22552-e22552
Author(s):  
Mia C. Weiss ◽  
Alan Blank ◽  
Steven Gitelis ◽  
Mary J. Fidler ◽  
Marta Batus
Keyword(s):  
Overall Survival ◽  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Clinical Decision Making ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Next Generation ◽  
Undifferentiated Sarcoma ◽  
The Impact ◽  
Generation Sequencing

e22552 Background: The overall survival for metastatic sarcoma has remained at only 18-20%. In the era of next generation sequencing (NGS), much research is ongoing on identifying optimal treatments. The MULTISARC trial aims to determine if NGS can lead to improved overall survival by randomizing patients with metastatic STS to receive NGS (followed by possible NGS-guided therapy) or not. We present our center’s experience with NGS in sarcomas patients. Methods: Patients with soft tissue and bone sarcomas at Rush that had the Foundation Medicine assay sent on tumor samples between August 2017 and August 2018 were analyzed retrospectively. The impact of NGS on clinical decision making was determined based on patients being prescribed off-label FDA-approved therapy targeting identified mutation. Results: Thirty-four patients with bone/soft tissue sarcomas that had NGS sent on specimens were identified. Median age at diagnosis: 43 (18-78 years); 18 males, 16 females. Histologic subtypes: synovial sarcoma, myxofibrosarcoma, leiomyosarcoma, chondrosarcoma, sclerosing epitheloid fibrosarcoma, PEcoma, pleomorphic undifferentiated sarcoma, MPNST, liposarcoma- well and de-differentiated, angiosarcoma, osteosarcoma. 16/34 patients had targetable mutations with approved therapies in tumor types other than sarcoma. Four of these patients had therapy changed based on NGS results, 1 patient with metastatic chondrosarcoma (PTEN mutation, everolimus added), 1 patient with metastatic liposarcoma (CDK4 mutation, palbociclib added), 1 patient with metastatic osteosarcoma (CCD1/CDK4 and a PDGFRA mutation for which palbociclib followed by imatinib was added), and 1 patient with metastatic pleomorphic undifferentiated sarcoma (CDK4 mutation, palbociclib added). Targetable mutations for which clinical trials are available were identified in 25/34 (73%) of the cases. Conclusions: NGS was readily able to identify actionable mutations in close to 50% of patients with clinical trial opportunities in close to 75%. Four patients had therapy changed as a result of NGS testing. Although our study size is small, our data show potential for the use of genomic profiling to identify actionable targets, tailor therapy, and hopefully improve outcomes. [Table: see text]

Molecular profiling of soft tissue sarcomas using next-generation sequencing: a pilot study toward precision therapeutics

2014 ◽  
Vol 45 (8) ◽  
pp. 1563-1571 ◽  
Author(s):  
George Jour ◽  
John D. Scarborough ◽  
Robin L. Jones ◽  
Elizabeth Loggers ◽  
Seth M. Pollack ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pilot Study ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Molecular Profiling ◽  
Next Generation ◽  
Generation Sequencing ◽  
Precision Therapeutics

Thank you, next: The impact of next-generation sequencing in clinical decision making.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13136-e13136
Author(s):  
William Davis ◽  
Gabriel Makar ◽  
Greg J. Kubicek
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Decision Making ◽  
Poor Response ◽  
Clinical Decision ◽  
Next Generation ◽  
Duration Of Treatment ◽  
Tissue Samples ◽  
Off Label ◽  
The Impact ◽  
Generation Sequencing

e13136 Background: Next Generation Sequencing (NGS) is increasingly used to identify actionable mutations for oncology treatment. We examined the results of NGS at our institution. Methods: We retrospectively reviewed the medical charts of 305 consecutive patients who had genomic testing performed on tumor samples from March 2014 to April 2017. Next Generation Sequencing was performed by Foundation One testing. Results: Of the 305 tissue samples sent to Foundation One, 189 reports were potentially usable. Reports were unusable due to an insufficient quantity of tissue (43), inadequate follow-up (32), cessation of oncologic care due to transferring to hospice or expiring (32), or a report not being generated due to the order being cancelled (4) or undocumented reasons (5). Of the 189 usable reports, 76 (40.21%) demonstrated an aberration targetable by on-label therapies, 126 (66.67%) via off-label therapies (66 of these had no available on-label treatment), and 170 (89.94%) revealed actionable aberrations via all potential avenues, including clinical trials. 19 (6.2%) yielded a change in management, 6 of these changes were utilizing on-label therapies, 6 were via off-label therapies, 3 were via enrollment in a clinical trial, and 4 involved discontinuing a medication with a predicted poor response. For the 6 patients with off-label use, median duration of treatment was 46 days and discontinued secondary to death (3 patients) or progression (3 patients). Conclusions: Only a minority of NGS assay results (6.2% percent of all tests ordered and 10% of useable tests) resulted in a management change. A small minority (6 patients, 1.9%) were started on off-label therapy based on NSG results and overall had poor responses to off-label treatment. While in theory NGS may improve oncology outcome, the results of our initial 305 patients who had NGS was poor.

scholarly journals Impact on Clinical Decision Making of Next-Generation Sequencing in Pediatric Epilepsy in a Tertiary Epilepsy Referral Center

2019 ◽  
Vol 51 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Hannes Hoelz ◽  
Christian Herdl ◽  
Lucia Gerstl ◽  
Moritz Tacke ◽  
Katharina Vill ◽  
...  
Keyword(s):  
Decision Making ◽  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Clinical Management ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pediatric Epilepsy ◽  
Next Generation ◽  
The Impact ◽  
Generation Sequencing

Background. Next-generation sequencing (NGS) describes new powerful techniques of nucleic acid analysis, which allow not only disease gene identification diagnostics but also applications for transcriptome/methylation analysis and meta-genomics. NGS helps identify many monogenic epilepsy syndromes. Pediatric epilepsy patients can be tested using NGS epilepsy panels to diagnose them, thereby influencing treatment choices. The primary objective of this study was to evaluate the impact of genetic testing on clinical decision making in pediatric epilepsy patients. Methods. We completed a single-center retrospective cohort study of 91 patients (43 male) aged 19 years or less undergoing NGS with epilepsy panels differing in size ranging from 5 to 434 genes from October 2013 to September 2017. Results. During a mean time of 3.6 years between symptom onset and genetic testing, subjects most frequently showed epileptic encephalopathy (40%), focal epilepsy (33%), and generalized epilepsy (18%). In 16 patients (18% of the study population), “pathogenic” or “likely pathogenic” results according to ACMG criteria were found. Ten of the 16 patients (63%) experienced changes in clinical management regarding their medication and avoidance of further diagnostic evaluation, that is, presurgical evaluation. Conclusion. NGS epilepsy panels contribute to the diagnosis of pediatric epilepsy patients and may change their clinical management with regard to both preventing unnecessary and potentially harmful diagnostic procedures and management. Thus, the present data support the early implementation in order to adopt clinical management in selected cases and prevent further invasive investigations. Given the relatively small sample size and heterogeneous panels a larger prospective study with more homogeneous panels would be helpful to further determine the impact of NGS on clinical decision making.

Larotrectinib followed by selitrectinib in a novel DCTN1–NTRK1 fusion undifferentiated pleomorphic sarcoma

2020 ◽  
pp. 107815522093884
Author(s):  
Xue Na Goh ◽  
Michaela Su-Fern Seng ◽  
Amos Hong Pheng Loh ◽  
Achint Gupta ◽  
Kenneth Tou En Chang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Gene Fusion ◽  
Acquired Resistance ◽  
Resistance Mutation ◽  
Soft Tissue Sarcomas ◽  
Next Generation ◽  
Pleomorphic Sarcoma ◽  
Trk Inhibitors ◽  
Generation Sequencing

Introduction Neurotrophic receptor tyrosine kinase fusions cause overexpression or activation of kinase and are believed to confer oncogenic potential in some non-rhabdomyosarcoma soft tissue sarcomas. TRK inhibitors have recently been shown to induce responses in these tumours though current experience with these agents is still limited. Case report We report a case of an adolescent with treatment-refractory non-rhabdomyosarcoma soft tissue sarcomas, carrying a novel DCTN1–NTRK1 gene fusion whose progressive disease was treated with multi-kinase and TRK inhibitors. Management and outcome: Our patient was started on pan-TRK inhibitor larotrectinib, as his disease progressed after chemotherapy, radiation therapy and surgery, based on next-generation sequencing test showing DCTN1–NTRK1 gene fusion. He responded quickly to larotrectinib with the improvement of symptoms and reduction of masses. However, this response was short-lived due to the development of acquired solvent front resistance mutation. This patient did not respond to next-generation TRK inhibitor selitrectinib and eventually succumbed to his disease. Discussion The initial rapid and drastic response of our patient to larotrectinib was not sustained due to the development of acquired resistance. This case emphasizes the need for upfront and periodic next-generation sequencing testing to guide treatment of patients with refractory non-rhabdomyosarcoma soft tissue sarcomas.

scholarly journals Suitability of Bronchoscopic Biopsy Tissue Samples for Next-Generation Sequencing

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 391
Author(s):  
Shuji Murakami ◽  
Tomoyuki Yokose ◽  
Daiji Nemoto ◽  
Masaki Suzuki ◽  
Ryou Usui ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Success Rate ◽  
Rna Sequencing ◽  
Surface Area ◽  
Endobronchial Ultrasound ◽  
Next Generation ◽  
Endobronchial Ultrasonography ◽  
Tissue Surface ◽  
The Impact ◽  
Generation Sequencing

A sufficiently large tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥1 mm2) and tumor content rate (≥30%) on the success rate of the Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

scholarly journals Next-Generation Sequencing: From Basic Research to Diagnostics

2009 ◽  
Vol 55 (4) ◽  
pp. 641-658 ◽  
Author(s):  
Karl V Voelkerding ◽  
Shale A Dames ◽  
Jacob D Durtschi
Keyword(s):  
Next Generation Sequencing ◽  
Dna Sequencing ◽  
Single Molecule ◽  
Basic Research ◽  
Clinical Diagnostics ◽  
Massively Parallel ◽  
Next Generation ◽  
New Paradigm ◽  
The Impact ◽  
Generation Sequencing

Abstract Background: For the past 30 years, the Sanger method has been the dominant approach and gold standard for DNA sequencing. The commercial launch of the first massively parallel pyrosequencing platform in 2005 ushered in the new era of high-throughput genomic analysis now referred to as next-generation sequencing (NGS). Content: This review describes fundamental principles of commercially available NGS platforms. Although the platforms differ in their engineering configurations and sequencing chemistries, they share a technical paradigm in that sequencing of spatially separated, clonally amplified DNA templates or single DNA molecules is performed in a flow cell in a massively parallel manner. Through iterative cycles of polymerase-mediated nucleotide extensions or, in one approach, through successive oligonucleotide ligations, sequence outputs in the range of hundreds of megabases to gigabases are now obtained routinely. Highlighted in this review are the impact of NGS on basic research, bioinformatics considerations, and translation of this technology into clinical diagnostics. Also presented is a view into future technologies, including real-time single-molecule DNA sequencing and nanopore-based sequencing. Summary: In the relatively short time frame since 2005, NGS has fundamentally altered genomics research and allowed investigators to conduct experiments that were previously not technically feasible or affordable. The various technologies that constitute this new paradigm continue to evolve, and further improvements in technology robustness and process streamlining will pave the path for translation into clinical diagnostics.

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