Assessing the Value of Next-Generation Sequencing Tests in a Dynamic Environment

2018 ◽  
pp. 139-146 ◽  
Author(s):  
Howard A. Burris ◽  
Leonard B. Saltz ◽  
Peter P. Yu
Keyword(s):  
Next Generation Sequencing ◽  
Cancer Biology ◽  
Health Care Policy ◽  
Clinical Care ◽  
Dynamic Environment ◽  
Investigational Drug ◽  
Next Generation ◽  
Genomic Alterations ◽  
Clinical Annotation ◽  
Generation Sequencing

Next-generation sequencing (NGS)–based technology has lowered the cost of cancer testing for genomic alterations and is now commercially available from a growing number of diagnostic laboratories. However, laboratories vary in the methodologies underlying their tests, the types and numbers of genomic alterations covered by the test, and the clinical annotation of the sequencing findings. Determining the value of NGS tests is dependent on whether it is used to support clinical trials or as a part of routine clinical care at a time when both the investigational drug pipeline and the list of U.S. Food and Drug Administration–approved or Compendium-listed therapeutics is in a high state of flux. Reimbursement policy for NGS testing by the Centers for Medicare & Medicaid is evolving as the value of NGS testing becomes more clearly defined for specific clinical situations. Patient care and clinical decisions-making are dependent on the oncologist’s knowledge of when NGS testing has value. Here, we review principles and practice for NGS testing in this dynamic confluence of technology, cancer biology, and health care policy.

Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 584-584
Author(s):  
Kristin Lynn Koenig ◽  
Jarred Burkart ◽  
Sameh Mikhail ◽  
Christina Sing-Ying Wu ◽  
Anne M. Noonan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Clinical Care ◽  
Comprehensive Cancer Center ◽  
Genomic Profiling ◽  
Next Generation ◽  
Wild Type ◽  
Genomic Alterations ◽  
Generation Sequencing

584 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 265 pts with GI malignancies underwent successful genomic profiling. 1205 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through next generation sequencing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.

scholarly journals Next-Generation Sequencing Approach to Non–Small Cell Lung Carcinoma Yields More Actionable Alterations

2017 ◽  
Vol 142 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Mitra Mehrad ◽  
Somak Roy ◽  
Humberto Trejo Bittar ◽  
Sanja Dacic
Keyword(s):  
Next Generation Sequencing ◽  
Lung Adenocarcinoma ◽  
Small Cell ◽  
Gene Panel ◽  
Next Generation ◽  
Small Cell Lung ◽  
Genomic Alterations ◽  
Generation Sequencing ◽  
Gene Alterations ◽  
Cancer Panel

Context.— Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance. Objective.— To determine the best testing algorithm for patients with lung cancer in our clinical practice. Design.— Two testing approaches for metastatic lung adenocarcinoma were offered between 2012–2015. One approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK, ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the 8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel. Results.— Of 1200 non–small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29 adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%) in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of 29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2 LCNECs showed investigational genomic alterations. Conclusions.— The NGS approach would result in the identification of a significant number of actionable gene alterations, increasing the therapeutic options for patients with advanced NSCLCs.

Correlation of genomic alterations between tumor tissue and circulating tumor DNA by next-generation sequencing

2018 ◽  
Vol 144 (11) ◽  
pp. 2167-2175 ◽  
Author(s):  
Ya-Sian Chang ◽  
Hsin-Yuan Fang ◽  
Yao-Ching Hung ◽  
Tao-Wei Ke ◽  
Chieh-Min Chang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Next Generation ◽  
Genomic Alterations ◽  
Tumor Dna ◽  
Generation Sequencing

Comutation of PIK3CA and TP53 in Residual Disease After Preoperative Anti-HER2 Therapy in ERBB2 (HER2)-Amplified Early Breast Cancer

2019 ◽  
pp. 1-26
Author(s):  
Frankie Ann Holmes ◽  
Maren K. Levin ◽  
Ying Cao ◽  
Sohail Balasubramanian ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Next Generation Sequencing ◽  
Residual Disease ◽  
Preoperative Treatment ◽  
Next Generation ◽  
Her2 Positive ◽  
Genomic Alterations ◽  
Pik3ca Mutations ◽  
Her2 Breast Cancer ◽  
Generation Sequencing

PURPOSE To identify proteomic and genomic alterations in residual disease (RD) for human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer (BC) after preoperative trastuzumab (H), lapatinib (L), or both (H+L) in combination with chemotherapy. PATIENTS AND METHODS Patients with stage II/III HER2+ BC (n = 100) were randomly assigned to preoperative treatment with H versus L 1,250mg versus H+L (L: 750 to 1,000 mg) plus 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel. After receiving institutional review board–approved informed consent, targeted next-generation sequencing was performed on 20 patients’ formalin-fixed paraffin embedded tumors to characterize genomic alterations across 287 cancer-related genes. Reverse phase protein array (RPPA) analysis was performed on both the baseline biopsy and RD specimens, when available. RESULTS Two of 20 RD tissues were HER2 negative per next-generation sequencing; one sample had insufficient tissue. Of six pretreatment biopsy specimens, four were comutated with TP53 and PIK3CA. Of 17 HER2+ RD, seven specimens (41%) had PIK3CA mutations always comutated with TP53, and four (24%) also had concurrent CDK12 amplification. Overall, CDK12 amplification was observed in eight of the 17 (47%) HER2+ RD specimens. A total of 12 RD specimens (71%) had TP53 mutations. Although prevalence of individual TP53 and PIK3CA mutations was only modestly higher than published estimates for those in HER2+ primary BCs (55% and 32% for TP53 and PIK3CA, respectively), prevalence of these as comutations appeared higher (41%), compared with less than 10% in several series. On RPPA analysis of the RD tissue with comutations, the strongest Spearman ρ correlations were limited to EGFR and phospho-AKT (ρ, 0.999; P = .019) and phospho-mTOR and phospho-S6 ribosomal protein (ρ, 0.994; P = .048). CONCLUSION HER2-amplified RD tissue after preoperative H, L, or H+L plus chemotherapy was enriched for PIK3CA and TP53 comutations, and the RD tissue demonstrated activation of EGFR/AKT/mTOR signaling on RPPA.

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