Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer

2021 ◽  
Vol 2021 (10) ◽  
Author(s):  
Farasat Kazmi ◽  
Nipun Shrestha ◽  
Stephen Booth ◽  
David Dodwell ◽  
Francesca Aroldi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Metastatic Cancer ◽  
Next Generation ◽  
Generation Sequencing

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: Targeting Targeted Therapies

2015 ◽  
Vol 21 (16) ◽  
pp. 3584-3585 ◽  
Author(s):  
Justine N. McCutcheon ◽  
Giuseppe Giaccone
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Clinical Targeted Next-Generation Sequencing to Identify Potentially Actionable Alterations in the Majority of Asian Cancer Patients

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 88s-88s
Author(s):  
S.L. Poon ◽  
Y.-J. Lu ◽  
R.-S. Jhou ◽  
Y.-T. Yang ◽  
P.-N. Yu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Hedgehog Signaling ◽  
Next Generation ◽  
Therapeutic Implications ◽  
Targeted Next Generation Sequencing ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Tissues ◽  
Tumor Types ◽  
Generation Sequencing

Background: Clinically innovative genomic diagnostics may expedite the selection of effective targeted therapies if the patient can be stratified correctly based on their unique cancer driven events/pathways during tumorigenesis. Aim: Here, we performed a pan-cancer analysis on the clinical utility of a targeted gene panel, ACTOnco+, in characterizing the prevalence of actionable mutations. Methods: A total of 229 formalin-fixed, paraffin-embedded (FFPE) tissues from 40 tumor types were subjected to next-generation sequencing (NGS) using the Ion Torrent Proton System. All coding exons in 440 cancer-related genes were assessed at average depth of > 800X. Therapeutic implications were based on information obtained from base substitutions, indels, and copy number alterations (CNAs). Results: 58.5% (n=134) patients harbored at least one actionable mutation while CNAs, including homozygous and heterozygous deletions, were detected in 83.9% (n=191) of patients. Across all tumor types, the most frequently altered pathway that can confer either sensitivity or resistance to targeted therapies was PI3K/AKT/mTOR signaling, contributed by PIK3CA and AKT1 activating mutations as well as NF1, NF2, PTEN, TSC1, STK11 and TSC2 inactivating mutations or deletions. In parallel, dysregulation of cell cycle was mostly owing to CCND1, CDK4 and CDK6 amplification and/or loss of CDKN2A. Notably, on top of BRCA1/ 2 mutations, deletion of BRCAness-related genes ( MRE11, RAD50, PALB2, FANCD2, ATM, ATR, CHEK1 and CHEK2) that may result in homologous recombination deficiency (HRD) was observed in 71.4% breast, 70.6% ovarian, 61.0% lung, 58.3% pancreatic, and 52.2% colorectal cancers. Other targetable alterations on receptor tyrosine kinase (RTK), angiogenic and hedgehog signaling pathways were also observed. Conclusion: A comprehensive pathway-based genomic profiling characterized significant actionable alterations across different solid tumors that may play a role in tissue-agnostic tailored treatment.

scholarly journals Pituitary Metastatic Composite Tumors: A Case Report with Next-Generation Sequencing and Review of the Literature

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Matthew Helton ◽  
Muhammad Abu-Rmaileh ◽  
Kevin Thomas ◽  
Murat Gokden ◽  
Alissa Kanaan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Vision Loss ◽  
Clear Cell ◽  
Metastatic Cancer ◽  
Postoperative Mortality ◽  
Initial Symptom ◽  
Next Generation ◽  
Endoscopic Endonasal ◽  
Primary Tumors ◽  
Generation Sequencing

Background. While pituitary tumors are well understood, little research has been done on metastasis from primary tumors into pituitary adenomas, also known as composite tumors. Because only 34 cases of composite tumors have been reported to date, we hope to better characterize these tumors by reviewing cases reported in the literature and reviewed our own documented case, which includes next-generation sequencing. Case Presentation. A 74-year-old man presented to the emergency department with left vision loss for 3 months. He had a history of colon cancer treated with colectomy and clear cell renal carcinoma treated with left nephrectomy. A preoperative MRI demonstrated growth of a peripherally enhancing, centrally necrotic mass with sellar expansion measuring 5.7×3.1×3.0 cm. Given these findings, an endoscopic endonasal transsphenoidal resection was performed. Histological assessment revealed a composite tumor: one neoplasm was a nonfunctioning pituitary adenoma, and another neoplasm was a clear cell carcinoma. Next-generation sequencing demonstrated that the tumors shared mutations in VHL and Notch2. The patient died 2 months later from systemic metastatic cancer. Conclusion. From our literature review, most metastatic lesions in these composite tumors originated from neoplasms of the lung and kidney. Approximately 63% patients presented with ophthalmoplegia as the initial symptom while 23% displayed hormonal abnormalities. Postoperative mortality had a median of 3.5 months. In our patient, the presence of VHL and Notch2 mutations in both tumors highlights the possibility of using next-generation sequencing to help identify therapeutic targets even in complex composite neoplasms.

Transcriptome (RNA next generation sequencing) for personalizing of cancer treatment: A correlation with previous clinical resistance.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15046-e15046
Author(s):  
Manuel Sureda ◽  
Joseba Rebollo ◽  
Ramón González-Manzano ◽  
Elena Ma Martínez ◽  
Roman Rostagno ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Next Generation Sequencing ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Alkylating Agents ◽  
Treatment Decision ◽  
Clinical Information ◽  
Next Generation ◽  
Clinical Resistance ◽  
Generation Sequencing

e15046 Background: RNA Next Generation Sequencing (transcriptome) is a potential useful tool to predict chemoresistance to available anticancer drug therapy. A correlation between previous clinical resistance and drug resistance profiling according to RNA NGS results has been studied. Methods: Since March 2018, whole transcriptome RNA NGS has been performed using Ion-Torrent GeneStudio S5 System in fresh-frozen biopsies obtained from tru-cut or surgical excision procedures from patients with resistant metastatic cancer. We have selected patients with clinically unequivocal drug resistance to previous therapies (tumor progressing to ongoing therapies or less than six months of stopped therapy). Drugs evaluated includes anthracyclines, alkylating agents (temozolomide), platinum derivatives, taxanes, TOPO 1 inhibitors (irinotecan and topotecan), antimetabolites (fluoropyrimidines, gemcitabine, methotrexate and pemetrexed), and more recently, immune checkpoint inhibitors. Results: A total of 111 procedures have been performed. In 64 patients an unequivocal clinical resistance to previous therapies could not be demonstrated, so the analyses has been performed in 47 patients with a number of different tumor histologies: colorectal cancer (13 patients), ovary/peritoneum (8), pancreas (4), NSCLC (4), breast (3), prostate (3), sarcoma (3), head and neck (2), uterus (2), kidney, bladder, cholangiocarcinoma, stomach and cervix (1 patient each). One hundred and fifty two drugs have been used in these patients (Median 3, Range 1 to 8) previous to the RNA NGS procedure. Resistance profile has been found in 120 out of 152 (78.9% of coincidence), and a favourable profile has been found in 32 (21%) previously used drugs, that could be re-used again in these patients. RNA NGS procedure gives additional information about drugs not previously used that helps in the treatment selection for the patients. Conclusions: Transcriptome provide drug resistance information that correlates in 78.9% of drugs with the previous clinical information. However, in 21% of the previously used drugs transcriptome informs as potentially active and could be tried again in subsequent therapies. Transcriptome (RNA sequencing) provides useful clinical information for treatment decision in the vast majority of pretreated cancer patients.

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