scholarly journals Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options

2017 ◽  
Vol 22 (7) ◽  
pp. 834-842 ◽  
Author(s):  
Laurie M. Gay ◽  
Sungeun Kim ◽  
Kyle Fedorchak ◽  
Madappa Kundranda ◽  
Yazmin Odia ◽  
...  
Keyword(s):  
Treatment Options ◽  
Additional Treatment ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling

scholarly journals Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Fiona Turkes ◽  
Juliet Carmichael ◽  
David Cunningham ◽  
Naureen Starling
Keyword(s):  
Clinical Trials ◽  
Biliary Tract ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Response To Treatment ◽  
Genomic Profiling ◽  
Biliary Tract Cancers ◽  
Comprehensive Genomic Profiling ◽  
Genomic Aberrations ◽  
Oncology Treatment

Biliary tract cancers (BTCs) are poor prognosis malignancies with limited treatment options. Capecitabine has recently emerged as an effective agent in the adjuvant setting; however, treatment of advanced disease is still limited to first-line cisplatin and gemcitabine chemotherapy. Recent global efforts in genomic profiling and molecular subtyping of BTCs have uncovered a wealth of genomic aberrations which may carry prognostic significance and/or predict response to treatment, and several targeted agents have shown promising results in clinical trials. As such, the uptake of comprehensive genomic profiling for patients with BTCs and the expansion of basket trials to include these patients are growing. This review describes the currently approved systemic therapies for BTCs and provides insight into the emerging targeted and immunotherapeutic agents, as well as conventional chemotherapeutic regimes, currently being investigated in clinical trials.

scholarly journals Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5181-5184 ◽  
Author(s):  
Lisa Giulino-Roth ◽  
Kai Wang ◽  
Theresa Y. MacDonald ◽  
Susan Mathew ◽  
Yifang Tam ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Genetic Basis ◽  
Treatment Options ◽  
Additional Treatment ◽  
Nucleosome Remodeling ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Comprehensive Genomic Profiling ◽  
Generation Sequencing ◽  
Formalin Fixed

Abstract To ascertain the genetic basis of pediatric Burkitt lymphoma (pBL), we performed clinical-grade next-generation sequencing of 182 cancer-related genes on 29 formalin-fixed, paraffin embedded primary pBL samples. Ninety percent of cases had at least one mutation or genetic alteration, most commonly involving MYC and TP53. EBV(−) cases were more likely than EBV(+) cases to have multiple mutations (P < .0001). Alterations in tumor-related genes not previously described in BL were identified. Truncating mutations in ARID1A, a member of the SWI/SNF nucleosome remodeling complex, were seen in 17% of cases. MCL1 pathway alterations were found in 22% of cases and confirmed in an expanded panel. Other clinically relevant genomic alterations were found in 20% of cases. Our data suggest the roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that comprehensive genomic profiling may identify additional treatment options in refractory disease.

scholarly journals TNS1- ALK Fusion in a Recurrent, Metastatic Uterine Mesenchymal Tumor Originally Diagnosed as Leiomyosarcoma

2019 ◽  
Vol 48 (1) ◽  
pp. 116
Author(s):  
Jessica Lee ◽  
Arun Singh ◽  
Siraj M. Ali ◽  
Douglas I. Lin ◽  
Samuel J. Klempner
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Standard Of Care ◽  
Genomic Profiling ◽  
Curative Intent ◽  
Case Identification ◽  
Complementary Role ◽  
Comprehensive Genomic Profiling ◽  
Standard Of Care Treatment

<p><strong>Objective.</strong> We report a female patient diagnosed with a leiomyosarcoma and who harbored a druggable target as identified by comprehensive genomic profiling in the course of clinical care.</p><p><strong>Case Report.</strong> The patient progressed five years after curative intent surgery and adjuvant treatment. After failure of multiple lines of chemotherapy,she was enrolled in a trial of an ALK inhibitor based on comprehensive genomic profiling (CGP) identifying an TNS1-ALK fusion.</p><p><strong>Conclusion. </strong>In this case, identification of the ALK kinase fusion permitted enrollment in a matched mechanism driven clinical trial after exhausting standard of care treatment options. CGP raises the possibility of uterine inflammatory myofibroblastic tumor as an alternative diagnosisto leiomyosarcoma, highlighting the complementary role of CGP beyond immunohistochemical analyses.</p>

Penile and uterine cervical squamous cell carcinomas: A comparative genomic profiling study.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 514-514 ◽  
Author(s):  
Joseph Jacob ◽  
Rubin Pinkhasov ◽  
Oleg Shapiro ◽  
Nick Liu ◽  
Laurie M. Gay ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Treatment Options ◽  
Cervical Squamous Cell Carcinoma ◽  
Mtor Pathway ◽  
Comparative Genomic ◽  
High Status ◽  
Genomic Profiling ◽  
Hpv Status ◽  
Comprehensive Genomic Profiling ◽  
Tumor Types

514 Background: Metastatic penile (mPSCC) and uterine cervical squamous cell carcinoma (mCSCC) are aggressive forms of malignancy with limited treatment options. We used comprehensive genomic profiling (CGP) to compare the genomic alterations (GA) and their potential impact on targeted and immunotherapy options of mPSCC and mCSCC. Methods: 78 metastatic mPSCC and 604 mCSCC underwent CGP using a hybrid-capture-based next-generation sequencing assay with a mean coverage depth of > 500X. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: The median age of mPSCC men was higher than mCSCC women. The HPV+/CDKN2A- status was more frequent in the mCSCC than mPSCC. The GA/tumor were similar for both tumor types (table). TP53 mutations were more common in mPSCC likely linked to loss of original HPV+ status. TERT, NOTCH1 and FAT1 GA were more frequent in mPSCC whereas PIK3CA GA were more common in mCSCC. MTOR pathway targets (GA in STK11, FBXW7 and PTEN) were more common in mCSCC. MSI-High status was extremely rare in all cases, but the relatively high frequencies of TMB ≥ 10/20 mut/Mb in both mPSCC and mCSCC were noteworthy. Examples of patients with mCSCC and mPSCC responding to targeted and immunotherapies will be presented. Conclusions: Although mCSCC and mPSCC share a variety of genomic features, the 2 tumor types can nonetheless be sharply differentiated on CGP. The TP53, CDKN2A and HPV status of the tumor types differ significantly with viral identification much higher in the mCSCC group. There are opportunities for targeted therapies in both groups predominantly identified in the MTOR pathway. Numerous cases with significantly elevated TMB in both mPSCC and mCSCC suggest that immunotherapies might be of benefit in a subset of patients. [Table: see text]

Employing RNA sequencing to enhance treatment options for cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3628-3628
Author(s):  
Gargi D. Basu ◽  
Janine LoBello ◽  
Audrey Ozols
Keyword(s):  
Rna Sequencing ◽  
Myogenic Differentiation ◽  
Treatment Options ◽  
Targeted Treatment ◽  
Low Grade ◽  
Genomic Profiling ◽  
Molecular Abnormalities ◽  
Transcript Variants ◽  
Comprehensive Genomic Profiling ◽  
Variant Detection

3628 Background: Fusions and translocations account for 20% of cancer mortality globally. Maximizing their detection enhances the utility of precision medicine for various solid and hematologic cancers. Practice guidelines stress the importance of RNA sequencing. Novel assay techniques employing a comprehensive genomic profiling approach, including RNA sequencing, yield information beyond conventional DNA next generation sequencing (NGS) alone. Methods: Tumor samples (N = 1517) were assayed combining whole transcriptome (RNA) sequencing, whole exome (DNA) sequencing, and comparison of tumor sequence vs. paired normal DNA. Results were analyzed to determine the frequency of rare and common RNA fusion and variant detection. Findings were mapped to a knowledge-base of targeted treatment options. Results: Analysis detected 79 (5.2%) actionable fusions and 15 (1%) transcript variants across major solid and heme-based malignancies. Notably, we observed actionable transcript variants that are not detectable at the DNA level including: EGFRvIII, EGFRvIVa and EGFRvIVb in GBM; ARv7 in prostate, and METe14 in TNBC. Many fusion cases (42%, n = 33) had no other actionable molecular abnormalities. Novel fusions included: SLC12A/ROS1 in low-grade spindle cell neoplasm with myogenic differentiation, KANK1/NTRK2 in ganglioneuroblastoma, ETV6/NTRK3 in metastatic mammary analogue secretory carcinoma, FGFR1/SCT in germ cell tumor, ZNF33B/RET fusion in GBM, SH3BP4/ERBB4 and EML4/ALK in RCC, VTCN1/NRG1 in pancreatic cancer, and AGRN/NRG1 in cholangiocarcinoma. More common actionable fusion events included: EML4/ALK in NSCLC, KIAA1549/BRAF in pilocytic astrocytoma, FGFR2 and FGFR3 in cholangiocarcinoma and urothelial cancers and ESR1 in endocrine therapy-resistant breast cancers. The fusion events detected in heme-based malignancies included MLLT10 and MLLT4 in AML, BCR/ABL in leukemias, TCF3/PBX1 in B cell ALL, NPM1/ALK in ALCL, and novel fusion CIITA/CD274 in DLBCL. All RNA fusions and transcript variants found were matched to FDA-approved or investigational treatment options. Conclusions: Maximizing the rate of variant detection for targeted therapy relies on precise identification of common and rare fusion events. Without the addition of RNA sequencing, 15 transcript variants in our cohort would have been missed and 33 of the fusions may have gone undetected by conventional DNA NGS testing, resulting in zero targeted treatment options for this vulnerable population. Further use of comprehensive genomic profiling is vital to optimizing cancer care.

Implementation of reflexive genomic profiling in non-squamous NSCLC: Results of single center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13010-e13010
Author(s):  
Jacqueline T Brown ◽  
Andrew R Moore ◽  
Joshua E Reuss ◽  
Nicholas I Simon ◽  
Ryan D. Gentzler ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Single Gene ◽  
Treatment Options ◽  
Driver Mutations ◽  
Genomic Profiling ◽  
Chi Square ◽  
Single Center Experience ◽  
Before And After ◽  
Comprehensive Genomic Profiling ◽  
Number Of Treatment

e13010 Background: Identification of oncogenic driver mutations (ODM) and targeted therapies have increased the number of treatment options for patients (pts) with non-squamous non-small cell lung cancer (ns-NSCLC). Different methods exist to detect ODM and there is no standard approach. This study examines the changes in detection of ODM over a 2-year period before and after implementing reflexive genomic testing using next generation sequencing (NGS) in January 2015. Methods: We retrospectively reviewed ns-NSCLC cases (stages I-IV) in 2014 and 2015 using the UVA Cancer Registry. We identified pts with pathologically-confirmed ns-NSCLC and reviewed any genotyping - single gene pyrosequencing, NGS, or FISH for gene rearrangements - within 90 days of pathologic confirmation. Comprehensive genomic profiling (CGP) was defined as both NGS and ALK/ROS1 FISH. Chi-square analyses were generated using SAS 9.4. Results: A total of 360 pts were included. 60% had genotyping while 19% underwent CGP. Mutations are summarized in the table below. From 2014 to 2015, genotyping increased from 50% to 69% (p<0.001), with CGP increasing from 2% to 48% of testing performed (p<0.001). Detection of oncogene driver mutations increased from 28% to 46% (p=0.009). Doubletons (pts with 2 driver mutations) increased from 0% to 5% (p=0.036). Conclusions: Reflexive CGP significantly increased the rate of detection of ODM at our center with results similar to previous studies. Previous studies detected low rates of doubleton mutations, perhaps due to lack of uniform NGS testing. Utilization of NGS may increase detection of doubleton mutations, for which further study is necessary to evaluate efficacy of targeted therapies. For centers without reflexive CGP, implementing this approach is likely to increase rates of ODM detection and expand treatment options. [Table: see text]

scholarly journals Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer

2014 ◽  
Vol 67 (9) ◽  
pp. 772-776 ◽  
Author(s):  
J S Ross ◽  
K Wang ◽  
O R Elkadi ◽  
A Tarasen ◽  
L Foulke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Small Cell ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Illumina Hiseq ◽  
Personalise Therapy ◽  
Comprehensive Genomic Profiling ◽  
New Treatment

AimsSmall cell lung cancer (SCLC) carries a poor prognosis, and the systemic therapies currently used as treatments are only modestly effective, as demonstrated by a low 5-year survival at only ∼5%. In this retrospective collected from March 2013 to study, we performed comprehensive genomic profiling of 98 small cell undifferentiated lung cancer (SCLC) samples to identify potential targets of therapy not currently searched for in routine clinical practice.MethodsDNA from 98 SCLC was sequenced to high, uniform coverage (Illumina HiSeq 2500) and analysed for all classes of genomic alterations.ResultsA total of 386 alterations were identified for an average of 3.9 alterations per tumour (range 1–10). Fifty-two (53%) of cases harboured at least 1 actionable alteration with the potential to personalise therapy including base substitutions, amplifications or homozygous deletions in RICTOR (10%), KIT (7%), PIK3CA (6%), EGFR (5%), PTEN (5%), KRAS (5%), MCL1 (4%), FGFR1 (4%), BRCA2, (4%), TSC1 (3%), NF1 (3%), EPHA3 (3%) and CCND1. The most common non-actionable genomic alterations were alterations in TP53 (86% of SCLC cases), RB1 (54%) and MLL2 (17%).ConclusionsGreater than 50% of the SCLC cases harboured at least one actionable alteration. Given the limited treatment options and poor prognosis of patients with SCLC, comprehensive genomic profiling has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease.

scholarly journals Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuhang Wang ◽  
Yuan Fang ◽  
Ning Jiang ◽  
Shujun Xing ◽  
Qin Li ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Human Leukocyte ◽  
Soft Tissue Tumors ◽  
Unknown Primary ◽  
Genomic Profiling ◽  
Therapeutic Modalities ◽  
Rare Tumors ◽  
Comprehensive Genomic Profiling

Treatment options for rare tumors are limited, and comprehensive genomic profiling may provide useful information for novel treatment strategies and improving outcomes. The aim of this study is to explore the treatment opportunities of patients with rare tumors using immune checkpoint inhibitors (ICIs) that have already been approved for routine treatment of common tumors. We collected immunotherapy-related indicators data from a total of 852 rare tumor patients from across China, including 136 programmed cell death ligand-1 (PD-L1) expression, 821 tumors mutational burden (TMB), 705 microsatellite instability (MSI) and 355 human leukocyte antigen class I (HLA-I) heterozygosity reports. We calculated the positive rates of these indicators and analyzed the consistency relationship between TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1. The prevalence of PD-L1 positive, TMB-H, MSI-, and HLA-I -heterozygous was 47.8%, 15.5%, 7.4%, and 78.9%, respectively. The consistency ratio of TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1 was 54.8% (78/135), 87.3% (598/685), and 47.4% (54/114), respectively. The prevalence of the four indicators varied widely across tumors systems and subtypes. The probability that neuroendocrine tumors (NETs) and biliary tumors may benefit from immunotherapy is high, since the proportion of TMB-H is as high as 50% and 25.4% respectively. The rates of PD-L1 positivity, TMB-H and MSI-H in carcinoma of unknown primary (CUP) were relatively high, while the rates of TMB-H and MSI-H in soft tissue tumors were both relatively low. Our study revealed the distribution of immunotherapeutic indicators in patients with rare tumors in China. Comprehensive genomic profiling may offer novel therapeutic modalities for patients with rare tumors to solve the dilemma of limited treatment options.

Conventional versus Mindfulness-based Interventions for Anxiety and Worry: A Review and Recommendations

2020 ◽  
Vol 16 (1) ◽  
pp. 60-67
Author(s):  
Deah Jo Abbott ◽  
Caleb Wayne Lack
Keyword(s):  
Treatment Options ◽  
Additional Treatment ◽  
Third Wave ◽  
Stage Model ◽  
Pharmacological Treatments ◽  
The Past ◽  
Behavioral Therapies ◽  
Cognitive Behavioral Therapies ◽  
Specific Disorders ◽  
Psychiatric Problems

Anxiety disorders are among the most prevalent and most functionally impairing psychiatric problems experienced by the population. Both pharmacological and psychological evidencebased treatments exist for a number of specific disorders, but may fail to fully relieve symptoms, pointing to the need for additional treatment options. Often considered to be part of the “third wave” of cognitive-behavioral therapies, treatments incorporating mindfulness have emerged in the past two decades as increasingly popular with clinicians and frequently sought out by consumers. The present article reviews the extant literature regarding the efficacy and effectiveness of mindfulnessbased treatments for anxiety, worry, and related problems. Although they have not attained the solid empirical status of CBT or certain pharmacological treatments, the extant research shows mindfulness- based interventions appear to be a promising and useful treatment for people suffering from anxiety and worry. Further work should be done, levels 3-5 of the NIH stage model to determine whether or not they should be further implemented.

Sign in / Sign up

Export Citation Format

Share Document