PCN139 Value Frameworks and Innovative Contracting for Comprehensive Genomic Profiling

After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.

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Making the Most of Complexity to Create Opportunities: Comprehensive Genomic Profiling and Molecular Tumor Board for Patients with Non-Small Cell Lung Cancer (NSCLC)

Cancers ◽

10.3390/cancers13040609 ◽

2021 ◽

Vol 13 (4) ◽

pp. 609

Author(s):

Caterina Fumagalli ◽

Elena Guerini-Rocco ◽

Massimo Barberis

Keyword(s):

Lung Cancer ◽

Small Cell ◽

Tumor Board ◽

Genomic Profiling ◽

Small Cell Lung ◽

Molecular Alterations ◽

Comprehensive Genomic Profiling ◽

Molecular Tumor Board ◽

Personalized Cancer Therapy ◽

Personalized Cancer

Personalized cancer therapy matches the plan of treatment with specific molecular alterations [...]

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Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab037 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Jianling Ji ◽

Kristiyana Kaneva ◽

Matthew C Hiemenz ◽

Girish Dhall ◽

Tom Belle Davidson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Utility ◽

Adolescent And Young Adult ◽

Cns Tumors ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Genomic Profiling ◽

Comprehensive Genomic Profiling ◽

Clinically Significant

Abstract Background Recent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity. Methods OncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146/222) of cases. Results NGS demonstrated clinically significant alterations in 66% (147/222) of cases. Diagnostic markers were identified in 62% (138/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49/222) and 18% (41/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome. Conclusions Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

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