Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group

PURPOSE Next-generation sequencing is increasingly used in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide matched therapy; however, outcome data are limited. We evaluate the effect of the degree of matching of tumors to treatment as well as compliance to MTB recommendations on outcomes. METHODS Overall, 164 patients with consecutive gynecologic and breast cancers presented at MTB were assessed for clinicopathologic data, next-generation sequencing results, MTB recommendations, therapy received, and outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment over total pathogenic alterations, and compliance to MTB recommendations were analyzed in context of oncologic outcomes. RESULTS Altogether, 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS ≥ 40% had higher overall response rate (30.8% v 7.1%; P = .001), progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI, 0.31 to 0.85; P = .002), and a trend toward improved overall survival (HR 0.64; 95% CI, 0.34 to 1.25; P = .082) in univariate analysis. The PFS advantage remained significant in multivariate analysis (HR 0.5; 95% CI, 0.3 to 0.8; P = .006). Higher MTB recommendation compliance was significantly associated with improved median PFS (9.0 months for complete; 6.0 months for partial; 4.0 months for no compliance; P = .004) and overall survival (17.1 months complete; 17.8 months partial; 10.8 months none; P = .046). Completely MTB-compliant patients had higher MS ( P < .001). In multivariate analysis comparing all versus none MTB compliance, overall response (HR 9.5; 95% CI, 2.6 to 35.0; P = .001) and clinical benefit (HR 8.8; 95% CI, 2.4 to 33.2; P = .001) rates were significantly improved with higher compliance. CONCLUSION Compliance to MTB recommendations resulted in higher degrees of matched therapy and correlates with improved outcomes in patients with gynecologic and breast cancers.

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Personalized Therapy of Molecular Tumor Board Participation With the Guidance of Next Generation Sequencing

Case Medical Research ◽

10.31525/ct1-nct03929653 ◽

2019 ◽

Author(s):

Keyword(s):

Next Generation Sequencing ◽

Personalized Therapy ◽

Tumor Board ◽

Next Generation ◽

Molecular Tumor Board ◽

Generation Sequencing

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Faculty Opinions recommendation of Bioinformatory-assisted analysis of next-generation sequencing data for precision medicine in pancreatic cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727775566.793536095 ◽

2017 ◽

Author(s):

Steve Pereira

Keyword(s):

Pancreatic Cancer ◽

Next Generation Sequencing ◽

Precision Medicine ◽

Next Generation Sequencing Data ◽

Next Generation ◽

Sequencing Data ◽

Assisted Analysis ◽

Generation Sequencing

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The integration of emerging omics approaches to advance precision medicine: How can regulatory science help?

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.330 ◽

2018 ◽

Vol 2 (5) ◽

pp. 295-300

Author(s):

Joan E. Adamo ◽

Robert V. Bienvenu ◽

F. Owen Fields ◽

Soma Ghosh ◽

Christina M. Jones ◽

...

Keyword(s):

Next Generation Sequencing ◽

Precision Medicine ◽

Working Group ◽

Regulatory Science ◽

Translational Science ◽

Next Generation ◽

Clinical Validity ◽

Knowledge Gaps ◽

Recent Advances ◽

Generation Sequencing

Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.

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Next-generation sequencing in patients with advanced cancer

Anti-Cancer Drugs ◽

10.1097/cad.0000000000000406 ◽

2016 ◽

Vol 27 (9) ◽

pp. 899-907 ◽

Cited By ~ 3

Author(s):

Tal Grenader ◽

Rachel Tauber ◽

Linda Shavit

Keyword(s):

Next Generation Sequencing ◽

Advanced Cancer ◽

Next Generation ◽

Generation Sequencing

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Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon

Frontiers in Oncology ◽

10.3389/fonc.2021.662260 ◽

2021 ◽

Vol 11 ◽

Author(s):

Emilie Darrigues ◽

Benjamin W. Elberson ◽

Annick De Loose ◽

Madison P. Lee ◽

Ebonye Green ◽

...

Keyword(s):

Brain Tumor ◽

Next Generation Sequencing ◽

Precision Medicine ◽

Critical Role ◽

First Year ◽

Histopathological Diagnosis ◽

Next Generation ◽

Cancer Predisposition Syndrome ◽

Generation Sequencing

Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.

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