2015 Annual Meeting

Clinical Application of Next Generation Sequencing for the Management of Patients with Solid Tumors

2015 Annual Meeting

Room CC 304/306, March 23 2015, 8:00am to 12:00pm

Matthew Meyerson, Jeffrey S. Ross, Marc Ladanyi

Special Course- Clinical Application of Next Generation Sequencing

Educational Objective

This half-day course is designed to familiarize the registrant with both the technical aspects and clinical applications of NGS for the solid tumor cancer patient. The first section of the course is organized into a didactic series of short lectures given by the course instructors to highlight the history of clinical DNA sequencing on cancer specimens focused on the search for potential therapy targets for patients with relapsed and refractory disease. The technical section will emphasize practical issues for pathologists including the types of samples that can be used, the quantity and proportion of tumor cells needed and the pre-analytic factors that can influence NGS test results. The remainder of the course will then convert to case analysis based on tumor type in a series of sections specifically devoted to lung cancer, breast cancer, colorectal cancer, melanoma, salivary gland tumors, kidney cancer, sarcomas and hepatic cholangiocarcinoma.Upon completion of the educational activity, participants should be able to:

  1. Contrast the differences, advantages and disadvantages between next generation sequencing (NGS) technologies and traditional “Sanger Sequencing” methods
  2. Understand the current limitations of “one off" single gene hotspot sequencing tests
  3. Contrast the advantages and disadvantages of the targeted NGS approach versus WES, WGS and whole transcriptome sequencing (WTS)
  4. Understand how next generation sequencing can be applied to detect all classes of genomic alterations including base substitutions , short insertions/deletions, fusions, translocations/fusions, and copy number alterations (amplifications and homozygous deletions) in a clinical grade, regulatory agency approved (CLIA/CAP) format using routine clinical FFPE samples
  5. Know how to preserve and prepare surgical pathology and cytologic samples including fluids and fine needle aspirations for NGS testing
  6. Be familiar with the potential use of NGS for cancer patients and how the technology has the potential to alter a cancer patient’s clinical outcome by identifying a genomic alteration that leads to a specific targeted therapy that would not have been considered if the NGS results had not been available
  • Have a basic understanding of assessing quality assurance, proficiency testing and general validation of NGS procedures used in clinical testing of patient samples

Session Credits: CME = 3 / SAMs = N/A

Agenda

8:00am
Special Course Course Director
Speaker: Jeffrey S. Ross, MD, Albany Medical Center, Albany NY and Foundation Medicine, Inc., Cambridge, MA
Access to Handouts
8:00am
Special Course Course Director
Speaker: Matthew L. Meyerson, MD, PhD, Dana Farber Cancer Institute, Boston, MA and The Broad Institute, Cambridge, MA
8:00am
Special Course Course Director
Speaker: Marc Ladanyi, MD, Memorial Sloan Kettering Cancer Center, New York, NY
8:00am
Introduction- History of DNA Sequencing of the Human Genome and Uses and Limitations of Sanger Sequencing and Other Methods
Speaker: Matthew Meyerson, MD, PhD, Dana Farber Cancer Institute, Boston, MA and The Broad Institute, Cambridge, MA
Access to Handouts
8:15am
Introduction- Basic Principles of NGS Technology
Speaker: Marc Ladanyi, MD, Memorial Sloan Kettering Cancer Center, New York, NY
  1. Current NGS platforms
  2. Statistical parameters (sensitivity, specificity, depth of coverage)
  3. Critical role of bio-informatics/computational biology
8:30am
Introduction- Practical Issues in Clinical NGS
Speaker: Jeffrey S. Ross, MD, Albany Medical Center, Albany, NY and Foundation Medicine, Inc., Cambridge, MA
  1. Types of samples that can be used (FFPE, FNAs, Cell blocks)
  2. Sample preparation and preservation
  3. Sample size and percentage of malignant cells requirements
  4. Impact of and strategies for successfully sequencing decalcified specimens
  5. Implications for germline status based on tumor DNA sequencing
8:45am
Case 1 Non-small Cell Lung Cancer
Speaker: Matthew L. Meyerson, MD, PhD, Dana Farber Cancer Institute, Boston, MA and The Broad Institute, Cambridge, MA

Genomic alterations and their significance to be discussed include:

  1. EGFR amplifications and mutations
  2. ERBB2 (HER2) amplifications and mutations
  3. BRAF mutations
  4. EML4-ALK fusions
  5. ROS1 fusions
  6. RET fusions
  7. NTRK1 fusions
  8. MET amplifications
  9. Other genomic alterations
9:10am
Case 2 Breast Cancer
Speaker: Jeffrey S. Ross, MD, Albany Medical Center, Albany, NY and Foundation Medicine, Inc., Cambridge, MA

Genomic alterations and their significance to be discussed include:

  1. ERBB2 (HER2) amplifications and mutations
  2. ESR1 (ER alpha) mutations
  3. PIK3CA alterations
  4. Other targetable alterations (EGFR, FGFR, MET, etc.)
9:30am
Break
10:00am
Case 3 Colorectal Cancer
Speaker: Marc Ladanyi, MD, Memorial Sloan Kettering Cancer Center, New York, NY

Genomic alterations and their significance to be discussed include:

  1. KRAS
  2. BRAF
  3. PIK3CA
  4. DNA mis-match repair/microsatellite instability
  5. ERBB2
  6. Other rarely encountered targetable genomic alterations
10:20am
Case 4 Melanoma
Speaker: Matthew L. Meyerson, MD, PhD, Dana Farber Cancer Institute, Boston, MA and The Broad Institute, Cambridge, MA

Genomic alterations and their significance to be discussed include:

  1. BRAF V600E
  2. BRAF non-V600E mutations
  3. KIT
  4. Other targetable genomic alterations
  5. Ocular melanoma
10:40am
Case 5 Cancer of Unknown Primary Site
Speaker: Jeffrey L. Ross, MD, Albany Medical Center, Albany, NY and Foundation Medicine, Inc., Cambridge, MA

Genomic alterations and their significance to be discussed include:

  1. Searching for the primary tumor site vs searching for driver alterations in a metastasis biopsy
  2. Clinical outcome of CUP with conventional treatment
  3. Clinical outcome of CUP with NGS based targeted therapy
11:20am
Case 6 Sarcoma
Speaker: Marc Ladanyi, MD, Memorial Sloan Kettering Cancer Center, New York, NY

Genomic alterations and their significance to be discussed include:

  1. Sarcoma fusion gene detection
  2. Potential role of RNA sequencing for sarcomas
  3. Targetable genomic alterations in sarcomas
11:40am
Questions and Conclusion

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