Cancer Clonality and Treatment Insights

MenariniSearch Training

• MenariniSearch is a comprehensive genomic profiling service from Menarini Silicon Biosystems.
• Training material, in July 2024, was focused on MenariniSearch and breast cancer.
• Comprehensive genomic profiling for breast cancer was a key topic in the training.
• The training included a patient journey example for metastatic breast cancer.

Patient Journey: Example Metastatic Breast Cancer Patient

• The patient journey covers initial diagnosis through various stages of treatment.
• Key factors include genetic counseling, pathology, disease staging, and regular follow-up care.
• The presented example includes metastatic breast cancer.
• The patient journey shows testing for various markers including estrogen receptor, progesterone receptor, HER2, Ki-67, BRCA1/2, PD-L1, PIK3CA, NTRK, MSI-H/dMMR, and TMB.
• There is a discussion of biopsies and liquid biopsies.
• Possible therapy approaches (1st and 2nd line therapy and subsequent lines) are discussed as part of the patient journey.

Applications of MSB Tests in BrCA Pathway

• The applications of MenariniSearch tests in the BRCA pathway were explained.
• This section shows how different tests (re-biopsy, liquid biopsy, and original biopsy) can affect the treatment pathway.
• A key step involves re-biopsy (tissue or blood) testing.
• Liquid biopsy testing, using circulating tumor cells and cfDNA/cfRNA, is also presented as a vital part of the pathway.

DNA, RNA, Protein

• DNA contains the instructions that tell our bodies how to work.
• RNA is created from DNA and contains the instructions for how to build proteins.
• Proteins are created from RNA and have many important functions in the body.

ERBB2 Gene

• Chromosomes are made up of DNA
• DNA is made up of genes.
• Genes are made up of introns and exons.
• RNA is created from DNA and contains information from exons.
• RNA serves as a template for proteins.
• ERBB2 (HER2) gene is responsible for producing the HER2 protein.
• This presentation discussed the ways ERBB2 can be amplified, mutated, or overexpressed.

Positioning MenariniSearch

• The presentation highlighted the position of MenariniSearch in the market.

The Only CLIA Lab That Offers CTCs + Comprehensive Genomic Profiles in Most Cancers

• MenariniSearch offers both circulating tumor cell and cfDNA/cfRNA testing coupled with comprehensive genomic profiles in most cancers.
• This combines circulating tumor cell testing (CTCs) with cfDNA/cfRNA testing for a more complete assessment in numerous cancers.

Example: Testing CTC-HER2 & MenariniSearch in Tandem

• The presentation offered an illustration of how CTC-HER2 and MenariniSearch are used tandem for treatment monitoring and/or new treatment selection.

Why MSB? Quick TAT

• The presentation highlighted the quick TAT (turnaround time) of MenariniSearch tests for faster treatment.
• The turnaround time for the liquid biopsy is less than 10 days.

Time to Treatment Could be Faster with CTC HER2 and MenariniSearch

• The presentation included a table showing how the speed of the test delivery pipeline enables faster treatment decisions.

Comprehensive RNA & DNA Profiles

• MenariniSearch provides comprehensive RNA and DNA profiles, powered by artificial intelligence and reviewed by pathologists.
• It accurately detects guideline-recommended biomarkers.

Why MenariniSearch? One Stop Shop

• A comprehensive, one-stop-shop analysis is provided for liquid and tissue biopsies.
• Liquid biopsies include assay sensitivity of over 25,000x depth of coverage and 0.1% sensitivity.
• Tissue biopsises reveal <1% QNS rate.
• The analysis provides insights into viruses, CHIP, fusion, clonality, RNA, and tumor mutations.

Beyond the Ordinary: Liquid Biopsy

• Providing a comprehensive analysis of liquid biopsies.
• Includes an overview of assay sensitivity (0.1% or less).

• 1000 samples have been clinically validated.

MenariniSearch Can Detect Most Types Of Cancers

• This presentation outlined various types of cancers (solid tumors and hematological malignancies), including specific examples of each type.
• It details which tests (liquid biopsy, and tissue biopsy/bone marrow) can be used to detect the specific types of cancer.
• Multiple tests are available for RNA analysis and cfDNA/cfRNA analysis.

Overview of MenariniSearch

• MenariniSearch offers a broad genetic overview, revealing actionable mutations like PIK3CA and ESR1.
• It uses cfRNA and cfDNA combined; this increases sensitivity for complete molecular profiling of the tumor.
• The test detects amplifications, mutations, gene expressions, exon skipping, fusions, chromosomal changes, viruses and TMB.

Collection and Shipping

• This section provided information on the collection and shipping details for different types of samples (peripheral blood, CSF, bone marrow and tissue).
• Detailed information on specimen requirements for liquid biopsies, CSF analysis, bone marrow biopsies, and tissue biopsies.
• All of this material should have been included on the form for patients.

Sample Types for MenarniSearch Profiles

• This section showcased the sample types (blood, CSF, bone marrow, tissue) and their corresponding tubes, amounts, and conditions for MenariniSearch tests.
• The presentation details the testing kits specific to blood analysis, CSF, bone marrow and tissue.

How To Order MenariniSearch Tests and Kits

• The presentation covered ordering MenariniSearch tests and kits.
• Paper requisitions and online ordering are both presented.

Two Ways To Order MenariniSearch Test

• This presentation detailed the options for ordering, both online and paper-based, with instructions to access patient reports.

Benefits of RNA Analysis

• This presentation explained the unique advantages of RNA analysis.

Comprehensive RNA Insights Matter

• RNA profiling analysis delivers deep insights into gene expression, alternative splicing, fusion analysis, and tumor heterogeneity.
• It also aids in predicting drug responses and monitoring treatment effectiveness.
• Sequencing > 1600 RNA and cfRNA genes is part of the test.

Benefits of cfDNA & cfRNA

• Analysis of both cfDNA and cfRNA allows for real-time monitoring and understanding tumor evolution under treatment pressure.
• cfRNA analysis identifies overexpressed genes/pathways that may be potential targets for therapy.
• cfDNA can identify genetic mutations for drug resistance.
• Comprehensive analysis of treatment response and resistance mechanisms may be tracked via gene expression levels identifiable through cfRNA.

Benefits of cfDNA & cfRNA

• The benefits of cfDNA and cfRNA analysis include enhanced and comprehensive tumor heterogeneity identification.
• Sensitivity is improved with complementary testing and early-stage cancer alterations are detectable more quickly.
• Diagnostic yield is increased due to RNA analysis of gene expression levels, splicing, complementary data, and the potential for mutations to cause low cfDNA abundance, or technical limitations.

RNA-Seq Superior Than DNA in Detecting Fusions

• RNA sequencing is better than DNA for detecting fusion events because RNA sequencing identifies functioning fusion transcripts.
• RNA sequencing is more accurate because it can discriminate between functionally significant fusion events and passenger mutations.
• DNA sequencing may not always detect a fusion event that exists.

Variant Allele Frequency

• VAF represents the fraction of variant reads over total reads in a given sample position.
• VAF, in combination with depth, can determine whether a mutation is somatic (acquired) or germline (inherited).

HER2 Amplification, Overexpression, Mutations

• HER2 amplification, overexpression and mutations are clinically important to consider when assessing breast cancer.
• This process is crucial to optimal treatment plan design because it enables precise diagnosis and appropriate monitoring.
• HER2 status is important in treatment, and there's a correlation between aggressive tumors and a lack of targeted therapies.
• Somatic mutations (2-5%) are present in primary breast cancer.

What is the chromosomal structural changes in cancer?

• Chromosomal structural changes are a driving force in cancer development and progression.
• Determining these changes uncovers therapeutic targets, assists with prognostic information and enabling personalized treatment strategies.
• Structural changes like amplifications, deletions, and translocations in myeloma have significant clinical implications.

Tumor Heterogeneity

• Heterogeneity (the differences in the subpopulations within cancers) is a critical, yet often overlooked, factor in cancer management.
• Tumor heterogeneity directly impacts treatment response and resistance. Understanding the differences helps in designing more effective combination therapies and reduces the risk of relapse.
• Heterogeneity in breast cancer is important to consider in treatment and can impact treatment efficacy.
• Understanding intratumoral heterogeneity helps select the most effective combination therapies.

HLA: How does HLA genotyping information help in cancer treatment?

• HLA typing is vital in cancer treatment, particularly for guiding immunotherapy treatments and for matching in allogeneic stem cell transplantation.
• HLA typing can aid in selecting the most effective immunotherapy by predicting a patient’s response to immune checkpoint inhibitors.
• More targeted approaches are frequently possible due to the ability to match HLA types between donors and recipients to reduce complications such as graft-versus-host disease (GvHD).

Clonality

• Assessing clonality helps understand tumor evolution and resistance mechanisms.
• Clonality determines the architecture of a tumor, allowing for better prediction of disease progression, aiding in strategizing and creating adaptive treatment approaches.
• The information allows for a better understanding of the disease progression and resistance to therapies for multiple myeloma.

Gene Expression: How does gene expression data help in treating cancer?

• Gene expression profiling uncovers genes that drive cancer growth.
• Identifying active genes helps inform targeted therapeutics and predict treatment responses.

Multiple Myeloma

• The presentation included details about Multiple Myeloma, including how MenariniSearch can assist with diagnosing and treating the condition.

Multiple Technologies in One Test

• MenariniSearch combines various technologies (including genomics, cytogenetics, and flow cytometry) in a single test.

Beyond the Ordinary: Liquid Biopsy

• This is a general overview of a liquid biopsy; it highlights the potential of MenariniSearch, particularly in identifying specific genetic alterations.
• It details the assays sensitivity (0.1% or less).
• Over 1000 samples have been clinically validated.

What is the chromosomal structural changes in cancer?

• Structural changes, like deletions, translocations, and amplifications, are common in multiple myeloma.
• Understanding these changes is critical in tailoring treatment approaches.

Tumor Heterogeneity

• This presentation discusses tumor heterogeneity and its importance in the context of treatment efficacy and reducing resistance

HLA Genotyping-Immunotherapy Response Prediction

• HLA genotyping can predict which patients are more likely to respond to immunotherapy.
• Matching donors and recipients in allogeneic stem cell transplantations with HLA genotyping greatly reduces graft-versus-host disease (GvHD) occurrences.
• HLA-matched donors are frequently crucial to stem cell transplant success, especially for multiple myeloma.

Competitive Comparison

• This section provides a comparison of MenariniSearch against competing brands and their products.

The Most Comprehensive CTC and cfDNA/cfRNA Menu

• Table comparing various CTC and cfDNA/cfRNA product menus.

Competition in Liquid Biopsy for Solid Tumors and Hematology

• Table detailing the competitive analysis between MSearch and other Liquid Biopsy products in the solid and hematological tumor markets, respectively.

Competitive Position: Against Guardant Health Tissue Biopsy

• Table comparing MenariniSearch and Guardant Health’s product in tissues for solid tumors and hematology.

Competitive Position: Against Caris Tissue Biopsy

• Comparison of MenariniSearch vs. Caris' tissue biopsy approach, including analysis limitations of some of the competing products.

Key Takeaways

• MenariniSearch is highly sensitive compared to Caris Assure.
• Sample types for MenariniSearch include CSF and Peripheral Blood.
• MenariniSearch offers a Hematological Malignancies menu.
• Increase the chances against Caris by positioning MenariniSearch for CSF testing and hematological malignancies.

MenariniSearch vs Tempus XF, XF+

• Comparing MenariniSearch against Tempus XF, XF+.

MenariniSearch vs Tempus – Liquid Biopsy

• A detailed comparative table of both products for different cancer types.

Key Takeaways

• MenariniSearch provides a broad genetic overview.
• CSF and peripheral blood are the tested sample types.

MenariniSearch Resources

• The presentation contained general details on resources for MenariniSearch.

To be Successful in Reimbursement

• The requirements to be successful in reimbursement from a physician’s perspective.

Soft-Launch Resources

• Various resources (forms, requisition forms, guidelines and kits) provided during the soft launch of the product.

MenariniSearch Collection Kits

• Displays the liquid and tissue biopsy collection kits that MenariniSearch provides.

Components Inside MenariniSearch Collection Kits

• Visual and textual description of the components found within the MenariniSearch collection kits; this part explains what the contents of each kit are.

This quiz delves into the significance of tumor clonality in cancer treatment, especially in breast cancer. It covers aspects of gene expression profiling, sampling requirements, and unique methodologies used in liquid biopsy assays. Enhance your understanding of how these factors influence adaptive treatment approaches and patient outcomes.