“Integrating Diverse Test Results for Cancer Patient Guidance”

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] Brad Power and Nanthana Ravichandran May 7, 2025 “Orthogonality is key, and decision-making is often relying on more than one data point.” – Joe Lennerz, MD, PhD “Many groups have started implementing what are called ‘order sets’... We've moved to a personalized diagnostic stage in precision oncology.

” – Joe Lennerz, MD, PhD Meeting Summary As cancer diagnostics evolve, patients and providers are faced with an overwhelming number of available tests—transcriptomics, proteomics, spatial and single-cell analysis, functional testing, liquid biopsies, and metabolomics, among others.

The first challenge is determining which tests are necessary, a decision that changes rapidly as new tools become available. The second challenge is integrating these diverse test results to form a coherent, actionable understanding of the disease. Without a structured approach, this complexity risks leading to fragmented decision-making and missed opportunities for precision care. Dr.

Joe Lennerz, with his expertise in integrated diagnostics, is uniquely qualified to address these challenges. He has experience as a Medical Director at Massachusetts General Hospital/Harvard Medical School and now as CSO at BostonGene, where he works on combining multimodal data to guide cancer treatment.

Why is integrating diagnostic tests (DNA, RNA, immune system, imaging, …) for your unique cancer portrait important for your treatment decision-making?

●Gain deeper insights into your tumor biology ●Identify more precise treatment options and develop more personalized treatment strategies ●Understand your tumor heterogeneity and evolution ●Detect potential resistance mechanisms How should you gather and integrate information from multiple tests into your personalized, comprehensive disease profile and treatment implications?

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] (analysis of DNA from your normal cells) to identify inherited changes in genes, particularly those related to an increased risk of cancer ●Get a liquid biopsy (typically a blood test, but can be saliva or other liquids) ●Get immune system profiling ●Use advanced analytics to correlate data across these different tests to inform your treatment strategies and understand your cancer's specific biological characteristics to go from rea

●Get a liquid biopsy (typically a blood test, but can be saliva or other liquids) ●Get immune system profiling ●Use advanced analytics to correlate data across these different tests to inform your treatment strategies and understand your cancer's specific biological characteristics to go from real world data -> real world evidence What emerging tests could potentially inform your treatment decisions?

●Single-cell diagnostic technologies : can help distinguish tumor cells from normal cells, determine the origin and genetic constitution of the cells within the sample, provide detailed tumor microenvironment characterization, and identify mutation distribution across tumor cells ●Phylogenetic cancer maps: visualizations of the evolutionary history of tumors, including how they develop, spread, and respond to treatments, which can trace metastasis trajectories, understand how different tumor clones spread, detect resistance mutations, and provide insights into tumor heterogeneity How can you advocate for your access to the right tests for you?

●Choose a medical team (pathologist and oncologist) that leans into getting more testing for more comprehensive data and is current on the diagnostic technologies, have expertise in multi-omics data interpretation, and can provide contextual insights beyond raw test results, especially if you are considering later-line treatments or if you have a rare cancer ●Inquire about additional testing options; ask specific questions about molecular profiling, multi-omics testing, and whether additional testing could provide actionable insights for your treatment, such as targeted therapies or clinical trials; request a detailed explanation of how specific tests might inform treatment decisions, particularly for complex or treatment-resistant cancers ●Be prepared to discuss and pursue insurance coverage and potential financial assistance programs for advanced diagnostic testing ●Provide positive feedback when tests are helpful, such as sending a thank you note when a molecular test reveals an actionable mutation How can you learn more about how to navigate the rapidly changing landscape of cancer diagnostics for personalized treatment guidance?

●Join professional networks and discussion groups in oncology and molecular diagnostics; attend conferences and webinars; identify professional organizations like ASCO (American Society of Clinical Oncology) that provide reliable sources of information; read publications on “multi-omics” (diverse diagnostic tests) in cancer research; identify key experts in the field.

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] ●Stay updated on the NCCN guidelines and emerging diagnostic technologies ●See our conversations with diagnostics experts: ○“The Latest

ting ●Consult with oncologists who are using advanced diagnostic techniques

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] ●Stay updated on the NCCN guidelines and emerging diagnostic technologies ●See our conversations with diagnostics experts: ○“The Latest Tests for Personalized Cancer Care” (Tony Magliocco) [#89] ○“The Potential of Personalized Cancer Vaccines, Starting with Brain Cancer” (Saskia Biskup, MD, PhD) [#141] ○“Testing Your RNA with Liquid Biopsies” (Alex Rolland) [#116] ○“How I Help Patients Access New Diagnostics” (Joanne Weidhaas, MD, PhD, MSM) [#138] ○“The BostonGene Tumor Portrait Report and How to Access It" (Michael Hensley and Michelle Lanman) [#72] ○“Multi-omic Analysis Guides the Decisions of Brian McCloskey” (Rana McKay, MD, and BostonGene) [#98] ○“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr.

Chris Apfel) [#84] ●Contact Michael Hensley at Michael.Hensley@bostongene.com.

The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. For the video recording of this conversation, please see here.

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] Meeting Notes KEYWORDS Integrated diagnostics, precision oncology, multi-omics, liquid biopsy, immune system profiling, tissue imaging, advanced analytics, treatment timelines, personalized diagnostics, companion diagnostics, phylogenetic cancer maps, single cell genomics, regulatory environment, clinical trials, oncologist collaboration.

SPEAKERS Joe Lennerz (86%), Roger Royse (10%), Chris Apfel (3%), Michael Hensley (1%) CHAT CONTRIBUTORS Emma Shtiivelman, Saed Sayad, Russ Hollyer, Brad Power, Nahuel Villegas, Cheng Cui, Rick Davis, Chris Apfel, Dun Liang, Jamie Dempsey Barber, Roger Royse, Michael Dorsey, Ari Akerstein, Helen SUMMARY Dr.

Joe Lennerz from BostonGene discussed integrated diagnostics and the challenges of navigating the complex landscape of cancer tests. He highlighted the importance of multi-omics approaches, including next-generation sequencing, liquid biopsy, and tissue imaging. Dr.

Lennerz emphasized the need for comprehensive testing, especially in late-stage or rare cancers, and the importance of contextual interpretation. He also addressed the challenges of tissue procurement, the potential of single-cell DNA genomics, and the regulatory environment for companion diagnostics.

t with oncologists who are using advanced diagnostic techniques

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] ●Stay updated on the NCCN guidelines and emerging diagnostic technologies ●See our conversations with diagnostics experts: ○“The Latest Tests for Personalized Cancer Care” (Tony Magliocco) [#89] ○“The Potential of Personalized Cancer Vaccines, Starting with Brain Cancer” (Saskia Biskup, MD, PhD) [#141] ○“Testing Your RNA with Liquid Biopsies” (Alex Rolland) [#116] ○“How I Help Patients Access New Diagnostics” (Joanne Weidhaas, MD, PhD, MSM) [#138] ○“The BostonGene Tumor Portrait Report and How to Access It" (Michael Hensley and Michelle Lanman) [#72] ○“Multi-omic Analysis Guides the Decisions of Brian McCloskey” (Rana McKay, MD, and BostonGene) [#98] ○“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr.

Chris Apfel) [#84] ●Contact Michael Hensley at Michael.Hensley@bostongene.com.

The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. For the video recording of this conversation, please see here.

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] Meeting Notes KEYWORDS Integrated diagnostics, precision oncology, multi-omics, liquid biopsy, immune system profiling, tissue imaging, advanced analytics, treatment timelines, personalized diagnostics, companion diagnostics, phylogenetic cancer maps, single cell genomics, regulatory environment, clinical trials, oncologist collaboration.

SPEAKERS Joe Lennerz (86%), Roger Royse (10%), Chris Apfel (3%), Michael Hensley (1%) CHAT CONTRIBUTORS Emma Shtiivelman, Saed Sayad, Russ Hollyer, Brad Power, Nahuel Villegas, Cheng Cui, Rick Davis, Chris Apfel, Dun Liang, Jamie Dempsey Barber, Roger Royse, Michael Dorsey, Ari Akerstein, Helen SUMMARY Dr.

Joe Lennerz from BostonGene discussed integrated diagnostics and the challenges of navigating the complex landscape of cancer tests. He highlighted the importance of multi-omics approaches, including next-generation sequencing, liquid biopsy, and tissue imaging. Dr.

Lennerz emphasized the need for comprehensive testing, especially in late-stage or rare cancers, and the importance of contextual interpretation. He also addressed the challenges of tissue procurement, the potential of single-cell DNA genomics, and the regulatory environment for companion diagnostics.

cially in late-stage or rare cancers, and the importance of contextual interpretation. He also addressed the challenges of tissue procurement, the potential of single-cell DNA genomics, and the regulatory environment for companion diagnostics. The discussion included the practicality of multi-site omics testing and the role of oncologists in recommending these tests.

OUTLINE Introduction and Speaker Background ●Dr. Joe Lennerz, CSO at BostonGene, discussed integrated diagnostics. ●He has experience as a medical director at Massachusetts General Hospital and Harvard Medical School. ●His work at BostonGene entails combining multimodal data to guide cancer treatment. Challenges in Precision Oncology ●Dr.

Joe Lennerz discussed the complexity of the landscape of tests in precision oncology. ●He highlighted the constant changes in guidelines and approvals, and the daily practice challenges faced by providers and patients. ●He introduced the concept of integrating diverse test results to address these challenges.

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] ●He mentioned the various technologies and use cases in cell-free or circulating tumor DNA, RNA, and biomarkers. BostonGene's Ecosystem of Tests ●Dr. Lennerz described BostonGene's ecosystem of tests, including next-generation sequencing, liquid biopsy, immune system profiling, and tissue imaging.

●He explained the different layers of data: raw data, process data, and advanced analytics. ●He emphasized the importance of orthogonality in decision-making and the need for more than one data point. ●He introduced the concept of moving from traditional diagnostics to multi-omics and the shift from profiling to portraits. Integration of Findings and Advanced Analytics ●Dr.

Lennerz discussed the integration of findings and the shift from traditional diagnostics to multi-omics. ●He explained the concept of system integration and data complexity, using a graph to illustrate the landscape. ●He introduced the idea of moving from profiling to portraits, with more comprehensive multi-modality solutions.

●He demonstrated advanced analytics and the use of comprehensive solutions for drug developers and researchers. Right Test at the Right Time ●Dr. Lennerz introduced the concept of finding the right test at the right time, using a paradigm shift from EGFR identification to immune checkpoint inhibitor therapy.

●He discussed the complexity of finding the right test and the emergence of order sets for certain tumors. ●He explained the personalized diagnostic stage in precision oncology and the challenges of prior authorization and payment. ●He emphasized the importance of finding the right partners and collaboration, using an example of a small cell lung cancer classifier.

Tissue Procurement and Low Tumor Content ●Getting enough tissue from pathologists remains an issue.

asized the importance of finding the right partners and collaboration, using an example of a small cell lung cancer classifier. Tissue Procurement and Low Tumor Content ●Getting enough tissue from pathologists remains an issue. ●Pancreatic cancer has low tumor content which makes it challenging to analyze such samples.

Reproducibility and RNA Testing in Prostate Cancer ●For reproducibility of results, anchor points are important in multi-omics. ●Validating multi-omics data is challenging and quality metrics are needed. ●The actionability of RNA testing in prostate cancer is demonstrated by certain findings like TMPRSS2:ERG fusion.

●There is emerging evidence for the value of RNA sequencing in prostate cancer and the potential for RNA-based signatures.

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] Correlating CNV (copy number variation) Data and Multi-Modality Biomarkers ●Correlating CNV data with biological consequences presents challenges and highlights the importance of having tumor-normal data. ●Orthogonal verification is needed and RNA data is important in determining oncogenic effects.

●Validating multi-modality biomarkers requires comprehensive data in early-phase trials. ●Emerging evidence can drive clinical utility and overcome the challenges of payer perspectives. Single Cell DNA Genomics and Phylogenetic Cancer Maps ●Chris Apfel asked about the relevance of single-cell DNA genomics in solid cancers, and Dr. Lennerz explained the technical challenges and potential benefits.

●Dr. Lennerz discussed the use of synthetic tissue algorithms like Cassandra to overcome the high cost of single-cell RNA Seq. ●Chris Apfel asked about the practicality of multi-site omics testing, and Dr. Lennerz explained the insights gained from multi-regional sampling. ●Dr. Lennerz discussed the work of Camila Naxalrova on tumor phylogenetics and the potential for phylogenetic cancer maps.

Regulatory Environment and Practicality of Surveillance ●Roger Royse asked about updates in the regulatory environment and CDX regulation, and Dr. Lennerz discussed the challenges of proving analytical compatibility for rare events. ●Roger Royse asked about the practicality of surveillance for emergent ESR1 mutations, and Dr.

Lennerz expressed uncertainty and the challenges of detecting mutations in circulating tumor DNA. ●Dr. Lennerz emphasized the importance of contextual interpretation in clinical testing and the need for meaningful application. ●Michael Hensley provided his contact information for clinical inquiries and emphasizes the importance of comprehensive testing in certain settings.

“Integrating Diverse Test Results for Cancer Patient Guidance” (Joe Lennerz, MD, PhD, MSc) [#142] TRANSCRIPT Roger Royse Welcome to this event by the Cancer Patient Lab. I'd like to introduce our speaker today, Dr. Joe Lennerz, who is the CSO at BostonGene. He's going to talk to us today about integrated dia