Hematology Oncology Grand Rounds

October 2025 Grand Rounds

October 17

“Too Sick to Treat, Too Young to Quit: Initiating Cancer Therapy in a Patient on ECMO”

Dr. Pohua Chen discussed a complex case of a 44-year-old man admitted with severerespiratory failure due to COVID-19 and ARDS, later found to have lung adenocarcinoma withbone metastases (stage IVB). Initially managed with ECMO and supportive care, his diagnosiswas confirmed through bronchoscopy and cytology, followed by molecular testing thatrevealed an EGFR exon 19 deletion. Dr. Chen reviewed NCCN guidelines for advanced NSCLC,emphasizing biomarker-driven therapy and discussed treatment options, including osimertinibmonotherapy, osimertinib plus chemotherapy (supported by FLAURA-2 trial), and amivantamabplus lazertinib (Mariposa trial). She highlighted that osimertinib is preferred first-line due tosuperior progression-free survival and CNS penetration, despite similar response rates to earlierTKIs, and noted its rapid onset of action. Given the patient’s critical condition and inability totolerate chemotherapy, osimertinib was initiated and later dose-adjusted, but no clinicalimprovement occurred, likely due to extensive lung injury from ARDS and infection. The caseunderscored challenges in treating critically ill cancer patients, timing of targeted therapy, andpractical limitations in hospital settings.

Pohua Chen, M.D., MPH
Hematology/Oncology Fellow PGY-5
Medical University of South Carolina

September 2025 Grand Rounds

September 12

“Urine-based ctDNA analysis”

Dr. Tim Lautenschlaeger discussed advancing cancer diagnostics through urine-based circulatingtumor DNA (ctDNA) analysis as a highly sensitive, non-invasive alternative to blood-basedassays. He explained that ctDNA originates from dying tumor cells and is widely used for guidingtherapy in colorectal cancer, monitoring advanced cancers, and assessing recurrence risk. Hehighlighted the promise of tumor-informed panels and a “phase variant” approach, whichreduces sequencing error rates enabling analysis of millions of molecules without falsepositives. These innovations could transform early-stage cancer monitoring, HPV screening, andpersonalized therapy decisions, with ongoing trials and multi-cancer cohorts aiming to validateclinical utility.

Tim Lautenschlaeger, M.D.
Associate Professor of Radiation Oncology
Indiana University School of Medicine

September 5

“Challenges & Opportunities For Professional Societies During Times Of Rapid Change”

Dr. Clifford Hudis discussed the role of professional societies in medicine and how they support education, research, and the development of standards that shape patient care. He reflected on ASCO’s history and growth into a global organization, emphasizing its focus on expanding access to cancer care, supporting a sustainable workforce, and improving the way reliable information is shared with clinicians. He highlighted ASCO’s investments in early-career researchers, its role in conducting clinical trials, and its efforts to address physician burnout by setting clearer expectations for academic careers. Dr. Hudis also described how ASCO is using new tools like an AI-powered guideline assistant to modernize education and resources, while strengthening practice quality through its certification programs. On the advocacy front, he stressed the importance of reducing administrative burdens, eliminating financial barriers such as copays, and addressing drug shortages, noting that consistent advocacy has helped maintain support for cancer research. He closed by underscoring volunteerism as the driving force behind ASCO’s impact and encouraged physicians to engage as a way to advance oncology and prepare for the challenges ahead.

Clifford Hudis, M.D.
Chief Executive Officer of the American Society of Clinical Oncology (ASCO)

August 2025 Grand Rounds

August 8

“Advancing Cancer Precision Medicine Through Genomics and AI”

Dr. Milan Radovich discussed the most advanced and forthcoming developments in precision oncology. He detailed the convergence of genomics, artificial intelligence, and high-end computing as the driving force behind modern cancer care. Key topics included the shift from targeted gene panels to comprehensive whole exome and transcriptome sequencing, the rising importance of protein biomarkers, and the evolution of liquid biopsy. Dr. Radovich emphasized the critical need to differentiate tumor-derived mutations from Clonal Hematopoiesis of Indeterminate Potential (CHIP) to ensure correct treatment. He showcased how AI, powered by massive datasets, was being used to predict a tumor's tissue of origin, identify misdiagnoses, and discover novel drug targets. He concluded by highlighting digital pathology AI, the analysis of H&E slides to predict mutations and patient outcomes, as the next revolutionary, cost-effective, and democratizing technology in precision medicine.

Milan Radovich, Ph.D.
Senior Vice President and Chief Scientific Officer at Caris Life Sciences

July 2025 Grand Rounds

July 18

“The 10 Mind-Blowing Secrets of Oligometastatic Disease You Never Knew”

Dr. Brian Lally, a radiation oncologist with extensive clinical and research experience, discussed the evolving concept of oligometastatic disease and its management. He explained that there is no universally agreed-upon definition, and an exact cutoff may never exist due to the complexity of the disease. However, evidence from multiple randomized trials supports the use of ablative therapies, particularly stereotactic ablative radiotherapy (SABR), which may improve survival and, in some cases, offer a curative outcome. While SABR is the most common modality, surgery and radiofrequency ablation are also used depending on the situation. Treating all visible lesions is generally recommended, and combining ablative therapies with immune checkpoint inhibitors has shown promise without increased toxicity. Dr. Lally highlighted challenges in clinical trial design and patient accrual, proposing a pragmatic approach called the "ROYALS" trial, which incorporates circulating tumor DNA to guide treatment decisions. His talk emphasized the importance of individualized treatment and innovative research to better understand and manage this complex disease state.

Brian Lally, M.D.
Associate Professor of Radiation Medicine
Medical University of South Carolina

June 2025 Grand Rounds

June 20

“Development of molecularly-targeted siRNA therapeutics for GI malignancies”

Dr. Justin Lo discussed his research on developing small interfering RNA (siRNA) delivery technologies to target KRAS and MCL1 in gastrointestinal cancers. He presented innovative approaches, including tumor-penetrating peptide-siRNA nanoparticles and albumin-binding lipid-siRNA conjugates, designed to enhance gene silencing and tumor penetration. Dr. Lo emphasized that while KRAS inhibition can prime cancer cells for apoptosis, it often requires a second target—such as MCL1—to achieve significant cell death. His studies in pancreatic and cholangiocarcinoma models showed that combining siRNA against both KRAS and MCL1 led to synergistic anti-tumor effects, reducing tumor burden and improving survival in preclinical models. He concluded that effective cancer therapy will likely depend on such combination strategies and continued advances in siRNA delivery systems.

Justin Lo, M.D., Ph.D.
Instructor in Medicine, Division of Hematology/Oncology, Department of Medicine
Vanderbilt University Medical Center

June 13

“The Short History and Tenuous Future of Professionalism in Medicine”

Dr. Matthew Wynia, discussed the evolution of medical professionalism, tracing its roots from the Hippocratic Oath to the 19th-century formation of formal ethical codes. He explored the persistent tensions within the profession, particularly the challenge of balancing responsibilities to individual patients with obligations to society. Dr. Wynia highlighted how professionalism is shaped by external influences like government and market forces, and he questioned whether the profession always acts in the public interest. He emphasized that true professionalism involves continuous engagement in ethical discourse and self-regulation, rather than simply claiming authority. Through historical examples and memorable quotes, he illustrated how professionalism requires accountability, integrity, and a commitment to ethical standards in the face of evolving healthcare challenges.

Matthew Wynia, M.D., MPH
Director, University of Colorado Center for Bioethics and Humanities
Professor, University of Colorado School of Medicine, Colorado School of Public Health

June 6

“Development and launch of a Structured Query Language Cancer Genomic database and web-app for HCC cancer patients”

Dr. Stephen P. Ethier discussed building and using SQL-based genomic databases to support precision oncology at MUSC. He shared how his early work at the University of Michigan led to the development of the SUM breast cancer cell lines and comprehensive genomic datasets, which evolved into publicly accessible platforms for data mining. With the help of computer scientist Dan Couch, Dr. Ethier expanded this work to include over 900 cancer cell lines and 650+ TCGA breast cancer specimens. At MUSC, he built a secure, HIPAA-compliant database using sequencing data from 330+ uterine cancer patients through Caris Life Sciences. This database includes information on gene copy number, mutations, and expression profiles. Using SQL queries, researchers can quickly identify key genomic features, analyze oncogene signatures, and explore patient-specific mutation patterns. Integration with tools like OncoKB and COSMIC allows for easy interpretation of clinical relevance. A user-friendly web dashboard was also developed, enabling clinicians to explore individual patient data, track tumor evolution, and identify potential therapeutic targets. Dr. Ethier emphasized the system’s flexibility and potential for broader use, including machine learning applications and pathway analysis. He concluded by encouraging the expansion of this initiative and recognized key collaborators for their support.

Stephen P. Ethier, Ph.D.
Professor, Department of Pathology and Laboratory Medicine
Medical University of South Carolina

April 2025 Grand Rounds

April 18

“Advances in Biomarkers, Molecular Classification, and Therapeutic Strategies in Advanced Endometrial Cancer”

Dr. Abed Alhalim Aljamal discussed the current molecular subtypes of advanced or recurrent endometrial cancer—POLE‑mutated, dMMR/MSI‑high, pMMR/NSMP, and p53‑aberrant—and highlighted how these classifications now guide treatment decisions. He emphasized the landmark NRG‑GY018 trial, which showed that adding pembrolizumab to standard chemotherapy significantly improves progression‑free survival for both dMMR (median not reached vs ~8.3 months; HR ~0.30) and pMMR patients (13.1 months vs 8.7 months; HR ~0.54), establishing chemo‑immunotherapy as a first‑line standard regardless of MMR status. He then reviewed the SIENDO phase III trial demonstrating that maintenance Selinexor after platinum‑taxane therapy modestly extended PFS overall (5.7 vs 3.8 months; HR ~0.70), but delivered striking benefit in prespecified TP53 wild‑type tumors—median PFS ~28.4 months vs 5.2 months, with consistent gains in both pMMR (~39.5 vs 4.9 months) and dMMR (~13.1 vs 3.7 months) subgroups—along with manageable toxicity and low discontinuation rates. His overview underscores a future where molecular profiling increasingly enables tailored therapies—immunotherapy for dMMR tumors, chemo‑plus‑checkpoint inhibitors for pMMR cases, and Selinexor maintenance for TP53 wild‑type patients—potentially transforming outcomes in this historically challenging disease space.

Abed Alhalim Aljamal, M.D.
Fellow
Medical University of South Carolina

March 2025 Grand Rounds

March 14

“The MYC Oncoprotein in Aggressive Liver Metastatic Pancreatic Cancer”

Dr. Rosalie Sears discussed the role of the MYC oncoprotein in driving aggressive, liver-metastatic pancreatic cancer. She explained that MYC, often hyperactivated in pancreatic cancer through mutant KRAS signaling, functions as a master gene expression regulator. Using a genetically engineered mouse model, her team showed that co-expression of MYC and oncogenic KRAS leads to rapid tumor growth and liver metastasis. Dr. Sears highlighted the significance of MYC phosphorylation at serine 62 (S62), a modification that stabilizes MYC and enhances its oncogenic activity. Tumors with high phospho-MYC S62 levels exhibited increased replication stress, DNA damage, and immune suppression. Importantly, S62 phosphorylation allows MYC to localize to DNA double-strand breaks and support DNA repair, helping cancer cells survive despite genomic instability. Her findings underscore the central role of MYC in both intrinsic tumor progression and modulation of the tumor microenvironment, offering insight into potential therapeutic targets for aggressive pancreatic cancer.

Rosalie C. Sears, Ph.D.
Professor, Molecular and Medical Genetics
Krista L. Lake Chair in Cancer Research
Co-Director, Brenden-Colson Center for Pancreatic Care
Knight Cancer Institute

February 2025 Grand Rounds

February 14

“Leveraging Genomics to Improve Breast Cancer Outcomes in Diverse Populations”

Dr. Sonya Reid discussed the role of genomics in improving breast cancer outcomes among diverse populations, with a focus on addressing racial disparities. She highlighted that Black women face a 40% higher breast cancer mortality rate than white women, despite a lower incidence of the disease, and that these disparities persist even after accounting for socioeconomic factors—pointing to underlying biological differences. Dr. Reid explained that Black patients are more likely to develop aggressive subtypes, such as basal-like and luminal B tumors, even within hormone receptor-positive, HER2-negative breast cancer. She discussed the utility of genomic assays like Oncotype DX and PAM50 in identifying high-risk patients who may benefit from chemotherapy, but noted that outcomes still differ by race, even when genomic risk scores are similar. To address these issues, Dr. Reid is leading the INSIGHT trial, which uses genomic testing to guide treatment decisions in metastatic hormone receptor-positive breast cancer, with an emphasis on enrolling a diverse patient population. She underscored that without greater representation in clinical trials, it will be impossible to fully understand and address the biological and non-biological drivers of racial disparities in breast cancer outcomes.

Sonya Reid, M.D., MPH
Assistant Professor of Medicine, Breast Oncology
Vanderbilt-Ingram Cancer Center

February 7

“Gene Therapy for Sickle Cell Disease”

Dr. Jean-Antoine Ribeil presented an overview of gene therapy approaches for treating sickle cell disease and beta-thalassemia, focusing on both gene addition and gene editing strategies. He explained that these inherited blood disorders can be addressed by either inserting a functional beta-globin gene or editing the BCL11A gene to boost fetal hemoglobin production. Early clinical trials using lentiviral gene addition showed encouraging outcomes, including sustained anti-sickling hemoglobin production and fewer vaso-occlusive crises, though challenges like repeated bone marrow harvests and low vector copy numbers initially limited success. Advances in manufacturing have since improved these results. Dr. Ribeil also discussed gene editing using CRISPR/Cas9, which has demonstrated strong potential by producing high levels of fetal hemoglobin and reducing disease symptoms. While both approaches show promise as transformative therapies, he noted the importance of monitoring long-term safety, particularly in light of rare but serious adverse events such as myelodysplastic syndrome and leukemia. Overall, he emphasized that while not yet curative, gene therapies represent a major step forward in the treatment of these hemoglobinopathies.

Jean-Antoine Ribeil, M.D., Ph.D.
Former Director of Sickle Cell Center at Boston Medical Center
CEO GLOB Therapy Consulting

January 2025 Grand Rounds

January 10

“Functional Interrogation of an essential high-plasticity cell state in lung cancer reveals a dependency on NF-kB”

Dr. Jason E. Chan discussed his research on tumor cell plasticity in lung adenocarcinoma and its implications for cancer maintenance and treatment. His work identified a “high plasticity cell state” that arises early in tumor development, makes up a small fraction of tumor cells, yet plays a critical role in sustaining tumor growth by generating other cell states. Using mouse models and patient-derived samples, Dr. Chan demonstrated that this plasticity is driven by the canonical NF-κB signaling pathway, specifically the p50/p65 complex. Targeting this cell population through genetic ablation or immunotherapy, particularly in combination with standard treatments like chemotherapy or KRAS inhibitors, significantly reduced tumor burden and improved therapeutic outcomes. His findings highlight the importance of targeting tumor plasticity as a strategy to enhance lung cancer treatment and better understand tumor heterogeneity and resistance.

Jason E. Chan, M.D., Ph.D.
Clinical Instructor Sarcoma Medical Oncology Service
Memorial Sloan Kettering Cancer Center