Medical Specialties Commons^™

Cost-Effectiveness Of Hes V2.0 And Galad For Hepatocellular Carcinoma Surveillance In Patients With Cirrhosis, Mert Sahinkoc, Gizem S Nemutlu, Hashem B El-Serag, Mary Linton B Peters, Ali Hajjar, Anthony E Samir, Leigh Anne Dageforde, Fasiha Kanwal, Jagpreet Chhatwal

Faculty, Staff and Students Publications

Background: Ultrasound-based surveillance for HCC is limited by suboptimal sensitivity and low adherence. Blood-based biomarkers are potential alternatives for routine HCC surveillance. We aimed to define optimal sensitivity, specificity, and cost parameters under which blood-based biomarkers could serve as cost-effective alternatives in patients with cirrhosis.

Methods: We developed a microsimulation model of the natural history of HCC in individuals with compensated cirrhosis. We compared the cost-effectiveness of biannual surveillance using 2 blood-based biomarkers-HES V2.0 and GALAD-versus ultrasound-based surveillance across a range of sensitivity, specificity, test costs, and adherence levels. Outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios …

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

Fgfr3::Tacc3 Fusion And Notch1 Loss-Of-Function In A Case Of Hpv-Associated Sinonasal Squamous Cell Carcinoma: Diagnostic Challenge And Implications For Targeted Therapy, Xu Cao, Hong Yu, Reham Hamdy Abdulazim Soliman, Pei Ying, Songlin Zhang, Li Liang

Faculty, Staff and Students Publications

Sinonasal squamous cell carcinoma (SNSCC) comprises a heterogeneous group of tumors with emerging molecular subtypes. Human papillomavirus (HPV)-associated SNSCC is a distinct entity, although actionable genomic alterations beyond HPV-driven pathways remain underexplored. Distinguishing HPV-associated SNSCC from carcinoma ex inverted papilloma can be particularly challenging in limited biopsy specimens, as these lesions may appear morphologically similar. We report a case of HPV-associated SNSCC with concurrent FGFR3::TACC3 fusion and NOTCH1 p.C1416 stop-gain mutation.

Oncocytic Intraductal Carcinoma Of The Parotid Gland With Strn::Alk Fusion, Reham H Soliman, Chris Shi, Kevin E Fisher, Hong Yu, Fouad El-Dana, Xu Cao, Li Liang, Pei Ying, Songlin Zhang

Faculty, Staff and Students Publications

Intraductal carcinoma (IDC) of the salivary gland is an uncommon epithelial neoplasm characterized by a predominantly intraductal or intracystic proliferation rimmed by a myoepithelial cell layer. Advances in molecular profiling have revealed recurrent gene fusions in IDC, most frequently involving RET, although fusions implicating other kinase genes have also been described. Among these, ALK rearrangements are rare and remain poorly characterized. Herein, we report a case of oncocytic IDC of the parotid gland harboring a STRN::ALK fusion, further expanding the molecular landscape of this tumor. Although this fusion has been previously reported in intercalated duct IDC, to our knowledge, this …

Lymph Node Dissection And Postoperative Complications After Lung Cancer Resection, Isheeta Madeka, Khaled Noueihed, Jacob Woodroof, Shale Mack, Hamza Rshaidat, Gregory L Whitehorn, Sneha Alaparthi, Scott H. Koeneman, Tyler R. Grenda, Nathaniel R. Evans, Iii, Olugbenga T. Okusanya

Department of Surgery Faculty Papers

Importance: Current lung cancer guidelines recommend lymph node sampling (LNS) with the 3 + 1 rule, which recommends station-based sampling with at least 3 N2 (mediastinal) and 1 N1 (hilar) nodal stations. Although there is oncologic benefit to rigorous LNS, potential negative impacts on surgical outcomes have not been well investigated. As adoption of the 3 + 1 rule increases given its formalization as guideline-concordant care, associations with adverse outcomes are crucial to characterize.

Objective: To evaluate whether satisfying the 3 + 1 rule is associated with increased postoperative complications.

Design, setting, and participants: This retrospective cohort study used the …

Axitinib-Pembrolizumab And Adverse Event Management In Patients With Advanced Renal Cell Carcinoma, Neil Shah, Yaa Ababio, Anthony Eccleston, Dharanija Rao, Scott Kelly, Jane Chang, Sarah Lucht, Caleb Paydar, Bryce Van Doren, Emily Bland, William John, Sarah Giegerich, Jalyna Laney, Bruce Feinberg, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Understanding approaches to managing treatment-related adverse events (AEs) in immunotherapy and tyrosine kinase inhibitor-based treatments in a clinical setting is critical for reaching optimal patient outcomes.

OBJECTIVE: To investigate the management of AEs in community practices during first-line axitinib plus pembrolizumab therapy for advanced renal cell carcinoma (aRCC).

DESIGN, SETTING, AND PARTICIPANTS: This study comprised a cross-sectional electronic physician survey and a multisite, retrospective cohort study of the medical records of US patients with aRCC who initiated first-line axitinib-pembrolizumab between April 22, 2019, and January 31, 2024. Data were analyzed from September 18 to December 20, 2024.

EXPOSURE: First-line …

Antibody-Drug Conjugates Beyond Her2 In Non-Small Cell Lung Cancer (Nsclc): Mechanisms, Emerging Targets, And Future Directions., Ahmed Ismail, Aakash Desai, George R Simon, Yanis Boumber

Oncology Articles

Antibody-drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of …

Seeing Skin, Seeking Evidence: Lessons From A Dermatology Internship, Isabella Floyd

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Indoor tanning exposes individuals to artificial ultraviolet (UV) radiation through devices such as tanning beds and sunlamps, increasing the risk of skin damage and malignancy. Prior research suggests associations between indoor tanning and melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), with potential variation based on age of initiation and cumulative exposure.

Purpose: The purpose of this literature review was to examine the association between indoor tanning and skin cancer risk, with a focus on age at first exposure, frequency, and duration of tanning bed use across melanoma, BCC, and SCC outcomes.

Methodology: A structured literature review …

Carcinoma Of The Bladder Diagnosed Incidentally Following Cesarean Section, Fatima Hussain, Mimi Rogers

Central & West Texas and San Antonio GME Research Day 2026

No abstract provided.

Initial Site Of Metastasis Influences Prognosis In Pancreatic Ductal Adenocarcinoma, Eleanor Mancheski, David Baek, Wilbur Bowne, Harish Lavu, Charles Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

METHODS: This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan-Meier survival analyses were performed. Cox regression was …

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Xiaoxia Wen, Seth T Gammon, Jorge Delacerda, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …

Outcomes With Single Tremelimumab Regular Interval Durvalumab (Stride) For Unresectable Hepatocellular Carcinoma In The Us Veterans Administration, Shalini Bansal, Priya Amin, Courtney Williamson, Stephen Valerio, David Kaplan

Student Papers, Posters & Projects

Background: HIMALAYA demonstrated that STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) compared with sorafenib in participants with unresectable hepatocellular carcinoma (HCC). This retrospective, real-world cohort study evaluated outcomes with STRIDE in veterans with HCC. Methods: Patients diagnosed with HCC between 1 January 2008 and 28 February 2024 who received ≥1 dose of STRIDE for unresectable disease were included. Data were collected from the Veteran Affairs Corporate Data Warehouse. Safety and efficacy were evaluated overall and for subgroups of patients with Child–Pugh A versus Child–Pugh B cirrhosis, viral versus non-viral HCC, and those with versus without prior …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani

Department of Medical Oncology Faculty Papers

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life …

Hes V2.0 Validation And Performance Compared To Galad And Asap In The Heds Cohort, Hashem B El-Serag, Camden Lopez, Michelle Luster, K Rajender Reddy, Neehar Parikh, Amit G Singal, Jorge A Marrero, Aaron P Thrift, Jagpreet Chhatwal, Ziding Feng, Stephanie Page-Lester, Qingchun Jin, Nabihah Tayob, Fasiha Kanwal

Faculty, Staff and Students Publications

Background & aims: We previously developed HES V2.0, a biomarker panel (age, ALT, platelets, etiology, AFP, AFP-L3, DCP, and their 1-year gradients) for early detection of hepatocellular carcinoma (HCC) among patients with cirrhosis. We externally validated HES V2.0 and compared its performance with HES V1.0, GALAD, and ASAP.

Methods: We conducted a PRoBE (prospective specimen-collection, retrospective blinded-evaluation) cohort study in the HEDS (Hepatocellular Carcinoma Early Detection Strategy) cohort of 1,485 patients with cirrhosis, of whom 119 developed HCC. Patient- and test-level true positive rates (TPR) for HCC were calculated at 6, 12, and 24 months before diagnosis, using thresholds at …

Linkage Disequilibrium Score Regression Identifies Genetic Correlations Between Hepatocellular Carcinoma And Clinically Relevant Traits, Younghun Han, Vikram R Shaw, Jinyoung Byun, Aaron P Thrift, Catherine Zhu, Donghui Li, Rikita I Hatia, Robin Kate Kelley, Sean P Cleary, Anna S Lok, Paige M Bracci, Jennifer B Permuth, Roxana Bucur, Jennifer Knox, Jian-Min Yuan, Amit G Singal, Prasun K Jalal, R Mark Ghobrial, Yuko Kono, Dimpy P Shah, Mindie H Nguyen, Neehar D Parikh, Richard Kim, Hui-Chen Wu, Hashem El-Serag, Ping Chang, Yun Shin Chun, Jian Gu, Chad Huff, Asif Rashid, Lu-Yu Hwang, Alison P Klein, Saira A Khaderi, Ahmed O Kaseb, Kathrine A Mcglynn, Lewis R Roberts, Manal M Hassan, Christopher I Amos

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) mortality is increasing globally, partly due to the growing prevalence of nonviral liver diseases. Genome-wide association studies (GWAS) have identified genetic variants associated with HCC development. Leveraging GWAS summary statistics and linkage disequilibrium score regression (LDSR), we investigated disease co-development with hepatitis C virus-negative (HCV-negative) HCC to provide unique insights into HCC etiology and prioritize relationships for further causal inquiry. We utilized the LDSR statistical framework to estimate the genetic correlation and heritability between HCV-negative HCC with 901 epidemiologic, behavioral, and clinical traits from the United Kingdom Biobank (UKBB). First, we set the threshold for observed scale …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Local Delivery Of Mir-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth, Nikhil S Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Geetika Wadhwa, Anurag N Paranjape, Stephen Y Lai, Flordeliza S Villanueva

Faculty, Staff and Student Publications

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Disease-Specific And Overall Survival For Patients With Lacrimal Gland Adenoid Cystic Carcinoma In Recent Decades, Bita Esmaeli, Zhouxuan Li, Tracy J Lu, Hila Goldberg, Jing Ning, James Matthew Debnam, Steven Jay Frank, Renata Ferrarotto

Faculty, Staff and Student Publications

Purpose: To evaluate the presenting symptoms, and the overall survival (OS) and disease-specific survival (DSS) in patients with lacrimal gland adenoid cystic carcinoma (LGACC).

Methods: This retrospective single-centre cohort study included all consecutive patients with LGACC treated by the primary author from November 1998 through August 2024. Demographic data, presenting symptoms, the histological subtype of LGACC, type of surgical treatment, adjuvant radiotherapy or chemotherapy, T category at presentation and survival data were reviewed. Correlations between histological subtypes, T-category, type of surgery (eye sparing vs orbital exenteration), and DSS and OS were analysed.

Results: 52 patients had a median age of …

Accuracy Of Frozen Section For Hpv-Associated Squamous Cell Carcinoma Of Unknown Primary, Sindhura Sridhar, Annie Moroco, Shravan Gowrishankar, Mitra Mehrad, Kim Ely, James Lewis, Madalina Tuluc, Stacey Gargano, Melanie Hicks, Kyle Mannion, Arielle Thal, Adam Luginbuhl, Joseph Curry, David Cognetti, Michael Topf

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

INTRODUCTION: Current guidelines for the management of metastatic squamous cell carcinoma of unknown primary (SCCUP) recommend submission of suspicious primary sites for frozen section analysis (FSA). This study aims to investigate the diagnostic accuracy of FSA for identification of HPV-associated SCCUP.

METHODS: A retrospective cohort study of patients with biopsy-proven p16-positive SCCUP who underwent diagnostic operation at two tertiary care institutions was performed. Sensitivity, specificity, PPV, and NPV of diagnostic FSA were assessed.

RESULTS: 77 patients were included in analysis. 66 patients underwent definitive TORS (diagnostic TORS operation with subsequent neck dissection after identification of the occult primary tumor), 7 …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

Tet2-Mutant Clonal Hematopoiesis Enhances Macrophage Antigen Presentation And Improves Immune Checkpoint Therapy In Solid Tumors, Shelley Herbrich, Mehdi Chaib, Swetha Anandhan, Samuel W Andrewes, Ashwat Nagarajan, Baoxiang Guan, Nishant Gandhi, Jared Gilliam, Milan Radovich, Padmanee Sharma

Faculty, Staff and Student Publications

Clonal hematopoiesis (CH) is detectable in upwards of 20% of patients with solid tumors and is associated with worsened prognosis; however, its role in tumor immunology and immune checkpoint therapy (ICT) is unknown. Using a bone marrow chimera model of Tet2+/mut CH in mice with solid tumors, we found the Tet2-mutant myeloid cells are abundant in the tumor microenvironment and contributed to an improved response to ICT. Mechanistically, Tet2+/mut macrophages inside the tumor act as immunogenic antigen-presenting cells that more effectively cross-prime naive CD8+ T cells in response to IFNγ. In human cohorts of 35,971 non-small cell lung cancer patients …

Deep-Learning Serial Ct Prediction Of Survival In Immunotherapy-Treated Non-Small Cell Lung Cancer., Chiharu Sako, Brenda F Kurland, Taly G Schmidt, Jing He, Marius De Groot, Arpan A Patel, Dwight H Owen, Arya Amini, Brendan D Curti, Ronan J Kelly, Ray D Page, Aurelie Swalduz, Jean-Paul Beregi, Jan Chrusciel, Stephane Sanchez, Jakob Weiss, An Liu, Olivier Gevaert, Alma Hart, George R Simon, Ravi B Parikh, Jasper Van Der Aart, Petr Jordan

Oncology Articles

IMPORTANCE: Reliable early response biomarkers for overall survival (OS) are lacking for patients receiving immune checkpoint inhibitor (ICI) therapy for advanced non-small cell lung cancer (NSCLC). Existing imaging-based measures, such as Response Evaluation Criteria in Solid Tumors (RECIST) and tumor volume change (TVC), have limited predictive value for long-term outcomes, and advanced imaging-based biomarkers may enhance decision-making in clinical practice and clinical trials.

OBJECTIVE: To develop and validate a fully automated deep-learning imaging-based biomarker using pretherapy and 12-week follow-up computed tomography (CT) scans.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study used retrospectively collected HER data from routine clinical practice (RCP) …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Phase 1 Trial Of Withania Somnifera Leaf Extract (Rh324) In Advanced Non-Small Cell Lung Cancer Including [18f]Fdg Pet/Ct As A Short-Term Metabolic Biomarker To Assess Efficacy: A Novel Model For Assessment Of Complimentary Therapies In Early Phase Human Clinical Trials, Jin Uk Heo, Santosh Rao, Herbert B Newton, Afshin Dowlati, Raymond F Muzic, Arash Kardan

Faculty, Staff and Students Publications

Background: Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

Methods: A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety …

The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra

Faculty, Staff and Student Publications

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …