Biomedical Informatics Commons^™

Early Ctdna Dynamics Inform First-Line Therapy In Patients With Extensive-Stage Small Cell Lung Cancer, Carmela Ciardullo, Luis Tobalina, T Hedley Carr, Philip Szekeres, Silvija Kraljevic, Lauren Averett Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis despite initial treatment responses. This study evaluates ctDNA for monitoring disease and assessing the efficacy of first-line therapy in patients with extensive-stage SCLC (1L ES-SCLC).

Experimental design: In the TAZMAN trial, 31 patients with 1L ES-SCLC received standard treatment with durvalumab and etoposide plus carboplatin or cisplatin. We analyzed 228 plasma samples from 27 of 31 patients using a liquid biopsy approach to detect somatic mutations and copy-number aberrations, while also accounting for clonal hematopoiesis mutations.

Results: Baseline ctDNA analysis detected somatic alterations in 96.3% of …

Hand Swelling And Other Non-Raynaud Phenomenon Symptoms As The Initial Presentation Of Systemic Sclerosis: Prevalence And Clinical Associations In Two Us Cohorts, Iqtidar Hanif, Shervin Assassi, Maureen D Mayes, Zsuzsanna H Mcmahan, Meng Zhang, Julio Charles, John M Vanburen, Jessica S Alvey, Kimia Ghaffari, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Jessica K Gordon, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Virginia D Steen, Elizabeth R Volkmann, Carleigh Zahn, Brian Skaug

Faculty, Staff and Student Publications

Objective: Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.

Methods: All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.

Results: In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 …

Microbial Signals In Primary And Metastatic Brain Tumors, Golnaz Morad, Ashish V Damania, Brenda Melendez, Bharat B Singh, Fabiana J Veguilla, Rebecca A Soto, Yasmine M Hoballah, Pranoti V Sahasrabhojane, Matthew C Wong, Mona M Ahmed, Rene N Rico, Kaitlyn N Lewis, Khalida Wani, Diana D Shamsutdinova, Rossana N Lazcano Segura, Davis R Ingram, Eric A Goethe, Abderrahman Day, Ivonne I Flores, Lauren K Mcdaniel, Manoj Chelvanambi, Sarah B Johnson, Florentia Dimitriou, Pravesh Gupta, Shivangi Oberai, M Anna Zal, Phoebe Doss, Mohamed A Jamal, Eiko Hayase, Chetna Wathoo, Lisa M Norberg, Stephanie L Jenkins, Sara Nass, Joy Gumin, Lihong Long, Jing Yang, Gina R Bradley, Mahesh Prasad Bekal, Antonio G Dono, Pavel S Pichardo-Rojas, Samuel W Andrewes, Leomar Y Ballester, Jillian S Losh, Jiyong Liang, Longfei Huo, Douglas C Nielsen, Brittany C Parker Kerrigan, Priscilla K Brastianos, Natalie Wall Fowlkes, Chia-Chi Chang, Robert R Jenq, Candelaria Gomez-Manzano, Jason T Huse, Michael A Davies, Alexander J Lazar, Krishna P Bhat, Nitin Tandon, Yoshua Esquenazi, Christine B Peterson, Vinay K Puduvalli, Frederick F Lang, Christopher D Johnston, Susan Bullman, Nadim J Ajami, Sherise D Ferguson, Jennifer A Wargo

Faculty, Staff and Student Publications

Gliomas and brain metastases are associated with poor prognosis, necessitating a deeper understanding of brain tumor biology and the development of effective therapeutic strategies. Although our group and others have demonstrated microbial presence in various tumors, recent controversies regarding cancer-type-specific intratumoral microbiota emphasize the importance of rigorous, orthogonal validation. This prospective, multi-institutional study included a total of 243 samples from 221 patients, comprising 168 glioma and brain metastases samples and 75 non-cancerous or tumor-adjacent tissues. Using stringent fluorescence in situ hybridization, immunohistochemistry and high-resolution spatial imaging, we detected intracellular bacterial 16S rRNA and lipopolysaccharides in both glioma and brain metastases …

Probabilistic Template Matching For Detecting Resting-State Functional Mri Language Network In Brain Tumor Patients, Jian Ming Teo, Vinodh A Kumar, Alexander M Khalaf, Kyle R Noll, Sherise D Ferguson, Chibawanye I Ene, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Intersubject variation among patients with brain tumors complicates the template matching process for detecting the resting-state (rs) functional MRI (fMRI) language network when using independent component analysis (ICA).

Purpose: This study aimed to develop methods that use a probabilistic language atlas to incorporate intersubject variation in brain tumor patients into the template matching process.

Methods: This retrospective study included 79 patients with brain tumors (average age, 50 ± 15 years) who underwent presurgical task-based (tb)-fMRI and rs-fMRI at clinical 3T scanners. At varying template generation thresholds (τ), binary and probabilistic templates were obtained from the language atlas. A binary …

Continuous Androgen Deprivation Therapy With Or Without Metastasis-Directed Therapy For Oligometastatic Prostate Cancer: The Multicenter Phase 2 Randomized Extend Trial, Alexander D Sherry, Bilal A Siddiqui, Cara Haymaker, Bryan M Fellman, Marina N Medina-Rosales, Tharakeswara K Bathala, Shuqi Wang, Suyu Liu, Aaron Seo, Kieko Hara, Hsinyi Lu, Patricia Troncoso, Stephen G Chun, Chul S Ha, Lauren L Mayo, Henry Mok, Ryan J Park, Brian F Chapin, Ryan M Phillips, Matthew P Deek, Craig A Kovitz, Ana Aparicio, Amado J Zurita, Patrick G Pilie, Lorenzo Cohen, Seungtaek L Choi, Alexandre Reuben, Phuoc T Tran, Paul G Corn, Sumit K Subudhi, Chad Tang

Faculty, Staff and Student Publications

Background and objective: Oligometastatic prostate cancer (omPC) is characterized by limited metastases. We hypothesized that metastasis-directed therapy (MDT) to all sites of omPC combined with androgen deprivation therapy (ADT) would improve clinical outcomes.

Methods: In the multicenter phase 2 EXTEND trial, patients with omPC were randomized 1:1 to ADT versus MDT + ADT in two independently powered and randomized baskets, one using intermittent ADT and one using continuous ADT. The primary endpoint was progression-free survival (PFS). The secondary endpoints included radiologic PFS (rPFS) and castration resistance-free survival (CRFS). Here, the primary results of the continuous ADT basket, the combined analysis …

Integration Of Genetic And Imaging Data For Alzheimer's Disease Diagnosis And Interpretation, Yanfei Wang, Qing Wang, Minghao Zhou, Jialu Liang, Lei You, Breton Asken, Xiaobo Zhou, Qianqian Song

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by complex interactions between genetic risk factors and structural brain changes. Traditional diagnostic approaches that rely on single-modality data, such as imaging or genomics alone, often fall short in both predictive accuracy and biological interpretability. To address these limitations, AlzCLIP, a novel contrastive learning framework that integrates single nucleotide polymorphism (SNP) profiles and MRI-derived imaging features into a unified embedding space is introduced. This joint representation captures disease-relevant interactions between genetic variation and brain structure, enabling both accurate diagnosis and mechanistic insight into AD. AlzCLIP is trained and evaluated on two …

Study Of 18 F-Fluciclovine Pet For Serial Assessment Of Glioblastoma Tumor Volumes During Surgery And Radiotherapy, Samir A Dagher, Jason M Johnson, Rania M M Mohamed, Shehbaz Ansari, Osama Mawlawi, Ho-Ling Liu, Max Wintermark, Dawid Schellingerhout, Lesley Flynt, Debra N Yeboa, Jeffrey S Weinberg, Sherise D Ferguson, Maria K Gule-Monroe

Faculty, Staff and Student Publications

PURPOSE: Recent evidence supports incorporating 18 F-Fluciclovine PET for glioblastoma treatment planning and monitoring, as it better captures tumor infiltration compared to conventional MRI. However, the relationship between PET- and MRI-defined tumor volumes remains unclear, particularly in the post-treatment setting. This study prospectively compares tumor volumes on MRI and PET at multiple timepoints throughout the treatment course and evaluates volumetric changes with therapy.

METHODS: We prospectively enrolled 8 adults with IDH-wildtype glioblastoma treated with surgery and chemoradiation between September 2019 and 2021. Participants underwent paired 18 F-Fluciclovine PET/CT and conventional MRI at four timepoints: preoperatively, pre-radiation, and at one- and …

Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed By Adjuvant Durvalumab In Resectable Nsclc, Tetsuya Mitsudomi, John V Heymach, Martin Reck, Janis M Taube, Shugeng Gao, Yoshitsugu Horio, Jian You, Gaofeng Li, Dinh Van Luong, Somcharoen Saeteng, Fumihiro Tanaka, Stefan B Watzka, Laszlo Urban, Zsuzsanna Szalai, Hiroaki Akamatsu, Jin Hyoung Kang, Francisco J Orlandi, Guzel Z Mukhametshina, Andreas Pircher, Carlos Henrique Andrade Teixeira, Mike Aperghis, Gary J Doherty, Ruth Doake, Tamer M Fouad, David Harpole

Faculty, Staff and Student Publications

Introduction: In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (p = 0.004) and pathologic complete response (p < 0.001; primary end points; modified intention-to-treat [mITT] population, which excluded patients with known EGFR or ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN.

Methods: Patients with treatment-naive R-NSCLC (stage II-IIIB [N2]) and Eastern Cooperative Oncology Group performance status 0 or 1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo intravenously (every 3 wk, 4 cycles) before surgery, followed by durvalumab or placebo (every 4 wk, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics.

Results: A total of 737 out of 740 mITT patients received treatment, 366 and 371 in the durvalumab and …

Final Analysis Of The Resonate-2 Study: Up To 10 Years Of Follow-Up Of First-Line Ibrutinib Treatment For Cll/Sll, Jan A Burger, Paul M Barr, Tadeusz Robak, Carolyn Owen, Alessandra Tedeschi, Anita Sarma, Piers E M Patten, Sebastian Grosicki, Helen Mccarthy, Fritz Offner, Edith Szafer-Glusman, Cathy Zhou, Anita Szoke, Lynne Neumayr, James P Dean, Paolo Ghia, Thomas J Kipps

Faculty, Staff and Student Publications

With up to 10 years of follow-up, we report results from the final analysis of RESONATE- 2, a phase 3 study of first-line ibrutinib vs chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients aged ≥65 years with previously untreated CLL/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg/d; n = 136) or chlorambucil (0.5-0.8 mg/kg; ≤12 cycles; n = 133). With a median follow-up of 9.6 years in the ibrutinib arm, the median progression-free survival (PFS) was 8.9 years (95% confidence interval [CI], 7.0 to not estimable [NE]) vs 1.3 years (95% …

Long-Term Results From The Agile Study Of Azacitidine Plus Ivosidenib Vs Placebo In Newly Diagnosed Idh1-Mutated Aml, Pau Montesinos, Dylan M Marchione, Christian Recher, Michael Heuser, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Marta Riva, Rodrigo T Calado, Andre C Schuh, Su-Peng Yeh, Adriana E Tron, Jianan Hui, Diego A Gianolio, Sung Choe, Prapti Patel, Stéphane De Botton, Courtney D Dinardo, Hartmut Döhner

Faculty, Staff and Student Publications

In the phase 3 AGILE study, after a 12.4-month median follow-up, ivosidenib, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, combined with azacitidine significantly improved event-free survival, overall survival (OS), and complete remission rates compared with placebo-azacitidine in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML), who were unfit for intensive chemotherapy. This post hoc analysis reports long-term follow-up results from AGILE after a median follow-up of 28.6 months. Overall, 148 patients were randomized to receive ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75). Median OS was significantly longer with ivosidenib (29.3 months; 95% confidence interval …

Distinct Spatiotemporal Patterns Of White Matter Hyperintensity Progression, Jinyong Chung, Gilsoon Park, Wi-Sun Ryu, Dawid Schellingerhout, Hang-Rai Kim, Dong-Seok Gwak, Elizabeth Haddad, Neda Jahanshad, Beom Joon Kim, Keun-Sik Hong, Hyerin Oh, Sang-Wuk Jeong, Joon-Tae Kim, Man Seok Park, Kang-Ho Choi, Kyungbok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Yong-Jin Cho, Byung-Chul Lee, Philip M Bath, Joanna M Wardlaw, Hee-Joon Bae, Hosung Kim, Dong-Eog Kim

Faculty, Staff and Student Publications

White matter hyperintensity, a key imaging biomarker for brain health, has prognostic implications for stroke. Using a multicenter MRI dataset of 9179 stroke patients plus the UK Biobank (n = 36,210 low/high risk controls), we employ Subtype and Stage Inference modeling and identify three distinct white matter hyperintensity progression subtypes: fronto-parietal, radial, and temporo-occipital. Longitudinal validation confirms classification stability. The fronto-parietal subtype shows delayed onset and more hypertension, while the temporo-occipital subtype has more atrial fibrillation and coronary heart disease. The fronto-parietal and radial subtypes are linked to small vessel stroke, while the temporo-occipital subtype is linked to cardioembolism. The …

Preoperative Brain Mapping Predicts Language Outcomes After Eloquent Tumor Resection, Matthew T Muir, Kyle Noll, Sarah Prinsloo, Hayley Michener, Jeffrey I Traylor, Vinodh A Kumar, Chibawanye I Ene, Sherise Ferguson, Ho-Ling Liu, Jeffrey S Weinberg, Frederick Lang, Brian A Taylor, Stephanie J Forkel, Sujit S Prabhu

Faculty, Staff and Student Publications

When operating on gliomas near critical language regions, surgeons risk either leaving residual tumor or inducing permanent postoperative language deficits (PLDs). Despite the advent of intraoperative mapping techniques, subjective judgments frequently determine important surgical decisions. We aim to inform data-driven surgery by constructing a non-invasive mapping approach that quantitatively predicts the impact of individual surgical decisions on long-term language function. This study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (TMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language …

Landscape And Clinicopathologic Features Of Ras Pathway Mutations In Chronic Myelomonocytic Leukemia, Guillermo Montalban-Bravo, Sanam Loghavi, Ziyi Li, Kelly Chien, Rashmi Kanagal-Shamanna, Alex Bataller, Anuya Natu, Mark Gurney, Alexandre Bazinet, Danielle Hammond, Koji Sasaki, Gautam Borthakur, Mahesh Swaminathan, Courtney Dinardo, Tapan Kadia, Farhad Ravandi, Naval Daver, Nicholas Short, Naveen Pemmaraju, Ghayas Issa, Terra L Lasho, Christy M Finke, Aref Al-Kali, Clifford Csizmar, Hassan Alkhateeb, Naseema Gangat, Abhishek A Mangaonkar, Carlos Bueso-Ramos, Ayalew Tefferi, Hagop Kantarjian, Guillermo Garcia-Manero, Mrinal M Patnaik

Faculty, Staff and Student Publications

RAS pathway (RASp) mutations induce proliferative features, and promote transformation in chronic myelomonocytic leukemia (CMML). However, the unique clonal landscape and hierarchy of distinct RASp mutations remain unexplored. To characterize the landscape, architecture, and implications of unique RASp mutations in CMML, we evaluated a cohort of 814 patients with CMML. We identified 461 RASp mutations among 342 patients (42%). N/KRAS and CBL mutations were the most common, frequently involved the P-loop or RING domains, respectively, and frequently appeared as dominant events (63% and 65%, respectively). BRAF, NF1, and PTPN11 mutations spanned throughout the gene structure, and frequently appeared as subclonal …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Ideate-Lung02: A Phase 3 Study Of Second-Line Ifinatamab Deruxtecan In Patients With Relapsed Small Cell Lung Cancer, Taofeek K Owonikoko, Lauren Byers, Ying Cheng, Hidetoshi Hayashi, Luis Paz-Ares, Maurice Pérol, Haichuan Hu, Meng Qian, Cecilio Roi Garcia, Juliette Godard, Mei Tang, Charles M Rudin

Faculty, Staff and Student Publications

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated …

Evaluating Dimensionality Reduction For Patient-Reported Outcome-Based Survival Modeling In Patients With Head And Neck Cancer, Eric Ababio Anyimadu, Yaohua Wang, Amy C Moreno, Clifton David Fuller, Xinhua Zhang, G Elisabeta Marai, Guadalupe M Canahuate

Faculty, Staff and Student Publications

Purpose: This study aims to improve survival modeling in head and neck cancer (HNC) by integrating patient-reported outcomes (PROs) using dimensionality reduction techniques. PROs capture symptom severity across the treatment timeline and offer key insights for personalized care. However, their high dimensionality poses challenges such as overfitting and computational complexity. This work focuses on transforming and incorporating PRO data to enhance model performance in HNC.

Materials and methods: We analyzed retrospective data of 923 patients with HNC treated at the University of Texas MD Anderson Cancer Center between 2010 and 2021. Baseline clinical data including demographic, treatment, and disease characteristics …

Surgical And Blood-Based Minimal Residual Disease In Patients With Ovarian Cancer After First-Line Therapy: Clinical Outcomes And Translational Opportunities, Anne Knisely, Yibo Dai, Graham L Barlow, Sanghoon Lee, Barrett Lawson, Helen Clark, Bryan Fellman, Ying Yuan, Wei Lu, Idania Carolina Lubo Julio, Rossana N Lazcano, Manoj Chelvanambi, Brenda Melendez, Bharat Singh, Bhavana Singh, Khalida Wani, Jianfeng Chen, Chih-Chen Yeh, Jianjun Gao, Sean Barnes, Ou Shi, Khaja B Khan, Alejandra G Serrano, Lorena I Gomez-Bolanos, Carly Bess Scalise, Samantha K Cheung, Punashi Dutta, Sharlene Velichko, Adam C Elnaggar, Minetta C Liu, Roni N Wilke, Jeffrey How, Lois M Ramondetta, David M Boruta, Gwyn Richardson, Aaron Shafer, Shannon N Westin, Travis Sims, Anil K Sood, Pedro T Ramirez, Alexander J Lazar, Pamela T Soliman, Karen Lu, Cara L Haymaker, Luisa M Solis Soto, Jennifer A Wargo, Rachel Grisham, Kai W Wucherpfennig, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy.

Experimental design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients.

Results: …

Performance Characteristics For Physiological Measures Of Progressive Pulmonary Fibrosis, Chad A Newton, Ashwatha Thenappan, Gabrielle Y Liu, Leda Yazbeck, Cathryn T Lee, Janelle Vu Pugashetti, Jennifer M Wang, Ethan White, Kevin R Flaherty, Elizabeth A Belloli, Jamie S Sheth, Nisha Mohan, Nazanin Nazemi, Andrew R Yu, Sahand Ghodrati, Kerri A Johannson, Veronica Marcoux, Jolene H Fisher, Deborah Assayag, Helene Manganas, Nasreen Khalil, Martin Kolb, Julie Morisset, Christine Kim Garcia, Felix Chua, Mary E Strek, Yet H Khor, Ayodeji Adegunsoye, Christopher J Ryerson, Philip L Molyneaux, Justin M Oldham

Faculty, Staff and Student Publications

Rationale: Clinical measures of progressive pulmonary fibrosis (PPF) have been proposed, but their clinical utility remains unclear.

Objectives: To determine performance characteristics of lung function-based PPF measures, including new guideline criteria for discriminating clinically relevant outcomes.

Methods: A multicenter retrospective cohort analysis was performed to assess the performance characteristics of eight categorical measures of FVC and DlCO decline, together with PPF guideline criteria (requiring two of the following: worsening respiratory symptoms, absolute decline in FVC ⩾5% or DlCO ⩾15%, or radiological progression) for discriminating 2-year death or lung transplant among patients fibrotic interstitial lung disease from the United States, United …

Precemtabart Tocentecan, An Anti-Ceacam5 Antibody-Drug Conjugate, In Metastatic Colorectal Cancer: A Phase 1 Trial, Scott Kopetz, Valentina Boni, Ken Kato, Kanwal P S Raghav, Maria Vieito, Athanasios Pallis, Christina Habermehl, Abdul Siddiqui, Perrine Courlet, Willem Sloot, Sabine Raab-Westphal, Felix Hart, Ildefonso Rodriguez-Rivera

Faculty, Staff and Student Publications

CEACAM5, a cell surface protein, is overexpressed in colorectal cancer (CRC). Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody–drug conjugate with the topoisomerase 1 inhibitor exatecan as payload. Precem-TcT demonstrated strong antitumor activity and potent bystander activity in preclinical models. Its toxicity profile in cynomolgus monkeys was consistent with that of exatecan. In the dose-escalation stage of the phase 1 trial of Precem-TcT (PROCEADE-CRC-01), 40 heavily pretreated patients with irinotecan-refractory metastatic CRC received Precem-TcT every 3 weeks across seven dose levels (DLs, 0.6–3.2 mg kg−1). Primary endpoints were dose-limiting toxicities (DLTs), adverse events and preliminary clinical activity to establish …

Updated Estimates Of Patients With Oropharyngeal Cancer In The Us, Caineng Cao, Anna Lee, Jung Julie Kang, Irini Yacoub, Kaveh Zakeri, Edward Christopher Dee, Nadeem Riaz, Achraf Shamseddine, Yao Yu, Jennifer Ma, Teeradon Treechairusame, Marc A Cohen, Jennifer R Cracchiolo, Richard J Wong, Winston Wong, Lara A Dunn, Eric J Sherman, Nancy Y Lee

Faculty, Staff and Student Publications

Importance: Updated estimates of oropharyngeal cancer (OPC) in the US are needed.

Objective: To calculate the most recent epidemiologic estimates of OPC in the US and provide projections for future trends up to 2040.

Design, setting, and participants: This cross-sectional epidemiological analysis used data from the recent National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. The SEER-22 (excluding Illinois and Massachusetts) database provided data for incidence, prevalence, survival, and initial treatment by OPC stage. Patients with OPC diagnosed according to International Classification of Diseases for Oncology, Third Edition morphology codes were included. The analysis was conducted from September …

Natural History Of Primary Retroperitoneal Extra-Visceral Perivascular Epithelioid Cell Tumors (Pec): A Study From Transatlantic And Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Eyal Mor, Sameer Apte, Catherine Mitchell, Carolyn Nessim, Max Almond, Bruno Vincenzi, Jose Antonio Gonzalez Lopez, Lee Cranmer, Michael J Wagner, Aviram Nissan, Miguel Henriques Abreu, Markus Albertsmeier, Mathilda Knoblauch, Adam Barlow, Emily Z Keung, Giovanni Grignani, Jason L Hornick, Alessandro Gronchi, David E Gyorki

Faculty, Staff and Student Publications

Background: Perivascular epithelioid cell tumors (PEComa) are a rare family of mesenchymal tumors that include several subtypes. There are very limited data describing the natural history of patients with extra-visceral retroperitoneal PEComas of the retroperitoneum. The aim of this study is to describe the clinical features, treatment patterns, outcomes, and diagnostic challenges of primary extra-visceral retroperitoneal or abdominopelvic PEComa over the past decade.

Patients and methods: This is a retrospective analysis of all extra-visceral, non-renal, retroperitoneal, or abdominopelvic PEComas treated at participating centers over the past 10 years.

Results: A total of 77 patients from 13 centers were included. The …

Imaging- And Tumor Biomarker-Based Multivariable Model For Early Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Beatriz E Adrada, Mary S Guirguis, Lei Huo, Clinton Yam, Debu Tripathy, Rosalind Candelaria, Wei Yang, Miral Patel, Tanya Moseley, Gary J Whitman, Jessica W T Leung, Huong Le-Petross, Deanna L Lane, Nour Abuhadra, Jennifer Litton, Vicente Valero, Kelly K Hunt, Banu Arun, Rania Mohamed, Jia Sun, Anil Korkut, Sanaz Pashapoor, Jason White, Alastair Thompson, Peng Wei, Jingfei Ma, Stacy Moulder, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose: The response of triple-negative breast cancer (TNBC) to neoadjuvant therapy (NAT) varies widely. This study aimed to determine the performance of clinicopathologic biomarkers and volumetric changes on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting pathologic complete response (pCR) to NAT in patients with TNBC.

Patients and methods: This study included 264 patients with stage I to III TNBC enrolled in a prospective clinical trial. These patients underwent DCE-MRI at baseline and after two and/or after four cycles of dose-dense anthracycline and cyclophosphamide. Tumor volume (TV) was calculated by measuring three tumor dimensions at each time point. Clinicopathologic markers …

Chromosome 20q Gene Signature Associated With Colorectal Cancer Progression, Jennifer Carter Jones, Apurva M Hegde, Yu-Jing Huang, Ganiraju Manyam, Vibhuti Srivastava, Jee Hoo Song, Yulan Cheng, Ralf Krahe, Warapen Treekitkarnmongkol, Stephen J Meltzer, Scott Kopetz, Stanley R Hamilton, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression …

Lesion Absorbed Dose-Response Relationship In Patients With Metastatic Castration-Resistant Prostate Cancer Undergoing [177lu]Lu-Psma-617 Radiopharmaceutical Therapy, Milan Grkovski, Simone S Krebs, Joseph A O'Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J Fox, Neeta Pandit-Taskar, Mark P Dunphy, Lisa Bodei, John L Humm, Heiko Schöder

Faculty, Staff and Student Publications

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD-response relationship at both the patient and lesion levels.

Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Impacts Of The Conductive Networks On Solid-State Battery Operation, Shimao Deng, Yixian Wang, Tianxiao Sun, Wenlong Li, Mingyuan Ge, Jian Wang, Peter Cloetens, Piero Pianetta, David Mitlin, Yijin Liu

Faculty, Staff and Student Publications

The micromorphology of composite cathodes is known to play a vital role in determining all‐solid‐state battery (ASSB) performance. However, much of our current understanding is derived from empirical observations, lacking a deeper mechanistic foundation. The “rocking chair” concept of battery chemistry requires maintaining charge neutrality, emphasizing the necessity of examining electrode micromorphology from the perspective of conductive networks. This study systematically investigates the microscopic electrochemical impacts of conductive network micromorphology by varying the Li+‐to‐e− channel ratio in cathodes comprising LiNbO3‐coated LiNi0.8Co0.1Mn0.1O2, Li6PS5Cl, and carbon fibers. Utilizing multiscale synchrotron‐based spectro‐microscopy, we unravel that unbalanced Li+ and e− conducting channels intensify charge …

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …

A Phase 2 Study Of Obinutuzumab Combined With Lenalidomide In Previously Untreated High Tumor Burden Follicular Lymphoma, Neha Akkad, Lei Feng, Jason R Westin, Fredrick B Hagemeister, Hun Ju Lee, Luis Fayad, Sairah Ahmed, Ranjit Nair, Maria Alma Rodriguez, Paolo Strati, Dai Chihara, Christopher R Flowers, Linda Claret, Karina Ibanez, Michael Wang, Nathan H Fowler, Jared Henderson, R Eric Davis, Sattva S Neelapu, Michael Green, Loretta J Nastoupil

Faculty, Staff and Student Publications

Follicular lymphoma (FL) has a clinical course that is often characterized by high response rates to first-line therapy, followed by multiple relapses over a prolonged natural history. Currently, there are multiple possible approaches to frontline therapy for untreated advanced-stage FL, but there is an ongoing debate around what is the preferred approach. Based on the benefits seen with combining lenalidomide, an immunomodulatory agent, with rituximab, an anti-CD20 antibody, we aimed to evaluate the safety and efficacy of lenalidomide in combination with obinuzutumab, an anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity. The eligibility criteria included a diagnosis of FL, grade 1 …