Biomedical Informatics Commons^™

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: …

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 …

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.

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 …

Fruquintinib In Less Pretreated Patients: Multivariate Profile-Matching Analysis Of Fresco-2 To Fresco, Arvind Dasari, Cathy Eng, Sara Lonardi, Rocio Garcia-Carbonero, Toshiki Masuishi, Chiara Cremolini, François Ghiringhelli, Joleen Hubbard, Tanios Bekaii-Saab, Jeremy Jones, Rui-Hua Xu, Lin Shen, Jianming Xu, Yuxian Bai, Yanhong Deng, Ying Yuan, Wei Wei, Jianchang Lin, Lucy Chen, Zhao Yang, William R Schelman, Shukui Qin, Jin Li

Faculty, Staff and Student Publications

Background: In the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies, fruquintinib vs placebo, plus best supportive care, significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC). These studies were conducted in temporally and geographically diverse populations that received distinct prior therapies; FRESCO patients were less pretreated than FRESCO-2 patients. This analysis assessed the efficacy and safety of fruquintinib in a less pretreated global population than the FRESCO-2 intention-to-treat (ITT) population.

Methods: In FRESCO and FRESCO-2, patients were randomized 2:1 to receive oral fruquintinib 5 mg or matched placebo. Profile matching was undertaken …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

Contemporary Outcomes Of Octa-Nonagenarians With Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Hagop M Kantarjian, Tapan M Kadia, Jeannot Kekedjian, Gautam Borthakur, Naval Daver, Courtney D Dinardo, Elias Jabbour, Prithviraj Bose, Nicholas J Short, Musa Yilmaz, Nitin Jain, Naveen Pemmaraju, Hussein A Abbas, Ghayas C Issa, Abhishek Maiti, Guillermo Montalban Bravo, Indraneel Deshmukh, Elizabeth Shpall, Partow Kebriaei, Uday Popat, Sanam Loghavi, Beenu Thakral, Guilin Tang, Fadi G Haddad, Yesid Alvarado, Guillermo Garcia Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation. Evaluating their outcomes with modern treatment approaches is important.

Methods: This retrospective study analyzed outcomes of patients ≥80 years old with newly diagnosed AML treated at our center from 2013-2023.

Results: A total of 289 patients (median age, 83 years; range, 80-95 years) were included. Venetoclax containing low-intensity therapy was administered to 107 patients (37.0%). AML subtypes included de novo (123, …

Frontline Acalabrutinib, Lenalidomide And Rituximab For Advanced Stage Follicular Lymphoma With High Tumor Burden: Phase Ii Trial, Paolo Strati, Lei Feng, Jason R Westin, Ranjit Nair, Luis E Fayad, Maria A Rodriguez, Dai Chihara, Luis Malpica, Jared Henderson, Mariana Gallardo, Marissa Rivera, Iris Wang, Anastasiia Bolshakova, Anastasia Radko, David Kurtz, Stefan K Alig, Christopher R Flowers, Ash A Alizadeh, Sattva S Neelapu

Faculty, Staff and Student Publications

This phase II trial aims to determine the efficacy and safety of frontline acalabrutinib, lenalidomide and rituximab for patients with advanced stage follicular lymphoma (FL) and high tumor burden. The primary endpoint was best complete response (CR) rate; the secondary endpoints were overall response rate (ORR), duration of response measured as CR at 30 months (CR30), progression of disease at 24 months (POD24) rate, progression-free survival (PFS), overall survival and safety. Twenty-four patients with previously untreated FL were included in this phase 2 single arm study (NCT04404088). The most common grade 3-4 adverse events were neutropenia (58%) and …

Histologic And Immune Characterization Of Cutaneous Immune-Related Adverse Events Induced By Immune Checkpoint Inhibitors, Omar Pacha, Anisha B Patel, Jonathan L Curry, Cara L Haymaker, Nejla Ozirmak Lermi, Dzifa Yawa Duose, Ken Chen, Joud Hajjar, Aung Naing

Faculty, Staff and Student Publications

Background: Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods: Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE …

Exploring Factors Affecting The Adoption And Use Of Digital Health Technologies Among Older Adults With Cancer: A Qualitative Study, Misun Hwang, Youmin Cho, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Although digital health technologies (DHTs) are promising to improve health outcomes in older adults with cancer, the low adoption and limited use remain significant gaps in their effective digital health care. Little is known about their concerns about adopting and using DHTs in routine life, particularly in the continued use phase. This study aims to explore factors affecting the initial adoption and continued use of DHTs among older adults with cancer.

Methods: A secondary analysis of qualitative data was conducted based on interviews with 21 older adults (≥ 65 years) with breast, prostate, lung, or colorectal cancer. The transcripts …

Efficacy And Safety Of Oral Decitabine/Cedazuridine In The Chronic Myelomonocytic Leukaemia Subpopulations From Phase 2 And 3 Studies, Michael R Savona, Olatoyosi Odenike, Gail J Roboz, Harshad Amin, Amy E Dezern, Elizabeth A Griffiths, Kim-Hien Dao, Amer M Zeidan, Bhavana Bhatnagar, Rena Buckstein, Brian Leber, Mary-Margaret Keating, Somedeb Ball, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

DNA methyltransferase inhibitors (DNMTis) are commonly used in treating chronic myelomonocytic leukaemia (CMML); however, data from prospective studies of DNMTis in CMML are limited. The present analysis evaluated the efficacy, safety and pharmacodynamics of the oral DNMTi decitabine/cedazuridine in the subset of patients with CMML from the phase 2 and 3 trials, which led to the approval of this agent for myelodysplastic syndromes and CMML in the United States and Canada. Potential prognostic factors also were analysed. In all, 34 patients with CMML were screened and 33 were treated. Most patients (76% [n = 25]) had myelodysplastic type-CMML and 77% …

Bayesian Counterfactual Machine Learning Individualizes Radiation Modality Selection To Mitigate Immunosuppression, Duo Yu, Michael J Kane, Yiqing Chen, Steven H Lin, Radhe Mohan, Brian P Hobbs

Faculty, Staff and Student Publications

Purpose: Lymphocytes play critical roles in cancer immunity and tumor surveillance. Radiation-induced lymphopenia (RIL) is a common side effect observed in patients with cancer undergoing chemoradiation therapy (CRT), leading to impaired immunity and worse clinical outcomes. Although proton beam therapy (PBT) has been suggested to reduce RIL risk compared with intensity-modulated radiation therapy (IMRT), this study used Bayesian counterfactual machine learning to identify distinct patient profiles and inform personalized radiation modality choice.

Methods: A novel Bayesian causal inferential technique is introduced and applied to a matched retrospective cohort of 510 patients with esophageal cancer undergoing CRT to identify patient profiles …

Associations Between Prostate Cancer And Dementia: A Nationwide Study In Sweden, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Jingkai Wei, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background and objective: Prostate cancer (PC) and dementia may commonly co-occur; yet, prior evidence for bidirectional associations is inconsistent. This study aims to determine the associations between PC and dementia in large population-based studies, which may further inform clinical care.

Methods: To assess the dementia risk in men with PC, a national cohort study was conducted in 178 746 men diagnosed with PC in 1998-2017 and 1 787 460 age-matched control men in Sweden without prior dementia. Cox regression was used to estimate hazard ratios (HRs) for Alzheimer's disease (AD) and vascular dementia (VaD) through 2018. Subanalyses explored differences by …

White Matter Abnormalities And Cognition In Aging And Alzheimer Disease, Christopher Peter, Aditi Sathe, Niranjana Shashikumar, Kimberly R Pechman, Abigail W Workmeister, T Bryan Jackson, Yuankai Huo, Shubhabrata Mukherjee, Jesse Mez, Logan C Dumitrescu, Katherine A Gifford, Corey J Bolton, Leslie S Gaynor, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun-Turgut, Mohamad Habes, Di Wang, Arthur W Toga, Paul M Thompson, Panpan Zhang, Kurt G Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Barbara B Bendlin, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Paul K Crane, Michael L Cuccaro, Timothy J Hohman, Derek B Archer, Dimitrios Zaras, Yisu Yang, Alaina Durant, Praitayini Kanakaraj, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Seo-Eun Choi, Brandon Klinedinst, Michael L Lee, Phoebe Scollard, Emily H Trittschuh, Elizabeth A Sanders

Faculty, Staff and Student Publications

Importance: There has yet to be a large-scale study quantifying the association between white matter microstructure and cognitive performance and decline in aging and Alzheimer disease (AD).

Objective: To investigate the associations between tract-specific white matter microstructure and cognitive performance and decline in aging and AD-related cognitive impairment.

Design setting and participants: This prognostic study of aging and AD, a secondary data analysis of multisite cohort studies, acquired data from 9 cohorts between September 2002 and November 2022. Participants were eligible if they had diffusion-weighted magnetic resonance imaging (dMRI) data, domain-specific cognitive composite z scores, demographic and clinical data, were …

The Significance Of Detecting An Unusual Myeloblast Immunophenotype In A Presumptive Clinical Diagnosis Of Myelodysplastic Syndromes, Fnu Sameeta, Wei Wang, Fatima Zahra Jelloul, Okechukwu V Nwogbo, Beenu Thakral, Jie Xu, Shaoying Li, Chi Young Ok, Guilin Tang, Fuli Jia, L Jeffrey Medeiros, Sanam Loghavi, Jeffrey L Jorgensen, Sa A Wang

Faculty, Staff and Student Publications

Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.

Objective.—: To investigate the occurrence of these cases, and to examine any unique molecular genetic features, and clinical relevance.

Design.—: More than 2000 flow cytometry immunophenotyping tests for MDS performed during a 5-year period were retrospectively reviewed. Chronic myelomonocytic leukemia and overt acute myeloid leukemia (AML) (≥20% blasts) were excluded.

Results.—: Approximately 800 cases had abnormal myeloblasts consistent with myeloid neoplasms; 96% of cases showed a typical primitive phenotype, but …

Timing Of Nodal Metastasis In Patients With Eyelid Sebaceous Carcinoma And Implications For Surveillance And Survival, Tracy Lu, Casey Anthony, Xinyang Jiang, Jing Ning, Ryan Goepfert, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: Sebaceous carcinoma (SC) is a rare cancer with periocular predilection. Studies focused on patterns and timing of nodal metastasis are scarce.Our aim is to report patterns of regional nodal metastasis in patients with eyelid SC, including results of sentinel lymph node biopsy (SLNB).

Methods: All consecutive patients with eyelid SC treated during 1999-2023 were retrospectively reviewed.All subjects had standard of care surgery for eyelid SC and regional lymph node evaluation using physical examination and ultrasonography (US) at baseline and during the surveillance period. 38 patients with negative findings on US had SLNB to rule out microscopic metastasis.The frequency and …

Detection Of Oncogenic Fusions In Colorectal Cancer Using A Partner-Agnostic Next-Generation Sequencing Approach, Andrew J Pellatt, Reagan M Barnett, Sante Gnerre, Kristin Edwards, Jason A Willis, Michael J Overmann, Kanwal Raghav, Christine M Parseghian, Arvind Dasari, M Pia Morelli, Alisha Bent, Madhulika Eluri, Nicholas Hornstein, Leylah M Drusbosky, Scott Kopetz, Van K Morris

Faculty, Staff and Student Publications

Background: Gene fusions exist with low prevalence in colorectal cancer (CRC), and the clinical utility of fusion testing in advanced CRC remains unclear. We sought to identify oncogenic fusions in patients with advanced CRC using a fusion partner-agnostic circulating tumor DNA (ctDNA) assay to better understand their clinical relevance.

Methods: We performed a retrospective analysis using de-identified data from 18,558 patients with advanced CRC who underwent ctDNA next-generation sequencing with Guardant360® from 2017 to 2022. These samples were subsequently reanalyzed with a partner-agnostic bioinformatics method to identify both clonal and non-clonal fusions. We analyzed for associations between fusions and MSI-H …

Ctdna Analysis In Erbb2-Amplified Colorectal Cancer: Biomarker Analysis Of The Mypathway Trial, Funda Meric-Bernstam, Kanwal Pratap Singh Raghav, Christopher J Sweeney, Charles Swanton, David R Spigel, Ron Bose, Howard A Burris, Claire F Friedman, Carin R Espenschied, Jessica M Grindheim, Julia Malato, Katja Schulze, Richard Price, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: A combination of two HER2-directed antibodies, pertuzumab and trastuzumab (P + T), has antitumor activity in HER2-positive colorectal cancer. Although liquid biopsies are increasingly being used in clinical oncology, the association between tumor and ctDNA ERBB2 status and ctDNA monitoring for early response and resistance are unknown.

Patients and methods: Eighty-five patients with ERBB2-amplified and/or -overexpressed colorectal cancer were treated with P + T in the MyPathway trial; 42 had ctDNA testing at cycle (C) 1 day (D) 1, and 38 had longitudinal plasma tested for ctDNA. We analyzed the ctDNA versus tissue ERBB2 concordance, genomic co-alterations, and ctDNA …

Nivolumab Plus Relatlimab For Patients With Relapsed Or Progressed B-Cell Malignancies In Relativity-022, Ajay K Gopal, Philippe Armand, Sattva S Neelapu, Nancy L Bartlett, Stephen E Spurgeon, John Kuruvilla, Kerry J Savage, John P Leonard, Arnold B Gelb, Nasir Ahmed, Shiqi Dong, Sai Praneeth Bathena, Rasika Suryawanshi, Jenny Qun Wu, Sheen Wang, Douglas E Gladstone

Faculty, Staff and Student Publications

Despite high response rates, anti-programmed death 1 (anti-PD-1) monotherapy eventually fails in most patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and is ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved in advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with R/R B-cell malignancies. We treated 106 patients and no dose-limiting toxicities were observed during …

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Long-Term Exposure To Multiple Air Pollutants And Multi-Level Socioeconomic Status: Joint Effects On Age-Related Macular Degeneration, Subsequent Ocular Comorbidity, And Death In Middle-Aged And Older Adults, Yang Yang, Liangkai Chen, Qichen Liu, Min Mu, Jing Huang, Guangming Zhang, Qianqian Song

Faculty, Staff and Student Publications

Background: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.

Methods: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were …

Long-Term Transfusion Independence With Luspatercept Versus Epoetin Alfa In Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes In The Commands Trial, Guillermo Garcia-Manero, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Veronika Pozharskaya, Shelonitda Rose, Karen Keeperman, Yinzhi Lai, Sameer Kalsekar, Barkha Aggarwal, Dimana Miteva, David Valcárcel, Pierre Fenaux, Jake Shortt, Matteo Giovanni Della Porta, Uwe Platzbecker

Faculty, Staff and Student Publications

Introduction: The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.

Methods: Eligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and …

Outcomes And Toxicity Following 3 Or More Definitive Courses Of Thoracic Radiation Therapy For Non-Small Cell Lung Cancer, Abigael Odwuor, Percy Lee, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Matthew S Ning

Faculty, Staff and Student Publications

Purpose: Salvage re-irradiation is increasingly utilized to manage non-small cell lung cancer (NSCLC) locoregional recurrence or new lung primaries in previously treated areas. There is sparse information on efficacy and toxicity profile. We report a large experience of patients treated with multiple courses of definitive radiation for new and recurrent NSCLC.

Methods and materials: Medical records of patients who underwent ≥ 3 definitive thoracic radiation therapy (RT) courses for new or recurrent NSCLC at our cancer center from 2012 through 2021 were retrospectively reviewed following institutional review board approval. Toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …

Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators

Faculty, Staff and Student Publications

Background: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P< 0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall …

Characterization And Clinical Implications Of P53 Dysfunction In Patients With Myelodysplastic Syndromes, Matteo Zampini, Elena Riva, Luca Lanino, Elisabetta Sauta, Rita Antunes Dos Reis, Rosa Maria Andres Ejarque, Giulia Maggioni, Alberto Termanini, Alessandra Merlotti, Alessia Campagna, Lorenzo Dall'olio, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Arturo Bonometti, Daoud Rahal, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Rossella Caselli, Serena Albertazzi, Gabriele Todisco, Marta Ubezio, Laura Crisafulli, Alessandro Frigo, Enrico Lugli, Ettore Mosca, Pamela Acha, Serena Ghisletti, Francesco Nicassio, Armando Santoro, Maria Diez-Campelo, Francesc Solé, Lionel Ades, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Torsten Haferlach, David Sallman, Guillermo Garcia-Manero, Domenico Mavilio, Daniel Remondini, Gastone Castellani, Saverio D'Amico, Amer M Zeidan, Rami Komrokji, Shahram Kordasti, Francesca Ficara, Matteo Giovanni Della Porta, Calr Consortium

Faculty, Staff and Student Publications

Purpose: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients and methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients.

Results: Biallelic TP53 inactivation was a powerful driver …