Life Sciences Commons^™

Trajectory, Interactions, And Predictors Of Higher Symptom Burden During Induction Therapy For Multiple Myeloma, Mona Kamal, Qiuling Shi, Shu-En Shen, Charles Cleeland, Xin Shelley Wang

Faculty, Staff and Student Publications

Background: Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy-induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.

Methodology: Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus …

Differential Infiltration Of Key Immune T-Cell Populations Across Malignancies Varying By Immunogenic Potential And The Likelihood Of Response To Immunotherapy., Islam Eljilany, Sam Coleman, Aik Choon Tan, Martin D. Mccarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle L. Churchman, Daniel Spakowicz, Bodour Salhia, Julian Marin, Shridar Ganesan, Aakrosh Ratan, Craig Shriver, Patrick Hwu, William S. Dalton, George J. Weiner, Jose R. Conejo-Garcia, Paulo Rodriguez, Ahmad A. Tarhini

Markey Cancer Center Faculty Publications

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing …

Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

METHODS: In this population-based case (n = 1812)-control (n = 1,381) study of invasive YOBC (ages <50 >years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes …

Individual Dynamic Prediction For Cure And Survival Based On Longitudinal Biomarkers, Can Xie, Xuelin Huang, Ruosha Li, Alexander Tsodikov, Kapil Bhalla

Faculty, Staff and Student Publications

To optimize personalized treatment strategies and extend patients' survival times, it is critical to accurately predict patients' prognoses at all stages, from disease diagnosis to follow-up visits. The longitudinal biomarker measurements during visits are essential for this prediction purpose. Patients' ultimate concerns are cure and survival. However, in many situations, there is no clear biomarker indicator for cure. We propose a comprehensive joint model of longitudinal and survival data and a landmark cure model, incorporating proportions of potentially cured patients. The survival distributions in the joint and landmark models are specified through flexible hazard functions with the proportional hazards as …

Psychophysical And Functional Outcomes In Chemotherapy-Induced Peripheral Neuropathy After Spinal Cord Stimulation: A Narrative Review And Case Series, Peter D Vu, Kathleen Erin Mcdonough, Patrick M Dougherty, Ryan S D'Souza, Saba Javed

Faculty, Staff and Student Publications

Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a complication that may occur after treatment with various anticancer drugs. In refractory CIPN cases, spinal cord stimulation (SCS) has garnered increased attention. The use of gait analysis and psychophysical quantitative sensory testing (QST) as an objective measurement of CIPN-related damage has burgeoned; however, these changes have not been reported for patients with CIPN after SCS implantation using either burst or tonic stimulation.

Materials and methods: This manuscript encompasses two parts: 1) a presentation of pain improvement in a series of patients who underwent tonic vs burst SCS for CIPN measured by gait and …

Adjuvant Rituximab And Elevated Intratumoural Cd8 Expression Are Associated With Sustained Disease Control After Radiotherapy In A Randomised Trial Of Systemic Therapy In Early-Stage Follicular Lymphoma, Michael P Macmanus, John F Seymour, Hennes Tsang, Richard Fisher, Colm Keane, Muhammed B Sabdia, Soi C Law, Jay Gunawardana, Karthik Nath, Stephen H Kazakoff, Mario L Marques-Piubelli, Daniela E Duenas, Michael R Green, Daniel Roos, Peter O'Brien, Andrew Mccann, Richard Tsang, Sidney Davis, David Christie, Chan Cheah, Benhur Amanuel, Tara Cochrane, Jason Butler, Anna Johnston, Mohamed Shanavas, Li Li, Claire Vajdic, Robert Kridel, Victoria Shelton, Samantha Hershenfield, Tara Baetz, David Lebrun, Nathalie Johnson, Marianne Brodtkorb, Maja Ludvigsen, Francesco D'Amore, Ella R Thompson, Piers Blombery, Maher K Gandhi, Joshua W D Tobin

Faculty, Staff and Student Publications

Background: We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.

Methods: Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).

Findings: Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at …

High Activity Of The New Myeloablative Regimen Of Gemcitabine/Clofarabine/Busulfan For Allogeneic Transplant For Aggressive Lymphomas, Jeremy Ramdial, Ruitao Lin, Peter F Thall, Benigno C Valdez, Chitra Hosing, Samer Srour, Uday Popat, Muzaffar Qazilbash, Amin Alousi, Melissa Barnett, Alison Gulbis, Terri Lynn Shigle, Elizabeth J Shpall, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Refractory aggressive lymphomas can be treated with allo-SCT, pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning is safe, tumors often progress rapidly, indicating the need for more active conditioning regimens. The preclinical synergy we saw between gemcitabine (Gem), clofarabine (Clo) and busulfan (Bu) against lymphoma cell lines led us to study Gem/Clo/Bu clinically. Eligibility: age 12-65, refractory aggressive B-NHL, T-NHL or Hodgkin, with a matched donor. Infusional Gem was dose-escalated on days (d) -6 and -4 (475-975 mg/m2/day), followed by Clo (40 mg/m2/day) and Bu (target AUC, 4000 μMol min/day) (d -6 to -3). CD20+ tumors received rituximab. GVHD prophylaxis …

Anti-Programmed Death Ligand 1 Plus Targeted Therapy In Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial, Maria E Cabanillas, Ramona Dadu, Renata Ferrarotto, Maria Gule-Monroe, Suyu Liu, Bryan Fellman, Michelle D Williams, Mark Zafereo, Jennifer R Wang, Charles Lu, Matthew Ning, Brian A Mckinley, Scott E Woodman, Dzifa Duose, Gary B Gunn, Naifa L Busaidy, Rare Tumor Initiative Team

Faculty, Staff and Student Publications

Importance: Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors.

Objective: To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS).

Design, setting, and participants: A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus …

Mortality Risks Associated With Depression In Men With Prostate Cancer, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC.

Objective: To determine the associations between major depression and mortality in a national cohort of men with PC.

Design, setting, and participants: A national cohort study was conducted of all 180 189 men diagnosed with PC in Sweden during 1998-2017. Subsequent diagnoses of major depression were ascertained from nationwide outpatient and inpatient records through 2018.

Outcome measurements and …

Sitravatinib In Patients With Solid Tumors Selected By Molecular Alterations: Results From A Phase Ib Study, Lyudmila Bazhenova, Dong-Wan Kim, Byoung Chul Cho, Sanjay Goel, Rebecca Heist, Theresa L Werner, Keith D Eaton, Judy S Wang, Shubham Pant, Douglas R Adkins, Collin M Blakely, Xiaohong Yan, Saskia Neuteboom, James G Christensen, Richard Chao, Todd Bauer

Faculty, Staff and Student Publications

No abstract provided.

Keratinocyte Carcinomas In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Christina Boull, Yan Chen, Cindy Im, Alan Geller, Yadav Sapkota, James E Bates, Rebecca Howell, Michael A Arnold, Miriam Conces, Louis S Constine, Leslie Robison, Yutaka Yasui, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established.

Objective: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS.

Methods: KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed < 21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics.

Results: Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted …

Drug And Biomarker Tissue Levels In A Randomized Presurgical Trial On Exemestane Alternative Schedules, Davide Serrano, Harriet Johansson, Bjørn-Erik Bertelsen, Sara Gandini, Gunnar Mellgren, Parijatham Thomas, Katherine D Crew, Nagi B Kumar, Debora Macis, Valentina Aristarco, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Mauro D'Amico, Tania Buttiron-Webber, Irene Maria Briata, Stefano Spinaci, Viviana Galimberti, Lana A Vornik, Eduardo Villar-Sanchez, Powel H Brown, Brandy M Heckman-Stoddard, Eva Szabo, Bernardo Bonanni, Andrea Decensi

Faculty, Staff and Student Publications

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a presurgical study of alternative exemestane schedules. Postmenopausal women candidates for breast surgery for estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg once daily (QD), 25 mg 3 times/week (TIW), or 25 mg per week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

The Prognostic Impact Of Tumor Deposits In Colorectal Cancer: More Than Just N1c, Neal Bhutiani, Oliver Peacock, Abhineet Uppal, Chung-Yuan Hu, Brian K Bednarski, Melissa W Taggart, Arvind Dasari, Van K Morris, Harmeet Kaur, Scott Kopetz, Emma B Holliday, Prajnan Das, Y Nancy You, George J Chang

Faculty, Staff and Student Publications

Background: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC.

Methods: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards …

Datopotamab-Deruxtecan In Early-Stage Breast Cancer: The Sequential Multiple Assignment Randomized I-Spy22 Phase 2 Trial, Katia Khoury, Jane L Meisel, Christina Yau, Hope S Rugo, Rita Nanda, Marie Davidian, Butch Tsiatis, A Jo Chien, Anne M Wallace, Mili Arora, Mariya Rozenblit, Dawn L Hershman, Alexandra Zimmer, Amy S Clark, Heather Beckwith, Anthony D Elias, Erica Stringer-Reasor, Judy C Boughey, Chaitali Nangia, Christos Vaklavas, Coral Omene, Kathy S Albain, Kevin M Kalinsky, Claudine Isaacs, Jennifer Tseng, Evanthia T Roussos Torres, Brittani Thomas, Alexandra Thomas, Amy Sanford, Ronald Balassanian, Cheryl Ewing, Kay Yeung, Candice Sauder, Tara Sanft, Lajos Pusztai, Meghna S Trivedi, Ashton Outhaythip, Wen Li, Natsuko Onishi, Adam L Asare, Philip Beineke, Peter Norwood, Lamorna Brown-Swigart, Gillian L Hirst, Jeffrey B Matthews, Brian Moore, W Fraser Symmans, Elissa Price, Carolyn Beedle, Jane Perlmutter, Paula Pohlmann, Rebecca A Shatsky, Angela Demichele, Douglas Yee, Laura J Van 'T Veer, Nola M Hylton, Laura J Esserman

Faculty, Staff and Student Publications

Among the goals of patient-centric care are the advancement of effective personalized treatment, minimising toxicity. The phase-2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimising individual outcomes. Here we tested datopotamab-deruxtecan (Dato-Dxd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomisation trial (SMART) design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent (Block A), a taxane-based regimen tailored to the tumour subtype (Block B), and doxorubicin/cyclophosphamide (Block C). Patients are randomised into …

Defining Breast Cryoablation Treatment Success: A Guide For The Curative And Palliative Treatment Of Breast Cancer, Monica L Huang, Deanna L Lane, Lauren Q Chang Sen, Rosalind P Candelaria, Henry M Kuerer, Kelly K Hunt, Catherine Akay, Bora Lim, Simona Shaitelman, Rosa F Hwang, Hui Chen, Rajani Katta, Lumarie Santiago

Faculty, Staff and Student Publications

Rationale and objectives: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives.

Materials and methods: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, …

Sleep Disturbances Based On Patient Reported Outcomes In Patients With Breast Cancer, Saadia A Faiz, Ashley S Knox, Bryan Fellman, Bibi Aneesah Jaumally, G Nancy Pacheco, Aneesa Das, Reeba Mathew, Rashmi Murthy, Jennifer K Litton, Diwakar D Balachandran, Lara Bashoura

Faculty, Staff and Student Publications

Purpose: Sleep disturbances are common in patients with breast cancer, but comprehensive evaluations with patient-reported outcomes (PRO) and sleep evaluation with polysomnography (PSG) are lacking. This study describes sleep disruption using PROs and PSG to identify underlying sleep disorders.

Methods: A retrospective review of patients with breast cancer undergoing formal sleep evaluation from 4/1/2009 to 7/31/2014 was performed. Clinical characteristics, PROs using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and PSG data were reviewed.

Results: 404 patients were identified with 43% early, 30% locally advanced and 17% metastatic disease. PSQI revealed poor sleep in 75%, and ESS …

Association Between Chronotype And Chronic Neuropathic Pain Sensitivity: A Pilot Prospective, Observational, Single-Center, Cross-Sectional Study, Michael Kim, Yuri C Martins, Kishan Patel, Chiu-Hsieh Hsu, Mohab Ibrahim, Vasudha Goel, Amol M Patwardhan, Sejal Jain

Faculty, Staff and Student Publications

Background: Chronotype defines an organism's biological preference for timing of activity and sleep. Being a morning chronotype (i.e., tending to wake up early and go to bed earlier at night) is associated with protection against chronic musculoskeletal pain and headaches, but the relationship between chronotype and neuropathic pain sensitivity remains unclear.

Objectives: The aim of this pilot study was to explore the relationship among chronotype, neuropathic pain sensitivity, and pain interference in patients with chronic neuropathic pain disorders.

Study design: This was a prospective, observational, single-center, cross-sectional study.

Setting: Patients were recruited from pain management clinics.

Methods: The Morningness-Eveningness Questionnaire …

Association Of Late Eating With Colorectal Adenomas: A Cross-Sectional Study, Darbaz Adnan, Edena R Khoshaba, Mostafa Abel-Reheem, Jonathan Q Trinh, Yin Cao, Faraz Bishehsari

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA).

Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four …

Gravity- Vs Wall Suction-Driven Large-Volume Thoracentesis: A Randomized Controlled Study, Samira Shojaee, Jasleen Pannu, Lonny Yarmus, Alberto Fantin, Christina Macrosty, Roland Bassett, Labib Debiane, Zachary S Depew, Saadia A Faiz, Carlos A Jimenez, Sameer K Avasarala, Erik Vakil, Andrew Demaio, Lara Bashoura, Keerthana Keshava, Travis Ferguson, Roberto Adachi, George A Eapen, David E Ost, Sami Bashour, Asad Khan, Vickie Shannon, Ajay Sheshadri, Roberto F Casal, Scott E Evans, Krystle Pew, Nadia Castaldo, Diwakar D Balachandran, Vincenzo Patruno, Robert Lentz, Cheryl Pai, Fabien Maldonado, Lance Roller, Junsheng Ma, Jhankruti Zaveri, Jenna Los, Luis Vaquero, Eva Ordonez, Gulmira Yermakhanova, Jason Akulian, Cole Burks, Roel-Rolando Almario, Marie Sauve, Jackson Pettee, Laila Z Noor, Muhammad H Arain, Horiana B Grosu

Faculty, Staff and Student Publications

Background: Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated.

Research question: Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis?

Study design and methods: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction …

Body Composition In Recurrent Prostate Cancer And The Role Of Steroidogenic Genotype, Neha Venkatesh, Rebecca S Tidwell, Yao Yu, Ana Aparicio, Amado J Zurita, Sumit K Subudhi, Bilal A Siddiqui, Sagar S Mukhida, Justin R Gregg, Paul G Corn, Efstratios Koutroumpakis, Jennifer L Mcquade, Daniel E Frigo, Patrick G Pilie, Chad Huff, Christopher J Logothetis, Andrew W Hahn

Faculty, Staff and Student Publications

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: i) CT imaging of L3 prior to and after treatment; and ii) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. …

Normal Breast Tissues Harbour Rare Populations Of Aneuploid Epithelial Cells, Yiyun Lin, Junke Wang, Kaile Wang, Shanshan Bai, Aatish Thennavan, Runmin Wei, Yun Yan, Jianzhuo Li, Heba Elgamal, Emi Sei, Anna Casasent, Mitchell Rao, Chenling Tang, Asha S Multani, Jin Ma, Jessica Montalvan, Chandandeep Nagi, Sebastian Winocour, Bora Lim, Alastair Thompson, Nicholas Navin

Faculty, Staff and Student Publications

Aneuploid epithelial cells are common in breast cancer

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Phase I Dose Escalation Study Of Io-108, An Anti-Lilrb2 Antibody, In Patients With Advanced Solid Tumors, Matthew H Taylor, Aung Naing, John Powderly, Paul Woodard, Luke Chung, Wen Hong Lin, Hongyu Tian, Nathan Siemers, Hong Xiang, Rong Deng, Kyu Hong, Donna Valencia, Tao Huang, Ying Zhu, X Charlene Liao, Xiao Min Schebye, Manish R Patel

Faculty, Staff and Student Publications

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1. Patients were treated with escalating doses of IO-108 every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. Safety and tolerability were the primary objectives. …

Outcomes Of Patients With Acute Myeloid Leukemia And Bone Marrow Fibrosis, Samuel Urrutia, Hagop M Kantarjian, Farhad Ravandi-Kashani, Carlos Bueso-Ramos, Rashmi Kanagal-Shamanna, Elias Jabbour, Guillermo Montalban-Bravo, Nicholas J Short, Naval Daver, Gautam Borthakur, Courtney D Dinardo, Tapan M Kadia, Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Guillermo Garcia-Manero, Koji Sasaki

Faculty, Staff and Student Publications

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics …

Long-Term Follow-Up Of Levonorgestrel Intrauterine Device For Atypical Hyperplasia And Early Endometrial Cancer Reveals Relapse Characterized By Immune Exhaustion, Mikayla B Bowen, Brenda Melendez, Qian Zhang, Richard K Yang, Bryan M Fellman, Barrett C Lawson, Naomi N Adjei, Joseph Celestino, Khalida M Wani, Bhavana Singh, Diana L Urbauer, Alexander J Lazar, Karen H Lu, Jennifer A Wargo, Shannon N Westin, Melinda S Yates

Faculty, Staff and Student Publications

Purpose: Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited.

Materials and methods: Follow-up data from patients in our prospective phase II trial of levonorgestrel intrauterine device (LIUD) for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse.

Results: Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen …

Association Of Clonal Hematopoiesis And Mosaic Chromosomal Alterations With Solid Malignancy Incidence And Mortality, Pinkal Desai, Ying Zhou, Justin Grenet, Samuel K Handelman, Cynthia M Crispino, Laura N Tarbay, Eric A Whitsel, Gail Roboz, Ana Barac, Michael Honigberg, Alexander Bick, Garnet Anderson, Jean Wactawski-Wende, Yasminka A Jakubek Swartzlander, Jason Bacon, Justin Wong, Xiaolong Ma, Paul Scheet, Zichan Li, Pashtoon Kasi, Ross Prentice, Paul Auer, Joann E Manson, Alexander Reiner, Michael Simon

Faculty, Staff and Student Publications

Background: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways.

Methods: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers.

Results: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or …

Personalized Composite Dosimetric Score-Based Machine Learning Model Of Severe Radiation-Induced Lymphopenia Among Patients With Esophageal Cancer, Yan Chu, Cong Zhu, Brian P Hobbs, Yiqing Chen, Peter S N Van Rossum, Clemens Grassberger, Degui Zhi, Steven H Lin, Radhe Mohan

Faculty, Staff and Student Publications

Purpose: Radiation-induced lymphopenia (RIL) is common among patients undergoing radiation therapy (RT)' Severe RIL has been linked to adverse outcomes. The severity and risk of RIL can be predicted from baseline clinical characteristics and dosimetric parameters. However, dosimetric parameters, e.g. dose-volume (DV) indices, are highly correlated with one another and are only weakly associated with RIL. Here we introduce the novel concept of "composite dosimetric score" (CDS) as the index that condenses the dose distribution in immune tissues of interest to study the dosimetric dependence of RIL. We derived an improved multivariate classification scheme for risk of grade 4 RIL …

The Il-1Β Inhibitor Canakinumab In Previously Treated Lower-Risk Myelodysplastic Syndromes: A Phase 2 Clinical Trial, Juan Jose Rodriguez-Sevilla, Vera Adema, Kelly S Chien, Sanam Loghavi, Feiyang Ma, Hui Yang, Guillermo Montalban-Bravo, Xuelin Huang, Xavier Calvo, Joby Joseph, Kristy Bodden, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells' (HSPCs') aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had …

Dna Methylation Classifier To Diagnose Pancreatic Ductal Adenocarcinoma Metastases From Different Anatomical Sites, Teodor G Calina, Eilís Perez, Elena Grafenhorst, Jamal Benhamida, Simon Schallenberg, Adrian Popescu, Ines Koch, Tobias Janik, Baoqing Chen, Jana Ihlow, Stephanie Roessler, Benjamin Goeppert, Bruno Sinn, Marcus Bahra, George A Calin, Eliane T Taube, Uwe Pelzer, Christopher C M Neumann, David Horst, Erik Knutsen, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.

Methods: For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the …