Life Sciences Commons^™

Il-2-Free Tumor-Infiltrating Lymphocyte Therapy With Pd-1 Blockade Demonstrates Potent Efficacy In Advanced Gynecologic Cancer, Jing Guo, Chunyan Wang, Ning Luo, Yuliang Wu, Wei Huang, Weihui Shi, Yao Ge, Chunhong Liu, Zhen Lu, Robert C Bast, Guihai Ai, Weihong Yang, Rui Wang, Caixia Li, Rong Chen, Shupeng Liu, Huajun Jin, Binghui Zhao, Zhongping Cheng

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer.

METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, …

Multiple Myeloma Patients With A Long Remission After Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Zhongya Wang, Denái R Milton, Mark R Tanner, Qaiser Bashir, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Guilin Tang, Partow Kebriaei, Yosra Aljawai, Hina N Khan, Hans C Lee, Christine Ye, Krina K Patel, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p < 0.001), more often had

The Long-Term Effects Of Blood Urea Nitrogen Levels On Cardiovascular Disease And All-Cause Mortality In Diabetes: A Prospective Cohort Study

Faculty, Staff and Student Publications

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes.

METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were …

Differences Between Acute Embolic And Atherosclerotic Middle Cerebral Artery Occlusion In Multiphase Arterial Spin-Labeling Imaging, Yasuhiro Ito, Taku Sugiyama, Shunsuke Terasaka, Hitoshi Matsuzawa, Kuniaki Harada, Masaki Ito, Miki Fujimura

Faculty, Staff and Student Publications

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) …

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …

Third-Party Fecal Microbiota Transplantation For High-Risk Treatment-Naïve Acute Gvhd Of The Lower Gi Tract, Zachariah Defilipp, Ashish V Damania, Haesook T Kim, Chia-Chi Chang, Areej El-Jawahri, Aj S Bottoms, Melissa M Smith, Maria Dolaher, Lindsey Perry, Meghan White, Brittany Diana, Sheila Connolly, Bimalangshu R Dey, Matthew J Frigault, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Michael K Mansour, Daniela Weber, Nadim J Ajami, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen

Faculty, Staff and Student Publications

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% …

Treatment Outcomes In Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid And/Or Rhabdoid Dedifferentiation After Progression On Immune Checkpoint Therapy, Andrew W Hahn, Devaki Shilpa Surasi, Paul V Viscuse, Tharakeswara K Bathala, Andrew J Wiele, Amado J Zurita, Eric Jonasch, Jianjun Gao, Sangeeta Goswami, Omar Alhalabi, Priya Rao, Kanishka Sircar, Nizar M Tannir, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated.

PATIENTS AND METHODS: Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for …

Evaluating The Heterogeneity Of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis Of Nrg Cc001, Hua-Ren R Cherng, Kai Sun, Søren Bentzen, Terri S Armstrong, Vinai Gondi, Minesh Mehta

Faculty, Staff and Student Publications

Background: Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.

Methods: An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup …

Response Of Treatment-Naive Brain Metastases To Stereotactic Radiosurgery, Chibawanye I Ene, Christina Abi Faraj, Thomas H Beckham, Jeffrey S Weinberg, Clark R Andersen, Ganesh Rao, Christopher A Alvarez-Brenkenridge, Betty Y S Kim, Amy B Heimberger, Ian E Mccutcheon, Sujit S Prabhu, Chenyang Michael Wang, Amol J Ghia, Susan L Mcgovern, Caroline Chung, Mary Frances Mcaleer, Martin C Tom, Subha Perni, Todd A Swanson, Debra N Yeboa, Tina M Briere, Jason T Huse, Gregory N Fuller, Frederick F Lang, Jing Li, Dima Suki, Raymond E Sawaya

Faculty, Staff and Student Publications

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) …

Using Genome And Transcriptome Data From African-Ancestry Female Participants To Identify Putative Breast Cancer Susceptibility Genes, Jie Ping, Guochong Jia, Qiuyin Cai, Xingyi Guo, Ran Tao, Dezheng Huo, Mollie E Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Esther M John, Christopher I Li, Katherine Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Michael F Press, Maureen Sanderson, Dale P Sandler, Toshio Yoshimatsu, Prisca O Adejumo, Thomas Ahearn, Abenaa M Brewster, Anselm J M Hennis, Timothy Makumbi, Paul Ndom, Katie M O'Brien, Andrew F Olshan, Mojisola M Oluwasanu, Sonya Reid, Song Yao, Ebonee N Butler, Maosheng Huang, Atara Ntekim, Bingshan Li, Melissa A Troester, Julie R Palmer, Christopher A Haiman, Jirong Long, Wei Zheng

Faculty, Staff and Student Publications

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum And Novel Clinical Observations In 241 Patients, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Enid S. Chelva, Sean Armstrong, Jose S. Pulido, Rebecca Procopio, Andrea L. Vincent, Lorenzo Bianco, Maurizio Battaglia Parodi, Lucia Ziccardi, Giulio Antonelli, Lucilla Barbano, João P. Marques, Sara Geada, Ana L. Carvalho, Wei C. Tang, Choi M. Chan, Camiel J. F. Boon, Jonathan Hensman, Ta-Ching Chen, Chien-Yu Lin, Pei-Lung Chen, Ajoy Vincent, Anupreet Tumber, Elise Heon, John R. Grigg, Robyn V. Jamieson, Elisa E. Cornish, Benjamin M. Nash, Shyamanga Borooah, Lauren N. Ayton, Alexis Ceecee Britten-Jones, Thomas L. Edwards, Jonathan B. Ruddle, Abhishek Sharma, Rowan G. Porter, Tina M. Lamey, Terri L. Mclaren, Samuel Mclenachan, Danial Roshandel, Fred K. Chen

Wills Eye Hospital Papers

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations.

RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, …

Key Variants Via The Alzheimer's Disease Sequencing Project Whole Genome Sequence Data, Nancy L Heard-Costa, Joshua C Bis, Elizabeth E Blue, Eric Boerwinkle, Philip L De Jager, Myriam Fornage, Ellen M Wijsman, Sudha Seshadri, Josée Dupuis, Gina M Peloso, Anita L Destefano

Faculty, Staff and Student Publications

INTRODUCTION: Genome-wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire genome and captures rare variations, may identify causal variants within GWAS loci.

METHODS: We performed single common variant association analysis and rare variant aggregate analyses in the pooled population (N cases = 2184, N controls = 2383) and targeted analyses in subpopulations using WGS data from the Alzheimer's Disease Sequencing Project (ADSP). The analyses were restricted to variants within 100 kb of 83 previously …

Montelukast As A Repurposable Additive Drug For Standard-Efficacy Multiple Sclerosis Treatment: Emulating Clinical Trials With Retrospective Administrative Health Claims Data

Faculty, Staff and Student Publications

BACKGROUND: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach.

OBJECTIVE: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS).

METHODS: In this retrospective case-control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18-65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics

RESULTS: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared …

Prevalence Of Distal Symmetrical Polyneuropathy By Diabetes Prevention Program Treatment Group, Diabetes Status, Duration Of Diabetes, And Cumulative Glycemic Exposure, Christine G Lee, Adam Ciarleglio, Sharon L Edelstein, Jill P Crandall, Dana Dabelea, Ronald B Goldberg, Steven E Kahn, William C Knowler, Maxwell T Ma, Neil H White, William H Herman, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

Research design and methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms …

Serial Cytoreductive Surgery And Survival Outcomes In Recurrent Adult-Type Ovarian Granulosa Cell Tumors, Jeffrey A How, Alejandra Flores Legarreta, Katelyn F Handley, Bryan Fellman, Katherine I Foster, Veena K Vuttaradhi, Barrett Lawson, Michael Frumovitz, Shannon N Westin, Lois M Ramondetta, David M Gershenson, Anil K Sood, R Tyler Hillman

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions.

OBJECTIVE: This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary.

STUDY …

A Randomized Trial Of Two Remote Health Care Delivery Models On The Uptake Of Genetic Testing And Impact On Patient-Reported Psychological Outcomes In Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, And Testing (Generate) Study, Nicolette J Rodriguez, C Sloane Furniss, Matthew B Yurgelun, Chinedu Ukaegbu, Pamela E Constantinou, Alyson Caruso, Jill E Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott H Nelson, Sydney Okumura, Alicia Y Zhou, Tara B Coffin, Hajime Uno, Miki Horiguchi, Allyson J Ocean, Florencia Mcallister, Andrew M Lowy, Alison P Klein, Lisa Madlensky, Gloria M Petersen, Judy E Garber, Scott M Lippman, Michael G Goggins, Anirban Maitra, Sapna Syngal

Faculty, Staff and Student Publications

Background & aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes.

Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session …

Revisiting Feeding Tube Utilization In Oropharynx Cancer: 6-Year Prospective Registry Analysis, Brady J Anderson, Amy C Moreno, Yun Qing, J Jack Lee, Faye M Johnson, Carly E A Barbon, Ariana Sahli, Vicki Piper, Neil Gross, Clifton D Fuller, Stephen Y Lai, Jeffrey N Myers, Katherine A Hutcheson

Faculty, Staff and Student Publications

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients.

STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021.

SETTING: Single-institution NCI-Designated Comprehensive Cancer Center.

METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during …

Benefit Of Axicabtagene Ciloleucel Versus Chemoimmunotherapy In Older Patients And/Or Patients With Poor Ecog Performance Status With Relapsed Or Refractory Large B-Cell Lymphoma After 2 Or More Lines Of Prior Therapy, Matthew A Lunning, Hai-Lin Wang, Zhen-Huan Hu, Frederick L Locke, Tanya Siddiqi, Sairah Ahmed, Yi Lin, Brian T Hill, Armin Ghobadi, Sattva S Neelapu, Jason Westin, Chrisopher Dieyi, Polly Field, Harry Miao, Shilpa A Shahani, Anik Patel, Clare Spooner, Christine Fu, David Muramoto, Hairong Xu, Marcelo C Pasquini

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients …

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Omar Y Mian, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

Effect Of Delayed Cell Infusion In Patients With Large B-Cell Lymphoma Treated With Chimeric Antigen Receptor T-Cell Therapy, Andrew P Jallouk, Naishu Kui, Ryan Sun, Jason R Westin, Raphael E Steiner, Loretta J Nastoupil, Ajlan Al Zaki, Misha Hawkins, Sherry Adkins, Mansoor Noorani, Kaberi Das, Jared Henderson, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Christopher R Flowers, Sattva S Neelapu, Sairah Ahmed, Paolo Strati

Faculty, Staff and Student Publications

Complications occurring after lymphodepleting chemotherapy (LDC) may delay chimeric antigen receptor (CAR) T-cell infusion. The effect of these delays on clinical outcomes is unclear. We performed a retrospective analysis of 240 patients with relapsed/refractory large B-cell lymphoma treated with standard-of-care axicabtagene ciloleucel (axi-cel) and identified 40 patients (16.7%) who had delay in axi-cel infusion. Of these, 85% had delay due to infection. At time of LDC initiation, patients with delayed infusion had lower absolute neutrophil count (P=0.006), lower platelets (P=0.004), lower hemoglobin (P5 days (4.6 vs. 8.2 months; P=0.036), but not 1 day (5.7 vs. 8.2 months; P=0.238). Following propensity …

Mechanical Venous Thrombectomy For Deep Venous Thrombosis In Cancer Patients: A Single-Center Retrospective Study, Riya M Patel, Koustav Pal, Syed Hadi Ahmed, Joshua D Kuban, Milan Patel, Peiman Habibollahi, Varshana Gurusamy, Sanjay Gupta, Cristhiam M Rojas-Hernandez, Vahid Afshar-Kharghan, Michael H Kroll, Rahul A Sheth

Faculty, Staff and Student Publications

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients.

METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival …

Automated, High-Throughput Platform To Generate A High-Reliability, Comprehensive Rectal Cancer Database, Neal Bhutiani, Mahmoud M G Yousef, Abdelrahman Yousef, Mohammad Zeineddine, Mark Knafl, Uditha P Fernando, Fadl A Zeineddine, Jeff Jin, Kristin Alfaro-Munoz, Drew Goldstein, George J Chang, Scott Kopetz, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Purpose: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution.

Methods: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and …

Survival Disparities In Non-Hispanic Black And White Cervical Cancer Patients Vary By Histology And Are Largely Explained By Modifiable Factors, Calen W Kucera, Nicole P Chappell, Chunqiao Tian, Michael T Richardson, Christopher M Tarney, John K Chan, Charles A Leath, Yovanni Casablanca, Christine Rojas, Collin A Sitler, Lari Wenzel, Ann Klopp, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Timothy D O'Connor, Craig D Shriver, Nicholas W Bateman, Thomas P Conrads, Neil T Phippen, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

Purpose: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.

Methods: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma …

Artificial Intelligence-Powered Assessment Of Pathologic Response To Neoadjuvant Atezolizumab In Patients With Nsclc: Results From The Lcmc3 Study, Sanja Dacic, William D Travis, Jennifer M Giltnane, Filip Kos, John Abel, Junya Fujimoto, Jon Ritter, Farah Khalil, Yi Liu, Amaro Taylor-Weiner, Murray Resnick, Hui Yu, Fred R Hirsch, Paul A Bunn, David P Carbone, Valerie Rusch, David J Kwiatkowski, Bruce E Johnson, Jay M Lee, Stephanie R Hennek, Ilan Wapinski, Alan Nicholas, Ann Johnson, Katja Schulze, Mark G Kris, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate.

Methods: We determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = …

Somatic Gene Mutation Patterns And Burden Influence Outcomes With Enasidenib In Relapsed/Refractory Idh2-Mutated Aml, Alberto Risueño, Wendy L See, Iryna Bluemmert, Stéphane De Botton, Courtney D Dinardo, Andre C Schuh, Paresh Vyas, Thomas Prebet, Anita Gandhi, Maroof Hasan

Faculty, Staff and Student Publications

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this …

Safety And Tolerability Of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy, Jasmijn M Westerhoff, Lois A Daamen, John P Christodouleas, Erwin L A Blezer, Ananya Choudhury, Beth A Erickson, Shaista Hafeez, Uulke A Van Der Heide, Martijn P W Intven, Anna M Kirby, Susan Lalondrelle, Bruce D Minsky, Stella Mook, Marlies E Nowee, Corrie A M Marijnen, Kristina M Orrling, Arjun Sahgal, Christopher J Schultz, Corinne Faivre-Finn, Robbert J H A Tersteeg, Alison C Tree, Chia-Lin Tseng, Tine Schytte, Dustin M Silk, Dave Eggert, Marco Luzzara, Jochem R N Van Der Voort Van Zyp, Helena M Verkooijen, William A Hall

Faculty, Staff and Student Publications

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy.

Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach).

Design, setting, and participants: This cohort study included adults with solid tumors treated with a …

Kras Allelic Variants In Biliary Tract Cancers, Gordon Taylor Moffat, Zishuo Ian Hu, Funda Meric-Bernstam, Elisabeth Kathleen Kong, Dean Pavlick, Karthikeyan Murugesan, Anaemy Danner De Armas, Anil Korkut, Milind Javle, Jennifer J Knox

Faculty, Staff and Student Publications

IMPORTANCE: Biliary tract cancers (BTCs) contain several actionable molecular alterations, including FGFR2, IDH1, ERBB2 (formerly HER2), and KRAS. KRAS allelic variants are found in 20% to 30% of BTCs, and multiple KRAS inhibitors are currently under clinical investigation.

OBJECTIVES: To describe the genomic landscape, co-sequence variations, immunophenotype, genomic ancestry, and survival outcomes of KRAS-mutated BTCs and to calculate the median overall survival (mOS) for the most common allelic variants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, multicenter, pooled cohort study obtained clinical and next-generation sequencing data from multiple databases between January 1, 2017, and December 31, 2022. These databases included Princess …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Impact Of Revised International Staging System 2 Risk Stratification On Outcomes Of Patients With Multiple Myeloma Receiving Autologous Haematopoietic Stem Cell Transplantation, Kamal Alzahrani, Oren Pasvolsky, Zhongya Wang, Denái R Milton, Mark R Tanner, Samer Srour, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Elisabet E Manasanch, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The second revision of the International Staging System (R2-ISS) is a simple tool to risk-stratify newly diagnosed multiple myeloma (NDMM) patients. Here, we completed a retrospective analysis to evaluate the utility of R2-ISS in NDMM patients who underwent up-front autologous haematopoietic stem cell transplantation (auto-HCT). A total of 1291 patients were included, with a median age of 62 years (range 29-83). The distribution of R2-ISS stages was: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III and 131 (10%) stage IV. With a median follow-up of 42.2 months (range 0.3-181.0), the median PFS was 73.0, 65.2, 44.0 …

Neoadjuvant Chemoimmunotherapy For Nsclc: A Systematic Review And Meta-Analysis, Mark Sorin, Connor Prosty, Louis Ghaleb, Kathy Nie, Khaled Katergi, Laurie-Rose Dubé, Anikka Swaby, Matthew Dankner, Trafford Crump, Logan A Walsh, Pierre O Fiset, Boris Sepesi, Patrick M Forde, Tina Cascone, Mariano Provencio, Jonathan D Spicer

Faculty, Staff and Student Publications

IMPORTANCE: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

OBJECTIVE: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

DATA SOURCES: MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of …