Genetic Phenomena Commons^™

Neoadjuvant Parpi Or Chemotherapy In Ovarian Cancer Informs Targeting Effector Treg Cells For Homologous-Recombination-Deficient Tumors, Yikai Luo, Yu Xia, Dan Liu, Xiong Li, Huayi Li, Jiahao Liu, Dongchen Zhou, Yu Dong, Xin Li, Yiyu Qian, Cheng Xu, Kangjia Tao, Guannan Li, Wen Pan, Qing Zhong, Xingzhe Liu, Sen Xu, Zhi Wang, Ronghua Liu, Wei Zhang, Wanying Shan, Tian Fang, Siyuan Wang, Zikun Peng, Ping Jin, Ning Jin, Shennan Shi, Yuxin Chen, Mengjie Wang, Xiaofei Jiao, Mengshi Luo, Wenjian Gong, Ya Wang, Yue Yao, Yi Zhao, Xinlin Huang, Xuwo Ji, Zhaoren He, Guangnian Zhao, Rong Liu, Mingfu Wu, Gang Chen, Li Hong, Cocpo Consortium, Ding Ma, Yong Fang, Han Liang, Qinglei Gao

Faculty, Staff and Student Publications

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD …

Tomivosertib Reduces Ectopic Activity In Dorsal Root Ganglion Neurons From Patients With Radiculopathy, Yan Li, Megan L Uhelski, Robert Y North, Juliet M Mwirigi, Claudio E Tatsui, Kathleen E Mcdonough, Juan P Cata, German Corrales, Greg Dussor, Theodore J Price, Patrick M Dougherty

Faculty, Staff and Student Publications

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors.

Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. …

Glycemic Control In Diabetic Patients Improved Overall Lung Cancer Survival Across Diverse Populations, Wayne Y Wu, Brian Luke, Xiao-Cheng Wu, J Jack Lee, Yong Yi, Samuel C Okpechi, Barry Gause, Paras Mehta, Steven I Sherman, Augusto Ochoa, Ethan Dmitrovsky, Xi Liu

Faculty, Staff and Student Publications

Background: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used 2 large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity.

Methods: The University of Texas MD Anderson Cancer Center database (32 643 lung cancer patients with 11 973 patients with diabetes) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features (age, sex, race, body mass index [BMI], insurance status, smoking, stage, and histopathology). Hemoglobin A1C (HgbA1c) and glucose levels assessed …

Dominant Missense Variants In Srebf2 Are Associated With Complex Dermatological, Neurological, And Skeletal Abnormalities, Matthew J Moulton, Kristhen Atala, Yiming Zheng, Debdeep Dutta, Dorothy K Grange, Wen-Wen Lin, Daniel J Wegner, Jennifer A Wambach, Angela L Duker, Michael B Bober, Lisa Kratz, Carol A Wise, Ila Oxendine, Anas Khanshour, Undiagnosed Diseases Network, Michael F Wangler, Shinya Yamamoto, F Sessions Cole, Jonathan Rios, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.

Methods: We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences …

Arcuate Dopaminergic/Gabaergic Neurons Project Within The Hypothalamus And To The Median Eminence, Somya Mittal, Benjamin R Arenkiel, Ariel M Lyons-Warren

Duncan NRI Faculty and Staff Publications

Cotransmission, meaning the release of multiple neurotransmitters from one synapse, allows for increased diversity of signaling in the brain. Dopamine (DA) and γ-aminobutyric acid (GABA) are known to coexpress in many regions such as the olfactory bulb and the ventral tegmental area. Tuberoinfundibular dopaminergic neurons (TIDA) in the arcuate nucleus of the hypothalamus (Arc) project to the median eminence (ME) and regulate prolactin release from the pituitary, and prior work suggests dopaminergic Arc neurons also cotransmit GABA. However, the extent of cotransmission, and the projection patterns of these neurons have not been fully revealed. Here, we used a genetic intersectional …

Long-Term Results Of The Sequential Combination Of Cladribine And Rituximab In Hairy Cell Leukemia, Jennifer Marvin-Peek, Wei-Ying Jen, Hagop M Kantarjian, David Mccue, Fadi G Haddad, William Wierda, Alessandra Ferrajoli, Jan Burger, Tareq Abusab, Jeffrey Jorgensen, Sa A Wang, Keyur Patel, Sanam Loghavi, Susan O'Brien, Farhad Ravandi

Faculty, Staff and Student Publications

We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event free survival (EFS) or overall survival (OS). With a median follow up of 7·8 years (range: 0·40–18·8), eight patients have experienced disease relapse (5·8%), …

Radiation Therapy Quality Assurance Analysis Of Alliance A021501: Preoperative Mfolfirinox Or Mfolfirinox Plus Hypofractionated Radiation Therapy For Borderline Resectable Adenocarcinoma Of The Pancreas, Leila T Tchelebi, Diana Segovia, Koren Smith, Qian Shi, T J Fitzgerald, Michael D Chuong, Tyler J Zemla, Eileen M O'Reilly, Jeffrey A Meyerhardt, Eugene J Koay, Jessica Lowenstein, Ardaman Shergill, Matthew H G Katz, Joseph M Herman

Faculty, Staff and Student Publications

Purpose: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered.

Methods and materials: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable …

Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann

Faculty, Staff and Student Publications

Combination approaches are needed to strengthen and extend the clinical response to KRASG12C inhibitors (KRASG12Ci). Here, we assessed the antitumor responses of KRASG12C mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRASG12C inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling. BI-3406 plus adagrasib treatment also delayed the emergence of acquired resistance and elicited antitumor responses from adagrasib-resistant models. Resistance to KRASG12Ci seemed to be driven by …

The Multi-Institutional Medullary Thyroid Cancer Collaborative Registry: Can A Rare Tumor Registry Accurately Represent The Real-World Patient Population?, Thomas Szabo Yamashita, Sophia M Williams-Perez, Sara Ehsan, Michelle Mulder, Daniel Kronenfeld, Chiang-Yu Huang, Hui Zhao, Kelly Merriman, Susan K Peterson, Mimi I Hu, Mark Zafereo, Julie Ann Sosa, Elizabeth G Grubbs

Faculty, Staff and Student Publications

Background: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries.

Methods: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer …

Racialized Inequities In Live Birth After Cancer: A Population-Based Study Of 63,000 Female Adolescents And Young Adults With Cancer, Andrea C Betts, Michael E Roth, Karen Albritton, Sandi L Pruitt, Philip J Lupo, Jennifer S Wang, L Aubree Shay, Marlyn A Allicock, Caitlin C Murphy

Faculty, Staff and Student Publications

Introduction: Fertility after cancer is a top concern for adolescents and young adults with cancer (AYAs) (15-39 years old at diagnosis). The authors characterized live births after cancer by race and ethnicity ("race/ethnicity") in a population-based sample of female AYAs.

Methods: This study used Texas Cancer Registry data linked to birth certificates (1995-2016) to estimate cumulative incidence of live birth, based on first live birth after cancer, and compared differences by race/ethnicity. Proportional subdistribution hazards models were used to estimate associations between race/ethnicity and live birth, adjusted for diagnosis age, cancer type, stage, year, and prior live birth, overall and …

Resin-Based 90 Y Tumor Dose As A Predictor Of Duration Of Response And Survival In Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study, Nima Kokabi, Linzi A Webster, Howard Dabbous, Anand Shah, David Brandon, James Galt, Minzhi Xing, Alexander Villalobos, Amir Davarpanahfakhr, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

Background: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization.

Patients and methods: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition …

Vascular Heterogeneity Of Tight Junction Claudins Guides Organotropic Metastasis, Xunian Zhou, Valerie S Lebleu, Eliot Fletcher-Sananikone, Jiha Kim, Jianli Dai, Bingrui Li, Chia-Chin Wu, Hikaru Sugimoto, Toru Miyake, Lisa M Becker, Olga V Volpert, Erica Lawson, Cristina Espinosa Da Silva, Sarah I Patel, Akane Kizu, Ehsan A Ehsanipour, Di Sha, Jose Antonio Karam, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Carcinomas are associated with metastasis to specific organs while sparing others. Breast cancer presents with lung metastasis but rarely kidney metastasis. Using this difference as an example, we queried the mechanism(s) behind the proclivity for organ-specific metastasis. We used spontaneous and implant models of metastatic mammary carcinoma coupled with inflammatory tissue fibrosis, single-cell sequencing analyses and functional studies to unravel the causal determinants of organ-specific metastasis. Here we show that lung metastasis is facilitated by angiopoietin 2 (Ang2)-mediated suppression of lung-specific endothelial tight junction protein Claudin 5, which is augmented by the inflammatory fibrotic microenvironment and prevented by anti-Ang2 blocking …

Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Nab-Paclitaxel In Patients With Advanced Solid Tumors, Christopher T Chen, Vishesh Khanna, Shivaani Kummar, Raghad M Abdul-Karim, David Sommerhalder, Anthony W Tolcher, Naoto T Ueno, Sarah Lindsey Davis, Douglas W Orr, Erika Hamilton, Manish R Patel, Alexander I Spira, Shekeab Jauhari, Vaia Florou, Maureen Duff, Rongda Xu, Jian Wang, Shravani R Barkund, Haiying Zhou, Aleksandr Pankov, Wayne Kong, Nadine S Jahchan, Erica L Jackson, Jessica D Sun, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Pamela N Munster

Faculty, Staff and Student Publications

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients and methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Results: ORIC-101 reversed …

Improving The Palliative-Procedure Decision-Making Process For Patients With Peritoneal Carcinomatosis: A Secondary Analysis, Jaclyn A Wall, Rachel A Pozzar, Andrea C Enzinger, Anna Tavormina, Catherine Howard, Ursula A Matulonis, Joyce F Liu, Neil Horowitz, Larissa A Meyer, Alexi A Wright

Faculty, Staff and Student Publications

Background: Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or procedures to manage disease-related complications and side effects. However, there are limited data regarding patients' and family caregivers' decision-making processes about these procedures. Thus, we sought to describe the decision-making experiences of patients with PC who elect to pursue palliative surgical procedures and their family caregivers.

Methods: We conducted a secondary analysis of qualitative data collected during a pilot randomized controlled trial of BOLSTER, a nurse-led telehealth intervention for patients with PC and their caregivers after an acute …

Image-Guided Patient-Specific Optimization Of Catheter Placement For Convection-Enhanced Nanoparticle Delivery In Recurrent Glioblastoma, Chengyue Wu, David A Hormuth, Chase D Christenson, Ryan T Woodall, Michael R A Abdelmalik, William T Phillips, Thomas J R Hughes, Andrew J Brenner, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (186Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM).

Methods: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient …

Response-Adapted Ultralow-Dose Radiation Therapy For Orbital Indolent B-Cell Lymphoma: A Phase 2 Nonrandomized Controlled Trial, Chelsea C Pinnix, Bouthaina S Dabaja, Jillian R Gunther, Penny Q Fang, Susan Y Wu, Loretta J Nastoupil, Paolo Strati, Ranjit Nair, Sairah Ahmed, Raphael Steiner, Jason Westin, Sattva Neelapu, Maria A Rodriguez, Hun Ju Lee, Michael Wang, Christopher Flowers, Lei Feng, Bita Esmaeli

Faculty, Staff and Student Publications

Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common.

Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity.

Design, setting, and participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between …

Psychological Distress And Mental Health Care Utilization Among Black Survivors Of Adolescent And Young Adult Cancer, Eunju Choi, Amy M Berkman, Aryce Battle, Andrea C Betts, John M Salsman, Joel Milam, Clark R Andersen, Kimberly A Miller, Susan K Peterson, Qian Lu, Christabel K Cheung, J A Livingston, Michelle A T Hildebrandt, Susan K Parsons, David R Freyer, Michael E Roth

Faculty, Staff and Student Publications

Background: Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population.

Methods: National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ2 tests. Logistic regression models, adjusted for survey weights, were used to evaluate …

Mitochondrial Complex I Promotes Kidney Cancer Metastasis, Divya Bezwada, Luigi Perelli, Nicholas P Lesner, Ling Cai, Bailey Brooks, Zheng Wu, Hieu S Vu, Varun Sondhi, Daniel L Cassidy, Stacy Kasitinon, Sherwin Kelekar, Feng Cai, Arin B Aurora, Mckenzie Patrick, Ashley Leach, Rashed Ghandour, Yuanyuan Zhang, Duyen Do, Phyllis Mcdaniel, Jessica Sudderth, Dennis Dumesnil, Sara House, Tracy Rosales, Alan M Poole, Yair Lotan, Solomon Woldu, Aditya Bagrodia, Xiaosong Meng, Jeffrey A Cadeddu, Prashant Mishra, Javier Garcia-Bermudez, Ivan Pedrosa, Payal Kapur, Kevin D Courtney, Craig R Malloy, Giannicola Genovese, Vitaly Margulis, Ralph J Deberardinis

Faculty, Staff and Student Publications

Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human …

Clinical Outcomes And Healthcare Resource Utilization For Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents, Guillermo Garcia-Manero, Rayna K Matsuno, Ali Mcbride, Hina Mohammed, Danny Idryo, Ronda Broome, Autumn Herriman, Tiffany Johnson, Kristiana Wilkinson, Andrew Schrag, Colden Johanson, Monika Izano, Adeola Makinde, Sudipto Mukherjee

Faculty, Staff and Student Publications

Introduction: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States.

Patients and methods: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary …

Overcoming Egfr-Tki Resistance By Targeting The Tumor Microenvironment, Jinsong Zhang, Natalie Vokes, Man Li, Jiachen Xu, Hua Bai, Jie Wang, Zhijie Wang, Jianjun Zhang

Faculty, Staff and Student Publications

Targeted therapy has ushered in a new era of precision medicine for non-small cell lung cancer (NSCLC). Currently, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) stand as the recommended first-line therapy for advanced NSCLC harboring sensitive EGFR mutations. Nevertheless, most patients inevitably confront the challenge of drug resistance. This phenomenon arises not solely from intrinsic alterations within cancer cells but also from the intricate dynamics of the tumor microenvironment and the complex interactions that occur between cancer cells and their immediate surroundings. This review consolidates the current knowledge regarding EGFR-TKI resistance mechanisms, with a specific emphasis on unraveling the …

Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann

Faculty, Staff and Student Publications

Combination approaches are needed to strengthen and extend the clinical response to KRAS

Eosinophilia During Lenalidomide Therapy In Myelodysplastic Syndrome, Koji Sasaki, Hagop Kantarjian, Guillermo Montalban-Bravo, Danielle Hammond, Elias Jabbour, Rashmi Kanagal-Shamanna, Kelly Chien, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Background: Lenalidomide is an immunomodulatory therapy used to treat multiple hematologic malignancies. The incidence of eosinophilia and hypereosinophilia during lenalidomide therapy, and the requirement for high-dose steroids are not well-defined PATIENTS AND METHODS: We retrospectively reviewed 44 patients with myelodysplastic syndromes who were treated with lenalidomide therapy from August 2006 and March 2023.

Results: Eosinophilia (0.5-1.5 × 109/L) and hypereosinophilia (>1.5 × 109/L) were observed in 6 patients (14%) and 4 patients (9%), respectively. The median duration of lenalidomide therapy was 6.5 months. Backward multivariate ordinary logistic regression identified higher absolute eosinophil count (OR, 4759.986; 95% CI, 11.223-2018772.073; P …

Ixazomib Plus Daratumumab And Dexamethasone: Final Analysis Of A Phase 2 Study Among Patients With Relapsed/Refractory Multiple Myeloma, Sosana Delimpasi, Meletios A Dimopoulos, Jan Straub, Argiris Symeonidis, Luděk Pour, Roman Hájek, Cyrille Touzeau, Viralkumar K Bhanderi, Jesus G Berdeja, Petr Pavlíček, Jeffrey V Matous, Pawel J Robak, Kaveri Suryanarayan, Alison Miller, Miguel Villarreal, Dasha Cherepanov, Jaydeep K Srimani, Huilan Yao, Richard Labotka, Robert Z Orlowski

Faculty, Staff and Student Publications

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity. Median age was 69 years; 14.8% of patients had International Staging System stage III disease; 14.8% had received three prior therapies. Patients received a median of 16 cycles of IDd. In 59 response-evaluable …

Quantitative Evaluation Of 90y-Pet/Ct And 90y-Spect/Ct-Based Dosimetry Following Yttrium-90 Radioembolization, Srinivas Cheenu Kappadath, Eric Courtney Henry, Benjamin P Lopez, Armeen Mahvash

Faculty, Staff and Student Publications

Background: Following yttrium-90 radioembolization (90Y-RE), 90Y-PET/CT and 90Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for 90Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between 90Y-PET/CT and 90Y-SPECT/CT.

Purpose: To quantitatively analyze and compare 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following 90Y-RE.

Methods: 90Y-PET/CT and 90Y-SPECT/CT imaging was acquired for 35 patients following 90Y-RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with …

Feasibility And Acceptability Of A Nurse-Led Telehealth Intervention (Bolster) To Support Patients With Peritoneal Carcinomatosis And Their Caregivers: A Pilot Randomized Clinical Trial, Rachel A Pozzar, Andrea C Enzinger, Catherine Howard, Anna Tavormina, Ursula A Matulonis, Susana Campos, Joyce F Liu, Neil Horowitz, Panagiotis A Konstantinopoulos, Carolyn Krasner, Jaclyn A Wall, Kate Sciacca, Larissa A Meyer, Charlotta Lindvall, Alexi A Wright

Faculty, Staff and Student Publications

Objective: Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP).

Methods: Pilot feasibility RCT. Recently hospitalized adults with advanced …

Errors In Genome Sequencing Result Disclosures: A Randomized Controlled Trial Comparing Neonatology Non-Genetics Healthcare Professionals And Genetic Counselors, Tanner F Coleman, Jada Pugh, Whitley V Kelley, Kelly M East, Veronica Greve, Candice R Finnila, Ava Henson, Bruce R Korf, Gregory S Barsh, Gregory M Cooper, Meagan E Cochran

Faculty, Staff and Student Publications

Purpose: We compared the rate of errors in genome sequencing (GS) result disclosures by genetic counselors (GC) and trained non-genetics healthcare professionals (NGHPs) in SouthSeq, a randomized trial utilizing GS in critically ill infants.

Methods: Over 400 recorded GS result disclosures were analyzed for major and minor errors. We used Fisher's exact test to compare error rates between GCs and NGHPs and performed a qualitative content analysis to characterize error themes.

Results: Major errors were identified in 7.5% of disclosures by NGHPs and in no disclosures by GCs. Minor errors were identified in 32.1% of disclosures by NGHPs and in …

A Comparison Of Methods For In Vivo Activity And Absorbed Dose Quantification With Pet/Ct Following Yttrium-90 Radioembolization, Eric Courtney Henry, Armeen Mahvash, Benjamin P Lopez, Srinivas Cheenu Kappadath

Faculty, Staff and Student Publications

Background: Yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y-radioembolization (90Y-RE). Yet, the accuracy of in vivo 90Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and 90Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood.

Purpose: The purpose of this study was to investigate the accuracy of 90Y-PET/CT-based activity estimates following 90Y-RE and characterize differences between 90Y-PET/CT-based voxel dosimetry algorithms.

Methods: Thirty-five patients underwent 90Y-PET/CT imaging after 90Y-RE with TheraSphere. The net administered 90Y activity (Aadmin) was …

Comparing The Diagnostic Yield Of Germline Exome Versus Panel Sequencing In The Diverse Population Of The Texas Kidscanseq Pediatric Cancer Study, Lauren R Desrosiers-Battu, Tao Wang, Jacquelyn Reuther, George Miles, Hongzheng Dai, Eunji Jo, Heidi Russell, Robin Raesz-Martinez, Alva Recinos, Stephanie Gutierrez, Amy Thomas, Emily Berenson, Jessica Corredor, Kimberly Nugent, Rachel Wyatt Castillo, Rebecca Althaus, Rebecca Littlejohn, Shawn Gessay, Gail Tomlinson, Jonathan Gill, Juan Carlos Bernini, Kelly Vallance, Timothy Griffin, Sarah Scollon, Frank Y Lin, Christine Eng, Shashikant Kulkarni, Susan G Hilsenbeck, Angshumoy Roy, Amy L Mcguire, D Williams Parsons, Sharon E Plon

Faculty, Staff and Student Publications

Purpose: To evaluate the relative diagnostic yield of clinical germline genomic tests in a diverse pediatric cancer population.

Patients and methods: The KidsCanSeq study enrolled pediatric cancer patients across six sites in Texas. Germline analysis included both exome sequencing and a therapy-focused pediatric cancer gene panel. The results were categorized by participants demographics, the presence of pathogenic or likely pathogenic (P/LP) variants, and variants of uncertain significance (VUS) in cancer predisposition genes (CPGs). Pediatric actionable CPGs were defined as those with cancer surveillance recommendations during childhood.

Results: Cancer P/LP variants were reported by at least one platform in 103 of …

Phase Ii Study Of Samotolisib In Children And Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target Of Rapamycin Pathway Alterations: Pediatric Match Apec1621d, Theodore W Laetsch, Kathleen Ludwig, P Mickey Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Joyce Mhlanga, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald Williams Parsons

Faculty, Staff and Students Publications

Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib.

Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was …

Satisfaction With Mode Of Delivery Of Genomic Sequencing Results In A Diverse National Sample Of Research Participants Through The Clinical Sequencing Evidence-Generating Research Consortium, Sarah Scollon, Jill O Robinson, Eunji Jo, Sabrina A Suckiel, Laura M Amendola, Ann Katherine M Foreman, Gail P Jarvik, Christine Rini, Tao Wang, Anne Slavotinek

Faculty, Staff and Students Publications

Purpose: Research that includes diverse patient populations is necessary to optimize implementation of telehealth.

Methods: As part of a Clinical Sequencing Evidence-Generating Research Consortium cross-site study, we assessed satisfaction with mode of return of results (RoR) delivery across a diverse sample of participants receiving genetic testing results in person vs telemedicine (TM).

Results: Ninety-eight percent of participants were satisfied with their mode of results delivery. Participants receiving results by TM were more likely to report a preference for receiving results in a different way and challenges with providers noticing difficulties with understanding. More than 90% reported satisfaction across all items …