Medical Specialties Commons^™

Summary Of Research: Efficacy Of Trastuzumab Deruxtecan In Her2-Expressing Solid Tumors By Enrollment Her2 Ihc Status: Post Hoc Analysis Of Destiny-Pantumor02, Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam

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of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects …

What Rankings, Ratings, And Utilities Do Breast Cancer Patients Place On Tissue- And Implant-Based Breast Reconstruction?, Haoqi Wang, Nsikak M Jackson, Danmeng Huang, Rachel E Alexander, Mary Catherine Bordes, Jun Liu, Tzuan A Chen, Fatima Merchant, Summer E Hanson, Mark Schaverien, Mia K Markey, Gregory P Reece, Scott B Cantor, Aubri S Hoffman

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Background: Utility analysis is well-established for comparing treatment options but challenging to assess with patients in clinical care. Preference assessment may be more feasible, but it is not yet known whether it correlates with utilities. The aims of this study were to (1) assess women's rankings, ratings, and utilities for tissue-based, implant-based, and no reconstruction after total mastectomy; and (2) explore assessment methods and correlations with clinical and psychosocial factors.

Methods: Forty patients considering or undergoing breast reconstruction completed 3 assessments-card ranking, visual analog scale, and standard gamble-and psychosocial questionnaires. Each woman rated 9 health states with case-matched images: 4 …

A Biomarker Signature-Guided Clinical Trial Design For Precision Medicine, Yuan Li, Dejian Lai, Ruosha Li, Han Chen, Xuelin Huang, Jing Ning

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Targeted cancer therapies aim to effectively treat patients with specific biomarker profiles. Nevertheless, these therapies may not always precisely hit their intended targets, leading to uncertainty about the specific subset of patients who will benefit. To address this uncertainty, the identification of sensitive patient subsets in clinical trials becomes crucial. Our proposed phase IIB/III clinical trial design seeks to pinpoint a biomarker signature with precision, ensuring the accurate identification of patients who will respond to a specific treatment. This approach allows for the selective enrollment of sensitive patients to maximize benefits for trial participants. We incorporate Bayesian methodology to facilitate …

A Phase 2 Study Of Decitabine With Or Without Carboplatin And Arsenic Trioxide In Patients With Mds And Aml, Patricia L Kropf, Woonbok Chung, Raji Shameem, Lianchun Xiao, Curt Balch, Xuelin Huang, Jean-Pierre J Issa

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Although decitabine (DAC) shows activity against myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), patient responses are limited, and prognoses remain poor. Preclinical studies have indicated that arsenic trioxide (ATO) and carboplatin (Carbo) enhance DAC's epigenetic gene derepression. Consequently, we initiated a randomized phase 2 clinical trial evaluating DAC alone, or with Carbo or ATO, in patients with MDS/AML. Thirty patients were initially randomized to receive DAC alone (20 mg/m2, days 1-5), DAC plus Carbo (AUC 5, day 8), or DAC plus ATO (0.15 mg/kg, days 1-5), followed by adaptive randomization of 61 patients, based on response rates, for at …

The Multilayered Transcriptional Architecture Of Glioblastoma Ecosystems, Masashi Nomura, Avishay Spitzer, Kevin C Johnson, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhfury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Roel G W Verhaak, Antonio Iavarone, Mario L Suvà, Itay Tirosh

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In isocitrate dehydrogenase wildtype glioblastoma (GBM), cellular heterogeneity across and within tumors may drive therapeutic resistance. Here we analyzed 121 primary and recurrent GBM samples from 59 patients using single-nucleus RNA sequencing and bulk tumor DNA sequencing to characterize GBM transcriptional heterogeneity. First, GBMs can be classified by their broad cellular composition, encompassing malignant and nonmalignant cell types. Second, in each cell type we describe the diversity of cellular states and their pathway activation, particularly an expanded set of malignant cell states, including glial progenitor cell-like, neuronal-like and cilia-like. Third, the remaining variation between GBMs highlights three baseline gene expression …

Deciphering The Longitudinal Trajectories Of Glioblastoma Ecosystems By Integrative Single-Cell Genomics, Avishay Spitzer, Kevin C Johnson, Masashi Nomura, Luciano Garofano, Djamel Nehar-Belaid, Noam Galili Darnell, Alissa C Greenwald, Lillian Bussema, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Antonio Iavarone, Roel G W Verhaak, Itay Tirosh, Mario L Suvà

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The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there …

Prospective Clinical Trials Of Venetoclax And Hypomethylating Agents For Relapsed Bpdcn, Naveen Pemmaraju, Luan Hai Phan, Geoffrey Fell, Marlise R Luskin, Mahesh Swaminathan, Sherry Pierce, Courtney Dinardo, Abhishek Maiti, Marina Konopleva, Andrew A Lane

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No abstract provided.

Further Delineation Of The Scaf4-Associated Neurodevelopmental Disorder, Cosima M Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Farah Ammouri, Urania Kotzaeridou, Vanda Mcniven, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B Haack, Ruth J Falb, Amelie J Müller, Tobias Linden, Chad R Haldeman-Englert, Charlotte W Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M Riedhammer, Houda Z Elloumi, Richard Person, Fanggeng Zou, Juliette J Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J M Nowaczyk, Reem M Elshafie, Hind Alsharhan, Paul R Hillman, Leslie A Dunnington, Hilde M H Braakman, Shane Mckee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G Steigerwald, Nicolas J Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier

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While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one …

Todo: A Triple-Outcome Double-Criterion Optimal Design For Dose Monitoring-And-Optimization In Multi-Dose Randomized Trials, Jingyi Zhang, Heng Zhou, Nolan A Wages, Zifang Guo, Fang Liu, Thomas Jemielita, Fangrong Yan, Ruitao Lin

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Detecting the efficacy signal and determining the optimal dose are critical steps to increase the probability of success and expedite the drug development in cancer treatment. After identifying a safe dose range through phase I studies, conducting a multidose randomized trial becomes an effective approach to achieve this objective. However, there have been limited formal statistical designs for such multidose trials, and dose selection in practice is often ad hoc, relying on descriptive statistics. We propose a Bayesian optimal two-stage design to facilitate rigorous dose monitoring and optimization. Utilizing a flexible Bayesian dynamic linear model for the dose-response relationship, we …

Gene Promoters Are Genomically Encoded To Facilitate Histone Exchange/Incorporation, Blaine Bartholomew

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Gene promoters are intrinsically hardwired not only to facilitate transcription preinitiation complex formation but also the release of paused RNA polymerase by H2A.Z. A new PLOS Biology study reveals poly (dA) tracts at promoters positively stimulate H2A.Z incorporation by the SWR complex in yeast.

Diroximel Fumarate Acts Through Nrf2 To Attenuate Methylglyoxal-Induced Nociception In Mice And Decrease Isr Activation In Drg Neurons, Muhammad Saad Yousuf, Marisol Mancilla Moreno, Brodie J Woodall, Vikram Thakur, Jiahe Li, Lucy He, Rohita Arjarapu, Danielle Royer, Jennifer Zhang, Munmun Chattopadhyay, Peter M Grace, Theodore J Price

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Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes pain hypersensitivity in mice by stimulating the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and subsequently activating the integrated stress response (ISR). We first established that Zucker diabetic fatty rats have enhanced MGO signaling, engage ISR, and develop pain hypersensitivity. Since nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins that neutralize MGO, we hypothesized that fumarates, like diroximel fumarate (DRF), will stimulate Nrf2 signaling, and prevent MGO-induced ISR and pain hypersensitivity. DRF (100 mg/kg) treated …

Glutamate Gating Of Ampa-Subtype Iglurs At Physiological Temperatures, Anish Kumar Mondal, Elisa Carrillo, Vasanthi Jayaraman, Edward C Twomey

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Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that mediate most excitatory neurotransmission1. iGluRs are gated by glutamate, where on glutamate binding, they open their ion channels to enable cation influx into postsynaptic neurons, initiating signal transduction1,2. The structural mechanics of how glutamate gating occurs in full-length iGluRs is not well understood. Here, using the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype iGluR (AMPAR), we identify the glutamate-gating mechanism. AMPAR activation by glutamate is augmented at physiological temperatures. By preparing AMPARs for cryogenic-electron microscopy at these temperatures, we captured the glutamate-gating mechanism. Activation by glutamate initiates ion channel opening that involves all ion …

Sustained Improvement In Health-Related Quality Of Life In Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, And Dexamethasone: Maia Final Analysis Of Patient-Reported Outcomes, Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel

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Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.

Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.

Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.

Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of …

T2-Weighted Imaging Of Rectal Cancer Using A 3d Fast Spin Echo Sequence With And Without Deep Learning Reconstruction: A Reader Study, Dan Nguyen, Sarah Palmquist, Ken-Pin Hwang, Jingfei Ma, Usama Salem, Jia Sun, Xinzeng Wang, Jong Bum Son, Randy Ernst, Peng Wei, Harmeet Kaur, Nir Stanietzky

Faculty, Staff and Student Publications

Purpose: To compare image quality and clinical utility of a T2-weighted (T2W) 3-dimensional (3D) fast spin echo (FSE) sequence using deep learning reconstruction (DLR) versus conventional reconstruction for rectal magnetic resonance imaging (MRI).

Methods: The study included 50 patients with rectal cancer who underwent rectal MRI consecutively between July 7, 2020 and January 20, 2021 using a T2W 3D FSE sequence with DLR and conventional reconstruction. Three radiologists reviewed the two sets of images, scoring overall SNR, motion artifacts, and overall image quality on a 3-point scale and indicating clinical preference for DLR or conventional reconstruction based on those three …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

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Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

Quantitative Ablation Confirmation Methods In Percutaneous Thermal Ablation Of Malignant Liver Tumors: Technical Insights, Clinical Evidence, And Future Outlook, Iwan Paolucci, Jessica Albuquerque Marques Silva, Yuan-Mao Lin, Alexander Shieh, Anna Maria Ierardi, Gianpaolo Caraffiello, Carlo Gazzera, Kyle A Jones, Paolo Fonio, Reto Bale, Kristy K Brock, Marco Calandri, Bruno C Odisio

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Percutaneous image-guided thermal ablation is an established local curative-intent treatment technique for the treatment of primary and secondary malignant liver tumors. Whereas margin assessment after surgical resection can be accomplished with microscopic examination of the resected specimen, margin assessment after percutaneous thermal ablation relies on cross-sectional imaging. The critical measure of technical success is the minimal ablative margin (MAM), defined as the minimum distance between the tumor and the edge of the ablation zone. Traditionally, the MAM has been assessed qualitatively using anatomic landmarks, which has suboptimal accuracy and reproducibility and is prone to operator bias. Consequently, specialized software-based methods …

Imaging In Pelvic Exenteration-A Multidisciplinary Practice Guide From The Esgar-Sar-Esur-Pelvex Collaborative Group, Stephanie Nougaret, Doenja M J Lambregts, Geerard L Beets, Regina G H Beets-Tan, Lennart Blomqvist, David Burling, Quentin Denost, Maria A Gambacorta, Benedetta Gui, Ann Klopp, Yulia Lakhman, Kate E Maturen, Riccardo Manfredi, Iva Petkovska, Luca Russo, Atul B Shinagare, James A Stephenson, Damian Tolan, Aradhana M Venkatesan, Aaron J Quyn, Rosemarie Forstner

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Pelvic exenteration (PE) is a radical surgical approach designed for the curative treatment of advanced pelvic malignancies, requiring en-bloc resection of multiple pelvic organs. While the procedure is radical, it has shown promise in enhancing long-term survival and is now comparable in surgical mortality to elective resections for primary pelvic cancers. Imaging plays a crucial role in preoperative planning, with MRI, CT, and PET/CT being pivotal in assessing the extent of cancer and formulating a surgical roadmap. This paper presents clinical practice guidelines for imaging in the context of PE, developed jointly by ESGAR, SAR, ESUR, and the PelvEx Collaborative. …

In Vivo Assessment Of Cardiac Radiofrequency Ablation In A Large-Animal Model Using Photoacoustic-Ultrasound Imaging, Nilesh Mathuria, Krithik Vishwanath, Blake C Fallon, Antonio Martino, Giorgio Brero, Richard C Willson, Miguel Valderrabano, Carly S Filgueira, Richard R Bouchard

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Despite advancements in catheter technology, intraoperative assessment of radiofrequency ablation (RFA) lesions remains elusive. Prior ex vivo data suggest photoacoustic imaging (PAI) can provide RFA lesion characteristics, but in vivo data are lacking. PAI involves delivering near-infrared light to tissue, leading to transient acoustic waves that can be detected by clinically available ultrasound transducers, providing optically based tissue characterization at depth. Three epicardial RFA lesions were delivered in an open-chest porcine model. In vivo PAI-based measurements of RFA lesion dimensions matched (< 0.7-mm error) gross pathologic assessment, yielding in vivo feasibility data of PAI to provide intraoperative RFA lesion dimensions.

Quantifying Photon Counting Detector (Pcd) Performance Using Pcd-Ct Images, Linying Zhan, Guang-Hong Chen, Ke Li

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Background: Photon counting detector CTs (PCD-CTs) have recently been introduced to clinical imaging. This development creates a new need for end-users to quantify and monitor the physical performance of PCDs. Traditionally, the characterization of PCD performance relied on detector counts, which are typically accessible to the manufacturer but are not usually available to clinical end-users.

Purpose: The goal of this work was to develop a new method for quantifying PCD performance using reconstructed PCD-CT images, without requiring access to the PCD counts.

Methods: The proposed method is based on a set of closed-form relationships that connect PCD-CT image noise, the …

Temporal Trends Of Subsequent Central Nervous System Malignancies Among Survivors Of Childhood Cancer, Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Susan Smith, Michael A Arnold, Miriam Conces, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

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Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS …

Lefitolimod In Combination With Ipilimumab In Patients With Advanced Solid Tumors: A Phase I Trial, Mirella Nardo, Mohamed A Gouda, Matthew J Reilley, Amadeo B Biter, Joann Lim, Stacie A Bean, Ly M Nguyen, Priya R Bhosale, Casey R Ager, Coline A Couillault, Sarina A Piha-Paul, Siqing Fu, Apostolia M Tsimberidou, Timothy A Yap, Aung Naing, Jordi Rodon, Vivek Subbiah, Daniel D Karp, Michael A Curran, David S Hong

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Introduction: TLR9 agonists are immunomodulators that have been of interest for combined use with cancer immunotherapy. TLR9 agonists, such as lefitolimod (MGN1703), significantly increased Th1 response in preclinical models and have demonstrated efficacy in early clinical trials. This trial assessed the safety and preliminary efficacy of the combination of lefitolimod and ipilimumab in patients with advanced solid tumors.

Methods: This was a single-center, open-label, investigator-initiated phase I trial conducted at The University of Texas MD Anderson Cancer Center. Patients received leftolimod either subcutaneously (at escalating doses of 15-120 mg) or intratumorally (at the maximum feasible dose) in combination with ipilimumab …

Tumoral And Circulating Genomic Landscape Inform Survival Differences In Colorectal Carcinomatosis, Michael G White, Reed I Ayabe, Mohammad A Zeineddine, Fadl A Zeineddine, Abdelrahman M G Yousef, Mahmoud Yousef, Norman J Galbraith, J Bryan Iorgulescu, Christopher Scally, Keith Fournier, Timothy E Newhook, Nancy Y You, Jason Willis, Scott Kopetz, George J Chang, John Paul Shen, Abhineet Uppal

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Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) …

Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim

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Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …

Using A Surgical Risk Predictor To Estimate Percutaneous Cryoablation Adverse Event Risk: A Single Center Comparative Analysis, Prisha Patel, Koustav Pal, Hadi Ahmed, Bill Tang, Iwan Paolucci, Mohammad Khavandi, Peiman Habibollahi, Ketan Shah, Steven Y Huang, Bruno C Odisio, Sanjay Gupta, Kamran Ahrar, Steven Yevich, Joshua D Kuban, Alda Tam, Rahul A Sheth

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Objective: To evaluate the relevance of established surgical risk calculators for predicting complications in patients undergoing percutaneous lung cryoablation (PLC).

Methods: The institution's database was queried for PLC procedures from March 2015 to May 2024, excluding those patients with concomitant local therapies or five or more lesions treated in a single setting. Demographics, frailty metrics as defined by the surgical literature, and procedural variables were collected. To evaluate the suitability of surgical risk estimate calculators, the requisite demographic data were input into the American College of Surgery surgical risk calculator; estimates for length of stay (LOS), serious complications, 30-day readmission, …

Natural History Models For Lung Cancer: A Scoping Review, Renu Sara Nargund, Sayaka Ishizawa, Maryam Eghbalizarch, Paul Yeh, Seyyed Mostafa Mousavi Janbeh Saray, Sara Nofal, Yimin Geng, Pianpian Cao, Edwin J Ostrin, Rafael Meza, Martin C Tammemägi, Robert J Volk, Maria A Lopez-Olivo, Iakovos Toumazis

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Introduction: Natural history models (NHMs) of lung cancer (LC) simulate the disease's natural progression providing a baseline for assessing the impact of interventions. NHMs have been increasingly used to inform public health policies, highlighting their utility. The objective of this scoping review was to summarize existing LC NHMs, identify their limitations, and propose a framework for future NHM development.

Methods: We searched MEDLINE, Embase, Web of Science, and IEEE Xplore from their inception to October 5, 2023, for peer-reviewed, full-length articles with an LC NHM. Model characteristics, their applications, data sources used, and limitations were extracted and narratively synthesized.

Results: …

Dose Prediction Via Deep Learning To Enhance Treatment Planning Of Lung Radiotherapy Including Simultaneous Integrated Boost Techniques, Wenhua Cao, Mary Gronberg, Stephen Bilton, Hana Baroudi, Skylar Gay, Christopher Peeler, Zhongxing Liao, Thomas J Whitaker, Karen Hoffman, Laurence E Court

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Background: Recent studies have shown deep learning techniques are able to predict three-dimensional (3D) dose distributions of radiotherapy treatment plans. However, their use in dose prediction for treatments with varied prescription doses including simultaneous integrated boost (SIB), that is, using multiple prescription doses within the same plan, and benefit in improving plan quality should be validated.

Purpose: To investigate the feasibility and potential benefit of using deep learning to predict dose distribution of volumetric modulated arc therapy (VMAT) including SIB techniques and improve treatment planning for patients with lung cancer.

Methods: The dose prediction model was trained with 93 retrospective …

Cross-Tissue Coordination Between Slc Nucleoside Transporters Regulates Reproduction In Caenorhabditis Elegans, Youchen Guan, Yong Yu, Shihong M Gao, Lang Ding, Qian Zhao, Meng C Wang

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Metabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation. However, the molecular mechanisms mediating these metabolite communications remain poorly understood. Here, we focus on nucleosides and nucleotides, essential metabolites involved in multiple cellular processes, and report the pivotal role of the SLC29A family of transporters in mediating nucleoside coordination between the soma and the germline. Through genetic analysis, we discovered that two Caenorhabditis elegans homologs of SLC29A transporters, Equilibrative Nucleoside Transporter …

Temi: Tissue-Expansion Mass-Spectrometry Imaging, Hua Zhang, Lang Ding, Amy Hu, Xudong Shi, Penghsuan Huang, Haiyan Lu, Paul W Tillberg, Meng C Wang, Lingjun Li

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The spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput in situ mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here we developed a tissue-expansion method compatible with matrix-assisted laser desorption/ionization mass-spectrometry imaging (TEMI). TEMI reaches single-cell spatial resolution without sacrificing voxel throughput and enables the profiling of hundreds of biomolecules, including lipids, metabolites, peptides (proteins), and N-glycans. Using TEMI, we mapped the spatial distribution of biomolecules across various mammalian tissues and uncovered metabolic heterogeneity in tumors. TEMI can be easily …

Chemotherapy-Free Treatment With Radiotherapy And Immunotherapy For Locally Advanced Non-Small Cell Lung Cancer, M Zeeshan Ozair, Balazs Halmos, Angelica D'Aiello, Jaewon Yun, Andrea R Filippi, Andreas Rimner, Steven H Lin, Charles B Simone, Nitin Ohri

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Background: Concurrent chemoradiotherapy (CRT) followed by immunotherapy is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), yet many patients are ineligible due to treatment-related toxicity or poor functional status. Chemotherapy-free approaches using radiotherapy (RT) and immunotherapy may offer a safer and equally effective alternative in select patient populations.

Methods: A comprehensive literature review was conducted using PubMed, Google Scholar, and relevant conference proceedings focusing on trials between 2000 and 2024. Studies investigating chemotherapy-free regimens combining RT and immunotherapy in LA-NSCLC were analyzed, with emphasis on clinical outcomes, biomarker use, treatment sequencing, radiation dose/fractionation, and safety.

Results: Multiple …

Neurotransmitter Power Plays: The Synaptic Communication Nexus Shaping Brain Cancer, Jayanta Mondal, Jason T Huse

Faculty, Staff and Student Publications

Gliomas and brain metastases are notorious for their dismal prognosis and low survival rates, a challenge exacerbated by our incomplete grasp of the complex dynamics that govern brain cancers. Recently, a groundbreaking paradigm shift has emerged, highlighting the crucial role of synaptic communication between neurons and brain tumor cells in reshaping neuronal signaling to favor tumor growth. This review delves into the pivotal interplay of synaptic mechanisms, focusing on excitatory glutamatergic and inhibitory GABAergic pathways. Glutamatergic synapses utilize glutamate to propagate excitatory signals, while GABAergic synapses employ gamma-aminobutyric acid (GABA) to inhibit neuronal firing. Glutamatergic signaling can be broadly classified …