Radiation Medicine Commons^™

Differentiation Stage Predicts Radiosensitivity In Mesenchymal-Like Pancreatic Cancer, Tingshi Su, Xinjian Yu, Mojtaba Hoseini-Ghahfarokhi, David B Flint, Scott J Bright, Joana I D S Antunes, David K J Martinus, Mandira Manandhar, Mariam Ben Kacem, Poliana C Marinello, Eurico J G Pereira, Hua-Sheng Chiu, Uwe Titt, David R Grosshans, Jan Schuemann, Henning Willers, Harald Paganetti, Pavel Sumazin, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Purpose: To derive a genomic classifier to predict radiosensitivity of pancreatic cancer cell lines and patients with pancreatic cancer to allow genomic-guided radiation therapy.

Methods and materials: We collected a comprehensive data set of full clonogenic cell survival curves of 45 pancreatic cancer cell lines irradiated with clinical photon and proton beams. We derived classifiers based on data from human embryonic and fetal pancreas single-cell RNA-sequencing to distinguish between epithelial and mesenchymal cells and to predict pancreas cell-line differentiation stage. Independent testing was done with an embryonic mouse pancreas single-cell RNA-sequencing data set. We then used bulk RNA-seq profiles from …

Cost-Effectiveness Of Personalized Policies For Implementing Organ-At-Risk Sparing Adaptive Radiation Therapy In Head And Neck Cancer, Seyedmohammadhossein Hosseinian, Daniel Suarez-Aguirre, Cem Dede, Raul Garcia, Lucas Mccullum, Mehdi Hemmati, Aysenur Karagoz, Abdallah S R Mohamed, Stephen Y Lai, Katherine A Hutcheson, Amy C Moreno, Kristy K Brock, Fatemeh Nosrat, Clifton D Fuller, Andrew J Schaefer

Faculty, Staff and Student Publications

Background and purpose: The principle of adaptive radiation therapy (ART) is to adjust radiation plans in response to anatomical changes during treatment. The purpose of this study was to develop a decision-making model for implementation of personalized ART that balances the costs and clinical benefits of radiation plan adaptations in head and neck cancer (HNC).

Materials and methods: Using retrospective imaging data from 52 HNC patients, a Markov decision process (MDP) model was developed to determine optimal timing for plan adaptations based on the difference in normal tissue complication probability (ΔNTCP) between planned and delivered doses to organs-at-risk. To capture …

Robust Automated Method Of Spatial Resolution Measurement In Radiotherapy Ct Simulation Images, Pavel Govyadinov, Rick R Layman, Tucker Netherton, Raymond Mumme, Aaron K Jones, Laurence E Court, Moiz Ahmad

Faculty, Staff and Student Publications

Background: Variation in imaging protocol, patient positioning, and the presence of artifacts can vary image quality in CT images used for radiotherapy planning. Automated methods for spatial resolution (SR) estimation exist but require further investigation and validation for wider adoption.

Purpose: To validated previously existing algorithm for SR estimation and introduce improvements that make it robust to patient positioning, CT protocol, site, and artifacts.

Method: A reference algorithm based on the previous gold standard was recreated and modified to improve robustness. The algorithms were tested on three different datasets: (1) a cylindrical ACR CT QC phantom scanned using a Siemens …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

Atr Inhibition Radiosensitizes Cells Through Augmented Dna Damage And G2 Cell Cycle Arrest Abrogation, Scott J Bright, Mandira Manandhar, David B Flint, Rishab Kolachina, Mariam Ben Kacem, David Kj Martinus, Broderick X Turner, Ilsa Qureshi, Conor H Mcfadden, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy. We assessed the ability of an ATR inhibitor, AZD6738, to sensitize cancer cell lines of various histologic types to photon and proton radiotherapy. We found that radiosensitization took place through persistent DNA damage and abrogated G2 …

Tools And Recommendations For Commissioning And Quality Assurance Of Deformable Image Registration In Radiotherapy, Lando S Bosma, Mohammad Hussein, Michael G Jameson, Soban Asghar, Kristy K Brock, Jamie R Mcclelland, Sara Poeta, Johnson Yuen, Cornel Zachiu, Adam U Yeo

Faculty, Staff and Student Publications

Multiple tools are available for commissioning and quality assurance of deformable image registration (DIR), each with their own advantages and disadvantages in the context of radiotherapy. The selection of appropriate tools should depend on the DIR application with its corresponding available input, desired output, and time requirement. Discussions were hosted by the ESTRO Physics Workshop 2021 on Commissioning and Quality Assurance for DIR in Radiotherapy. A consensus was reached on what requirements are needed for commissioning and quality assurance for different applications, and what combination of tools is associated with this. For commissioning, we recommend the target registration error of …

Financial Toxicity In Breast Cancer Patients Receiving Regional Nodal Irradiation: Variation By Cancer Subtype, Grace L Smith, Benjamin D Smith, Chi-Fang Wu, Simona F Shaitelman, Mariana Chavez-Macgregor, Rashmi Murthy, Kelsey Kaiser, Kimberly S Ku, Julia J Shi, Sanjay S Shete, Ying-Shiuan Chen, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Karen E Hoffman

Faculty, Staff and Student Publications

BACKGROUND: We evaluated sociodemographic and clinical predictors of financial toxicity (FT) among patients with breast cancer with higher risk clinical factors warranting regional nodal irradiation (RNI).

METHODS: Among 183 participants in a clinical trial of conventional vs. hypofractionated treatment with RNI, 125 (68 %) completed a pilot survey of FT measured using the validated Economic Strain and Resilience in Cancer (ENRICh) instrument, scored from 0 (minimal) to 10 (severe) FT. Associations with predictors were evaluated using Pearson correlation coefficients and Kruskal Wallis, Mann-Whitney U, and Jonckheere-Terpstra tests. Predictors of severe FT (ENRICh≥5) were tested using multivariable logistic regression with odds …

Exploiting The Heavy Chain Glycans For The Improvement Of Radioimmunoconjugates, Cindy Rodriguez

Dissertations, Theses, and Capstone Projects

Radiolabeled antibodies have become indispensable tools in nuclear medicine. However, the natural roles of antibodies within the immune system mean that they have several intrinsic limitations as a platform for radiopharmaceuticals. A handful of recent preclinical studies suggest that binding by FcR and particularly FcyRI can affect the pharmacokinetic profiles of 89Zr-labeled radioimmunoconjugates. Fc receptors (FcR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcRs affect the in vivo performance of radiolabeled antibodies. Antibodies …

Proton Therapy Toxicity Outcomes For Localized Prostate Cancer: Long-Term Results At A Comprehensive Cancer Center, Alan J Sosa, Michael K Rooney, Howard D Thames, Jeremiah W Sanders, David M Swanson, Seungtaek L Choi, Quynh-Nhu Nguyen, Henry Mok, Deborah A Kuban, X Ron Zhu, Shalin Shah, Lauren L Mayo, Karen E Hoffman, Chad Tang, Sean E Mcguire, Narayan Sahoo, Xiaodong Zhang, Andrew K Lee, Thomas J Pugh, Usama Mahmood, John W Davis, Brian F Chapin, Paul Corn, Reena Kudchadker, Noveen Ausat, Steven J Frank

Faculty, Staff and Student Publications

BACKGROUND: Proton therapy (PT) has unique biologic properties with excellent clinical outcomes for the management of localized prostate cancer. Here, we aim to characterize the toxicity of PT for patients with localized prostate cancer and propose mitigation strategies using a large institutional database.

METHODS: We reviewed medical records of 2772 patients with localized prostate cancer treated with definitive PT between May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 849]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high …

Highly Reusable Electrochemical Immunosensor For Ultrasensitive Protein Detection, Kavya L Singampalli, Camille Neal-Harris, Cassian Yee, Jamie S Lin, Peter B Lillehoj

Faculty, Staff and Student Publications

The detection and quantification of protein biomarkers in bodily fluids is important for many clinical applications, including disease diagnosis and health monitoring. Current techniques for ultrasensitive protein detection, such as enzyme-linked immunosorbent assay (ELISA) and electrochemical sensing, involve long incubation times (1.5-3 hr) and rely on single-use sensing electrodes which can be costly and generate excessive waste. This work demonstrates a reusable electrochemical immunosensor employing magnetic nanoparticles (MNPs) and dually labeled gold nanoparticles (AuNPs) for ultrasensitive measurements of protein biomarkers. As proof of concept, this platform was used to detect C-X-C motif chemokine ligand 9 (CXCL9), a biomarker associated with …

Analyzing The Relationship Between Dose And Geometric Agreement Metrics For Auto-Contouring In Head And Neck Normal Tissues, Barbara Marquez, Zachary T Wooten, Ramon M Salazar, Christine B Peterson, David T Fuentes, T J Whitaker, Anuja Jhingran, Julianne Pollard-Larkin, Surendra Prajapati, Beth Beadle, Carlos E Cardenas, Tucker J Netherton, Laurence E Court

Faculty, Staff and Student Publications

This study aimed to determine the relationship between geometric and dosimetric agreement metrics in head and neck (H&N) cancer radiotherapy plans. A total 287 plans were retrospectively analyzed, comparing auto-contoured and clinically used contours using a Dice similarity coefficient (DSC), surface DSC (sDSC), and Hausdorff distance (HD). Organs-at-risk (OARs) with ≥200 cGy dose differences from the clinical contour in terms of Dmax (D0.01cc) and Dmean were further examined against proximity to the planning target volume (PTV). A secondary set of 91 plans from multiple institutions validated these findings. For 4995 contour pairs across 19 OARs, 90% had a DSC, sDSC, …

Data-Driven Gated Positron Emission Tomography/Computed Tomography For Radiotherapy, Tinsu Pan, Dershan Luo

Faculty, Staff and Student Publications

PURPOSE: Software-based data-driven gated (DDG) positron emission tomography/computed tomography (PET/CT) has replaced hardware-based 4D PET/CT. The purpose of this article was to review DDG PET/CT, which could improve the accuracy of treatment response assessment, tumor motion evaluation, and target tumor contouring with whole-body (WB) PET/CT for radiotherapy (RT).

MATERIAL AND METHODS: This review covered the topics of 4D PET/CT with hardware gating, advancements in PET instrumentation, DDG PET, DDG CT, and DDG PET/CT based on a systematic literature review. It included a discussion of the large axial field-of-view (AFOV) PET detector and a review of the clinical results of DDG …

Scanless Two-Photon Voltage Imaging, Ruth R Sims, Imane Bendifallah, Christiane Grimm, Aysha S Mohamed Lafirdeen, Soledad Domínguez, Chung Yuen Chan, Xiaoyu Lu, Benoît C Forget, François St-Pierre, Eirini Papagiakoumou, Valentina Emiliani

Faculty, Staff and Students Publications

Two-photon voltage imaging has long been heralded as a transformative approach capable of answering many long-standing questions in modern neuroscience. However, exploiting its full potential requires the development of novel imaging approaches well suited to the photophysical properties of genetically encoded voltage indicators. We demonstrate that parallel excitation approaches developed for scanless two-photon photostimulation enable high-SNR two-photon voltage imaging. We use whole-cell patch-clamp electrophysiology to perform a thorough characterization of scanless two-photon voltage imaging using three parallel illumination approaches and lasers with different repetition rates and wavelengths. We demonstrate voltage recordings of high-frequency spike trains and sub-threshold depolarizations from neurons …

Adding 6 Months Of Androgen Deprivation Therapy To Postoperative Radiotherapy For Prostate Cancer: A Comparison Of Short-Course Versus No Androgen Deprivation Therapy In The Radicals-Hd Randomised Controlled Trial, Chris C Parker, Noel W Clarke, Adrian D Cook, Howard Kynaston, Charles N Catton, William R Cross, Peter M Petersen, Rajendra A Persad, Fred Saad, Lorna C Bower, John Logue, Heather Payne, Silvia Forcat, Cindy Goldstein, Claire Murphy, Juliette Anderson, Maroie Barkati, David M Bottomley, Jennifer Branagan, Ananya Choudhury, Peter W M Chung, Lyn Cogley, Chee L Goh, Peter Hoskin, Vincent Khoo, Shawn C Malone, Lindsey Masters, Stephen L Morris, Abdenour Nabid, Aldrich D Ong, Rakesh Raman, Kathryn L Tarver, Alison C Tree, Jane Worlding, James P Wylie, Anjali M Zarkar, Wendy R Parulekar, Mahesh K B Parmar, Matthew R Sydes, Radicals Investigators

Faculty, Staff and Student Publications

BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.

METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy …

Longitudinal Changes In The Carotid Arteries Of Head And Neck Cancer Patients Following Radiation Therapy: Results From A Prospective Serial Imaging Biomarker Characterization Study, Efstratios Koutroumpakis, Abdallah Sherif Radwan Mohamed, Peter Chaftari, David I Rosenthal, Dorothy Gujral, Christopher Nutting, Serageldin Kamel, Mohamed A Naser, Peter Kim, Roland Bassett, Clifton D Fuller, Elie Mouhayar, Md Anderson Head Neck Radiation Oncology Cardiovascular Working Group

Faculty, Staff and Student Publications

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer.

METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated.

RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; …

An International Phantom Study Of Inter-Site Variability In Technetium-99m Image Quantification: Analyses From The Target Radioembolization Study, Grace Keane, Rob Van Rooij, Marnix Lam, S Cheenu Kappadath, Bilal Kovan, Stephanie Leon, Matthew Dreher, Kirk Fowers, Hugo De Jong

Faculty, Staff and Student Publications

BACKGROUND: Personalised multi-compartment dosimetry based on [

RESULTS: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6-10.1%). A standardised protocol did not improve variation (interquartile range 8.4-9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5-0.7 and 0.6-0.8 respectively), however the standardised protocol did improve accuracy of …

A Novel Positive-Contrast Magnetic Resonance Imaging Line Marker For High-Dose-Rate (Hdr) Mri-Assisted Radiosurgery (Mars), Li Wang, Yao Ding, Teresa L Bruno, R Jason Stafford, Eric Lin, Tharakeswara K Bathala, Jeremiah W Sanders, Matthew S Ning, Jingfei Ma, Ann H Klopp, Aradhana Venkatesan, Jihong Wang, Karen S Martirosyan, Steven J Frank

Faculty, Staff and Student Publications

Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T …

Mammographic Density Mediates The Protective Effect Of Early-Life Body Size On Breast Cancer Risk, Marina Vabistsevits, George Davey Smith, Tom G Richardson, Rebecca C Richmond, Weiva Sieh, Joseph H Rothstein, Laurel A Habel, Stacey E Alexeeff, Bethan Lloyd-Lewis, Eleanor Sanderson

Faculty, Staff and Student Publications

The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. …

Mr-Guided Stereotactic Radiation Therapy For Head And Neck Cancers, He Wang, Jinzhong Yang, Anna Lee, Jack Phan, Tze Yee Lim, Clifton D Fuller, Eun Young Han, Dong Joo Rhee, Travis Salzillo, Yao Zhao, Nitish Chopra, Mary Pham, Pam Castillo, Angela Sobremonte, Amy C Moreno, Jay P Reddy, David Rosenthal, Adam S Garden, Xin Wang

Faculty, Staff and Student Publications

PURPOSE: MR-guided radiotherapy (MRgRT) has the advantage of utilizing high soft tissue contrast imaging to track daily changes in target and critical organs throughout the entire radiation treatment course. Head and neck (HN) stereotactic body radiation therapy (SBRT) has been increasingly used to treat localized lesions within a shorter timeframe. The purpose of this study is to examine the dosimetric difference between the step-and-shot intensity modulated radiation therapy (IMRT) plans on Elekta Unity and our clinical volumetric modulated arc therapy (VMAT) plans on Varian TrueBeam for HN SBRT.

METHOD: Fourteen patients treated on TrueBeam sTx with VMAT treatment plans were …

Long-Term Patient-Reported Dyspareunia After Definitive Chemoradiation For Anal Cancer: Using The Anterior Vaginal Wall As An Organ-At-Risk To Define An Actionable Dosimetric Goal, Michael K Rooney, Joshua S Niedzielski, Ramon M Salazar, Angelica Arzola, Prajnan Das, Eugene J Koay, Albert Koong, Ethan B Ludmir, Bruce D Minsky, Sonal Noticewala, Grace L Smith, Cullen Taniguchi, Emma B Holliday

Faculty, Staff and Student Publications

PURPOSE: Chemoradiation therapy (CRT) is the standard treatment for squamous cell carcinoma of the anus (SCCA). This study aimed to investigate the relationship between vaginal dosimetry and long-term patient-reported dyspareunia after treatment. We further aimed to use the anterior vaginal wall (AVW) as an organ at risk to define an actionable dosimetric clinical goal to decrease the risk of patient-reported dyspareunia.

METHODS AND MATERIALS: Women with SCCA treated with intensity modulated radiation therapy-based CRT were surveyed at least 2 years after successfully completing therapy. A Female Sexual Function Index (FSFI) pain subscore ≤4 was used to define dyspareunia. Dosimetric parameters …

Acute Pain Prediction In Oral Cavity And Oropharyngeal Cancer Patients Receiving Radiation Therapy, Vivian Salama

Dissertations and Theses (Open Access)

Oral-Cavity and oropharyngeal cancers (OC/OPC) are types of head and neck cancers that are increasing in incidence domestically. Radiation therapy (RT) is crucial in OC/OPC management. Pain is a common and challenging symptom for most patients during therapy, as nearly all patients undergoing locoregional RT in OC/OPC require analgesia for acute iatrogenic pain. Moreover, about 45% of long-term survivors report chronic pain, with more than 10% exhibiting severe chronic pain. Pain control is challenging due to the multifactorial clinical, molecular, and cellular etiology of cancer/therapy pain, as well as variation in pain assessment and the non-uniform management of pain between …

New Horizons In Hyperpolarized13c Mri, Myriam M Chaumeil, James A Bankson, Kevin M Brindle, Shdema Epstein, Ferdia A Gallagher, Martin Grashei, Caroline Guglielmetti, Joshua D Kaggie, Kayvan R Keshari, Stephan Knecht, Christoffer Laustsen, Andreas B Schmidt, Daniel Vigneron, Yi-Fen Yen, Franz Schilling

Faculty, Staff and Student Publications

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons …

High-Density Glass Scintillators For Proton Radiography-Relative Luminosity, Proton Response, And Spatial Resolution, Ethan Stolen, Ryan Fullarton, Rain Hein, Robin L Conner, Luiz G Jacobsohn, Charles-Antoine Collins-Fekete, Sam Beddar, Ugur Akgun, Daniel Robertson

Faculty, Staff and Student Publications

Proton radiography is a promising development in proton therapy, and researchers are currently exploring optimal detector materials to construct proton radiography detector arrays. High-density glass scintillators may improve integrating-mode proton radiography detectors by increasing spatial resolution and decreasing detector thickness. We evaluated several new scintillators, activated with europium or terbium, with proton response measurements and Monte Carlo simulations, characterizing relative luminosity, ionization quenching, and proton radiograph spatial resolution. We applied a correction based on Birks's analytical model for ionization quenching. The data demonstrate increased relative luminosity with increased activation element concentration, and higher relative luminosity for samples activated with europium. …

Clinical And Dosimetric Results Of Proton Or Photon Radiation Therapy For Large (>5 Cm) Hepatocellular Carcinoma: A Retrospective Analysis, Rodney Cheng-En Hsieh, Ching-Hsin Lee, Hsiao-Chieh Huang, Shu-Wei Wu, Chen-Yu Chou, Sheng-Ping Hung, Chao-Wei Lee, Sunil Krishnan, Bhanu Prasad Venkatesulu, Jin-Chiao Lee, Yung-Chih Chou, Kun-Ming Chan, Po-Ting Lin, Wei-Chen Lee, Chen-Chun Lin, Shen-Yen Lin, Ji-Hong Hong

Faculty, Staff and Student Publications

Purpose: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy.

Methods and materials: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison.

Results: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 …

Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using …

Fully Automated Deep Learning Based Auto-Contouring Of Liver Segments And Spleen On Contrast-Enhanced Ct Images, Aashish C Gupta, Guillaume Cazoulat, Mais Al Taie, Sireesha Yedururi, Bastien Rigaud, Austin Castelo, John Wood, Cenji Yu, Caleb O'Connor, Usama Salem, Jessica Albuquerque Marques Silva, Aaron Kyle Jones, Molly Mcculloch, Bruno C Odisio, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), …

Tumor Treating Fields Increases Blood-Brain Barrier Permeability And Relative Cerebral Blood Volume In Patients With Glioblastoma, Michael Iv, Lewis Naya, Sajal Sanan, Samuel L Van Buskirk, Seema Nagpal, Reena P Thomas, Lawrence D Recht, Chirag B Patel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: 200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans.

METHODS: Each patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (V

RESULTS: Among 13 pMRI datasets …

Predicting Radiotherapy Patient Outcomes With Real-Time Clinical Data Using Mathematical Modelling, Alexander P Browning, Thomas D Lewin, Ruth E Baker, Philip K Maini, Eduardo G Moros, Jimmy Caudell, Helen M Byrne, Heiko Enderling

Faculty, Staff and Student Publications

Longitudinal tumour volume data from head-and-neck cancer patients show that tumours of comparable pre-treatment size and stage may respond very differently to the same radiotherapy fractionation protocol. Mathematical models are often proposed to predict treatment outcome in this context, and have the potential to guide clinical decision-making and inform personalised fractionation protocols. Hindering effective use of models in this context is the sparsity of clinical measurements juxtaposed with the model complexity required to produce the full range of possible patient responses. In this work, we present a compartment model of tumour volume and tumour composition, which, despite relative simplicity, is …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

A Look-Up-Table Development To Facilitate Ct Simulation Of Mr-Linac Treatment, Neil Hughes, Travis C Salzillo, Sastry Vedam, Tze Yee Lim, Xin Wang, He Wang, Mustefa Mohammedsaid, Clifton D Fuller, Jihong Wang, Jinzhong Yang

Faculty, Staff and Student Publications

While current MR-Linac (MRL) treatment workflows utilize a large table overlay during CT simulation to convert indexing between the two machines, we developed a look-up-table (LUT) as an alternative approach. After populating the LUT, index conversion factors were verified at three separate table locations. The resultant root-mean-square isocenter shifts on the MRL were 0.04/0.08 cm, 0.08/0.07 cm, and 0.09/0.08 cm with/without using the table overlay during simulation in the lateral, longitudinal, and vertical directions, respectively, which is within registration tolerance. Clinical implementation of the LUT has resulted in a more efficient MRL treatment workflow while maintaining accurate patient setup.