Radiation Medicine Commons^™

Chemoradiation Treatment With Or Without Concurrent Tumor-Treating Fields (Ttfields) Therapy In Newly Diagnosed Glioblastoma (Gbm) Patients In China, Liping Liang, Lingchao Chen, Chunxia Ni, Wenyin Shi, Zhirui Zhou, Shu Chen, Wenjia Zhu, Jiabing Liu, Xianxin Qiu, Wanzun Lin, Junyan Zhang, Zhiyong Qin, Yang Wang

Department of Radiation Oncology Faculty Papers

BACKGROUND: Tumor-treating fields (TTFields) therapy and radiotherapy may have synergistic anti-glioma effect based on preclinical studies. The combination of chemoradiation therapy (CRT) with TTFields therapy has noticeably attracted clinicians' attention. This study aimed to provide insights into the clinical outcomes of patients with newly diagnosed glioblastoma who received either concurrent CRT and TTFields therapy or adjuvant TTFields therapy following CRT. The findings were based on a cohort of patients who were treated at Huashan Hospital (Shanghai, China).

METHODS: This retrospective study analyzed ndGBM patients' clinical outcomes who were treated at Huashan Hospital and received TTFields therapy. Patients were categorized into …

Durable Local Control With Hypofractionated Radiation Therapy For Unresectable Or Metastatic Melanoma, Sydney A Keatts, Aya F Salem, David M Swanson, Ahsan S Farooqi, Andrew J Bishop, Rodabe N Amaria, Jennifer L Mcquade, Isabella C Glitza Oliva, Adi Diab, Roi Weiser, Sarah B Fisher, Ryan P Goepfert, Merrick I Ross, B Ashleigh Guadagnolo, Devarati Mitra

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: As patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location.

MATERIALS AND METHODS: We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12-17 fractions HFRT at …

Ai-Assisted Segmentation Tool For Brain Tumor Mr Image Analysis, Myungeun Lee, Jong Hyo Kim, Wookjin Choi, Ki Hong Lee

Department of Radiation Oncology Faculty Papers

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) …

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 …

Evaluation Of A Balloon Implant For Simultaneous Magnetic Nanoparticle Hyperthermia And High-Dose-Rate Brachytherapy Of Brain Tumor Resection Cavities, Shuying Wan, Dario Rodrigues, Janet Kwiatkowski, Omaditya Khanna, Kevin Judy, Robert Goldstein, Marty Overbeek Bloem, Yan Yu, Sophia Rooks, Wenyin Shi, Mark Hurwitz, Paul Stauffer

Department of Radiation Oncology Faculty Papers

Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs …

Case Report: Durable Response Of Gliomatosis Cerebri With Concurrent Tumor-Treating Fields (Ttfields) And Chemoradiotherapy Treatment, Alex M. Desjarlais, Ryan C. Miller, Ayesha S. Ali, Muneeb Z. Niazi, Louis Cappelli, Jon Glass, Christopher J. Farrell, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Background: Gliomatosis cerebri (GC) is a rare and aggressive form of widely disseminated glioma infiltrating at least 3 lobes of the brain. It is a diffuse pattern of growth seen in glioma rather than a distinct pathological diagnosis based on new Word Health Organization (WHO) classification. Despite this, it is associated with worse prognosis than equally graded gliomas. Tumor treating fields (TTFields) treatment is a more recent advancement in glioma treatment delivered through low energy, intermediate frequency (200 kHz) electromagnetic fields, with multi-modal mechanisms of action. It is Food and Drug Administration (FDA) approved for newly diagnosed and recurrent glioblastoma …

Nrg/Rtog 0837: Randomized, Phase Ii, Double-Blind, Placebo-Controlled Trial Of Chemoradiation With Or Without Cediranib In Newly Diagnosed Glioblastoma, Tracy T. Batchelor, Minhee Won, Arnab Chakravarti, Costas G. Hadjipanayis, Wenyin Shi, Lynn S. Ashby, Volker W. Stieber, H. Ian Robins, Heidi J. Gray, Alfredo Voloschin, John B. Fiveash, Clifford G. Robinson, Ushasree Chamarthy, Young Kwok, Terrence P. Cescon, Anand K. Sharma, Rekha Chaudhary, Mei-Yin Polley, Minesh P. Mehta

Department of Radiation Oncology Faculty Papers

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided …

Efficacy Of Scalp-Sparing Volumetric-Modulated Arc Therapy Approach In Reducing Scalp Radiation Dose For Patients With Glioblastoma: A Cross-Sectional Study, Muneeb Khan Niazi, Olga Russial, Louis Cappelli, Ryan Miller, Yingxuan Chen, Yelena Vakhnenko, Haisong Lui, Wenyin Shi

Department of Radiation Oncology Faculty Papers

BACKGROUND: Radiation is integral to the treatment of glioblastoma (GBM). However, radiation-induced scalp toxicity can negatively impact patients' quality of life. Volumetric modulated arc therapy (VMAT) optimizes the dose to organs at risk (OARs). We hypothesize that a scalp-sparing VMAT (SSV) approach can significantly reduce undesirable doses to the scalp without compromising the target dose.

METHODS: This is a retrospective cross-sectional study of GBM patients who originally received radiation with non-SSV. We contoured the scalp as a 5 mm rind-like structure beneath the skin above the level of the foramen magnum. We replanned our patients using SSV techniques. We compared …

Advances In The Radiological Evaluation Of And Theranostics For Glioblastoma, Grayson W Hooper, Shehbaz Ansari, Jason M Johnson, Daniel T Ginat

Faculty, Staff and Student Publications

Imaging is essential for evaluating patients with glioblastoma. Traditionally a multimodality undertaking, CT, including CT cerebral blood profusion, PET/CT with traditional fluorine-18 fluorodeoxyglucose (18F-FDG), and MRI have been the mainstays for diagnosis and post-therapeutic assessment. However, recent advances in these modalities, in league with the emerging fields of radiomics and theranostics, may prove helpful in improving diagnostic accuracy and treating the disease.

Federated Learning Enables Big Data For Rare Cancer Boundary Detection, Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela Lamontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard Mckinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. Van Der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. Van Den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu'aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, Spyridon Bakas

Department of Radiation Oncology Faculty Papers

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically …

Tumor Treating Fields With Radiation For Glioblastoma: A Narrative Review, Ryan C. Miller, Muneeb Khan Niazi, Olga Russial, Spencer Poiset, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Background and objective: With a phase 3 clinical trial (EF-32, ClinicalTrials.gov: NCT04471844) currently underway examining the potential benefit of concurrent chemoradiation and tumor treating fields (TTFields) for patients with glioblastoma (GBM), we present the following narrative review to highlight the current evidence that supports this approach. The current management paradigm for GBM includes maximal safe surgical resection followed by concurrent chemoradiation with further temozolomide (TMZ) and TTFields used as maintenance therapy. Despite several treatment advances over the past few decades, the overall prognosis remains poor and new strategies are currently under investigation, including the use of chemoradiation concurrently with …

Impact Of Lymphopenia On Survival For Elderly Patients With Glioblastoma: A Secondary Analysis Of The Cctg Ce.6 (Eortc 26062-22061, Trog03.01) Randomized Clinical Trial, Andrew Song, Keyue Ding, Iyad Alnahhas, Normand J Laperriere, James Perry, Warren P Mason, Chad Winch, Chris J O'Callaghan, Johan J Menten, Alba A Brandes, Claire Phillips, Michael F Fay, Ryo Nishikawa, David Osoba, J Gregory Cairncross, Wilson Roa, Wolfgang Wick, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Background: Lymphopenia may lead to worse outcomes for glioblastoma patients. This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on lymphopenia, and effects of lymphopenia on overall survival (OS).

Methods: CCTG CE.6 randomized elderly glioblastoma patients (≥ 65 years) to short-course radiation alone (RT) or short-course radiation with temozolomide (RT + TMZ). Lymphopenia (mild-moderate: grade 1-2; severe: grade 3-4) was defined per CTCAE v3.0, and measured at baseline, 1 week and 4 weeks post-RT. Preselected key factors for analysis included age, sex, ECOG, resection extent, MGMT methylation, Mini-Mental State Examination, and …

Targeting Accuracy Considerations For Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy., Sharmi Biswas, Irina Kapitanova, Sabrina Divekar, Jimm Grimm, Ian J Butterwick, Daniel Garren, Lawrence R Kleinberg, Kristin J Redmond, Michel Lacroix, Anand Mahadevan, Kenneth M Forster

College of Health Professions Faculty Papers

Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of …

Brain Extraction On Mri Scans In Presence Of Diffuse Glioma: Multi-Institutional Performance Evaluation Of Deep Learning Methods And Robust Modality-Agnostic Training, Siddhesh Thakur, Jimit Doshi, Sarthak Pati, Saima Rathore, Chiharu Sako, Michel Bilello, Sung Min Ha, Gaurav Shukla, Adam Flanders, Aikaterini Kotrotsou, Mikhail Milchenko, Spencer Liem, Bs, Gregory S Alexander, Joseph Lombardo, Joshua D Palmer, Pamela Lamontagne, Arash Nazeri, Sanjay Talbar, Uday Kulkarni, Daniel Marcus, Rivka Colen, Christos Davatzikos, Guray Erus, Spyridon Bakas

Department of Radiation Oncology Faculty Papers

Brain extraction, or skull-stripping, is an essential pre-processing step in neuro-imaging that has a direct impact on the quality of all subsequent processing and analyses steps. It is also a key requirement in multi-institutional collaborations to comply with privacy-preserving regulations. Existing automated methods, including Deep Learning (DL) based methods that have obtained state-of-the-art results in recent years, have primarily targeted brain extraction without considering pathologically-affected brains. Accordingly, they perform sub-optimally when applied on magnetic resonance imaging (MRI) brain scans with apparent pathologies such as brain tumors. Furthermore, existing methods focus on using only T1-weighted MRI scans, even though multi-parametric MRI …

Atrx Loss In Pediatric Glioma Results In Epigenetic Dysregulation Of G2/M Checkpoint Maintenance And Sensitivity To Atm Inhibition, Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann

Medical Student Research Symposium

ATRX is a histone chaperone protein recurrently mutated in pediatric glioma. The mechanism which mediates the proliferative advantage of ATRX loss in pediatric glioma remains unexplained. Recent data revealed a distinct pattern of DNA binding sites of the ATRX protein using ChIP-seq in mouse neuronal precursor cells (mNPCs). Using the ATRX peaks identified in p53^-/- mNPCs, we confirmed that ATRX binding sites were significantly enriched in gene promoters (p < 0.0001) and CpG islands (p < 0.0001) compared with random regions. Gene set enrichment (GSE) analysis identified that cell cycle and regulation of cell cycle were among the most significantly enriched gene sets (p=2.52e-16 and 1.61e-9, respectively). We found that ATRX loss resulted in dysfunction of G2/M checkpoint maintenance: (1) ATRX-deficient pediatric glioblastoma (GBM) cells exhibited a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation, and (2) murine GBM cells with ATRX knockdown demonstrated impaired pChk1 signaling on western blot at multiple time points after radiation compared to controls (p=0.0187). Notably, the ATM signaling (pChk2) remained intact in those cells, suggesting a potential therapeutic target. ATRX-deficient mouse cells were uniquely sensitive to ATM inhibitors at 1 uM alongside 8 Gy radiation compared to controls with intact ATRX (AZD0156: p=0.0027 and AZD01390: p=0.0436). Mice intra-cranially implanted with ATRX-deficient GBM cells showed improved survival (n=10, p=0.0018) when treated with AZD0156 combined with radiation. Our findings suggest that ATRX loss in glioma results in unique sensitivity to ATM inhibition via epigenetic dysregulation of G2/M checkpoint maintenance.