Medicine and Health Sciences Commons^™

Personalized Nutrition As A Key Contributor To Improving Radiation Response In Breast Cancer, Anuradha A. Shastri, Joseph Lombardo, Samantha C Okere, Stephanie Higgins, Brittany C Smith, Tiziana Deangelis, Ajay Palagani, Kamryn Hines, Daniel A. Monti, Stella Volpe, Edith P. Mitchell, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Understanding metabolic and immune regulation inherent to patient populations is key to improving the radiation response for our patients. To date, radiation therapy regimens are prescribed based on tumor type and stage. Patient populations who are noted to have a poor response to radiation such as those of African American descent, those who have obesity or metabolic syndrome, or senior adult oncology patients, should be considered for concurrent therapies with radiation that will improve response. Here, we explore these populations of breast cancer patients, who frequently display radiation resistance and increased mortality rates, and identify the molecular underpinnings that are, …

Development Of A Financial Toxicity Screening Tool For Radiation Oncology: A Secondary Analysis Of A Pilot Prospective Patient-Reported Outcomes Study, Rahul N Prasad, Tejash Patel, Scott W Keith, Harriet Eldredge-Hindy, Scot A Fisher, Joshua D Palmer

Department of Radiation Oncology Faculty Papers

Purpose: Financial toxicity is highly prevalent in oncology. Early identification of at-risk patients is essential because financial toxicity is associated with inferior outcomes. Validated general oncology screening tools are cumbersome and not specific to challenges related to radiation therapy, such as daily treatments. In the population of radiation oncology patients, no standardized, validated, rapid screening tool exists. We sought to develop a rapid, no-cost, and reliable financial-toxicity screening tool for clinical radiation oncology.

Methods and materials: We retrospectively analyzed data from a prospective survey study conducted at a large referral center with a heterogeneous population. Before treatment, a 25-item modified …

Feasibility Evaluation Of Metamaterial Microwave Sensors For Non-Invasive Blood Glucose Monitoring, Lukas Malena, Ondrej Fiser, Paul R. Stauffer, Tomas Drizdal, Jan Vrba, David Vrba

Department of Radiation Oncology Faculty Papers

The use of microwave technology is currently under investigation for non-invasive estimation of glycemia in patients with diabetes. Due to their construction, metamaterial (MTM)-based sensors have the potential to provide higher sensitivity of the phase shift of the S21 parameter (∠S21 ) to changes in glucose concentration compared to standard microstrip transmission line (MSTL)-based sensors. In this study, a MSTL sensor and three MTM sensors with 5, 7, and 9 MTM unit cells are exposed to liquid phantoms with different dielectric properties mimicking a change in blood glucose concentration from 0 to 14 mmol/L. Numerical models were created for the …

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 …

Conservatively Managed Chronic Bronchopleural Fistula After Lung Cancer Tri-Modality Therapy: A Case Report, Nilanjan Haldar, Christian Fernandez, Nathaniel R. Evans Iii, Maria Werner-Wasik

Division of Cardiology Faculty Papers

No abstract provided.

Interactive Machine Learning-Based Multi-Label Segmentation Of Solid Tumors And Organs, Dimitrios Bounias, Ashish Singh, Spyridon Bakas, Sarthak Pati, Saima Rathore, Hamed Akbari, Michel Bilello, Benjamin Greenberger, Joseph Lombardo, Rhea Chitalia, Nariman Jahani, Aimilia Gastounioti, Michelle Hershman, Leonid Roshkovan, Sharyn Katz, Bardia Yousefi, Carolyn Lou, Amber Simpson, Richard Do, Russell Shinohara, Despina Kontos, Konstantina Nikita, Christos Davatzikos

Department of Radiation Oncology Faculty Papers

We seek the development and evaluation of a fast, accurate, and consistent method for general-purpose segmentation, based on interactive machine learning (IML). To validate our method, we identified retrospective cohorts of 20 brain, 50 breast, and 50 lung cancer patients, as well as 20 spleen scans, with corresponding ground truth annotations. Utilizing very brief user training annotations and the adaptive geodesic distance transform, an ensemble of SVMs is trained, providing a patient-specific model applied to the whole image. Two experts segmented each cohort twice with our method and twice manually. The IML method was faster than manual annotation by 53.1% …

Estimating The Tolerance Of Brachial Plexus To Hypofractionated Stereotactic Body Radiotherapy: A Modelling-Based Approach From Clinical Experience., Irina Kapitanova, Sharmi Biswas, Sabrina Divekar, Eric J. Kemmerer, Robert A. Rostock, Kenneth M Forster, Rachel J. Grimm, Carla J Scofield, Jimm Grimm, Bahman Emami, Anand Mahadevan

Department of Radiation Oncology Faculty Papers

BACKGROUND: Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor.

METHODS: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies …

Comparative Analysis Of 1152 African-American And European-American Men With Prostate Cancer Identifies Distinct Genomic And Immunological Differences., Walter Rayford, Alp Tuna Beksac, Jordan Alger, Mohammed Alshalalfa, Mohsen Ahmed, Irtaza Khan, Ugo G. Falagario, Yang Liu, Elai Davicioni, Daniel E. Spratt, Edward M. Schaeffer, Felix Y. Feng, Brandon Mahal, Paul L Nguyen, Robert B. Den, Mark D. Greenberger, Randy Bradley, Justin M. Watson, Matthew Beamer, Lambros Stamatakis, Darrell J. Carmen, Shivanshu Awasthi, Jonathan Hwang, Rachel Weil, Harri Merisaari, Nihal Mohamed, Leslie A. Deane, Dimple Chakravarty, Kamlesh K. Yadav, Kosj Yamoah, Sujit S. Nair, Ashutosh K. Tewari

Department of Radiation Oncology Faculty Papers

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Nbtxr3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across A Large Panel Of Human Cancer Models., Ping Zhang, Julie Marill, Audrey Darmon, Naeemunnisa Mohamed Anesary, Bo Lu, Md, Sébastien Paris

Department of Radiation Oncology Faculty Papers

Purpose: The side effects of radiotherapy induced on healthy tissue limit its use. To overcome this issue and fully exploit the potential of radiotherapy to treat cancers, the first-in-class radioenhancer NBTXR3 (functionalized hafnium oxide nanoparticles) has been designed to amplify the effects of radiotherapy.

Patients and Methods: Thanks to its physical mode of action, NBTXR3 has the potential to be used to treat any type of solid tumor. Here we demonstrate that NBTXR3 can be used to treat a wide variety of solid cancers. For this, we evaluated different parameters on a large panel of human cancer models, such as …

Targeting Resistance To Radiation-Immunotherapy In Cold Hnsccs By Modulating The Treg-Dendritic Cell Axis., Michael W. Knitz, Thomas E. Bickett, Laurel B. Darragh, Ayman J. Oweida, Shilpa Bhatia, Benjamin Van Court, Shiv Bhuvane, Miles Piper, Jacob Gadwa, Adam C. Mueller, Diemmy Nguyen, Varuna Nangia, Douglas G. Osborne, Xiyuan Bai, Sarah E. Ferrara, Mary-Keara Boss, Andrew Goodspeed, Matthew A. Burchill, Beth A. Jirón Tamburini, Edward D. Chan, Curtis R. Pickering, Eric T. Clambey, Sana D. Karam

Department of Radiation Oncology Faculty Papers

BACKGROUND: Numerous trials combining radiation therapy (RT) and immunotherapy in head and neck squamous cell carcinoma (HNSCC) are failing. Using preclinical immune cold models of HNSCC resistant to RT-immune checkpoint inhibitors, we investigate therapeutic approaches of overcoming such resistance by examining the differential microenvironmental response to RT.

METHODS: We subjected two HPV-negative orthotopic mouse models of HNSCC to combination RT, regulatory T cells (Treg) depletion, and/or CD137 agonism. Tumor growth was measured and intratumorous and lymph node immune populations were compared among treatment groups. Human gene sets, genetically engineered mouse models DEREG and BATF3-/-, flow and time-of-flight cytometry, RNA-Seq, …

Initial Clinical Experience Of Mr-Guided Radiotherapy For Non-Small Cell Lung Cancer., Cathryn B. Crockett, Pamela Samson, Robert Chuter, Michael Dubec, Corinne Faivre-Finn, Olga L. Green, Sara L. Hackett, Fiona Mcdonald, Clifford Robinson, Anna-Maria Shiarli, Michael W Straza, Joost J.C. Verhoeff, Maria Werner-Wasik, Gregory Vlacich, David Cobben

Department of Radiation Oncology Faculty Papers

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and …

High-Dose-Rate Brachytherapy For The Treatment Of Basal And Squamous Cell Carcinomas On Sensitive Areas Of The Face: A Report Of Clinical Outcomes And Acute And Subacute Toxicities, James M. Taylor, Bahar Dasgeb, Spencer Liem, Ayesha Ali, Amy Harrison, Mitchell Finkelstein, Jisun Cha, Rani Anne, Steven Greenbaum, William Sherwin, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Purpose Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face.

Methods and Materials Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos …

Stereotactic Body Radiation Therapy (Sbrt) For Patients With Stage I Non-Small Cell Lung Cancer Is Applicable To More Tumors Than Sublobar Resection, Andrew Song, Nathaniel R. Evans Iii, Scott W. Cowan, Jenny Guo, Tingting Zhan, Bo Lu, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

Background: Virtually all patients with medically inoperable stage I non-small cell lung cancer (NSCLC) can receive stereotactic body radiation therapy. However, the percentage of such patients in whom sublobar resection is technically feasible is unknown. This discrepancy can confound clinical trial eligibility and designs comparing stereotactic body radiation therapy vs. sublobar resection.

Methods: A total of 137 patients treated with stereotactic body radiation therapy for lung lesions (3/2013-11/2017) underwent retrospective review. Diagnostic CT chest and PET/CT images, stereotactic body radiation therapy dates, and demographic data were collected on 100 of 137 patients. Two experienced board-certified thoracic surgeons independently reviewed anonymized …

Mir-21 Plays A Dual Role In Tumor Formation And Cytotoxic Response In Breast Tumors, Tu Dan, Anuradha A. Shastri, Ajay Palagani, Simone Buraschi, Thomas Neill, Jason E Savage, Aastha Kapoor, Tiziana Deangelis, Sankar Addya, Kevin Camphausen, Renato V. Iozzo, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Breast cancer (BrCa) relies on specific microRNAs to drive disease progression. Oncogenic miR-21 is upregulated in many cancers, including BrCa, and is associated with poor survival and treatment resistance. We sought to determine the role of miR-21 in BrCa tumor initiation, progression and treatment response. In a triple-negative BrCa model, radiation exposure increased miR-21 in both primary tumor and metastases. In vitro, miR-21 knockdown decreased survival in all BrCa subtypes in the presence of radiation. The role of miR-21 in BrCa initiation was evaluated by implanting wild-type miR-21 BrCa cells into genetically engineered mouse models where miR-21 was intact, heterozygous …

Combined High-Dose Lattice Radiation Therapy And Immune Checkpoint Blockade For Advanced Bulky Tumors: The Concept And A Case Report, Liuqing Jiang, Xiaobo Li, Jianping Zhang, Wenyao Li, Fangfen Dong, Cheng Chen, Qingliang Lin, Chonglin Zhang, Fen Zheng, Weisi Yan, Yi Zheng, Xiaodong Wu, Benhua Xu

Department of Radiation Oncology Faculty Papers

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. …

Safety And Efficacy Of Hypofractionated Stereotactic Radiosurgery For High-Grade Gliomas At First Recurrence: A Single-Center Experience., Yun Guan, Ji Xiong, Mingyuan Pan, Wenyin Shi, Jing Li, Huaguang Zhu, Xiu Gong, Chao Li, Guanghai Mei, Xiaoxia Liu, Li Pan, Jiazhong Dai, Yang Wang, Enmin Wang, Xin Wang

Department of Radiation Oncology Faculty Papers

BACKGROUND: The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.

METHODS: Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of …

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 …