Medicine and Health Sciences Commons^™

Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer

Department of Radiation Oncology Faculty Papers

No abstract provided.

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael Chuong, Percy Lee, Daniel Low, Joshua Kim, Kathryn Mittauer, Michael Bassetti, Carri Glide-Hurst, Ann Raldow, Yingli Yang, Lorraine Portelance, Kyle Padgett, Bassem Zaki, Rongxiao Zhang, Hyun Kim, Lauren Henke, Alex Price, Joseph Mancias, Christopher Williams, John Ng, Ryan Pennell, M Raphael Pfeffer, Daphne Levin, Adam Mueller, Karen Mooney, Patrick Kelly, Amish Shah, Luca Boldrini, Lorenzo Placidi, Martin Fuss, Parag Jitendra Parikh

Department of Radiation Oncology Faculty Papers

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

A Survival Analysis Of High-Grade Gliomas In Sub-Himalayan Population Including The Times Of Lockdown During Covid 19 Pandemic: A Single Institutional Experience, Pooja Kalra, Meenu Gupta, Vipul Nautiyal, Ranjeet Kumar, Sanjeev Pandey, Nazia Shirazi, Brijesh Tiwari, Mushtaq Ahmad

Research Symposium

Background and Objectives: High Grade Gliomas are categorised as Grade III and IV and have high mortality rate with poor prognosis. How we should adopt clinical practice in neuro-oncology during Covid 19 Pandemic is another area of scientific exploration . Hypofractionated radiotherapy protocols can be easily utilised in high grade gliomas during Covid 19 pandemic .

Materials and Methods: Retrospective analysis of 147 patients with diagnosis of high-grade gliomas between January 2009 till December 2020 including Covid-19 pandemic lockdown time was done. Age , gender , KPS , symptoms , extent of surgery and use of concurrent temozolamide , were …

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 …

Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Improved Tumor Control Following Radiosensitization With Ultrasound-Sensitive Oxygen Microbubbles And Tumor Mitochondrial Respiration Inhibitors In A Preclinical Model Of Head And Neck Cancer, Quezia Lacerda, Hebah Falatah, Ji-Bin Liu, Corinne Wessner, Brian Oeffinger, Ankit K. Rochani, Dennis B. Leeper, Flemming Forsberg, Joseph M. Curry, Gagan Kaushal, Scott W Keith, Patrick O'Kane, Margaret A Wheatley, John R. Eisenbrey

Department of Radiology Faculty Papers

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. …

High Local Control And Low Ocular Toxicity Using Ultra-Low-Dose “Boom-Boom” Radiotherapy For Indolent Orbital Lymphoma, Sanjna Shelukar, Christian Fernandez, Zeynep Bas, Lydia Komarnicky, Sara E. Lally, Carol L Shields, Adam Binder, Pierluigi Porcu, Onder Alpdogan, Ubaldo Martinez-Outschoorn, Wenyin Shi

Department of Medical Oncology Faculty Papers

Background: The first line definitive treatment for early-stage indolent B-cell lymphoma is radiation therapy (RT). Due to the sensitivity of orbital structures to radiation, ultra-low-dose RT (4 Gy in 2 fractions, "boom-boom") has and been utilized as an attractive option for orbital lymphoma. In this retrospective study, we evaluated the outcome and toxicity of "boom-boom" RT for indolent orbital lymphoma with an emphasis on ophthalmologic toxicity.

Methods: This is a retrospective case series with 17 patients with orbital lymphoma who received boom-boom RT at a single tertiary referral center between January 2017 and June 2022. Medical records, imaging and radiation …

Quantifying The Dosimetric Impact Of Target Margins In The Oligometastatic Setting, Jessica E. Strang

Culminating Experience Projects

Introduction

With advancements in cancer treatment therapies, patients are living longer with oligometastatic disease. These patients may have multiple targets and may be treated in a single isocenter to reduce overall treatment time. However, the most considerable risk of treating multiple lesions in a single isocenter is a geometric miss. It can be challenging to perform daily alignment of multiple lesions creating a need to prioritize one lesion alignment over others or abort treatment.

Methods

This study quantified the dosimetric impact of total lung exposure as the planning target volume (PTV) margin incrementally increased for multiple intrathoracic lesions.

The analysis …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Automating 4dct-Ventilation Imaging Generation Using Ai-Based Advanced Lung Contours, Yingxuan Chen, Sohrab Pahlavan, Paul Jacobs, Farnoush Forghani, Edward Castillo, Richard Castillo, Yevgeniy Vinogradskiy

Conference Presentation Abstracts

Purpose: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional lung. A novel form of lung functional imaging applied for functional avoidance uses 4DCT imaging to calculating 4DCT-based lung ventilation (4DCT-ventilation). The process of generating 4DCT-ventilation images requires advanced lung segmentation (consisting of a standard lung with airway and vasculature removed) which is a manual and time-consuming process. The purpose of this work is to automate 4DCT-ventilation imaging generation using AI-based auto-segmentation techniques for advanced lung contouring.

Methods: 429 patients with 4DCT data from two institutions were used. Three methods …

The Prognostic Significance Of Glucose-6-Phosphate Dehydrogenase As A Biomarker In Head And Neck Squamous Cell Carcinomas Treated With Conventional Chemoradiation, Kenneth H. Barker, Barbara L. Pruetz, Jessica D. Arden, Thomas J. Quinn, George D. Wilson

Posters

INTRODUCTION
The prognosis of patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation can be predicted using p16 as a surrogate biomarker of Human Papilloma Virus (HPV) status, but a subset of patients continues to do poorly despite a positive or negative p16 status. This project attempted to identify another biomarker, glucose-6-phosphate dehydrogenase (G6PD) as a marker for prognosis in HNSCC patients. Radiation induces oxidative damage to destroy tumor cells, and G6PD is a key enzyme involved in protecting cells from oxidative damage. The goal of this project was to identify a prognostic biomarker that would aid …

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

Dissertations & Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We …

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations & Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …

Role Of Surgery In Multifocal Glioblastoma, Syeda Kubra Kishwar Jafri, Syed Sarmad Bukhari, Muhammad Shahzad Shamim

Section of Neurosurgery

The management of multifocal glioblastomas is a point of constant discussion amongst neuro-oncologists. Best outcomes in glioblastoma management come from gross total resection (GTR) followed by concomitant radiation and chemotherapy (CCRT). Multifocal disease is resistant to GTR. Conventional management of these lesion is usually biopsy only followed by CCRT. Recent evidence has shown that there may be some benefit to attempting GTR of the largest lesion whenever safe to do so.

Exosomal Mirnas As Biomarkers For Radiation Toxicity In Breast Cancer Patients, Mina V. Mcginn

Theses and Dissertations

Radiotherapy (RT) is a standard treatment for most breast cancer patients (BCPs), but is often accompanied by acute and late toxic effects in normal tissue. Exosomes are nano vesicles about 30-150nm in size that originate from the endosomal network and are found in most body fluids. Exosomes are a fundamental driver of intercellular communication by transferring proteins, lipids and microRNA (miRNA). Exosomal miRNA (Exo-miRNA) signatures may serve as non-invasive prediction biomarkers of post-radiation toxicities of BCPs. Eighty six BCPs treated in the Radiation Oncology Department were enrolled in an IRB approved study. BCPs were evaluated weekly during RT and at …

Implementation Barriers To Integrating Exercise As Medicine In Oncology: An Ecological Scoping Review, Mary A. Kennedy, Sara Bayes, Robert U. Newton, Yvonne Zissiadis, Nigel Spry, Dennis Taaffe, Nicolas H. Hart, Daniel A. Galvao

Research outputs 2014 to 2021

Purpose

While calls have been made for exercise to become standard practice in oncology, barriers to implementation in real-world settings are not well described. This systematic scoping review aimed to comprehensively describe barriers impeding integration of exercise into routine oncology care within healthcare systems.

Methods

A systematic literature search was conducted across six electronic databases (since 2010) to identify barriers to implementing exercise into real-world settings. An ecological framework was used to classify barriers according to their respective level within the healthcare system.

Results

A total of 1,376 results were retrieved; 50 articles describing implementation barriers in real-world exercise oncology …

Building The Plane While It’S Flying: Implementation Lessons From Integrating A Co-Located Exercise Clinic Into Oncology Care, Mary A. Kennedy, Sara Bayes, Robert U. Newton, Yvonne Zissiadis, Nigel A. Spry, Dennis R. Taaffe, Nicolas H. Hart, Daniel A. Galvão

Research outputs 2022 to 2026

Background:

Despite its therapeutic role during cancer treatment, exercise is not routinely integrated into care and implementation efforts are largely absent from the literature. The aim of this study was to evaluate a strategy to integrate the workflow of a co-located exercise clinic into routine care within a private oncology setting in two clinics in the metropolitan region of Western Australia.

Methods:

This prospective evaluation utilised a mixed methods approach to summarise lessons learned during the implementation of an integrated exercise workflow and supporting implementation plan. Data collection was informed by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Reports …

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 …

Induction Of Hypopituitarism Following Ipilimumab/ Nivolumab Therapy Followed By Radiation In The Treatment Of Metastatic Scalp Melanoma, Joshua K. Salabei, Dhaval Upadhyay, Sripal A. Padam

HCA Healthcare Journal of Medicine

Immune checkpoint inhibitors (ICI) are antagonistic antibodies that block specific immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. With FDA approval, the use of these checkpoint inhibitors has led to long-lasting tumor responses. However, by stimulating the immune system, checkpoint inhibitors can cause immune-related adverse events involving the endocrine organs, among others. Pituitary dysfunction (hypophysitis) leading to secondary adrenal insufficiency, or primary adrenal insufficiency caused by immune checkpoint inhibitors, have been documented. In this report, we present a case of a 70-year-old man with scalp melanoma with metastasis to …

Treatment And Outcomes Of Soft Tissue Sarcoma Of Groin, Hip And Thigh: A Retrospective Review From A Tertiary Care Hospital, Masood Umer, Javeria Saeed, Zaid Ahmed Shamsi, Muhammad Usman Tariq

Section of Orthopaedic Surgery

Objective: To study the frequency of the thigh, hip and groin soft tissue sarcomas and retrospectively analyse the management, treatment results, and outcomes of these uncommon malignant tumours, in a tertiary care hospital of the city of Karachi.
Methodology: Data of soft tissue tumours registered from 2017-2018 was retrieved during January 2019 to March 2019 from Aga Khan University Hospital, Karachi bone and soft tissue tumour registry. A retrospective review was performed and all soft tissue tumour cases treated with surgical intervention (with adjuvant /neoadjuvant therapy) or palliative intention were included.
Results: Total 119 cases of soft tissue tumours (STS) …

Impact Of Flattening Filter-Free Field On Online Adaptive Radiotherapy Using Virtual Couch Shift (Vcs) Technique, Q Liu, J Liang, D Yan

Conference Presentation Abstracts

No abstract provided.

Complete Versus Subtotal Resection Of Paediatric Craniopharyngioma, Wardah Pervez, Saqib Kamran Bakhshi, Farhan A. Mirza, Muhammad Shahzad Shamim

Section of Neurosurgery

Optimal management of craniopharyngioma is challenging and requires multidisciplinary efforts for a successful outcome. The debate over radical versus a conservative resection followed by radiotherapy, continues. Current literature reports no difference in disease freedom and overall survival between the two surgical viewpoints, and favours conservative resection and radiotherapy, leading to lower morbidity and superior functional outcomes.

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 …

Target Treatment With Stereotactic Radiation For Recurrent Gliomas, Ayesha Ali, Victor E. Chen, Claire Zurlo, James M Taylor, Christian Fernandez, Wenyin Shi

Department of Radiation Oncology Faculty Papers

High grade gliomas (HGG) have a propensity to recur locally and have poor outcomes. As such, safe and effective treatment is paramount. Target treatment with stereotactic radiation allows safe re-irradiation through minimizing normal brain tissue radiation due to its high precision. In this review, we evaluated the clinical experiences using SRS and FSRT for re-irradiation in HGG. We report the radiobiological advantages and disadvantages of both modalities as well as the safety and efficacy published in current literature.

A Systematic Review Of Home-Based Dietary Interventions During Radiation Therapy For Cancer., Taylor H Allenby, Megan L Crenshaw, Katlynn Mathis, Colin E Champ, Nicole L Simone, Kathryn H Schmitz, Leila T Tchelebi, Nicholas G Zaorsky

Department of Radiation Oncology Faculty Papers

Purpose: Our objectives are to assess (1) the acceptability and feasibility of dietary interventions for patients undergoing radiation therapy (RT), and (2) the impact of dietary interventions on patient reported outcomes, toxicities, and survival.

Methods: A PICOS/PRISMA/MOOSE selection protocol was used to include articles that evaluate adding dietary interventions to patients receiving RT. Acceptability was defined as (# accepting/# approached); feasibility was (# completing/# approached). Patient-reported outcomes were reported based on questionnaires used in each study and survival was measured from the date of diagnosis until death in each study. Level of evidence was assessed with Center for Evidence-Based Medicine …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

Case Report: Co-Existence Of Brca2 And Palb2 Germline Mutations In Familial Prostate Cancer With Solitary Lung Metastasis., Tang Tang, Lin-Ang Wang, Peng Wang, Dali Tong, Gaolei Liu, Jun Zhang, Nan Dai, Yao Zhang, Gang Yuan, Kyla Geary, Dianzheng Zhang, Qiuli Liu, Jun Jiang

PCOM Scholarly Papers

Background: Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions.

Methods: Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband's peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband's family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue.

Results: Two previously unreported germline mutations in the DDR pathway,

Conclusions: The newly …

Examining The Role Of Metabolic Pathways As Therapeutic Modalities For Triple Negative Breast Cancer, Jeremy Andrew Johnson

Theses and Dissertations--Toxicology and Cancer Biology

Triple negative breast cancer (TNBC) comprises 15-20% of breast cancers, affects a younger patient population than other subtypes, and is very aggressive. TNBC is comprised of a diverse group of tumors that have proven refractory to targeted therapy and can be difficult to treat. Patients generally receive neoadjuvant chemotherapy (NAC), surgery, and radiotherapy. The standard of care for NAC includes a taxane, an anthracycline, and/or cyclophosphamide, and administration of NAC has resulted in pathological complete response (pCR) in 30-40% of patients. However, a majority of TNBC patients will not reach pCR and instead have residual disease (RD), which is associated …

Spatially Fractionated Radiation Therapy: History, Present And The Future, Weisi Yan, Mohammad K. Khan, Xiaodong Wu, Charles B. Simone Ii, Jiajin Fan, Eric Gressen, Xin Zhang, Charles L. Limoli, Houda Bahig, Slavisa Tubin, Waleed F. Mourad

Department of Radiation Oncology Faculty Papers

No abstract provided.

Combined Modality Therapies For High-Risk Prostate Cancer: Narrative Review Of Current Understanding And New Directions., Benjamin A. Greenberger, Victor E. Chen, Robert B. Den

Department of Radiation Oncology Faculty Papers

Despite the many prospective randomized trials that have been available in the past decade regarding the optimization of radiation, hormonal, and surgical therapies for high-risk prostate cancer (PCa), many questions remain. There is currently a lack of level I evidence regarding the relative efficacy of radical prostatectomy (RP) followed by adjuvant radiation compared to radiation therapy (RT) combined with androgen deprivation therapy (ADT) for high-risk PCa. Current retrospective series have also described an improvement in biochemical outcomes and PCa-specific mortality through the use of augmented radiation strategies incorporating brachytherapy. The relative efficacy of modern augmented RT compared to RP is …