Medicine and Health Sciences Commons^™

Use Of A Cancer Registry To Evaluate Patient-Reported Outcomes Of Immune Checkpoint Inhibitors., Heather S L Jim, Sarah L Eisel, Aasha I Hoogland, Sandra Shaw, Jennifer C King, Adam P Dicker

Department of Radiation Oncology Faculty Papers

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, butfew studies have reported on patient-reported outcomes (PROs) outside the context of a clinicaltrial. The goal of the current study was to assess PROs in participants of a lung cancer registry whohad been treated with an ICI. Patients participating in the GO2Foundation’s Lung Cancer Registrywho reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited toparticipate in a survey about their experiences during treatment. Quality of life was evaluated usingthe Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverseevents were evaluated using an item bank generated for ICIs. Internationally, 226 …

Upfront Treatment Of Flt3-Mutated Aml: A Look Back At The Ratify Trial And Beyond., Gina Keiffer, Kimberly L Aderhold, Neil D Palmisiano

Department of Medical Oncology Faculty Papers

In April 2017, following the results of the RATIFY trial (1), midostaurin, a multikinase FLT3 inhibitor, became the first FDA approved targeted agent for the treatment of acute myeloid leukemia (AML) (2). The addition of midostaurin to standard induction therapy with anthracycline and cytarabine (7 + 3) rapidly became the new standard of care for treatment-naïve, fit patients with FLT3-mutated (FLTmut+) AML (3). More recently, gilteritinib, a selective FLT3 inhibitor, showed superiority to chemotherapy in the treatment of relapsed or refractory FLTmut+ AML (4). With two FLT3 inhibitors now approved by the FDA—that is, the more selective gilteritinib and the …

Dimensions Of Misinformation About The Hpv Vaccine On Instagram: Content And Network Analysis Of Social Media Characteristics., Philip M. Massey, Matthew D. Kearney, Michael K. Hauer, Preethi Selvan, Emmanuel Koku, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram.

OBJECTIVE: The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine …

Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl

Department of Medical Oncology Faculty Papers

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients and Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent …

A Phase Ii Study Of The Insulin-Like Growth Factor Type I Receptor Inhibitor Imc-A12 In Patients With Metastatic Uveal Melanoma., Jane Mattei, Alexej Ballhausen, Roland Bassett, Michael Shephard, Chandrani Chattopadhyay, Courtney Hudgens, Michael Tetzlaff, Scott Woodman, Takami Sato, Sapna P Patel

Department of Medical Oncology Faculty Papers

Uveal melanoma is a rare and aggressive malignancy and up to half of all patients will develop metastatic disease despite the effective treatment of the primary tumor. Insulin-like growth factors I/II play a fundamental role in the cell migration, proliferation, and apoptosis. IMC-A12, a mAb specifically targets insulin-like growth factor type I receptor, has shown promise in preclinical studies. We performed a multicenter phase II study for patients with metastatic uveal melanoma administered IMC-A12 10 mg/kg IV every two weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response (proportion of patients with complete or partial response), …

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 …

Molecular Landscape And Actionable Alterations In A Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis For Therapy Choice (Nci-Match)., Keith T Flaherty, Robert J Gray, Alice P Chen, Shuli Li, Lisa M Mcshane, David Patton, Stanley R Hamilton, P Mickey Williams, A John Iafrate, Jeffrey Sklar, Edith P Mitchell, Lyndsay N Harris, Naoko Takebe, David J Sims, Brent Coffey, Tony Fu, Mark Routbort, James A Zwiebel, Larry V Rubinstein, Richard F Little, Carlos L Arteaga, Robert Comis, Jeffrey S Abrams, Peter J O'Dwyer, Barbara A Conley

Department of Medical Oncology Faculty Papers

PURPOSE: Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols.

PATIENTS AND METHODS: Tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with …

Photopsia And Visual Loss In A Patient With Lung Cancer., Eric Shiuey, Sara E. Lally, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling., Rakshamani Tripathi, Zulong Liu, Aditi Jain,, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Department of Medical Oncology Faculty Papers

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2^{nd …}

The Impact Of Prostate Cancer Treatment On Quality Of Life: A Narrative Review With A Focus On Randomized Data., James M Taylor, Victor E. Chen, Ryan C. Miller, Benjamin A. Greenberger

Department of Radiation Oncology Faculty Papers

Despite excellent oncologic outcomes, the management of localized prostate cancer remains complex and is dependent on multiple factors, including patient life expectancy, medical comorbidities, tumor characteristics, and genetic risk factors. Decades of iterative clinical trials have improved the optimization and utilization of surgical and radiation-based modalities, as well as their combinatorial use with anti-androgen and systemic therapies. While cure rates are high and converging on equivalent disease control should an upfront surgical or radiotherapeutic approach be optimized, the long-term side effects of surgical and radiation-based treatments can differ significantly in nature. Decisions regarding the selection of therapy are therefore best …

Early Evidence Of Dose-Dependent Pharmacodynamic Activity Following Treatment With Sy-5609, A Highly Selective And Potent Oral Cdk7 Inhibitor, In Patients With Advanced Solid Tumors, Kyriakos P. Papadopoulos, Manish R. Sharma, Erika Hamilton, Debra Richardson, Babar Bashir, Graeme Hodgson, Nan Ke, Qing Kang-Fortner, Li Zhou, William Zamboni, Hina A. Jolin, Catherine Madigan, Michael J. Kelly, David A. Roth

Department of Medical Oncology Faculty Papers

No abstract provided.

Measurable Residual Disease-Guided Treatment To Prevent Relapse In Acute Myeloid Leukemia And Myelodysplastic Syndrome., Jonathan Pan, Daniel Altman, Lindsay Wilde

Department of Medical Oncology Faculty Papers

No abstract provided.

Comparison Of Outcomes Of Hct In Blast Phase Of Bcr-Abl1- Mpn With De Novo Aml And With Aml Following Mds, Vikas Gupta, Soyoung Kim, Zhen-Huan Hu, Ying Liu, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Shahinaz M Gadalla, Robert Peter Gale, Siddhartha Ganguly, Biju George, Aaron T Gerds, Usama Gergis, Betty K Hamilton, Shahrukh Hashmi, Gerhard C Hildebrandt, Rammurti T Kamble, Tamila Kindwall-Keller, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Richard T Maziarz, Taiga Nishihori, Richard F Olsson, David Rizzieri, Bipin N Savani, Sachiko Seo, Melhem Solh, Jeff Szer, Leo F Verdonck, Baldeep Wirk, Ann Woolfrey, Jean A Yared, Edwin P Alyea, Uday R Popat, Ronald M Sobecks, Bart L Scott, Ryotaro Nakamura, Wael Saber

Department of Medical Oncology Faculty Papers

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1- myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with …

Feasibility Of Removable Balloon Implant For Simultaneous Magnetic Nanoparticle Heating And Hdr Brachytherapy Of Brain Tumor Resection Cavities., Paul R. Stauffer, Dario B. Rodrigues, Robert Goldstein, Thinh Nguyen, Yan Yu, Shuying Wan, Richard Woodward, Michael Gibbs, Ilya L. Vasilchenko, Alexey M. Osintsev, Voichita Bar-Ad, Dennis B. Leeper, Wenyin Shi, Kevin D. Judy, Mark D. Hurwitz

Department of Radiation Oncology Faculty Papers

AIM: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant.

METHODS: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency …

Photodynamic Therapy In Ocular Oncology., Mehdi Mazloumi, Lauren A Dalvin, Seyed-Hossein Abtahi, Negin Yavari, Antonio Yaghy, Arman Mashayekhi, Jerry A Shields, Carol L Shields

Wills Eye Hospital Papers

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.

Breast Carcinoma Metastasis In A Resected Meningioma With Early Diagnosis Of Oligometastatic Disease: A Case Report., Christian Fernandez, Louis Cappelli, Sara Chapin,, Lawrence Kenyon, Christopher J Farrell, Wenyin Shi

Department of Radiation Oncology Faculty Papers

Tumor-to-tumor metastasis describes the ability of primary tumors to metastasize to other primary tumors. These events generally occur in aggressive and widely-metastatic disease, with the appropriate management and significance of these events unknown. A 56-year-old woman with a history of bilateral, localized, invasive lobular breast carcinoma treated with surgery, systemic therapy, and adjuvant radiation presented five and two years post-treatment with progressive neurological symptoms. Imaging revealed an intracranial meningioma, and the patient underwent resection. Pathology revealed metastatic invasive lobular carcinoma cells within the resected meningioma, and the patient was treated with postoperative radiation without sequelae. Subsequent staging scans revealed a …

Early Evidence Of Dose-Dependent Pharmacodynamic Activity Following Treatment With Sy-5609, A Highly Selective And Potent Oral Cdk7 Inhibitor, In Patients With Advanced Solid Tumors, Kyriakos P. Papadopoulos, Manish R. Sharma, Erika Hamilton, Debra Richardson, Babar Bashir, Dejan Juric, Geoffrey Shapiro, Graeme Hodgson, Nan Ke, Anthony D'Ippolito, Liv Johannessen, Qing Kang-Fortner, Li Zhou, Maria Rosario, William Zamboni, Hina A. Jolin, Catherine Madigan, Michael J. Kelly, David A. Roth

Department of Medical Oncology Posters

No abstract provided.

Virtual Connectivity During Quarantine: The Role Of Social Media For Radiation Oncology During Covid-19, Miriam A Knoll, Mudit Chowdhary, Adam Dicker, Thomas Eichler

Kimmel Cancer Center Faculty Papers

No abstract provided.

Announcing The Isev2020 Special Achievement Award Recipients: Andrew Hill And Edit Buzás; And The Recipient Of The Isev2020 Special Education Award: Carolina Soekmadji., Kenneth W Witwer, Lucia R Languino, Alissa M Weaver, Marca H Wauben

Kimmel Cancer Center Faculty Papers

No abstract provided.

Knowledge And Practice Regarding Prostate Cancer Germline Testing Among Urologists: Gaps To Address For Optimal Implementation, Stacy Loeb, Nataliya Byrne, Dawn Walter, Danil V Makarov, David R Wise, Daniel Becker, Veda N Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. …

Soluble Glycoprotein Vi Is A Predictor Of Major Bleeding In Patients With Suspected Heparin-Induced Thrombocytopenia, Allyson M Pishko, Robert K Andrews, Elizabeth E Gardiner, Daniel S Lefler, Adam Cuker

Department of Medical Oncology Faculty Papers

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day …

The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G Pestell, Yunguang Sun, Jun Zhao, Mathew C Casimiro, Zhiping Li, Michael P Lisanti, Peter Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G Pestell

Department of Cancer Biology Faculty Papers

The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1-S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine …

Endogenous Cyclin D1 Promotes The Rate Of Onset And Magnitude Of Mitogenic Signaling Via Akt1 Ser473 Phosphorylation., Ke Chen, Xuanmao Jiao, Agnese Di Rocco, Duanwen Shen, Shaohua Xu, Adam Ertel, Zuoren Yu, Gabriele Di Sante, Min Wang, Zhiping Li, Timothy G Pestell, Mathew C Casimiro, Emmanuel Skordalakes, Samuel Achilefu, Richard G Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrates in the mammary gland is reduced by cyclin D1 genetic deletion and is induced by mammary-gland-targeted cyclin D1 overexpression. Cyclin D1 is associated with Akt1 and augments the rate of onset and maximal cellular Akt1 activity induced by mitogens. Cyclin D1 is identified in a cytoplasmic-membrane-associated pool, and cytoplasmic-membrane-localized cyclin D1-but not nuclear-localized cyclin D1-recapitulates Akt1 …

Translocase Of The Outer Mitochondrial Membrane Complex Subunit 20 (Tomm20) Facilitates Cancer Aggressiveness And Therapeutic Resistance In Chondrosarcoma., Megan E Roche, Zhao Lin, Diana Whitaker-Menezes, Tingting Zhan, Karoly Szuhai, Judith V M G Bovee, John A Abraham, Wei Jiang, Ubaldo Martinez-Outschoorn, Atrayee Basu-Mallick

Department of Medical Oncology Faculty Papers

Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma …

Caring For Aml Patients During The Covid-19 Crisis: An American And Italian Experience., Lindsay Wilde, Md, Alessandro Isidori, Gina Keiffer, Md, Neil D. Palmisiano, Md, Margaret Kasner

Department of Medical Oncology Faculty Papers

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent pandemic have impacted every aspect of oncology care worldwide. Healthcare systems have been forced to rapidly change practices in order to maximize the safety of patients and healthcare providers and preserve scare resources. Patients with acute myeloid leukemia are at increased risk of complications from SARS-CoV-2 not only due to immune compromise related to the malignancy but also due to the acuity of the disease and intensity of treatment. These issues have created unique challenges during this difficult time. In this article, we present the approaches taken …

Dosimetric Differences Between Cesium-131 And Iodine-125 Brachytherapy For The Treatment Of Resected Brain Metastases, Menachem Yondorf, Shahdabul Faraz, Andrew Smith, Albert Sabbas, Bhupesh Parashar, Theodore Schwartz, Gabriella Wernicke

Department of Radiation Oncology Faculty Papers

Purpose: To compare treatment plans and evaluate dosimetric characteristics of permanent cesium-131 (131Cs) vs. iodine-125 (125I) implants used in brain brachytherapy. Material and methods: Twenty-four patients with 131Cs implants from a prospective phase I/II trial were re-planned with 125I implants. In order to evaluate the volume of brain tissue exposed to radiation therapy (RT), the dose volume histogram was generated for both radioisotopes. To evaluate the dosimetric differences of the two radioisotopes we compared homogeneity (HI) and conformity indices (CI), and dose covering 100% (D100), 90% (D90), 80% (D80), and 50% (D50) of the clinical target volume (CTV). Results: At …

Is Host Metabolism The Missing Link To Improving Cancer Outcomes?, Christopher M Wright, Anuradha A. Shastri, Emily K Bongiorno, Ajay Palagani, Ulrich Rodeck, Nicole L Simone

Kimmel Cancer Center Faculty Papers

For the past 100 years, oncologists have relentlessly pursued the destruction of tumor cells by surgical, chemotherapeutic or radiation oncological means. Consistent with this focus, treatment plans are typically based on key characteristics of the tumor itself such as disease site, histology and staging based on local, regional and systemic dissemination. Precision medicine is similarly built on the premise that detailed knowledge of molecular alterations of tumor cells themselves enables better and more effective tumor cell destruction. Recently, host factors within the tumor microenvironment including the vasculature and immune systems have been recognized as modifiers of disease progression and are …

The Effect Of Neighborhood Social Environment On Prostate Cancer Development In Black And White Men At High Risk For Prostate Cancer, Shannon M Lynch, Elizabeth Handorf, Kristen A Sorice, Elizabeth Blackman, Lisa Bealin, Veda N. Giri, Elias Obeid, Camille Ragin, Mary Daly

Department of Medical Oncology Faculty Papers

INTRODUCTION: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment.

MATERIALS AND METHODS: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), …

Chimeric Ad5.F35 Vector Evades Anti-Adenovirus Serotype 5 Neutralization Opposing Gucy2c-Targeted Antitumor Immunity, John C. Flickinger, Jagmohan Singh, Robert D Carlson, Elinor Leong, Trevor R. Baybutt, Joshua Barton, Ellen M. Caparosa, Amanda M. Pattison, Jeff A. Rappaport, Jamin Roh, Tingting Zhan, Babar Bashir, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Adenovirus serotype 5 (Ad5) is a commonly used viral vector for transient delivery of transgenes, primarily for vaccination against pathogen and tumor antigens. However, endemic infections with Ad5 produce virus-specific neutralizing antibodies (NAbs) that limit transgene delivery and constrain target-directed immunity following exposure to Ad5-based vaccines. Indeed, clinical trials have revealed the limitations that virus-specific NAbs impose on the efficacy of Ad5-based vaccines. In that context, the emerging focus on immunological approaches targeting cancer self-antigens or neoepitopes underscores the unmet therapeutic need for more efficacious vaccine vectors.

METHODS: Here, we evaluated the ability of a chimeric adenoviral vector (Ad5.F35) …