Medicine and Health Sciences Commons^™

Temporal Considerations In Brain Metastases Radiation Therapy: The Intersection Of Chronobiology And Patient Profiles, Nicolas Nelson, Sara Burke, Louis Cappelli, Lauren Matlack, Alexandria Smith, Noelle Francois, Joseph Lombardo, Yash Shah, Kuang-Yi Wen, Ayesha A Shafi, Nicole Simone

Department of Radiation Oncology Faculty Papers

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival …

Isoform Alterations In The Ubiquitination Machinery Impacting Gastrointestinal Malignancies, Srimathi Kasturirangan, Derek Nancarrow, Ayush Shah, Kiran Lagisetty, Theodore Lawrence, David Beer, Dipankar Ray

Department of Medicine Faculty Papers

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied. Characterizing these changes could be instrumental in improving cancer outcomes via the identification of novel biomarkers and targetable signaling pathways. In this review, we …

Integrating Primary Care, Shared Decision Making, And Community Engagement To Facilitate Equitable Access To Multi-Cancer Early Detection Clinical Trials, Cheryl L. Thompson, Adam H. Buchanan, Ronald E. Myers, David S. Weinberg

Department of Medical Oncology Faculty Papers

Effective implementation of cancer screening programs can reduce disease-specific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is sub-optimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many …

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

Department of Radiation Oncology Faculty Papers

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

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

Social Needs Risk And Patient Outcomes With Supportive Oncology Care, Rebecca Cammy, Lcsw, Joshua Banks, Ma

Department of Medical Oncology Posters

Objective

This study utilized social risk data in the electronic heath record collected in routine clinical practice and examined relationships with supportive oncology care contacts and patient outcomes.

Prognostic Properties Of Kras Gene Mutation Subtypes In Resected Pancreatic Cancer, Faria Nusrat, Eliyahu Gorgov, Md, Wilbur Bowne, Md, Obehioye Isesele, Akshay Khanna, Harish Lavu, Md, Aditi Jain, Phd, Charles J. Yeo, Md, Avinoam Nevler, Md

Alpha Omega Alpha Research Symposium Posters

Introduction

• Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and therapy-resistant cancer with an overall 5-year survival rate of almost 12%, making it among the most lethal of all major cancers.¹
• PDAC has a distinct genomic profile, with somatic KRAS protooncogene mutations in ~90% of cases.^2,3
• Current literature has not reached a consensus on disease prognosis based on KRAS mutation subtype.^2-5

Therapeutic Antibodies For The Prevention And Treatment Of Cancer, Mukesh Kumar, Akansha Jalota, Sushil Kumar Sahu, Shabirul Haque

Department of Medical Oncology Faculty Papers

The developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the antibody, isotype, affinity, avidity and mechanism of action. With better understanding of mechanism of cancer progression and immune manipulation, recombinant formats of antibodies are used to develop therapeutic modalities for manipulating the immune cells of patients by targeting specific molecules to control the disease. These molecules have been successful in minimizing the side effects instead caused by small molecules or systemic chemotherapy but because of the developing therapeutic resistance against …

Chlormethine Gel In Combination With Other Therapies For Treatment Of Mycosis Fungoides: A Review With Patient Cases, Marco Ardigò, Neda Nikbakht, Miriam Teoli, Laura Gleason, Liliana Crisan, Christiane Querfeld

Department of Dermatology and Cutaneous Biology Faculty Papers

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients …

Addressing Burden In Caregivers Of Older Adults With Cancer, Lora Rhodes, Lcsw, Kristine Swartz, Md, Caroline Glavin, Lsw, Charlotte Zuber, Kuang-Yi Wen, Phd

Department of Medical Oncology Posters

Background

Forty-two million adults in the United States are providing unpaid care for a family member or friend over the age of 50. For approximately 2.5 million of these caregivers, cancer is the primary illness or disability of their care recipient (National Alliance for Caregiving and AARP, 2020). As baby boomers continue to age, and the number of cancer survivors continues to increase, the need for informal caregivers will expand exponentially.

While Comprehensive Geriatric Assessment (CGA) is recommended for older patients with cancer and distress screening is recommended for all cancer patients, there are currently no recommendations regarding screening for …

Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson

Kimmel Cancer Center Faculty Papers

BACKGROUND: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.

METHODS: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, …

Prt543, A Protein Arginine Methyltransferase 5 Inhibitor, In Patients With Advanced Adenoid Cystic Carcinoma: An Open-Label, Phase I Dose-Expansion Study, Renata Ferrarotto, Paul Swiecicki, Dan Zandberg, Robert Baiocchi, Robert Wesolowski, Cristina Rodriguez, Meredith Mckean, Hyunseok Kang, Varun Monga, Rajneesh Nath, Neil Palmisiano, Naveen Babbar, William Sun, Glenn Hanna

Department of Medical Oncology Faculty Papers

OBJECTIVES: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

MATERIALS AND METHODS: This phase I multicentre, open-label, sequential-cohort, dose-escalation and dose-expansion study (NCT03886831) enrolled patients with advanced solid tumours and select haematologic malignancies. Dose-escalation study design and results were reported previously. In the dose expansion, patients with R/M ACC …

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 …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance And Immune Evasion In Lethal Prostate Cancer, Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal, Daniel P. Petrylak, William Kevin Kelly, E. Premkumar Reddy, Liguo Wang, Matthew J. Schiewer, Amaia Lujambio, Jeffrey Karnes, Karen E. Knudsen, Carlos Cordon-Cardo, Haidong Dong, Haojie Huang, Arkaitz Carracedo, Yujin Hoshida, Veronica Rodriguez-Bravo, Josep Domingo-Domenech

Department of Medical Oncology Faculty Papers

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif …

Identification Of Ct-Based Non-Invasive Radiomic Biomarkers For Overall Survival Prediction In Oral Cavity Squamous Cell Carcinoma, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Ranee Mehra, Daria A. Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

This study addresses the limited non-invasive tools for Oral Cavity Squamous Cell Carcinoma (OSCC) survival prediction by identifying Computed Tomography (CT)-based biomarkers to improve prognosis prediction. A retrospective analysis was conducted on data from 149 OSCC patients, including CT radiomics and clinical information. An ensemble approach involving correlation analysis, score screening, and the Sparse-L1 algorithm was used to select functional features, which were then used to build Cox Proportional Hazards models (CPH). Our CPH achieved a 0.70 concordance index in testing. The model identified two CT-based radiomics features, Gradient-Neighboring-Gray-Tone-Difference-Matrix-Strength (GNS) and normalized-Wavelet-LLL-Gray-Level-Dependence-Matrix-Large-Dependence-High-Gray-Level-Emphasis (HLE), as well as stage and alcohol usage, …

Cancer Disparities In Southeast Asia: Intersectionality And A Call To Action, Erin Jay G. Feliciano, Frances Dominique V. Ho, Kaisin Yee, Joseph A. Paguio, Michelle Ann B. Eala, Janine Patricia G. Robredo, Kenrick Ng, Jasmine Lim, Khin Thuzar Pyone, Catherine A. Peralta, Jerickson Abbie Flores, J. Seth Yao, Patricia Mae G. Santos, Christian Daniel U. Ang, Gideon Lasco, Jeffrey Shi Kai Chan, Gary Tse, Enrico D. Tangco, T. Peter Kingham, Imjai Chitapanarux, Nirmala Bhoo-Pathy, Gerardo D. Legaspi, Edward Christopher Dee

Einstein Health Papers

No abstract provided.

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 …

Intensity Modulated Radiation Therapy With Stereotactic Body Radiation Therapy Boost For Unfavorable Prostate Cancer: Five-Year Outcomes, Michael Carrasquilla, Tamir Sholklapper, Abigail Pepin, Nicole Hodgins, Siyuan Lei, Abdul Rashid, Malika Danner, Alan Zwart, Grecia Bolanos, Marilyn Ayoob, Thomas Yung, Nima Aghdam, Brian Collins, Simeng Suy, Deepak Kumar, Ryan Hankins, Keith Kowalczyk, Nancy Dawson, Sean Collins

Einstein Health Papers

PURPOSE: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.

MATERIALS AND METHODS: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided …

Clinical And Dosimetric Impact Of 2d Kv Motion Monitoring And Intervention In Liver Stereotactic Body Radiation Therapy., Andrew Santoso, Yevgeniy Vinogradskiy, Tyler Robin, Karyn Goodman, Tracey Schefter, Moyed Miften, Bernard Jones

Department of Radiation Oncology Faculty Papers

PURPOSE: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose.

METHODS AND MATERIALS: Data from 33 patients treated with 41 courses …

Atm Deficiency Confers Specific Therapeutic Vulnerabilities In Bladder Cancer, Yuzhen Zhou, Judit Börcsök, Elio Adib, Sophia C. Kamran, Alexander J. Neil, Konrad Stawiski, Dory Freeman, Dag Rune Stormoen, Zsofia Sztupinszki, Amruta Samant, Amin Nassar, Raie T. Bekele, Timothy Hanlon, Henkel Valentine, Ilana Epstein, Bijaya Sharma, Kristen Felt, Philip Abbosh, Chin-Lee Wu, Jason A. Efstathiou, David T. Miyamoto, William Anderson, Zoltan Szallasi, Kent W. Mouw

Einstein Health Papers

Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss …

Allogeneic Hematopoietic Cell Transplantation For Blastic Plasmacytoid Dendritic Cell Neoplasm: A Cibmtr Analysis, Hemant S. Murthy, Mei-Jie Zhang, Karen Chen, Sairah Ahmed, Uday Deotare, Siddhartha Ganguly, Ankit Kansagra, Fotios V. Michelis, Taiga Nishihori, Mrinal Patnaik, Muhammad Bilal Abid, Mahmoud Aljurf, Yasuyuki Arai, Ulrike Bacher, Talha Badar, Sherif M. Badawy, Karen Ballen, Minoo Battiwalla, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Valerie I. Brown, Rodrigo Martino, Jean-Yves Cahn, Paul Castillo, Jan Cerny, Saurabh Chhabra, Edward Copelan, Andrew Daly, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, César O. Freytes, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Omer Jamy, Jacinth Joseph, Christopher G. Kanakry, Nandita Khera, Maxwell M. Krem, Yachiyo Kuwatsuka, Hillard M. Lazarus, Lazaros J. Lekakis, Hongtao Liu, Dipenkumar Modi, Pashna N. Munshi, Alberto Mussetti, Neil D. Palmisiano, Sagar S. Patel, David A. Rizzieri, Sachiko Seo, Mithun Vinod Shah, Akshay Sharma, Melhm Sohl, Scott R. Solomon, Matthew Ulrickson, Celalettin Ustun, Marjolein Van Der Poel, Leo F. Verdonck, John L. Wagner, Trent Wang, Baldeep Wirk, Amer Zeidan, Mark Litzow, Partow Kebriaei, Christopher S. Hourigan, Daniel J. Weisdorf, Wael Saber, Mohamed A. Kharfan-Dabaja

Department of Medical Oncology Faculty Papers

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), …

Primary Care Patient Interest In Multi-Cancer Early Detection For Cancer Screening, Ronald Myers, Mie Hallman, Ayako Shimada, Melissa Dicarlo, Kaitlyn Davis, William Leach, Hattie Jackson, Amanda Indictor, Christopher Chambers

Department of Medical Oncology Faculty Papers

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Feasibility Of A Text Messaging-Integrated And Chatbot-Interfaced Self-Management Program For Symptom Control In Patients With Gastrointestinal Cancer Undergoing Chemotherapy: Pilot Mixed Methods Study, Sameh Gomaa, James Posey, Babar Bashir, Atrayee Mallick, Eleanor Vanderklok, Max Schnoll, Tingting Zhan, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

BACKGROUND: Outpatient chemotherapy often leaves patients to grapple with a range of complex side effects at home. Leveraging tailored evidence-based content to monitor and manage these symptoms remains an untapped potential among patients with gastrointestinal (GI) cancer.

OBJECTIVE: This study aims to bridge the gap in outpatient chemotherapy care by integrating a cutting-edge text messaging system with a chatbot interface. This approach seeks to enable real-time monitoring and proactive management of side effects in patients with GI cancer undergoing intravenous chemotherapy.

METHODS: Real-Time Chemotherapy-Associated Side Effects Monitoring Supportive System (RT-CAMSS) was developed iteratively, incorporating patient-centered inputs and evidence-based information. It …

Preoperative 18f-Fdg Pet/Ct And Ct Radiomics For Identifying Aggressive Histopathological Subtypes In Early Stage Lung Adenocarcinoma, Wookjin Choi, Chia-Ju Liu, Sadegh Riyahi Alam, Jung Hun Oh, Raj Vaghjiani, John Humm, Wolfgang Weber, Prasad Adusumilli, Joseph Deasy, Wei Lu

Department of Radiation Oncology Faculty Papers

Lung adenocarcinoma (ADC) is the most common non-small cell lung cancer. Surgical resection is the primary treatment for early-stage lung ADC while lung-sparing surgery is an alternative for non-aggressive cases. Identifying histopathologic subtypes before surgery helps determine the optimal surgical approach. Predominantly solid or micropapillary (MIP) subtypes are aggressive and associated with a higher likelihood of recurrence and metastasis and lower survival rates. This study aims to non-invasively identify these aggressive subtypes using preoperative ¹⁸F-FDG PET/CT and diagnostic CT radiomics analysis. We retrospectively studied 119 patients with stage I lung ADC and tumors ≤ 2 cm, where 23 had …

A Multicenter Study Validates The Who 2022 Classification For Conjunctival Melanocytic Intraepithelial Lesions With Clinical And Prognostic Relevance, Hardeep Singh Mudhar, Yamini Krishna, Simon Cross, Claudia Auw-Haedrich, Raymond Barnhill, Svetlana Cherepanoff, Ralph Eagle, James Farmer, Robert Folberg, Hans Grossniklaus, Martina C. Herwig-Carl, Martin Hyrcza, Sandra Lassalle, Karin U. Loeffler, Alexandre Moulin, Tatyana Milman, Robert M. Verdijk, Steffen Heegaard, Sarah E. Coupland

Wills Eye Hospital Papers

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology …

Individual- And Neighborhood-Level Characteristics Of Lung Cancer Screening Participants Undergoing Telemedicine Shared Decision Making, Christine S. Shusted, Hee-Soon Juon, Brooke Ruane, Brian M. Till, Charnita Zeigler-Johnson, Russell K. Mcintire, Tyler Grenda, Olugbenga Okusanya, Nathaniel R. Evans, Gregory C. Kane, Julie Barta

Division of Pulmonary and Critical Care Medicine Faculty Papers

BACKGROUND: Although lung cancer screening (LCS) for high-risk individuals reduces lung cancer mortality in clinical trial settings, many questions remain about how to implement high-quality LCS in real-world programs. With the increasing use of telemedicine in healthcare, studies examining this approach in the context of LCS are urgently needed. We aimed to identify sociodemographic and other factors associated with screening completion among individuals undergoing telemedicine Shared Decision Making (SDM) for LCS.

METHODS: This retrospective study examined patients who completed Shared Decision Making (SDM) via telemedicine between May 4, 2020 - March 18, 2021 in a centralized LCS program. Individuals were …

Varenicline Combined With Oral Nicotine Replacement Therapy And Smartphone-Based Medication Reminders For Smoking Cessation: Feasibility Randomized Controlled Trial, Munjireen Sifat, Emily Hébert, Jasjit Ahluwalia, Michael Businelle, Joseph Waring, Summer Frank-Pearce, Chase Bryer, Lizbeth Benson, Stefani Madison, Lourdes Planas, Irina Baranskaya, Darla Kendzor

Department of Medical Oncology Faculty Papers

BACKGROUND: Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. In addition, smoking cessation medication adherence is often poor, thus, challenging the ability to evaluate medication efficacy.

OBJECTIVE: This study examined the effects of combined varenicline and oral NRT and smartphone medication reminders on pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment.

METHODS: A 2×2 factorial design was used. Participants (N=34) were randomized to (1) varenicline + oral NRT (VAR+NRT) or varenicline alone (VAR) and (2) smartphone medication reminder messages …

Impacting T-Cell Fitness In Multiple Myeloma: Potential Roles For Selinexor And Xpo1 Inhibitors, Adam Binder, Christopher Walker, Tomer Mark, Muhamed Baljevic

Department of Medical Oncology Faculty Papers

Competent T-cells with sufficient levels of fitness combat cancer formation and progression. In multiple myeloma (MM), T-cell exhaustion is caused by several factors including tumor burden, constant immune activation due to chronic disease, age, nutritional status, and certain MM treatments such as alkylating agents and proteasome inhibitors. Many currently used therapies, including bispecific T-cell engagers, anti-CD38 antibodies, proteasome inhibitors, and CART-cells, directly or indirectly depend on the anti-cancer activity of T-cells. Reduced T-cell fitness not only diminishes immune defenses, increasing patient susceptibility to opportunistic infections, but can impact effectiveness MM therapy effectiveness, bringing into focus sequencing strategies that could modulate …

A Phase I Trial Of Sirolimus With "7&3" Induction Chemotherapy In Patients With Newly Diagnosed Acute Myeloid Leukemia, Neil Palmisiano, Grace Jeschke, Lindsay Wilde, Onder Alpdogan, Matthew Carabasi, Joanne Filicko-O'Hara, Dolores Grosso, Thomas Klumpp, Ubaldo Martinez, John L Wagner, Martin Carroll, Alexander Perl, Margaret Kasner

Department of Medicine Faculty Papers

Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this combination in newly diagnosed AML and the pharmacodynamic analysis of pS6 before and after treatment. Subjects received sirolimus (12 mg on day 1, 4 mg daily, days 2-10), then idarubicin and cytarabine (days 4-10). Response was assessed at hematologic recovery or by day 42 using a modified IWG criteria. Fifty-five patients received sirolimus. Toxicity was similar to …