Medicine and Health Sciences Commons^™

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml., Jayakumar Vadakekolathu, Catherine Lai, Stephen Reeder, Sarah E Church, Tressa Hood, Anbarasu Lourdusamy, Michael P Rettig, Ibrahim Aldoss, Anjali S Advani, John E Godwin, Matthew J Wieduwilt, Martha Arellano, John Muth, Tung On Yau, Farhad Ravandi, Kendra Sweet, Heidi Altmann, Gemma A Foulds, Friedrich Stölzel, Jan Moritz Middeke, Marilena Ciciarello, Antonio Curti, Peter J M Valk, Bob Löwenberg, Ivana Gojo, Martin Bornhäuser, John F Dipersio, Jan K Davidson-Moncada, Sergio Rutella

Articles, Abstracts, and Reports

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) …

Navigating The Paradox Of Scarcity: The Case For Radiologist-Driven Care., Daniel A Ortiz, Kevin M Cregan, Join Y Luh, Taj M Kattapuram

Articles, Abstracts, and Reports

No abstract provided.

Enhanced Detection Of Community-Acquired Pneumonia Pathogens With The Biofire® Pneumonia Filmarray® Panel., David Gilbert, James E Leggett, Lian Wang, Shirin Ferdosian, Gita D Gelfer, Michael L Johnston, Brent Footer, Kathryn W Hendrickson, Hiromichi Park, Emma White, John Heffner

Articles, Abstracts, and Reports

Background: Although most observational studies identify viral or bacterial pathogens in 50% or less of patients hospitalized with community-acquired pneumonia (CAP), we previously demonstrated that a multi-test bundle (MTB) detected a potential pathogen in 73% of patients. This study compares detection rates for potential pathogens with the MTB versus the Biofire® Pneumonia FilmArray® panel (BPFA) multiplex PCR platform and presents an approach for integrating BPFA results as a foundation for subsequent antibiotic stewardship (AS) activities.

Methods: Between January 2017 to March 2018, all patients admitted for CAP were enrolled. Patients were considered evaluable if all elements of the MTB and …

No Time To Die: The Consensus Immunoscore For Predicting Survival And Response To Chemotherapy Of Locally Advanced Colon Cancer Patients In A Multicenter International Study., Paolo A Ascierto, Francesco M Marincola, Bernard A Fox, Jérôme Galon

Articles, Abstracts, and Reports

The multicenter international Society for Immunotherapy of Cancer (SITC) study of the consensus Immunoscore demonstrated the prediction of survival and response to chemotherapy in 763 Stage III colon cancer (CC) patients. Similar Immunoscore groups were found in elderly patients, and densities of immune cells and intratumoral T-cell repertoire were not decreasing with age in the tumor microenvironment. In two independent cohorts, Immunoscore significantly predicted time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS), including within high-risk (T4 or N2) and low-risk (T1-3, N1) patients. In stratified Cox multivariable analysis for TTR, DFS, and OS, Immunoscore's association to outcomes …

Feasibility Of Treating High Grade Gliomas In Children With Tumor-Treating Fields: A Case Series., John Crawford, Marlon G Saria, Girish Dhall, Ashley Margol, Santosh Kesari

Articles, Abstracts, and Reports

Children diagnosed with high grade gliomas (HGG) have dismal prognoses and treatment options remain limited. Tumor treating fields (TTFields) in combination with temozolomide (TMZ) is approved for the treatment of newly diagnosed and recurrent glioblastoma (GBM) in adult patients. However, clinical experience with TTFields in the pediatric HGG population is lacking. This retrospective review of four clinical cases was undertaken to evaluate the feasibility of treating children diagnosed with HGG off-label with TTFields. Patients were evaluated for device compliance, safety, and outcome. Treatment with TTFields was delivered via four transducer arrays placed on the shaved scalp, which were connected to …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume I-Conceptual Challenges., Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano

Articles, Abstracts, and Reports

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial …

The Society For Immunotherapy Of Cancer (Sitc) Clinical Practice Guideline On Immunotherapy For The Treatment Of Acute Leukemia., Michael M Boyiadzis, Ivan Aksentijevich, Daniel A Arber, John Barrett, Renier J Brentjens, Jill Brufsky, Jorge Cortes, Marcos De Lima, Stephen J Forman, Ephraim J Fuchs, Linda J Fukas, Steven D Gore, Mark R Litzow, Jeffrey S Miller, John M Pagel, Edmund K Waller, Martin S Tallman

Articles, Abstracts, and Reports

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of …

Nivolumab In Advanced Hepatocellular Carcinoma: Safety Profile And Select Treatment-Related Adverse Events From The Checkmate 040 Study., Karen Julien, Hiu Tung Leung, Carmen Fuertes, Megumi Mori, Miao-Jen Wang, Jocelyn Teo, Lisa Weiss, Sara Hamilton, Holly Difebo, Yoon Jin Noh, Aralee Galway, Jane Koh, Edith Brutcher, Huanyu Zhao, Yun Shen, Marina Tschaika, Yue-Yun To

Articles, Abstracts, and Reports

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study.

MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and …

Prediction Of Opioid-Induced Respiratory Depression On Inpatient Wards Using Continuous Capnography And Oximetry: An International Prospective, Observational Trial., Ashish K Khanna, Sergio D Bergese, Carla R Jungquist, Hiroshi Morimatsu, Shoichi Uezono, Simon Lee, Lian Kah Ti, Richard D Urman, Robert Mcintyre, Carlos Tornero, Albert Dahan, Leif Saager, Toby N Weingarten, Maria Wittmann, Dennis Auckley, Luca Brazzi, Morgan Le Guen, Roy Soto, Frank Schramm, Sabry Ayad, Roop Kaw, Paola Di Stefano, Daniel I Sessler, Alberto Uribe, Vanessa Moll, Susan J Dempsey, Wolfgang Buhre, Frank J Overdyk, Marianne Tanios, Eva Rivas, Miluska Mejia, Kavita Elliott, Assad Ali, Juan Fiorda-Diaz, Ruben Carrasco-Moyano, Ana Mavarez-Martinez, Alicia Gonzalez-Zacarias, Cory Roeth, January Kim, Alan Esparza-Gutierrez, Carleara Weiss, Chiahui Chen, Arata Taniguchi, Yuko Mihara, Makiko Ariyoshi, Ichiro Kondo, Kentaro Yamakawa, Yoshifumi Suga, Kohei Ikeda, Koji Takano, Yuuki Kuwabara, Nicole Carignan, Joyce Rankin, Katherine Egan, Lakeisha Waters, Ming Ann Sim, Lyn Li Lean, Qi En Lydia Liew, Lawrence Siu-Chun Law, James Gosnell, Salina Shrestha, Chisom Okponyia, Mohammed H Al-Musawi, María José Parra Gonzalez, Claudia Neumann, Vera Guttenthaler, Olja Männer, Achilles Delis, Anja Winkler, Bahareh Marchand, Frauke Schmal, Fuad Aleskerov, Mohammedumer Nagori, Muhammad Shafi, Gloria Mcphee, Cynthia Newman, Elizabeth Lopez, Sabrina Ma Har, Moumen Asbahi, Kim Nordstrom Mccaw, Maurice Theunissen, Valerie Smit-Fun

Articles, Abstracts, and Reports

BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring.

METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and …

2021: Will It Be The Best Season For International Spine Meetings Ever?, Karsten Wiechert, Jens R Chapman, Jeffrey C Wang

Articles, Abstracts, and Reports

No abstract provided.

Full-Thickness Resection Device (Ftrd) For Treatment Of Upper Gastrointestinal Tract Lesions: The First International Experience., Kaveh Hajifathalian, Yervant Ichkhanian, Qais Dawod, Alexander Meining, Arthur Schmidt, Nicholas Glaser, Kia Vosoughi, David L Diehl, Ian S Grimm, Theodore James, Adam W Templeton, Jason B Samarasena, Nabil El Hage Chehade, John G Lee, Kenneth J Chang, Meir Mizrahi, Mohammed Barawi, Shayan Irani, Shai Friedland, Paul Korc, Abdul Aziz Aadam, Mohammad Al-Haddad, Thomas E Kowalski, George Smallfield, Gregory G Ginsberg, Norio Fukami, Michael Lajin, Nikhil A Kumta, Shou-Jiang Tang, Yehia Naga, Stuart K Amateau, Franklin Kasmin, Martin Goetz, Stefan Seewald, Vivek Kumbhari, Saowanee Ngamruengphong, Srihari Mahdev, Saurabh Mukewar, Kartik Sampath, David L Carr-Locke, Mouen A Khashab, Reem Z Sharaiha

Articles, Abstracts, and Reports

Background and study aims The Full-Thickness Resection Device (FTRD) provides a novel treatment option for lesions not amenable to conventional endoscopic resection techniques. There are limited data on the efficacy and safety of FTRD for resection of upper gastrointestinal tract (GIT) lesions. Patients and methods This was an international multicenter retrospective study, including patients who had an endoscopic resection of an upper GIT lesion using the FTRD between January 2017 and February 2019. Results Fifty-six patients from 13 centers were included. The most common lesions were mesenchymal neoplasms (n = 23, 41 %), adenomas (n = 7, 13 %), and …

Classifying Complications: Assessing Adult Spinal Deformity 2-Year Surgical Outcomes., Eric O Klineberg, Peter G Passias, Gregory W Poorman, Cyrus M Jalai, Abiola Atanda, Nancy Worley, Samantha Horn, Daniel M Sciubba, D Kojo Hamilton, Douglas C Burton, Munish Chandra Gupta, Justin S Smith, Alexandra Soroceanu, Robert A Hart, Brian Neuman, Christopher P Ames, Frank J Schwab, Virginie Lafage

Articles, Abstracts, and Reports

STUDY DESIGN: Retrospective review of prospective database.

OBJECTIVE: Complication rates for adult spinal deformity (ASD) surgery vary widely because there is no accepted system for categorization. Our objective was to identify the impact of complication occurrence, minor-major complication, and Clavien-Dindo complication classification (Cc) on clinical variables and patient-reported outcomes.

METHODS: Complications in surgical ASD patients with complete baseline and 2-year data were considered intraoperatively, perioperatively (<6 >weeks), and postoperatively (>6 weeks). Primary outcome measures were complication timing and severity according to 3 scales: complication presence (yes/no), minor-major, and Cc score. Secondary outcomes were surgical outcomes (estimated blood loss [EBL], …

Untargeted Longitudinal Analysis Of A Wellness Cohort Identifies Markers Of Metastatic Cancer Years Prior To Diagnosis., Andrew T Magis, Noa Rappaport, Matthew P Conomos, Gilbert S Omenn, Jennifer C Lovejoy, Leroy Hood, Nathan D Price

Articles, Abstracts, and Reports

We analyzed 1196 proteins in longitudinal plasma samples from participants in a commercial wellness program, including samples collected pre-diagnosis from ten cancer patients and 69 controls. For three individuals ultimately diagnosed with metastatic breast, lung, or pancreatic cancer, CEACAM5 was a persistent longitudinal outlier as early as 26.5 months pre-diagnosis. CALCA, a biomarker for medullary thyroid cancer, was hypersecreted in metastatic pancreatic cancer at least 16.5 months pre-diagnosis. ERBB2 levels spiked in metastatic breast cancer between 10.0 and 4.0 months pre-diagnosis. Our results support the value of deep phenotyping seemingly healthy individuals in prospectively inferring disease transitions.

Lenvatinib Plus Pembrolizumab In Patients With Advanced Endometrial Cancer., Vicky Makker, Matthew H Taylor, Carol Aghajanian, Ana Oaknin, James Mier, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Christopher Disimone, Mark Messing, Daniel E Stepan, Corina E Dutcus, Jane Wu, Emmett V Schmidt, Robert Orlowski, Pallavi Sachdev, Robert Shumaker, Antonio Casado Herraez

Articles, Abstracts, and Reports

PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.

METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR

RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR

CONCLUSION: Lenvatinib plus pembrolizumab showed …

Functional Outcome Of Traumatic Spinopelvic Instabilities Treated With Lumbopelvic Fixation., Emre Yilmaz, Martin F Hoffmann, Alexander Von Glinski, Christiane Kruppa, Uwe Hamsen, Cameron K Schmidt, Ahmet Oernek, Matthias Koenigshausen, Marcel Dudda, Thomas A Schildhauer

Articles, Abstracts, and Reports

The aim of this study was to assess the functional outcome after lumbopelvic fixation (LPF) using the SMFA (short musculoskeletal functional assessment) score and discuss the results in the context of the existing literature. The last consecutive 50 patients who underwent a LPF from January 1st 2011 to December 31st 2014 were identified and administered the SMFA-questionnaire. Inclusion criteria were: (1) patient underwent LPF at our institution, (2) complete medical records, (3) minimum follow-up of 12 months. Out of the 50 recipients, 22 questionnaires were returned. Five questionnaires were incomplete and therefore seventeen were included for analysis. The mean age …

Perspectives In Melanoma: Meeting Report From The "Melanoma Bridge" (December 5th-7th, 2019, Naples, Italy)., Paolo A Ascierto, Igor Puzanov, Sanjiv S Agarwala, Christian Blank, Richard D Carvajal, Sandra Demaria, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Bernard A Fox, Thomas F Gajewski, Claus Garbe, Patrick Hwu, Roger S Lo, Georgina V Long, Jason J Luke, Iman Osman, Michael A Postow, Ryan J Sullivan, Janis M Taube, Giorgio Trinchieri, Hassane M Zarour, Corrado Caracò, Magdalena Thurin

Articles, Abstracts, and Reports

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including …

Application Of Freire's Adult Education Model In Modifying The Psychological Constructs Of Health Belief Model In Self-Medication Behaviors Of Older Adults: A Randomized Controlled Trial., Kasra Gharouni, Arash Ardalan, Marzieh Araban, Farzad Ebrahimzadeh, Katayon Bakhtiar, Mohammad Almasian, Fatemeh Bastami

Articles, Abstracts, and Reports

BACKGROUND: Self-medication by older adults has been always a public health concern. The present study aimed to modify the psychological constructs of Health Belief Model (HBM) in relation to self-medication behaviors using Freire's Adult Education Model (FAEM) among older adults in Khorramabad, Iran, from 2017 to 2018.

METHODS: The mean age of the older adults was 66.28 ± 7.18 years. This was a randomized controlled trial study conducted on 132 individuals older than 60 who were referred from different health care centers. The participants were selected using multistage sampling method and randomly divided into two groups of intervention and control. …

Sequential Complications Of Hypercalcemia, Necrotizing Granulomatous Vasculitis, And Aplastic Anemia Occurring In One Patient With Angioimmunoblastic T-Cell Lymphoma., Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P Quick

Articles, Abstracts, and Reports

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. …

Third-Generation Medium Cross-Linked Polyethylene Demonstrates Very Low Wear In Total Hip Arthroplasty., Omid Jalali, Travis S Scudday, Marie-Claire Fickenscher, Steven L Barnett, Robert S Gorab

Articles, Abstracts, and Reports

Background: Cross-linked polyethylene (XLPE) liners have shown lower wear rates than conventional polyethylene liners in total hip arthroplasty. The primary aim of our study was to report our most recent analysis of wear rates and clinical outcomes of a third-generation XLPE liner. Secondary aims were to investigate the rate of adverse events related to mechanical failure or oxidation of this liner.

Methods: A series of 266 total hip arthroplasties using a specific XLPE liner were retrospectively reviewed. Radiographs were examined to determine linear and volumetric wear rates and presence of osteolysis. Clinical outcomes, revision rates, mechanical failures, and risk factors …

Defining The Proteolytic Landscape During Enterovirus Infection., Mohsan Saeed, Sebastian Kapell, Nicholas T Hertz, Xianfang Wu, Kierstin Bell, Alison W Ashbrook, Milica Tesic Mark, Henry A Zebroski, Maxwell L Neal, Malin Flodström-Tullberg, Margaret R Macdonald, John D Aitchison, Henrik Molina, Charles M Rice

Articles, Abstracts, and Reports

Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a …

Correction To: Medical Neglect As A Contributor To Poorly Controlled Asthma In Childhood., Barbara L Knox, Francois M Luyet, Debra Esernio-Jenssen

Articles, Abstracts, and Reports

[This corrects the article DOI: 10.1007/s40653-019-00290-0.].

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

Nonrecurrent Early Post-Transplantation Focal Segmental Glomerulosclerosis., Momina M Ahmed, Massini A Merzkani, Matthew R D'Costa, Muhannad A Leghrouz, Mary E Fidler, Haraldur Bjarnason, Patrick G Dean, Fernando C Fervenza, Sanjit Reddy, Hatem Amer

Articles, Abstracts, and Reports

No abstract provided.

Gsj Gets A Fresh New Look, Jeffrey C Wang, Jens R Chapman, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

Long Term Survival And Local Control Outcomes From Single Dose Targeted Intraoperative Radiotherapy During Lumpectomy (Targit-Iort) For Early Breast Cancer: Targit-A Randomised Clinical Trial., Jayant S Vaidya, Max Bulsara, Michael Baum, Frederik Wenz, Samuele Massarut, Steffi Pigorsch, Michael Alvarado, Michael Douek, Christobel Saunders, Henrik L Flyger, Wolfgang Eiermann, Chris Brew-Graves, Norman R Williams, Ingrid Potyka, Nicholas Roberts, Marcelle Bernstein, Douglas Brown, Elena Sperk, Siobhan Laws, Marc Sütterlin, Tammy Corica, Steinar Lundgren, Dennis R Holmes, Lorenzo Vinante, Fernando Bozza, Montserrat Pazos, Magali Le Blanc-Onfroy, Günther Gruber, Wojciech Polkowski, Konstantin J Dedes, Marcus Niewald, Jens Blohmer, David Mccready, Richard Hoefer, Pond Kelemen, Gloria Petralia, Mary Falzon, David J Joseph, Jeffrey S Tobias

Articles, Abstracts, and Reports

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: …

Molecular Profiling Of Melanoma Brain Metastases Compared To Primary Cutaneous Melanoma And To Extracranial Metastases., Gino K In, Kelsey Poorman, Michelle Saul, Steven O'Day, Jeffrey M Farma, Anthony J Olszanski, Michael S Gordon, Jacob S Thomas, Burton Eisenberg, Lawrence Flaherty, Amy Weise, Steven Daveluy, Geoffrey Gibney, Michael B Atkins, Ari Vanderwalde

Articles, Abstracts, and Reports

BACKGROUND: Brain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases.

MATERIALS AND METHODS: We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM.

RESULTS: The most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency …

Artificial Intelligence For Rapid Meta-Analysis: Case Study On Ocular Toxicity Of Hydroxychloroquine., Matthew Michelson, Tiffany Chow, Neil A Martin, Mike Ross, Amelia Tee Qiao Ying, Steven Minton

Articles, Abstracts, and Reports

BACKGROUND: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance.

OBJECTIVE: We aimed to evaluate whether RMA can generate meaningful clinical insights, but crucially, in a much faster processing time than traditional meta-analysis, using a relevant, real-world example.

METHODS: The development of our RMA approach was motivated by a currently relevant clinical question: is ocular toxicity and …

Incorporating Breast Cancer Recurrence Events Into Population-Based Cancer Registries Using Medical Claims: Cohort Study., Teresa A'Mar, J David Beatty, Catherine Fedorenko, Daniel Markowitz, Thomas Corey, Jane Lange, Stephen M Schwartz, Bin Huang, Jessica Chubak, Ruth Etzioni

Articles, Abstracts, and Reports

BACKGROUND: There is a need for automated approaches to incorporate information on cancer recurrence events into population-based cancer registries.

OBJECTIVE: The aim of this study is to determine the accuracy of a novel data mining algorithm to extract information from linked registry and medical claims data on the occurrence and timing of second breast cancer events (SBCE).

METHODS: We used supervised data from 3092 stage I and II breast cancer cases (with 394 recurrences), diagnosed between 1993 and 2006 inclusive, of patients at Kaiser Permanente Washington and cases in the Puget Sound Cancer Surveillance System. Our goal was to classify …

Prospective Home-Use Study On Non-Invasive Neuromodulation Therapy For Essential Tremor., Stuart H Isaacson, Elizabeth Peckham, Winona Tse, Olga Waln, Christopher Way, Melita T Petrossian, Nabila Dahodwala, Michael J Soileau, Mark Lew, Cameron Dietiker, Nijee Luthra, Pinky Agarwal, Rohit Dhall, John Morgan, Nicole Calakos, Theresa A Zesiewicz, Ejaz A Shamim, Rajeev Kumar, Peter Lewitt, Holly A Shill, Adam Simmons, Fernando L Pagan, Pravin Khemani, Jessica Tate, Brian Maddux, Lan Luo, William Ondo, Mark Hallett, Apoorva Rajagopal, Paula Chidester, Kathryn H Rosenbluth, Scott L Delp, Rajesh Pahwa

Articles, Abstracts, and Reports

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients.

Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use.

Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 …