Medicine and Health Sciences Commons^™

Phase Iib, Randomized, Double-Blind Trial Of Gc4419 Versus Placebo To Reduce Severe Oral Mucositis Due To Concurrent Radiotherapy And Cisplatin For Head And Neck Cancer., Carryn M Anderson, Christopher M Lee, Deborah P Saunders, Amarinthia Curtis, Neal Dunlap, Chaitali Nangia, Arielle S Lee, Sharon M Gordon, Philip Kovoor, Roberto Arevalo-Araujo, Voichita Bar-Ad, Abhinand Peddada, Kyle Colvett, Douglas Miller, Anshu K Jain, James Wheeler, Dukagjin Blakaj, Marcelo Bonomi, Sanjiv S Agarwala, Madhur Garg, Francis Worden, Jon Holmlund, Jeffrey M Brill, Matt Downs, Stephen T Sonis, Sanford Katz, John M Buatti

Articles, Abstracts, and Reports

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).

PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly …

Epigenetic Hypomethylation And Upregulation Of Gd3s In Triple Negative Breast Cancer., Wan Li, Xiangjin Zheng, Liwen Ren, Weiqi Fu, Jinyi Liu, Jun Xv, Shiwei Liu, Jinhua Wang, Guanhua Du

Articles, Abstracts, and Reports

Background: Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear.

Methods:

Results:

Conclusions: In summary, these results suggest that GD3s …

Peritumoral Administration Of Dribbles-Pulsed Antigen-Presenting Cells Enhances The Antitumor Efficacy Of Anti-Gitr And Anti-Pd-1 Antibodies Via An Antigen Presenting Independent Mechanism., Jaina M Patel, Zhihua Cui, Zhi-Fa Wen, Catherine T Dinh, Hong-Ming Hu

Articles, Abstracts, and Reports

BACKGROUND: TNF receptor family agonists and checkpoint blockade combination therapies lead to minimal tumor clearance of poorly immunogenic tumors. Therefore, a need to enhance the efficacy of this combination therapy arises. Antigen-presenting cells (APCs) present antigen to T cells and steer the immune response through chemokine and cytokine secretion. DRibbles (DR) are tumor-derived autophagosomes containing tumor antigens and innate inflammatory adjuvants.

METHODS: Using preclinical murine lung and pancreatic cancer models, we assessed the triple combination therapy of GITR agonist and PD-1 blocking antibodies with peritumoral injections of DRibbles-pulsed-bone marrow cells (BMCs), which consisted mainly of APCs, or CD103+ cross-presenting dendritic …

Biological Intratumoral Therapy For The High-Grade Glioma Part I: Intratumoral Delivery And Immunotoxins., Joshua Loya, Charlie Zhang, Emily J Cox, Achal Singh Achrol, Santosh Kesari

Articles, Abstracts, and Reports

Management of high-grade gliomas remains a complex challenge. Standard of care consists of microsurgical resection, chemotherapy and radiation, but despite these aggressive multimodality therapies the overall prognosis remains poor. A major focus of ongoing translational research studies is to develop novel therapeutic strategies that can maximize tumor cell eradication while minimizing collateral side effects. Particularly, biological intratumoral therapies have been the focus of new translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two-part review will provide an overview of biological intratumoral therapies and summarize key advances and remaining challenges in intratumoral …

Targeting Dna Repair In Metastatic Castration-Resistant Prostate Cancer (Mcrpc): Genomic Screening For A Clinical Trial Of Rucaparib, Alan Bryce, Mitchell E. Gross, Charles Redfern, Nicholas Vogelzang, Matthew Rettig, Thomas Stanton, Julie N. Graff, Sandhya Srinivas, Andrea Loehr, Wassim Abida

Articles, Abstracts, and Reports

Objectives: The high prevalence of men with mCRPC carrying pathogenic mutations in DNA damage repair (DDR) genes may have implications for clinical treatment, as poly(ADP-ribose) polymerase (PARP) inhibitors, such as rucaparib, have shown preliminary evidence of activity in these patients. The ongoing phase 2 TRITON2 study (NCT02952534) is evaluating rucaparib in mCRPC patients harboring a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or other DDR gene. Here we present results from genomic screening of tissue and plasma samples from mCRPC patients.

Methods: Comprehensive genomic profiling was performed by Foundation Medicine, Inc., using FFPE tumor tissue …

Biological Intratumoral Therapy For The High-Grade Glioma Part Ii: Vector- And Cell-Based Therapies And Radioimmunotherapy., Joshua Loya, Charlie Zhang, Emily J Cox, Achal Singh Achrol, Santosh Kesari

Articles, Abstracts, and Reports

Management of high-grade gliomas (HGGs) remains a complex challenge with an overall poor prognosis despite aggressive multimodal treatment. New translational research has focused on maximizing tumor cell eradication through improved tumor cell targeting while minimizing collateral systemic side effects. In particular, biological intratumoral therapies have been the focus of novel translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two part review will provide an overview of biological intratumoral therapies that have been evaluated in human clinical trials in HGGs, and summarize key advances and remaining challenges in the development of these …

Publisher Correction: Shared Heritability And Functional Enrichment Across Six Solid Cancers., Xia Jiang, Hilary K Finucane, Fredrick R Schumacher, Stephanie L Schmit, Jonathan P Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B Kuchenbaecker, Joe Dennis, David V Conti, Graham Casey, Mia M Gaudet, Jeroen R Huyghe, Demetrius Albanes, Melinda C Aldrich, Angeline S Andrew, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Natalia N Antonenkova, Susanne M Arnold, Kristan J Aronson, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Jyotsna Batra, Matthias W Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I Berndt, Heike Bickeböller, Stephanie A Bien, Carl Blomqvist, Stefania Boccia, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Hiltrud Brauch, Hermann Brenner, James D Brenton, Mark N Brook, Joan Brunet, Hans Brunnström, Daniel D Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A Caligo, Ian Campbell, Peter T Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L Carvalho, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, Chu Chen, David C Christiani, Kathleen B M Claes, Frank Claessens, Judith Clements, J Margriet Collée, Marcia Cruz Correa, Fergus J Couch, Angela Cox, Julie M Cunningham, Cezary Cybulski, Kamila Czene, Mary B Daly, Anna Defazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L Donovan, Thilo Dörk, Eric J Duell, Alison M Dunning, Miriam Dwek, Diana M Eccles, Christopher K Edlund, Digna R Velez Edwards, Carolina Ellberg, D Gareth Evans, Peter A Fasching, Robert L Ferris, Triantafillos Liloglou, Jane C Figueiredo, Olivia Fletcher, Renée T Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J Gallinger, Patricia A Ganz, Judy Garber, José A García-Sáenz, Simon A Gayther, Graham G Giles, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Ellen L Goode, Marc T Goodman, Gary E Goodman, Kjell Grankvist, Mark H Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C Hamdy, Robert J Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L Hopper, Richard Houlston, Peter J Hulick, David J Hunter, David G Huntsman, Gregory Idos, Evgeny N Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A Jenkins, Mattias Johansson, Mikael Johansson, Esther M John, Amit D Joshi, Radka Kaneva, Beth Y Karlan, Linda E Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S Kibel, Lambertus A Kiemeney, Jeri Kim, Susanne K Kjaer, Julia A Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A Levine, Li Li, Christopher I Li, Annika Lindblom, Noralane M Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley Mcguffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L Milne, Robert J Macinnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, David E Neal, Andrew R Ness, Susan L Neuhausen, Heli Nevanlinna, Polly A Newcomb, Lisa F Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G Nordestgaard, Robert L Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I Olopade, Andrew F Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y Park, Nora Pashayan, Michael T Parsons, Tanja Pejovic, Kathryn L Penney, Wilbert H M Peters, Catherine M Phelan, Amanda I Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J Ramus, Leon Raskin, Gad Rennert, Hedy S Rennert, Elizabeth J Van Rensburg, Marjorie J Riggan, Harvey A Risch, Angela Risch, Monique J Roobol, Barry S Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P Sandler, Elinor J Sawyer, Matthew B Schabath, Johanna Schleutker, Marjanka K Schmidt, V Wendy Setiawan, Hongbing Shen, Erin M Siegel, Weiva Sieh, Christian F Singer, Martha L Slattery, Karina Dalsgaard Sorensen, Melissa C Southey, Amanda B Spurdle, Janet L Stanford, Victoria L Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J Swerdlow, Eloiza H Tajara, Catherine M Tangen, Adonina Tardon, Jack A Taylor, M Dawn Teare, Manuel R Teixeira, Mary Beth Terry, Kathryn L Terry, Stephen N Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E Toland, Diana Torres, Paul A Townsend, Ruth C Travis, Nadine Tung, Shelley S Tworoger, Cornelia M Ulrich, Nawaid Usmani, Celine M Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M Webb, Clarice R Weinberg, Stephanie Weinstein, Mark C Weissler, Jeffrey N Weitzel, Catharine M L West, Emily White, Alice S Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K Zorn, Jacqueline M Lane, Richa Saxena, Duncan Thomas, Rayjean J Hung, Brenda Diergaarde, James Mckay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A Eeles, Georgia Chenevix-Trench, Paul J Brennan, Christopher A Haiman, Jacques Simard, Douglas F Easton, Stephen B Gruber, Paul D P Pharoah, Alkes L Price, Bogdan Pasaniuc, Christopher I Amos, Peter Kraft, Sara Lindström

Articles, Abstracts, and Reports

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Preliminary Observations On Soluble Programmed Cell Death Protein-1 As A Prognostic And Predictive Biomarker In Patients With Metastatic Melanoma Treated With Patient-Specific Autologous Vaccines., Robert O Dillman, Gabriel I Nistor, Bryce T Mclelland, Candace Hsieh, Aleksandra J Poole, Andrew N Cornforth, Hans S Keirstead

Articles, Abstracts, and Reports

Because of its role as an immune checkpoint, levels of soluble programmed cell death protein-1 (sPD-1) could be useful as a prognostic biomarker or predictive biomarker in cancer patients treated with vaccines. Very low levels of sPD-1 may indicate lack of an existing anti-cancer immune response; very high levels may indicate an active immune response that is suppressed. In between these extremes, a decrease in PD-1 following injections of an anti-cancer vaccine may indicate an enhanced immune response that has not been suppressed. Blood samples obtained during a randomized trial in patients with metastatic melanoma were tested from 22 patients …

Phase 1 Trial Of Fruquintinib In Patients With Advanced Solid Tumors: Results Of The Dose Escalation Phase., A Wang-Gillam, H Park, H Yeckes-Rodin, Thomas Stanton, M Kosmo, S Fan, N Sauter, M Kanie

Articles, Abstracts, and Reports

Background: Fruquintinib (Fruq) is a potent, highly selective, novel vascular endothelial growth factor receptor (VEGFR) -1, -2, and -3 tyrosine kinase inhibitor. In the Phase III FRESCO trial¹ that led to the drug approval in China, Fruq improved the median overall survival in patients with metastatic colorectal cancer (mCRC) in the third line or later setting when compared to placebo (9.3 vs 6.6 months); hazard ratio 0.65 (95% CI, 0.51-0.83; P < .001),

Methods: This is a Phase 1 open-label, dose escalation/dose expansion study conducted in the US (NCT03251378). The primary objectives are to evaluate the safety and tolerability of Fruq …

Liquid Biopsy-Based Single-Cell Metabolic Phenotyping Of Lung Cancer Patients For Informative Diagnostics., Ziming Li, Zhuo Wang, Yin Tang, Xiang Lu, Jie Chen, Yu Dong, Baojun Wu, Chunying Wang, Liu Yang, Zhili Guo, Min Xue, Shun Lu, Wei Wei, Qihui Shi

Articles, Abstracts, and Reports

Accurate prediction of chemo- or targeted therapy responses for patients with similar driver oncogenes through a simple and least-invasive assay represents an unmet need in the clinical diagnosis of non-small cell lung cancer. Using a single-cell on-chip metabolic cytometry and fluorescent metabolic probes, we show metabolic phenotyping on the rare disseminated tumor cells in pleural effusions across a panel of 32 lung adenocarcinoma patients. Our results reveal extensive metabolic heterogeneity of tumor cells that differentially engage in glycolysis and mitochondrial oxidation. The cell number ratio of the two metabolic phenotypes is found to be predictive for patient therapy response, physiological …

Anti-Pd-1 Monoclonal Antibody Medi0680 In A Phase I Study Of Patients With Advanced Solid Malignancies., Aung Naing, Jeffrey Infante, Sanjay Goel, Howard Burris, Chelsea Black, Shannon Marshall, Ikbel Achour, Susannah Barbee, Rena May, Chris Morehouse, Kristen Pollizzi, Xuyang Song, Keith Steele, Nairouz Elgeioushi, Farzana Walcott, Joyson Karakunnel, Patricia Lorusso, Amy Weise, Joseph Eder, Brendan Curti, Michael Oberst

Articles, Abstracts, and Reports

BACKGROUND: The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies.

METHODS: MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics.

RESULTS: Fifty-eight patients were treated. Median age was 62.5 …

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …

Chemo-Immunotherapy For Older Patients With Chronic Lymphocytic Leukemia - Passé Yet?, Alexey V Danilov, John M Pagel, Jennifer R Brown, Brian T Hill

Articles, Abstracts, and Reports

No abstract provided.

Cranial And Intra-Axial Metastasis Originating From A Primary Ovarian Dysgerminoma., Tiffany L Beck, Hitomi Momose, Jeffrey M Dym, Vikas Y Rao, Randy Bohart, Bram H Goldstein

Articles, Abstracts, and Reports

Dysgerminomas are aggressive germ cell tumors that typically have a favorable prognosis, especially in patients diagnosed with early stage disease. We recount the history of a 23-year-old woman who was treated for a stage IA ovarian dysgerminoma in November 2017. Postoperatively, the patient was noncompliant insofar as obtaining routine lab evaluations; ten months later, she was diagnosed with a cranial metastasis that extended into the meninges. The patient subsequently underwent a posterior fossa craniotomy and adjuvant etoposide, bleomycin and cisplatin chemotherapy to which she initially responded; however, during cycle 4, she developed pancytopenia whereupon the chemotherapy was summarily discontinued. Thereafter, …

Cervical Cancer In Tanzania: A Systematic Review Of Current Challenges In Six Domains., Ava S Runge, Megan E Bernstein, Alexa N Lucas, Krishnansu S Tewari

Articles, Abstracts, and Reports

Cervical cancer is the most common cancer in Tanzania. After excluding human immunodeficiency virus, lower respiratory infections, malaria, diarrheal diseases, and tuberculosis, cervical cancer kills more women than any other form of illness in the country. Unfortunately, Tanzania has a low doctor-to-patient ratio (1:50,000) and nearly 7000 women die each year from this disease. The clinical problem is further magnified by the country's lack of resources and prevailing poverty, sporadic cervical cancer screening, prevalence of high-risk oncogenic human papillomavirus subtypes, and relatively high rates of human immunodeficiency virus co-infection. In recent years, addressing the cervical cancer problem has become a …

The Society For Immunotherapy Of Cancer Consensus Statement On Immunotherapy For The Treatment Of Squamous Cell Carcinoma Of The Head And Neck (Hnscc)., Ezra E W Cohen, Richard Bryan Bell, Carlo Bifulco, Barbara Burtness, Maura L Gillison, Kevin J Harrington, Quynh-Thu Le, Nancy Y Lee, Rom Leidner, Rebecca L Lewis, Lisa Licitra, Hisham Mehanna, Loren K Mell, Adam Raben, Andrew G Sikora, Ravindra Uppaluri, Fernanda Whitworth, Dan P Zandberg, Robert L Ferris

Articles, Abstracts, and Reports

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the …

Tumor-Released Autophagosomes Induces Cd4, Yong-Qiang Chen, Peng-Cheng Li, Ning Pan, Rong Gao, Zhi-Fa Wen, Tian-Yu Zhang, Fang Huang, Fang-Yuan Wu, Xi-Long Ou, Jin-Ping Zhang, Xue-Jun Zhu, Hong-Ming Hu, Kang Chen, Yun-Lang Cai, Li-Xin Wang

Articles, Abstracts, and Reports

BACKGROUND: CD4

METHODS: TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4

RESULTS: Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4

CONCLUSIONS: HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD4

Blockade Of Tgf-Β Signaling To Enhance The Antitumor Response Is Accompanied By Dysregulation Of The Functional Activity Of Cd4, Magdalena J Polanczyk, Edwin Walker, Daniel Haley, Bella S Guerrouahen, Emmanuel T Akporiaye

Articles, Abstracts, and Reports

BACKGROUND: The pleiotropic cytokine, transforming growth factor (TGF)-β, and CD4

METHODS: Using BALB/c, FoxP3eGFP and Rag

RESULTS: SM16 abrogates TGF-β-induced Treg generation in vitro but does not prevent global homeostatic expansion of CD4

CONCLUSIONS: These findings suggest that blockade of TGF-β signaling is a potentially useful strategy for blunting Treg function to enhance the anti-tumor response. Our data further suggest that the overall dampening of Treg function may involve the expansion of a quiescent Treg precursor population, which is CD4

Correction To: Toward A Comprehensive View Of Cancer Immune Responsiveness: A Synopsis From The Sitc Workshop., Davide Bedognetti, Michele Ceccarelli, Lorenzo Galluzzi, Rongze Lu, Karolina Palucka, Josue Samayoa, Stefani Spranger, Sarah Warren, Kwok-Kin Wong, Elad Ziv, Diego Chowell, Lisa M Coussens, Daniel D De Carvalho, David G Denardo, Jérôme Galon, Howard L Kaufman, Tomas Kirchhoff, Michael T Lotze, Jason J Luke, Andy J Minn, Katerina Politi, Leonard D Shultz, Richard Simon, Vésteinn Thorsson, Joanne B Weidhaas, Maria Libera Ascierto, Paolo Antonio Ascierto, James M Barnes, Valentin Barsan, Praveen K Bommareddy, Adrian Bot, Sarah E Church, Gennaro Ciliberto, Andrea De Maria, Dobrin Draganov, Winson S Ho, Heather M Mcgee, Anne Monette, Joseph F Murphy, Paola Nisticò, Wungki Park, Maulik Patel, Michael Quigley, Laszlo Radvanyi, Harry Raftopoulos, Nils-Petter Rudqvist, Alexandra Snyder, Randy F Sweis, Sara Valpione, Roberta Zappasodi, Lisa H Butterfield, Mary L Disis, Bernard A Fox, Alessandra Cesano, Francesco M Marincola

Articles, Abstracts, and Reports

Following publication of the original article [1], the author reported that an author name, Roberta Zappasodi, was missed in the authorship list.

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …

Diagnosis Of Non-Small Cell Lung Cancer For Early Stage Asymptomatic Patients., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND/AIM: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers.

PATIENTS AND METHODS: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV).

RESULTS: We identified 33 protein biomarkers and developed a classifier using …

Survivin Is A Prognostic Marker And Therapeutic Target For Extranodal, Nasal-Type Natural Killer/T Cell Lymphoma., Li Zhang, Yi Wei, Xiaowei Yan, Na Li, Haolan Song, Li Yang, Yang Wu, Yu-Feng Xi, Hua-Wei Weng, Jian-Hua Li, Edward H Lin, Li-Qun Zou

Articles, Abstracts, and Reports

Background: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy.

Methods: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm.

Results: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients …

Preoperative Stimulation Of Resolution And Inflammation Blockade Eradicates Micrometastases., Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M Gilligan, Megan L Sulciner, Swati S Bhasin, Diane R Bielenberg, Jaimie Chang, Birgitta A Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A Sparks, Steven J Staffa, Vidula Sukhatme, Bruce D Hammock, Mark W Kieran, Sui Huang, Manoj Bhasin, Charles N Serhan, Vikas P Sukhatme

Articles, Abstracts, and Reports

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 …

Real-World Treatment Patterns And Adverse Events In Metastatic Renal Cell Carcinoma From A Large Us Claims Database., Sumanta Pal, Jun Gong, Shivani K Mhatre, Shih-Wen Lin, Andy Surinach, Sarika Ogale, Rini Vohra, Herschel Wallen, Daniel George

Articles, Abstracts, and Reports

BACKGROUND: Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC.

METHODS: US administrative claims data (Truven Health MarketScan Commercial Databases) were used to …

Downregulation Of Cenpf Remodels Prostate Cancer Cells And Alters Cellular Metabolism., Muhammad Shahid, Minhyung Kim, Min Young Lee, Austin Yeon, Sungyong You, Hyung L Kim, Jayoung Kim

Articles, Abstracts, and Reports

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the …

Patient-Specific Dendritic Cell Vaccines With Autologous Tumor Antigens In 72 Patients With Metastatic Melanoma., Robert O Dillman, Andrew N Cornforth, Edward F Mcclay, Carol Depriest

Articles, Abstracts, and Reports

Aim: Metastatic melanoma patients were treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines.

Patients & methods: A total of 72 patients were enrolled in a single-arm Phase I/II (NCT00948480) trial or a randomized Phase II (NCT00436930).

Results: Toxicity was minimal. Median overall survival (OS) was 49.4 months; 5-year OS 46%. A 5-year OS was 72% for 18 recurrent stage 3 without measurable disease when treated and 53% for 30 stage 4 without measurable disease when treated. A total of 24 patients with measurable stage 4 when treated …

A Retrospective Comparison Of Venetoclax Alone Or In Combination With An Anti-Cd20 Monoclonal Antibody In R/R Cll., Anthony R Mato, Lindsey E Roeker, Toby A Eyre, Chadi Nabhan, Nicole Lamanna, Brian T Hill, Danielle M Brander, Paul M Barr, Frederick Lansigan, Bruce D Cheson, Arun K Singavi, Maryam Sarraf Yazdy, Nirav N Shah, John N Allan, Erica B Bhavsar, Joanna Rhodes, Kaitlin Kennard, Stephen J Schuster, Annalynn M Williams, Alan P Skarbnik, Andre H Goy, Julie M Goodfriend, Colleen Dorsey, Catherine C Coombs, Hande Tuncer, Chaitra S Ujjani, Ryan Jacobs, Allison M Winter, John M Pagel, Neil Bailey, Anna Schuh, Mazyar Shadman, Andrea Sitlinger, Hanna Weissbrot, Sivraj Muralikrishnan, Andrew Zelenetz, Amy A Kirkwood, Christopher P Fox

Articles, Abstracts, and Reports

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one …

Toward A Comprehensive View Of Cancer Immune Responsiveness: A Synopsis From The Sitc Workshop., Davide Bedognetti, Michele Ceccarelli, Lorenzo Galluzzi, Rongze Lu, Karolina Palucka, Josue Samayoa, Stefani Spranger, Sarah Warren, Kwok-Kin Wong, Elad Ziv, Diego Chowell, Lisa M Coussens, Daniel D De Carvalho, David G Denardo, Jérôme Galon, Howard L Kaufman, Tomas Kirchhoff, Michael T Lotze, Jason J Luke, Andy J Minn, Katerina Politi, Leonard D Shultz, Richard Simon, Vésteinn Thórsson, Joanne B Weidhaas, Maria Libera Ascierto, Paolo Antonio Ascierto, James M Barnes, Valentin Barsan, Praveen K Bommareddy, Adrian Bot, Sarah E Church, Gennaro Ciliberto, Andrea De Maria, Dobrin Draganov, Winson S Ho, Heather M Mcgee, Anne Monette, Joseph F Murphy, Paola Nisticò, Wungki Park, Maulik Patel, Michael Quigley, Laszlo Radvanyi, Harry Raftopoulos, Nils-Petter Rudqvist, Alexandra Snyder, Randy F Sweis, Sara Valpione, Lisa H Butterfield, Mary L Disis, Bernard A Fox, Alessandra Cesano, Francesco M Marincola

Articles, Abstracts, and Reports

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes …

Acalabrutinib Monotherapy In Patients With Chronic Lymphocytic Leukemia Who Are Intolerant To Ibrutinib., Farrukh T Awan, Anna Schuh, Jennifer R Brown, Richard R Furman, John M Pagel, Peter Hillmen, Deborah M Stephens, Jennifer Woyach, Elena Bibikova, Prista Charuworn, Melanie M Frigault, Ahmed Hamdy, Raquel Izumi, Bolan Linghu, Priti Patel, Min Hui Wang, John C Byrd

Articles, Abstracts, and Reports

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in chronic lymphocytic leukemia (CLL); however, some patients experience adverse events (AEs) leading to discontinuation. Acalabrutinib is a potent, covalent BTK inhibitor with greater selectivity than ibrutinib. We evaluated the safety and efficacy of 100 mg of acalabrutinib twice daily or 200 mg once daily in patients with CLL who discontinued ibrutinib because of intolerance as determined by the investigators. Among 33 treated patients (61% men; median age, 64 years; range, 50-82 years), median duration of prior ibrutinib treatment was 11.6 months (range, 1-62 months); median time from ibrutinib discontinuation …