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Redifferentiation therapy-Returning to our roots in a post-kinase inhibitor world. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-27 Maria E Cabanillas,Naifa L Busaidy,Steven I Sherman
Radioactive iodine (RAI) treatment is an effective treatment for differentiated thyroid cancer (DTC), however, many patients are refractory. Using targeted drugs to re-induce RAI sensitivity ("redifferentiation therapy") has long been sought after as the holy grail in endocrine oncology.
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Targeting the DNA Damage Response Pathways and Replication Stress in Colorectal Cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-26 Erika Durinikova,Nicole M Reilly,Kristi Buzo,Elisa Mariella,Rosaria Chilà,Annalisa Lorenzato,João M L Dias,Gaia Grasso,Federica Pisati,Simona Lamba,Giorgio Corti,Andrea Degasperi,Carlotta Cancelliere,Gianluca Mauri,Pietro Andrei,Michael Linnebacher,Silvia Marsoni,Salvatore Siena,Andrea Sartore-Bianchi,Serena Nik-Zainal,Federica Di Nicolantonio,Alberto Bardelli,Sabrina Arena
PURPOSE Genomic instability is a hallmark of cancer and targeting DNA damage response (DDR) is emerging as a promising therapeutic strategy in different solid tumors. The effectiveness of targeting DDR in colorectal cancer has not been extensively explored. EXPERIMENTAL DESIGN We challenged 112 cell models recapitulating the genomic landscape of metastatic colorectal cancer with ATM, ATR, CHK1, WEE1
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Large-scale in vitro and in vivo CRISPR-Cas9 knockout screens identify a 16-gene fitness score for improved risk assessment in acute myeloid leukemia. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-25 Peng Jin,Qiqi Jin,Xiaoling Wang,Ming Zhao,Fangyi Dong,Ge Jiang,Zeyi Li,Jie Shen,Wei Zhang,Shishuang Wu,Ran Li,Yunxiang Zhang,Xiaoyang Li,Junmin Li
PURPOSE The molecular complexity of acute myeloid leukemia (AML) presents a considerable challenge to implementation of clinical genetic testing for accurate risk stratification. Identification of better biomarkers therefore remains a high priority to enable improving established stratification and guiding risk-adapted therapy decisions. EXPERIMENTAL DESIGN We systematically integrated and analyzed
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A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple Negative Breast Cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-25 Kai Sun,Yitian Xu,Licheng Zhang,Polly Niravath,Jorge Darcourt,Tejal Patel,Bin S Teh,Andrew M Farach,Carlo Guerrero,Sunil Mathur,Mark A Sultenfuss,Nakul Gupta,Mary R Schwartz,Susan L Haley,Sindhu Nair,Xiaoxian Li,Thi Truc Anh Nguyen,Joseph D Butner,Joe Ensor,Jaime A Mejia,Zhuyong Mei,E Brian Butler,Shu-Hsia Chen,Eric H Bernicker,Jenny C Chang
PURPOSE A Phase 2 trial of stereotactic radiation therapy and in situ cytotoxic virus therapy in metastatic triple-negative breast cancer (mTNBC) patients followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with ADV/HSV-tk plus valacyclovir gene therapy and SBRT in mTNBC patients. METHODS In this single-arm, open-label Phase
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Clinico-Genomic Characterization of Patients with Metastatic Urothelial Carcinoma in Real-World Practice Identifies a Novel Bladder Immune Performance Index (BIPI). Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-25 Bernadett Szabados,Mariano Ponz-Sarvis,Robson Machado,Diego Saldana,Edward E Kadel,Romain Banchereau,Fanny Bouquet,Marius Garmhausen,Thomas Powles,Carsten Schr der
PURPOSE This retrospective analysis of the largest available clinico-genomic database used de-identified patient-level electronic health record-derived real-world data (RWD) combined with FoundationOne® comprehensive genomic profiling (CGP) to characterize patients with metastatic urothelial carcinoma (mUC) treated in the real-world setting, detect potential biomarkers, and develop a bladder immune
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Unrelated Allogeneic Stem Cell Transplant in Relapsed/Refractory AML: Widening the Yellow Brick Road. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-25 Diego Andres Adrianzen Herrera,Aditi Shastri
A sizable proportion of AML patients fail to achieve remission. HSCT is the only intervention with potential of long-term survival. A recent AWLP/EBMT analysis reports substantial post-transplant survival gains for patients transplanted with active disease. Decreased relapse was the largest contributor to survival, a cause for optimism in this challenging population.
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WNT medulloblastoma limbo: How low can we go? Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-22 Marc Remke,Vijay Ramaswamy
Survival rates for average-risk medulloblastoma exceed 80%, however long-term sequelae are substantial. A study from Mumbai evaluated the role of omission of craniospinal irradiation. Albeit unsuccessful, this study raises the crucial question of how low therapy can be safely de-escalated with the intent of improving quality of survival.
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The Challenges of HLA Class I Loss in Cancer Immunotherapy: Facts and Hopes. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-21 Natalia Aptsiauri,Federico Garrido
HLA class I molecules are key in tumor recognition and T-cell mediated elimination. Loss of tumor HLA class I expression with different underlying molecular defects results in reduced antigen presentation and facilitates cancer immune evasion. It is also linked to significant changes in tumor microenvironment and tissue architecture. In this review we summarize the current advances and future perspectives
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Preclinical development of [211At]meta-astatobenzylguanidine ([211At]MABG) as an alpha particle radiopharmaceutical therapy for neuroblastoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-21 Vandana Batra,Minu Samanta,Mehran Makvandi,David Groff,Paul Martorano,Jimmy Elias,Pietro Ranieri,Matthew Tsang,Catherine Hou,Yimei Li,Bruce Pawel,Daniel Martinez,Ganesan Vaidyanathan,Sean Carlin,Daniel A Pryma,John M Maris
PURPOSE [131I]meta-iodobenzylguanidine ([131I]MIBG) is a targeted radiotherapeutic administered systemically to deliver beta particle radiation in neuroblastoma. However, relapses in the bone marrow are common. [211At]meta-astatobenzylguanidine [211At]MABG is an alpha particle emitter with higher biological effectiveness and short path length which effectively sterilizes microscopic residual disease
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HPV DNA as a biomarker in oropharyngeal cancer: A step in the right direction. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-21 Alexander D Colevas
Lack of prospectively planned followup and minimal characterization of the patient population studied complicate interpretation of circulating HPV DNA as a prognostic biomarker for HPV associated oropharyngeal carcinoma patients treated with curative intent.
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Broadening the MIND: tafasitamab and lenalidomide versus synthetic controls. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-21 Hua-Jay J Cherng,Jason R Westin
Tafasitamab and lenalidomide was approved for second-line treatment of diffuse large B-cell lymphoma (DLBCL) based on a single-arm phase II study. This combination was superior to routine immunochemotherapy regimens when comparing matched observational cohorts. "Synthetic" control groups may support use of novel DLBCL therapies in the absence of randomized studies.
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Upfront biology-guided therapy in diffuse intrinsic pontine glioma: therapeutic, molecular, and biomarker outcomes from PNOC003. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-19 Cassie Kline,Payal Jain,Lindsay Kilburn,Erin R Bonner,Nalin Gupta,John R Crawford,Anu Banerjee,Roger J Packer,Javier Villanueva-Meyer,Tracy Luks,Yalan Zhang,Madhuri Kambhampati,Jie Zhang,Sridevi Yadavilli,Bo Zhang,Krutika S Gaonkar,Jo Lynne Rokita,Adam Kraya,John Kuhn,Winnie Liang,Sara Byron,Michael Berens,Annette Molinaro,Michael Prados,Adam Resnick,Sebastian M Waszak,Javad Nazarian,Sabine Mueller
BACKGROUND PNOC003 is a multi-center precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG). METHODS Patients (3-25 years) were enrolled based on imaging consistent with DIPG. Biopsy tissue was collected for whole exome and mRNA sequencing. After radiation therapy (RT), patients were assigned up to four FDA-approved drugs based on molecular
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Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase 2 Study of an MRD-driven Approach. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-19 Lindsey E Roeker,Tatyana A Feldman,Jacob D Soumerai,Victoria Falco,Gail Panton,Colleen Dorsey,Andrew D Zelenetz,Lorenzo Falchi,Jae H Park,David J Straus,Camila Pena Velasquez,Sonia Lebowitz,Yehudit Fox,Kristen Battiato,Carissa Laudati,Meghan C Thompson,Elizabeth McCarthy,Sabrina Kdiry,Rosalba Martignetti,Teja Turpuseema,Michelle Purdom,Dana Paskalis,Hari P Miskin,Peter Sportelli,Lori A Leslie,Anthony
PURPOSE Ibrutinib has transformed the management of CLL, though its use is limited by toxicity and resistance. In this study, we utilized an "add on" approach for patients treated with ibrutinib in the front-line or R/R settings with detectable MRD. Umbralisib and ublituximab (U2) were added on to ibrutinib, patients were treated until achieving undetectable-MRD (U-MRD), and then they entered a period
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PD-1T TILs as a predictive biomarker for clinical benefit to PD-1 blockade in patients with advanced NSCLC. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-19 Karlijn Hummelink,Vincent van der Noort,Mirte Muller,Robert D Schouten,Ferry Lalezari,Dennis Peters,Willemijn S M E Theelen,Viktor H Koelzer,Kirsten D Mertz,Alfred Zippelius,Michel M van den Heuvel,Annegien Broeks,John B A G Haanen,Ton N Schumacher,Gerrit A Meijer,Egbert F Smit,Kim Monkhorst,Daniela S Thommen
PURPOSE Durable clinical benefit to PD-1 blockade in NSCLC is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1T TILs, with predictive potential in NSCLC. Here, we examined PD-1T TILs as biomarker in NSCLC. EXPERIMENTAL DESIGN PD-1T TILs were digitally quantified
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Highly sensitive EGFRvIII detection in circulating extracellular vesicle RNA of glioma patients. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-18 Syeda Maheen Batool,Koushik Muralidharan,Tiffaney Hsia,Sarah Falotico,Austin S Gamblin,Yulia B Rosenfeld,Sirena K Khanna,Leonora Balaj,Bob S Carter
PURPOSE Liquid biopsy offers an attractive platform for non-invasive tumor diagnosis, prognostication and prediction of glioblastoma clinical outcomes. Prior studies report that 30-50% of GBM lesions characterized by EGFR amplification also harbor the EGFRvIII mutation. EXPERIMENTAL DESIGN A novel digital droplet PCR (ddPCR) assay for high GC content amplicons was developed and optimized for sensitive
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Impaired Chromatin Remodeling Predicts Survival to Modified Gemcitabine and S-1 plus Nivolumab in Advanced Biliary Tract Cancer: A Phase II T1219 Study. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-18 Nai-Jung Chiang,Kien Thiam Tan,Li-Yuan Bai,Chin-Fu Hsiao,Chung-Yu Huang,Yi-Ping Hung,Chien-Jui Huang,San-Chi Chen,Yan-Shen Shan,Yee Chao,Yi-Hsiang Huang,I-Cheng Lee,Pei-Chang Lee,Yung-Yeh Su,Shu-Jen Chen,Chun-Nan Yeh,Li-Tzong Chen,Ming-Huang Chen
PURPOSE Modified Gemcitabine and S-1 is an active regimen for patients with advanced biliary tract cancer (ABTC) in our previous study. Herein, we report the results of a single-arm phase II of Nivolumab plus modified GS (NGS) as first-line treatment in ABTC. PATIENTS AND METHODS Patients received Nivolumab 240 mg and 800 mg/m2 Gemcitabine on day 1 plus daily 80/100/120 mg of S-1 (based on body surface
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Acetylated HOXB13 Regulated Super Enhancer Genes Define Therapeutic Vulnerabilities of Castration-Resistant Prostate Cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-18 Duy T Nguyen,Wei Yang,Arun Renganathan,Cody Weimholt,Duminduni H Angappulige,Thanh Nguyen,Robert W Sprung,Gerald L Andriole,Eric H Kim,Nupam P Mahajan,Kiran Mahajan
PURPOSE Androgen Receptor (AR) antagonism is exacerbated by HOXB13 in Castration Resistant Prostate Cancers (CRPCs). However, it is unclear when and how does HOXB13 prime CRPCs for AR antagonism. By mass-spectrometry analysis of CRPC extract we uncovered a novel lysine 13 (K13) acetylation in HOXB13 mediated by CBP/p300. To determine whether acetylated K13-HOXB13 is a clinical biomarker of CRPC development
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Microsatellite instability-high endometrial cancers with MLH1 promoter hypermethylation have distinct molecular and clinical profiles. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-18 Beryl L Manning-Geist,Ying L Liu,Kelly A Devereaux,Arnaud Da Cruz Paula,Qin C Zhou,Weining Ma,Pier Selenica,Ozge Ceyhan-Birsoy,Lea A Moukarzel,Timothy Hoang,Sushmita Gordhandas,Maria M Rubinstein,Claire F Friedman,Carol Aghajanian,Nadeem R Abu-Rustum,Zsofia K Stadler,Jorge S Reis-Filho,Alexia Iasonos,Dmitriy Zamarin,Lora H Ellenson,Yulia Lakhman,Diana L Mandelker,Britta Weigelt
PURPOSE Microsatellite instability-high (MSI-H) endometrial carcinomas (ECs) are underpinned by distinct mechanisms of DNA mismatch repair deficiencies (MMR-D). We sought to characterize clinical and genetic features of MSI-H ECs harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph). DESIGN Of >1,100 EC patients that underwent clinical tumor-normal sequencing
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Clinical, pathological, and molecular prognostic factors in patients with early-stage EGFR mutant NSCLC. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-15 Hyun Ae Jung,Jinyeong Lim,Yoon-La Choi,Se-Hoon Lee,Je-Gun Joung,Yeong Jeong Jeon,Jae Won Choi,Sumin Shin,Jong Ho Cho,Hong Kwan Kim,Yong Soo Choi,Jae Ill Zo,Young Mog Shim,Sehhoon Park,Jong-Mu Sun,Jin Seok Ahn,Myung Ju Ahn,Joungho Han,Woong-Yang Park,Jhingook Kim,Keunchil Park
PURPOSE In early-stage, Epidermal growth factor receptor mutation-positive (EGFR-M+) NSCLC, surgery remains the primary treatment, without personalized treatments. We aimed to identify risk factors for recurrence-free survival (RFS) to suggest personalized strategies. PATIENTS AND METHODS From January 2008 to August 2020, a total of 1,181 patients with pathological stage (pStage) IB-IIIA, non-squamous
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Statistical considerations for analyses of time-to-event endpoints in oncology clinical trials: Illustrations with CAR-T immunotherapy studies. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-15 Yimei Li,Wei-Ting Hwang,Shannon L Maude,David T Teachey,Noelle V Frey,Regina M Myers,Allison Barz Leahy,Hongyan Liu,David L Porter,Stephan A Grupp,Pamela A Shaw
Chimeric antigen receptor T-cell (CAR-T) therapy is an exciting development in the field of cancer immunology and has received a lot of interest in recent years. Many time-to-event (TTE) endpoints related to relapse, disease progression, and remission are analyzed in CAR-T studies to assess treatment efficacy. Definitions of these TTE endpoints are not always consistent, even for the same outcomes
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GITR antibodies in cancer: not ready for prime time. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-14 Tatiana Hernandez-Guerrero,Victor Moreno
GITR agonistic antibodies are expected to increase the antitumor response mainly by reducing the effect of Foxp3+ T regulatory cells. TRX-518 is a novel GITR agonist that has shown good pharmacodynamic activity by depleting T regs in preclinical models, with limited clinical activity demonstrated in patients with advanced solid tumors.
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Combined MEK/PD-L1 inhibition alters peripheral cytokines and lymphocyte populations correlating with improved clinical outcomes in advanced biliary tract cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-14 Amanda N Ruggieri,Mark Yarchoan,Subir Goyal,Yuan Liu,Elad Sharon,Helen X Chen,Brian M Olson,Chrystal M Paulos,Bassel F El-Rayes,Shishir K Maithel,Nilofer S Azad,Gregory B Lesinski
PURPOSE Biliary tract cancers (BTCs) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibitor (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC. EXPERIMENTAL DESIGN We
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Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non-Muscle-Invasive Bladder Cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-14 Eugene J Pietzak,Karissa Whiting,Preethi Srinivasan,Chaitanya Bandlamudi,Aliya Khurram,Vijai Joseph,Aleksandra Walasek,Emily Bochner,Timothy Clinton,Nima Almassi,Hong Truong,Manuel R de Jesus Escano,Michal Wiseman,Diana Mandelker,Yelena Kemel,Liying Zhang,Michael F Walsh,Karen A Cadoo,Jonathan A Coleman,Hikmat Al-Ahmadie,Jonathan E Rosenberg,Gopakumar V Iyer,David B Solit,Irina Ostrovnaya,Kenneth Offit
PURPOSE Identification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non-muscle invasive bladder cancer (NMIBC), the most
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Safety and efficacy of 90Y-FAPI-46 radioligand therapy in patients with advanced sarcoma and other cancer entities. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-14 Wolfgang P Fendler,Kim M Pabst,Lukas Kessler,Pedro Fragoso Costa,Justin Ferdinandus,Manuel Weber,Maria Lippert,Katharina Lueckerath,Lale Umutlu,Karina Kostbade,Ilektra A Mavroeidi,Martin Schuler,Marit Ahrens,Christoph Rischpler,Sebastian Bauer,Ken Herrmann,Jens T Siveke,Rainer Hamacher
PURPOSE We report efficacy and safety of 90Y-FAPI-46-RLT in patients with advanced sarcoma, pancreatic cancer (PDAC) and other cancer entities. EXPERIMENTAL DESIGN Up to four cycles of RLT were offered to patients with (a) progressive metastatic malignancy, (b) exhaustion of approved therapies, and (c) high fibroblast activation protein (FAP) expression, defined as SUVmax≥10 in more than 50% of tumor
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A Phase I Trial of TB-403 in Relapsed Medulloblastoma, Neuroblastoma, Ewing Sarcoma, and Alveolar Rhabdomyosarcoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-14 Giselle Saulnier Sholler,Dan G Duda,Genevieve Bergendahl,David Ebb,Matija Snuderl,Theodore W Laetsch,Jennifer Michlitsch,Derek Hanson,Michael S Isakoff,Kevin Bielamowicz,Jacqueline M Kraveka,William Ferguson,Peter Carmeliet,Andy De Deene,Lore Gijsen,Rakesh K Jain
PURPOSE Placental growth factor (PlGF) and its receptor neuropilin 1 (NRP-1) are elevated in malignant embryonal tumors and mediate tumor progression by promoting cell proliferation, survival, and metastasis. TB-403 is a blocking monoclonal antibody against PlGF that inhibits tumor growth and increases survival in orthotopic medulloblastoma (MB) models. PATIENTS AND METHODS We conducted a phase 1,
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A Phase II Study of Nivolumab Plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11). Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-12 Hyun Ae Jung,Keon-Uk Park,Sanghee Cho,Jinyeong Lim,Keun-Wook Lee,Min Hee Hong,Tak Yun,Ho Jung An,Woong-Yang Park,Sergio Pereira,Chan-Young Ock,Bhumsuk Keam
PURPOSE This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with platinum failed NPC. PATIENTS AND METHODS This is a phase II, multicenter, open-label, single-arm study. Patients with recurrent or metastatic NPC received nivolumab 3 mg/kg and gemcitabine 1,250 mg/m2 every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free
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Are the pieces starting to come together for management of desmoid tumors? Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-12 Anna C Greene,Brian A Van Tine
Desmoid tumor research is changing how desmoid tumors are managed with the prospective documentation that growing desmoid tumors spontaneously regress one-third of the time. Patient partnership through the Desmoid Research Tumor Foundation and academia is leading to rapid advancement in desmoid tumor biology understanding and treatment.
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Facts and hopes for immunotherapy in renal cell carcinoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-12 Chen Yao,Tian Zhang,Tuoqi Wu,James Brugarolas
Immunotherapy has made a significant impact in many solid tumors, including renal cell carcinoma (RCC). RCC has been known to be immune responsive since the cytokine era of interferon-alfa and interleukin-2, but only a small number of patients had durable clinical benefit. Since then, discoveries of key tumor drivers, as well as an understanding of the contribution of angiogenesis and the tumor microenvironment
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Phase 1b Study of the BET Inhibitor GS-5829 as Monotherapy and Combined with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-11 Rahul Aggarwal,Alexander N Starodub,Brian D Koh,Guan Xing,Andrew J Armstrong,Michael A Carducci
PURPOSE A Phase 1b study (1604) was conducted to evaluate the safety and efficacy of GS-5829, an oral bromodomain and extra-terminal inhibitor, alone and in combination with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). A Phase 1 study (1599) in solid tumors/lymphoma was also conducted. PATIENTS AND METHODS Men with confirmed mCRPC and disease progression despite abiraterone
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Molecular subclasses of clear cell ovarian carcinoma and their impact on disease behavior and outcomes. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-11 Kelly L Bolton,Denise Chen,Rosario I Corona de la Fuente,Zhuxuan Fu,Rajmohan Murali,Martin K Bel,Yanis Tazi,Julie M Cunningham,Irenaeus C C Chan,Brian J Wiley,Lea A Moukarzel,Stacey J Winham,Sebastian M Armasu,Jenny Lester,Esther Elishaev,Angela Laslavic,Catherine J Kennedy,Anna Piskorz,Magdalena Sekowska,Alison H Brand,Yoke-Eng Chiew,Paul Pharoah,Kevin M Elias,Ronny Drapkin,Michael Churchman,Charlie
PURPOSE To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes. EXPERIMENTAL DESIGN We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly-defined subgroups were identified and
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Anti-GD2 antibodies conjugated to IL15 and IL21 mediate potent anti-tumor cytotoxicity against neuroblastoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-08 Rosa Nguyen,Xiyuan Zhang,Ming Sun,Shahroze Abbas,Charlie Seibert,Michael C Kelly,Jack F Shern,Carol J Thiele
PURPOSE Half of the patients with high-risk neuroblastoma (NB) who receive GD2-targeted monoclonal antibody do not achieve long-term remissions. Recently, the antibody hu14.18 has been linked to interleukin (IL)2 (hu14.18-IL2) to enhance its efficacy and shown promising preclinical and clinical activity. We developed two new immunocytokines (ICs) by linking two other γc cytokines, IL15 and IL21, to
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Transcriptomic Correlates of Tumor Cell PD-L1 Expression and Response to Nivolumab Monotherapy in Metastatic Clear Cell Renal Cell Carcinoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-08 Thomas Denize,Yue Hou,Jean-Christophe Pignon,Emily Walton,Destiny J West,Gordon J Freeman,David A Braun,Catherine J Wu,Saurabh Gupta,Robert J Motzer,Michael B Atkins,David McDermott,Toni K Choueiri,Sachet A Shukla,Sabina Signoretti
PURPOSE PD-L1 expression on tumor cells (TC) is associated with response to anti-PD-1-based therapies in some tumor types, but its significance in ccRCC is uncertain. We leveraged tumor heterogeneity to identify molecular correlates of TC PD-L1 expression in ccRCC and assessed their role in predicting response to anti-PD-1 monotherapy. EXPERIMENTAL DESIGN RNA-sequencing was performed on paired TC PD-L1
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Comprehensive genome profiling in patients with metastatic non-small cell lung cancer: the precision medicine phase 2 randomized SAFIR02-Lung trial. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-08 Fabrice Barlesi,Pascale Tomasini,Maryam Karimi,Stefan Michiels,Judith Raimbourg,Catherine Daniel,Henri Janicot,Anne Madroszyk,Clarisse Audigier-Valette,Elisabeth Quoix,Julien Mazieres,Denis Moro-Sibilot,Eric Dansin,Olivier Molinier,Hugues Morel,Eric Pichon,Alexis Cortot,Josiane Otto,Fran Ois Chomy,Pierre-Jean Souquet,Nicolas Cloarec,Etienne Giroux Leprieur,Ivan Bieche,Ludovic Lacroix,Sandrine Boyault
PURPOSE Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non-small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown. EXPERIMENTAL DESIGN SAFIR02-Lung was an open-label, randomized, phase 2 trial, involving 33 centers in France. We investigated
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De-escalated neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC): Impact of molecular markers and survival analysis of the WSG-ADAPT-TN trial. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-07 Oleg Gluz,Ulrike Nitz,Cornelia Kolberg-Liedtke,Aleix Prat,Matthias Christgen,Sherko Kuemmel,Mohammad Parsa Mohammadian,Daniel Gebauer,Ronald Kates,Laia Paré,Eva-Maria Grischke,Helmut Forstbauer,Michael Braun,Mathias Warm,John Hackmann,Christoph Uleer,Bahriye Aktas,Claudia Schumacher,Rachel Wuerstlein,Monika Graeser,Enrico Pelz,Katarzyna Jóźwiak,Christine Zu Eulenburg,Hans Heinrich Kreipe,Nadia Harbeck
PURPOSE While optimal treatment in early TNBC remains unclear, de-escalated chemotherapy (CT) appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial. EXPERIMENTAL DESIGN ADAPT-TN is a randomized
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Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-07 Fuyang Li,Kathryn M Bondra,Samson Ghilu,Adam Studebaker,Qianqian Liu,Joel E Michalek,Mari Kogiso,Xiao-Nan Li,John A Kalapurakal,C David James,Sandeep Burma,Raushan T Kurmasheva,Peter J Houghton
PURPOSE We investigated why three patient derived xenograft (PDX) childhood BRAFV600E-mutant brain tumor models are highly sensitive to trametinib. Mechanisms of acquired resistance selected in situ, and approaches to prevent resistance were also examined, which may translate to both LGG molecular subtypes. EXPERIMENTAL DESIGN Sensitivity to trametinib (MEKi) alone or in combination with rapamycin
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A cathepsin targeted quenched activity-based probe facilitates enhanced detection of human tumors during resection. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-06 Gregory T Kennedy,David E Holt,Feredun S Azari,Elizabeth Bernstein,Bilal Nadeem,Ashley Chang,Neil T Sullivan,Alix Segil,Charuhas Deshpande,Eric Bensen,John T Santini,John C Kucharczuk,Edward J Delikatny,Matthew Bogyo,A J Matthew Egan,Charles W Bradley,Evgeniy Eruslanov,Jason D Lickliter,Gavin Wright,Sunil Singhal
PURPOSE Fluorescence-guided surgery using tumor-targeted contrast agents has been developed to improve the completeness of oncologic resections. Quenched activity-based probes that fluoresce after covalently binding to tumor-specific enzymes have been proposed to improve specificity, but none have been tested in humans. Here, we report the successful clinical translation of a cathepsin activity-based
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Rb tumor suppressor in small cell lung cancer: Combined genomic and immunohistochemical analysis with a description of a distinct Rb-proficient subset. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-06 Christopher A Febres Aldana,Jason C Chang,Ryan Ptashkin,Yuhan Wang,Erika Gedvilaite,Marina K Baine,William D Travis,Katia Ventura,Francis Bodd,Helena A Yu,Alvaro Quintanal-Villalonga,W Victoria Lai,Jacklynn V Egger,Michael Offin,Marc Ladanyi,Charles M Rudin,Natasha Rekhtman
PURPOSE RB1 mutations and loss of Rb expression represent consistent but not entirely invariable hallmarks of small cell lung cancer (SCLC). The prevalence and characteristics of SCLC retaining wild-type Rb are not well-established. Furthermore, the performance of targeted next-generation sequencing (NGS) vs immunohistochemistry for Rb assessment are not well-defined. EXPERIMENTAL DESIGN 208 clinical
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Agonizing over the stimulatory immune checkpoint ICOS. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-06 Jerry C Lee,Lawrence Fong
Vopratelimab, an anti-ICOS agonist, alone and in combination with nivolumab possesses limited toxicity and modest clinical activity in a large phase I/II trial. This treatment induced ICOS expression of CD4+ T cells, which may enable biomarkers for patient selection. Nevertheless, T cell agonists as cancer immunotherapies continues to be challenging.
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Facts and Hopes in Immunotherapy of Pancreatic Cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-07-01 Bruno Bockorny,Joseph E Grossman,Manuel Hidalgo
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancers to treat. For patients with advanced and metastatic disease, chemotherapy has yielded only modest incremental benefits which are not durable. Immunotherapy has revolutionized the treatment of other solid tumors by leading to cures where none existed only a decade ago, yet it has made few inroads with PDAC. A host of
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Systemic and oligo-acquired resistance to PD-(L)1 blockade in lung cancer. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-29 Adam J Schoenfeld,Hira A Rizvi,Danish Memon,Narek Shaverdian,Matthew J Bott,Jennifer L Sauter,Chiaojung Jillian Tsai,Jayon Lihm,David Hoyos,Andrew J Plodkowski,Rocio Perez-Johnston,Peter Sawan,Jacklynn V Egger,Benjamin D Greenbaum,Andreas Rimner,Gregory J Riely,Charles M Rudin,Valerie W Rusch,Daniel R Gomez,Matthew D Hellmann
PURPOSE Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood. EXPERIMENTAL DESIGN All cases of metastatic lung cancer treated with PD-(L)1 blockade at Memorial Sloan Kettering were reviewed. In acquired resistance (complete/partial response per RECIST, followed by progression), clinical patterns were distinguished as oligo (OligoAR
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Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-29 Zhanjie Zhang,Bian Wu,Gang Peng,Guixiang Xiao,Jing Huang,Qian Ding,Chengzhang Yang,Xingao Xiong,Hui Ma,Liangliang Shi,Jinsong Yang,Xiaohua Hong,Jielin Wei,You Qin,Chao Wan,Yi Zhong,Yan Zhou,Xueyan Zhao,Yangming Leng,Tao Zhang,Gang Wu,Min Yao,Xiaomeng Zhang,Kunyu Yang
PURPOSE This study aimed to assess the antitumor activity and safety of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN In this single-center, single-arm, phase 2 trial, patients with resectable stage III-IVB HNSCC received chemotherapy [albumin-bound paclitaxel 260 mg/m2 (or docetaxel
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Extracellular vesicles may predict response to radioembolization and sorafenib treatment in advanced hepatocellular carcinoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-28 Timothy Wai Ho Shuen,Marianna Alunni-Fabbroni,Elif Öcal,Peter Malfertheiner,Moritz Wildgruber,Regina Schinner,Maciej Pech,Julia Benckert,Bruno Sangro,Christiane Kuhl,Antonio Gasbarrini,Pierce Kah Hoe Chow,Han Chong Toh,Jens Ricke
PURPOSE SORAMIC is a randomized controlled trial in advanced HCC patients undergoing sorafenib+/- selective internal radiation therapy (SIRT). We investigated the value of extracellular vesicle (EV)-based proteomics for treatment response prediction. EXPERIMENTAL DESIGN The analysis population comprised 25 patients receiving SIRT+sorafenib and 20 patients receiving sorafenib-alone. Patients were classified
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Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-24 Diwakar Davar,Hassane M Zarour
Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) proteins transformed the management of advanced cancers. Many tumor-intrinsic factors modulate immunological and clinical responses to such therapies, but ample evidence also implicates the gut microbiome in responses. The gut microbiome, comprising the bacteria, archaea,
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Classification of BRCA2 variants of uncertain significance (VUS) using an ACMG/AMP model incorporating a homology directed repair (HDR) functional assay. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-23 Chunling Hu,Lisa R Susswein,Maegan E Roberts,Hana Yang,Megan L Marshall,Susan Hiraki,Windy Berkofsky-Fessler,Sounak Gupta,Wei Shen,Carolyn A Dunn,Huaizhi Huang,Jie Na,Susan M Domchek,Siddhartha Yadav,Alvaro N A Monteiro,Eric C Polley,Steven N Hart,Kathleen S Hruska,Fergus J Couch
PURPOSE The identification of variants of uncertain significance (VUS) in the BRCA1 and BRCA2 genes by hereditary cancer testing poses great challenges for the clinical management of variant carriers. The ACMG/AMP variant classification framework, which incorporates multiple sources of evidence, has the potential to establish the clinical relevance of many VUS. We sought to classify the clinical relevance
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Tumor immune microenvironment changes by multiplex immunofluorescence staining in a pilot study of neoadjuvant talazoparib for early-stage breast cancer patients with a hereditary BRCA mutation. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-23 Tapsi Kumar,Evthokia Hobbs,Fei Yang,Jeffrey T Chang,Alejandro Contreras,Edwin R Parra Cuentas,Haven Garber,Sanghoon Lee,Yiling Lu,Marion E Scoggins,Beatriz E Adrada,Gary J Whitman,Banu K Arun,Elizabeth A Mittendorf,Jennifer K Litton
Purpose The immunological profile of early-stage breast cancer treated with neoadjuvant PARP inhibitors has not been described. The aim of this study was to delineate the changes in the tumor immune microenvironment (TiME) induced by talazoparib. Methods Patients with operable germline BRCA1/2 pathogenic variant (gBRCA1/2+) breast cancer were enrolled in a feasibility study of neoadjuvant talazoparib
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Shining a FLASHlight on ultrahigh dose rate radiation and possible late toxicity. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-23 Amit Maity,Constantinos Koumenis
A recent study reported results from a clinical trial in cats and from experiments in minipigs in which a single dose of radiation was delivered at ultrahigh dose rates (FLASH). There was acceptable acute toxicity; however, some animals suffered severe late toxicity, raising caution in the design of future trials.
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FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-23 Andrea C Baines,Rachel Ershler,Bindu Kanapuru,Qing Xu,Guoxiang Shen,Liang Li,Lian Ma,Olanrewaju O Okusanya,Natalie E Simpson,Wanda Nguyen,Marc R Theoret,Richard Pazdur,Nicole J Gormley
On August 5, 2020, the Food and Drug Administration granted accelerated approval to belantamab mafodotin-blmf (BLENREP; GlaxoSmithKline) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Substantial evidence of effectiveness was
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Targeting Ferroptosis Vulnerability in Synovial Sarcoma: Is it all about ME1? Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Vivek Subbiah,Boyi Gan
Understanding metabolic dependencies and their therapeutic vulnerabilities are key to precision oncology. Malic enzyme1 (ME1) is frequently overexpressed in cancers with pro-tumorigenic effects. In contrast, consistent loss of ME1 expression in synovial sarcoma compared with other sarcomas indicates a unique ferroptosis liability for precision therapy in this form of cancer.
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Combination therapies for advanced hepatocellular carcinoma: biomarkers and unmet needs. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Sarah Cappuyns,Josep M Llovet
The novel combination of checkpoint inhibitors targeting the PD(L)1 pathway and anti-VEGFA therapy has revolutionized the treatment landscape of advanced HCC. However, biomarkers predictive of response to these therapies are still lacking, representing a major clinical challenge.
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FDA Approval Summary: Belzutifan for von Hippel-Lindau disease associated tumors. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Jaleh Fallah,Michael H Brave,Chana Weinstock,Gautam U Mehta,Diana Bradford,Haley Gittleman,Erik W Bloomquist,Rosane Charlab,Salaheldin S Hamed,Claudia P Miller,Sarah E Dorff,Wiley A Chambers,Bronwyn D Mixter,Jeannette Dinin,William F Pierce,Tiffany K Ricks,Shenghui Tang,Martha Donoghue,Richard Pazdur,Laleh Amiri-Kordestani,Amna Ibrahim,Julia A Beaver
On August 13, 2021, the United States Food and Drug Administration (FDA) approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate
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Novel Radiomic Measurements of Tumor-Associated Vasculature Morphology on Clinical Imaging as a Biomarker of Treatment Response in Multiple Cancers. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Nathaniel Braman,Prateek Prasanna,Kaustav Bera,Mehdi Alilou,Mohammadhadi Khorrami,Patrick Leo,Maryam Etesami,Manasa Vulchi,Paulette Turk,Amit Gupta,Prantesh Jain,Pingfu Fu,Nathan Pennell,Vamsidhar Velcheti,Jame Abraham,Donna Plecha,Anant Madabhushi
PURPOSE Tumor-associated vasculature is distinguished its convolutedness, leakiness, and chaotic architecture, which facilitates the creation of a treatment resistant tumor microenvironment. Measurable differences in these attributes might help stratify patients by potential benefit of systemic therapy. In this work, we present a new category of radiomic quantitative tumor-associated vasculature (QuanTAV)
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Membrane-anchored and tumor-targeted IL-12 (attIL12)-PBMC therapy for osteosarcoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Qing Yang,Jiemiao Hu,Zhiliang Jia,Qi Wang,Jing Wang,LongHoang Dao,Wendong Zhang,Sheng Zhang,Xueqing Xia,Richard Gorlick,Shulin Li
PURPOSE Chimeric antigen receptor (CAR) T cell therapy has shown great promise for treating hematologic malignancies but requires a long duration of T-cell expansion, is associated with severe toxicity, and has limited efficacy for treating solid tumors. We designed experiments to address those challenges. EXPERIMENTAL DESIGN We generated a cell membrane-anchored and tumor-targeted interleukin-12 (attIL12)
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Lenalidomide plus R-GDP (R2-GDP) in Relapsed/Refractory Diffuse Large B Cell Lymphoma. Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker subanalysis. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Natalia Palaz N-Carri N,Alejandro Mart N Garc A-Sancho,Esteban Nogales-Fern Ndez,Carlos Jim Nez-Cortegana,Fernando Carnicero-Gonz Lez,Eduardo R Os-Herranz,F Tima de la Cruz-Vicente,Guillermo Rodr Guez-Garc A,Rub N Fern Ndez-Lvarez,Natividad Mart Nez-Banaclocha,Josep Gum-Padr,Jos G Mez-Codina,Antonio Salar-Silvestre,Delvys Rodr Guez-Abreu,Laura G Lvez-Carvajal,Jorge Labrador,Mar A Guirado-Risue O,Daniel
PURPOSE New therapeutic options are needed in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). Lenalidomide based schedules can reverse rituximab refractoriness in lymphoma. EXPERIMENTAL DESIGN In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with R2-GDP schedule: lenalidomide 10 mg d1-14, rituximab 375 mg/m2 d1, cisplatin 60
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Anti-cancer activity of the combination of cabozantinib and temozolomide in uterine sarcoma. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Joseph J Noh,Young-Jae Cho,Ji-Yoon Ryu,Jung-Joo Choi,Jae Ryoung Hwang,Ju-Yeon Choi,Jeong-Won Lee
PURPOSE To evaluate the anti-cancer effects of cabozantinib, temozolomide, and their combination in uterine sarcoma cell lines and mouse xenograft models. EXPERIMENTAL DESIGN Human uterine sarcoma cell lines (SK-LMS-1, SK-UT-1, MES-SA, and SKN) were used to evaluate the anti-cancer activity of cabozantinib, temozolomide, and their combination. The optimal dose of each drug was determined by MTT assay
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Mechanistic Modeling of Central Nervous System Pharmacokinetics and Target Engagement of HER2 Tyrosine Kinase Inhibitors to Inform Treatment of Breast Cancer Brain Metastases. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-21 Jing Li,Jun Jiang,Xun Bao,Vineet Kumar,Stephen C Alley,Scott Peterson,Anthony J Lee
PURPOSE This study evaluated the central nervous system (CNS) pharmacokinetics and target engagement of lapatinib, neratinib, and tucatinib in patients with cancer, using a physiologically based pharmacokinetic (PBPK) modeling approach. EXPERIMENTAL DESIGN Drug-specific parameters for in vitro metabolism, binding to plasma proteins and brain tissues, transcellular passive permeability, and interactions
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Circulating tumor DNA (ctDNA) kinetics predict progression-free and overall survival in EGFR TKI-treated patients with EGFR-mutant NSCLC (SWOG S1403). Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-17 Philip C Mack,Jieling Miao,Mary W Redman,James Moon,Sarah B Goldberg,Roy S Herbst,Mary Ann Melnick,Zenta Walther,Fred R Hirsch,Katerina Politi,Karen Kelly,David R Gandara
PURPOSE Dynamic changes in circulating tumor DNA (ctDNA) are under investigation as an early indicator of treatment outcome. EXPERIMENTAL DESIGN Serial plasma ctDNA (baseline, 8 weeks and at progression) was prospectively incorporated into the SWOG S1403 clinical trial of afatinib +/- cetuximab in TKI-naive, EGFR-mutation tissue-positive NSCLC. RESULTS EGFR mutations were detected in baseline ctDNA
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Neoadjuvant Trastuzumab and Pyrotinib for Locally Advanced HER2-Positive Breast Cancer (NeoATP): Primary Analysis of a Phase II Study. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-17 Wenjin Yin,Yaohui Wang,Ziping Wu,Yumei Ye,Liheng Zhou,Shuguang Xu,Yanping Lin,Yueyao Du,Tingting Yan,Fan Yang,Jie Zhang,Qiang Liu,Jinsong Lu
PURPOSE Despite accumulating evidence on dual blockade of human epidermal growth factor receptor 2 (HER2) for locally advanced HER2-positive breast cancer, no robust evidence supports the addition of pyrotinib to trastuzumab in the neoadjuvant setting. The NeoATP trial aimed to evaluate the efficacy and safety of pyrotinib with neoadjuvant trastuzumab and chemotherapy. METHODS The phase II NeoATP trial
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Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-grade Dysplasia. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-15 Ming Yu,Helen R Moinova,Amber Willbanks,Victoria K Cannon,Ting Wang,Kelly Carter,Andrew Kaz,Deepti Reddi,John Inadomi,Georg Luebeck,Prasad G Iyer,Marcia I Canto,Jean S Wang,Nicholas J Shaheen,Prashanthi N Thota,Joseph E Willis,Thomas LaFramboise,Amitabh Chak,Sanford D Markowitz,William M Grady
PURPOSE Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high grade dysplasia (HGD) from normal
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Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell Associated Neurotoxicity Syndrome in B-Cell ALL Patients Receiving CART19. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-15 Caroline Diorio,Rawan Shraim,Regina Myers,Edward M Behrens,Scott Canna,Hamid Bassiri,Richard Aplenc,Chakkapong Burudpakdee,Fang Chen,Amanda M DiNofia,Saar Gill,Vanessa Gonzalez,Michele P Lambert,Allison Barz Leahy,Bruce L Levine,Robert B Lindell,Shannon L Maude,J Joseph Melenhorst,Haley Newman,Jessica Perazzelli,Alix E Seif,Simon F Lacey,Carl H June,David M Barrett,Stephan A Grupp,David T Teachey
PURPOSE Study the biology and identify markers of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in children post chimeric antigen receptor T-cell (CART) treatment. EXPERIMENTAL DESIGN We use comprehensive proteomic profiling to measure over 1400 serum proteins at multiple serial timepoints in a cohort of patients with B-cell acute lymphoblastic
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Safety and tolerability of MEDI0562, an OX40 agonist monoclonal antibody, in combination with durvalumab or tremelimumab in adult patients with advanced solid tumors. Clin. Cancer Res. (IF 13.801) Pub Date : 2022-06-14 Jonathan W Goldman,Sarina A Piha-Paul,Brendan Curti,Katrina S Pedersen,Todd M Bauer,Stefanie L Groenland,Richard D Carvajal,Vaishali Chhaya,Gray Kirby,Kelly McGlinchey,Scott A Hammond,Katie L Streicher,Danielle Townsley,Young Kwang Chae,Jens Voortman,Aurelien Marabelle,John Powderly
PURPOSE Combination therapies targeting immunological checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1K OX40 monoclonal antibody, in combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), in adult patients with previously treated advanced solid tumors. EXPERIMENTAL DESIGN In this phase 1, multicenter,