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1دورية أكاديمية
المؤلفون: Bin Li, Jun Li, Tian Chen, Uwe M Martens, Lazar Vujanovic, Rom Leidner, Robert L Ferris, William Sharfman, Chrisann Kyi, Suzanne L Topalian, Janis M Taube, Christine H Chung, William C Spanos, Anthony Gonçalves, Lot A Devriese, Helene Gauthier, Simon I Chiosea, Julie E Stein, Adam Barrows
المصدر: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 6 (2021)
مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Background Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting.Methods The phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria.Results From November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III–IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3–4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR.Conclusions Neoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach.Trial registration number ClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759Test.
وصف الملف: electronic resource
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المؤلفون: Adam Barrows
المصدر: Time & Society. 28:1311-1314
مصطلحات موضوعية: Sociology and Political Science, Ecology (disciplines), media_common.quotation_subject, Art history, Art, media_common
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::cf8bb3baf3e18162e1580b8098c8692bTest
https://doi.org/10.1177/0961463x19846373Test -
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المؤلفون: Adam Barrows
المصدر: Time in Variance ISBN: 9789004470170
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::f98879a98cd7b666ef48eeae4600162bTest
https://doi.org/10.1163/9789004470170_008Test -
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المؤلفون: Lazar Vujanovic, Jun Li, Anthony Gonçalves, Julie E. Stein, Chrisann Kyi, Rom Leidner, Christine H. Chung, Hélène Gauthier, Janis M. Taube, Uwe M Martens, Tian Chen, Robert L. Ferris, William H. Sharfman, Bin Li, Simon I. Chiosea, Lot A. Devriese, William C. Spanos, Suzanne L. Topalian, Adam Barrows
المصدر: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 6 (2021)
مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Immunology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Biopsy, Clinical endpoint, Immunology and Allergy, Medicine, Stage (cooking), Adverse effect, RC254-282, Pharmacology, medicine.diagnostic_test, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunotherapy, 030104 developmental biology, Tolerability, Tumor progression, 030220 oncology & carcinogenesis, Molecular Medicine, Nivolumab, business
الوصف: BackgroundHead and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting.MethodsThe phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria.ResultsFrom November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III–IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3–4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR.ConclusionsNeoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach.Trial registration numberClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759Test.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07a9f0d3402b33758610051fccbc0a24Test
https://jitc.bmj.com/content/9/6/e002568.fullTest -
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المؤلفون: Adam Barrows
المصدر: KronoScope. 20:154-156
مصطلحات موضوعية: Philosophy, History and Philosophy of Science, Art history, Astronomy and Astrophysics, Social Sciences (miscellaneous)
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0702f5c26b02fb83b287bd37820d0642Test
https://doi.org/10.1163/15685241-12341461Test -
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المؤلفون: Adam Barrows
المصدر: Journal of Literary & Cultural Disability Studies. 12:391-405
مصطلحات موضوعية: Health (social science), Psychoanalysis, Distrust, media_common.quotation_subject, General Social Sciences, Temporality, Mental illness, medicine.disease, Disability studies, Reading (process), General Health Professions, medicine, Normative, Criticism, Narrative, Psychology, media_common
الوصف: The article demonstrates how the insights of literary critical disability studies can help to refocus our reading of Kurt Vonnegut's 1969 novel, Slaughterhouse-Five, away from a diagnosis of the disability of its main character and toward an understanding of the ways in which the work disables normative assumptions about the social body and its functions. The novel's "schizophrenic" temporal structure is not reflective of the temporality of mental illness, as a diagnostic reading would have it, but rather exposes the ways in which normative time and temporality have been complicit in diagnosing and disenfranchising disabled people. Vonnegut's disabling of the entire temporal structure of Slaughterhouse-Five draws attention to ways in which different paces, rhythms, and tempos can be accommodated in narrative; yet, criticism has persisted in meeting this narrative accommodation with clinical distrust and ironic detachment. Reading Billy Pilgrim as diagnosable with a clinically recognizable disease and forcing the text to reveal a true nature underneath the illusions and delusions of both character and author is a way of disavowing Vonnegut's most radical claim: that health, truth, and even reality itself are sociological constructs.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0114210695ab9248bd7d99b558fac11dTest
https://doi.org/10.3828/jlcds.2018.32Test -
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المؤلفون: Ragini R. Kudchadkar, Uwe M. Martens, Paul Nghiem, Robert L. Ferris, Julie E. Stein, Junchen Gu, Suzanne L. Topalian, Michi M. Shinohara, Adam Barrows, Christine H. Chung, Rima M. Kulikauskas, Jean Pierre Delord, Lara Dunn, Andrea Horvath, Janis M. Taube, Shailender Bhatia, Lot A. Devriese, William H. Sharfman, Bin Li, Céleste Lebbé, Tian Chen, Asim Amin, Elizabeth L. Engle, Christopher D. Lao
المصدر: J Clin Oncol
مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Cancer Research, Skin Neoplasms, Merkel cell polyomavirus, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antineoplastic Agents, Immunological, medicine, Carcinoma, Biomarkers, Tumor, Humans, Basal cell, Survival rate, Aged, Aged, 80 and over, biology, Merkel cell carcinoma, business.industry, Middle Aged, medicine.disease, biology.organism_classification, Prognosis, Neoadjuvant Therapy, Clinical trial, Carcinoma, Merkel Cell, Gene Expression Regulation, Neoplastic, Survival Rate, 030104 developmental biology, Nivolumab, Oncology, Rapid Communications, 030220 oncology & carcinogenesis, Cancer research, Female, Skin cancer, Neoplasm Recurrence, Local, business, Follow-Up Studies
الوصف: PURPOSE Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti–PD-1 in the neoadjuvant setting for resectable MCC. METHODS In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies. RESULTS Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received ≥ 1 nivolumab dose. Three patients (7.7%) did not undergo surgery because of tumor progression (n = 1) or adverse events (n = 2). Any-grade treatment-related adverse events occurred in 18 patients (46.2%), and grade 3-4 events in 3 patients (7.7%), with no unexpected toxicities. Among 36 patients who underwent surgery, 17 (47.2%) achieved a pathologic complete response (pCR). Among 33 radiographically evaluable patients who underwent surgery, 18 (54.5%) had tumor reductions ≥ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation. CONCLUSION Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9101eb30d12f818b206c8acb3f4f9b3fTest
https://pubmed.ncbi.nlm.nih.gov/32324435Test -
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المؤلفون: Adam Barrows
مصطلحات موضوعية: Literature, Politics, business.industry, media_common.quotation_subject, Modernism (music), Literary criticism, Art, business, media_common
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c6116c73d2daebab575cdbc8b9a90fd8Test
https://doi.org/10.1525/9780520948150-003Test
النص الكامل