Author
Alan Mitchell
Other affiliations: Fred Hutchinson Cancer Research Center
Bio: Alan Mitchell is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Multiple myeloma & Lung cancer. The author has an hindex of 17, co-authored 35 publications receiving 4512 citations. Previous affiliations of Alan Mitchell include Fred Hutchinson Cancer Research Center.
Papers
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Imperial College London1, University of Barcelona2, Keio University3, University of Duisburg-Essen4, Queen's University5, Peter MacCallum Cancer Centre6, University of Michigan7, University of São Paulo8, Yale University9, Northern General Hospital10, University of Caen Lower Normandy11, Fred Hutchinson Cancer Research Center12, University of Oxford13, Memorial Sloan Kettering Cancer Center14, University of Sydney15, Sungkyunkwan University16, Seoul National University17, Kyorin University18, University of Copenhagen19, Nippon Medical School20, Katholieke Universiteit Leuven21, University of Texas MD Anderson Cancer Center22, University of Antwerp23, Hyogo College of Medicine24, University of Western Australia25, Glenfield Hospital26, Cleveland Clinic27, Icahn School of Medicine at Mount Sinai28, University of Turin29, Université libre de Bruxelles30, Juntendo University31, National Cancer Research Institute32, Mayo Clinic33, University of Toronto34, Sinai Grace Hospital35, Netherlands Cancer Institute36, Hiroshima University37, City of Hope National Medical Center38, University of Chicago39, New York University40, Georgetown University41, University of Tokushima42, University of Pisa43, Osaka University44, University of Valencia45, Good Samaritan Hospital46, Military Medical Academy47, Fundación Favaloro48, Autonomous University of Barcelona49, Complutense University of Madrid50, University of Oviedo51, National and Kapodistrian University of Athens52, Rovira i Virgili University53, Autonomous University of Madrid54, Ghent University55
TL;DR: The methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition of the TNM Classification for lung cancer due to be published late 2016 are described.
2,826 citations
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University of Washington Medical Center1, Johns Hopkins University School of Medicine2, Emory University3, University of Washington4, Merck & Co.5, Johns Hopkins University6, University of California, San Francisco7, Fred Hutchinson Cancer Research Center8, Icahn School of Medicine at Mount Sinai9, Yale University10, Stanford University11, Ohio State University12, National Institutes of Health13
TL;DR: First-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56% and effectiveness was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.
Abstract: BackgroundMerkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1. MethodsIn this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti–PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing. ResultsA total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patient...
997 citations
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Memorial Sloan Kettering Cancer Center1, Keio University2, Beth Israel Deaconess Medical Center3, Mount Sinai Hospital4, Yale University5, Fox Chase Cancer Center6, New Generation University College7, University of Chicago8, New York University9, Imperial College London10, Radboud University Nijmegen11, University of Barcelona12, Peter MacCallum Cancer Centre13, University of Michigan14, University of São Paulo15, Fred Hutchinson Cancer Research Center16, University of Duisburg-Essen17, Northern General Hospital18, University of Caen Lower Normandy19, Churchill Hospital20, Queen's University21, University of Sydney22, Sungkyunkwan University23, Seoul National University24, Kyorin University25, University of Copenhagen26, Nippon Medical School27, Katholieke Universiteit Leuven28, British Hospital29, University of Texas MD Anderson Cancer Center30, University of Antwerp31, Hyogo College of Medicine32, University of Western Australia33, Glenfield Hospital34, Cleveland Clinic35, Icahn School of Medicine at Mount Sinai36, University of Turin37, Université libre de Bruxelles38, Juntendo University39, National Cancer Research Institute40, Mayo Clinic41, Princess Margaret Cancer Centre42, Sinai Grace Hospital43, Netherlands Cancer Institute44, Hiroshima University45, City of Hope National Medical Center46, Georgetown University47, University of Tokushima48, University of Pisa49, Osaka University50
TL;DR: Codes for the primary tumor categories of AIS and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part‐solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer are proposed.
431 citations
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TL;DR: It is shown that extramedullary disease is more prevalent in genomically defined high-risk multiple myeloma and is associated with shorter progression-free survival and overall survival, even in the era of novel agents.
Abstract: Background Extramedullary disease is an uncommon manifestation in multiple myeloma and can either accompany newly diagnosed disease or develop with disease progression or relapse. We evaluated the impact of this disease feature on patients' outcome in the context of novel agents.Design and Methods We analyzed clinical and biological features of extramedullary disease in 936 patients with multiple myeloma enrolled in Total Therapy protocols, 240 patients in non-Total Therapy protocols, and 789 non-protocol patients, all of whom had baseline positron emission tomography scans to document extramedullary disease at diagnosis and its subsequent development at the time of disease progression or relapse.Results The most common sites for extramedullary disease at diagnosis were skin and soft tissue whereas liver involvement was the striking feature in extramedullary disease at disease relapse or progression. Regardless of therapy, extramedullary disease was associated with shorter progression-free and overall survival, as well as the presence of anemia, thrombocytopenia, elevated serum lactate dehydrogenase, cytogenetic abnormalities, and high-risk features in 70-and 80-gene risk models in univariate analysis. Multivariate analysis with logistic regression revealed that this disease feature was more prevalent in patients with an elevated centrosome index, as determined by gene expression profiling, as well as in myeloma molecular subtypes that are more prone to relapse. These include the MF subtype (also called the “MAF” subtype, associated with over-expression of the MAF gene seen with chromosome translocation 14;16 or 14;20) and the PR subtype (also called the “Proliferation” subtype, associated with overexpression of pro-proliferative genes).Conclusions These data show that extramedullary disease is more prevalent in genomically defined high-risk multiple myeloma and is associated with shorter progression-free survival and overall survival, even in the era of novel agents. All clinical trials included in the analyses were registered with www.clinicaltrials.gov (NCT00083551, NCT00083876, NCT00081939, NCT00572169, NCT00644228,NCT00002548,NCT00734877).
285 citations
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TL;DR: New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy, and evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways.
Abstract: The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte–associated protein 4 (CTLA-4) or the programmed cell death 1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the preexistence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long-lasting disease control, yet one-third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
3,736 citations
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Mayo Clinic1, National and Kapodistrian University of Athens2, University of Turin3, Heidelberg University4, Harvard University5, Memorial Sloan Kettering Cancer Center6, University of Navarra7, University of Pennsylvania8, VU University Medical Center9, Emory University10, University of Bologna11, Mount Sinai Hospital12, Memorial Hospital of South Bend13, Karolinska University Hospital14, Carolinas Healthcare System15, Aalborg University16, Ankara University17, Cedars-Sinai Medical Center18
TL;DR: The disease definition of multiple myeloma is updated to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions), and specific metrics that new biomarkers should meet for inclusion in the disease definition are provided.
Abstract: This International Myeloma Working Group consensus updates the disease defi nition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identifi cation of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfi l the criteria for the presence of myeloma-defi ning CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specifi c metrics that new biomarkers should meet for inclusion in the disease defi nition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any diff erences in outcome that might occur as a result of the new disease defi nition.
3,049 citations
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Imperial College London1, University of Barcelona2, Keio University3, University of Duisburg-Essen4, Queen's University5, Peter MacCallum Cancer Centre6, University of Michigan7, University of São Paulo8, Yale University9, Northern General Hospital10, University of Caen Lower Normandy11, Fred Hutchinson Cancer Research Center12, University of Oxford13, Memorial Sloan Kettering Cancer Center14, University of Sydney15, Sungkyunkwan University16, Seoul National University17, Kyorin University18, University of Copenhagen19, Nippon Medical School20, Katholieke Universiteit Leuven21, University of Texas MD Anderson Cancer Center22, University of Antwerp23, Hyogo College of Medicine24, University of Western Australia25, Glenfield Hospital26, Cleveland Clinic27, Icahn School of Medicine at Mount Sinai28, University of Turin29, Université libre de Bruxelles30, Juntendo University31, National Cancer Research Institute32, Mayo Clinic33, University of Toronto34, Sinai Grace Hospital35, Netherlands Cancer Institute36, Hiroshima University37, City of Hope National Medical Center38, University of Chicago39, New York University40, Georgetown University41, University of Tokushima42, University of Pisa43, Osaka University44, University of Valencia45, Good Samaritan Hospital46, Military Medical Academy47, Fundación Favaloro48, Autonomous University of Barcelona49, Complutense University of Madrid50, University of Oviedo51, National and Kapodistrian University of Athens52, Rovira i Virgili University53, Autonomous University of Madrid54, Ghent University55
TL;DR: The methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition of the TNM Classification for lung cancer due to be published late 2016 are described.
2,826 citations
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TL;DR: Continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
Abstract: Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
2,410 citations
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University of Turin1, Aix-Marseille University2, University Hospital of South Manchester NHS Foundation Trust3, National Health Service4, University of Ljubljana5, Karolinska University Hospital6, Centre Hospitalier Universitaire de Grenoble7, University of Aberdeen8, The Royal Marsden NHS Foundation Trust9, VU University Medical Center10, University of Salamanca11, Katholieke Universiteit Leuven12, University Hospital of Lausanne13
TL;DR: The ESMO Guidelines Committee concluded that current state-of-the-art oncology practices in France, Belgium, and the Netherlands are suitable for frontline use and recommend further research into these practices.
2,349 citations