Cancer Biotherapy and Radiopharmaceuticals, Volume 34, Issue 6, Page 345-354, August 2019.
Cancer Biotherapy and Radiopharmaceuticals, Volume 34, Issue 6, Page 405-412, August 2019.
Cancer Biotherapy and Radiopharmaceuticals, Volume 34, Issue 6, Page 417-417, August 2019.
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Abstract Backgrounds This study was designed to evaluate the role of thoracic radiotherapy (TRT) in a selected patient population with oligometastatic extensive stage small-cell lung cancer (ES-SCLC) without brain or liver involved. The underlying hypothesis was that TRT will improve outcomes in this favorable patient population. Methods 305 patients were...
Abstract Purpose Peripheral T cell lymphomas (PTCL) are a rare and heterogeneous group of aggressive non-Hodgkin lymphomas, showing a generally poor prognosis. In this retrospective analysis, we aimed to investigate the impact of autologous stem cell transplantation (autoSCT) in PTCL. Methods A retrospective analysis of 58 consecutive unselected PTCL patients...
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Publication date: October 2019Source: Cancer Epidemiology, Volume 62Author(s): Mercè Grau-Pérez, Camila Cabello, Jesús-María González-Martín, Leopoldo Borrego, Gregorio CarreteroAbstractBackgroundAn early diagnosis of cutaneous melanoma remains determinant for improved survival. Low educational attainment has been associated with a late-stage diagnosis in settings where access to healthcare is restricted. Little evidence is available from regions with universal healthcare. We aimed at analysing whether...
Publication date: October 2019Source: Cancer Epidemiology, Volume 62Author(s): Ismael Galván, Ângela Inácio, María Dañino, Rosa Corbí-Llopis, María T. Monserrat, José Bernabeu-WittelAbstractBackgroundMelanoma is one of the highest metastatic cancers and its incidence is rapidly increasing. A great effort has been devoted to determine gene mutations and expression profiles in melanoma cells, but less attention has been given to the possible influence of melanin synthesis in melanocytes on melanomagenesis....
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Abstract Purpose Published results of quality of life (QoL) studies mostly concern whole brain radiotherapy for limited or multiple brain metastases. This prospective multicentre study was designed to compare the QoL of patients with limited (1–3) brain metastases treated with either whole brain (WBRT) or stereotactic radiotherapy (SRT). Methods From 01/2007–03/2011,...
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Removal of colorectal adenomas is an effective strategy to reduce colorectal cancer (CRC) mortality rates. However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. The present study aimed to characterize adenomas by in‐depth molecular profiling, to obtain insights into altered biology associated with the colorectal adenoma‐to‐carcinoma progression. We obtained low‐coverage whole genome sequencing, RNA sequencing and tandem mass spectrometry data for 30...
Inflammation is currently considered a hallmark of cancer and plays a decisive role in different stages of tumorigenesis, including initiation, promotion, progression, metastasis and resistance to antitumor therapies. Colorectal cancer is a disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter cancer progression. Several reports have noted the ability of various parasitic infections to modulate cancer development,...
Immigration in Europe has increased considerably over the past decades with the immigrant population similarly expanding in Finland. Our aim was to study childhood cancer mortality and survival in immigrants. In all, 4,437 patients diagnosed with cancer under the age of 20 years between 1990 and 2009 were identified from the Finnish Cancer Registry and their parents from the Population Register Center. Information on demographic factors was obtained from Statistics Finland. Poisson regression modelling...
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Publication date: Available online 14 August 2019Source: Cancer/RadiothérapieAuthor(s): P. Graff, P. Blanchard, J. Thariat, S. Racadot, M. LapeyreRésuméLa surveillance post-thérapeutique des patients atteints de cancer ORL s’inscrit dans une multidisciplinarité forte. L’oncologue radiothérapeute doit y prendre une part active. Sa connaissance oncologique d’une part et son expertise technique d’autre part en font un acteur majeur dans la détection du risque de récidive de la tumeur primitive, de l’apparition...
Publication date: Available online 14 August 2019Source: Cancer/RadiothérapieAuthor(s): A. Modesto, N. Carrère, R. Guimbaud, M. Rives, É. Deutsch, L. Quéro, G. CréhangeRésuméLa prise en charge des cancers de l’œsophage résécables repose sur un traitement multimodal associant de la radio-chimiothérapie (RCT) néoadjuvante avant une prise en charge chirurgicale. Cette séquence thérapeutique permet un taux de survie sans maladie à 2 ans autour de 45 % au prix d’une morbidité post-opératoire qui reste...
Publication date: Available online 14 August 2019Source: Cancer/RadiothérapieAuthor(s): T. Frédéric-Moreau, L. Piram, R. Bellini, F. Martin, J. Miroir, N. Saroul, N. Pham Dang, J. Biau, M. LapeyreRésuméCet article propose le concept de la sélectivité des zones péritumorales microscopiques à traiter de principe par irradiation pour les tumeurs de la glande sous-mandibulaire en se basant sur le mode d’extension des cancers. Il présente les différentes délimitations des volumes cibles anatomocliniques...
Publication date: Available online 14 August 2019Source: Cancer/RadiothérapieAuthor(s): M. Baty, G. Créhange, D. Pasquier, X. Palard, A. Deleuze, K. Gnep, S. Key, L. Beuzit, J. Castelli, R. de CrevoisierAbstractPurposeLiterature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer.Materials and methodsA total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate...
Publication date: Available online 14 August 2019Source: Cancer/RadiothérapieAuthor(s): L. Quéro, S. Guillerm, P. Castelnau-Marchand, M. Labidi, C. HennequinRésuméAvec le chirurgien, le gastroentérologue et le médecin traitant, l’oncologue-radiothérapeute est impliqué dans le suivi post-thérapeutique des patients atteints d’un cancer du rectum traité par irradiation. Un suivi est recommandé par de nombreuses sociétés savantes ainsi que des groupes d’experts. Celui-ci consiste à réaliser un examen...
Publication date: Available online 13 August 2019Source: Cancer/RadiothérapieAuthor(s): V. FavaudonRésuméLes progrès de la radiothérapie anticancéreuse au cours des dernières décennies sont venus, pour l’essentiel, des avancées de l’imagerie, de la balistique et de la dosimétrie. En revanche, les technologies embarquées dans les accélérateurs linéaires d’électrons utilisés en conversion électrons/photons ainsi que les modalités de délivrance de la dose, avec un débit de dose voisin du gray par minute,...
Publication date: Available online 13 August 2019Source: Cancer/RadiothérapieAuthor(s): P. Blanchard, J. Biau, J. Castelli, Y. Tao, P. Graff, F. NguyenRésuméLes cancers des voies aérodigestives supérieures correspondent à un ensemble de maladies variées, pour lesquelles les volumes de traitement et la dose prescrite sont à individualiser en fonction de chaque patient. L’objectif de cet article est de passer en revue les principaux facteurs décisionnels concernant la définition des volumes cibles,...
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Journal of Adolescent and Young Adult Oncology, Ahead of Print.
Journal of Adolescent and Young Adult Oncology, Ahead of Print.
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Cancers, Vol. 11, Pages 1189: How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis Cancers doi: 10.3390/cancers11081189 Authors: Galvano Incorvaia Badalamenti Rizzo Guarini Cusenza Castellana Barraco Calò Cutaia Currò Silvestris Beretta Bazan Russo Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated...
Cancers, Vol. 11, Pages 1190: FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: Today, Tomorrow, and Beyond Cancers doi: 10.3390/cancers11081190 Authors: Hildebrandt Lauridsen Vogsen Holm Vilstrup Braad Gerke Thomassen Ewertz Høilund-Carlsen (PREMIO) While current international guidelines include imaging of the target lesion for response monitoring in metastatic breast cancer, they do not provide specific recommendations for choice...
Cancers, Vol. 11, Pages 1187: 4-Methylumbelliferone Inhibits Cancer Stem Cell Activation and Overcomes Chemoresistance in Ovarian Cancer Cancers doi: 10.3390/cancers11081187 Authors: Noor A. Lokman Zoe K. Price Emily K. Hawkins Anne M. Macpherson Martin K. Oehler Carmela Ricciardelli We have recently shown that the extracellular matrix molecule hyaluronan (HA) plays a role in the development of ovarian cancer chemoresistance. This present study determined if HA production...
Cancers, Vol. 11, Pages 1188: Anaplastic Thyroid Cancer: Clinical Picture of the Last Two Decades at a Single Oncology Referral Centre and Novel Therapeutic Options Cancers doi: 10.3390/cancers11081188 Authors: Joana Simões-Pereira Ricardo Capitão Edward Limbert Valeriano Leite Anaplastic thyroid cancer (ATC) is a rare tumour but also one of the most lethal malignancies. Therapeutic modalities have usually been limited, but clinical trials with new drugs are now being implemented....
Cancers, Vol. 11, Pages 1180: Third Epidemiological Analysis of Nasopharyngeal Carcinoma in the Central Region of Japan from 2006 to 2015 Cancers doi: 10.3390/cancers11081180 Authors: Masafumi Kanno Norihiko Narita Yasushi Fujimoto Naohiro Wakisaka Tomokazu Yoshizaki Takeshi Kodaira Chiyoko Makita Yuichiro Sato Keisuke Yamazaki Takanori Wakaoka Yuzo Shimode Hiroyuki Tsuji Ryosuke Kito Hajime Ishinaga Seiji Hosokawa Hiromasa Takakura Kunihiro...
Cancers, Vol. 11, Pages 1182: NF-κB Signaling in Ovarian Cancer Cancers doi: 10.3390/cancers11081182 Authors: Brittney S. Harrington Christina M. Annunziata The NF-κB signaling pathway is a master and commander in ovarian cancer (OC) that promotes chemoresistance, cancer stem cell maintenance, metastasis and immune evasion. Many signaling pathways are dysregulated in OC and can activate NF-κB signaling through canonical or non-canonical pathways which have both...
Cancers, Vol. 11, Pages 1185: Targeted Treatment Options of Recurrent Radioactive Iodine Refractory Hürthle Cell Cancer Cancers doi: 10.3390/cancers11081185 Authors: Mehtap Derya Aydemirli Willem Corver Ruben Beuk Paul Roepman Nienke Solleveld-Westerink Tom van Wezel Ellen Kapiteijn Hans Morreau Objective: To evaluate the efficacy and treatment rationale of Hürthle cell carcinoma (HCC) following a patient with progressive and metastatic HCC. HCC was recently...
Cancers, Vol. 11, Pages 1184: TIMP-1-Mediated Chemoresistance via Induction of IL-6 in NSCLC Cancers doi: 10.3390/cancers11081184 Authors: Wei Xiao Lan Wang John Howard Ravindra Kolhe Amyn M. Rojiani Mumtaz V. Rojiani Elevated tissue inhibitor of metalloproteinase-1 (TIMP-1) is a negative prognosticator in non-small cell lung carcinoma NSCLC patients. This study sought to identify mechanisms whereby TIMP-1 impacts anticancer therapy. Using NSCLC cells and their TIMP-1...
Cancers, Vol. 11, Pages 1183: Hyperthermia Treatment Planning Including Convective Flow in Cerebrospinal Fluid for Brain Tumour Hyperthermia Treatment Using a Novel Dedicated Paediatric Brain Applicator Cancers doi: 10.3390/cancers11081183 Authors: Gerben Schooneveldt Hana Dobšíček Trefná Mikael Persson Theo de Reijke Klas Blomgren Petra Kok Hans Crezee Hyperthermia therapy (40–44 °C) is a promising option to increase efficacy of radiotherapy/chemotherapy...
Cancers, Vol. 11, Pages 1181: Unravelling the Diagnostic Dilemma: A MicroRNA Panel of Circulating MiR-16 and MiR-877 as A Diagnostic Classifier for Distal Bile Duct Tumors Cancers doi: 10.3390/cancers11081181 Authors: Laura L. Meijer Jisce R. Puik Tessa Y.S. Le Large Michal Heger Frederike Dijk Niccola Funel Thomas Wurdinger Ingrid Garajová Nicole C.T. van Grieken Mark A. van de Wiel Elisa Giovannetti Geert Kazemier Accurate diagnosis of pancreatic head...
Cancers, Vol. 11, Pages 1186: Clinical Relevance of Collagen Protein Degradation Markers C3M and C4M in the Serum of Breast Cancer Patients Treated with Neoadjuvant Therapy in the GeparQuinto Trial Cancers doi: 10.3390/cancers11081186 Authors: Malgorzata Banys-Paluchowski Sibylle Loibl Isabell Witzel Christoph Mundhenke Bianca Lederer Christine Solbach Thomas Karn Frederik Marmé Valentina Nekljudova Christian Schem Elmar Stickeler Nicholas Willumsen Morten...
Cancers, Vol. 11, Pages 1179: Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes Cancers doi: 10.3390/cancers11081179 Authors: Jaideep Chakladar Wei Tse Li Michael Bouvet Eric Y. Chang Jessica Wang-Rodriguez Weg M. Ongkeko Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This...
Cancers, Vol. 11, Pages 1177: Electrochemotherapy Causes Caspase-Independent Necrotic-Like Death in Pancreatic Cancer Cells Cancers doi: 10.3390/cancers11081177 Authors: Philana Fernandes Tracey R. O’Donovan Sharon L. McKenna Patrick F. Forde Pancreatic cancer represents a major challenge in oncology. Poor permeability of the pancreas and resistance to currently available therapies are impediments to improved patient survival. By transiently increasing cell membrane porosity...
Cancers, Vol. 11, Pages 1176: Adaptive Responses as Mechanisms of Resistance to BRAF Inhibitors in Melanoma Cancers doi: 10.3390/cancers11081176 Authors: Saei Eichhorn : The introduction of v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors in melanoma patients with BRAF (V600E) mutations has demonstrated significant clinical benefits. However, rarely do tumours regress completely. Frequently, the reason for this is that therapies targeting specific oncogenic mutations...
Cancers, Vol. 11, Pages 1175: Multi-Drug/Gene NASH Therapy Delivery and Selective Hyperspectral NIR Imaging Using Chirality-Sorted Single-Walled Carbon Nanotubes Cancers doi: 10.3390/cancers11081175 Authors: Md. Tanvir Hasan Elizabeth Campbell Olga Sizova Veronica Lyle Giridhar Akkaraju D. Lynn Kirkpatrick Anton V. Naumov Single-walled carbon nanotubes (SWCNTs) can serve as drug delivery/biological imaging agents, as they exhibit intrinsic fluorescence in the near-infrared,...
Cancers, Vol. 11, Pages 1178: p21 in Cancer Research Cancers doi: 10.3390/cancers11081178 Authors: Shamloo Usluer p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer,...
Cancers, Vol. 11, Pages 1169: The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma Cancers doi: 10.3390/cancers11081169 Authors: Sioletic Stefano Scambia Giovanni Soft tissue sarcoma (STS) is a rare malignancy of mesenchymal origin classified into more than 50 different subtypes with distinct clinical and pathologic features. Despite the poor prognosis in the majority of patients, only modest improvements in treatment strategies have been achieved, largely due to the rarity and heterogeneity...
Cancers, Vol. 11, Pages 1174: Use of Antibiotics and Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies Cancers doi: 10.3390/cancers11081174 Authors: Fausto Petrelli Michele Ghidini Antonio Ghidini Gianluca Perego Mary Cabiddu Shelize Khakoo Emanuela Oggionni Chiara Abeni Jens Claus Hahne Gianluca Tomasello Alberto Zaniboni The association between antibiotic use and risk of cancer development is unclear, and clinical trials are...
Cancers, Vol. 11, Pages 1172: The Tumor Microenvironment in Colorectal Cancer Therapy Cancers doi: 10.3390/cancers11081172 Authors: Leire Pedrosa Francis Esposito Timothy M. Thomson Joan Maurel The current standard-of-care for metastatic colorectal cancer (mCRC) includes chemotherapy and anti-angiogenic or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, even though the addition of anti-angiogenic agents to backbone chemotherapy provides little benefit for...
Cancers, Vol. 11, Pages 1171: Untargeted Assessment of Tumor Fractions in Plasma for Monitoring and Prognostication from Metastatic Breast Cancer Patients Undergoing Systemic Treatment Cancers doi: 10.3390/cancers11081171 Authors: Christoph Suppan Iva Brcic Verena Tiran Hannah D Mueller Florian Posch Martina Auer Erkan Ercan Peter Ulz Richard J Cote Ram H Datar Nadia Dandachi Ellen Heitzer Marija Balic The aim of this study was to assess the prognostic...
Cancers, Vol. 11, Pages 1170: Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies Cancers doi: 10.3390/cancers11081170 Authors: Barbara Pardini Alexandru Anton Sabo Giovanni Birolo George Adrian Calin The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease....
Cancers, Vol. 11, Pages 1173: Comparative Cytogenetic Abnormalities in Paired Choroidal Melanoma Samples Obtained Before and After Proton Beam Irradiation by Transscleral Fine-Needle Aspiration Biopsy and Endoresection Cancers doi: 10.3390/cancers11081173 Authors: Alexandre Matet Khadija Aït Raïs Denis Malaise Martina Angi Rémi Dendale Sarah Tick Livia Lumbroso-Le Rouic Christine Lévy-Gabriel Manuel Rodrigues Gaëlle Pierron Nathalie Cassoux This study compared...
Cancers, Vol. 11, Pages 1167: TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors Cancers doi: 10.3390/cancers11081167 Authors: Ufuk Mert Alshaimaa Adawy Elisabeth Scharff Pierre Teichmann Anna Willms Verena Haselmann Cynthia Colmorgen Johannes Lemke Silvia von Karstedt Jürgen Fritsch Anna Trauzold Binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to the plasma membrane TRAIL-R1/-R2 selectively...
Cancers, Vol. 11, Pages 1168: Incorporation of a Hydrophilic Spacer Reduces Hepatic Uptake of HER2-Targeting Affibody–DM1 Drug Conjugates Cancers doi: 10.3390/cancers11081168 Authors: Haozhong Ding Mohamed Altai Sara S. Rinne Anzhelika Vorobyeva Vladimir Tolmachev Torbjörn Gräslund Anna Orlova Affibody molecules are small affinity-engineered scaffold proteins which can be engineered to bind to desired targets. The therapeutic potential of using an affibody molecule...
Cancers, Vol. 11, Pages 1165: Long-Term Dynamics of Three Dimensional Telomere Profiles in Circulating Tumor Cells in High-Risk Prostate Cancer Patients Undergoing Androgen-Deprivation and Radiation Therapy Cancers doi: 10.3390/cancers11081165 Authors: Landon Wark Harvey Quon Aldrich Ong Darrel Drachenberg Aline Rangel-Pozzo Sabine Mai Patient-specific assessment, disease monitoring, and the development of an accurate early surrogate of the therapeutic efficacy of locally...
Cancers, Vol. 11, Pages 1166: Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles Cancers doi: 10.3390/cancers11081166 Authors: Xin-Hui Khoo Ian C. Paterson Bey-Hing Goh Wai-Leng Lee Drug resistance remains a severe problem in most chemotherapy regimes. Recently, it has been suggested that cancer cell-derived extracellular vesicles (EVs) could mediate drug resistance. In this study, the role of EVs in mediating the response...
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Purpose:In breast cancer, pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) is associated with favorable long-term outcome. Trastuzumab emtansine as additional adjuvant therapy improves recurrence-free survival of patients with HER2-positive breast cancer without pCR, but it is uncertain whether all patients without pCR need additional therapy. We evaluated the prognostic value of residual disease after trastuzumab-based NST in patients with HER2-positive breast cancer using...
Purpose:In research settings, circulating tumor DNA (ctDNA) shows promise as a tumor-specific biomarker for pancreatic ductal adenocarcinoma (PDAC). This study aims to perform analytical and clinical validation of a KRAS ctDNA assay in a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathology–certified clinical laboratory. Experimental Design:Digital-droplet PCR was used to detect the major PDAC-associated somatic KRAS mutations (G12D, G12V, G12R, and Q61H) in liquid...
Purpose:Transcription factors are commonly deregulated in cancer, and they have been widely considered as difficult to target due to their nonenzymatic mechanism of action. Altered expression levels of members of the ETS-transcription factors are often observed in many different tumors, including lymphomas. Here, we characterized two small molecules, YK-4-279 and its clinical derivative, TK-216, targeting ETS factors via blocking the protein–protein interaction with RNA helicases, for their antilymphoma...
Purpose:Uveal melanoma is a primary malignancy of the eye with oncogenic mutations in GNAQ, GNA11, or CYSLTR2, and additional mutations in BAP1 (usually associated with LOH of Chr 3), SF3B1, or EIF1AX. There are other characteristic chromosomal alterations, but their significance is not clear. Experimental Design:To investigate genes driving chromosomal alterations, we integrated copy number, transcriptome, and mutation data from three cohorts and followed up key findings. Results:We observed significant...
Purpose:To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design:We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results:On the basis of...
Purpose:Leiomyosarcoma and liposarcoma are common subtypes of soft tissue sarcoma (STS). Patients with metastatic leiomyosarcoma or dedifferentiated liposarcoma (DDLPS) typically have worse outcomes compared with localized leiomyosarcoma or well-differentiated liposarcoma (WDLPS). A better understanding of genetic changes between primary/metastatic leiomyosarcoma and between WDLPS/DDLPS may provide insight into their genetic evolution. Experimental Design:We interrogated whole-exome sequencing (WES)...
Purpose:The response to acute and long-term arginine starvation results in a conditional adaptive metabolic reprogramming that can be harnessed for therapeutic opportunities in ASS1-negative tumors. Here, we investigate the underlying biology of priming ASS1– tumors with arginine deiminase (ADI-PEG20) before treatment with gemcitabine (GEM) and docetaxel (DTX) in sarcoma, pancreatic cancer, and melanoma cell lines. Experimental Design:ASS1– tumor cell lines were treated to create LTAT (long-term...
Purpose:Small-cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among SCLC subtypes is largely unexplored. In this study, we aimed to determine whether metabolic vulnerabilities exist between SCLC subtypes that can be therapeutically exploited. Experimental Design:We performed steady state metabolomics on tumors isolated from distinct genetically engineered mouse models (GEMM)...
Purpose:High-grade glioma (HGG) treatment is limited by the inability of otherwise potentially efficacious drugs to penetrate the blood–brain barrier. We evaluate the unique intracavity delivery mode and translational potential of a blend of poly(DL-lactic acid-co-glycolic acid; PLGA) and poly(ethylene glycol; PEG) paste combining temozolomide and etoposide to treat surgically resected HGG. Experimental Design:To prolong stability of temozolomide prodrug, combined in vitro drug release was quantitatively...
Purpose:Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non–small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit. Experimental Design:We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with...
Purpose:Immune checkpoint inhibitors (ICI) have revolutionized cancer management. However, molecular determinants of response to ICIs remain incompletely understood. Experimental Design:We performed genomic profiling of 78 patients with non–small cell lung cancer (NSCLC) who underwent anti–PD-(L)1 therapies by both whole-exome and targeted next-generation sequencing (a 422-cancer-gene panel) to explore the predictive biomarkers of ICI response. Tumor mutation burden (TMB), and specific somatic mutations...
Purpose:Aberrant activation of MET (hepatocyte growth factor receptor) signaling is implicated in the tumorigenesis of human cancers. This phase I study assessed the safety, tolerability, and MTD of the potent and selective MET inhibitor, savolitinib (AZD6094, HMPL-504, volitinib). Patients and Methods:This open-label, multicenter dose-escalation and -expansion study evaluated oral savolitinib for patients with locally advanced or metastatic solid tumors. A 3 + 3 design assessed repeated daily (QD)...
Purpose:We discuss designs and interpretable metrics of bias and statistical efficiency of "externally controlled" trials (ECT) and compare ECT performance to randomized and single-arm designs. Experimental Design:We specify an ECT design that leverages information from real-world data (RWD) and prior clinical trials to reduce bias associated with interstudy variations of the enrolled populations. We then used a collection of clinical studies in glioblastoma (GBM) and RWD from patients treated with...
Purpose:BN-CV301 is a poxviral-based vaccine comprised of recombinant (rec.) modified vaccinia Ankara (MVA-BN-CV301; prime) and rec. fowlpox (FPV-CV301; boost). Like its predecessor PANVAC, BN-CV301 contains transgenes encoding tumor-associated antigens MUC1 and CEA as well as costimulatory molecules (B7.1, ICAM-1, and LFA-3). PANVAC was reengineered to make it safer and more antigenic. Patients and Methods:This open-label, 3+3 design, dose-escalation trial evaluated three dose levels (DL) of MVA-BN-CV301:...
Purpose:KIT mutations (KIT+) are common in core binding factor (CBF) AML and have been associated with varying prognostic significance. We sought to define the functional and clinical significance of distinct KIT mutations in CBF pediatric AML. Experimental Design:Following transfection of exon 17 (E17) and exon 8 (E8) mutations into HEK293 and Ba/F3 cells, KIT phosphorylation, cytokine-independent growth, and response to tyrosine kinase inhibitors (TKI) were evaluated. Clinical outcomes of patients...
Purpose:The first-in-human clinical trial with human bolus intravenous infusion IL15 (rhIL15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and clinical activity of rhIL15 administered as a 10-day continuous intravenous infusion (CIV) to patients with cancers in a phase I trial. Patients and Methods:Patients received treatment for 10 days with CIV rhIL15 in doses of 0.125, 0.25, 0.5, 1, 2, or 4 μg/kg/day. Correlative laboratory tests included IL15 pharmacokinetic...
Purpose:New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy–refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERR) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC50 = 0.006 μmol/L), selective, and orally available ERR inverse agonist for NIS enhancement in ATC. Experimental Design:We sought to identify better...
Purpose:mAbs including cetuximab can induce antibody-dependent cellular cytotoxicity (ADCC) and cytokine production mediated via innate immune cells with the ability to recognize mAb-coated tumors. Preclinical modeling has shown that costimulation of natural killer (NK) cells via the Fc receptor and the IL12 receptor promotes NK-cell–mediated ADCC and production of cytokines. Patients and Methods:This phase I/II trial evaluated the combination of cetuximab with IL12 for the treatment of EGFR-expressing...
Purpose:The tumor microenvironment has a profound impact on prognosis and immunotherapy. However, the landscape of the triple-negative breast cancer (TNBC) microenvironment has not been fully understood. Experimental Design:Using the largest original multi-omics dataset of TNBC (n = 386), we conducted an extensive immunogenomic analysis to explore the heterogeneity and prognostic significance of the TNBC microenvironment. We further analyzed the potential immune escape mechanisms of TNBC. Results:The...
Purpose:NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. Experimental Design:Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)–certified genomics laboratory and that underwent fusion testing by anchored...
Purpose:Prediction of spatially variant response to cancer therapies can inform risk-adaptive management within precision oncology. We developed the "Voxel Forecast" multiscale regression framework for predicting spatially variant tumor response to chemoradiotherapy on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging. Experimental Design:Twenty-five patients with locally advanced non–small cell lung cancer, enrolled on the FLARE-RT phase II trial (NCT02773238),...
Purpose:After cisplatin-based neoadjuvant chemotherapy (NAC), 60% of patients with muscle-invasive bladder cancer (MIBC) still have residual invasive disease at radical cystectomy. The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied. Experimental Design:Radical cystectomy samples were available for gene expression analysis from 133 patients with residual invasive disease after cisplatin-based NAC, of whom 116 had matched pre-NAC samples. Unsupervised...
Purpose:Genomic analyses of small-cell lung cancer (SCLC) are limited by the availability of tumor specimens. This study aimed to investigate the suitability of single-cell sequencing of circulating tumor cells (CTC) as a method of inferring the evolution and progression of SCLCs. Experimental Design:Between July 1, 2011, and July 28, 2014, 48 consecutively diagnosed patients with SCLC were recruited for this study. CTCs were captured from each patient with CellSearch system. Somatic mutations and...
Purpose:The histone deacetylase (HDAC) inhibitor panobinostat potentiates anthracycline and cytarabine cytotoxicity in acute myeloid leukemia (AML) cells. We hypothesized that panobinostat prior to and during induction chemotherapy would be tolerable and augment response in patients showing increased histone acetylation. Patients and Methods:Patients received panobinostat 20–60 mg oral daily on days 1, 3, 5, and 8 with daunorubicin 60 mg/m2/day intravenously on days 3 to 5 and cytarabine 100 mg/m2/day...
Purpose:The oral proteasome inhibitor oprozomib has shown preclinical antitumor activity. Here, we report phase Ib/II study results investigating single-agent oprozomib in patients with relapsed multiple myeloma and Waldenström macroglobulinemia. Patients and Methods:The primary objectives were to determine the MTD, safety, and tolerability of oprozomib (phase Ib) as well as overall response rate (ORR; phase II). Oprozomib was administered once daily on days 1, 2, 8, and 9 (2/7 schedule) or days...
Purpose:Myelofibrosis is characterized by bone marrow fibrosis, atypical megakaryocytes, splenomegaly, constitutional symptoms, thrombotic and hemorrhagic complications, and a risk of evolution to acute leukemia. The JAK kinase inhibitor ruxolitinib provides therapeutic benefit, but the effects are limited. The purpose of this study was to determine whether targeting AURKA, which has been shown to increase maturation of atypical megakaryocytes, has potential benefit for patients with myelofibrosis....
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