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Solid tumor oncology

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https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#1
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#2
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28817373/cabozantinib-as-salvage-therapy-for-patients-with-tyrosine-kinase-inhibitor-refractory-differentiated-thyroid-cancer-results-of-a-multicenter-phase-ii-international-thyroid-oncology-group-trial
#3
Maria E Cabanillas, Jonas A de Souza, Susan Geyer, Lori J Wirth, Michael E Menefee, Stephen V Liu, Komal Shah, John Wright, Manisha H Shah
Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28814194/real-world-utilization-of-darbepoetin-alfa-in-cancer-chemotherapy-patients
#4
Xiaoyun Lucy Pan, Beth L Nordstrom, Sharon MacLachlan, Junji Lin, Hairong Xu, Anjali Sharma, David Chandler, Xiaoyan Shawn Li
Objectives To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. Study design This is a retrospective cohort study using a proprietary outpatient oncology database. Methods Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin <10 g/dL during 2011-2015 were identified. The analysis was restricted to the first continuous exposure to chemotherapy agents (maximum allowable gap of 90 days between consecutive exposures) with darbepoetin alfa for each eligible patient...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28812098/-radiological-response-assessment-of-modern-immunotherapy-using-irecist
#5
REVIEW
T Persigehl, T D Poeppel, O Sedlaczek
CLINICAL/METHODICAL ISSUE: Modern immunotherapies in oncology show tumor response patterns differing from conventional chemotherapies including initial pseudo-progression. STANDARD RADIOLOGICAL METHODS: Response evaluation criteria in solid tumors (RECIST 1.1) represent the currently most used response criteria for conventional chemotherapy of solid tumors. However, atypical response patterns of immunotherapies are not correctly classified using RECIST 1.1 so that the effectiveness is also incorrectly interpreted...
August 15, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28809610/phase-iii-study-comparing-a-reduced-dose-of-cabazitaxel-20-mg-m-2-and-the-currently-approved-dose-25-mg-m-2-in-postdocetaxel-patients-with-metastatic-castration-resistant-prostate-cancer-proselica
#6
Mario Eisenberger, Anne-Claire Hardy-Bessard, Choung Soo Kim, Lajos Géczi, Daniel Ford, Loïc Mourey, Joan Carles, Phillip Parente, Albert Font, Gabriel Kacso, Mustapha Chadjaa, Wenping Zhang, John Bernard, Johann de Bono
Purpose Cabazitaxel 25 mg/m(2) (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m(2) (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28796559/improvements-in-patient-and-health-system-outcomes-using-an-integrated-oncology-and-palliative-medicine-approach-on-a-solid-tumor-inpatient-service
#7
Richard F Riedel, Kim Slusser, Steve Power, Christopher A Jones, Thomas W LeBlanc, Arif H Kamal, Devi Desai, Deborah Allen, Yinxi Yu, Steven Wolf, Anthony N Galanos
PURPOSE: Early palliative care (PC) improves outcomes for outpatients with advanced cancer. Its effect on hospitalized patients with cancer is unknown. Herein, we report on the influence of a novel, fully integrated inpatient medical oncology and PC partnership at a tertiary medical center during its first year of implementation. METHODS: We conducted a retrospective, longitudinal, pre- and postintervention cohort study at Duke University Hospital. Pre- and postintervention cohorts were defined as all patients admitted to the solid tumor inpatient service from September 1, 2009, to June 30, 2010, and September 1, 2011 to June 30, 2012, respectively...
August 10, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28777143/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immuno-oncology-biomarkers-working-group-part-2-tils-in-melanoma-gastrointestinal-tract-carcinomas-non
#8
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma...
August 2, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28777142/assessing-tumor-infiltrating-lymphocytes-in-solid-tumors-a-practical-review-for-pathologists-and-proposal-for-a-standardized-method-from-the-international-immunooncology-biomarkers-working-group-part-1-assessing-the-host-immune-response-tils-in-invasive-breast
#9
Shona Hendry, Roberto Salgado, Thomas Gevaert, Prudence A Russell, Tom John, Bibhusal Thapa, Michael Christie, Koen van de Vijver, M V Estrada, Paula I Gonzalez-Ericsson, Melinda Sanders, Benjamin Solomon, Cinzia Solinas, Gert G G M Van den Eynden, Yves Allory, Matthias Preusser, Johannes Hainfellner, Giancarlo Pruneri, Andrea Vingiani, Sandra Demaria, Fraser Symmans, Paolo Nuciforo, Laura Comerma, E A Thompson, Sunil Lakhani, Seong-Rim Kim, Stuart Schnitt, Cecile Colpaert, Christos Sotiriou, Stefan J Scherer, Michail Ignatiadis, Sunil Badve, Robert H Pierce, Giuseppe Viale, Nicolas Sirtaine, Frederique Penault-Llorca, Tomohagu Sugie, Susan Fineberg, Soonmyung Paik, Ashok Srinivasan, Andrea Richardson, Yihong Wang, Ewa Chmielik, Jane Brock, Douglas B Johnson, Justin Balko, Stephan Wienert, Veerle Bossuyt, Stefan Michiels, Nils Ternes, Nicole Burchardi, Stephen J Luen, Peter Savas, Frederick Klauschen, Peter H Watson, Brad H Nelson, Carmen Criscitiello, Sandra O'Toole, Denis Larsimont, Roland de Wind, Giuseppe Curigliano, Fabrice André, Magali Lacroix-Triki, Mark van de Vijver, Federico Rojo, Giuseppe Floris, Shahinaz Bedri, Joseph Sparano, David Rimm, Torsten Nielsen, Zuzana Kos, Stephen Hewitt, Baljit Singh, Gelareh Farshid, Sibylle Loibl, Kimberly H Allison, Nadine Tung, Sylvia Adams, Karen Willard-Gallo, Hugo M Horlings, Leena Gandhi, Andre Moreira, Fred Hirsch, Maria V Dieci, Maria Urbanowicz, Iva Brcic, Konstanty Korski, Fabien Gaire, Hartmut Koeppen, Amy Lo, Jennifer Giltnane, Marlon C Rebelatto, Keith E Steele, Jiping Zha, Kenneth Emancipator, Jonathan W Juco, Carsten Denkert, Jorge Reis-Filho, Sherene Loi, Stephen B Fox
Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment...
September 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28772084/inpatient-palliative-care-consultation-and-30-day-readmissions-in-oncology
#10
Lisa D DiMartino, Bryan J Weiner, Laura C Hanson, Morris Weinberger, Sarah A Birken, Katherine Reeder-Hayes, Justin G Trogdon
BACKGROUND: Prior research indicates that hospice and palliative care delivered in outpatient settings are associated with reduced hospital readmissions for cancer patients. However, little is known about how inpatient palliative care affects readmissions in oncology. OBJECTIVE: To examine associations among inpatient palliative care consultation, hospice use (discharge), and 30-day readmissions among patients with solid tumor cancers. METHODS: We identified all live discharges from a large tertiary cancer hospital between 2010 and 2016...
August 3, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28770610/amino-acid-profiles-as-potential-biomarkers-for-pediatric-cancers-a-preliminary-communication
#11
Anna Synakiewicz, Malgorzata Sawicka-Zukowska, Natalia Adrianowska, Grazyna Galezowska, Joanna Ratajczyk, Anna Owczarzak, Lucyna Konieczna, Teresa Stachowicz-Stencel
AIM: Childhood cancer remains one of the main cause of death in the pediatric population. Amino acids (AAs) level alterations in plasma are considered to play a role in carcinogenesis and further course of the disease. METHODS: Seventy-seven children with cancer, including 47 with hematological and 30 with solid tumors were enrolled in this study and compared with healthy children. Twenty-two plasma-free AAs were determined by HPLC with fluorometric detection. RESULTS: The results revealed significant decrease in glutamine levels for oncological patients and significant increase in aspartic acid, glutamic acid, asparagine, serine, citrulline, alanine, GABA, tryptophan, methionine, valine, phenylalanine and isoleucine levels in cancer children versus control...
August 3, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28766004/-psychosocial-stress-in-patients-with-prostate-cancer-experiences-by-using-psychooncological-screening-questionnaires
#12
D L Dräger, N N Harke, K-D Sievert, C Protzel, O W Hakenberg
BACKGROUND: Prostate cancer is the most common malignancy in men and accounts for most surgical procedures in uro-oncology. Stressful sequelae of radical prostatectomy are incontinence and erectile dysfunction. Hormone ablation and radiation therapy are also known stressors. Mental stress has a low prevalence compared to other tumor entities. It is highly probable that there is an underexpression of verbally reported emotional experiences. Therefore, a low-threshold access to psycho-oncological services and accurate identification of patients with mental comorbidities is important...
August 1, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28760910/epacadostat-shows-value-in-two-scchn-trials
#13
(no author information available yet)
In the ECHO-202/KEYNOTE-037 and ECHO-204 trials reported at the 2017 Annual Meeting of the American Society of Clinical Oncology, patients with squamous cell carcinoma of the head and neck responded well to the combinations of epacadostat plus pembrolizumab and epacadostat plus nivolumab. An IDO1 inhibitor, epacadostat also demonstrated promising activity in combination with the PD-1 checkpoint inhibitors in other solid tumors, including melanoma, urothelial carcinoma, renal cell carcinoma, and non-small cell lung cancer...
July 31, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28751444/pediatric-phase-1-trial-and-pharmacokinetic-study-of-trebananib-in-relapsed-solid-tumors-advl1115-a-children-s-oncology-group-phase-1-consortium-report
#14
Sarah E S Leary, Julie R Park, Joel M Reid, Andrew T Ralya, Sylvain Baruchel, Bing Wu, Timothy P L Roberts, Xiaowei Liu, Charles G Minard, Elizabeth Fox, Brenda J Weigel, Susan Blaney
Trebananib is a first-in-class anti-angiogenic peptibody (peptide-Fc fusion protein) that inhibits Angiopoietin 1 and 2. A pediatric phase 1 trial was performed to define trebananib dose limiting toxicities (DLT), recommended phase 2 dose (RP2D) and pharmacokinetics (PK).<br /><br />Experimental Design: Trebananib was administered by weekly infusion. Three dose levels (10, 15 or 30 mg/kg/dose) were evaluated using a rolling-six design. Part 2 evaluated a cohort of subjects with primary central nervous system (CNS) tumors...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28747518/targeted-molecular-radiotherapy-of-pediatric-solid-tumors-using-a-radioiodinated-alkyl-phospholipid-ether-analog
#15
Dana C Baiu, Ian R Marsh, Alexander E Boruch, Ankita Shahi, Saswati Bhattacharya, Justin J Jeffery, Qianqian Zhao, Lance Hall, Jamey P Weichert, Bryan Bednarz, Mario Otto
External beam radiotherapy plays a critical role in the treatment of most pediatric solid tumors. Particularly in children, achieving an optimal therapeutic index to avoid damage to normal tissue is extremely important. Consequently, in metastatic disease, the utility of external beam radiotherapy is very limited. Molecular radiotherapy with tumor-targeted radionuclides may overcome some of these challenges, but to date no single cancer selective agent exists, capable of treating various pediatric malignancies independent of their histopathological origin...
July 26, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28746152/intraoperative-molecular-imaging-combined-with-positron-emission-tomography-improves-surgical-management-of-peripheral-malignant-pulmonary-nodules
#16
Jarrod D Predina, Andrew D Newton, Jane Keating, Eduardo M Barbosa, Olugbenga Okusanya, Leilei Xia, Ashley Dunbar, Courtney Connolly, Michael P Baldassari, Jack Mizelle, Edward J Delikatny, John C Kucharczuk, Charuhas Deshpande, Sumith A Kularatne, Phillip Low, Jeffrey Drebin, Sunil Singhal
OBJECTIVE: To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules. BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (PET) is commonly utilized in preoperative assessment of patients with solid malignancies; however, false negatives and false positives remain major limitations. Using patients with pulmonary nodules as a study model, we hypothesized that IMI with a folate receptor targeted near-infrared contrast agent (OTL38) can improve malignant pulmonary nodule identification when combined with PET...
September 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28735365/an-update-on-the-use-of-immunotherapy-in-the-treatment-of-lymphoma
#17
REVIEW
Thomas U Marron, Matko Kalac, Joshua Brody
PURPOSE OF REVIEW: Throughout the field of oncology, immunotherapy is moving further towards the first-line setting, and there is encouraging data for the use of these novel therapies in the management of lymphomas, utilizing treatments approved for both solid and hematologic malignancies. Herein, we review promising advances in this rapidly moving field from the past year. RECENT FINDINGS: In the last year, we have seen promising clinical data on engineered antibody therapies for the treatment of lymphomas, as well as further optimization of engineered antibody fragments fused onto linkers or chimeric T cell receptors, both of the modalities capable of transforming non-specific T cells into tumor-specific, serial killer cells...
July 22, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28729154/tremelimumab-as-second-line-or-third-line-treatment-in-relapsed-malignant-mesothelioma-determine-a-multicentre-international-randomised-double-blind-placebo-controlled-phase-2b-trial
#18
Michele Maio, Arnaud Scherpereel, Luana Calabrò, Joachim Aerts, Susana Cedres Perez, Alessandra Bearz, Kristiaan Nackaerts, Dean A Fennell, Dariusz Kowalski, Anne S Tsao, Paul Taylor, Federica Grosso, Scott J Antonia, Anna K Nowak, Maria Taboada, Martina Puglisi, Paul K Stockman, Hedy L Kindler
BACKGROUND: New therapeutic strategies for malignant mesothelioma are urgently needed. In the DETERMINE study, we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma. METHODS: DETERMINE was a double-blind, placebo-controlled, phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28729151/standard-dose-pembrolizumab-in-combination-with-reduced-dose-ipilimumab-for-patients-with-advanced-melanoma-keynote-029-an-open-label-phase-1b-trial
#19
Georgina V Long, Victoria Atkinson, Jonathan S Cebon, Michael B Jameson, Bernie M Fitzharris, Catriona M McNeil, Andrew G Hill, Antoni Ribas, Michael B Atkins, John A Thompson, Wen-Jen Hwu, F Stephen Hodi, Alexander M Menzies, Alexander D Guminski, Richard Kefford, Benjamin Y Kong, Babak Tamjid, Archana Srivastava, Anna J Lomax, Mohammed Islam, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S Carlino
BACKGROUND: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab. METHODS: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28726491/interview-with-thomas-powles-the-use-of-durvalumab-in-urothelial-cancer-the-latest-strides-in-immuno-oncology
#20
Thomas Powles
Thomas Powles speaks to Sebastian Dennis-Beron, Commissioning Editor: Dr. Thomas Powles is a clinical professor of genitourinary oncology and the lead for solid tumor research at Barts Cancer Institute in London. His main research interests are in genital and urinary cancers, in which he leads a spectrum of clinical studies from Phase I to randomized Phase III investigating novel targeted and immune therapies. His research also focuses on correlation of novel biomarkers and aims to define markers with prognostic value that may predict response or resistance to therapy...
July 20, 2017: Future Oncology
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