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Response evaluation of solid tumors

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https://www.readbyqxmd.com/read/29028787/relationship-between-pd-l1-expression-and-cd8-t-cell-immune-responses-in-hepatocellular-carcinoma
#1
Chun-Yu Huang, Ying Wang, Guang-Yu Luo, Feng Han, Yong-Qiang Li, Zhong-Guo Zhou, Guo-Liang Xu
As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8...
November 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29026685/pharmacokinetics-of-carfilzomib-in-patients-with-advanced-malignancies-and-varying-degrees-of-hepatic-impairment-an-open-label-single-arm-phase-1-study
#2
Jennifer Brown, Ruth Plummer, Todd M Bauer, Stephen Anthony, John Sarantopoulos, Filip De Vos, Mike White, Marco Schupp, Ying Ou, Ulka Vaishampayan
BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. METHODS: Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29025987/preclinical-development-of-cd38-targeted-89-zr-zr-dfo-daratumumab-for-imaging-multiple-myeloma
#3
Anchal Ghai, Dolonchampa Maji, Michael Rettig, Chantiya Chanswangphuwana, John DiPersio, Walter Akers, Samuel Achilefu, Farrokh Dehdashti, Ravi Vij, Monica Shokeen
Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. Despite improvements in survival, heterogeneity in response remains a major challenge in MM. Cluster of differentiation 38 (CD38) is a type II transmembrane glycoprotein over-expressed in myeloma cells and is implicated in MM cell signaling. Daratumumab is US Food and Drug Administration approved high-affinity monoclonal antibody targeting CD38 that is clinically benefiting refractory MM patients. Here, we evaluated [(89)Zr]Zr-DFO-daratumumab positron emission tomography/computed tomography (PET/CT) imaging in MM tumor models...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29025983/predictive-value-of-fdg-pet-in-patients-with-advanced-medullary-thyroid-carcinoma-treated-with-vandetanib
#4
Rudolf A Werner, Jan Stefan Schmid, Takahiro Higuchi, Mehrbod Som Javadi, Steven P Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K Buck, Michael Kreissl, Constantin Lapa
Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We aimed to assess the role of metabolic imaging using 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline (18)F-FDG PET/CT prior to and 3 months after TKI treatment initiation...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29022496/antitumor-and-radiosensitizing-synergistic-effects-of-apigenin-and-cryptotanshinone-against-solid-ehrlich-carcinoma-in-female-mice
#5
Amina M Medhat, Khaled Sh Azab, Mahmoud M Said, Neama M El Fatih, Nermeen M El Bakary
Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29018574/continuing-egfr-tki-beyond-radiological-progression-in-patients-with-advanced-or-recurrent-egfr-mutation-positive-non-small-cell-lung-cancer-an-observational-study
#6
Yasushi Goto, Chiharu Tanai, Kiyotaka Yoh, Yukio Hosomi, Hiroshi Sakai, Terufumi Kato, Takayuki Kaburagi, Makoto Nishio, Young Hak Kim, Akira Inoue, Yoshinori Hasegawa, Hiroshi Isobe, Yoshio Tomizawa, Yoshiaki Mori, Koichi Minato, Kazuhiko Yamada, Yasuo Ohashi, Hideo Kunitoh
BACKGROUND: Some patients with advanced or recurrent, epidermal growth factor receptor (EGFR) mutation-positive (EGFR M+) non-small-cell lung cancer (NSCLC) continue to receive EGFR tyrosine kinase inhibitors (TKIs) beyond radiological progression. METHODS: We analysed a cohort of 577 patients with EGFR M+ NSCLC, who had received a first-line EGFR-TKI. We classified patients according to clinical course and treatment patterns at Response Evaluation Criteria in Solid Tumors (RECIST) progressive disease (PD)...
2017: ESMO Open
https://www.readbyqxmd.com/read/29016998/phase-ii-study-of-cabozantinib-in-patients-with-progressive-glioblastoma-subset-analysis-of-patients-naive-to-antiangiogenic-therapy
#7
Patrick Y Wen, Jan Drappatz, John de Groot, Michael D Prados, David A Reardon, David Schiff, Marc Chamberlain, Tom Mikkelsen, Annick Desjardins, Jaymes Holland, Jerry Ping, Ron Weitzman, Timothy F Cloughesy
Background: Cabozantinib is a tyrosine kinase inhibitor with activity against VEGFR2 and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM; NCT00704288). Methods: Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity...
August 14, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28993945/drug-eluting-bead-transarterial-chemoembolization-in-the-treatment-for-unresectable-soft-tissue-sarcoma-refractory-to-systemic-chemotherapy-a-preliminary-evaluation-of-efficacy-and-safety
#8
Jia-Yan Ni, Hong-Liang Sun, Yao-Ting Chen, Jiang-Hong Luo, Wei-Dong Wang, Xiong-Ying Jiang, Dong Chen, Lin-Feng Xu
PURPOSE: To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. METHODS: Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs)...
October 9, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28990403/redox-potential-and-ros-mediated-nanomedicines-for-improving-cancer-therapy
#9
Sterling Glass, Laura Gonzalez Fajardo, Andre Beringhs, Xiuling Lu
SIGNIFICANCE: The overabundance of reactive oxygen species (ROS) and antioxidants in cancer cells represents a challenge for therapeutic intervention, while also providing an opportunity for the development of new strategies to improve clinical therapeutic outcomes. Recent Advances: Nanotechnology has advanced tremendously in recent decades and now offers many potential opportunities to leverage altered redox status to improve conventional therapies. Highly tunable nanoparticle delivery systems have shown great promise for improving: 1) chemotherapy via selective redox-sensitive drug release in tumor cells and limited systemic toxicity; 2) photodynamic therapy via enhancing photoactivation and/or ROS production; and 3) radiation therapy via enhancing ROS production...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28988646/pembrolizumab-in-advanced-soft-tissue-sarcoma-and-bone-sarcoma-sarc028-a-multicentre-two-cohort-single-arm-open-label-phase-2-trial
#10
Hussein A Tawbi, Melissa Burgess, Vanessa Bolejack, Brian A Van Tine, Scott M Schuetze, James Hu, Sandra D'Angelo, Steven Attia, Richard F Riedel, Dennis A Priebat, Sujana Movva, Lara E Davis, Scott H Okuno, Damon R Reed, John Crowley, Lisa H Butterfield, Ruth Salazar, Jaime Rodriguez-Canales, Alexander J Lazar, Ignacio I Wistuba, Laurence H Baker, Robert G Maki, Denise Reinke, Shreyaskumar Patel
BACKGROUND: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma. METHODS: In this two-cohort, single-arm, open-label, phase 2 study, we enrolled patients with soft-tissue sarcoma or bone sarcoma from 12 academic centres in the USA that were members of the Sarcoma Alliance for Research through Collaboration (SARC)...
October 4, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28982886/parenchymal-liver-blood-volume-and-dynamic-volume-perfusion-ct-measurements-of-hepatocellular-carcinoma-in-patients-undergoing-transarterial-chemoembolization
#11
Nils Rathmann, Kerim Kara, Johannes Budjan, Thomas Henzler, Arman Smakic, Stefan O Schoenberg, Steffen J Diehl
AIM: Prospective comparison of cone beam C-Arm CT based parenchymal liver blood volume (PLBV) and dynamic volume perfusion CT (dVPCT) measurements in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolisation (TACE) with drug-eluting beads (DEB). PATIENTS AND METHODS: In 16 patients, changes of PLBV and dVPCT measurements [arterial liver parenchyma (ALP); temporal maximum intensity projection (MIP); hepatic perfusion index (HPI); portal venous parenchyma] were correlated to one another and to the modified Response Evaluation Criteria in Solid Tumors (mRECIST)...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28980061/applications-of-contrast-enhanced-ultrasound-in-the-pediatric-abdomen
#12
Aikaterini Ntoulia, Sudha A Anupindi, Kassa Darge, Susan J Back
Contrast-enhanced ultrasound (CEUS) is a radiation-free, safe, and in specific clinical settings, highly sensitive imaging modality. Over the recent decades, there is cumulating experience and a large volume of published safety and efficacy data on pediatric CEUS applications. Many of these applications have been directly translated from adults, while others are unique to the pediatric population. The most frequently reported intravenous abdominal applications of CEUS in children are the characterization of focal liver lesions, monitoring of solid abdominal tumor response to treatment, and the evaluation of intra-abdominal parenchymal injuries in selected cases of blunt abdominal trauma...
October 4, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28980060/phase-i-study-of-a-chloroquine-gemcitabine-combination-in-patients-with-metastatic-or-unresectable-pancreatic-cancer
#13
Panagiotis Samaras, Marina Tusup, Thi Dan Linh Nguyen-Kim, Burkhardt Seifert, Helga Bachmann, Roger von Moos, Alexander Knuth, Steve Pascolo
PURPOSE: Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer. METHODS: In this 3 + 3 dose escalation study, patients received a single weekly standard dose of intravenous gemcitabine, followed by single weekly oral intake of 100, 200 or 300 mg of chloroquine...
October 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28976556/first-in-human-trial-of-the-pi3k%C3%AE-selective-inhibitor-sar260301-in-patients-with-advanced-solid-tumors
#14
Philippe L Bédard, Michael A Davies, Scott Kopetz, Dejan Juric, Geoffrey I Shapiro, Jason J Luke, Anna Spreafico, Bin Wu, Christelle Castell, Corinne Gomez, Sylvaine Cartot-Cotton, Florent Mazuir, Michel Dubar, Sandrine Micallef, Brigitte Demers, Keith T Flaherty
BACKGROUND: Phosphoinositide 3-kinase (PI3K) β is the dominant isoform for PI3K activity in many phosphatase and tensin homolog (PTEN)-deficient tumor models. This was a first-in-human study to determine the maximum tolerated dose, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of SAR260301, a potent PI3Kβ-selective inhibitor (clinicaltrials.gov identifier NCT01673737). METHODS: Successive cohorts of patients with advanced solid tumors received increasing doses of oral SAR260301 according to a Bayesian escalation with an overdose-control process based on the occurrence of dose-limiting toxicity in the first 28-day cycle...
October 4, 2017: Cancer
https://www.readbyqxmd.com/read/28973403/a-phase-1-1b-tolerability-study-of-rilotumumab-alone-or-in-combination-with-cisplatin-and-capecitabine-in-japanese-patients-with-gastric-cancer
#15
Toshihiko Doi, Kensei Yamaguchi, Yoshito Komatsu, Kei Muro, Tomohiro Nishina, Takako Eguchi Nakajima, Rui Tang, Hui Yang, Yilong Zhang, A Scott Jung, Agnes Ang, Hirofumi Yasui
Objective: To evaluate the safety (including adverse events and dose-limiting toxicities [DLTs]), tolerability, pharmacokinetics and antitumor activity of the investigational MET inhibitor rilotumumab alone in patients with advanced solid tumors (Part 1) or in combination with cisplatin plus capecitabine (CX) in patients with MET-positive advanced gastric or gastroesophageal junction cancer (Part 2). Methods: Adult patients received 10 or 20 mg/kg intravenous (IV) rilotumumab every 2 weeks (Part 1) or 15 mg/kg IV rilotumumab every 3 weeks plus 80 mg/m2 cisplatin on Day 1 and 1000 mg/m2 capecitabine twice daily on Days 1-14 of every 21-day cycle (Part 2)...
August 22, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28971749/nonconventional-patterns-of-benefit-of-solid-tumors-treated-with-pd-l-1-inhibitors-a-systematic-review
#16
Omar Abdel-Rahman
AIM: The use of immune checkpoint inhibitors in the treatment of solid tumors has been expanding recently. Standard response evaluation criteria are not well suited to evaluate the clinical benefit from these agents. To systematically review the incidence and characteristics of nonconventional patterns of benefit observed in solid tumors treated with immune checkpoint inhibitors. MATERIALS & METHODS: MEDLINE and EMBASE databases have been searched. Moreover, reference lists of relevant articles were checked for cross-references...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/28969086/efficacy-and-safety-of-apatinib-in-stage-iv-sarcomas-experience-of-a-major-sarcoma-center-in-china
#17
Feng Li, Zhichao Liao, Jun Zhao, Gang Zhao, Xubin Li, Xiaoling Du, Yun Yang, Jilong Yang
PURPOSE: This study was conducted to review the efficacy and safety of Apatinib in stage IV sarcoma patients who failed previous chemotherapy. MATERIALS AND METHODS: The clinical information on 16 patients with stage IV sarcomas who failed in prior chemotherapy and subsequently received Apatinib treatment was collected. Apatinib was given 500mg/daily and 4 weeks as a cycle. All patients had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968167/gefitinib-plus-chemotherapy-versus-chemotherapy-in-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-resistant-to-first-line-gefitinib-impress-overall-survival-and-biomarker-analyses
#18
Tony S K Mok, Sang-We Kim, Yi-Long Wu, Kazuhiko Nakagawa, Jin-Ji Yang, Myung-Ju Ahn, Jie Wang, James Chih-Hsin Yang, You Lu, Shinji Atagi, Santiago Ponce, Xiaojin Shi, Yuri Rukazenkov, Vincent Haddad, Kenneth S Thress, Jean-Charles Soria
Purpose The Iressa Mutation-Positive Multicentre Treatment Beyond ProgRESsion Study (IMPRESS) compared the continuation of gefitinib plus chemotherapy with placebo plus chemotherapy in patients with epidermal growth factor receptor ( EGFR) mutation-positive advanced non-small-cell lung cancer with progression (Response Evaluation Criteria in Solid Tumors 1.1) after first-line gefitinib. Primary results indicated no difference between treatments in terms of progression-free survival (PFS). The current analysis presents final, mature, overall survival (OS) data, together with exploratory analyses that examined whether specific biomarkers, including T790M mutation status, were able to differentiate a relative treatment effect...
October 2, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28967485/first-line-pembrolizumab-in-cisplatin-ineligible-patients-with-locally-advanced-and-unresectable-or-metastatic-urothelial-cancer-keynote-052-a-multicentre-single-arm-phase-2-study
#19
Arjun V Balar, Daniel Castellano, Peter H O'Donnell, Petros Grivas, Jacqueline Vuky, Thomas Powles, Elizabeth R Plimack, Noah M Hahn, Ronald de Wit, Lei Pang, Mary J Savage, Rodolfo F Perini, Stephen M Keefe, Dean Bajorin, Joaquim Bellmunt
BACKGROUND: More than half of all patients with advanced urothelial cancer cannot receive standard, first-line cisplatin-based chemotherapy because of renal dysfunction, poor performance status, or other comorbidities. We assessed the activity and safety of first-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer. METHODS: In this multicentre, single-arm, phase 2 study (KEYNOTE-052), cisplatin-ineligible patients with advanced urothelial cancer who had not been previously treated with systemic chemotherapy were recruited from 91 academic medical centres in 20 countries...
September 26, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28961837/antitumor-activity-of-lurbinectedin-pm01183-and-doxorubicin-in-relapsed-small-cell-lung-cancer-results-from-a-phase-i-study
#20
E Calvo, V Moreno, M Flynn, E Holgado, M E Olmedo, M P Lopez Criado, C Kahatt, J A Lopez-Vilariño, M Siguero, C Fernandez-Teruel, M Cullell-Young, A Soto Matos-Pita, M Forster
Background: Lurbinectedin (PM01183) has synergistic antitumor activity when combined with doxorubicin in mice with xenografted tumors. This phase I trial determined the recommended dose (RD) of doxorubicin (bolus) and PM01183 (1-h intravenous infusion) on day 1 every 3 weeks (q3wk), and obtained preliminary evidence of antitumor activity for this combination in small-cell lung cancer (SCLC). Patients and methods: Patients with advanced solid tumors received doxorubicin and PM01183 following a standard dose escalation design and expansion at the RD...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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