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Response evaluation of solid tumors

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https://www.readbyqxmd.com/read/28223062/nivolumab-for-previously-treated-unresectable-metastatic-anal-cancer-nci9673-a-multicentre-single-arm-phase-2-study
#1
Van K Morris, Mohamed E Salem, Halla Nimeiri, Syma Iqbal, Preet Singh, Kristen Ciombor, Blase Polite, Dustin Deming, Emily Chan, James L Wade, Lianchun Xiao, Tanios Bekaii-Saab, Luis Vence, Jorge Blando, Armeen Mahvash, Wai Chin Foo, Chimela Ohaji, Manolo Pasia, Gail Bland, Aki Ohinata, Jane Rogers, Amir Mehdizadeh, Kimberly Banks, Richard Lanman, Robert A Wolff, Howard Streicher, James Allison, Padmanee Sharma, Cathy Eng
BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA...
February 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#2
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28218707/fkbp51-immunohistochemical-expression-a-new-prognostic-biomarker-for-oscc
#3
Daniela Russo, Francesco Merolla, Massimo Mascolo, Gennaro Ilardi, Simona Romano, Silvia Varricchio, Virginia Napolitano, Angela Celetti, Loredana Postiglione, Pier Paolo Di Lorenzo, Luigi Califano, Giovanni Orabona Dell'Aversana, Fabio Astarita, Maria Fiammetta Romano, Stefania Staibano
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28217920/impact-of-target-area-selection-in-125-iodine-seed-brachytherapy-on-locoregional-recurrence-in-patients-with-non-small-cell-lung-cancer
#4
Wei-Liang Yan, Jin-Shuang Lv, Zhi-Yu Guan, Li-Yang Wang, Jing-Kui Yang, Ji-Xiang Liang
BACKGROUND: Computed tomography (CT)-guided percutaneous implantation of (125) Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). METHOD: We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT...
February 20, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28216622/effects-of-gene-polymorphisms-in-the-endoplasmic-reticulum-stress-pathway-on-clinical-outcomes-of-chemoradiotherapy-in-chinese-patients-with-nasopharyngeal-carcinoma
#5
Xiao-Bin Guo, Wan-le Ma, Li-Juan Liu, Yu-Ling Huang, Jing Wang, Li-Hua Huang, Xiang-Dong Peng, Ji-Ye Yin, Jin-Gao Li, Shao-Jun Chen, Guo-Ping Yang, Hui Wang, Cheng-Xian Guo
There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28212290/defining-clinical-response-criteria-and-early-response-criteria-for-precision-oncology-current-state-of-the-art-and-future-perspectives
#6
Vivek Subbiah, Hubert H Chuang, Dhiraj Gambhire, Kalevi Kairemo
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016...
February 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/28211941/upfront-window-vincristine-irinotecan-treatment-of-high-risk-hepatoblastoma-a-report-from-the-children-s-oncology-group-ahep0731-study-committee
#7
Howard M Katzenstein, Wayne L Furman, Marcio H Malogolowkin, Mark D Krailo, M Beth McCarville, Alexander J Towbin, Greg M Tiao, Milton J Finegold, Sarangarajan Ranganathan, Stephen P Dunn, Max R Langham, Eugene D McGahren, Carlos Rodriguez-Galindo, Rebecka L Meyers
BACKGROUND: The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Children's Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma. METHODS: Patients with newly diagnosed metastatic hepatoblastoma or those with a serum α-fetoprotein (AFP) level <100 ng/mL were eligible...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28208747/multinucleated-giant-cancer-cells-produced-in-response-to-ionizing-radiation-retain-viability-and-replicate-their-genome
#8
Razmik Mirzayans, Bonnie Andrais, April Scott, Ying W Wang, Piyush Kumar, David Murray
Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21(WAF1) (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28199751/impact-of-polymorphisms-in-angiogenesis-related-genes-on-clinical-outcomes-of-radiotherapy-in-patients-with-nasopharyngeal-carcinoma
#9
Wan-Le Ma, Rong Liu, Li-Hua Huang, Chan Zou, Jie Huang, Jing Wang, Shao-Jun Chen, Xiang-Guang Meng, Jing-Ke Yang, Han Li, Guo-Ping Yang, Cheng-Xian Guo
PURPOSE: To assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. METHODS: The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The Response Evaluation Criteria in Solid Tumors were used for assessing efficacies. And The criteria of Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation...
February 15, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28197367/targeting-ewing-sarcoma-with-activated-and-gd2-specific-chimeric-antigen-receptor-engineered-human-nk-cells-induces-upregulation-of-immune-inhibitory-hla-g
#10
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196905/a-phase-i-iia-study-of-dhp107-a-novel-oral-paclitaxel-formulation-in-patients-with-advanced-solid-tumors-or-gastric-cancer
#11
Min-Hee Ryu, Baek-Yeol Ryoo, Tae Won Kim, Sung Bae Kim, Hyeong-Seok Lim, Kyun-Seop Bae, Sook Ryun Park, Yeong-Woo Jo, Hyun Ju Cho, Yoon-Koo Kang
LESSONS LEARNED: Ideally, patients should have access to an oral formulation of paclitaxel, as well as an intravenous formulation, to allow development of regimens exploring alternate schedules and to avoid reactions to Cremophor EL (BASF Corp., Ludwigshafen, Germany, https://www.basf.com).DHP107 is a novel oral paclitaxel formulation that is a tolerable and feasible regimen for patients with gastric cancer, with data suggesting efficacy similar to that of intravenous paclitaxel. BACKGROUND: We evaluated the maximum tolerated dose (MTD) of DHP107, a novel oral paclitaxel formulation, and the efficacy and safety of the agent in patients with advanced solid tumors...
February 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28194539/phase-i-trial-of-mek-1-2-inhibitor-pimasertib-combined-with-mtor-inhibitor-temsirolimus-in-patients-with-advanced-solid-tumors
#12
Monica Mita, Siqing Fu, Sarina Anne Piha-Paul, Filip Janku, Alain Mita, Ronald Natale, Wei Guo, Charles Zhao, Razelle Kurzrock, Aung Naing
Background Dual inhibition of activated MAPK and mTOR signaling pathways may enhance the antitumor efficacy of the MEK 1/2 inhibitor pimasertib and the mTOR inhibitor temsirolimus given in combination. Methods In this phase I study, patients with refractory advanced solid tumors (NCT01378377) received once-weekly temsirolimus plus once-daily oral pimasertib in 21-day cycles in a modified 3 + 3 dose-escalation design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of pimasertib in combination with temsirolimus, safety and pharmacokinetics (PK) were investigated...
February 13, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28188748/association-between-high-avidity-t-cell-receptors-induced-by-alpha-fetoprotein-derived-peptides-and-anti-tumor-effects-in-patients-with-hepatocellular-carcinoma
#13
Hidetoshi Nakagawa, Eishiro Mizukoshi, Eiji Kobayashi, Toshikatsu Tamai, Hiroshi Hamana, Tatsuhiko Ozawa, Hiroyuki Kishi, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Atsushi Muraguchi, Shuichi Kaneko
BACKGROUND & AIMS: Levels of alpha fetoprotein (AFP) are measured for surveillance and diagnosis of hepatocellular carcinoma (HCC). We performed a phase 1 trial to evaluate the safety and efficacy of AFP-derived peptides as an anti-tumor vaccine for patients with advanced HCC, and characterized induction of AFP-specific T-cell receptors (TCRs). METHODS: We performed a prospective study, of 15 patients with HCC seen at Kanazawa University Hospital in Japan from March 2010 through March 2012...
February 7, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#14
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28179454/fda-approval-summary-pembrolizumab-for-the-treatment-of-patients-with-unresectable-or-metastatic-melanoma
#15
Amy Barone, Maitreyee Hazarika, Marc R Theoret, Pallavi Mishra-Kalyani, Huanyu Chen, Kun He, Rajeshwari Sridhara, Sriram Subramaniam, Elimika Pfuma, Yaning Wang, Hongshan Li, Hong Zhao, Jeanne Fourie Zirkelbach, Patricia Keegan, Richard Pazdur
On December 18, 2015, the U.S. Food and Drug Administration (FDA) granted regular approval to pembrolizumab (KEYTRUDA®; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma, based on results of two randomized, open-label, active-controlled clinical trials. In Trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg intravenously (IV) every 2 (q2w) or 3 (q3w) weeks until disease progression or ipilimumab 3 mg/kg q3w for up to four doses...
February 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28179320/detection-of-somatic-mutations-in-gastroenteropancreatic-neuroendocrine-tumors-using-targeted-deep-sequencing
#16
Samuel Backman, Olov Norlén, Barbro Eriksson, Britt Skogseid, Peter Stålberg, Joakim Crona
: Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28174141/checkpoint-inhibition-for-advanced-mucosal-melanoma
#17
Julia Thierauf, Johannes A Veit, Jochen Hess, Nicolai Treiber, Catharina Lisson, Stephanie E Weissinger, Martin Bommer, Thomas K Hoffmann
BACKGROUND: Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. OBJECTIVES: To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. MATERIAL & METHODS: We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage...
February 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28168937/outcomes-of-spatially-fractionated-radiotherapy-grid-for-bulky-soft-tissue-sarcomas-in-a-large-animal-model
#18
Michael W Nolan, Tracy L Gieger, Alexander A Karakashian, Mariana N Nikolova-Karakashian, Lysa P Posner, Donald M Roback, Judith N Rivera, Sha Chang
GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later...
January 1, 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/28165649/intracellular-ph-measured-by-31-p-mr-spectroscopy-might-predict-site-of-progression-in-recurrent-glioblastoma-under-antiangiogenic-therapy
#19
Katharina J Wenger, Elke Hattingen, Kea Franz, Joachim P Steinbach, Oliver Bähr, Ulrich Pilatus
PURPOSE: In solid tumors, changes in the expression/activity of plasma membrane ion transporters facilitate proton efflux and enable tumor cells to maintain a higher intracellular pH (pHi ), while the microenvironment (pHe ) is commonly more acidic. This supports various tumor-promoting mechanisms. We propose that these changes in pH take place before a magnetic resonance imaging (MRI)-detectable brain tumor recurrence occurs. MATERIALS AND METHODS: We enrolled 66 patients with recurrent glioblastoma, treated with bevacizumab...
February 6, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28165332/exhaled-breath-and-oral-cavity-vocs-as-potential-biomarkers-in-oral-cancer-patients
#20
Marcos Bouza, Jesus Gonzalez-Soto, Rosario Pereiro, Juan Carlos de Vicente, Alfredo Sanz-Medel
Corporal mechanisms attributed to cancer, such as oxidative stress or the action of cytochrome P450 enzymes, seem to be responsible of the generation of a variety of volatile organic compounds (VOCs) that could be used as non-invasive diagnosis biomarkers. The present work presents an attempt of using VOCs from exhaled breath and oral cavity air as biomarkers for oral squamous cell carcinoma (OSCC) patients. 52 breath samples were collected (3 L Tedlar bags) from 26 OSCC patients and 26 cancer-free controls...
February 6, 2017: Journal of Breath Research
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