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Response evaluation of solid tumors

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https://www.readbyqxmd.com/read/28551386/influence-of-mucinous-and-necrotic-tissue-in-colorectal-cancer-samples-on-kras-mutation-analysis
#1
Juliane Büttner, Annika Lehmann, Frederick Klauschen, Michael Hummel, Dido Lenze, Manfred Dietel, Korinna Jöhrens
Evaluation of the RAS mutation status is necessary for patients with advanced colorectal cancer to predict the response to anti-EGFR therapy. In routine diagnostics, FFPE tissue samples are tested by sequencing (amplicon-based NGS and Sanger) to obtain the RAS status of the patient. Samples that are collected after chemotherapy occasionally contain necrotic tissue. Furthermore, colorectal cancer tissue sometimes has mucinous components. This may pose a challenge to molecular analysis because mucinous tumor samples often contain only few tumor cells compared to solid tumor samples...
May 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28548889/therapy-of-advanced-non-small-cell-lung-cancer-with-an-sn-38-anti-trop-2-drug-conjugate-sacituzumab-govitecan
#2
Rebecca Suk Heist, Michael J Guarino, Gregory Masters, W Thomas Purcell, Alexander N Starodub, Leora Horn, Ronald J Scheff, Aditya Bardia, Wells A Messersmith, Jordan Berlin, Allyson J Ocean, Serengulam V Govindan, Pius Maliakal, Boyd Mudenda, William A Wegener, Robert M Sharkey, David M Goldenberg, D Ross Camidge
Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points...
May 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28548103/an-aavp-based-solid-phase-transducing-matrix-for-transgene-delivery-potential-for-translational-applications
#3
T L Smith, G R Souza, R L Sidman, W Arap, R Pasqualini
A hybrid vector of adeno-associated virus and phage (termed AAVP) has been introduced as a platform for systemic ligand-directed delivery of transgenes to tumors over the past decade. A series of studies have evaluated the AAVP platform for potential theranostic or purely therapeutic applications in several tumor models. Sufficient ligand-directed tumor targeting consistently resulted in specific molecular-genetic imaging and/or anti-tumor responses to 'suicide' transgene delivery. However, efforts to optimize transduction efficiency are still ongoing...
May 26, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28546135/neoadjuvant-hypofractionated-radiotherapy-and-chemotherapy-in-high-grade-extremity-soft-tissue-sarcomas-phase-2-clinical-trial-protocol
#4
Ranyell Msb Spencer, Samuel Aguiar Junior, Fabio O Ferreira, Paulo R Stevanato Filho, Bruna Ec Kupper, Maria Lg Silva, Celso A Mello, Tiago S Bezerra, Ademar Lopes
BACKGROUND: Neoadjuvant radiotherapy (RT) and chemotherapy are applied to large, high-grade extremity soft tissue sarcomas to treat metastatic disease earlier and sterilize margins to perform R0 surgery. However, preoperative RT increases wound complication rates (rWC), delaying adjuvant chemotherapy or preventing it from being administered altogether. Hypofractionated neoadjuvant RT can be offered in this situation, concomitant to chemotherapy, allowing patients to receive chemotherapy as a preoperative treatment in less time with an acceptable rWC...
May 25, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28536023/development-of-long-circulating-docetaxel-loaded-poly-3-hydroxybutyrate-co-3-hydroxyvalerate-nanoparticles-optimization-pharmacokinetic-cytotoxicity-and-in-vivo-assessments
#5
Harsh Vardhan, Pooja Mittal, Sandeep K Reddy Adena, Mansi Upadhyay, Brahmeshwar Mishra
Long-circulating Nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett-Burman (PBD) and Box-Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39±0...
May 20, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28534349/an-overview-of-high-dose-chemotherapy-with-autologous-stem-cell-rescue-for-germ-cell-tumors-in-current-practice
#6
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Testicular cancer is a frequent tumor of adolescent and young adult males. Chemotherapy has been reported to provide cure rates as high as 80% even in the presence of advanced testicular cancer. Studies regarding testicular cancer started after the advent of high dose chemotherapy (HDC) plus atologous stem cell rescue (ASCR) for the treatment of solid tumors in 1980s. Testicular cancer is highly responsive to HDC. Einhorn et al. have reported long-lasting remissions reaching up to 40% among patients with platinum-refractory disease...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28533473/u-s-food-and-drug-administration-approval-summary-pembrolizumab-for-the-treatment-of-recurrent-or-metastatic-head-and-neck-squamous-cell-carcinoma-with-disease-progression-on-or-after-platinum-containing-chemotherapy
#7
Erin Larkins, Gideon M Blumenthal, Weishi Yuan, Kun He, Rajeshwari Sridhara, Sriram Subramaniam, Hong Zhao, Chao Liu, Jingyu Yu, Kirsten B Goldberg, Amy E McKee, Patricia Keegan, Richard Pazdur
On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy...
May 22, 2017: Oncologist
https://www.readbyqxmd.com/read/28526418/prevalence-of-measurable-disease-in-metastatic-castration-resistant-prostate-cancer
#8
Guru Sonpavde, Ankit Madan, Mary K Baker, Jori E May, Gurudatta Naik, Sejong Bae
BACKGROUND: Because of the low historical prevalence of measurable disease in metastatic castration-resistant prostate cancer (mCRPC), phase II trials have used prostate-specific antigen (PSA) and bone scan changes as primary end points. Frequent whole-body imaging and improved computed tomography technology currently identify measurable disease more frequently, warranting consideration of objective response as a major end point. PATIENTS AND METHODS: Data from reported phase III trials of mCRPC were analyzed...
April 26, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28521076/phase-i-study-of-perifosine-monotherapy-in-patients-with-recurrent-or-refractory-neuroblastoma
#9
Kimikazu Matsumoto, Hiroyuki Shichino, Hiroshi Kawamoto, Yoshiyuki Kosaka, Motoaki Chin, Koji Kato, Hideo Mugishima
PURPOSE: Perifosine is an alkylphospholipid analog that inhibits or modulates signaling through signal transduction pathways such as Akt, which is enhanced in neuroblastoma (NB) by activation of tyrosine kinase receptors. We conducted a phase I study of perifosine in Japanese patients with recurrent or refractory NB. EXPERIMENTAL DESIGN: All patients enrolled were over 2 years of age; all had refractory or relapsed NB and a performance status of greater than 50%...
May 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28510616/salvage-high-dose-chemotherapy-in-female-patients-with-relapsed-refractory-germ-cell-tumors-a-retrospective-analysis-of-the-european-group-for-blood-and-marrow-transplantation-ebmt
#10
U De Giorgi, S Richard, M Badoglio, E Kanfer, J H Bourrhis, E Nicolas-Virelizier, K Vettenranta, B Lioure, S Martin, P Dreger, M K Schuler, K Thomson, E Scarpi, G Rosti, F Selle, G Mangili, F Lanza, M Bregni
Background: High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation (EBMT). Patients and methods: Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC...
May 16, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28508253/image-guided-transarterial-chemoembolization-with-drug-eluting-beads-loaded-with-doxorubicin-debdox-for-unresectable-hepatic-metastases-from-melanoma-technique-and-outcomes
#11
Jack Rostas, Alda Tam, Takami Sato, Larry Kelly, Cliff Tatum, Charles Scoggins, Kelly McMasters, Robert C G Martin
PURPOSE: Hepatic metastasis from melanoma represents a therapeutic dilemma, with limited effective options for the 85% of cases deemed unresectable. Systemic agents confer toxicity and, along with traditional local hepatic arterial-directed therapies such as transarterial chemoembolization, have not led to a significant increase in survival. The aim of this study was to investigate the safety and dose-limiting toxicity of DEBDOX for the treatment of unresectable hepatic metastases from melanoma...
May 15, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28506521/role-of-imaging-in-response-assessment-and-individualised-treatment-for-sarcomas
#12
H Choi
The first systematic response evaluation criteria were established by WHO, based on the tumor size changes shortly after the computed tomography (CT) technique became available to the daily practice. RECIST, a simplified version of WHO criteria, and its newer version, RECIST1.1 are the currently available international response evaluation criteria in solid tumors and remains based on tumor size changes. While the introduction of molecularly targeted drugs has significantly improved the survival in patient with sarcomas, the evaluation of tumor response has become more complicated...
May 12, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28498413/cpg-oligodeoxynucleotides-augment-antitumor-efficacy-of-folate-receptor-%C3%AE-based-dna-vaccine
#13
Zheng Qiu, Lijun Xing, Xueqing Zhang, Xu Qiang, Yifeng Xu, Mei Zhang, Zhengpin Zhou, Juan Zhang, Fang Zhang, Min Wang
Folate receptor α (FRα) is overexpressed in a variety of solid tumors and has become an attractive target antigen for immunotherapy purposes. A DNA vaccine was generated by ligation of FRα cDNA into the eukaryotic vector pcDNA3.1. Expression of FRα was confirmed in transiently transfected B16 cells. B16 cell lines that stably express FRα were set up by G418 selection. A total of 100 µg purified plasmid DNA alone or in combination with CpG oligodeoxynucleotides (CpG ODN) was injected intramuscularly in C57BL/6 mice four times at one week intervals...
May 8, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498256/paragon-anzgog-0903-phase-2-study-of-anastrozole-in-women-with-estrogen-or-progesterone-receptor-positive-platinum-resistant-or-refractory-recurrent-ovarian-cancer
#14
Anthony Bonaventura, Rachel L OʼConnell, Cristina Mapagu, Philip J Beale, Orla M McNally, Linda R Mileshkin, Peter T Grant, Alison M Hadley, Jeffery C H Goh, Katrin M Sjoquist, Julie Martyn, Anna DeFazio, James Scurry, Michael L Friedlander
BACKGROUND: There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptor-positive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer. METHODS: Postmenopausal women who had estrogen and/or progesterone receptor-positive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28490981/robotic-radiosurgery-for-the-treatment-of-liver-metastases
#15
Rafael García, Iciar Santa-Olalla, Jose Luis Lopez Guerra, Silvia Sanchez, Ignacio Azinovic
AIM: This study evaluates the toxicity and outcome in patients treated with robotic radiosurgery for liver metastases. BACKGROUND: Modern technologies allow the delivery of high doses to the liver metastases while lowering the dose to the neighboring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known yet. METHODS AND MATERIALS: A total of 9 patients with 17 liver metastases have been treated with robotic stereotactic body radiotherapy SBRT from March 2011 to December 2014...
March 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/28490472/-18-f-fdg-pet-ct-for-very-early-response-evaluation-predicts-ct-response-in-erlotinib-treated-nsclc-patients-a-comparison-of-assessment-methods
#16
Joan Fledelius, Anne Winther-Larsen, Azza Ahmed Khalil, Catharina Mølgaard Bylov, Karin Hjorthaug, Aksel Bertelsen, Jørgen Frøkiær, Peter Meldgaard
The purpose of this study was to determine which method for early response evaluation with (18)F-fluoro-D-glucose positron emission tomography combined with whole body computed tomography ((18)F-FDG-PET/CT) performed most optimal for prediction of response on a later CT-scan in erlotinib treated non-small cell lung cancer (NSCLC) patients. Methods:(18)F-FDG-PET/CT scans were performed prior to and after 7-10 days of erlotinib treatment in 50 NSCLC patients. The scans were evaluated using a qualitative approach and various semi-quantitative methods including percentage change in Standardized Uptake values, lean body mass corrected (SUL) SULpeak, SULmax and Total Lesion Glycolysis (TLG)...
May 10, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28490463/a-first-in-human-phase-i-dose-escalation-study-of-tak-117-a-selective-pi3k-alpha-isoform-inhibitor-in-patients-with-advanced-solid-malignancies
#17
Dejan Juric, Johann S de Bono, Patricia M LoRusso, John Nemunaitis, Elisabeth I Heath, Eunice L Kwak, Teresa Macarulla Mercadé, Elena Geuna, Maria Jose de Miguel-Luken, Chirag Patel, Keisuke Kuida, Serap Sankoh, Eric H Westin, Fabian Zohren, Yaping Shou, Josep Tabernero
Purpose: To evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of TAK-117 (MLN1117/INK1117), an investigational PI3Kα-selective inhibitor, in patients with advanced solid tumors. <p>Experimental Design: Seventy-one patients received oral TAK-117 once daily (QD, 100-300 mg [n = 24]), or 3 days per week (Mon-Wed-Fri [MWF], 200-1200 mg [n = 27]; Mon-Tue-Wed [MTuW], 200-900 mg [n = 20]), in 21-day cycles. Dose escalation proceeded via a 3+3 design...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28489985/preclinical-evaluation-of-the-imipridone-family-analogues-of-clinical-stage-anti-cancer-small-molecule-onc201-reveals-potent-anti-cancer-effects-of-onc212
#18
Jessica Wagner, Christina Leah Kline, Marie D Ralff, Avital Lev, Amriti Lulla, Lanlan Zhou, Gary L Olson, Bhaskara Rao Nallaganchu, Cyril H Benes, Joshua E Allen, Varun V Prabhu, Martin Stogniew, Wolfgang Oster, Wafik S El-Deiry
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives...
May 10, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28489510/safety-and-antitumor-activity-of-pembrolizumab-in-advanced-programmed-death-ligand-1-positive-endometrial-cancer-results-from-the-keynote-028-study
#19
Patrick A Ott, Yung-Jue Bang, Dominique Berton-Rigaud, Elena Elez, Michael J Pishvaian, Hope S Rugo, Igor Puzanov, Janice M Mehnert, Kyaw L Aung, Juanita Lopez, Marion Carrigan, Sanatan Saraf, Mei Chen, Jean-Charles Soria
Purpose The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods Female patients with locally advanced or metastatic PD-L1-positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28489509/akt-inhibition-in-solid-tumors-with-akt1-mutations
#20
David M Hyman, Lillian M Smyth, Mark T A Donoghue, Shannon N Westin, Philippe L Bedard, Emma J Dean, Hideaki Bando, Anthony B El-Khoueiry, José A Pérez-Fidalgo, Alain Mita, Jan H M Schellens, Matthew T Chang, Jonathan B Reichel, Nancy Bouvier, S Duygu Selcuklu, Tara E Soumerai, Jean Torrisi, Joseph P Erinjeri, Helen Ambrose, J Carl Barrett, Brian Dougherty, Andrew Foxley, Justin P O Lindemann, Robert McEwen, Martin Pass, Gaia Schiavon, Michael F Berger, Sarat Chandarlapaty, David B Solit, Udai Banerji, José Baselga, Barry S Taylor
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST)...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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