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https://www.readbyqxmd.com/read/28331615/nuclear-irf-1-expression-as-a-mechanism-to-assess-capability-to-express-pd-l1-and-response-to-pd-1-therapy-in-metastatic-melanoma
#1
James W Smithy, Lauren M Moore, Vasiliki Pelekanou, Jamaal Rehman, Patricia Gaule, Pok Fai Wong, Veronique M Neumeister, Mario Sznol, Harriet M Kluger, David L Rimm
BACKGROUND: Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize that capacity to express PD-L1, as assessed by an assay for a PD-L1 transcription factor, interferon regulatory factor 1 (IRF-1), may better distinguish patients likely to benefit from anti-PD-1 immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331050/first-in-human-clinical-trial-of-oral-onc201-in-patients-with-refractory-solid-tumors
#2
Mark N Stein, Joseph R Bertino, Howard L Kaufman, Tina Mayer, Rebecca Moss, Ann Silk, Nancy Chan, Jyoti Malhotra, Lorna Rodriguez-Rodriguez, Joseph Aisner, Robert D Aiken, Bruce G Haffty, Robert S DiPaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Siobhan Dickerson, Ling Zheng, Wafik S El-Deiry, Joshua Allen, Martin Stogniew, Wolfgang Oster, Janice M Mehnert
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28330468/tumor-burden-monitoring-using-cell-free-tumor-dna-could-be-limited-by-tumor-heterogeneity-in-advanced-breast-cancer-and-should-be-evaluated-together-with-radiographic-imaging
#3
José Angel García-Saenz, Patricia Ayllón, Marion Laig, Daniel Acosta-Eyzaguirre, Marta García-Esquinas, Myriam Montes, Julián Sanz, Miguel Barquín, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Díaz-Rubio, Trinidad Caldes, Atocha Romero
BACKGROUND: Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification. METHODS: Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging...
March 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28328955/treatment-monitoring-in-metastatic-colorectal-cancer-patients-by-quantification-and-kras-genotyping-of-circulating-cell-free-dna
#4
Andreas W Berger, Daniel Schwerdel, Hanna Welz, Ralf Marienfeld, Stefan A Schmidt, Alexander Kleger, Thomas J Ettrich, Thomas Seufferlein
Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool...
2017: PloS One
https://www.readbyqxmd.com/read/28327969/circulating-tumour-dna-predicts-response-to-anti-pd1-antibodies-in-metastatic-melanoma
#5
J H Lee, G V Long, S Boyd, S Lo, A M Menzies, V Tembe, A Guminski, V Jakrot, R A Scolyer, G J Mann, R F Kefford, M S Carlino, H Rizos
Background: Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information. Patients and methods: We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab. Results: ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327897/towards-a-global-cancer-knowledge-network-dissecting-the-current-international-cancer-genomic-sequencing-landscape
#6
D J Vis, J Lewin, R G Liao, M Mao, F Andre, R L Ward, F Calvo, B T Teh, A A Camargo, B M Knoppers, C Sawyers, L F A Wessels, M Lawler, L L Siu, E Voest
Background: While next generation sequencing has enhanced our understanding of the biological basis of malignancy, current knowledge on global practices for sequencing cancer samples is limited. To address this deficiency, we developed a survey to provide a snapshot of current sequencing activities globally, identify barriers to data sharing and use this information to develop sustainable solutions for the cancer research community. Methods: A multi-item survey was conducted assessing demographics, clinical data collection, genomic platforms, privacy/ethics concerns, funding sources and data sharing barriers for sequencing initiatives globally...
February 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28324920/an-open-label-randomized-parallel-phase-ii-trial-to-evaluate-the-efficacy-and-safety-of-a-cremophor-free-polymeric-micelle-formulation-of-paclitaxel-as-first-line-treatment-for-ovarian-cancer-a-korean-gynecologic-oncology-group-study-kgog-3021
#7
Shin-Wha Lee, Yong-Man Kim, Chi Heum Cho, Young Tae Kim, Seok Mo Kim, Soo Young Hur, Jae-Hoon Kim, Byoung-Gie Kim, Seung-Cheol Kim, Hee-Sug Ryu, Soon Beom Kang
Purpose: Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here we compared efficacy and safety of Genexol-PM plus carboplatin vs. Genexol plus carboplatin for ovarian cancer treatment. Materials and Methods: In this multicenter, randomized, phase II study, patients with FIGO IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 with 5 AUC carboplatin every three weeks (6 cycles)...
March 21, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28324265/cardiac-safety-efficacy-and-correlation-of-serial-serum-her2-extracellular-domain-shed-antigen-measurement-with-the-outcome-of-the-combined-trastuzumab-plus-cmf-in-women-with-her2-positive-metastatic-breast-cancer-results-from-the-eortc-10995-phase-ii-study
#8
Konstantinos Tryfonidis, S Marreaud, H Khaled, B De Valk, J Vermorken, M Welnicka-Jaskiewicz, K Aalders, J M S Bartlett, L Biganzoli, J Bogaerts, David Cameron
PURPOSE: Cardiotoxicity is a side effect of trastuzumab. We assessed efficacy and cardiac safety of CMF with trastuzumab (CMF+T) in HER2-positive metastatic breast cancer patients (MBC). METHODS: In this phase II study, centrally confirmed, previously treated HER2-positive MBC patients with measurable disease (per RECIST v 1.0) were enrolled. Initially, patients were randomized between 8 CMF cycles alone or combined with trastuzumab during chemotherapy, followed by 3-weekly trastuzumab maintenance till progression...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28321816/cancer-imaging-in-immunotherapy
#9
Yousra Eleneen, Rivka R Colen
Immune therapeutics are revolutionizing cancer treatments. In tandem, new and confounding imaging characteristics have appeared that are distinct from those typically seen with conventional cytotoxic therapies. In fact, only 10% of patients on immunotherapy may show tumor shrinkage, typical of positive responses on conventional therapy. Conversely, those on immune therapies may initially demonstrate a delayed response, transient enlargement followed by tumor shrinkage, stable size, or the appearance of new lesions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28317088/phase-i-trial-of-the-oral-smoothened-inhibitor-sonidegib-in-combination-with-paclitaxel-in-patients-with-advanced-solid-tumors
#10
A Stathis, D Hess, R von Moos, K Homicsko, G Griguolo, M Joerger, M Mark, C J Ackermann, S Allegrini, C V Catapano, A Xyrafas, M Enoiu, S Berardi, P Gargiulo, C Sessa
Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m(2) on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28317063/prognostic-value-of-pretreatment-diffusion-weighted-magnetic-resonance-imaging-for-outcome-prediction-of-colorectal-cancer-liver-metastases-undergoing-90y-microsphere-radioembolization
#11
Frederic Carsten Schmeel, Birgit Simon, Julian Alexander Luetkens, Frank Träber, Carsten Meyer, Leonard Christopher Schmeel, Amir Sabet, Samer Ezziddin, Hans Heinz Schild, Dariusch Reza Hadizadeh
PURPOSE: To investigate the clinical potential of pretreatment apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DWI) for therapy response and outcome prediction in patients with liver-predominant metastatic colorectal cancer (CRC) undergoing radioembolization with (90)Yttrium-microspheres (90Y-RE). METHODS: Forty-six consecutive patients with unresectable CRC liver metastases underwent standardized clinical DWI on a 1.5 T MR scanner prior to and 4-6 weeks after 90Y-RE...
March 19, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28316212/-evaluation-and-classification-of-drug-therapy-for-breast-cancer-with-bone-only-metastasis
#12
X Y Meng, S T Song
Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT...
March 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28306548/repeated-diffusion-mri-reveals-earliest-time-point-for-stratification-of-radiotherapy-response-in-brain-metastases
#13
Faisal Mahmood, Helle H Johannesen, Poul Geertsen, Rasmus H Hansen
An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases...
March 17, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28302097/objective-response-to-mtor-inhibition-in-a-metastatic-collision-tumor-of-the-liver-composed-of-melanoma-and-adenocarcinoma-with-tsc1-loss-a-case-report
#14
Munveer S Bhangoo, Jenny Y Zhou, Siraj M Ali, Russell Madison, Alexa B Schrock, Carrie Costantini
BACKGROUND: Collision tumors are uncommon but well described clinical entities composed of distinct tumor histologies occurring within the same anatomic site. Optimal management of patients with collision tumors remains highly variable and depends on clinical characteristics such as the involved tumor types, predominant histology, as well as the extent of disease. Comprehensive genomic profiling is a means of identifying genomic alterations to suggest benefit from targeted therapy. CASE PRESENTATION: A 78-year-old woman presented to medical oncology with liver metastases occurring within the background of a 1-year history of uveal melanoma...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28291905/long-term-results-of-therapy-with-sunitinib-in-metastatic-alveolar-soft-part-sarcoma
#15
Paulina Jagodzińska-Mucha, Tomasz Świtaj, Katarzyna Kozak, Hanna Koseła-Paterczyk, Anna Klimczak, Iwona Ługowska, Pawel Rogala, Michał Wągrodzki, Sławomir Falkowski, Piotr Rutkowski
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare, highly vascularized soft tissue sarcoma characterized by a high frequency of metastatic disease and resistance to classical chemotherapy. The purpose of our analysis was to assess long-term sunitinib activity in the treatment of metastatic ASPS. PATIENTS AND METHODS: Between 2009 and 2015, 15 patients were diagnosed with metastatic ASPS and received therapy with sunitinib at initial continuous daily dosing of 37...
March 8, 2017: Tumori
https://www.readbyqxmd.com/read/28291584/clinical-safety-and-activity-of-pembrolizumab-in-patients-with-malignant-pleural-mesothelioma-keynote-028-preliminary-results-from-a-non-randomised-open-label-phase-1b-trial
#16
Evan W Alley, Juanita Lopez, Armando Santoro, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Emilie van Brummelen
BACKGROUND: Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort. METHODS: Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries...
March 10, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28289864/correlation-between-clinical-response-to-sorafenib-in-hepatocellular-carcinoma-treatment-and-polymorphisms-of-p-glycoprotein-abcb1-and-of-breast-cancer-resistance-protein-abcg2-monocentric-study
#17
Mahamadou Tandia, Asma Mhiri, Bernard Paule, Raphaël Saffroy, Valérie Cailliez, Gaëlle Noé, Robert Farinotti, Laurence Bonhomme-Faivre
OBJECTIVES: We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma. METHODS: At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28288839/the-role-of-high-dose-interleukin-2-in-the-era-of-targeted-therapy
#18
Jessie Gills, William P Parker, Scott Pate, Sida Niu, Peter Van Veldhuizen, Moben Mirza, Jeffery M Holzbeierlein, Eugene K Lee
OBJECTIVE: To assess survival outcomes following high dose IL-2 (HDIL-2) in a contemporary cohort of patients during the era of targeted agents. METHODS: Retrospective review of metastatic RCC patients treated with HDIL-2 between July 2007 and September 2014. Clinicopathologic data were abstracted and patient response to therapy was based on RECIST v1.1 criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) for the entire cohort, response to HDIL-2 in regards to previous targeted agent therapy, and response to targeted agent in relationship to response to HDIL-2...
March 10, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28284173/patient-derived-solitary-fibrous-tumour-xenografts-predict-high-sensitivity-to-doxorubicin-dacarbazine-combination-confirmed-in-the-clinic-and-highlight-the-potential-effectiveness-of-trabectedin-or-eribulin-against-this-tumour
#19
S Stacchiotti, M Saponara, R Frapolli, M Tortoreto, D Cominetti, S Provenzano, T Negri, G P Dagrada, A Gronchi, C Colombo, B Vincenzi, G Badalamenti, V Zuco, S L Renne, P Collini, C Morosi, A P Dei Tos, E Bello, S Pilotti, P G Casali, M D'Incalci, N Zaffaroni
BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice...
March 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28283779/phase-ib-study-of-the-mitochondrial-inhibitor-me-344-plus-topotecan-in-patients-with-previously-treated-locally-advanced-or-metastatic-small-cell-lung-ovarian-and-cervical-cancers
#20
Jennifer R Diamond, Barbara Goff, Martin D Forster, Johanna C Bendell, Carolyn D Britten, Michael S Gordon, Hani Gabra, David M Waterhouse, Mark Poole, D Ross Camidge, Erika Hamilton, Kathleen M Moore
Background This multicenter, open-label, phase Ib study was designed to assess the safety, pharmacokinetics and preliminary efficacy of ME-344, a mitochondrial inhibitor, administered in combination with the topoisomerase I inhibitor, topotecan, in patients with previously treated, locally advanced or metastatic small cell lung (SCLC), ovarian and cervical cancers. Patients and methods In Part 1, patients received ME-344 10 mg/kg intravenously weekly on days 1, 8, 15 and 22 in combination with topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28 day cycle...
March 10, 2017: Investigational New Drugs
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