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Precision oncology

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https://www.readbyqxmd.com/read/28546227/keyboard-a-novel-bayesian-toxicity-probability-interval-design-for-phase-i-clinical-trials
#1
Fangrong Yan, Sumithra J Mandrekar, Ying Yuan
The primary objective of phase I oncology trials is to find the maximum tolerated dose (MTD). The 3+3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval...
May 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28545463/cve-an-r-package-for-interactive-variant-prioritisation-in-precision-oncology
#2
Andreas Mock, Suzanne Murphy, James Morris, Francesco Marass, Nitzan Rosenfeld, Charlie Massie
BACKGROUND: An increasing number of precision oncology programmes are being launched world-wide. To support this development, we present the Cancer Variant Explorer (CVE), an R package with an interactive Shiny web browser interface. RESULTS: Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability. We present example applications including the analysis of an individual patient and a cohort-wide study, and provide a first extension of CVE by adding a tumour-specific co-expression network...
May 25, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28535106/value-tools-in-managed-care-decision-making-current-hurdles-and-future-opportunities
#3
Jeremy Schafer, Dominic Galante, Jason Shafrin
BACKGROUND: Organizations such as the National Comprehensive Cancer Network, American Society of Clinical Oncology, Institute for Clinical and Economic Review, and Memorial Sloan Kettering have created distinct tools to help different stakeholders assess the value of oncology treatments. However, the oncology value tools were not necessarily created for payers, and it is unclear whether payers are using these tools as part of their drug management process. OBJECTIVE: To understand what value tools payers are using in oncology management and what benefits and shortcomings the tools may have from the payer perspective...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28529704/towards-a-systems-approach-for-chronic-diseases-based-on-health-state-modeling
#4
Michael Rebhan
Rising pressure from chronic diseases means that we need to learn how to deal with challenges at a different level, including the use of systems approaches that better connect across fragments, such as disciplines, stakeholders, institutions, and technologies. By learning from progress in leading areas of health innovation (including oncology and AIDS), as well as complementary indications (Alzheimer's disease), I try to extract the most enabling innovation paradigms, and discuss their extension to additional areas of application within a systems approach...
2017: F1000Research
https://www.readbyqxmd.com/read/28528264/baseline-and-longitudinal-variability-of-normal-tissue-uptake-values-of-18-f-fluorothymidine-pet-images
#5
Matthijs C F Cysouw, Gerbrand M Kramer, Virginie Frings, Adrianus J De Langen, Mariëlle J Wondergem, Laura M Kenny, Eric O Aboagye, Carsten Kobe, Jürgen Wolf, Otto S Hoekstra, Ronald Boellaard
PURPOSE: [(18)F]-fluorothymidine ([(18)F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution. METHODS: (18)F-FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated...
May 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28522743/forward-to-the-past-the-case-for-quantitative-pet-imaging
#6
Adriaan A Lammertsma
Positron emission tomography (PET) was developed in the 1970's as an in vivo method to measure regional pathophysiological processes. In the 1990's the focus moved to the detection of local increases in uptake, first in the brain (activation studies) and later in oncology (finding metastases), where (18)F-FDG emerged as a highly sensitive staging technique. This focus on sensitivity has overshadowed the other main characteristic of PET, its quantitative nature. In recent years there has been a new shift. PET is now seen as a promising tool for drug development and precision medicine, i...
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28514737/integration-of-phytochemicals-and-phytotherapy-into-cancer-precision-medicine
#7
REVIEW
Thomas Efferth, Mohamed E M Saeed, Elhaj Mirghani, Awadh Alim, Zahir Yassin, Elfatih Saeed, Hassan E Khalid, Salah Daak
Concepts of individualized therapy in the 1970s and 1980s attempted to develop predictive in vitro tests for individual drug responsiveness without reaching clinical routine. Precision medicine attempts to device novel individual cancer therapy strategies. Using bioinformatics, relevant knowledge is extracted from huge data amounts. However, tumor heterogeneity challenges chemotherapy due to genetically and phenotypically different cell subpopulations, which may lead to refractory tumors. Natural products always served as vital resources for cancer therapy (e...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511612/ngs-analysis-on-tumor-tissue-and-cfdna-for-genotype-directed-therapy-in-metastatic-nsclc-patients-between-hope-and-hype
#8
Alexander T Falk, Simon Heeke, Véronique Hofman, Virginie Lespinet, Camille Ribeyre, Olivier Bordone, Michel Poudenx, Josiane Otto, Georges Garnier, Olivier Castelnau, Joël Guigay, Sylvie Leroy, Charles-Hugo Marquette, Paul Hofman, Marius Ilié
The advent of genomic based precision medicine led to the implementation of biomarker testing in metastatic non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented to routine diagnostic requirements in lung oncology. Areas covered: Two cases of patients with metastatic NSCLC for whom NGS analysis performed on both tumor and liquid biopsy has not improved the clinical course of their disease are reported. These cases illustrate the difficulty of the so-called "personalized or precision" medicine in clinical routine practice for metastatic NSCLC...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28511094/isolation-and-genetic-analysis-of-pure-cells-from-forensic-biological-mixtures-the-precision-of-a-digital-approach
#9
F Fontana, C Rapone, G Bregola, R Aversa, A de Meo, G Signorini, M Sergio, A Ferrarini, R Lanzellotto, G Medoro, G Giorgini, N Manaresi, A Berti
Latest genotyping technologies allow to achieve a reliable genetic profile for the offender identification even from extremely minute biological evidence. The ultimate challenge occurs when genetic profiles need to be retrieved from a mixture, which is composed of biological material from two or more individuals. In this case, DNA profiling will often result in a complex genetic profile, which is then subject matter for statistical analysis. In principle, when more individuals contribute to a mixture with different biological fluids, their single genetic profiles can be obtained by separating the distinct cell types (e...
May 1, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28499618/applying-precision-oncology-to-renal-cell-carcinoma-emerging-challenges
#10
EDITORIAL
John T Leppert
No abstract text is available yet for this article.
May 9, 2017: European Urology
https://www.readbyqxmd.com/read/28498238/nomogram-predicting-overall-survival-in-operable-cervical-cancer-patients
#11
Ru-Ru Zheng, Xiao-Wan Huang, Wen-Yue Liu, Rong-Rong Lin, Fei-Yun Zheng, Feng Lin
OBJECTIVE: Nomograms are widely used as predictive tools to predict oncological outcomes intuitively and precisely. The aim of our study was to develop a nomogram for predicting overall survival (OS) of patients with early stage cervical cancer. METHODS: In this retrospective study, the clinical, pathological, and hematological data and prognosis of 795 cervical cancer patients were investigated. We identified and incorporated independent significant prognostic factors for OS to develop a nomogram...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28497027/data-based-radiation-oncology-design-of-clinical-trials-in-the-toxicity-biomarkers-era
#12
REVIEW
David Azria, Ariane Lapierre, Sophie Gourgou, Dirk De Ruysscher, Jacques Colinge, Philippe Lambin, Muriel Brengues, Tim Ward, Søren M Bentzen, Hubert Thierens, Tiziana Rancati, Christopher J Talbot, Ana Vega, Sarah L Kerns, Christian Nicolaj Andreassen, Jenny Chang-Claude, Catharine M L West, Corey M Gill, Barry S Rosenstein
The ability to stratify patients using a set of biomarkers, which predict that toxicity risk would allow for radiotherapy (RT) modulation and serve as a valuable tool for precision medicine and personalized RT. For patients presenting with tumors with a low risk of recurrence, modifying RT schedules to avoid toxicity would be clinically advantageous. Indeed, for the patient at low risk of developing radiation-associated toxicity, use of a hypofractionated protocol could be proposed leading to treatment time reduction and a cost-utility advantage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28493527/characterization-of-a-sandwich-elisa-for-the-quantification-of%C3%A2-all-human-periostin-isoforms
#13
Elisabeth Gadermaier, Manfred Tesarz, Andreea Ana-Maria Suciu, Jacqueline Wallwitz, Gabriela Berg, Gottfried Himmler
BACKGROUND: Periostin (osteoblast-specific factor OSF-2) is a secreted protein occurring in seven known isoforms, and it is involved in a variety of biological processes in osteology, tissue repair, oncology, cardiovascular and respiratory systems or allergic manifestations. To analyze functional aspects of periostin, or the ability of periostin as potential biomarker in physiological and pathological conditions, there is the need for a precise, well-characterized assay that detects periostin in peripheral blood...
May 11, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28493033/is-there-a-genetic-anticipation-in-breast-and-or-ovarian-cancer-families-with-the-germline-c-3481_3491del11-mutation
#14
R El Tannouri, E Albuisson, P Jonveaux, E Luporsi
The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine...
May 10, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28486397/targeting-intracellular-calcium-signaling-ca-2-i-to-overcome-acquired-multidrug-resistance-of-cancer-cells-a-mini-overview
#15
REVIEW
Dietrich Büsselberg, Ana-Maria Florea
Cancer is a main public health problem all over the world. It affects millions of humans no matter their age, gender, education, or social status. Although chemotherapy is the main strategy for the treatment of cancer, a major problem limiting its success is the intrinsic or acquired drug resistance. Therefore, cancer drug resistance is a major impediment in medical oncology resulting in a failure of a successful cancer treatment. This mini-overview focuses on the interdependent relationship between intracellular calcium ([Ca(2+)]i) signaling and multidrug resistance of cancer cells, acquired upon treatment of tumors with anticancer drugs...
May 9, 2017: Cancers
https://www.readbyqxmd.com/read/28481359/mutational-landscape-of-metastatic-cancer-revealed-from-prospective-clinical-sequencing-of-10-000-patients
#16
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha, Hyunjae R Kim, Preethi Srinivasan, Jianjiong Gao, Debyani Chakravarty, Sean M Devlin, Matthew D Hellmann, David A Barron, Alison M Schram, Meera Hameed, Snjezana Dogan, Dara S Ross, Jaclyn F Hechtman, Deborah F DeLair, JinJuan Yao, Diana L Mandelker, Donavan T Cheng, Raghu Chandramohan, Abhinita S Mohanty, Ryan N Ptashkin, Gowtham Jayakumaran, Meera Prasad, Mustafa H Syed, Anoop Balakrishnan Rema, Zhen Y Liu, Khedoudja Nafa, Laetitia Borsu, Justyna Sadowska, Jacklyn Casanova, Ruben Bacares, Iwona J Kiecka, Anna Razumova, Julie B Son, Lisa Stewart, Tessara Baldi, Kerry A Mullaney, Hikmat Al-Ahmadie, Efsevia Vakiani, Adam A Abeshouse, Alexander V Penson, Philip Jonsson, Niedzica Camacho, Matthew T Chang, Helen H Won, Benjamin E Gross, Ritika Kundra, Zachary J Heins, Hsiao-Wei Chen, Sarah Phillips, Hongxin Zhang, Jiaojiao Wang, Angelica Ochoa, Jonathan Wills, Michael Eubank, Stacy B Thomas, Stuart M Gardos, Dalicia N Reales, Jesse Galle, Robert Durany, Roy Cambria, Wassim Abida, Andrea Cercek, Darren R Feldman, Mrinal M Gounder, A Ari Hakimi, James J Harding, Gopa Iyer, Yelena Y Janjigian, Emmet J Jordan, Ciara M Kelly, Maeve A Lowery, Luc G T Morris, Antonio M Omuro, Nitya Raj, Pedram Razavi, Alexander N Shoushtari, Neerav Shukla, Tara E Soumerai, Anna M Varghese, Rona Yaeger, Jonathan Coleman, Bernard Bochner, Gregory J Riely, Leonard B Saltz, Howard I Scher, Paul J Sabbatini, Mark E Robson, David S Klimstra, Barry S Taylor, Jose Baselga, Nikolaus Schultz, David M Hyman, Maria E Arcila, David B Solit, Marc Ladanyi, Michael F Berger
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations...
May 8, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28480192/localized-irradiation-of-mouse-legs-using-an-image-guided-robotic-linear-accelerator
#17
Markus Kufeld, Helena Escobar, Andreas Marg, Diana Pasemann, Volker Budach, Simone Spuler
BACKGROUND: To investigate the potential of human satellite cells in muscle regeneration small animal models are useful to evaluate muscle regeneration. To suppress the inherent regeneration ability of the tibialis muscle of mice before transplantation of human muscle fibers, a localized irradiation of the mouse leg should be conducted. We analyzed the feasibility of an image-guided robotic irradiation procedure, a routine treatment method in radiation oncology, for the focal irradiation of mouse legs...
April 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28472335/tools-for-the-precision-medicine-era-how-to-develop-highly-personalized-treatment-recommendations-from-cohort-and-registry-data-using-q-learning
#18
Elizabeth F Krakow, Michael Hemmer, Tao Wang, Brent Logan, Mukta Arora, Stephen Spellman, Daniel Couriel, Amin Alousi, Joseph Pidala, Michael Last, Silvy Lachance, Erica E M Moodie
Q-learning is a method of reinforcement learning that employs backwards stage-wise estimation to identify sequences of actions that maximize some long-term reward. The method can be applied to sequential multiple-assignment randomized trials to develop personalized adaptive treatment strategies (ATSs) - longitudinal practice guidelines highly tailored to time-varying attributes of individual patients. Sometimes, the basis for choosing which ATSs to include in a sequential multiple-assignment randomized trial (or randomized controlled trial) may be inadequate...
May 3, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28472276/reliability-of-algorithmic-somatic-copy-number-alteration-detection-from-targeted-capture-data
#19
Nora Rieber, Regina Bohnert, Ulrike Ziehm, Gunther Jansen
Motivation: Whole exome and gene panel sequencing are increasingly used for oncological diagnostics. To investigate the accuracy of SCNA detection algorithms on simulated and clinical tumor samples, the precision and sensitivity of four SCNA callers were measured using 50 simulated whole exome and 50 simulated targeted gene panel data sets, and using 119 TCGA tumor samples for which SNP array data were available. Results: On synthetic exome and panel data, VarScan2 mostly called false positives, whereas Control-FREEC was precise (>90% correct calls) at the cost of low sensitivity (<40% detected)...
May 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28470451/precision-reproductive-medicine-multigene-panel-testing-for-infertility-risk-assessment
#20
REVIEW
Stephen C Collins
The concept of precision medicine relies on a thorough understanding of the consequences of unique features of individual patients, such as environmental exposures and genetic profiles. A key component of implementing individualized care in this paradigm will be improved assessment of genetic risk. Compared with single gene tests, multigene panel testing-which has recently become commercially available for female infertility-offers the possibility of a more comprehensive and efficient risk evaluation. However, as the use of multigene panel testing for breast cancer risk has shown, this approach must be used judiciously to ensure its usefulness in a clinical setting...
May 3, 2017: Journal of Assisted Reproduction and Genetics
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