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Stratified medicine in cancer

Christopher R Friese, Yun Li, Irina Bondarenko, Timothy P Hofer, Kevin C Ward, Ann S Hamilton, Dennis Deapen, Allison W Kurian, Steven J Katz
BACKGROUND: The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making. METHODS: This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%)...
October 24, 2016: Cancer
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
Chana Wiesman, Esther Rose, Allison Grant, Adam Zimilover, Susan Klugman, Nicole Schreiber-Agus
PURPOSE: The notion of offering population-based screening to the Ashkenazi Jewish (AJ) population for the BRCA1/2 founder mutations continues to gain support. A program called the BRCAcommunity initiative was designed to identify the benefits and barriers associated with implementing this screening in a clinical setting. METHODS: Interested AJ individuals were stratified into high-risk (HR) and low-risk (LR) groups based on self-reported cancer histories. Those at HR were offered traditional genetic counseling/testing; those at LR were offered group genetic counseling and subsidized AJ BRCA founder mutation testing...
October 13, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
John L Moran, Patricia J Solomon
Recent viewpoints on critical care have expressed frustration at the slow development of new therapeutic agents and the failure of investigator-initiated trials. Several new directions have been proposed: personalised medicine and the embracing of "omic" technologies, resolving the heterogeneity of treatment effects, and adaptive trial designs. We examine these approaches in the context of analysis of randomised controlled trials (RCTs). The curse of treatment effect heterogeneity is found not only in critical care but also in cancer oncology...
September 2016: Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine
Crispin T Hiley, John Le Quesne, George Santis, Rowena Sharpe, David Gonzalez de Castro, Gary Middleton, Charles Swanton
Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1...
September 3, 2016: Lancet
Lauren L Siewertsz van Reesema, Vasilena Zheleva, Janet S Winston, Rick J Jansen, Carolyn F O'Connor, Andrew J Isbell, Minglei Bian, Rui Qin, Patricia T Bassett, Virginia J Hinson, Kimberly A Dorsch, Brad W Kirby, Robert E Van Sciver, Angela M Tang-Tan, Elizabeth A Harden, David Z Chang, Cynthia A Allen, Roger R Perry, Richard A Hoefer, Amy H Tang
BACKGROUND: Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS "pathway" activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine...
September 2016: EBioMedicine
Poonam Nagpal, Mohamed R Akl, Nehad M Ayoub, Tatsunari Tomiyama, Tasheka Cousins, Betty Tai, Nicole Carroll, Themba Nyrenda, Pritish Bhattacharyya, Michael B Harris, Andre Goy, Andrew Pecora, K Stephen Suh
Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging...
August 22, 2016: Oncotarget
Matthew Frampton, Richard S Houlston
PURPOSE: This study investigated the utility of modeling modifiable lifestyle risk factors in addition to genetic variation in colorectal cancer (CRC) screening/prevention. METHODS: We derived a polygenic risk score for CRC susceptibility variants in combination with the established nongenetic risk factors of inflammatory bowel disease (IBD), adiposity, alcohol, red meat, fruit, vegetables, smoking, physical activity, and aspirin. We used the 37 known risk variants and 50 and 100% of all risk variants as calculated from a heritability estimate...
August 4, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Fang Zhang, Bing Li, Hong-Yan Wu, Li-Xin Shang
BACKGROUND: Many studies have examined the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with cervical cancer susceptibility. However, the results of these studies are inconsistent. To further assess the effects of XRCC1 Arg399Gln polymorphism on the risk of cervical cancer in the Chinese population, a meta-analysis was performed. METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through December 2015...
August 4, 2016: Gynecologic and Obstetric Investigation
Sophie Day, R Charles Coombes, Louise McGrath-Lone, Claudia Schoenborn, Helen Ward
We conducted ethnographic research in collaboration with a large, research-intensive London breast cancer service in 2013-2014 so as to understand the practices and potential effects of stratified medicine. Stratified medicine is often seen as a synonym for both personalised and precision medicine but these three terms, we found, also related to distinct facets of treatment and care. Personalised medicine is the term adopted for the developing 2016 NHS England Strategy, in which breast cancer care is considered a prime example of improved biological precision and better patient outcomes...
July 27, 2016: Sociology of Health & Illness
Ian Cromwell, Dean A Regier, Stuart J Peacock, Catherine F Poh
BACKGROUND: Management of low-grade oral dysplasias (LGDs) is complicated, as only a small percentage of lesions will progress to invasive disease. The current standard of care requires patients to undergo regular monitoring of their lesions, with intervention occurring as a response to meaningful clinical changes. Recent improvements in molecular technologies and understanding of the biology of LGDs may allow clinicians to manage lesions based on their genome-guided risk. METHODS: We used a decision-analytic Markov model to estimate the cost-effectiveness of risk-stratified care using a genomic assay...
September 2016: Oncologist
Igor Karp, Marie-Pierre Sylvestre, Michal Abrahamowicz, Karen Leffondré, Jack Siemiatycki
Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001...
July 11, 2016: European Journal of Epidemiology
Kim Ah Nicolaije, Nicole Pm Ezendam, Johanna Ma Pijnenborg, Dorry Boll, Maria Caroline Vos, Roy Fpm Kruitwagen, Lonneke V van de Poll-Franse
BACKGROUND: The Institute of Medicine recommends Survivorship Care Plans (SCPs) for all cancer survivors. However, it is unclear whether certain patient groups may or may not benefit from SCPs. OBJECTIVE: The aim was to assess whether the effects of an automatically generated paper SCP on patients' satisfaction with information provision and care, illness perceptions, and health care utilization were moderated by disease-related Internet use. METHODS: Twelve hospitals were randomized to either SCP care or usual care in the pragmatic cluster randomized Registrationsystem Oncological GYnecology (ROGY) Care trial...
2016: Journal of Medical Internet Research
Xiaofeng Dai, Liangjian Xiang, Ting Li, Zhonghu Bai
Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks...
2016: Journal of Cancer
Ali Abdel Raheem, Dae Keun Kim, Glen Denmer Santok, Ibrahim Alabdulaali, Byung Ha Chung, Young Deuk Choi, Koon Ho Rha
OBJECTIVE: To report the 5-year oncological outcomes of robot-assisted radical prostatectomy from the largest series ever reported from Asia. METHODS: A retrospective analysis of 800 Asian patients who were treated with robot-assisted radical prostatectomy from July 2005 to May 2010 in the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea was carried out. The primary end-point was to evaluate the biochemical recurrence...
September 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Stefania Tommasi, Rosamaria Pinto, Katia Danza, Brunella Pilato, Orazio Palumbo, Lucia Micale, Simona De Summa
In recent years, the assessment of biomarkers useful for "precision medicine" has been a hot topic in research. The involvement of microRNAs in the pathogenesis of breast cancer has been highly investigated with the aim of being able to molecularly stratify this highly heterogeneous disease. Our aim was to identify microRNAs targeting DNA repair machinery, through Affymetrix GeneChip miRNA Arrays, in a cohort of BRCA-related and sporadic breast cancers. Moreover, we analyzed microRNA expression taking into account our previous results on the expression of PARP1, because of its importance in targeted therapy...
June 30, 2016: Oncotarget
Riku Louhimo, Marko Laakso, Denis Belitskin, Juha Klefström, Rainer Lehtonen, Sampsa Hautaniemi
BACKGROUND: Genomic alterations affecting drug target proteins occur in several tumor types and are prime candidates for patient-specific tailored treatments. Increasingly, patients likely to benefit from targeted cancer therapy are selected based on molecular alterations. The selection of a precision therapy benefiting most patients is challenging but can be enhanced with integration of multiple types of molecular data. Data integration approaches for drug prioritization have successfully integrated diverse molecular data but do not take full advantage of existing data and literature...
2016: BioData Mining
Ghim Siong Ow, Zhiqun Tang, Vladimir A Kuznetsov
The era of big data and precision medicine has led to accumulation of massive datasets of gene expression data and clinical information of patients. For a new patient, we propose that identification of a highly similar reference patient from an existing patient database via similarity matching of both clinical and expression data could be useful for predicting the prognostic risk or therapeutic efficacy.Here, we propose a novel methodology to predict disease/treatment outcome via analysis of the similarity between any pair of patients who are each characterized by a certain set of pre-defined biological variables (biomarkers or clinical features) represented initially as a prognostic binary variable vector (PBVV) and subsequently transformed to a prognostic signature vector (PSV)...
May 24, 2016: Oncotarget
Michael McCulloch, Helen Ly, Michael Broffman, Caylie See, Jen Clemons, Raymond Chang
Background Chinese herbal medicines reportedly increase efficacy and minimize toxicity of chemotherapy; however, little attention has been paid to how poor study quality can bias outcomes. Methods We systematically searched MEDLINE, TCMLARS, EMBASE, and Cochrane Library for randomized controlled trials of Chinese herbal medicines combined with fluorouracil-based chemotherapy compared with the same chemotherapy alone. We screened for eligibility, extracted data, and pooled data with random-effects meta-analysis...
September 2016: Integrative Cancer Therapies
Cheryl A Mather, Sean D Mooney, Stephen J Salipante, Sheena Scroggins, David Wu, Colin C Pritchard, Brian H Shirts
PURPOSE: Several in silico tools have been shown to have reasonable research sensitivity and specificity for classifying sequence variants in coding regions. The recently developed combined annotation-dependent depletion (CADD) method generates predictive scores for single-nucleotide variants (SNVs) in all areas of the genome, including noncoding regions. We sought for non-coding variants to determine the clinical validity of common CADD scores. METHODS: We evaluated 12,391 unique SNVs in 624 patient samples submitted for germ-line mutation testing in a cancer-related gene panel...
May 5, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
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