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  • 1
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    Cancer patients’ acceptance, understanding, and willingness-to-pay for pharmacogenomic testing
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Pharmacogenetics and Genomics Vol. 24, No. 7 ( 2014-07), p. 348-355
    Details
    In: Pharmacogenetics and Genomics, Ovid Technologies (Wolters Kluwer Health), Vol. 24, No. 7 ( 2014-07), p. 348-355
    Type of Medium: Online Resource
    ISSN: 1744-6872
    URL: Article
    DOI: 10.1097/FPC.0000000000000061
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 2048376-4
    SSG: 15,3
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  • 2
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    Willingness of patients to provide biologic samples for pharmacogenomic testing.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 6543-6543
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 6543-6543
    Abstract: 6543 Background: Additional biopsies and/or blood sampling (i.e.: germline and plasma markers, circulating DNA or tumour cells) may be necessary to complete pharmacogenomic testing (PGT) in some patients. Cancer patients’ perspectives on providing additional biospecimens are important in addressing potential knowledge translation barriers. Methods: 790 clinic patients from the Princess Margaret Cancer Centre (Toronto, Canada) were interviewed with a standardized questionnaire, representing a wide distribution of adult solid and hematological disease sites. Study endpoints included patient preferences and willingness to provide biological samples (new blood, new biopsy, or pre-existing tumor samples) on a 5-point Likert scale. Univariate and multivariate models were created using SAS 9.3. Results: Patients were 49% female; 77% Caucasian/12% Asian; median age 58 years; and 67% had completed high school. Median household income was evenly trichotomized at $50K and $100K. Despite 33% of the patients being uncomfortable with the level of their knowledge about PGT, 75% agreed that additional tests would be beneficial to their health. Patient willingness to provide new samples was 88% for blood and 53% for biopsy, and 27% preferred existing tumor samples to be used in lieu of additional sampling. Caucasians and those with the highest incomes were more agreeable to providing blood and/or biopsy samples, whereas non-Caucasians and low-income earners preferred utilization of existing tumor samples over additional blood sampling (p 〈 0.05). Conclusions: Patients were more willing to provide a new blood sample than a biopsy sample for PGT. Despite the vast majority agreeing to the potential benefit of additional sampling, only half were willing to provide a new biopsy sample. Level of willingness was related to sociocultural and economic factors. Improved patient education and increased efforts to design blood-based markers may improve uptake of PGT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.6543
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Association of BRM promoter polymorphisms and esophageal adenocarcinoma outcome
    Impact Journals, LLC ; 2017
    In:  Oncotarget Vol. 8, No. 17 ( 2017-04-25), p. 28093-28100
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 17 ( 2017-04-25), p. 28093-28100
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v8i17
    DOI: 10.18632/oncotarget.15890
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 4
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    Effect of BRM promoter variants on survival outcomes of stage III-IV non-small cell lung cancer (NSCLC) patients.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 11057-11057
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 11057-11057
    Abstract: 11057 Background: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene in NSCLC. Loss of BRM expression occurs in 15% of NSCLC, and has been linked to adverse outcome. Recently, our group has shown that variants of two novel BRM promoter insertion polymorphisms (BRM-741, BRM-1321) lead to loss of BRM expression by recruiting histone deacetylases; individuals carrying homozygous variants for both polymorphisms have doubled NSCLC risk; pharmacological reversal of these epigenetic changes is a potentially viable therapeutic strategy. We thus evaluated the effect of BRM promoter variants on survival outcomes of advanced NSCLC patients, where initial clinical trials are likely to be focused. Methods: 564 stage III-IV NSCLC patients were genotyped for the BRM promoter variants using Taqman. Association of BRM variants and overall (OS) and progression-free survival (PFS) were assessed using Cox proportional hazard models adjusted for prognostic variables. Results: Among our patients, 73% were Caucasian, 52% male, median age 63yrs, 55% stage IV disease, and 67% adenocarcinoma. Median OS was 1.6yrs; median follow up, 3.6yrs. The frequency of homozygosity was BRM-741, 23%; BRM-1321, 21%; both, 12%. Homozygous variants of BRM-741 were strongly associated with worse OS (adjusted HR [aHR] 2.3 [p=2x10E-8] ) and PFS (aHR 2.0 [p=2x10E-7]) compared to the wild types. Similar findings were observed for BRM-1321 homozygous variants (aHR for OS 1.8 [p=8x10E-5] and aHR for PFS 1.6 [p=2x10E-4]). Carrying homozygous variants of both BRM-741 and BRM-1321 was associated with substantially worse OS (aHR 2.3 [p=1x10E-5] ) and PFS (aHR 2.2 [p=3x10E-6]), with similar associations seen among the stage III (aHR for OS 2.3 [p=6x10E-6] ) and stage IV (aHR for OS 2.5 [p=5x10E-6]) patients. Conclusions: The same two homozygous BRM promoter variants that are associated with increased risk of NSCLC are also strongly associated with adverse OS and PFS in this cohort of stage III-IV NSCLC patients. Validation of results in a clinical trial dataset is underway, and will better elucidate the prognostic significance of these BRM promoter variants.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.11057
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Cancer patients’ and physicians’ preferences for decision making regarding pharmacogenomic testing (PGT).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 34_suppl ( 2012-12-01), p. 13-13
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 34_suppl ( 2012-12-01), p. 13-13
    Abstract: 13 Background: Pharmacogenomics is increasingly utilized in oncology; however, there is little knowledge concerning cancer patients’ or oncologists’ attitudes toward PGT decision-making in clinical practice. Methods: A broad cross-section of cancer patients were interviewed regarding their attitudes toward PGT using hypothetical time, efficacy and toxicity trade-off and willingness-to-pay scenarios (N=278) and/or quantitative choice-based conjoint analysis surveys (N=264); 64 cancer specialists/physicians in training were surveyed similarly. Results: Of patients participating in the trade-off scenario phase of study, 〉 94% accepted chemotherapy, and of these, 〉 98% wanted PGT that identifies a subset of patients either benefiting from chemotheraphy or who were at risk of severe toxicity. Patients were willing to pay between CAD $1,000-$1,900 for PGT and accept wait times for results of 2-3 weeks. Similar findings were observed in the conjoint phase of the study, with preferences for PGT starting to decline when the out-of-pocket costs reached CAD $500-$1,500, wait time for results exceeded 14 days, and when the prevalence of the genetic variant fell below 25%. Adjuvant patients’ acceptance of PGT was most influenced by cost (decision weight [DW]=41%) and prevalence of the genetic variant associated with lack of benefit from chemo (DW=26%). Metastatic patients were most influenced by cost (DW=49%) and wait times (DW=31%). More patients reported difficulty understanding conjoint surveys (14%) than trade-off scenarios (7%; p=0.01). 81% of patients wanted to be involved in decision-making regarding PGT; while 30% of physicians felt it should be a physician-only decision (p=0.006). However, 21% of patients and 5% of physicians admitted to not understanding PGT, while just 14% of physicians rated themselves as very knowledgeable regarding PGT. Conclusions: Cancer patients overwhelmingly accept and want to be involved in decision-making regarding PGT, to a greater extent than what physicians prefer. However, communication of PGT information was a potential barrier, as a considerable minority lacked the necessary knowledge to facilitate informed decision-making. Improved patient and physician education is necessary.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.34_suppl.13
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Cancer patient acceptance, understanding, and willingness to pay for pharmacogenetic testing (PGT).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 6005-6005
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 6005-6005
    Abstract: 6005 Background: PGT offers the potential to improve cancer therapy through the use of specialized tests that can predict the level of efficacy and/or toxicity of specific treatments in an individual. However, there is currently little knowledge concerning cancer patient attitudes towards such testing in the clinical setting. Methods: We interviewed a broad cross-section of 278 cancer patients (20% lung, 19% breast, 20% colorectal, 40% other) using hypothetical time, efficacy, toxicity and willingness-to-pay trade-off PGT scenarios. Results: 153 potentially curable patients and 125 incurable patients received a separate series of trade-off scenarios. For curative patients, 70% accepted chemo that had a 5% absolute improvement in cure rate and 〈 5% of severe toxicity. Of these, 99% wanted PGT where the test identifies a subset of patients benefiting from chemo; the same individuals were willing to pay a median $2,000 (range: $0-25,000) for PGT and would accept a median wait time for PGT results of 21 days (0-90). Patient preferences were insensitive to variation of fractions of individuals carrying the genetics associated with lack of benefit. In the incurable scenario, 90% of patients accepted palliative chemo with an 80% response rate and a severe side effect rate of 5%. Of these, 98% wanted PGT, where there test identifies individuals at highest risk of severe toxicity; the same individuals were willing to pay a median $1,000 ($0-15,000) for PGT, and would accept PGT turnaround times of 14 days (1-90). Patient preferences were insensitive to variation of fractions of individuals carrying the genetics associated with severe toxicity. The majority of patients (76% adjuvant; 87% metastatic) wanted to be involved in decision making regarding PGT; however, one in five patients (20% adjuvant; 22% metastatic) admitted that they lacked a basic understanding of what PGT means and its clinical implications. Conclusions: Among cancer patients willing to undergo chemo, almost all wanted PGT and were willing to pay for it, waiting several weeks for results. While patients had a strong desire to be involved in decision making for PGT, a considerable proportion lacked the necessary knowledge to make informed choices.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.6005
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Single nucleotide polymorphisms (SNPs) of the platinum pharmacogenetic and VEGF pathways: Association with survival of platinum-treated stage IV non-small cell lung cancer (NSCLC) patients.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 7586-7586
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 7586-7586
    Abstract: 7586 Background: Two potentially important host pathways in lung cancer systemic therapy are: (i) the pharmacogenetic pathway of platinum agents (DNA repair, metabolism, and multidrug resistance genes); and (ii) the vascular endothelial growth factor (VEGF) pathway. We investigated the relationship between SNPs in these two pathways and clinical outcome in platinum-treated NSCLC patients. Methods: 188 platinum-treated Stage IV NSCLC patients underwent SNP genotyping for the platinum-related (48 SNPs in 7 genes) and VEGF (64 SNPs in 3 genes) pathways. SNPs were selected from the literature and through tagging. Association of SNPs and overall (OS) and progression free survival (PFS) were assessed using multivariate Cox proportional hazards models. Results: 72% were Caucasian; 73%, adenocarcinoma; 92%, ECOG PS 0-1; median age, 60 years; 54% received 〉 one line of systemic therapy; 10% received anti-VEGF therapy/placebo; Median OS, 1.3 yrs; median follow up, 2.2 yrs. The top significant SNPs in the platinum-related pathway were in ABCC2 (rs8187710 and rs2756109, r 2 =0.68). The G variants of the top SNP, ABCC2 rs8187710 (4554G 〉 A), were associated with worse OS (adjusted hazard ratio [aHR], 2.62; 95%CI: 1.5-4.5; p=0.0005) and PFS (aHR, 1.97; 95%CI: 1.2-3.4; p=0.01). Functionally, 4554G 〉 A impairs ATP-ase activity and is associated with higher cellular accumulation of ABCC2 substrates [PMID: 22027652]; furthermore, ABCC2 expression is associated with cisplatin resistance and clinical outcome in other cancers [PMID: 17145840] . Within the VEGF pathway, the top significant SNPs were in the same haplotype block of VEGFR1/FLT1 (rs1324057, rs7324547, r 2 =1.0): for rs1324057, the aHR for OS was 1.59 (95%CI 1.2-2.1); p=0.001; and the aHR for PFS, 1.48 (95%CI 1.1-1.9); p=0.004. VEGFR1/FLT1 rs7324547 has been associated with esophageal cancer risk [PMID: 21751195], but has not been assessed in lung cancer. Conclusions: SNPS of the VEGFR1 and ABCC2 genes are strongly associated with OS and PFS in this cohort of platinum-treated advanced NSCLC patients. Future studies should assess whether these are predictive or prognostic markers.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.7586
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Promoter polymorphisms of the SWI/SNF chromatin remodeling complex molecule, BRM, and esophageal adenocarcinoma outcome.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 4077-4077
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4077-4077
    Abstract: 4077 Background: Better understanding of the biology of esophageal cancer may help improve its treatment. The SWI/SNF chromatin remodeling complex is an important regulator of gene expression that has been linked to cancer development and outcome. Expression of Brahma (BRM), a critical catalytic subunit of SWI/SNF, is lost in a variety of solid tumors. Two novel BRM promoter polymorphisms (BRM -741 and BRM -1321) have been correlated with BRM loss and elevated cancer risk in upper aerodigestive cancers (Wang et al, Carcinogenesis, 2012) and more recently in lung cancer outcome (Cuffe et al, ESMO, 2012) by our research teams. Objectives: We evaluated BRM polymorphisms and their role in the survival of esophageal cancer patients. Methods: 223 histologically-confirmed esophageal adenocarcinoma patients of all stages were evaluated. The two BRM polymorphisms utilized Taqman genotyping. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 85% were male; the mean age was 63 years. 37% had stage IV advanced tumors. The median PFS was 1.03 years, while median OS was 1.82 years. After adjustment for known prognostic clinical variables, carrying homozygous variants of both BRM polymorphisms (double homozygotes) was associated with a worse outcome: aHR 1.84 (1.06-2.34, p=0.03) for OS and aHR 1.93 (1.10-2.48, p=0.02) for PFS. The direction and magnitude of associations were similar in subsets of patients by age, gender, smoking status, use of platinum agents, and disease stage. Non-significant trends in the same direction but of aHR magnitudes 1.34-1.54 were seen in the patients who carried one homozygous variant or who were double heterozygotes. Conclusions: We report the initial association of BRM polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.4077
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
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  • 9
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    Developing a comprehensive smoking cessation program in patients with lung cancer: The role of social smoking environments.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 34_suppl ( 2012-12-01), p. 75-75
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 34_suppl ( 2012-12-01), p. 75-75
    Abstract: 75 Background: Smoking during cancer treatment negatively impacts outcome, survival, and quality of life. Social smoking environments (SSEs) (i.e., smoking in household, peers, and spouse) influence cessation rates in non-cancer patients, but are understudied in cancer patients. Methods: Lung cancer patients, recruited from Princess Margaret Hospital (2006-2012) were given baseline and follow-up questionnaires (median of 2 years apart) evaluating changes in smoking habits and SSEs. Multivariate logistic regression and Cox-proportional hazard models evaluated the association of socio-demographics, clinicopathological and SSE factors with smoking cessation and time to quitting, respectively. Results: 721 patients completed both questionnaires. Of the 261 current smokers at diagnosis, 180 (69%) had quit by follow-up. Among 318 ex-smokers, 5 re-started smoking after diagnosis. All of the 140 never smokers remained non-smoking. Home smoke exposure (OR=9.4; 95% CI: 3.4-26.2; p=2.0 x 10E-5), spousal smoking (OR=4.7, 95% CI:1.7-12.6; p=3.0 x 10E-3) and peer smoking (OR=2.6; 95% CI:1.1-6.1; p=0.03) were each associated with reduced cessation, adjusted for a base multivariate model that included education and past history of depression. Individuals with no SSE factors had a much higher chance of quitting smoking when compared to patients with multiple areas of SSEs (0 vs. 3, OR=16.4; 95% CI: 4.1-66.7; p=7.3 x 10E-5). Similar results were seen when using time-to-quitting as the outcome (0 vs 3, OR=4.4, 95% CI=1.4-14.1, p=0.01). Time to quitting analysis found that 60% of patients with at least one SSE who did quit, did so within 6 months of diagnosis. Subgroup analysis revealed similar associations in early- and late-stage patient groups. Conclusions: SSE is a key factor in smoking cessation, where household smoke exposures reduces the chance of quitting up to 9-fold. SSEs should be a key consideration when developing smoking cessation programs in lung cancer patients, as part of quality improvement strategies. Approaches incorporating household members or spouses into the smoking cessation intervention, around the time of diagnosis, should be researched further. GL and WX are co-senior authors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.34_suppl.75
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 10
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    ABCC2 polymorphisms and survival in the Princess Margaret cohort study and the NCIC clinical trials group BR.24 trial of platinum-treated advanced stage non-small cell lung cancer patients
    Elsevier BV ; 2016
    In:  Cancer Epidemiology Vol. 41 ( 2016-04), p. 50-56
    Details
    In: Cancer Epidemiology, Elsevier BV, Vol. 41 ( 2016-04), p. 50-56
    Type of Medium: Online Resource
    ISSN: 1877-7821
    URL: Article
    DOI: 10.1016/j.canep.2015.12.012
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2498032-8
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