Showing papers by "Cancer Research UK published in 2017"

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

Abstract: BackgroundCoronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. MethodsWe randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. ResultsAt 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference i...

Novel Androgen Receptor Coregulator GRHL2 Exerts Both Oncogenic and Antimetastatic Functions in Prostate Cancer.

Abstract: Alteration to the expression and activity of androgen receptor (AR) coregulators in prostate cancer is an important mechanism driving disease progression and therapy resistance. Using a novel proteomic technique, we identified a new AR coregulator, the transcription factor Grainyhead-like 2 (GRHL2), and demonstrated its essential role in the oncogenic AR signaling axis. GRHL2 colocalized with AR in prostate tumors and was frequently amplified and upregulated in prostate cancer. Importantly, GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR9s transcriptional activity, and colocated with AR at specific sites on chromatin to regulate genes relevant to disease progression. GRHL2 is itself an AR-regulated gene, creating a positive feedback loop between the two factors. The link between GRHL2 and AR also applied to constitutively active truncated AR variants (ARV), as GRHL2 interacted with and regulated ARVs and vice versa. These oncogenic functions of GRHL2 were counterbalanced by its ability to suppress epithelial–mesenchymal transition and cell invasion. Mechanistic evidence suggested that AR assisted GRHL2 in maintaining the epithelial phenotype. In summary, this study has identified a new AR coregulator with a multifaceted role in prostate cancer, functioning as an enhancer of the oncogenic AR signaling pathway but also as a suppressor of metastasis-related phenotypes. Cancer Res; 77(13); 3417–30. ©2017 AACR.

Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma.

Abstract: This work was principally supported by the National Institutes of Health (R21DK099804 to MMM and R01CA136725 to TLV and DCW). Support for studies related to the Oxford data set was granted by the Esophageal Adenocarcinoma GenE Consortia incorporating the ChOPIN project (grant C548/A5675) and Inherited Predisposition of neoplasia analysis of genomic DNA (IPOD) from AspECT and BOSS clinical trials project (grant MGAG1G7R); Cancer Research UK (AspECT, grants C548/A4584 and D9612L00090, and Histological AssessmeNt Determining EpitheliaL Response (HANDEL), grant C548/A9085); AstraZeneca UK educational grant; University Hospitals of Leicester R and D grant; and AspECT (T91 5211 University of Oxford grant HDRMJQ0).

Exploring the rationale, experience and impact of using Cancer Information and Support (CIS) services: an international qualitative study

Abstract: The aim of this study was to develop an in-depth understanding of the rationale, experiences, evaluation and outcomes of using Cancer Information and Support (CIS) services in Australia, the UK and USA. Semi-structured interviews were used to gather data between November 2015 and January 2016. Telephone interviews were recorded, de-identified, transcribed and thematically analysed. Ten users from each of three international CIS services (n = 30 in total) were recruited. Participants were eligible for inclusion if they had utilised the CIS in 2015 via telephone contact with a cancer nurse and identified as a patient or cancer survivor, or friend or family member of such a person. Four major themes were derived and included a total of 25 sub-themes. Key themes included (i) drivers for access, (ii) experience of the service, (iii) impact and (iv) an adjunct to cancer treatment services. Cancer Information and Support nurses internationally act as expert navigators, educators and compassionate communicators who ‘listen between the lines’ to enable callers to better understand and contextualise their situation and discuss it with their healthcare team and family and friends. Use of the service can result in reduced worry, extend support repertoires and enable use of new knowledge and language as a tool to getting the most from the healthcare team. The positioning of CIS alongside cancer treatment services aids fuller integration of supportive care, benefiting both patients and clinicians.

Long-Term Follow-Up of the Intergroup Exemestane Study

Abstract: Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non-breast cancer-related deaths now reported, breast cancer-free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P < .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, -0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, -0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality.

Erratum to: "Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer", [Breast Cancer Research, 19, (2017) (17)] DOI: 10.1186/s13058-017-0809-6

Abstract: © The Author(s). 2017.In the version of this article that was published on PubMed [1] the author's name Mark A. Dane was formatted incorrectly in the XML mark up and therefore appeared incorrectly on PubMed. In the XML mark up, the middle initial A was added as a Particle when it should have been included as a Given Name. Due to this error, the author's name was incorrectly formatted in PubMed as A Dane M and not as Dane MA . The author's name is correct on the BioMed Central website. The author's name in the XML of the original article [1] has been updated accordingly.

Linking the English Cancer Patient Experience Survey to Cancer registration: relating patient experience to outcomes, a step towards better services and outcomes: IJPDS (2017) Issue 1, Vol 1:143, Proceedings of the IPDLN Conference (August 2016)

Abstract: ObjectivesTo link the English Cancer Patient Experience Survey (CPES) to Public Health England’s cancer registration records and allow new exploration of the association between patient experience and outcomes and eventually improve service provision and patient outcomes. ApproachPatients’ responses from the first 4 waves (2010, 2011/12, 2013, 2014) of CPES were linked to tumour level cancer registration records. Cancer registration is available via the Cancer Analysis System (CAS). A patient may have multiple tumour records in CAS. Therefore, the same CPES survey result could be mapped onto multiple tumour records in the cancer registration data. It was necessary to match the patient records to identify the tumour records in CAS that most likely corresponded to the correct CPES response. The following criteria were used to match records at patient-tumour level: a match in the ICD-10 diagnosis codes from both datasets; and the time frames from diagnosis to discharge to best assess the correct match. In order to increase the matching yield, the linkage also flagged related tumour types in the two datasets, following consultation with clinical and research experts in the field. ResultsOver 75% of records in the survey cohort were successfully linked for each year of the survey waves. Analysis based on concordance between data items in both CPES and cancer registrations were mostly the same in the two datasets. As an example of the linkage potential, the overall experience of patient care was compared with stage at diagnosis. The results show that patients diagnosed at later stages have significantly lower scores of overall care. To our knowledge, this is the first time these two variables have been analysed together in regards to the care of cancer patients in England and emphasise the need for earlier cancer diagnosis. ConclusionThis is the first time the CPES has been linked to cancer registrations. The new linkage provides insight into how well represented the overall cancer patient population is within CPES and also assess concordance of data between them. This work is essential to support a programme of further analysis at NCRAS, in partnership with Macmillan Cancer Support and Cancer Research UK.

Lymphoma: Now you see it...

Abstract: Scherer et al. show that analysis of circulating tumour DNA can provide prognostic information and predict relapse in patients with diffuse large B-cell lymphoma.