The first 1000 patients on an internet-based colorectal neoplasia database across private and public medicine in australia: Development of a binational model for the colorectal surgical society of Australia and New Zealand

Background: Collection of multi-institutional data pertaining to the treatment of bowel cancer has been hindered by poor clinician compliance with data entry and the lack of incentive to participate. Objective: This study aimed to establish if a novel browser-based model of data collection results in complete data capture. Design: A Web-based data collection interface was custom written, offering automated reporting modules for clinical outcome to participants and an automated reporting system for outstanding data fields, and summary reporting of surgical quality outcomes. The software was combined with a clinical feedback system incorporating fortnightly data review meetings, at the time of clinical multidisciplinary meetings. Patients And Setting: Selected were 932 consecutive patients with opt-out consent from 3 hospital sites, including public and private medicine. Main Outcome Measures: The primary outcomes measured were the analysis of data completeness and accuracy and ensuring that the highest-quality data were used for clinical audit of the surgical practices of Australian colorectal surgeons for the purpose of quality assurance. Results: A total of 932 men and women, 22 to 94 years of age, treated for colorectal neoplasia were evaluated. We obtained 100% completion (>27,000 data points) of perioperative data registered by 8 specialist colorectal surgeons and a full-time database manager. Conclusions: Data completeness and validity are essential for clinical databases to serve the purpose of quality assurance, benchmarking, and research. The results confirm the safety and efficacy of colorectal cancer surgery in both the public and private sector in Australia. The combination of a simple multiuser interface, defined data points, automated result-reporting modules, and data-deficiency reminder module resulted in 100% data compliance in nearly 1000 clinical episodes. The unprecedented success of this model has lead to the Colorectal Surgical Society of Australia and New Zealand adopting this model for data collection for Australia and New Zealand as the binational database. © The ASCRS 2014

The ALCCaS Trial: a randomized controlled trial comparing quality of life following laparoscopic versus open colectomy for colon cancer

Background: This study reports the quality-of-life assessment of the ALCCaS trial. The ALCCaS trial compared laparoscopic and open resection for colon cancer. It reported equivalence of survival at 5 years. Quality of life was measured as a secondary outcome. Objective: This study aimed to report on the quality of life data of the ALCCaS Trial. Design: This study reports a randomized controlled trial comparing laparoscopic with open colonic resection. Settings: The study was conducted in Australasia. Patients: Patients with a single adenocarcinoma of the right, left, or sigmoid colon, presenting for elective treatment, were eligible for randomization. Interventions: Open and laparoscopic colonic resections were performed. Main Outcome Measures: Patient symptoms and quality of life were measured using the Symptoms Distress Scale, the Quality of Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2 weeks, and 2 months postoperatively. Results: Of the 592 patients enrolled in ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8% of cohort). Those who received the laparoscopic intervention had better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01), Quality of Life Index (p < 0.01), and Global Quality of Life (p < 0.01). In intention-to-treat analyses, those assigned to laparoscopic surgery had a better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01) and Quality of Life Index (p < 0.01), whereas Global Quality of Life was not significant (p = 0.056). The subscales better for laparoscopic resection at all 3 postoperative time points were appetite, insomnia, pain, fatigue, bowel, daily living, and health (p < 0.05). Limitations: The primary limitation was the different response rates for the 3 quality-of-life measures. Conclusions: There was a short-term gain in quality of life maintained at 2 months postsurgery for those who received laparoscopic relative to open colonic resection. See Video Abstract at http://links.lww.com/DCR/A691.Andrew M. McCombie, Frank Frizelle, Philip Frederick Bagshaw, Chris M. Frampton, Peter J. Hewett, Paul John McMurrick, Nicholas Rieger, Michael J. Solomon, Andrew R. Stevenso

Serum concentrations of brain-derived neurotrophic factor (BDNF) are decreased in colorectal cancer patients

OBJECTIVE: To determine the usefulness of brain-derived neurotrophic factor (BDNF) as a diagnostic biomarker for colorectal cancer (CRC). MATERIALS AND METHODS: ELISA immunoassay was used to examine BDNF concentrations in the sera of two different retrospective cohorts consisting of CRC patients and age/gender matched controls. Cohort 1 consisted of 99 controls and 97 CRC patients, whereas cohort 2 consisted of 47 controls and 91 CRC patients. RESULTS: In cohort 1, the median concentration of BDNF was significantly (p< 0.0001) lower in CRC patient samples (18.8 ng/mL, range 4.0-56.5 ng/mL) than control samples (23.4 ng/mL, range 3.0-43.1 ng/mL). This finding was validated in an independent patient cohort (CRC patients: 23.0 ng/mL, range 6.0-45.9 ng/mL; control patients: 32.3 ng/mL, range 14.2-62.4 ng/mL). BDNF concentrations did not differ significantly between Dukes' staging in the patient cohort, however patients with Stages A, B, C and D (p< 0.01 for each stage) tumours had significantly reduced BDNF levels compared to healthy controls. Receiver operating characteristic analysis was performed to determine the ability of BDNF to discriminate between healthy controls and those with CRC. At 95% specificity, BDNF concentrations distinguished CRC patients with 25% and 18% sensitivity, respectively, in cohorts 1 and 2 (cohort 1: AUC=0.79, 95% CI 0.70-0.87; cohort 2: AUC =0.69, 95% CI 0.61-0.76). CONCLUSION: The serum levels of BDNF were significantly lower in colorectal cancer patients when compared to a control population, and this did not differ between different Dukes' stages.G.V. Brierley, I.K. Priebe, L. Purins, K.Y.C. Fung, B. Tabor, T. Lockett, E. Nice, P. Gibbs, J. Tie, P. McMurrick, J. Moore, A. Ruszkiewicz, A. Burgess and L.J. Cosgrov

Performance of serum lipocalin 2 as a diagnostic marker for colorectal cancer

Background: Lipocalin 2 has been implicated in colorectal tumorigenesis but its usefulness as a diagnostic marker for the disease has previously never been determined. Methods: We have used ELISA immunoassay to measure the level of serum lipocalin 2 in a cohort consisting of colorectal cancer patients (n=196) and age/gender matched controls (n=99). Results: The median concentration of lipocalin 2 was found to be significantly higher (p< 0.0001) in the patient group (105.9 ng/mL, range 10.8-444.7 ng/mL) when compared to the control subjects (86.4 ng/mL, range 17.1-190.0 ng/mL). Additionally, no significant difference was observed between disease stage (Dukes' or T stage) in the patient cohort. Receiver operating characteristic analysis was performed to determine its performance as a diagnostic marker. The area under the curve was found to be 0.641 (95% confidence interval 0.576-0.706). Furthermore, the sensitivity of lipocalin 2 was found to be 24% at 90% specificity. Conclusions: Our study indicates that lipocalin 2 is not a suitable serum biomarker for the diagnosis of CRC.Kim Y.C. Fung, Ilka Priebe, Leanne Purins, Bruce Tabor, Gemma V. Brierley, Trevor Lockett, Edouard Nice, Peter Gibbs, Jeannie Tie, Paul McMurrick, James Moore, Andrew Ruszkiewicz , Antony Burgess and Leah J. Cosgrov

Blood-Based Protein Biomarker Panel for the Detection of Colorectal Cancer

BACKGROUND: The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second most common internal cancer in Australia, only 30 per cent of the population considered to have risk factors participate in stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase screening compliance. A number of potential diagnostic blood-based protein biomarkers for CRC have been reported, but all lack sensitivity or specificity for use as a stand-alone diagnostic. The aim of this study was to identify and validate a panel of protein-based biomarkers in independent cohorts that could be translated to a reliable, non-invasive blood-based screening test. PRINCIPAL FINDINGS: In two independent cohorts (n = 145 and n = 197), we evaluated seven single biomarkers in serum of CRC patients and age/gender matched controls that showed a significant difference between controls and CRC, but individually lack the sensitivity for diagnostic application. Using logistic regression strategies, we identified a panel of three biomarkers that discriminated between controls and CRC with 73% sensitivity at 95% specificity, when applied to either of the two cohorts. This panel comprised of Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2). CONCLUSIONS: Due to the heterogeneous nature of CRC, a single biomarker is unlikely to have sufficient sensitivity or specificity for use as a stand-alone diagnostic screening test and a panel of markers may be more effective. We have identified a 3 biomarker panel that has higher sensitivity and specificity for early stage (Stage I and -II) disease than the faecal occult blood test, raising the possibility for its use as a non-invasive blood diagnostic or screening test

“Cancer 2015”:A prospective, population-based cancer cohort—phase 1: Feasibility of genomics-guided precision medicine in the clinic

“Cancer 2015” is a longitudinal and prospective cohort. It is a phased study whose aim was to pilot recruiting 1000 patients during phase 1 to establish the feasibility of providing a population-based genomics cohort. Newly diagnosed adult patients with solid cancers, with residual tumour material for molecular genomics testing, were recruited into the cohort for the collection of a dataset containing clinical, molecular pathology, health resource use and outcomes data. 1685 patients have been recruited over almost 3 years from five hospitals. Thirty-two percent are aged between 61–70 years old, with a median age of 63 years. Diagnostic tumour samples were obtained for 90% of these patients for multiple parallel sequencing. Patients identified with somatic mutations of potentially “actionable” variants represented almost 10% of those tumours sequenced, while 42% of the cohort had no mutations identified. These genomic data were annotated with information such as cancer site, stage, morphology, treatment and patient outcomes and health resource use and cost. This cohort has delivered its main objective of establishing an upscalable genomics cohort within a clinical setting and in phase 2 aims to develop a protocol for how genomics testing can be used in real-time clinical decision-making, providing evidence on the value of precision medicine to clinical practice.</p

KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer.

PURPOSE: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse. EXPERIMENTAL DESIGN: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial. RESULTS: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P &lt; 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial. CONCLUSIONS: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies