Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

Real-world Safety of Bevacizumab with First-line Combination Chemotherapy in Patients with Metastatic Colorectal Cancer: Population-based Retrospective Cohort Studies in Three Canadian Provinces.

AIMS: To examine the real-world safety of adding bevacizumab to first-line irinotecan-based chemotherapy for patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: Patients diagnosed with CRC in three Canadian provinces (Ontario, Saskatchewan and British Columbia) who received publicly funded bevacizumab and/or irinotecan from 2000 to 2016 were identified from cancer registries. Propensity score 1:1 matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to contemporaneous and historical controls, adjusting for baseline demographic and clinical characteristics. Safety end points evaluated during first-line treatment plus 30 days included mortality within 30 days and all-cause-, chemotherapy- and bevacizumab-related hospitalisations. Chemotherapy- and bevacizumab-related visits were defined as hospitalisations for specific conditions commonly associated with chemotherapy (e.g. infections) or bevacizumab (e.g. arteriovenous thromboembolism) using most responsible diagnosis codes. In PSM and IPTW-weighted cohorts, we assessed event frequencies using odds ratios from logistic regressions and event rate ratios using negative binomial regression models. The results from each province and comparison were pooled using random-effects meta-analysis. RESULTS: We identified 16 250 mCRC patients who received first-line irinotecan-based treatment. In PSM cohorts, bevacizumab was associated with fewer deaths within 30 days of treatment compared with contemporaneous (pooled odds ratio = 0.62; 95% confidence interval 0.50-0.75) and historical controls (pooled odds ratio = 0.73; 95% confidence interval 0.58-0.93). Hospitalisations were more frequent among patients treated with bevacizumab compared with historical controls but similar to contemporaneous controls. As patients receiving bevacizumab were exposed to a longer average treatment duration, across their full treatment duration, patients receiving bevacizumab had significantly lower rates of hospitalisations (contemporaneous pooled rate ratio = 0.56; 95% confidence interval 0.47-0.67; historical pooled rate ratio = 0.73; 95% confidence interval 0.56-0.95). Similar trends were observed for chemotherapy- and bevacizumab-related hospitalisations and in IPTW-weighted cohorts. DISCUSSION: We did not observe any increase in rates of hospitalisation or death within 30 days of treatment among mCRC patients treated with bevacizumab plus chemotherapy versus chemotherapy alone; these findings should be interpreted with caution due to the risk of residual confounding.

Quality of life in a real-world study of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.

Background: Quality of life (qol) is important for oncology patients, especially for those with late-stage disease. The present study was initiated to address the lack of published prospective data about the qol benefits of trifluridine/tipiracil (ftd/tpi) compared with best supportive care (bsc) in patients with refractory metastatic colorectal cancer (mcrc). Methods: This prospective, cross-sectional, non-interventional study used multidimensional validated scales to evaluate patient-reported qol in two study cohorts of patients and also to measure differences in mcrc-related symptoms and pain in a real-world clinical setting. Results: Our findings demonstrate that patients with refractory mcrc report better overall qol when treated with ftd/tpi than with bsc alone. In that population, statistically significant differences in mean qol measures favoured ftd/tpi over bsc for physical symptom distress, psychological distress, activity impairment, overall valuation of life, and symptomatology. The overall better qol for patients receiving ftd/tpi implies that treatment was well tolerated and was associated with a lower symptom burden. No significant differences for pain were observed between the groups. Conclusions: This study suggests that ftd/tpi is a well-tolerated option for the treatment of patients with refractory mcrc, showcasing the value of capturing real-world qol data in routine clinical practice.

A catalyst for transforming health systems and person-centred care: Canadian national position statement on patient-reported outcomes.

Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.

Subtype-specific risk factors for postmenopausal breast cancer: findings from the PLCO trial.

OBJECTIVE: The aim of this analysis is to evaluate the relative weight of different epidemiological risk factors on the development of different breast cancer subtypes (i.e. luminal, Her2+ overexpressed or triple negative). METHODS: De-identified datasets of female participants recruited within the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial were accessed. Multivariate Cox regression analysis was utilized to assess factors affecting the development of breast cancer (regardless of subtype). Additional multivariate analyses were conducted to assess factors affecting the development of the three principal subtypes of breast cancer (ER+/Her2- breast cancer; Her2 overexpressed breast cancer and ER-/Her2- breast cancer). RESULTS: A total of 73,570 eligible participants were evaluated in the current analysis of which 2370 participants subsequently developed breast cancer. The following factors were associated with a higher risk of ER+/Her2- breast cancer: white race (P < 0.001), nulliparity (P < 0.001), higher body mass index (P = 0.003), prior exposure to hormone treatment (P = 0.004) and breast cancer in first-degree female relatives (P < 0.001). The following factors were associated with a higher risk of Her2 overexpressed breast cancer: prior exposure to hormone treatment (P = 0.002) and breast cancer in first-degree female relatives (P = 0.001). The following factors were associated with a higher risk of ER-/Her2- breast cancer: black race (P = 0.013), younger age (P = 0.017) and breast cancer in first-degree female relatives (P 0.023). CONCLUSIONS: There is considerable heterogeneity in risk factors among patients with different subtypes of breast cancer. In particular, factors associated with high estrogen levels seem to be associated with luminal breast cancer rather than other breast cancer subtypes.

Role of real-world evidence in informing cancer care: lessons from colorectal cancer.

The term "real-world evidence" (rwe) describes the analysis of data that are collected beyond the context of clinical trials. The use and application of rwe have become increasingly common and relevant, especially in oncology, because there is growing recognition that randomized controlled trials (rcts) might not be sufficiently representative of the entire patient population that is affected by cancer, and that specific clinical research questions might be best addressed by real-world data. In this brief review, our main aim is to highlight the role of rwe in informing cancer care, particularly focusing on specific examples from colorectal cancer. Our hope is to illustrate the ways in which rwe can complement rcts in improving the understanding of cancer management and how rwe can facilitate cancer treatment decisions for real-world patients encountered in routine clinical care.

Real-world use of trifluridine/tipiracil for patients with metastatic colorectal cancer in Canada.

Background: Outcomes for patients with metastatic colorectal cancer (mcrc) are improving with the introduction of new treatments. Treatment for patients who are still fit after failure of all available therapies represents a significant unmet need. In the present study, we analyzed real-world treatment patterns for patients enrolled in Health Canada's trifluridine/tipiracil (ftd/tpi) Special Access Program (sap) and Taiho Pharma Canada's Patient Support Program (psp). Methods: Demographic information and clinical treatment data were collected from adults with mcrc who were previously treated with, or were not candidates for, available therapies and who were enrolled in the sap and psp. For all patients, ftd/tpi treatment status, discontinuation reasons, and prior therapies were examined. Results: The analysis included 717 Canadian patients enrolled in the ftd/tpi sap and psp from September 2017 to October 2018. In that cohort, 59.7% were men, median age was 65 years, and median duration of therapy was 77 days (25%-75% interquartile range: 43-106 days). Of treated patients, 67.1% maintained the same dose for the duration of therapy; 28.0% had a dose reduction.On multivariable analysis, duration of therapy was not influenced by sex, age, province, RAS mutation status, or prior therapies. However, prior oxaliplatin-based chemotherapy (capox or folfox) appeared to be associated with higher rates of discontinuation because of death or disease progression. Conclusions: In advanced mcrc, ftd/tpi is a well-tolerated therapy. The large number of patients enrolled in the access programs within a short period of time is reflective of major clinical need in this area, with many patients being eligible and interested in pursuing treatment in the refractory setting.

Patient-reported outcomes in Alberta: rationale, scope, and design of a database initiative.

Background: The collection of patient reported outcomes (pros) is a standard of care in many cancer organizations. In Alberta, pros have been integrated into routine clinical practice since 2012. This longitudinal collection of pros provides a wealth of data and a unique research opportunity to improve cancer care. The goal of this pro data initiative is to establish a robust repository of information for ongoing clinical care and research focused on pros. In this paper, we describe the rationale, scope, and design of this initiative. Implementation: The initiative consists of pros and other administrative health data from the province of Alberta. Retrieval of health data from a variety of provincially governed sources will create a platform of information on pros, health outcomes, cancer data, other health conditions, and demographics. The aims of the initiative are to use the data to inform best practices at the point of care; to conduct health services research, particularly clinical epidemiology studies; and to evaluate a variety of pro-related outcomes. Discussion: Because this effort represents our first to integrate routinely collected pros with other administrative health data, a unique and robust data repository will be created. The ability to integrate various types of data will provide a comprehensive mechanism to evaluate a variety of outcomes. Because cancer care in Alberta is governed by a single health care system, the data linkages will include population health and psychosocial cancer data. We anticipate that research related to this initiative will ultimately help to inform more patient-centred care.

Active treatment in low-risk prostate cancer: a population-based study.

Background: Active surveillance instead of active treatment (at) is preferred for patients with low-risk prostate cancer (lr-pca), but practice varies widely. We conducted a population-based study to assess the proportion of patients who underwent at between January 2011 and December 2014, and to evaluate factors associated with at. Methods: The provincial cancer registry was linked to administrative health datasets to identify patients with lr-pca and to acquire demographic, tumour, and treatment data. The primary outcome was receipt of at during the first 12 months after diagnosis, defined as any receipt of external-beam radiotherapy, brachytherapy, radical prostatectomy, cryotherapy, or androgen deprivation. Univariate and multivariate logistic regression were used to analyze the correlation between patient and tumour factors and at. Results: Of 1565 patients with lr-pca, 554 (35.4%) underwent at within 12 months of diagnosis. Radical prostatectomy was the most common treatment (58%), followed by brachytherapy (29.6%). Younger age [odds ratio (or) 0.92; 95% confidence interval (ci): 0.91 to 0.94], lower score (≥3) on the Charlson comorbidity index (OR: 0.36; 95% ci: 0.19 to 0.68), T2 stage (or: 3.05; 95% ci: 2.03 to 4.58), higher prostate-specific antigen (psa) at diagnosis (or: 1.13; 95% ci: 1.06 to 1.21), radiation oncologist consultation (or: 3.35; 95% ci: 2.55 to 4.39), and earlier diagnosis year (2012 or: 0.46; 95% ci: 0.34 to 0.63; 2013 or: 0.45; 95% ci: 0.32 to 0.63; 2014 or: 0.33; 95% ci: 0.23 to 0.47) were associated with a higher probability of at. Conclusions: This contemporary population-based study demonstrates that approximately one third of patients with lr-pca undergo at. Patients of younger age, with less comorbidity, a higher tumour stage, higher psa, earlier year of diagnosis, and radiation oncologist consultation were more likely to undergo at. Further investigation is needed to identify strategies that could minimize overtreatment.

The economic impact of the transition from branded to generic oncology drugs.

Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems.

A population-level comparison of cancer-related and non-cancer-related health care costs using publicly available provincial administrative data.

Introduction: Costs associated with cancer care are increasing. Cancer costs in the context of other common non-cancer diagnoses have not been extensively studied at the population level. Knowledge from such analyses can inform health care resource allocation and highlight strategies to reduce overall costs. Methods: Using cross-sectional data from publicly available population-level administrative data sources (health insurance claims, physician billing, and hospital discharge abstracts), we calculated incidence-adjusted health care costs (in 2014 Canadian dollars) for cancers and common non-cancer diagnoses in the adult population in a large Canadian province. Subgroup analyses were also performed for various provincial health administrative regions. Results: Total costs related to cancer care amounted to $495 million for the province, of which at least $67 million (14%) was attributable to radiation and chemotherapy. Of the various cancer subtypes, hematologic malignancies were most costly at $70 million, accounting for 14% of the total cancer budget. Colon cancer followed at $51 million (10%), and lung cancer, at $44 million (9%). Cancer costs (with and without costs for radiation and chemotherapy) exceeded those for cardiovascular disease, diabetes mellitus, mental health, and trauma (p < 0.001). In addition, the costs of specific cancer subtypes varied by region, but hematologic and lung cancers were typically the most costly no matter the health region. Conclusions: Using provincial administrative data to establish cost trends can help to inform health care allocation and budget decisions, and can facilitate comparisons between provinces.

Generalisability of Common Oncology Clinical Trial Eligibility Criteria in the Real World.

AIMS: Strict oncology clinical trial eligibility criteria can contribute to low accrual and result in poorly generalisable study findings. Using common eligibility criteria, we sought to (i) determine how many patients would be eligible versus ineligible and (ii) describe real-world patterns of treatments and outcomes between those considered trial eligible and ineligible. MATERIALS AND METHODS: The Alberta Cancer Registry was used to assemble a population-based cohort of patients diagnosed with 11 common malignancies between 2004 and 2015. We considered age >75 years, anaemia, comorbid conditions (heart disease, uncontrolled diabetes, kidney disease, liver disease) and history of a prior malignancy or immunosuppression to be exclusion criteria. Logistic regression was used to characterise the likelihood of receiving treatment. Cox regression models were constructed to determine cancer-specific and overall survival. RESULTS: We identified 125 316 cancer patients, of whom 53% were men; the median age was 66 (interquartile range 48-84) years. Approximately 38% of patients were considered trial ineligible. The most common reasons for ineligibility were advanced age (24%) and heart disease (16%). In this ineligible group, 12, 47 and 19% still underwent chemotherapy, surgery and radiotherapy, respectively. Compared with ineligible patients, eligible patients were more likely to undergo chemotherapy (odds ratio 1.98, 95% confidence interval 1.89-2.07, P < 0.0001), surgery (odds ratio 1.39, 95% confidence interval 1.32-1.46, P < 0.0001) and radiotherapy (odds ratio 1.46, 95% confidence interval 1.4-1.52, P < 0.0001). Compared with ineligible patients who did not receive treatment, those considered ineligible but who still received treatment experienced improved cancer-specific survival (hazard ratio 0.75, 95% confidence interval 0.74-0.77, P < 0.0001) and overall survival (hazard ratio 0.89, 95% confidence interval 0.87-0.90, P < 0.0001). CONCLUSIONS: A significant proportion of real-world patients are unable to participate in clinical trials due to stringent exclusion criteria, but many still receive treatment in routine practice. The eligibility criteria of oncology clinical trials should be broadened.

Performance evaluation of a self-administered home oral glucose tolerance test kit in a controlled clinical research setting.

AIM: To evaluate the performance of the current, pre-production version of a novel home oral glucose tolerance test (Home OGTT) device when administered by trained research nurses, compared with a reference laboratory glucose analyser and a second laboratory analyser, incorporating a sample processing delay to simulate normal practice. METHODS: One hundred women (aged 19-48 years), with and without known glucose intolerance were recruited. Following an overnight fast, participants attended for a 75-g OGTT. A fasting capillary sample was applied to the Home OGTT device with a corresponding venous sample collected and measured immediately on the reference YSI 2300 stat plus analyser, and following a 1-h delay on the Randox Daytona Plus analyser. The sampling process was repeated 2 h after the oral glucose load. RESULTS: Some 97% of tested devices gave complete data for analysis. Good agreement was observed between the reference glucose analyser and the Home OGTT device, with the Home OGTT device displaying a small negative bias (-0.18 mmol/l, -1.75 to 1.39 mmol/mol; -1.0%, -26.4% to 24.5%; absolute and relative mean, 95% limits of agreement). When classified as normal glucose tolerant or glucose intolerant, the Home OGTT device showed 100% and 90% sensitivity, and 99% and 99% specificity using fasting plasma glucose and 2-h glucose respectively. Similar sensitivity (100% and 100%) and specificity (96% and 99%) for fasting plasma glucose and 2-h glucose were observed using the secondary analyser. CONCLUSIONS: The novel Home OGTT device was reliable and easy to use and showed excellent agreement with two separate laboratory analysers. The Home OGTT offers potential as an effective alternative for clinic-based OGTT testing.

Effect of structured self-monitoring of blood glucose, with and without additional TeleCare support, on overall glycaemic control in non-insulin treated Type 2 diabetes: the SMBG Study, a 12-month randomized controlled trial.

AIM: To examine the impact of structured self-monitoring of blood glucose, with or without TeleCare support, on glycaemic control in people with sub-optimally controlled Type 2 diabetes. METHODS: We conducted a 12-month, multicentre, randomized controlled trial in people with established (>1 year) Type 2 diabetes not on insulin therapy, with sub-optimal glycaemic control [HbA1c ≥58 to ≤119 mmol/mol (≥7.5% to ≤13%)]. A total of 446 participants were randomized to a control group (n =151) receiving usual diabetes care, a group using structured self-monitoring of blood glucose alone (n =147) or a group using structured self-monitoring of blood glucose with additional monthly 'TeleCare' support (n =148). The primary outcome was HbA1c at 12 months. RESULTS: A total of 323 participants (72%) completed the study; 116 (77%) in the control group, 99 (67%) in the self-monitoring of blood glucose alone group and 108 (73%) in the self-monitoring of blood glucose plus TeleCare group. Compared to baseline, the mean HbA1c was lower in all groups at 12 months, with reductions of 3.3 mmol/mol (95% CI -5.71 to -0.78) or 0.3% (95% CI -0.52 to -0.07; P=0.01) in the control group, 11.4 mmol/mol (95% CI -14.11 to -8.76) or 1.1% (-1.29 to -0.81; P<0.0001) in the group using self-monitoring of blood glucose alone and 12.8 mmol/mol (95% CI -15.34 to -10.31) or 1.2% (95% CI -1.40 to -0.94; P<0.0001) in the group using self-monitoring of blood glucose plus TeleCare. This represents a reduction in HbA1c of 8.9 mmol/mol (95% CI -11.97 to -5.84) or 0.8% (95% CI -1.10 to -0.54; P≤0.0001) with structured self-monitoring of blood glucose compared to the control group. Participants with lower baseline HbA1c , shorter duration of diabetes and higher educational achievement were more likely to achieve HbA1c ≤53 mmol/mol (7.0%). CONCLUSIONS: Structured self-monitoring of blood glucose provides clinical and statistical improvements in glycaemic control in Type 2 diabetes. No additional benefit, over and above the use of structured self-monitoring of blood glucose, was observed in glycaemic control with the addition of once-monthly TeleCare support. (Clinical trial registration no.: ISRCTN21390608).

Prognostic effect of sidedness in early stage versus advanced colon cancer.

BACKGROUND AND AIMS: The prognostic effect of sidedness in colorectal cancer has been evaluated in numerous prospective and retrospective cohorts. Most of these have reported overall survival data; there is scant relapse-free survival data in early stage disease. This study aimed to determine the effect of tumor sidedness in survival in early stage and relapsed colon cancer. METHODS: Patients with stage I-III colorectal cancer were identified from the BC Cancer Agency Gastrointestinal Cancer Outcomes Unit. Survival analysis by stage and sidedness was compared with the log-rank test. Baseline characteristics were controlled by multivariate Cox-proportional hazard models. In relapsed patients, bevacizumab and EGFR inhibitor (EGFRI) treatments were included and tested for interaction. RESULTS: Among 5378 patients with stage I-III colon cancer, patients with right-sided stage II tumors experienced better relapse-free survival compared with those with left-sided tumors; right-sidedness was not prognostic for RFS in stage III disease. When survival was considered in patients who relapsed, right-sided tumors had inferior survival after relapse in both stage II and stage III tumors. At relapse, right-sided outcomes were inferior regardless of biologic therapy. An interaction test revealed a significant association between sidedness and survival with EGFRIs. CONCLUSIONS: In this large, population-based study, right-sided presentation has a significant prognostic impact: in early stage, right-sidedness is favorably prognostic among stage II tumors and not prognostic in stage III disease. After relapse, right- sidedness is associated with an inferior prognosis, regardless of initial stage of presentation. Colon tumor sidedness is independently prognostic and may be considered in treatment assignment for both early stage and advanced disease.

Risk and predictors of suicide in colorectal cancer patients: a Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: The risk of suicide is higher for patients with colorectal cancer (crc) than for the general population. Given known differences in morbidity and sites of recurrence, we sought to compare the predictors of suicide for patients with colon cancer and with rectal cancer. METHODS: Using the U.S. Surveillance, Epidemiology, and End Results database, adult patients with confirmed adenocarcinoma of the colon or rectum during 1973-2009 were identified. Parametric and nonparametric tests were used to assess selected variables, and Cox proportional hazards regression models were used to determine predictors of suicide. RESULTS: The database identified 187,996 patients with rectal cancer and 443,368 with colon cancer. Compared with the rectal cancer group, the colon cancer group was older (median age: 70 years vs. 67 years; p < 0.001) and included more women (51% vs. 43%, p < 0.001). Suicide rates were similar in the colon and rectal cancer groups [611 (0.14%) vs. 337 (0.18%), p < 0.001]. On univariate analysis, rectal cancer was a predictor of suicide [hazard ratio (hr): 1.26; 95% confidence interval (ci): 1.10 to 1.43]. However, after adjusting for clinical and pathology factors, rectal cancer was not a predictor of suicide (hr: 1.05; 95% ci: 0.83 to 1.33). In the colon cancer cohort, independent predictors of suicide included older age, male sex, white race, and lack of primary resection. The aforementioned predictors, plus metastatic disease, similarly predicted suicide in the rectal cancer cohort. CONCLUSIONS: The suicide risk in crc patients is low (<0.2%), and no difference was found based on location of the primary tumour. Sex, age, race, distant spread of disease, and intact primary tumour were the main predictors of suicide among crc patients. Further studies and interventions are needed to target these high-risk groups.

Validation of the Crohn's and Ulcerative Colitis questionnaire in patients with acute severe ulcerative colitis.

BACKGROUND: The Crohn's and Ulcerative Colitis questionnaire (CUCQ) has previously been validated in patients with mild to moderate Crohn's and ulcerative colitis (UC). The aim of this study was to validate the tool in patients with acute severe UC. METHODS: We undertook a validation of the CUCQ in patients recruited to the COmparison of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis Trial (CONSTRUCT). We carried out psychometric analysis to examine the underlying dimensions of the scale, internal consistency and construct validity. We carried out stepwise regression to examine which items accounted for the greatest variance in the scale. RESULTS: We obtained complete data for 270 patients. The internal consistency of the CUCQ was excellent (Cronbach's alpha > 0.8). The CUCQ scores achieved significant correlations with two generic quality of life scales (SF-12 and EQ-5D), demonstrating good construct validity. Stepwise regression identified 16 items that accounted for greater than 95% of the variance of the CUCQ. Only three of the eight items selected for a short form in mild to moderate patients were selected for patients with acute severe UC. CONCLUSIONS: The CUCQ demonstrated good validity in our sample of acute severe UC patients. Stepwise regression identified potential to shorten the tool, but that different items would be selected compared with less severe patients. If the tool is to be applied across the spectrum of disease it would be more appropriate to use the full 32 items in the scale. Further work to explore test-retest is required in acute patients.

Patterns of practice with third-line anti-EGFR antibody for metastatic colorectal cancer.

BACKGROUND: Therapy with anti-epidermal growth factor receptor (egfr) monoclonal antibody improves outcomes for patients with metastatic colorectal cancer (mcrc) in the first-, second-, and third-line trial settings. In British Columbia, the use of egfr inhibitors (egfris) is confined to third-line therapy, which might lower the proportion of patients who receive this therapy. The objective of the present study was to describe egfri treatment patterns when those agents are limited to the third-line setting. The results will inform decisions about optimal use of egfri agents, including earlier in the course of therapy for metastatic disease. METHODS: All patients with newly diagnosed mcrc who were referred to BC Cancer Agency clinics in 2009 were included in the study. Prognostic and treatment information was prospectively collected; KRAS test results were determined by chart review. RESULTS: The study included 443 patients with a median age of 66 years. For the 321 patients who received systemic therapy, median survival was 22.3 months. Of the 117 patients who were treated with 5-fluorouracil, oxaliplatin, and irinotecan, and who were potentially eligible for egfri therapy, 90% (105 patients) were tested for KRAS status. Of the 60 patients with KRAS wild-type tumours, 82% (49 patients) received egfri therapy. CONCLUSIONS: When egfri therapy is limited to the third-line setting, only a small proportion of patients receive such therapy, with death and poor performance status preventing its use in the rest. Availability of egfri in earlier lines of therapy could increase the proportion of patients treated with all active systemic agents.

Population-based trends in systemic therapy use and cost for cancer patients in the last year of life.

BACKGROUND: The use of systemic therapy near the end of life can expose cancer patients to severe toxicity for minimal survival gain and comes with a high cost. Early palliative care is recommended, but there is evidence that aggressive care remains common. To better understand those patterns, the present study set out to describe trends in systemic therapy use and cost for cancer patients in the last year of life. METHODS: Using the BC Cancer Registry, a retrospective population-based cohort of cancer decedents (2002-2007) was identified and linked to systemic therapy records. The outcomes of interest were any systemic therapy use and total systemic therapy costs during the last year of life. Multiple logistic regression (systemic therapy use) and generalized linear regression (costs) were conducted, adjusting for age, sex, and survival. Subgroup analyses were performed for patients with primary colorectal, lung, prostate, or breast cancer. RESULTS: From 2002 to 2007, use of systemic therapy in the last 12-4 months of life increased by 21% (95% ci: 10% to 33%); no significant change in use in the last 3 months of life was observed. Costs for both periods increased over time, by 48% (95% ci: 36% to 63%) and by 33% (95% ci: 19% to 49%) respectively. The trends varied across cancer sites, with the greatest increases being observed for lung and colorectal cancer patients. CONCLUSIONS: The use and costs of systemic therapy have generally been increasing, putting pressure on health care providers and payers, but the quality-of-life implications for patients must be better understood.

Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer.

BACKGROUND: Studies of clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) are limited. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database. PATIENTS AND METHODS: Data for patients diagnosed with LARC who received nCRT and curative-intent surgery between 2005 and 2012 were collected from five major Canadian cancer centers. Age was analyzed as a continuous and dichotomous variable (< 70 versus ≥ 70 years) and correlated with disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Cox regression models were used to adjust for important prognostic factors. RESULTS: Of 1172 patients included, 295 (25%) were ≥ 70 years, and they were less likely to receive adjuvant chemotherapy (ACT; 60% versus 79%, P < 0.0001), oxaliplatin-based ACT (12% versus 31%, P < 0.0001), less likely to complete nCT (76% versus 86%, P < 0.001), and more likely to be anemic at initiation of nCRT (42% versus 30%, P = 0.0004). In multivariate analyses, age ≥ 70 years was associated with similar DFS [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.68-1.26, P = 0.63], similar CSS (HR 0.81, 95% CI 0.46-1.41, P = 0.45), and similar OS (HR 1.28, 95% CI 0.88-1.86, P = 0.20), compared with the younger age group. As a continuous variable, increasing age was not predictive of DFS (HR 1.00, 95% CI 0.99-1.02, P = 0.49) or CSS (HR 1.002, 95% CI 0.98-1.02, P = 0.88); however, it correlated with an inferior OS (HR 1.02, 95% CI 1.00-1.03, P = 0.04). CONCLUSIONS: Elderly patients (≥ 70 years) who receive nCRT followed by surgery appear to have similar outcomes compared with younger patients. Decisions regarding eligibility for nCRT and surgery should not be based on age alone.