A multicentre, open-label phase II study of Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO) as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Purpose Chemotherapy remains the primary treatment for metastatic gastric/GEJ cancer but optimal agents and schedule remain controversial. This study examined the safety and efficacy of first-line Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO). Patients and Methods Eligible patients with HER2-unamplified/unknown, metastatic gastric/GEJ adenocarcinoma were treated with 21-day cycle IXO at dose level 1 (DL1: Day 1 O-100 mg/m2 & I-160 mg/m2 IV, Day 2-15 X-1900 mg/m2/day PO divided doses) or modified IXO (mIXO): Day 1 O-85 mg/m2 & I-120 mg/m2 IV, Day 2-15 X-1425 mg/m2/day PO divided doses). This Bryant and Day two-stage designed study had dual primary endpoints of objective response rate (ORR) and toxicity. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results Fifty patients were enrolled and received a median of 7 cycles. After accrual of 9 patients at DL1, evaluable RR was 88% however dose limiting toxicity (DLT) rate was 56% thus doses were adjusted to mIXO. Fifteen patients accrued at mIXO had a RR of 60% and DLT rate of 13% allowing continuation to stage 2. Overall, 48 and 49 patients were evaluable for efficacy and safety, respectively, with ORR of 54% and DLTs in 24% of patients (DL1 = 56%; mIXO = 18%). Disease control rate was 85%. The most frequent grade 3/4 adverse events were diarrhea, neutropenia, fatigue, hypokalemia, and nausea. Median PFS and OS were 7.5 and 13.0 months, respectively, with a median follow-up of 9.7 months. Conclusion mIXO demonstrates promising ORR, PFS, OS, and acceptable toxicity compared to standard triplet regimens. IXO should be evaluated in phase III trials.

Regional Lymph Nodes Status and Ratio of Metastatic to Examined Lymph Nodes Correlate with Survival in Stage IV Colorectal Cancer.

BACKGROUND: Although lymph nodes status and the ratio of metastatic to examined lymph node (LNR) are important prognostic factors in early-stage colorectal cancer (CRC), their significance in patients with metastatic disease remains unknown. The study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC. METHODS: A cohort of 1109 eligible patients who were diagnosed with synchronous metastatic CRC in Saskatchewan during 1992-2010 and underwent primary tumor resection was evaluated. We conducted the Cox proportional multivariate analyses to determine the prognostic significance of nodal status and LNR. RESULTS: Median age was 70 years (22-98) and M:F was 1.2:1. Rectal cancer was found in 26 % of patients; 96 % had T3/T4 tumor, and 82 % had node positive disease. The median LNR was 0.36 (0-1.0). Fifty-four percent received chemotherapy. Median overall survival of patients who had LNR of <0.36 and received chemotherapy was 29.7 months (95 % CI 26.6-32.9) compared with 15.6 months (95 % CI 13.6-17.6) with LNR of ≥0.36 (P < .001). On multivariate analyses, no chemotherapy (HR 2.36 [2.0-2.79]), not having metastasectomy (HR 1.94 [1.63-2.32]), LNR ≥0.36 (HR 1.59 [1.38-1.84]). nodal status (HR 1.34 [1.14-1.59]), and T status (HR 1.23 [1.07-1.40]) were correlated with survival. Test for interaction was positive for LNR and high-grade cancer (HR 1.51 [1.10-2.10]). CONCLUSIONS: Our results suggest that nodal status and LNR are important prognostic factors independent of chemotherapy and metastasectomy in stage IV CRC patients.

Predictive Factors of the Use of Systemic Therapy in Stage IV Colorectal Cancer: Who Gets Chemotherapy?

BACKGROUND: Chemotherapy improves survival in patients with stage IV colorectal cancer (CRC). Although in a clinical trial setting, strict eligibility criteria are used for chemotherapy, little is known about the use of chemotherapy in the general population. The study aims to assess clinicopathological variables that correlate with the use of chemotherapy in patients with stage IV CRC. METHODS: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan was carried out. A logistic regression analysis was performed to assess the correlation of various clinicopathological factors with the use of chemotherapy. RESULTS: A total of 1,237 eligible patients were identified. Their median age was 70 years (range: 22-98) and the male:female ratio was 1.3:1. 23.8% had an ECOG performance status (PS) of ≥2 and 61.8% of the patients had a comorbid illness. 46.8% of the patients received chemotherapy. The multivariate logistic regression analysis revealed that an age of <65 years [odds ratio (OR) 3.82, 95% CI: 2.59-5.63], metastasectomy (OR 3.60, 95% CI: 1.82-7.10), normal albumin (OR 3.26, 95% CI: 2.44-4.36), no comorbid illness (OR 2.87, 95% CI: 1.34-6.16), ECOG PS of <2 (OR 2.72, 95% CI: 1.94-3.82), normal blood urea nitrogen (OR 2.24, 95% CI: 1.40-3.59), palliative radiation (OR 2.03, 95% CI: 1.38-2.99), primary tumor resection (OR 2.00, 95% CI: 1.47-2.73), and the time period (OR 1.85, 95% CI: 1.41-2.42) were significantly correlated with the use of chemotherapy. CONCLUSIONS: The use of chemotherapy appears to be increasing in stage IV CRC. Patients treated with curative intention or who underwent primary tumor resection were more likely to receive chemotherapy. Despite a known benefit of chemotherapy in elderly patients, a differential use of chemotherapy was noted in this population.

Survival impact of surgical resection of primary tumor in patients with stage IV colorectal cancer: results from a large population-based cohort study.

BACKGROUND: Currently, there is very low-quality evidence available regarding benefit of surgical resection of the primary tumor (SRPT), in patients with stage IV colorectal cancer (CRC). In the absence of randomization, the reported benefit may reflect selection of younger and healthier patients with good performance status. A large population-based cohort study was undertaken to determine the survival benefit of SRPT in advanced CRC by eliminating various biases reported in the literature. METHODS: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan, Canada. Survival was estimated by using the Kaplan-Meier method. Survival distribution was compared by log-rank test. Cox proportional multivariate regression analysis was performed to determine survival benefit of SRPT by controlling other prognostic variables. RESULTS: A total of 1378 eligible patients were identified. Their median age was 70 years (range, 22-98 years) and male:female ratio was 1.3:1; 944 (68.5%) of them underwent SRPT. Among 1378 patients, 42.3% received chemotherapy and 19.1% received second-generation therapy. Patients who underwent SRPT and received chemotherapy had median overall survival of 18.3 months (95% confidence interval [CI] = 16.6-20 months) compared with 8.4 months (95% CI = 7.1-9.7 months) if they were treated with chemotherapy alone (P < .0001). Cox proportional analysis revealed that use of chemotherapy (hazard ratio [HR] = 0.47, 95% CI = 0.41-0.54), SRPT (HR = 0.49, 95% CI = 0.41-0.58), second-line chemotherapy (HR = 0.47, 95% CI = 0.45-0.64), and metastasectomy (HR = 0.54, 95% CI = 0.45-0.64) were correlated with superior survival. CONCLUSIONS: SRPT improves survival in patients with stage IV CRC, independent of other prognostic variables including age, performance status, comorbid illness and chemotherapy.

Intravenous chemotherapy preparation errors: patient safety risks identified in a pan-Canadian exploratory study.

BACKGROUND: This exploratory study was launched following a critical chemotherapy medication incident to thoroughly and proactively examine the current processes for ordering, preparing, labeling, verifying, administering, and documenting ambulatory intravenous chemotherapy in Canada, and to identify factors that may contribute to preventable adverse drug events. METHODS: Field observations in six Canadian cancer centers to identify end-to-end processes in clinic, pharmacy, and treatment areas; analysis of processes to identify risks. RESULTS: Three types of previously locally unrecognized potential chemotherapy preparation errors in Canadian oncology pharmacies were uncovered, all of which are undetectable if they occur. Although the frequency of these errors is unknown, their impact is potentially catastrophic. INTERPRETATION: Dispensing errors in high-risk intravenous preparation have been studied in the past, but it is unlikely that these studies have detected these errors because of the inherent limitations of the detection methods used. Research on preparation errors using more sensitive methods is therefore urgently needed to establish the extent to which pharmacy preparation practices may be error-prone, and to allow reliable evaluation of the impact of mitigation strategies. Widespread practice changes in Canadian oncology pharmacies are necessary, and are currently underway.

Courage, collaboration, complexity and chemotherapy safety: the view from the sharp end.

The Canadian oncology community was devastated by the news in August 2006 that a patient had died from an overdose of fluorouracil. Where we once thought our checks and balances ensured patient safety, we now knew they were not enough. Practice immediately began to change around the country. However, the incident report highlighted that there was much we still didn't know about safety issues in intravenous ambulatory chemotherapy safety in Canada. In response, an interdisciplinary, pan-Canadian team launched an 18-month exploratory study, resulting in a report identifying several safety issues and associated recommendations. This paper summarizes the key insights we have gathered for Canadian oncology nurses in being part of this study: that we need courage to come forward and disclose safety concerns; we should collaborate to come up with safety improvements that work for everyone; and we should strive to simplify our work at the sharp end by reducing complexity upstream and throughout the system.

Esophageal ulcer in a patient who received bevacizumab.

A 60-year-old woman with metastatic rectal cancer who after surgical resection of the primary and creation of a palliative ileostomy in May 2006, was started on a regimen of bevacizumab, irinotecan, 5-fluouracil and leucovorin. After 3 cycles, she presented with solid food dysphagia. An endoscopy showed a large, deep ulcer in the lower third of the esophagus. We assumed that it was related to bevacizumab treatment. Bevacizumab was stopped and she was started on pantoprazole. Over the ensuing months, the ulcer improved notably. To the best of our knowledge, an esophageal ulcer associated with bevacizumab treatment has not been reported. This is likely the precursor lesion to a gastrointestinal tract perforation.

Primary Tumor Location and Survival in the General Population With Metastatic Colorectal Cancer.

BACKGROUND: Recent evidence from clinical trials suggests that primary tumor location in patients with metastatic colorectal cancer correlates with differential outcomes, and patients with tumors originating in the right side of the colon have inferior survival. We conducted a large population-based cohort study using individual patient data to confirm the prognostic importance of primary tumor location in the general population with metastatic colorectal cancer. METHODS: A cohort of 1947 patients who were diagnosed with metastatic colorectal cancer from 1992 to 2010 was studied. Ascending and transverse colon cancers were defined as right-sided tumors. Cox proportional multivariate analyses were done to determine prognostic significance of primary tumor location. RESULTS: The median age was 70 years (interquartile range, 60-78 years), and the male to female ratio was 1.3:1. Twenty-nine percent had World Health Organization performance status of > 1. Seven-hundred and seventy (39%) patients had right-sided tumors, and 908 (47%) received chemotherapy. The median overall survival of patients with right-sided tumors was 14 months (95% confidence interval [CI], 12.7-15.3 months) compared with 20.5 months (95% CI, 18.5-22.5 months) of patients with left-sided tumors (P < .001). On multivariate analysis, right-sided tumors (hazard ratio [HR], 1.40; 95% CI, 1.20-1.60), no metastasectomy (HR, 2.40; 95% CI, 1.90-2.90), intact primary tumor (HR, 1.60; 95% CI, 1.32-1.90), an elevated carcinoembryonic antigen level (HR, 1.54; 95% CI, 1.30-1.90), lack of combination chemotherapy (HR, 1.52; 95% CI, 1.31-1.80), stage IVb disease (HR, 1.50; 95% CI, 1.17-1.86), leukocytosis (HR, 1.44; 95% CI, 1.28-1.73), and World Health Organization performance status > 1 (HR, 1.30; 95% CI, 1.10-1.55) were correlated with inferior survival. CONCLUSIONS: Our results confirm that individuals with metastatic colorectal cancer and right-sided tumors who received chemotherapy have inferior survival independent of other known prognostic variables. Future studies are required to understand the underlying pathophysiology.

Comparing assessment frameworks for cancer drugs between Canada and Europe: What can we learn from the differences?

The increasing burden of costs associated with novel cancer therapies is becoming untenable. In Europe and Canada, assessment frameworks have been developed to attribute value to novel therapies and ultimately facilitate access to cancer drug funding. A review of the two frameworks has not previously been undertaken. This review provides insight into the relative strengths and benefits of each approach, the various perspectives of value (patient, physician and societal) and how the frameworks relate to their unique context and core principles. Both frameworks assess the clinical benefit of a new cancer therapy. The European framework considers effectiveness, quality of life, and toxicity in its determination of benefit and has the advantage of providing a simple summary score to facilitate priority setting. The Canadian framework considers other elements including cost-effectiveness, patient preferences and adoption feasibility; its deliberative framework precludes a simple summative presentation of value but can address complex and nuanced drug funding considerations with flexibility. Both frameworks have evolved to meet the needs unique to their jurisdictions and offer potentially complementary tools in the assessment of new cancer drugs. Lessons learnt in both systems can be applied to future iterations of the frameworks, which remain works in progress.

Surgical Management of the Primary Tumor in Stage IV Colorectal Cancer: A Confirmatory Retrospective Cohort Study.

BACKGROUND: Observational studies have suggested that patients with stage IV colorectal cancer who undergo surgical resection of the primary tumor (SRPT) have better survival. Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control prognostic variables such as performance status are major critiques to the findings of the observational studies. We previously have shown that SRPT, independent of chemotherapy and performance status, improves survival of stage IV CRC patients. The current study aims to validate our findings in patients with stage IV CRC who were diagnosed during the period of modern chemotherapy. METHODS: A cohort of 569 patients with stage IV CRC diagnosed during 2006-2010 in the province of Saskatchewan was evaluated. Cox regression model was used for the adjustment of prognostic variables. RESULTS: Median age was 69 years (59-95) and M: F was 1.4:1. Fifty-seven percent received chemotherapy, 91.4% received FOLFIRI or FOLFOX & 67% received a biologic agent. Median overall survival (OS) of patients who underwent SRPT and received chemotherapy was 27 months compared with 14 months of the non-resection group (p<0.0001). Median OS of patients who received all active agents and had SRPT was 39 months (95%CI: 25.1-52.9). On multivariate analysis, SRPT, hazard ratio (HR):0.44 (95%CI: 0.35-0.56), use of chemotherapy, HR: 0.33 (95%CI: 0.26-0.43), metastasectomy, HR: 0.43 (95%CI: 0.31-0.58), second line therapy, HR: 0.50 (95%CI: 0.35-0.70), and third line therapy, HR: 0.58 (95%CI: 0.41-0.83) were correlated with superior survival. CONCLUSIONS: This study confirms our findings and supports a favorable association between SRPT and survival in patients with stage IV CRC who are treated with modern therapy.

Phase II randomized study of ISIS 3521 and ISIS 5132 in patients with locally advanced or metastatic colorectal cancer: a National Cancer Institute of Canada clinical trials group study.

BACKGROUND: Because treatment of metastatic colon cancer is noncurative, new treatments are needed. This trial evaluated the antitumor effects of two targeted anticancer agents: (a) ISIS 3521, an antisense inhibitor of the protein kinase C alpha; and (b) ISIS 5132, an antisense inhibitor of c-raf kinase in patients untreated previously with recurrent or metastatic colorectal carcinoma. PATIENTS AND METHODS: All patients had colorectal adenocarcinoma with measurable disease and no prior chemotherapy for metastatic disease. Patients were randomized to receive either ISIS 3521 or ISIS 5132 at a dose of 2 mg/kg/day as a continuous i.v. infusion 21 of 28 days. Cycles were repeated as long as progression was not seen, and doses of both agents were modified according to toxic effects. A two-arm study design was used with each study arm considered independently. Steady-state blood levels of both antisense molecules were measured on days 8, 15, and 22 of the first cycle of therapy. RESULTS: Thirty-seven eligible patients were enrolled, and 32 were evaluable for response (17 receiving ISIS 3521 and 15 receiving ISIS 5132). No responses were noted. Four of the patients receiving ISIS 3521 had stable disease, and 5 patients receiving ISIS 5132 were stable. CONCLUSION: Neither ISIS 5132 nor ISIS 3521given in the dose and schedule studied induced objective responses in untreated colorectal cancer patients.

Innovation in Healthcare Delivery: Commentary on an Evolutionary Approach.

Zwarenstein (2015) proposes a novel approach to healthcare innovation that parallels biological evolution, based on stimulation and reward of multiple small competing innovation projects conducted in the field by decentralized teams. Projects would be designed with explicit outcome targets and results would be widely disseminated and publicly available. More successful projects would be grown and spread. Critical to the model is accepting and reporting failure as well as success, for the benefit of future project design. Examining biological evolution for lessons for healthcare delivery innovation illuminates the need for diversity among healthcare systems to achieve optimum application of best practice interventions across jurisdictions with differing population, provider and facility characteristics. However, careful coordination will be needed to achieve the balance between diversity and harmony across jurisdictions necessary for effective governance and interaction. There are important methodological issues to be addressed to reduce the uncertainty inherent in comparisons of results among discrete innovation projects, especially when observed improvements over the baseline are modest. As well as evolutionary improvement in healthcare outcomes, the model should progressively increase decentralized capacity and expertise in innovation processes.

Surgical Resection of Primary Tumor in Asymptomatic or Minimally Symptomatic Patients With Stage IV Colorectal Cancer: A Canadian Province Experience.

BACKGROUND: Surgical resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Survival benefit reported in the literature has been attributed to the selection of younger and healthier patients with good performance status. We have recently reported that resection of the primary tumor improved survival of patients with stage IV CRC. In this study we examined survival benefit of surgery in patients with asymptomatic or minimally symptomatic primary tumor. PATIENTS AND METHODS: A cohort of patients with stage IV CRC and asymptomatic or minimally symptomatic primary tumor, who were diagnosed during the period of 1992 to 2005, in the province of Saskatchewan Canada, was evaluated. The Kaplan-Meier method was used to determine survival. A multivariate Cox proportional hazard regression analysis was performed to determine prognostic importance of resection of primary tumor. A test for interaction was performed for resection of primary tumor and other important clinicopathological variables. RESULTS: A total of 834 patients with a median age of 70 years (range, 22-93) and male:female ratio of 58:42 were identified. Among them 521 (63%) patients underwent surgery and 361 (43.3%) received chemotherapy. Patients who underwent surgery and received any chemotherapy had a median overall survival of 19.7 months (95% confidence interval [CI], 16.9-22.6) compared with 8.4 months (95% CI, 6.9-10.0) if they did not have surgery (P < .0001). In multivariate analysis, 5-fluorouracil-based chemotherapy (hazard ratio [HR], 0.43; 95% CI, 0.36-0.53), surgical resection of the primary tumor (HR, 0.47; 95% CI, 0.39-0.57), metastasectomy (HR, 0.48; 95% CI, 0.38-0.62), and second-line chemotherapy (HR, 0.72; 95% CI, 0.58-0.92) were correlated with superior survival. A test for interaction between ≥ 1 metastatic sites and surgery was significant, which suggests a larger benefit of surgery in patients with stage IVA disease. CONCLUSION: Results of this large population-based cohort study suggest that resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV CRC improved survival independent of other prognostic variables. The benefit was more pronounced in stage IVA disease.

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province.

BACKGROUND: Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. METHODS: In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. RESULTS: A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70-79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001). CONCLUSIONS: The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

Systematic review of management of colorectal cancer in elderly patients.

This study is designed to clarify the benefits and risks of chemotherapy and radiation therapy in elderly patients with colorectal cancer through a systematic review of the literature. Searches of the Medline, Embase, and Cochrane Library databases; PDQ Cancer Information Summaries, American Society of Clinical Oncology Guidelines, Cancer Care Ontario Practice Guideline Initiative, Interprovincial Drug Strategies and Guidelines Group, and OncoLink Web sites; and manual searches of meeting proceedings and bibliographies were performed. Additional studies known to the authors were also identified. Randomized controlled trials, reviews, and guidelines evaluating the impact of age on overall survival and/or toxicity with adjuvant and palliative therapies for colorectal adenocarcinoma were selected. A preset study selection form was applied to all identified studies. All selected studies underwent a preset study appraisal. Analyses of the effect of age on overall survival benefits and/or toxicity of therapy were extracted. A qualitative synthesis and narrative review was undertaken. There is good evidence to support that patients = 80 years of age have similar overall survival benefits with adjuvant 5-fluorouracil (5-FU)-based chemotherapy for colon cancer and with palliative first-line monotherapy for metastatic colorectal cancer, as do younger patients. Data are limited with regard to toxicity of therapy in older patients in these settings. An increase in toxicity with bolus 5-FU chemotherapy regimens is evident. There is a paucity of data regarding adjuvant treatment of older patients with rectal cancer. More elderly patients need to be enrolled in clinical trials in order to fully evaluate the outcomes of colorectal cancer therapy in this population. Further studies are warranted.

Exposure to Mn/Zn ethylene-bis-dithiocarbamate and glyphosate pesticides leads to neurodegeneration in Caenorhabditis elegans.

Epidemiological evidence suggests positive correlations between pesticide usage and the incidence of Parkinson's disease (PD). To further explore this relationship, we used wild type (N2) Caenorhabditis elegans (C. elegans) to test the following hypothesis: Exposure to a glyphosate-containing herbicide (TD) and/or a manganese/zinc ethylene-bis-dithiocarbamate-containing fungicide (MZ) may lead to neurotoxicity. We exposed N2 worms to varying concentrations of TD or MZ for 30 min (acute) or 24h (chronic). To replicate agricultural usage, a third population was exposed to TD (acute) followed by MZ (acute). For acute TD exposure, the LC(50)=8.0% (r(2)=0.6890), while the chronic LC(50)=5.7% (r(2)=0.9433). Acute MZ exposure led to an LC(50)=0.22% (r(2)=0.5093), and chronic LC(50)=0.50% (r(2)=0.9733). The combined treatment for TD+MZ yielded an LC(50)=12.5% (r(2)=0.6367). Further studies in NW1229 worms, a pan-neuronally green fluorescent protein (GFP) tagged strain, indicated a statistically significant (p<0.05) and dose-dependent reduction in green pixel number in neurons of treated worms following each paradigm. This reduction of pixel number was accompanied by visual neurodegeneration in photomicrographs. For the dual treatment, Bliss analysis suggested synergistic interactions. Taken together, these data suggest neuronal degeneration occurs in C. elegans following treatment with environmentally relevant concentrations of TD or MZ.

Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581.

PURPOSE: We conducted a randomized trial comparing adjuvant treatment with edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome. PATIENTS AND METHODS: After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of edrecolomab at 28-day intervals or observation without adjuvant therapy. RESULTS: Final accrual included 1,738 patients; 865 patients received edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer. CONCLUSION: Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.

Synoptic surgical reporting for breast cancer surgery: an innovation in knowledge translation.

BACKGROUND: Extensive literature identifies that the quality of surgery not only influences morbidity and mortality but also long-term survival and function. This mandates that we develop a system to capture this information on a real-time basis. METHODS: A synoptic surgical template for breast cancer was created; this was digitized and made available to all surgeons in Alberta. RESULTS: The data reference 1,392 breast cancer procedures. Ninety-one percent of reports were submitted within 1 hour and 97% of reports were submitted within 24 hours. Fifty-two percent of reports were completed within 5 minutes. Information quality with respect to completeness of staging information was present in 89%. Eighty-four percent complied with practice guidelines and 89% of breast surgeons adopted the template. Seventy-five percent of users were moderately or highly satisfied with the system. CONCLUSIONS: The experience with the development and implementation of synoptic surgical reporting has proven to be a successful tool for generating quality surgical data.