Patterns of emergency department visits preceding colorectal cancer diagnosis: a population-based study.

Aim: To assess the patterns of emergency department (ED) visits in the 3 months preceding a diagnosis of colorectal cancer (CRC) in a real-world, population-based context. Materials & methods: Linked provincial registries in Alberta, Canada, were accessed and patients with CRC diagnosed between 2004 and 2018 were identified. The National Ambulatory Care reporting system was used to identify patients who visited an ED within 3 months of a diagnosis of CRC. Multivariable logistic regression analysis was used to identify factors associated with any ED visits as well as frequent (≥3) ED visits. Results: A total of 25,310 patients with CRC were included in the current study. These include 10,126 patients (40%) who had at least one visit to the ED in the 3 months before a diagnosis of CRC diagnosis and 613 patients (2.4%) who visited the ED multiple (≥3) times. The following factors were associated with any visit to an ED: older age (odds ratio [OR]: 1.010; 95% CI: 1.008-1.012), female gender (OR: 1.23; 95% CI: 1.16-1.30), higher comorbidity index (OR: 1.38; 95% CI: 1.35-1.41), metastatic disease (OR: 2.37; 95% CI: 2.23-2.53), proximal tumors (OR: 1.59; 95% CI: 1.50-1.68) and North zone (OR vs south zone: 1.75; 95% CI: 1.55-1.98). Conclusion: It is not uncommon for CRC patients to visit the ED at least once in the 3 months prior to having such a diagnosis. Factors associated with frequent pre diagnosis emergency visits included female gender, higher burden of comorbid disease, advanced stage, proximal tumors and living in the North zone of Alberta (where there is limited access to specialist care).

hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA.

Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.

Real-world Patterns of Adjuvant Chemotherapy Following Neoadjuvant Chemoradiation for Patients With Resected Rectal Adenocarcinoma.

OBJECTIVE: The objective of this study was to analyze patterns of adjuvant chemotherapy among patients with resected rectal adenocarcinomas following neoadjuvant chemoradiation and surgical resection. METHODS: Alberta Cancer Registry and other provincial electronic medical registries (2004 to 2018) identified patients with nonmetastatic rectal cancer who received neoadjuvant chemoradiation followed by surgical resection and either oxaliplatin-based or fluoropyrimidine-only adjuvant chemotherapy. Multivariable logistic regression analysis was then undertaken to identify factors associated with the use of either regimen. Kaplan-Meier survival estimates were used to compare overall survival between both groups and multivariable Cox regression analysis was then used to identify factors associated with worse overall survival. RESULTS: A total of 532 patients who fulfilled eligibility criteria were included in the current study: 347 patients received adjuvant fluoropyrimidine-only chemotherapy and 185 patients received adjuvant oxaliplatin-based chemotherapy. The following variables were associated with use of fluoropyrimidine-only adjuvant chemotherapy: older age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), higher Charlson comorbidity index (OR: 1.47; 95% CI: 1.00-2.15), and no involved lymph nodes in the surgical pathology (OR: 5.55; 95% CI: 3.66-8.41). Using Kaplan-Meier survival estimates, no difference in overall survival between patients treated with adjuvant oxaliplatin-based chemotherapy and those treated with adjuvant fluoropyrimidine-only chemotherapy was identified (P=0.152). Within multivariable Cox regression analysis, type of chemotherapy was not associated with a difference in overall survival (hazard ratio for fluoropyrimidine-only chemotherapy vs. oxaliplatin-based chemotherapy: 1.02; 95% CI: 0.61-1.71). CONCLUSION: Oxaliplatin-based adjuvant chemotherapy is not associated with improved survival outcomes compared with fluoropyrimidine-only chemotherapy in this real-world study.

The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.

OBJECTIVE AND BACKGROUND: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. METHODS: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. RESULTS: There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. CONCLUSIONS: R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer: Secondary Analysis of the TRIO-013/LOGiC Randomized Clinical Trial.

IMPORTANCE: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. OBJECTIVE: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib. Proton pump inhibitor use was identified by medication records. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with PPIs vs patients who were not. Specific subgroups were accounted for, such as younger age (<60 years), Asian ethnicity, female sex, and disease stage (metastatic/advanced) in multivariate Cox proportional hazards modeling. The TRIO-013 trial accrued and randomized patients between June 2008 and January 2012; this analysis took place in January 2014. INTERVENTIONS: Patients were divided based on PPI exposure. MAIN OUTCOMES AND MEASURES: Primary study outcome was PFS and OS between patients treated with PPIs vs patients who were not. Secondary outcomes included disease response rates and toxicities. RESULTS: Of the 545 patients with GEC (median age, 60 years; 406 men [74%]) included in the study, 229 received PPIs (42.0%) and were evenly distributed between arms. In the placebo arm, PPI-treated patients had poorer median PFS, 4.2 vs 5.7 months (hazard ratio [HR], 1.55; 95% CI, 1.29-1.81, P < .001); OS, 9.2 vs 11.3 months (HR, 1.34; 95% CI, 1.06-1.62; P = .04); and disease control rate (83% vs 72%; P = .02) vs patients not treated with PPIs. In multivariate analysis considering age, race, disease stage, and sex, PPI-treated patients had poorer PFS (HR, 1.68; 95% CI, 1.42-1.94; P < .001) and OS (HR, 1.41; 95% CI, 1.11-1.71; P = .001). In patients treated with CapeOx and lapatinib, PPIs had less effect on PFS (HR, 1.08; P = .54) and OS (HR, 1.26; P = .10); however, multivariate analysis in this group demonstrated a significant difference in OS (HR, 1.38; 95% CI, 1.06-1.66; P = .03). CONCLUSIONS AND RELEVANCE: Proton pump inhibitors negatively effected capecitabine efficacy by possibly raising gastric pH levels, leading to altered dissolution and absorption. These results are consistent with previous erlotinib and sunitinib studies. Whether PPIs affected lapatinib is unclear given concurrent capecitabine. Given capecitabine's prevalence in treatment breast cancer and colon cancer, further studies are under way. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00680901.

Script-theory virtual case: A novel tool for education and research.

Context/Setting: The script theory of diagnostic reasoning proposes that clinicians evaluate cases in the context of an "illness script," iteratively testing internal hypotheses against new information eventually reaching a diagnosis. We present a novel tool for teaching diagnostic reasoning to undergraduate medical students based on an adaptation of script theory. INTERVENTION: We developed a virtual patient case that used clinically authentic audio and video, interactive three-dimensional (3D) body images, and a simulated electronic medical record. Next, we used interactive slide bars to record respondents' likelihood estimates of diagnostic possibilities at various stages of the case. Responses were dynamically compared to data from expert clinicians and peers. Comparative frequency distributions were presented to the learner and final diagnostic likelihood estimates were analyzed. Detailed student feedback was collected. OBSERVATIONS: Over two academic years, 322 students participated. Student diagnostic likelihood estimates were similar year to year, but were consistently different from expert clinician estimates. Student feedback was overwhelmingly positive: students found the case was novel, innovative, clinically authentic, and a valuable learning experience. DISCUSSION: We demonstrate the successful implementation of a novel approach to teaching diagnostic reasoning. Future study may delineate reasoning processes associated with differences between novice and expert responses.

A Uridine Glucuronosyltransferase 2B7 Polymorphism Predicts Epirubicin Clearance and Outcomes in Early-Stage Breast Cancer.

BACKGROUND: Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. PATIENTS AND METHODS: A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS: The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P = .002). The CC homozygous patients had an increased risk of grade 3 to 4 leukopenia compared with the TT homozygotes or heterozygotes (P = .038 and P = .032, respectively). TT homozygotes or heterozygotes had an increased risk of early recurrence (P = .039; χ(2) test). CONCLUSION: The results of the present prospective pharmacogenetic study suggest that the UGT2B7 -161 C > T SNP correlate with drug metabolism, toxicity, and efficacy in patients receiving epirubicin chemotherapy. Further studies of this UGT2B7 SNP as a predictor of epirubicin toxicity and efficacy are warranted.

Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.

PURPOSE: Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown. PATIENTS AND METHODS: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy. RESULTS: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001). CONCLUSION: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.

Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial.

BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. METHODS: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)1= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)1 = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)1 = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients. CONCLUSIONS: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Timeliness of cancer care from diagnosis to treatment: a comparison between patients with breast, colon, rectal or lung cancer.

OBJECTIVE: The purpose of this study was to assess the value in measuring specific time intervals across cancer sites to identify potentially important variation in the timeliness of cancer care that may inform needed changes and/or improvements in coordination of care. DESIGN: Retrospective population-level study. Demographic and treatment information were obtained from the Alberta Cancer Registry. Date of oncologist-consult was obtained from cancer medical records. SETTING: Alberta, Canada. PARTICIPANTS: All patients diagnosed in 2005 with breast, colon, rectal or lung cancer who were residents of Alberta, Canada. MAIN OUTCOME MEASURES: (i) Number of days from diagnosis to first treatment by treatment modality and cancer site, (ii) number of days from surgery to post-surgery consultation and subsequent treatment and (iii) relationship between clinical and demographic factors and the cancer-specific provincial median time for outcome measures (i) and (ii). RESULTS: Time from diagnosis to surgery, if first treatment, was ∼4 months for lung cancer compared with 1-2 months for breast and colorectal cancers. Factors associated with this time interval for breast and colorectal cancers was stage at diagnosis but was region of residence for lung cancer. CONCLUSIONS: Important variation within and across cancer sites identified in the care intervals evaluated in this study provides relevant information to inform local areas for improvement. Comparisons of these intervals across healthcare systems may also provide insights into strengths of different models for coordinating care.

Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.

CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Reasons physicians do not recommend and patients refuse adjuvant chemotherapy for stage III colon cancer: a population based chart review.

BACKGROUND: Surgery followed by adjuvant chemotherapy has been the standard of care for the treatment of stage III colon cancer since the early 1990's. Despite this, large proportions of patients do not receive adjuvant chemotherapy. We aimed to identify physicians' and patients' reasons for treatment decisions. METHODS: A retrospective population based study was conducted that included all surgically treated stage III colon cancer patients diagnosed in Alberta between 2002 and 2005 who had an oncologist-consult to discuss post-surgical treatment options. Patient demographics and stage were obtained from the Alberta Cancer Registry. Chart reviews were conducted to extract treatment details, the oncologists' reasons for not recommending chemotherapy, and patients' reasons for refusing chemotherapy. The number and proportion of patients who were not recommended or refused chemotherapy were calculated. RESULTS: A total of 613 patients had surgery followed by an oncologist-consult. Overall, 168 (27%) patients did not receive chemotherapy. It was not recommended for 111 (18%) patients; the most frequent reason was presence of one or more co-morbidities (34%) or combination of co-morbidity and age or frailty (22%). Fifty-eight (9%) patients declined chemotherapy, 22% of whom declined due to concerns about toxicity. CONCLUSION: Some co-morbidities are clinical indications for not receiving adjuvant chemotherapy, however, the high percentage of patients who were not recommended adjuvant chemotherapy due to co-morbidities according to clinical notes but who had a low Charlson co-morbidity score suggests variation in practice patterns of consulting oncologists. In addition, patients' reasons for refusing treatment need to be systematically assessed to ensure patients' preferences and treatment benefits are properly weighed when making treatment decisions.

The role of bevacizumab in colorectal cancer: understanding its benefits and limitations.

INTRODUCTION: Angiogenesis is a key factor in the development of aberrant blood vessels required for malignant growth, invasion and progression. Inhibiting VEGF is by far the most clinically advanced anti-angiogenic target. Bevacizumab (BV), the only humanized mAb directed against VEGF, is approved for use in multiple tumor types after successful clinical trial results demonstrated benefits in progression-free survival and/or overall survival when combined with common cytotoxic chemotherapies. AREAS COVERED: The review focuses on the use of BV in colorectal cancer, discusses the clinical trial data supporting its increasing use and explores its limitations. Readers will gain a succinct description of the trial data demonstrating a modest survival benefit in metastatic colorectal cancer (mCRC) and the lack of benefit of BV when utilized in the adjuvant setting. A review of common BV toxicities and a discussion about possible BV resistance mechanisms are also provided. EXPERT OPINION: Although BV has demonstrated efficacy in mCRC, there is an urgent need to improve the understanding of its mechanism of action and the development of BV resistance. Furthermore, there is a need for delineating predictive markers of BV efficacy and toxicity.

Association between receipt and timing of adjuvant chemotherapy and survival for patients with stage III colon cancer in Alberta, Canada.

BACKGROUND: Surgery followed by adjuvant chemotherapy has been standard treatment for stage III colon cancer since 1990. However, to date, clinical trials have not been conducted to determine the definitive outer time limit by which adjuvant chemotherapy should be received for optimal survival benefit. The objective of the current study was to assess the association between the receipt/timing of adjuvant chemotherapy and patient survival in clinical practice. METHODS: Residents of Alberta who were diagnosed with stage III colon adenocarcinoma in years 2000 to 2005 who underwent surgery were included in the study. Patients were identified from the Alberta Cancer Registry and were linked to hospital data and neighborhood-level socioeconomic data from the 2001 Canadian Census. Cox proportional hazards models were used to estimate hazard ratios of death according to the timing of chemotherapy. RESULTS: There were 1053 patients in the study; 648 (61%) initiated adjuvant chemotherapy within 16 weeks of surgery. There was no difference in overall survival or colon cancer-specific survival between those who received adjuvant chemotherapy from 8 to 12 weeks postsurgery compared with those who received it within 8 weeks. However, those who received chemotherapy 12 to 16 weeks after surgery and those who either received it >16 weeks after surgery or received no treatment had a 43% and 107% greater risk of dying, respectively, than those who received chemotherapy within 8 weeks of surgery (hazard ratio, 1.43 [95% confidence interval, 0.96-2.13] and hazard ratio, 2.07 [95% confidence interval, 1.56-2.76], respectively). Analyses were controlled for age, year, and region of residence at diagnosis; sex; neighborhood-level socioeconomic factors; and number of comorbidities. CONCLUSIONS: The results from this study were consistent with current guideline recommendations in Alberta that patients with stage III adenocarcinoma should receive chemotherapy within 12 weeks of surgery.

Characteristics of patients with stage III colon adenocarcinoma who fail to receive guideline-recommended treatment.

BACKGROUND: Many patients with stage III colon adenocarcinoma do not receive adjuvant chemotherapy despite the proven survival advantage it offers. To enhance the provision of optimal cancer care, patient characteristics associated with not receiving guideline-adherent treatment must be identified among patients with operable, stage III colon adenocarcinoma. METHODS: This was a population-based, retrospective study of all patients who underwent surgery for stage III colon adenocarcinoma diagnosed from 2002 through 2005 in Alberta, Canada. Demographic and treatment information captured in the Alberta Cancer Registry were linked to: 1) hospital discharge data to determine comorbidities, 2) electronic medical records to identify consults with oncologists, and 3) the 2001 Canadian census for neighborhood-level socioeconomic data. Multivariate log-binomial regression models were used to identify patient characteristics that were associated with not having a consultation with a medical oncologist and not receiving adjuvant chemotherapy. RESULTS: Of the 772 patients who underwent surgery for stage III colon adenocarcinoma and met the eligibility criteria, 618 patients (80%) had a consultation with an oncologist. Of those, 388 patients (63%) initiated adjuvant chemotherapy within 84 days of their surgery. Patient characteristics that were associated with not having a consultation with an oncologist were neighborhood income, geography, age, and comorbidities. Of those patients who had a consultation, after adjusting for comorbidities, only older age was related to not receiving adjuvant chemotherapy. CONCLUSIONS: The current results indicated that the proportion of patients with stage III colon adenocarcinoma who did not receive treatment according to evidence-based guidelines was appreciable. The authors concluded that the association of this failure with patient age, geography, and income is concerning and that evaluation of referral patterns and interventions are needed.

Survival of metastatic colorectal cancer patients treated with chemotherapy in Alberta (1995-2004).

GOALS OF WORK: Clinical trials have suggested that advances in chemotherapy significantly improve the survival of patients with metastatic colorectal cancer. Comparable evidence from clinical practice is scarce. This study aims to investigate the survival of patients with metastatic colorectal cancer treated with chemotherapy in Alberta, Canada. PATIENTS AND METHODS: Trends of relative survival of patients diagnosed in 1994-2003 were assessed using Alberta Cancer Registry (ACR) data. The median overall survival (OS) of patients diagnosed in 2004 was determined by linking Cancer Registry data with Electronic Medical Records (EMR). Cox regression models were fitted to calculate the hazard ratio for patients treated with chemotherapy. RESULTS: The 2-year relative survival for patients with metastatic colorectal cancer who received chemotherapy increased significantly from 29% to 41% over the 10 years (1994-2003, p < 0.015). A 69% reduction in the risk of mortality was observed in the 168 patients who received chemotherapy compared to the 87 patients who did not, after adjusting for age, gender, and number of metastases. The median OS of patients who received chemotherapy was 17.5 months. This is comparable to the 18-20 months seen in recently published clinical trials, considering the patients in this study were from the real clinical practice, nearly half of them were older than 70, and many of them might have important co-morbidities. CONCLUSIONS: The survival of patients diagnosed with metastatic colorectal cancer in Alberta has improved in recent years; this is most likely attributable in large part to the use of chemotherapy.

Antiangiogenic agents in advanced gastrointestinal malignancies: past, present and a novel future.

Advanced gastrointestinal (GI) malignancies are varied in presentation, prognosis, and treatment options. With the exception of resectable recurrent colorectal cancer, metastatic GI malignancies are incurable. Cytotoxic chemotherapies have been the mainstay of therapy for decades but limited extension of survival or clinical benefit has been achieved in non-colorectal GI cancers. There has been great interest in the incorporation of antiangiogenic strategies to improve outcomes for these patients. Clear benefits have been identified with bevacizumab and sorafenib in colorectal cancer and hepatocellular cancer, respectively; other GI tumor sites have lacked impressive results with antiangiogenic agents. In this review, we will present the benefits, or lack thereof, of clinically tested antiangiogenic compounds in GI malignancies and explore some potential new therapeutic anti-angiogenesis options for these diseases.

Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity.

PURPOSE: Evidence suggests that lean body mass (LBM) may be useful to normalize doses of chemotherapy. Data from a prospective study were used to determine if the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin. EXPERIMENTAL DESIGN: Toxicity after cycle 1 was graded according to National Cancer Institute Common Toxicity Criteria, version 2.0. Muscle tissue was measured by computerized tomography. An extrapolation to the LBM compartment of the whole body was employed. RESULTS: Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity (P = 0.005). This observation was pertinent to women (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low proportion of LBM relative to their body surface area. CONCLUSION: Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area. We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition.

Final results of a phase II clinical trial of weekly docetaxel in combination with capecitabine in anthracycline-pretreated metastatic breast cancer.

The addition of capecitabine to docetaxel on a 3-week schedule resulted in superior response rate, increased time to progression (TTP), and improved overall survival in patients with anthracycline-pretreated metastatic breast cancer (MBC). Because the toxicity profile of weekly docetaxel differs from the standard 21-day docetaxel schedule, we performed a phase I/II trial to test the efficacy and safety of weekly docetaxel in combination with capecitabine given for 14 days every 21 days. The phase I study identified the doses of docetaxel (30 mg/m2 weekly) and capecitabine (900 mg/m2 twice daily on days 1-14 every 21 days) used in phase II. Twenty female patients with measurable or assessable MBC were enrolled. Eighteen patients had previously received anthracyclines; 2 had contraindications to anthracyclines. Patients remained on study for a maximum of eight 3-week cycles or until tumor progression or unacceptable toxicity occurred; response assessments were scheduled after cycle 2, 5, and 8. Seventeen patients were assessed after cycle 2; 3 subjects (18%) had a partial response (PR), 9 had stable disease (53%; SD), and 5 patients (29%) had progressive disease (PD). Ten patients were assessable after cycle 5. Two patients (20%) had a PR, 5 patients (50%) had SD, and 3 patients (30%) had PD. The most common grade 3 toxicities were nail loss (45%), asthenia (30%), and hand-foot syndrome (30%), and toxicities led to study discontinuation in 10 patients. The median time to treatment failure was 10 weeks and median TTP was 26 weeks. The median duration of response was 9 weeks and the median duration of SD was 16 weeks. The median overall survival was 82 weeks. This schedule of weekly docetaxel in combination with day 1-14 capecitabine has activity; however, toxicity discourages the use of this schedule in lieu of the standard docetaxel/capecitabine regimen.