Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers.

BACKGROUND: CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the unfolded protein response, has recently been identified as a metastasis suppressor in both breast and bladder cancer. METHODS: Quantitative real time PCR (qPCR) and immunoblotting were used to determine the impact of histone deacetylation and DNA methylation inhibitors on CREB3L1 expression in breast cancer cell lines. Breast cancer cell lines and tumor samples were analyzed similarly, and CREB3L1 gene methylation was determined using sodium bisulfite conversion and DNA sequencing. Immunohistochemistry was used to determine nuclear versus cytoplasmic CREB3L1 protein. Large breast cancer database analyses were carried out to examine relationships between CREB3L1 gene methylation and mRNA expression in addition to CREB3L1 mRNA expression and prognosis. RESULTS: This study demonstrates that the low CREB3L1 expression previously seen in highly metastatic breast cancer cell lines is caused in part by epigenetic silencing. Treatment of several highly metastatic breast cancer cell lines that had low CREB3L1 expression with DNA methyltransferase and histone deacetylase inhibitors induced expression of CREB3L1, both mRNA and protein. In human breast tumors, CREB3L1 mRNA expression was upregulated in low and medium-grade tumors, most frequently of the luminal and HER2 amplified subtypes. In contrast, CREB3L1 expression was repressed in high-grade tumors, and its loss was most frequently associated with triple negative breast cancers (TNBCs). Importantly, bioinformatics analyses of tumor databases support these findings, with methylation of the CREB3L1 gene associated with TNBCs, and strongly negatively correlated with CREB3L1 mRNA expression. Decreased CREB3L1 mRNA expression was associated with increased tumor grade and reduced progression-free survival. An immunohistochemistry analysis revealed that low-grade breast tumors frequently had nuclear CREB3L1 protein, in contrast to the high-grade breast tumors in which CREB3L1 was cytoplasmic, suggesting that differential localization may also regulate CREB3L1 effectiveness in metastasis suppression. CONCLUSIONS: Our data further strengthens the role for CREB3L1 as a metastasis suppressor in breast cancer and demonstrates that epigenetic silencing is a major regulator of the loss of CREB3L1 expression. We also highlight that CREB3L1 expression is frequently altered in many cancer types suggesting that it could have a broader role in cancer progression and metastasis.

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.

Low-serum GTA-446 anti-inflammatory fatty acid levels as a new risk factor for colon cancer.

Gastrointestinal tract acid-446 (GTA-446) is a long-chain polyunsaturated fatty acid present in the serum. A reduction of GTA-446 levels in colorectal cancer (CRC) patients has been reported previously. Our study compared GTA-446 levels in subjects diagnosed with CRC at the time of colonoscopy to the general population. Serum samples and pathology data were collected from 4,923 representative subjects undergoing colonoscopy and from 964 subjects from the general population. Serum GTA-446 levels were determined using a triple-quadrupole tandem mass spectrometry method. A low-serum GTA-446 level was based on the bottom tenth percentile of subjects with low risk based on age (40-49 years old) in the general population. Eighty-six percent of newly diagnosed CRC subjects (87% for stages 0-II and 85% for stages III-IV) showed low-serum GTA-446 levels. A significant increase in the CRC incidence rate with age was observed in subjects with low GTA-446 levels (p = 0.019), but not in subjects with normal levels (p = 0.86). The relative risk of CRC given a low GTA-446 level was the highest for subjects under age 50 (10.1, 95% confidence interval [C.I.] = 6.4-16.4 in the reference population, and 7.7, 95% C.I. = 4.4-14.1 in the colonoscopy population, both p < 0.0001), and declined with age thereafter. The CRC incidence rate in subjects undergoing colonoscopy with low GTA-446 levels was over six times higher than for subjects with normal GTA-446 levels and twice that of subjects with gastrointestinal symptoms. The results show that a low-serum GTA-446 level is a significant risk factor for CRC, and a sensitive predictor of early-stage disease.

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's RWE Data Working Group.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8-11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration's Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

Real-World Cost-Effectiveness of Bevacizumab With First-Line Combination Chemotherapy in Patients With Metastatic Colorectal Cancer: Population-Based Retrospective Cohort Studies in Three Canadian Provinces.

Background. Real-world evidence can be a valuable tool when clinical trial data are incomplete or uncertain. Bevacizumab was adopted as first-line therapy for metastatic colorectal cancer (mCRC) based on significant survival improvements in initial clinical trials; however, survival benefit diminished in subsequent analyses. Consequently, there is uncertainty surrounding the cost-effectiveness of bevacizumab therapy achieved in practice. Objective. To assess real-world cost-effectiveness of first-line bevacizumab with irinotecan-based chemotherapy versus irinotecan-based chemotherapy alone for mCRC in British Columbia (BC), Saskatchewan, and Ontario, Canada. Methods. Using provincial cancer registries and linked administrative databases, we identified mCRC patients who initiated publicly funded irinotecan-based chemotherapy, with or without bevacizumab, in 2000 to 2015. We compared bevacizumab-treated patients to historical controls (treated before bevacizumab funding) and contemporaneous controls (receiving chemotherapy without bevacizumab), using inverse-probability-of-treatment weighting with propensity scores to balance baseline covariates. We calculated incremental cost-effectiveness ratios (ICER) using 5-year cost and survival adjusted for censoring, with bootstrapping to characterize uncertainty. We also conducted one-way sensitivity analysis for key drivers of cost-effectiveness. Results. The cohorts included 12,112 (Ontario), 1,161 (Saskatchewan), and 2,977 (BC) patients. Bevacizumab significantly increased treatment costs, with mean ICERs between $78,000 and $84,000/LYG (life-year gained) in the contemporaneous comparisons and $75,000 and $101,000/LYG in the historical comparisons. Reducing the cost of bevacizumab by 50% brought ICERs in all comparisons below $61,000/LYG. Limitations. Residual confounding in observational data may bias results, while the use of original list prices overestimates current bevacizumab cost. Conclusion. The addition of bevacizumab to irinotecan-based chemotherapy extended survival for mCRC patients but at significant cost. At original list prices bevacizumab can only be considered cost-effective with certainty at a willingness-to-pay threshold over $100,000/LYG, but price reductions or discounts have a significant impact on cost-effectiveness.

Early discontinuation but not the timing of adjuvant therapy affects survival of patients with high-risk colorectal cancer: a population-based study.

BACKGROUND: Adjuvant therapy results in significant improvement in survival of patients with high-risk colorectal cancer. Little is known about the significance of timing and early discontinuation of adjuvant treatment in such patients. Our study aims to determine the prognostic impact of timing and completion of adjuvant therapy in patients with high-risk colorectal cancer. METHODS: Medical records of patients with stage III colon and stage II/III rectal cancer diagnosed between 1993 and 2000 in the province of Saskatchewan were reviewed. Cox proportional hazards models were used to analyze the impact of timing and completion of adjuvant therapy on survival. RESULTS: Six hundred sixty-three eligible patients with a median age of 66 years were identified. Sixty-five percent patients received adjuvant <56 days after surgery and 79% patients completed planned treatment. Median follow-up was 54.6 months. Five-year disease-free survival and overall survival of patients who received adjuvant therapy <56 days after surgery was 54.6% and 59.5%, respectively, compared with 51.9% and 57.1%, respectively, of patients who received therapy ≥56 days after surgery (P = NS). The five-year disease disease-free survival and overall survival of patients who completed planned treatment was 56.7% and 62.3%, respectively, compared with 42.1% and 45%, respectively, of patients who required early treatment discontinuation (P < .0001). On multivariate analysis, age ≥65 years, T4 tumor, grade 3 cancer, node-positive disease, rectal tumor, and early treatment discontinuation were identified as poor prognostic factors. CONCLUSIONS: Although time to adjuvant therapy following surgical resection did not impact the outcomes, failure to complete planned therapy was associated with adverse prognosis.

Cancer drug expenditure in British Columbia and Saskatchewan: a trend analysis.

BACKGROUND: Expenditure on systemic therapy for cancer has been increasing quickly owing to population growth, increased use, both in the number of users and in prescription volume, and rising drug prices. Our objective was to describe trends in expenditure in British Columbia and Saskatchewan's cancer care systems and to elucidate these drivers of growth. METHODS: In this trend analysis, we obtained pharmacy dispensing records from the BC Cancer and Saskatchewan Cancer Agency pharmacies for all anticancer therapies dispensed in 2006-2013. We calculated total annual expenditure directly from the data and conducted a trend analysis of crude and standardized annual expenditure using generalized linear models. We estimated trends in the following components of total expenditure: cancer incidence, number of systemic therapy users per incident case, number of dispensed prescriptions per user and cost per prescription. Analysis was stratified by patient age group, cancer site and route of administration (oral or intravenous/other). RESULTS: Expenditure on systemic therapies, adjusted for population growth and aging, increased an average of 9.2% (95% confidence interval [CI] 7.2 to 11.2) per year in Saskatchewan and 6.4% (95% CI 5.3 to 7.6) per year in BC. Growth in expenditure on orally administered agents was more than 2 times higher than growth in expenditure on intravenous/other agents. Growth rates varied significantly by cancer site. In both provinces, rising cost per prescription was the largest contributor to overall growth. INTERPRETATION: Price is the primary driver of growth in systemic therapy expenditure in both BC and Saskatchewan. Understanding the mechanisms of expenditure growth may inform system planning and support policy-makers' efforts to manage rising costs.

Across-province standardization and comparative analysis of time-to-care intervals for cancer.

BACKGROUND: A set of consistent, standardized definitions of intervals and populations on which to report across provinces is needed to inform the Provincial/Territorial Deputy Ministries of Health on progress of the Ten-Year Plan to Strengthen Health Care. The objectives of this project were to: 1) identify a set of criteria and variables needed to create comparable measures of important time-to-cancer-care intervals that could be applied across provinces and 2) use the measures to compare time-to-care across participating provinces for lung and colorectal cancer patients diagnosed in 2004. METHODS: A broad-based group of stakeholders from each of the three participating cancer agencies was assembled to identify criteria for time-to-care intervals to standardize, evaluate possible intervals and their corresponding start and end time points, and finalize the selection of intervals to pursue. Inclusion/exclusion criteria were identified for the patient population and the selected time points to reduce potential selection bias. The provincial 2004 colorectal and lung cancer data were used to illustrate across-province comparisons for the selected time-to-care intervals. RESULTS: Criteria identified as critical for time-to-care intervals and corresponding start and end points were: 1) relevant to patients, 2) relevant to clinical care, 3) unequivocally defined, and 4) currently captured consistently across cancer agencies. Time from diagnosis to first radiation or chemotherapy treatment and the smaller components, time from diagnosis to first consult with an oncologist and time from first consult to first radiation or chemotherapy treatment, were the only intervals that met all four criteria. Timeliness of care for the intervals evaluated was similar between the provinces for lung cancer patients but significant differences were found for colorectal cancer patients. CONCLUSION: We identified criteria important for selecting time-to-care intervals and appropriate inclusion criteria that were robust across the agencies that did not result in an overly selective sample of patients to be compared. Comparisons of data across three provinces of the selected time-to-care intervals identified several important differences related to treatment and access that require further attention. Expanding this collaboration across Canada would facilitate improvement of and equitable access to quality cancer care at a national level.

Time to adjuvant therapy and other variables in localized gastric and gastroesophageal junction (GEJ) cancer (IJGC-D-13-00162).

BACKGROUND: Adjuvant chemotherapy with or without radiation in patients with completely resected gastric and gastroesophageal (GE) junction cancer has been associated with better outcomes. In practice, however, there are often delays in commencing adjuvant therapy. The study aims to determine the prognostic importance of timing of adjuvant therapy in such patients. METHODS: A cohort of patients with early stage (IB-IVM0) gastric and GE junction cancer diagnosed between 2002 and 2007 in the province of Saskatchewan was assessed. Cox proportional hazard analysis was used to identify various clinic-pathological factors that correlate with disease-free survival (DFS). RESULTS: One hundred seventy-four eligible patients with a median age of 71 years (range 36-93) and M/F ratio of 113:61 were identified. Of 174 patients, 60 (35%) received adjuvant therapy. Median follow-up was 18 months (interquartile range 9-37). Twenty-eight percent received adjuvant therapy within 56 days. Median DFS of patients who received adjuvant therapy within 56 days was 37 months (95% CI 6.6-67.3) versus 33 months (95% CI 18.3-47.7) if adjuvant therapy was administered beyond 56 days (p = 0.67). On multivariate analysis, state III-IVM0 disease, hazard ratio (HR) 2.4 (95% CI 1.6-3.5), and age ≥65 years, HR 2.2 (95% CI 1.4-3.5), were significantly correlated with inferior disease-free survival. CONCLUSIONS: Only about one third of patients who received adjuvant therapy were treated within 56 days of surgery. Although stages III and IVM0 and older age were associated with inferior outcome, delay in adjuvant therapy was not associated with inferior survival.

Comparison of treatment received versus long-standing guidelines for stage III colon and stage II/III rectal cancer patients diagnosed in Alberta, Saskatchewan, and Manitoba in 2004.

PURPOSE: Guideline-recommended treatment for stage II/III colorectal cancer includes postsurgical chemotherapy and/or radiation as standard of care. This study measures adherence to guidelines across 3 Canadian provinces and evaluates the relationship of patient characteristics with receiving standard care. PATIENTS AND METHODS: All surgically treated patients diagnosed in 2004 with stage III colon or stage II/III rectal cancer and residing in Alberta, Saskatchewan, or Manitoba were identified from provincial cancer registries. Sex, age at diagnosis, and area of residence were also obtained from the cancer registry. The primary outcome of interest was receipt of standard care: surgery followed by chemotherapy or radiation therapy (adjuvant therapy). chi2 tests and binary regression with log link assessed the relationship of patient demographic characteristics (age, sex, residence, cancer disease stage) with receipt of standard care. RESULTS: About half of the patients received adjuvant therapy. Patients with stage III rectal cancer were more likely to receive adjuvant treatment than stage II patients in Alberta and Saskatchewan. There was a large decrease in the percentage of patients who received adjuvant treatment with increasing age in all the provinces (P < .001), ranging from about 80% of those aged < 65 years to about 20% of those aged >or= 75 years for colon cancer patients and from about 70% to 30%, respectively, for rectal cancer patients. The decrease of adjuvant treatment with increasing age was most marked in Alberta. CONCLUSION: The percentage of patients receiving guideline-recommended treatment is low. Reasons for lack of adherence to guidelines need to be addressed.

Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT).

PURPOSE: Prostate cancer is the leading form of cancer diagnosed among North American men. Most patients present with localized disease, which can be effectively treated with a variety of different modalities. These are associated with widely different acute and late effects, which can be both physical and psychological in nature. HRQoL concerns are therefore important for these patients for selecting between the different treatment options. MATERIALS AND METHODS: One year after receiving radiotherapy for localised prostate cancer 117 patients with localized prostate cancer were invited to participate in a quality of life (QoL) self reported survey. 111 patients consented and participated in the survey, one year after completion of their treatment. 88 patients received EBRT and 23 received EBRT and HDRBT. QoL was compared in the two groups by using a modified version of Functional Assessment of Cancer Therapy-Prostate (FACT-P) survey instrument. RESULTS: One year after completion of treatment, there was no significant difference in overall QoL scores between the two groups of patients. For each component of the modified FACT-P survey, i.e. physical, social/family, emotional, and functional well-being; there were no statistically significant differences in the mean scores between the two groups. CONCLUSION: In prostate cancer patients treated with EBRT alone versus combined EBRT and HDRBT, there was no significant difference in the QoL scores at one year post-treatment.

Extrapulmonary small cell cancer: a Canadian province's experience.

BACKGROUND: The objective of this study was to determine variables that correlate with the survival of patients with extrapulmonary small cell carcinoma (EPSCC). METHODS: Medical records of 101 eligible patients with EPSCC who were diagnosed in Saskatchewan from 1971 to 2002 were reviewed. Survival was calculated by using the Kaplan-Meier method. A logistic regression analysis with a backward elimination was carried out to determine prognostic variables that predicted mortality. RESULTS: The median patient age was 72 years (range, 24-100 years), and the male-to-female ratio was 1.4:1. The primary disease sites were as follows: breast, 9%; gastrointestinal, 20%; genitourinary, 18%; gynecologic, 11%; head and neck, 10%; thymus, 2%; and unknown primary site, 31%. Fifty-one patients had limited disease (LD), and 50 patients had extensive disease (ED). Patients with LD had a median overall survival of 34 months (range, 0.2-276 months) compared with 2 months (range, 0.1-108 months) in patients with ED (P < .0001). Among different primary sites, patients with gynecologic small cell cancer (SCC) had a median survival of 54.4 months, whereas patients with SCC of an unknown primary site had a survival of 2.5 months. Among various variables that were examined with respect to their prognostic importance, an abnormal white blood cell count (odds ratio [OR], 6.9; 95% confidence interval [95% CI], 3.4-14.1), an Eastern Cooperative Oncology Group performance status >2 (OR, 4.5; 95% CI, 2.1-9.9), and ED (OR, 2.7; 95% CI, 1.4-5.0) were found to be correlated significantly with mortality. CONCLUSIONS: The gastrointestinal and genitourinary tracts were the 2 major sites involved by EPSCC in the current series. Survival varied according to the primary sites, and patients with gynecologic tumors had the best prognosis. An abnormal white blood cell count, a poor performance status, and disease extent were important factors in predicting survival.

Women with multiple primary breast cancers diagnosed within a five year period, 1994-1998.

INTRODUCTION: Women diagnosed with a primary breast cancer are at higher risk for a second primary. Few studies have focused on a comparison of women with single breast primary cancers and women with multiple primary breast cancers. The 1994-1998 NAACCR dataset aggregated from high quality registries representing more than one-third of the US population provides a unique opportunity to examine the incidence of multiple primary breast cancers in a large population. MATERIALS AND METHODS: Using this multi-registry dataset, we describe the incidence pattern of malignant synchronous (within 2 months) and short-term metachronous (from 3 to 60 months) multiple primaries and single primary breast cancers by demographic and tumor characteristics. RESULTS: Synchronous multiple primary tumors were more similar in age, stage, and tumor grade to single breast tumors than they were to short-term metachronous tumors. The short-term metachronous tumors did not resemble either the synchronous tumors or the single primaries. DISCUSSION: These findings may indicate that while synchronous multiple primaries may have treatment implications different from single primaries, their etiology may be similar to single breast primaries. Further, they may actually be multi-centric single primaries. The two-month interval between multiple primaries is arbitrary and may not distinguish between the synchronous tumors and those occurring within 12 months of the index tumor. The rules for defining and counting breast primaries have implications for interpretation of incidence rates and temporal trends. These data also suggest the need for standard definitions for multiple primary breast tumors among clinicians, pathologists, and surveillance epidemiologists.