Does the presence of an intact primary increase the risk of nonelective colorectal surgery in patients treated with bevacizumab?

AIM: In patients with incurable metastatic colorectal cancer (mCRC), resection of the primary tumour is debated; however, patients with intact primaries may be at a higher risk of complications requiring surgery when receiving treatment with bevacizumab. Our aim was to estimate the risk of nonelective colorectal surgery in patients undergoing bevacizumab therapy for mCRC and evaluate the association between intact primary tumours and risk of nonelective surgery. METHOD: We designed a population-based, retrospective cohort study using administrative and cancer registry data in Ontario, Canada. We included patients with mCRC who received bevacizumab from 1 January 2008 to 31 December 2014. The primary outcome was nonelective colorectal surgery after initiation of bevacizumab. We determined the cumulative incidence of nonelective colorectal surgery among patients with previously resected and unresected primaries, accounting for the competing risk of death. We explored the relationship between previous resection of the primary and need for nonelective surgery using a cause-specific hazards model, controlling for patient, tumour and treatment factors. RESULTS: We identified 1840 (32.7%) patients with intact primaries and 3784 (67.3%) patients with prior resection. The cumulative incidence of nonelective surgery 1 year after initiating bevacizumab for all patients was 3.9% (95% CI 3.4-4.5%). One-year cumulative incidence was higher in those with intact primaries than in those with resected primaries (6.1% vs 2.9%, P < 0.0001). After adjustment, an intact primary remained strongly associated with nonelective colorectal surgery (hazard ratio = 2.89, 95% CI 2.32-3.61; P < 0.0001). CONCLUSION: Bevacizumab is associated with a low but meaningful risk for serious gastrointestinal complications, necessitating vigilance, particularly among patients with an intact primary tumour.

Population-based study of the prevalence and management of self-reported high pain scores in patients with non-resected pancreatic adenocarcinoma.

BACKGROUND: Pain is a common debilitating symptom in pancreatic adenocarcinoma. This cohort study examined the use of, and factors associated with, pain-directed interventions for a high pain score in patients with non-curable pancreatic adenocarcinoma. METHODS: Administrative databases were linked and patients with non-resected pancreatic adenocarcinoma diagnosed between 2010 and 2016, who reported one or more Edmonton Symptom Assessment System (ESAS) score, were identified. A high pain score was defined as an ESAS score of at least 4. Outcomes were pain-directed interventions: opiates (in patients aged 65 years or more with universal drug coverage), nerve block and radiation therapy for a high pain score. Reduction in pain score of at least 1 point after pain-directed intervention was also evaluated. Modified Poisson regression was used to examine factors associated with pain-directed intervention. RESULTS: Among 2623 patients with a median age of 67 years, 1223 (46·6 per cent) were women, and 1621 (61·8 per cent) reported a high pain score at a median of 38 days after diagnosis. Of those with a high pain score, 75·6 per cent (688 of 910) received opiates, 13·5 per cent (219 of 1621) radiation and 1·2 per cent (19 of 1621) nerve block. The pain score decreased in 62·1 per cent of patients after administration of opiates, 73·4 per cent after radiation and all patients after nerve block. In multivariable analysis, no patient factor (age, sex, co-morbidity burden, rurality, income quintile) was associated with receipt of non-opiate pain-directed intervention for a high pain score. In patients aged at least 65 years, advanced age was associated with lower odds of opiate use. CONCLUSION: Opiates are the most common pain-directed intervention for non-curable pancreatic adenocarcinoma, whereas radiation therapy and nerve blocks are seldom used. The lack of association between pain-directed interventions and patient factors points toward practice-driven patterns.

ANTECEDENTES: El dolor es un síntoma debilitante frecuente en el adenocarcinoma de páncreas. Este estudio de cohortes examinó el uso de las intervenciones dirigidas para el tratamiento del dolor y los factores asociados a las mismas en pacientes con adenocarcinoma pancreático incurable que presentaban puntuaciones altas de dolor. MÉTODOS: Se revisaron las bases de datos administrativas y se identificaron los pacientes con adenocarcinoma pancreático no resecado diagnosticados entre 2010-2016 con puntuaciones > 1 del Sistema de Evaluación de Síntomas de Edmonton (Edmonton Symptom Assessment System, ESAS). La puntuación alta de dolor se definió como ESAS > 4. Los resultados evaluados fueron las intervenciones dirigidas contra el dolor: opiáceos (en pacientes mayores de 65 años con cobertura universal de medicamentos), bloqueo nervioso y radioterapia en el caso de puntuación alta del dolor. También se evaluó la reducción en la puntuación del dolor (> 1 punto) después de la intervención dirigida contra el dolor. Los factores asociados a la intervención contra el dolor se analizaron mediante una regresión de Poisson modificada. RESULTADOS: De los 2.623 pacientes con una mediana de edad de 67 años, 1.223 (46,6%) eran mujeres, y 1.621 (61.8%) presentaron una puntuación alta de dolor con una mediana de 38 días desde el momento del diagnóstico. De aquellos con puntuación alta de dolor, el 75,6% recibió opiáceos (n = 688/910), el 13,5% radiación (n = 219/1.621) y el 1,2% bloqueo nervioso (n = 19/1.621). La puntuación del dolor disminuyó en el 62,2% después del tratamiento con los opiáceos, en el 73,8% después de la radiación y en el 100% después del bloqueo nervioso. En el análisis multivariable, ningún factor relacionado con el paciente (edad, sexo, comorbilidades, vivir en una zona rural, quintil de ingresos) se asoció con una intervención dirigida contra dolor sin opiáceos en los casos de puntuación alta del dolor. En pacientes mayores de 65 años, la edad avanzada se asoció con menor probabilidad de uso de opiáceos. CONCLUSIÓN: Mientras que los opiáceos son la intervención dirigida contra dolor más común para el adenocarcinoma pancreático no resecable, la radioterapia y el bloqueo nervioso rara vez se usan. La falta de asociación de las intervenciones dirigidas contra el dolor con los factores del paciente apunta hacia el uso de patrones terapéuticos basados ​​en la práctica clínica.

Mental health services use by melanoma patients receiving adjuvant interferon: association of pre-treatment mental health care with early discontinuation.

BACKGROUND: Although high-dose interferon (hd-ifn) is the sole approved adjuvant systemic treatment for melanoma in many jurisdictions, it is toxic. We sought to assess the population-level effects of hd-ifn toxicity, particularly neuropsychiatric toxicity, hypothesizing that such toxicity would have the greatest effect on mental health services use in advanced resected melanoma. METHODS: This retrospective population-based registry study considered all melanoma patients receiving adjuvant hd-ifn in Ontario during 2008-2012. Toxicity was investigated through health services use compatible with hd-ifn toxicity (for example, mental health physician billings). Using stage data reported from cancer centres about a subset of patients (stages iib-iiic), a propensity-matched analysis compared such service use in patients who did and did not receive hd-ifn. Associations between early hd-ifn discontinuation and health services use were examined. RESULTS: Of 718 melanoma patients who received hd-ifn, 12% were 65 years of age and older, and 83% had few or no comorbidities. One third of the patients experienced 1 or more toxicity-associated health care utilization events within 1 year of starting hd-ifn. Of 420 utilization events, 364 (87%) were mental health-related, with 54% being family practitioner visits, and 39% being psychiatrist visits. In the propensity-matched analysis, patients receiving hd-ifn were more likely than untreated matched controls to use a mental health service (p = 0.01), with 42% of the control group and 51% of the hd-ifn group using a mental health service in the period spanning the 12 months before to the 24 months after diagnosis. In the multivariable analysis, early drug discontinuation was more likely in the presence of pre-existing mental health issues (odds ratio: 2.0; 95% confidence limits: 1.1, 3.4). CONCLUSIONS: Stage iib-iiic melanoma patients carry a substantial burden of mental health services use whether or not receiving hd-ifn, highlighting an important survivorship issue for these patients. High-dose interferon is associated with more use of mental health services, and pre-treatment use of mental health services is associated with treatment discontinuation. That association should be kept in mind when hd-ifn is being considered.

Radiation costing methods: a systematic review.

OBJECTIVE: Costs for radiation therapy (rt) and the methods used to cost rt are highly diverse across the literature. To date, no study has compared various costing methods in detail. Our objective was to perform a thorough review of the radiation costing literature to identify sources of costs and methods used. METHODS: A systematic review of Ovid medline, Ovid oldmedline, embase, Ovid HealthStar, and EconLit from 2005 to 23 March 2015 used search terms such as "radiation," "radiotherapy," "neoplasm," "cost," " cost analysis," and "cost benefit analysis" to locate relevant articles. Original papers were reviewed for detailed costing methods. Cost sources and methods were extracted for papers investigating rt modalities, including three-dimensional conformal rt (3D-crt), intensity-modulated rt (imrt), stereotactic body rt (sbrt), and brachytherapy (bt). All costs were translated into 2014 U.S. dollars. RESULTS: Most of the studies (91%) reported in the 33 articles retrieved provided rt costs from the health system perspective. The cost of rt ranged from US$2,687.87 to US$111,900.60 per treatment for imrt, followed by US$5,583.28 to US$90,055 for 3D-crt, US$10,544.22 to US$78,667.40 for bt, and US$6,520.58 to US$19,602.68 for sbrt. Cost drivers were professional or personnel costs and the cost of rt treatment. Most studies did not address the cost of rt equipment (85%) and institutional or facility costs (66%). CONCLUSIONS: Costing methods and sources were widely variable across studies, highlighting the need for consistency in the reporting of rt costs. More work to promote comparability and consistency across studies is needed.

Trends in health care utilization and costs attributable to hepatocellular carcinoma, 2002-2009: a population-based cohort study.

BACKGROUND: The incidence of hepatocellular carcinoma (hcc) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to hcc in Ontario, and rate ratios of resource use at various stages of care. METHODS: This population-based retrospective cohort study identified hcc patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (hcc patients vs. the matched control subjects) and net costs of care attributable to hcc. Generalized linear models were used to analyze rate ratios of resource use. RESULTS: We identified 2832 hcc patients and 2808 matched control subjects. In comparison with the control subjects, hcc patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient-days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008-2009 and 2002-2003 respectively). CONCLUSIONS: In hcc, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control.

Predictors of adjuvant treatment for pancreatic adenocarcinoma at the population level.

BACKGROUND: In the present study, we aimed to describe, at the population level, patterns of adjuvant treatment use after curative-intent resection for pancreatic adenocarcinoma (pcc) and to identify independent predictors of adjuvant treatment use. METHODS: In this observational cohort study, patients undergoing pcc resection in the province of Ontario (population 13 million) during 2005-2010 were identified using the provincial cancer registry and were linked to administrative databases that include all treatments received and outcomes experienced in the province. Patients were defined as having received chemotherapy (ctx), chemoradiation (crt), or observation (obs). Clinicopathologic factors associated with the use of ctx, crt, or obs were identified by chi-square test. Logistic regression analyses were used to identify independent predictors of adjuvant treatment versus obs, and ctx versus crt. RESULTS: Of the 397 patients included, 75.3% received adjuvant treatment (27.2% crt, 48.1% ctx) and 24.7% received obs. Within a single-payer health care system with universal coverage of costs for ctx and crt, substantial variation by geographic region was observed. Although the likelihood of receiving adjuvant treatment increased from 2005 to 2010 (p = 0.002), multivariate analysis revealed widespread variation between the treating hospitals (p = 0.001), and even between high-volume hepatopancreatobiliary hospitals (p = 0.0006). Younger age, positive lymph nodes, and positive surgical resection margins predicted an increased likelihood of receiving adjuvant treatment. Among patients receiving adjuvant treatment, positive margins and a low comorbidity burden were associated with crt compared with ctx. CONCLUSIONS: Interinstitutional medical practice variation contributes significantly to differential patterns in the rate of adjuvant treatment for pcc. Whether such variation is warranted or unwarranted requires further investigation.

A population-based study of the epidemiology of pancreatic cancer: a brief report.

OBJECTIVE: Administrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc. METHODS: Incident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. RESULTS: During the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. CONCLUSIONS: The mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

Population-based utilization of radiation therapy by a Canadian breast cancer cohort.

We examined trends in radiation therapy (rt) utilization by a population-based breast cancer cohort in Ontario. The provincial cancer registry provided a breast cancer cohort based on diagnosis dates from April 1, 2005, to March 31, 2010. Staging information was also available. The cohort was then linked, by encrypted health card number, to linkable administrative datasets, including rt utilization. The average age in the identified female breast cancer cohort (n = 39,656) was 61.6 ± 14.0 years. Almost two thirds of the patients (n = 25,225) received rt, and staging information was available for 22,988 patients (9541 stage i, 8516 stage ii, 4050 stage iii, and 881 stage iv). The average number of rt courses received by the patients was 1.4 ± 0.7 for stage i, 1.8 ± 1.1 for stage ii, 2.5 ± 1.3 for stage iii, and 2.8 ± 2.4 for stage iv. The ratio of conventional rt to intensity-modulated rt was 70.9%:16.6% for stage i, 71.6%:11.3% for stage ii, 74.6%:4.6% for stage iii, and 89.6%:2.2% for stage iv. From 2005 to 2010, almost two thirds of a Canadian female breast cancer cohort received rt, and the average number of courses increased with disease severity. A similar trend was observed with the type of rt (use of conventional rt increased with disease severity). The next step is to apply unit costs to the number of fractions and to obtain rt planning and radiation therapist times.

Health system costs for stage-specific breast cancer: a population-based approach.

OBJECTIVE: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage. METHODS: Incident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. RESULTS: This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. CONCLUSIONS: Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

Comparative Effectiveness of FOLFIRINOX Versus Gemcitabine and Nab-paclitaxel in Initially Unresectable Locally Advanced Pancreatic Cancer: A Population-based Study to Assess Subsequent Surgical Resection and Overall Survival.

AIMS: First-line FOLFIRINOX (FOLinic acid, Fluorouracil, IRINotecan, and OXaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have been publicly funded for patients with unresectable locally advanced pancreatic cancer (uLAPC) in Ontario, Canada. We examined the overall survival and surgical resection rate after first-line FOLFIRINOX or GnP and determined the association between resection and overall survival in patients with uLAPC. MATERIALS AND METHODS: We conducted a retrospective population-based study including patients with uLAPC who received first-line treatment FOLFIRINOX or GnP from April 2015 to March 2019. The cohort was linked to administrative databases to ascertain demographic and clinical characteristics. Propensity score methods were used to balance differences between FOLFIRINOX and GnP. The Kaplan-Meier method was used to calculate overall survival. Cox regression was used to determine the association between receipt of treatment and overall survival, adjusting for time-dependent surgical resections. RESULTS: We identified 723 patients with uLAPC (mean age = 65.8, 43.5% female) who received FOLFIRINOX (55.2%) or GnP (44.8%). The median overall survival and 1-year overall survival probability were higher for FOLFIRINOX (13.7 months, 54.6%) than for GnP (8.7 months, 34.0%). Post-chemotherapy surgical resection occurred in 89 (12.3%) patients (FOLFIRINOX: 74 [18.5%] versus GnP: 15 [4.6%]), with no difference in survival since surgery between FOLFIRINOX and GnP (P = 0.29). After adjusting time-dependent post-treatment surgical resection, FOLFIRINOX (inverse probability treatment weighting hazard ratio 0.72, 95% confidence interval 0.61, 0.84) was independently associated with improved overall survival. CONCLUSIONS: In this real-world population-based study of patients with uLAPC, FOLFIRINOX was associated with improved survival and higher resection rates. FOLFIRINOX was associated with improved survival in patients with uLAPC after accounting for the effect of post-chemotherapy surgical resection, suggesting the benefit of FOLFIRINOX was not solely due to improving resectability.

Population-based home care services in breast cancer: utilization and costs.

OBJECTIVE: To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc). METHODS: Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005-2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis. RESULTS: Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient-year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient-year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased. INTERPRETATION: Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population.

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

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

Meeting the 12 lymph node (LN) benchmark in colon cancer.

BACKGROUND: Examining >or=12 LN in colon cancer has been suggested as a quality metric. The purpose of this study was to determine whether the 12 LN benchmark is achieved at NCCN centers compared to a US population-based sample. METHODS: Patients with stage I-III disease resected at NCCN centers were identified from a prospective database (n = 718) and were compared to 12,845 stage I-III patients diagnosed in a SEER region. Age, gender, location, stage, number of positive nodes were compared for NCCN and SEER data in regards to number of nodes evaluated. Multivariate logistic regression models were developed to identify factors associated with evaluating 12 LNs. RESULTS: 92% of NCCN and 58% of SEER patients had >or=12 LN evaluated. For patients treated at NCCN centers, factors associated with not meeting the 12 LN target were left-sided tumors, stage I disease and BMI >30. CONCLUSIONS: >or=12 LN are almost always evaluated in NCCN patients. In contrast, this target is achieved in 58% of SEER patients. With longer follow-up of the NCCN cohort we will be able to link this quality metric to patterns of recurrence and survival and thereby better understand whether increasing the number of nodes evaluated is a priority for cancer control.

Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer.

BACKGROUND: Recent studies have examined the addition of docetaxel to fluorouracil and cisplatin in advanced esophagogastric cancer. PATIENTS AND METHODS: We carried out a phase I dose-escalation study of weekly docetaxel, cisplatin, and irinotecan (TPC), given on days 1 and 8 every 3 weeks, in patients with chemonaive solid tumors. Subsequently, we completed a multiinstitutional phase II study of TPC in patients with previously untreated, metastatic esophagogastric cancer. RESULTS: Thirty-nine patients were enrolled in the phase I trial; a weekly schedule of TPC was well tolerated. On that basis, docetaxel 30 mg/m(2), cisplatin 25 mg/m(2), and irinotecan 65 mg/m(2) were selected for the phase II trial, where in the first 18 patients irinotecan 65 mg/m(2) caused too much diarrhea and was reduced to 50 mg/m(2). Among 56 eligible patients with previously untreated, metastatic esophagogastric cancer enrolled in the phase II trial, three complete and 27 partial responses were observed (overall response rate=54%), and 15 patients (30%) had stable disease. Median progression-free survival was 7.1 months, and median survival was 11.9 months. At the final irinotecan dose of 50 mg/m(2), grade 3 or higher toxicity included diarrhea (26%), neutropenia (21%), nausea (18%), fatigue (16%), anorexia (13%), and thrombosis/embolism (13%). CONCLUSIONS: Weekly TPC is an active and well-tolerated regimen for patients with esophagogastric cancer.

Effect of lymph node retrieval rates on the utilization of adjuvant chemotherapy in stage II colon cancer.

BACKGROUND: Failing to meet the benchmark of 12 lymph nodes in resection specimens is an indication for adjuvant chemotherapy in stage II colon cancer. METHODS: Among consecutive eligible patients with pathologic stage II colon cancer treated at eight NCI-designated comprehensive cancer centers between September 1, 2005 and February 19, 2008, we analyzed receipt of adjuvant chemotherapy, with less than 12 versus 12+ lymph nodes removed and examined the primary explanatory variable of interest. RESULTS: Among 258 patients, 46% received adjuvant chemotherapy. An oxaliplatin-containing regimen was used 67% of the time. Younger age (<50 years, P < 0.001), presence of lymphovascular invasion (P = 0.007), and higher T stage (P = 0.007) were independently associated with adjuvant chemotherapy use. There was significant inter-institutional variability in practice with the proportion receiving treatment ranging from 17% to 64% (P < 0.05). Notably, presence of less than 12 lymph nodes in the surgical specimen was a strong predictor of treatment (P = 0.008). CONCLUSIONS: Adjuvant chemotherapy use after resection of stage II colon cancer is common, but by no means standard practice at National Comprehensive Cancer Network (NCCN) institutions. More attention to achieving the recommended benchmark for lymph node dissection has the potential to decrease exposure to the toxicity of adjuvant treatment.

Lessons learned from a cancer knowledge translation grants program: results of an evaluation.

Background: A novel way to build capacity in knowledge translation (kt) is through kt-focused grant competitions. Since 2009, the Knowledge Translation Research Network (KT-Net) has had a cancer-related kt grants program. We undertook an evaluation of the program to determine if KT-Net was achieving its aims of building capacity in cancer kt, advancing the science of kt, building partnerships, and leveraging funding. Methods: An adapted framework guided the evaluation. Nine funded studies from 4 competitions were included. Semi-structured telephone interviews were held with researchers, stakeholders (including knowledge users), members of grant review panels, and experts in kt. Interview transcripts were audio-recorded, transcribed, and analyzed thematically. A review of proposal and report documents was also conducted. Results: Funded researchers indicated that the grant competition was an essential funding program for cancer kt research. Competitions were perceived to build capacity in cancer kt among early-career researchers and to encourage innovative cancer kt research for which alternative funding sources are limited. The grants program resulted in incremental gains in advancing the science of kt. Suggestions to improve the program included stronger partnerships between the funder and the provincial cancer-system organization to optimize the application of research that is relevant to the organization's strategic objectives. Conclusions: The grants program met many of its aims by providing cancer researchers with an opportunity to gain capacity in cancer kt and by making incremental advances in kt science. Suggestions to improve the program included closer partnerships between the funder and the cancer-system organization.

Population-based study of the impact of surgical and adjuvant therapy at the same or a different institution on survival of patients with pancreatic adenocarcinoma.

Background: Pancreatic cancer surgery is increasingly regionalized in high-volume centres. Provision of adjuvant chemotherapy in the same institution can place a burden on patients, whereas receiving adjuvant chemotherapy at a different institution closer to home may create disparities in care. This study compared long-term outcomes of patients with pancreatic adenocarcinoma receiving adjuvant chemotherapy at the institution where they had undergone surgery with outcomes for those receiving chemotherapy at a different institution. Methods: This was a population-based study of patients receiving adjuvant chemotherapy after resection of pancreatic adenocarcinoma performed at ten designated hepatopancreatobiliary centres in Ontario, Canada, between 2004 and 2014. Patients were divided into those receiving chemotherapy at the same institution as surgery or a different institution from where surgery was performed. The primary outcome was overall survival (OS). Multivariable Cox regression assessed the association between OS and each chemotherapy group, adjusted for potential confounders. Results: Of 589 patients, 374 (63·5 per cent) received adjuvant chemotherapy at the same institution as surgery. After adjusting for age, sex, co-morbidity, socioeconomic status, rural living, tumour stage, margin positivity and year of surgery, the location of adjuvant chemotherapy was not independently associated with OS (hazard ratio 1·03, 95 per cent c.i. 0·85 to 1·24). For patients who underwent chemotherapy at a different institution, mean travel distance to receive chemotherapy was less (22·9 km) than that needed for surgery (106·7 km). Conclusion: After pancreatectomy for pancreatic adenocarcinoma at specialized hepatopancreatobiliary surgery centres, OS was not affected by the location of the centre delivering adjuvant chemotherapy. Receiving this treatment in a local centre reduced patients' travel burden.

The generation of two specific cancer costing algorithms using Ontario administrative databases.

Cancer treatment and management have become increasingly economically burdensome. Consequently, to help with planning health service delivery, it is vital to understand the associated costs. Administrative databases can be used to help understand and generate real-world system-level costs. Using databases to generate costs can take one of two approaches: top-down or bottom-up. Top-down approaches disaggregate the total health care spending from a global health care budget by sector and provider. A bottom-up approach begins with individual-level health care use and its costs, which are then aggregated.

The north-south and east-west gradient in colorectal cancer risk: a look at the distribution of modifiable risk factors and incidence across Canada.

Colorectal cancer (crc) is the 2nd most common cancer in Canada and the 2nd leading cause of cancer death. That heavy burden can be mitigated given the preventability of crc through lifestyle changes and screening. Here, we describe the extent of the variation in crc incidence rates across Canada and the disparities, by jurisdiction, in the prevalence of modifiable risk factors known to contribute to the crc burden. Findings suggest that there is a north-south and east-west gradient in crc modifiable risk factors, including excess weight, physical inactivity, excessive alcohol consumption, and low fruit and vegetable consumption, with the highest prevalence of risk factors typically found in the territories and Atlantic provinces. In general, that pattern reflects the crc incidence rates seen across Canada. Given the substantial interjurisdictional variation, more work is needed to increase prevention efforts, including promoting a healthier diet and lifestyle, especially in jurisdictions facing disproportionately higher burdens of crc. Based on current knowledge, the most effective approaches to reduce the burden of crc include adopting public policies that create healthier environments in which people live, work, learn, and play; making healthy choices easier; and continuing to emphasize screening and early detection. Strategic approaches to modifiable risk factors and mechanisms for early cancer detection have the potential to translate into positive effects for population health and fewer Canadians developing and dying from cancer.

Outcomes research in oncology: history, conceptual framework, and trends in the literature.

"Outcomes research" is a commonly used term, but what does it really mean? In this review article, we 1) briefly review the historic background of outcomes research, paying particular attention to the social and political movements that helped shape the field; 2) present a conceptual framework to help classify the major areas of research and provide a working definition of outcomes research; and 3) review the oncology literature in the English language from 1966 through 1998 to examine temporal trends and characterize the body of work being presented to the practicing oncology community. We conclude that outcomes research is a broad concept, which, in its current usage, describes an array of distinct types of research. However, common themes are apparent when outcomes research is viewed in the context of its historic origins and is contrasted with other established disciplines, especially clinical trials. Our literature review shows that outcomes studies are increasing in absolute numbers, in relative proportion of the oncology literature, and in quality. We suggest that as different branches of investigation develop their own literature and methodology-in effect, outgrowing the generic label of outcomes research-they become identified by separate, more precise terms.