Industry Funding of Oncology Randomised Controlled Trials: Implications for Design, Results and Interpretation.

AIMS: Most randomised controlled trials (RCTs) in oncology are now funded by the pharmaceutical industry. We explore the extent to which RCT design, results and interpretation differ between industry-funded and non-industry-funded RCTs. MATERIALS AND METHODS: In this cross-sectional analysis, a structured literature search was used to identify all oncology RCTs published globally during 2014-2017. Industry funding was identified based on explicit statements in the publication. Descriptive statistics were used to compare elements of trial methodology and output between industry- and non-industry-funded RCTs. RESULTS: The study sample included 694 RCTs; 71% were funded by industry. Industry-funded trials were more likely to test systemic therapy (97% versus 62%; P < 0.001), palliative-intent therapy (71% versus 41%; P < 0.001) and study breast cancer (20% versus 12%; P < 0.001). Industry-funded trials were larger (median sample size 474 versus 375; P < 0.001) and more likely to meet their primary end point (49% versus 41%; P < 0.001). Among positive trials, there were no differences in the magnitude of benefit between industry- and non-industry-funded RCTs. Trials funded by industry were published in journals that had a significantly higher median impact factor (21, interquartile range 7, 28) than non-industry-funded trials (impact factor 12, interquartile range 5, 24; P = 0.005); this persisted when adjusted for whether a trial was positive or negative. CONCLUSIONS: The vast majority of oncology RCTs are now funded by industry. Industry-funded trials are larger, more likely to be positive, predominantly test systemic therapies in the palliative setting and are published in higher impact journals than trials without industry support.

Medical Oncology Workload in Europe: One Continent, Several Worlds.

AIMS: The workload pressure on medical oncologists will increase in the near future. There are no comprehensive data available about the current workload of medical oncologists in Europe. Here we report the European results of a global survey of the workload of medical oncologists. MATERIALS AND METHODS: An online survey was distributed through a snowball method via national oncology societies to chemotherapy-prescribing physicians in 21 European countries. We compared the workload of medical oncologists in Eastern European countries (EECs) and Western European countries (WECs). The primary measure of workload was the annual number of new cancer patient consults seen per oncologist. RESULTS: In total, 495 oncologists from 16 European countries completed our survey: 100 from seven EECs and 395 from nine WECs. The median number of annual consults per medical oncologist was 225 in EECs compared with 175 in WECs (P < 0.001). The proportion of medical oncologists seeing more than 300 consults/year was 35% (35/100) in EECs compared with 18% (68/395) in WECs. The median number of patients seen in a full day clinic was 25 in EECs and 15 in WECs (P < 0.001). Eastern European medical oncologists reported spending a median of 25 min per new consultation compared with 45 min in WECs (P < 0.001). The top two reported barriers in both EECs and WECs to patient care were high clinical volumes and insufficient time for reading. CONCLUSION: The clinical workload of medical oncologists in EECs was substantially higher than in WECs. European health policymakers and educators need to address existing disparities in the workload of medical oncologist, undertake plans for future workforce supply and consider alternative models of care.

Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study.

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. INTRODUCTION: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. METHODS: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. RESULTS: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. CONCLUSIONS: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.

Medical oncology workload in Canada: infrastructure, supports, and delivery of clinical care.

Background: In 2000, a Canadian task force recommended that medical oncologists (mos) meet a target of 160-175 new patient consultations per year. Here, we report the Canadian results of a global survey of mo workload compared with mo workload in other high-income countries (hics). Methods: Using a snowball method, an online survey was distributed by national oncology societies to chemotherapy-prescribing physicians in 22 hics (World Bank criteria). The survey was distributed within Canada to all members of the Canadian Association of Medical Oncologists. Workload was measured as the annual number of new cancer patient consults per oncologist. Results: The survey was completed by 782 oncologists from hics, including 58 from Canada. Median annual consults per mo were 175 in Canada compared with 125 in other hics. The proportions of mos having 100 or fewer consults or more than 300 consults per year were 3% (2/58) and 5% (3/58) in Canada compared with 31% (222/724) and 16% (116/724) in other hics (p < 0.001 and p = 0.023 respectively). The median number of patients seen in a full-day clinic was 15 in Canada and 25 in other hics (p = 0.220). Canadian mos reported spending a median of 55 minutes per new consultation; new consultations of 35 minutes were reported in other hics (p < 0.001). Median hours worked per week was 55 in Canada and 45 in other hics (p = 0.200). Conclusions: Although the median annual clinical volume for Canadian mos aligns with recommended targets, half the respondents exceeded that level of activity. Health policymakers and educators have to consider mo workforce supply and alternative models of care in preparation for the anticipated surge in cancer incidence in the coming decade.

Adjuvant treatment in older patients with rectal cancer: a population-based review.

Background: Little is known about the benefits of adjuvant chemotherapy (adj) in the older population with locally advanced rectal cancer (larc). We evaluated use of adj, survival outcomes, and adj-related toxicity in older patients with larc. Methods: Our retrospective review included 286 patients with larc (stages ii and iii) diagnosed between January 2010 and December 2013 in Nova Scotia who underwent curative-intent surgery. Baseline patient, tumour, and treatment characteristics were collected. The survival analysis used the Kaplan-Meier method and Cox regression statistics. Results: Of 286 identified patients, 152 were 65 years of age or older, and 92 were 70 years of age or older. Median follow-up was 46 months, and 163 patients (57%) received neoadjuvant chemoradiation. Although adj was given to 81% of patients (n = 109) less than 65 years of age, only 29% patients (n = 27) 70 years of age and older received adj. Kaplan-Meier analysis suggested a potential survival advantage for adj regardless of age. In multivariate Cox regression analysis, Eastern Cooperative Oncology Group performance status, T stage, and adj were significant predictors of overall survival (p < 0.04); age was not. Similarly, N stage, neoadjuvant chemoradiation, and adj were significant predictors of disease-free survival (p < 0.01). Poor Eastern Cooperative Oncology Group performance status was the most common cause of adj omission. In patients 70 years of age and older, grade 1 or greater chemotherapy-related toxicities were experienced significantly more often by those treated with adj (85% vs. 68% for those not treated with adj, p < 0.05). Conclusions: Regardless of age, patients with larc seem to experience a survival benefit with adj. However, older patients are less likely to receive adj, and when they do, they experience more chemotherapy-related toxicities.

Toward improved goals-of-care documentation in advanced cancer: report on the development of a quality improvement initiative.

BACKGROUND: Documentation of advance care planning for patients with terminal cancer is known to be poor. Here, we describe a quality improvement initiative. METHODS: Patients receiving palliative chemotherapy for metastatic lung, pancreatic, colorectal, and breast cancer during 2010-2015 at the Cancer Centre of Southeastern Ontario were identified from electronic pharmacy records. Clinical notes were reviewed to identify documentation of care plans in the event of acute deterioration. After establishing baseline practice, we sought to improve documentation of goals of care and referral rates to palliative care. Using quality improvement methodology, we developed a guideline, a standardized documentation system, and a process to facilitate early referral to palliative care. RESULTS: During 2010-2015, 456 patients were included in the baseline cohort: 63% with lung cancer, 16% with colorectal cancer, 13% with pancreatic cancer, and 7% with breast cancer. Care goals in the event of an acute illness were documented by medical oncologists in 6% of cases (26 of 456). Of the 456 patients, 47% (n = 214) were seen by palliative care; care goals were documented by palliative care in 48% of the patients seen (103 of 214). With those baseline data in hand, a local practice guideline and process was developed to facilitate the identification of patients for whom advance care planning and early palliative care referral should be considered. A system was also established so that goals-of-care documentation will be supported with a written framework and broadly accessible in the electronic medical record. CONCLUSIONS: Low rates of documentation of advance care planning and referral to palliative care persist and have stimulated a local quality improvement initiative.

Shifting practice in definitive chemoradiation for localized esophageal cancer.

BACKGROUND: The efficacy of carboplatin-paclitaxel in the trimodality setting was demonstrated in the cross trial. Because of better tolerance, that regimen has been adopted as an alternative for patients receiving definitive chemoradiation (dcrt). The purpose of our study was to compare outcomes in patients with localized esophageal and gastroesophageal junction (gej) cancer who received dcrt using either platinum-5-fluorouracil (5fu) or carboplatin-paclitaxel. METHODS: Medical records and outcomes for all patients diagnosed with localized carcinoma of the esophagus and gej at our centre between 2008 and 2015 were reviewed. All patients who underwent dcrt using cisplatin-5fu, carboplatin-5fu, or carboplatin-paclitaxel were included. RESULTS: The 73 identified patients (34 cisplatin-5fu, 13 carboplatin-5fu, 26 carboplatin-paclitaxel) were all prescribed concomitant radiotherapy of 50 Gy in 25 daily fractions. The diagnosis was adenocarcinoma in 64% and squamous cell carcinoma in 36%. Median overall survival (os) duration for the cisplatin-5fu group was 28 months [95% confidence interval (ci): 19 to 41 months], with a 3-year os rate of 44%, in contrast to the 15 months (95% ci: 11 to 17 months) and 15% in the carboplatin-paclitaxel group (log-rank p = 0.0047). Median os duration for the carboplatin-5fu group was 17 months (95% ci: 11 to 68 months) with a 3-year os rate of 31%. Adjusting for patient and disease factors, better os durations and rates were associated with cisplatin-5fu (hazard ratio: 0.34; p = 0.0016) and carboplatin-5fu (hazard ratio: 0.55; p = 0.20) than with carboplatin-paclitaxel. CONCLUSIONS: In a dcrt regimen, a better os is associated with cisplatin-5fu than with carboplatin-paclitaxel. Clinical trials to determine optimal chemotherapy regimens are warranted for patients who are not suitable for surgery.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Background: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. Methods: RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. Results: About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Conclusion: Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs.

Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study.

INTRODUCTION: There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. AIM: Our objective was to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. METHODS: This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH-BAT were completed by study personnel. RESULTS: A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82). Carriers had higher mean bleeding scores (BS) compared with age-matched controls (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r2  = -0.36, P < 0.001). CONCLUSION: Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH-BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment.

A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival.

BACKGROUND: Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. METHODS: After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan-Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. RESULTS: We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). CONCLUSIONS: Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses.

A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival.

BACKGROUND: Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. METHODS: We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). RESULTS: We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). CONCLUSIONS: Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses.

Prognosis, Treatment Benefit and Goals of Care: What do Oncologists Discuss with Patients who have Incurable Cancer?

AIMS: Documentation of advance directives among patients with terminal cancer is known to be poor. Here we describe documentation of prognosis, treatment benefit and goals of care discussions in outpatients with advanced cancer. MATERIALS AND METHODS: All patients receiving first-line palliative chemotherapy for metastatic pancreas or lung cancers during 2010-2013 at the Cancer Centre of Southeastern Ontario were identified from electronic pharmacy records. Clinical notes from medical oncology were reviewed to identify documentation of discussions regarding prognosis, treatment benefit and goals of care. Differences between groups were tested using the chi-squared test. RESULTS: In total, 222 patients were included: 80% (177/222) with lung cancer and 20% (45/222) with pancreas cancer. Medical oncology notes documented discussion of prognosis in 64% (142/222), palliative intent of therapy in 82% (182/222), magnitude of treatment benefit in 29% (64/222) and goals of care in 4% (9/222) of patients. An estimate of survival was documented in 36% (79/222) of cases. Across medical oncology providers there was substantial variation in the frequency of discussing prognosis (range 33-90%, P < 0.001), treatment intent (range 55-100%, P < 0.001) and goals of care (range 0-17%, P = 0.034). In total, 41% (93/222) of patients were seen by palliative care; substantial medical oncology provider variation was observed (range 27-58%, P = 0.020). Referral rates to palliative care did not increase over time (41-44%, P = 0.250). CONCLUSIONS: In this cohort of ambulatory patients with an estimated life expectancy of 1 year or less, medical oncology documentation of prognosis, treatment benefit and goals of care was poor. Less than half the patients were seen by palliative care. Initiatives to improve documentation and referral to palliative care are needed.

Generation and optimization of the self-administered bleeding assessment tool and its validation as a screening test for von Willebrand disease.

INTRODUCTION/AIM: Our aim was to generate, optimize and validate a self-administered bleeding assessment tool (self-BAT) for von Willebrand disease (VWD). METHODS: In Phase 1, medical terminology in the expert-administered International Society on Thrombosis and Haemostasis (ISTH)-BAT was converted into a Grade 4 reading level to produce the first version of the Self-BAT which was then optimized to ensure agreement with the ISTH-BAT. In Phase 2, the normal range of bleeding scores (BSs) was determined and test-retest reliability analysed. In Phase 3, the optimized Self-BAT was tested as a screening tool for first time referrals to the Haematology clinic. RESULTS: Bleeding score from the final optimized version of the Self-BAT showed an excellent intra-class correlation coefficient (ICC) of 0.87 with ISTH-BAT BS in Phase 1. In Phase 2, the normal range of BSs for the optimized Self-BAT was determined to be 0 to +5 for females and 0 to +3 for males and excellent test-retest reliability was shown (ICC = 0.95). In Phase 3, we showed that a positive Self-BAT BS (≥6 for females, ≥4 for males) has a sensitivity of 78%, specificity of 23%, positive predictive value (PPV) of 0.15 and negative predictive value (NPV) of 0.86 for VWD; these figures improved when just the females were analysed; sensitivity of 100%, specificity of 21%, PPV = 0.17 and NPV = 1.0. CONCLUSION: We show an optimized Self-BAT can generate comparable BS to the expert-administered ISTH-BAT and is a reliable, effective screening tool to incorporate into the assessment of individuals, particularly women, referred for a possible bleeding disorder.

Interferon-gamma release assays piloted as a latent tuberculous infection screening tool in Canadian federal inmates.

BACKGROUND: Interferon-gamma release assays (IGRAs) may be useful in diagnosing latent tuberculous infection (LTBI) in inmates; however, published experience in these settings is limited. OBJECTIVE: To identify variables associated with IGRA positivity among Canadian federal inmates with positive tuberculin skin test (TST) results. DESIGN: On intake, TST-positive (≥10 mm) inmates were offered an IGRA (QuantiFERON(®)-TB Gold), and demographic and historical data were collected. IGRA-positive and -negative inmates were compared using the χ(2) test and multivariable logistic regression; the final model's goodness of fit was assessed using Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC). RESULTS: Of 96 TST-positive inmates, 31 (32.3%) were IGRA-positive. Variables associated with positive IGRA were age >45 years (11/20 vs. 20/75, P = 0.016) and previous LTBI treatment (9/20 vs. 13/55, P = 0.032) in univariate analysis, and being from a country with a moderate or high estimated tuberculosis (TB) incidence (OR 3.5, 95%CI 1.3-9.4, P = 0.013) and absence of bacille Calmette-Guérin (BCG) vaccination (OR 3.3, 95%CI 1.2-9.0, P = 0.017) in multivariable analysis. The data fit the model well, classifying the group better than chance alone (AUC 0.67, P = 0.007). CONCLUSION: High discordance with TST, particularly among BCG-vaccinated inmates and those from low TB incidence countries, suggest that IGRA may be useful in Canadian federal penitentiary screening programmes.

The role of psycho-education in improving outcome at a general hospital psychiatry clinic in Uganda.

OBJECTIVE: While psychoeducation has been shown to positively affect outcomes in psychiatric disorders, its utility has been little studied in developing countries. The current study sought to examine the role of psychoeducation at a general psychiatric outpatient clinic in Kampala, Uganda in improving clinic attendance, treatment adherence, and clinical outcomes. METHOD: A prospective case-control study using a quasi-experimental design was conducted in 117 patients suffering various psychiatric disorders. Participants were recruited for two months and then followed for a further three months after recruitment ended. Participants in the intervention group received formalized psychoeducation sessions at each clinic visit in addition to the usual psychiatric evaluation and care. Participants in the control group received the usual clinical care. Measured outcomes were knowledge of mental illness, compliance with medications and follow-up, and Clinical Global Impression (CGI). RESULTS: The groups did not differ with respect to sociodemographic characteristics or attendance at scheduled follow-up visits. Both groups significantly improved on the CGI, but with no significant difference between the groups. However, the intervention group was more likely to adhere to medication, and their knowledge of mental illness was significantly higher at follow-up. CONCLUSION: These data suggest that psychoeducation is a beneficial mental health intervention in a developing country that may increase compliance with medication and result in greater knowledge of mental illness. However, other factors such as distance from a centralized clinic or cost of treatment may impact outcomes, including attendance at scheduled follow-up visits.

Real-world impact of granulocyte-colony stimulating factor on febrile neutropenia.

BACKGROUND: Primary prophylaxis with granulocyte colony-stimulating factors (pp-g-csf) is recommended in patients undergoing chemotherapy carrying a febrile neutropenia (fn) risk of 20% or more. In the present study, we examined clinical practice patterns and the impact of pp-g-csf on fn incidence in women with early-stage breast cancer (ebc) treated with modern adjuvant chemotherapy (act). METHODS: This single-centre retrospective cohort study of women with ebc, who were identified from the pharmacy database and who received at least 1 cycle of modern act from January 2009 to December 2011, was conducted at the Cancer Centre of Southeastern Ontario. Data on patient demographics, pathology, stage distribution, chemotherapy, pp-g-csf use, dose reductions, chemotherapy delays, treatment discontinuation, relative dose intensity, and fn events were collected. Chi-square tests, t-tests, univariate and multivariate logistic regression analyses, and nonparametric Mann-Whitney U-tests were used for data analysis. RESULTS: Of the 239 women eligible for analysis, 145 (61%) received pp-g-csf, and 50 (21%) developed at least 1 episode of fn. Use of pp-g-csf was associated with a significantly lower rate of fn (14% vs. 31%, p = 0.002) and trends to fewer dose delays (17% vs. 27%, p = 0.060) and dose reductions (19% vs. 25%, p = 0.28). Among women receiving pp-g-csf, higher fn rates were associated with an age of 65 years or older, taxane-based chemotherapy, and prophylaxis with filgrastim. CONCLUSIONS: Clinical practice patterns at our institution showed that more than 50% of ebc patients treated with modern act received pp-g-csf, which led to fewer fn episodes and increased delivery of planned act. The observed high fn risk despite pp-g-csf was linked to older age, taxane-based chemotherapy, and filgrastim.

Pain and health-related quality of life in people with chronic leg ulcers.

INTRODUCTION: Venous leg ulceration is associated with pain and poor health-related quality of life (HRQL). The purpose of this study was to identify demographic and clinical characteristics associated with pain and decreased HRQL in patients with active venous ulcers. METHODS: Baseline data were combined from two trials that took place between 2001 and 2007 (n = 564). Pain was measured using the Numeric Pain Scale (NPS), and HRQL was measured using the Medical Outcomes Survey 12-item Short Form (SF-12), which generates a Physical (PCS) and Mental Component Summary (MCS). Analyses included logistic and linear regression (for pain and HRQL, respectively). RESULTS: Mean age was 66.5 years; 47% were male. Median NPS score was 2.2 (out of 10) and mean PCS and MCS scores were 38.0 and 50.5, respectively (scores are standardized to a mean of 50 representing average HRQL). Younger age, living with others, and arthritis were associated with pain. Poorer PCS was associated with being female, venous/mixed ulcer etiology, larger ulcers, longer ulcer duration, cardiovascular disease, arthritis and higher pain intensity. Poorer MCS was associated with younger age, longer ulcer duration, comorbidity and higher pain intensity. CONCLUSION: Research is needed to test strategies to reduce pain and possibly improve HRQL in high risk groups.

TITLE: Douleur et qualité de vie liée à la santé chez les personnes souffrant d'ulcères chroniques aux jambes. INTRODUCTION: L'ulcération veineuse de la jambe est associée à de la douleur et à une mauvaise qualité de vie liée à la santé (QVLS). Cette étude visait à définir les caractéristiques démographiques et cliniques associées à la douleur et à une diminution de la QVLS chez les patients présentant des ulcères veineux actifs. MÉTHODOLOGIE: Les données de base obtenues dans le cadre de deux essais menés entre 2001 et 2007 (n = 564) ont été combinées. La douleur a été mesurée à l'aide de l'échelle numérique de la douleur (END), et la QVLS a été mesurée à l'aide du formulaire abrégé comportant 12 questions de l'Enquête sur la santé (SF-12), qui produit un sommaire de la composante physique (SCP) et un sommaire de la composante mentale (SCM). Les analyses ont notamment été effectuées par régression logistique (pour la douleur) et par régression linéaire (pour la QVLS). RÉSULTATS: L'âge moyen était de 66,5 ans; 47 % étaient des hommes. Le score médian sur l'END était de 2,2 (sur 10) et les scores moyens du SCP et du SCM étaient respectivement de 38,0 et de 50,5 (les scores sont normalisés à une moyenne de 50, qui représente la QVLS moyenne). Le jeune âge, le fait de vivre avec d'autres personnes et l'arthrite ont été associés à la douleur. Un score plus faible pour le SCP a été associé au fait d'être une femme, aux ulcères d'origine veineuse/mixte, aux gros ulcères, aux ulcères de longue durée, aux maladies cardiovasculaires, à l'arthrite et la douleur intense. Un score plus faible pour le SCM a été associé au jeune âge, aux ulcères de longue durée, aux affections concomitantes et à la douleur intense. CONCLUSION: Il convient de mener des recherches pour mettre à l'essai des stratégies d'atténuation de la douleur et d'amélioration potentielle de la QVLS chez les groupes à risque élevé.

Real-world experience with adjuvant fec-d chemotherapy in four Ontario regional cancer centres.

BACKGROUND: The efficacy of adjuvant chemotherapy with fec-d (5-fluorouracil-epirubicin-cyclophosphamide followed by docetaxel) is superior to that with fec-100 alone in women with early-stage breast cancer. As the use of fec-d increased in clinical practice, health care providers anecdotally noted higher-than-expected toxicity rates and frequent early treatment discontinuations because of toxicity. In the present study, we compared the rates of serious adverse events in patients who received adjuvant fec-d chemotherapy in routine clinical practice with the rates reported in the pacs-01 trial. METHODS: We retrospectively reviewed all patients prescribed adjuvant fec-d for early-stage breast cancer at 4 regional cancer centres in Ontario. Information was collected from electronic and paper charts by a physician investigator from each centre. Data were analyzed using chi-square tests, independent samples t-tests, one-way analysis of variance, and univariate regression. RESULTS: The 671 electronic and paper patient records reviewed showed a median patient age of 52.2 years, 229 patients (34.1%) with N0 disease, 508 patients (75.7%) with estrogen or progesterone receptor-positive disease (or both), and 113 patients (26%) with her2/neu-overexpressing breast cancer. Febrile neutropenia occurred in 152 patients (22.7%), most frequently at cycle 4, coincident with the initiation of docetaxel [78/152 (51.3%)]. Primary prophylaxis with hematopoietic growth factor support was used in 235 patients (35%), and the rate of febrile neutropenia was significantly lower in those who received prophylaxis than in those who did not [15/235 (6.4%) vs. 137/436 (31.4%); p < 0.001; risk ratio: 0.20]. CONCLUSIONS: In routine clinical practice, treatment with fec-d is associated with a higher-than-expected rate of febrile neutropenia, in light of which, primary prophylaxis with growth factor should be considered, per international guidelines. Adoption based on clinical trial reports of new therapies into mainstream practice must be done carefully and with scrutiny.