Risk of arterial and venous thromboembolic events among patients with colorectal carcinoma: a real-world, population-based study.

Objective: To assess real-world patterns of arterial and venous thromboembolism among patients with colorectal carcinoma. Methods: The Alberta provincial cancer registry and other provincial medical records were used to identify patients with colorectal cancer (2004-2018) with no preceding or succeeding cancer diagnosis. The incidence of both arterial and venous thromboembolism in this patient population as well as factors associated with these thromboembolic events were examined through logistic regression analysis. Results: A total of 17,296 patients were found eligible and were included into the current study. We observed that 1564 patients (9%) experienced a thromboembolic event and 15,732 patients (91%) did not. The following factors were associated with any thromboembolic event: male sex (odds ratio [OR]: 1.20; 95% CI: 1.08-1.34), higher comorbidity (OR: 1.36; 95% CI: 1.31-1.41), metastatic disease (OR for nonmetastatic vs metastatic disease: 0.53; 95% CI: 0.47-0.60), living within North zone (OR for Edmonton zone vs North zone: 0.70; 95% CI: 0.59-0.84), treatment with fluoropyrimidines (OR for no fluoropyrimidines vs fluoropyrimidines: 0.53; 95% CI: 0.47-0.60) and treatment with bevacizumab (OR: for no bevacizumab vs bevacizumab: 0.53; 95% CI: 0.47-0.60). Factors associated with venous thromboembolism include, younger age (continuous OR with increasing age: 0.99; 95% CI: 0.98-0.99), higher comorbidity (OR: 1.10; 95% CI: 1.04-1.17), metastatic disease (OR for nonmetastatic disease vs metastatic disease: 0.40; 95% CI: 0.35-0.47), North zone (OR for Edmonton zone vs North zone: 0.70; 95% CI: 0.56-0.86), treatment with fluoropyrimidines (OR for no fluoropyrimidines vs fluoropyrimidines: 0.45; 95% CI: 0.39-0.53) and treatment with bevacizumab (OR for no bevacizumab vs bevacizumab: 0.73; 95% CI: 0.58-0.93). Conclusion: Thromboembolic events are not uncommon among colorectal cancer patients, and the risk is increased with male sex, higher comorbidity, presence of metastatic disease, living within the North zone of the province (where there is limited access to tertiary care centers) and treatment with fluoropyrimidines or bevacizumab.

Lay abstract In this analysis of patients who have been diagnosed of colon and rectal cancers in Alberta, Canada, development of blood clots was not uncommon. Certain patient and treatment risk factors seem to increase the risk of this phenomenon.

Outcomes of Patients With Advanced Gastrointestinal Cancer in Relationship to Opioid Use: Findings From Eight Clinical Trials.

BACKGROUND: This study assessed the patterns of opioid use among patients with advanced gastrointestinal cancers who were included in 8 clinical trials and evaluated the impact of opioid use on survival outcomes of included patients. METHODS: Deidentified datasets from 8 clinical trials evaluating first-line systemic treatment of advanced gastrointestinal cancers were accessed from the Project Data Sphere platform (ClinicalTrial.gov identifiers: NCT01124786, NCT00844649, NCT00290966, NCT00678535, NCT00699374, NCT00272051, NCT00305188, and NCT00384176). These trials evaluated patients with pancreatic carcinoma, gastric carcinoma, hepatocellular carcinoma (HCC), and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was then used to further assess the impact of opioid use on survival outcomes in each disease entity. RESULTS: A total of 3,441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age at diagnosis (odds ratio [OR], 0.990; 95% CI, 0.984-0.997; P=.004), nonwhite race (OR for white vs nonwhite, 0.749; 95% CI, 0.600-0.933; P=.010), higher ECOG score (OR for 1 vs 0, 1.751; 95% CI, 1.490-2.058; P<.001), and pancreatic primary site (OR for colorectal vs pancreatic, 0.241; 95% CI, 0.198-0.295; P<.001). Use of opioids was consistently associated with worse overall survival (OS) in Kaplan-Meier survival estimates of each disease entity (P=.008 for pancreatic cancer; P<.001 for gastric cancer, HCC, and colorectal cancer). In multivariable Cox regression analysis, opioid use was associated with worse OS among patients with pancreatic cancer (hazard ratio [HR], 1.245; 95% CI, 1.063-1.459; P=.007), gastric cancer (HR, 1.725; 95% CI, 1.403-2.122; P<.001), HCC (HR, 1.841; 95% CI, 1.480-2.290; P<.001), and colorectal cancer (HR, 1.651; 95% CI, 1.380-1.975; P<.001). CONCLUSIONS: Study findings suggest that opioid use is consistently associated with worse OS among patients with different gastrointestinal cancers. Further studies are needed to understand the underlying mechanisms of this observation and its potential implications.

Feasibility of performance-based functional assessment in brain tumour survivors.

INTRODUCTION: Rehabilitation and exercise interventions are beneficial for the physical and psychological health of cancer survivors. Current clinic-based performance status measures do not accurately capture the survivor's functioning, or rehabilitation and exercise needs. Our primary objective was to explore the feasibility of performing a performance-based functional assessment with brain tumour survivors as a means to inform needs for rehabilitation and exercise. METHODS: A feasibility study was conducted with survivors of brain and other neurological cancers attending new patient or follow-up clinics. Survivors were assessed using the Short Physical Performance Battery (SPPB), grip strength and Rosow-Breslau Physical Activity Self-Assessment (RSB). RESULTS: We approached 40 survivors with brain tumours, and 30 agreed to participate in the study. The SPPB was inversely correlated with Eastern Cooperative Oncology Group (ECOG) scores (r = -.73; p < .01), but scores on the SPPB for individuals classified as ECOG 1 ranged from 5 to 12 out of 12, indicating a large variability in functional scores within this ECOG grade. CONCLUSION: Implementation of objective functional testing is feasible in the neuro-oncology outpatient clinic. The SPPB appears to best inform the functional status of survivors with brain tumours, facilitating more individualised exercise and rehabilitation referrals.

ClotAssist: A program to treat cancer-associated thrombosis in an outpatient pharmacy setting.

Stable cancer patients diagnosed with a pulmonary embolus or deep vein thrombosis are commonly referred to the emergency department for management. This practice strains an already overburdened emergency department and is associated with long wait times and poor disease/injection education for patients. This pilot study sought to determine if stable cancer patients with newly diagnosed cancer-associated thrombosis could be effectively managed by community-based pharmacists who followed an evidence-based protocol to prescribe and initiate low-molecular weight heparin therapy. We hypothesized that this novel care pathway could provide faster patient care with more comprehensive disease education, self-injection training, and follow-up. Fifty-five patients with various cancers, including gastroesophageal, urogenital, breast, brain, and lung were enrolled into this pilot study. We observed that this alternative first-dose treatment pathway provided safe and effective treatment of venous thromboembolism combined with excellent patient satisfaction. Following their interaction with the pharmacist, patients felt confident about their ability to self-inject and about their venous thromboembolism management overall. No occurrences of bleeding or other side-effects were observed. This pilot study demonstrates that community-based pharmacists are capable of delivering complex care services in the outpatient environment, particularly in the management of venous thromboembolism.

Evaluation of laboratory disturbance risk when adding low-dose cotrimoxazole for PJP prophylaxis to regimens of high-grade glioma patients taking RAAS inhibitors.

BACKGROUND: Cotrimoxazole is associated with the development of hyponatremia, hyperkalemia and elevated serum creatinine, especially when combined with inhibitors of the renin-angiotensin-aldosterone system (RAAS). Pneumocystis jirovecii pneumonia (PJP) prophylaxis is the standard of care for high-grade glioma (HGG) patients receiving temozolomide concurrently with radiotherapy, low-dose cotrimoxazole being the preferred agent. Many of these patients are also taking renin-angiotensin-aldosterone system inhibitors, however the risk of significant laboratory disturbance in these patients remains undescribed. OBJECTIVE: We evaluated whether high-grade glioma patients taking renin-angiotensin-aldosterone system inhibitors receiving low-dose cotrimoxazole for Pneumocystis jirovecii pneumonia prophylaxis are at additional risk of laboratory disturbances in comparison with their non-renin-angiotensin-aldosterone system counterparts. METHODS: We conducted a retrospective chart review of adult neuro-oncology patients treated for WHO Grade III or IV glioma between 2013 and 2016. Patient serum Na, K, creatinine, and eGFR were compared (renin-angiotensin-aldosterone system vs. non-renin-angiotensin-aldosterone system) using the chi-square test. Binary logistic regression analysis was then performed to account for differences between cohorts. RESULTS: Of 63 patients (35 non-renin-angiotensin-aldosterone system, 28 renin-angiotensin-aldosterone system), patients in the renin-angiotensin-aldosterone system cohort were more likely to experience a laboratory disturbance (odds ratio=3.17, p = 0.03). Overall, these disturbances were moderate, but were slightly more common and slightly more severe in the renin-angiotensin-aldosterone system cohort. CONCLUSION: Adding low-dose cotrimoxazole for Pneumocystis jirovecii pneumonia prophylaxis to the regimens of patients with high-grade glioma taking renin-angiotensin-aldosterone system inhibitors increases the risk of laboratory disturbances. While these are generally moderate, some patients are at risk of significant electrolyte abnormalities requiring intervention.

Exercise preferences and associations between fitness parameters, physical activity, and quality of life in high-grade glioma patients.

PURPOSE: Exercise has numerous benefits for cancer survivors, but very limited research to date has exclusively examined brain cancer patients, specifically those diagnosed with high-grade glioma (HGG). This study examined (1) the feasibility of recruiting HGG patients to an exercise-based study and performing fitness assessments; (2) exercise counseling and programming preferences; and (3) associations between fitness, physical activity (PA), and quality of life (QOL). METHODS: Participants completed assessments prior to starting Temozolamide chemotherapy with radiation (T1), at 2 months and 8 months. Fitness was measured with an incremental cycling exercise test to volitional exhaustion (VO2peak) and hand grip dynamometry. The Godin leisure time questionnaire measured PA and the functional assessment for cancer therapy, brain cancer module (FACT-Br) measured QOL. RESULTS: Of the 35 approached, N = 16 participated. Due to safety concerns, the aerobic fitness test protocol was altered. Participants preferred to exercise during treatment, alone and unsupervised, at home, and at a moderate intensity. Few participants (<25%) met guidelines for PA at any time point. At T1, aerobic capacity was associated with the FACT Trial Outcome Index (TOI) (r = 0.619, p < 0.05). At 2 months, PA minutes were associated with FACT-TOI (r = 0.653, p = 0.057), FACT-G (r = 0.711, p < 0.05), and FACT-Br scores (r = 0.722, p < 0.05). CONCLUSIONS: Recruitment rate was similar to a previous study in HGG populations, but study completion rate was lower. Most exercise counseling and programming preferences were similar to previous brain cancer patients. Assessing aerobic fitness to VO2peak was not feasible. Aerobic fitness and PA were positively associated with QOL.

Association between cytoplasmic CRABP2, altered retinoic acid signaling, and poor prognosis in glioblastoma.

Retinoic acid (RA), a metabolite of vitamin A, is required for the regulation of growth and development. Aberrant expression of molecules involved in RA signaling has been reported in various cancer types including glioblastoma multiforme (GBM). Cellular retinoic acid-binding protein 2 (CRABP2) has previously been shown to play a key role in the transport of RA to retinoic acid receptors (RARs) to activate their transcription regulatory activity. Here, we demonstrate that CRABP2 is predominantly located in the cytoplasm of GBM tumors. Cytoplasmic, but not nuclear, CRABP2 levels in GBM tumors are associated with poor patient survival. Treatment of malignant glioma cell lines with RA results in a dose-dependent increase in accumulation of CRABP2 in the cytoplasm. CRABP2 knockdown reduces proliferation rates of malignant glioma cells, and enhances RA-induced RAR activation. Levels of CRYAB, a small heat shock protein with anti-apoptotic activity, and GFAP, an astrocyte-specific intermediate filament protein, are greatly reduced in CRABP2-depleted cells. Restoration of CRYAB expression partially but significantly reversed the effect of CRABP2 depletion on RAR activation. Our combined in vivo and in vitro data indicate that: (i) CRABP2 is an important determinant of clinical outcome in GBM patients, and (ii) the mechanism of action of CRABP2 in GBM involves sequestration of RA in the cytoplasm and activation of an anti-apoptotic pathway, thereby enhancing proliferation and preventing RA-mediated cell death and differentiation. We propose that reducing CRABP2 levels may enhance the therapeutic index of RA in GBM patients.

Population based analysis ependymoma patients in Alberta from 1975 to 2007.

BACKGROUND: Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR). METHODS: This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada. RESULTS: Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022). CONCLUSIONS: This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.

Switch to generic formulation of temozolomide results in statistically significant increase in grade 3 and 4 bone marrow toxicity in glioma patients in the province of Alberta.

Background: Temozolomide (TMZ) is an oral, systemic chemotherapy used chiefly for treating high-grade glioma. Due to the rising costs of systemic chemotherapy, many jurisdictions have replaced brand name with generic formulations. The aim of this study was to determine whether or not there was difference in the incidence of grade 3 or 4 bone marrow toxicity and median overall survival in patients treated with brand name versus generic TMZ in the province of Alberta, Canada. The province suspended the use of generic TMZ based on preliminary data pointing to excess toxicity. Methods: This multicenter, retrospective study included data from patients with newly diagnosed high-grade glioma that received treatment with TMZ in Alberta. Multivariate logistic regression analysis was performed to determine the association between grade 3 or 4 toxicity to generic versus brand name TMZ exposure, ECOG score, and age. Kaplan-Meier survival estimates and log-rank testing were used to determine differences in overall survival between the brand name and generic TMZ cohorts, as well as the cytopenic versus non-cytopenic patients. Furthermore, a screening analysis for grade 3 or 4 bone marrow toxicity was conducted on all de novo glioma patients treated with brand name TMZ after Alberta preemptively stopped generic TMZ. Results: Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15% and 19% of patients treated with generic TMZ (n = 156) as compared to 3% and 5% of patients (n = 100) treated with brand name TMZ-treated patients; P= .003 and .001. A trend toward increased median overall survival in glioblastoma patients treated with generic TMZ (13.7 months) versus brand name (15.8 months, P = .178.) was also observed through meeting statistical significance. Based on these results, the province stopped the use of generic TMZ and reverted to the Merck TMZ. An initial review of all new glioma patients (n = 89) treated with Merck TMZ since the province stopped the generic drug demonstrated 3.4% and 10.1% grade 3 or 4 neutropenia, respectively. Conclusions: The statistically significant difference in toxicity profile has prompted the province of Alberta to replace generic TMZ with brand name TMZ in high-grade glioma patients pending more detailed analysis. Our study provides evidence supporting the importance of conducting prospective studies on long-term safety for generic chemotherapies.

Implementing routine screening for distress, the sixth vital sign, for patients with head and neck and neurologic cancers.

This study examined the benefits of incorporating screening for distress as a routine part of care for patients with head and neck and neurologic cancers in a tertiary cancer center. Using a comparative 2-cohort pre-post implementation sequential design, consecutive outpatients with head and neck and neurologic cancers were recruited into 2 separate cohorts. Cohort 1 included patients attending clinics during April 2010, before the implementation of the screening program. The program was then implemented and patients completed the Screening for Distress Minimum Dataset (the Edmonton Symptom Assessment System [ESAS] and the Canadian Problem Checklist [CPC]) at each clinic visit. Cohort 2 included patients attending clinics during March 2011. Consenting patients completed screening and outcome measures (ESAS, CPC, and either the Functional Assessment of Cancer Therapy-Brain or the Functional Assessment of Cancer Therapy-Head and Neck). A total of 146 patients (78 head and neck and 68 neurologic) provided data for Cohort 1, and 143 (81 head and neck and 62 neurologic) provided data for Cohort 2. Compared with Cohort 1, patients with neurologic cancers in Cohort 2 reported significantly higher scores on the Functional Assessment of Cancer Therapy: General total and emotional quality of life subscale; fewer high scores (≥ 4) on the ESAS breathlessness item; and fewer problems with fears/worries, frustration/anger, finding meaning in life, and worry about friends/family. Head and neck patients in Cohort 2 reported significantly higher emotional quality of life and fewer problems with eating and weight than those in Cohort 1. Although no definitive causal attributions can be made, patients exposed to routine screening for distress reported better well-being and fewer emotional, physical, and practical problems than historical controls.

Management of recurrent medulloblastoma in adult patients: a systematic review and recommendations.

Medulloblastoma accounts for almost one-third of pediatric central nervous system (CNS) cancers, but is very rare in the adult population. As a result, adult patients with medulloblastoma are often treated according to therapies developed for children with similarly staged disease at diagnosis, based on the assumption that adult and pediatric tumors have similar properties. The purpose of this review was to summarize the evidence and to make recommendations for the management of recurrent disease in adult patients with medulloblastoma. We conducted a systematic literature search to find publications addressing treatment of recurrent medulloblastoma in adults. Current treatment strategies for adult patients with relapsed medulloblastoma are based on the results of retrospective case series and published consensus recommendations, and include maximal safe re-resection where possible, combined with chemotherapy and/or re-irradiation. We describe the results of 13 publications involving 66 adult patients treated with high-dose chemotherapy (HDCT) plus stem cell transplantation for recurrent medulloblastoma. HDCT with stem cell transplantation may be a treatment option for a small proportion of adult patients who are unlikely to benefit from conventional chemotherapy and who are fit and have their disease recurrence contained within the CNS. Potential cases in which stem cell transplantation is being considered should be discussed at a multidisciplinary tumor board which includes involvement by hematologic oncologists and transplant specialists.

Lipidized glioblastoma: pathological and molecular characteristics.

We report a rare case of a 33-year-old man with a lipidized glioblastoma multiforme (GBM) in the right posterior frontal region. Histologically the tumor had all the typical features of a GBM but with the rare observation of lipidized differentiation. There were multiple mitoses, extensive vascular proliferation, focal necrosis and the tumor cells had abundant xanthomatous cytoplasm and marked nuclear pleomorphism. The tumor showed immunoreactivity with GFAP. The O(6) - methylguanine methyltransferase (MGMT) promoter was methylated and there were no isocitrate dehydrogenase (IDH)1 and IDH2 mutations. To the best of our knowledge, this is the first time MGMT promoter status and IDH mutation assessment have been reported in a case of lipidized GBM.

Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRα neurogenic pathway.

BACKGROUND: Glioblastoma (GBM) stem-like cells (GSCs) are crucial drivers of treatment resistance and tumor recurrence. While the concept of "migrating" cancer stem cells was proposed a decade ago, the roles and underlying mechanisms of the heterogeneous populations of GSCs remain poorly defined. METHODS: Cell migration using GBM cell lines and patient-derived GSCs was examined using Transwell inserts and the scratch assay. Single-cell RNA sequencing data analysis were used to map GSC drivers to specific GBM cell populations. Xenografted mice were used to model the role of brain-type fatty acid-binding protein 7 (FABP7) in GBM infiltration and expansion. The mechanism by which FABP7 and its fatty acid ligands promote GSC migration was examined by gel shift and luciferase gene reporter assays. RESULTS: A subpopulation of FABP7-expressing migratory GSCs was identified, with FABP7 upregulating SOX2, a key modulator for GBM stemness and plasticity, and ZEB1, a prominent factor in GBM epithelial-mesenchymal transition and invasiveness. Our data indicate that GSC migration is driven by nuclear FABP7 through activation of RXRα, a nuclear receptor activated by polyunsaturated fatty acids (PUFAs). CONCLUSION: Infiltrative progression in GBM is driven by migratory GSCs through activation of a PUFA-FABP7-RXRα neurogenic pathway.

Phase II trial of concurrent sunitinib, temozolomide, and radiotherapy with adjuvant temozolomide for newly diagnosed MGMT unmethylated glioblastoma.

Background: The overall prognosis of glioblastoma (GBM) remains dismal, particularly for patients with unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter. In this phase II trial, we tested the combination of the antiangiogenic agent sunitinib with radiotherapy and temozolomide (TMZ) for newly diagnosed unmethylated MGMT GBM patients. Methods: We enrolled 37 patients with unmethylated MGMT promoter GBM, age 18-70, and KPS ≥70. Patients received 12.5 mg of daily sunitinib for 7 days, followed by concurrent chemoradiation plus 12.5 mg sunitinib, then adjuvant TMZ. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), safety, and neutrophil-to-lymphocyte ratio (NLR) biomarker. Results: At a median follow-up time of 15.3 months (range: 3.1-71.3 months), the median PFS was 7.15 months (95% CI: 5.4-10.5) and the 6-month PFS was 54.0%. Median OS was 15.0 months (95% CI: 13.8-19.4) and 2-year OS rate was 17.1%. Patients receiving >3 cycles of adjuvant TMZ, undergoing surgery at progression, and presenting a post-concurrent NLR ≤6 experienced a significant improved OS with hazard ratios of 0.197 (P = .001), 0.46 (P = .049), and 0.38 (P = .021), respectively, on multivariable analysis. Age >65 years predicted for worse OS with hazard ratio of 3.92 (P = .037). Grade ≥3 thrombocytopenia occurred in 22.9%, grade ≥3 neutropenia in 20%, and grade ≥3 thromboembolic events in 14.3% of patients. There were no grade 5 events. Conclusion: Our findings suggest a potential benefit of combining sunitinib with chemoradiation in newly diagnosed GBM patients with unmethylated MGMT status and provide a strong rationale to test this combination in future studies.

A phase I study of temozolomide and everolimus (RAD001) in patients with newly diagnosed and progressive glioblastoma either receiving or not receiving enzyme-inducing anticonvulsants: an NCIC CTG study.

PURPOSE: This phase I trial was designed to determine the recommended phase II dose(s) of everolimus (RAD001) with temozolomide (TMZ) in patients with glioblastoma (GBM). Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and those not receiving EIAEDs (NEIAEDs) were studied separately. PATIENTS AND METHODS: Enrollment was restricted to patients with proven GBM, either newly diagnosed or at first progression. Temozolomide was administered at a starting dose of 150 mg/m(2)/day for 5 days every 28 days, and everolimus was administered continuously at a starting dose of 2.5 mg orally on a daily schedule starting on day 2 of cycle 1 in 28-day cycles. RESULTS: Thirteen patients receiving EIAEDs and 19 not receiving EIAEDs were enrolled and received 83 and 116 cycles respectively. Everolimus 10 mg daily plus TMZ 150 mg/m(2)/day for 5 days was declared the recommended phase II dose for the NEIAEDs cohort. In the EIAEDs group, doses were well tolerated without DLTs, and pharmacokinetic parameters indicated decreased everolimus exposure. Temozolomide pharmacokinetic parameters were unaffected by EIAEDs or everolimus. In the subset of 28 patients with measurable disease, 3 had partial responses (all NEIAEDs) and 16 had stable disease. CONCLUSION: A dosage of 10 mg everolimus daily with TMZ 150 mg/m(2)/day for five consecutive days every 28 days in patients is the recommended dose for this regimen. Everolimus clearance is increased by EIAEDs, and patients receiving EIAEDs should be switched to NEIAEDs before starting this regimen.

Extended adjuvant temozolomide for treatment of newly diagnosed glioblastoma multiforme.

The standard of care for newly diagnosed glioblastoma multiforme (GBM) is temozolomide (TMZ) chemotherapy given concurrently with radiation for 6 weeks followed by 6 months of adjuvant TMZ. Originally, patients in Alberta were treated with only six cycles of adjuvant TMZ regardless of clinical status but institutional policy was amended to allow up to 12 cycles of adjuvant therapy for patients experiencing at least stable disease and minimal toxicity. We conducted a population-based analysis to determine if extended adjuvant TMZ treatment (i.e., more than six cycles) confers a survival advantage as compared to the standard six cycles for newly diagnosed GBM patients. Patient data was collected from the Alberta Cancer Registry and patient charts. Progression free--and overall survival was determined in patients receiving six cycles of adjuvant TMZ and compared with that of patients receiving more than six cycles. Patients in whom adjuvant chemotherapy was stopped at cycle six experienced a median survival of 16.5 months, whereas, those who received more than six cycles survived for 24.6 months (p = 0.031). Extended adjuvant therapy was not associated with increased toxicity. In multivariate analysis, adjuvant monthly Temozolomide for more than six cycles was an independent prognostic factor for both progression free--and overall survival. These data suggest extended adjuvant temozolomide (i.e., more than six cycles) should be considered in patients with newly diagnosed GBM.

Is there a role for clinical practice guidelines in multidisciplinary tumor board meetings? A descriptive study of knowledge transfer between research and practice.

The aim of this study was to characterize practice patterns and decision-making processes of healthcare providers attending weekly neuro-oncology tumor board meetings, and to assess their familiarity with clinical practice guidelines (CPGs) in neuro-oncology. Members of the Neuro-Oncology Tumor Team at two tertiary cancer centers completed a web-based questionnaire assessing characteristics of weekly tumor board meetings and perceptions of CPGs. Twenty-three (66%) tumor team members responded. Diagnostic imaging results and interpretation, medical, surgical, and/or radiation treatment planning, and pathology results and interpretation were the most commonly identified aspects of patient care discussed at tumor board meetings, and almost all respondents indicated that these meetings were "very beneficial" to their own practice. When deciding on a treatment plan, respondents rely most on the clinical expertise of colleagues, medical literature, personal experience, active clinical trial protocols, and published CPGs. Opinions of the local CPGs varied considerably, and while 56% of respondents supported regular discussion of them during meetings, only 32% indicated that they were routinely reviewed. Updating the literature more frequently, implementing a formal grading system for the evidence, and incorporating clinical care pathways were the most frequently cited methods to improve the CPGs. Tumor board meetings are beneficial to the treatment planning process for neuro-oncology patients.

How well do European patients understand cancer-associated thrombosis? A patient survey.

Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess cancer-associated thrombosis (CAT) knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind among patients/caregivers with CAT. It identified significant gaps in patient awareness and knowledge of CAT as well as a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide awareness of what/when information should be shared with patients/caregivers. Notably, the importance of providing information on how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to identify CAT symptoms early. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.

Feasibility of Implementing Cancer-Specific Community-Based Exercise Programming: A Multi-Centre Randomized Trial.

BACKGROUND: There is growing recognition of the importance of reporting preliminary work on the feasibility of a trial. The present study aimed to assess the feasibility of (1) a proposed fitness testing battery, and (2) processes related to the implementation of cancer-specific exercise programming in a community setting. METHODS/DESIGN: A randomized controlled implementation feasibility trial was performed in advance of a large-scale implementation study. Eligible participants within 18 months of a cancer diagnosis were randomized to immediate or delayed community-based exercise at YMCA locations in Calgary and Edmonton, Canada for an 8-week period. The primary outcome for the trial was the feasibility of the physical fitness testing battery, defined as a 70% or greater completion rate across the 24-week study period. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was used to evaluate processes related to implementation of the exercise program across the two sites. RESULTS: Eighty participants were recruited, 73 (91%) completed the 8-week trial, and 68 (85%) completed the 16- and 24-week follow-ups. Sixty participants (75%) completed the full physical fitness test battery at each time point, and 59 (74%) completed the patient-reported outcome measures. Statistically significant between-group differences were found in favor of the exercise group for functional aerobic capacity, upper and lower extremity strength, and symptoms. Differences were found between the sites, however, in completion rates and processes related to program implementation. DISCUSSION: Findings suggest the need for minor adaptations to the physical fitness battery and outcome measures to better fit the community context. While findings support feasibility, context-specific challenges related to implementation processes were identified.

ACE-Neuro: A tailored exercise oncology program for neuro-oncology patients - Study protocol.

Background: Patients with primary brain tumours (i.e., neuro-oncology patients) lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise - Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness. Methods: Neuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro and other cancer rehabilitation services (including physiatry, physiotherapy, occupational therapy, and exercise physiology). In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes and functional fitness, and objective physical activity tracked across the 12-week program. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching. Conclusion: We are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.