Randomized Controlled Trial of Virtually Delivered Cognitive Behavioral Therapy for Insomnia to Address Perceived Cancer-Related Cognitive Impairment in Cancer Survivors.

PURPOSE: Comorbid insomnia and cancer-related cognitive impairment (CRCI) are experienced by up to 26% of individuals diagnosed with cancer. This study examined the efficacy and durability of cognitive behavioral therapy for insomnia (CBT-I) on perceived CRCI in cancer survivors. METHODS: Atlantic Canadian cancer survivors with insomnia and CRCI were randomly assigned to receive seven weekly virtual CBT-I sessions (n = 63) or placed in a waitlist control group (n = 69) to receive treatment after the waiting period. Participants completed assessments at baseline, 1 month (mid-treatment), and 2 months (post-treatment). Age- and education-adjusted mixed-effects models using intention-to-treat principles assessed change at post-treatment. Data from both groups were then pooled to assess the durability of effects at 3 and 6 months. A mediation analysis examined whether change in insomnia symptoms mediated the effect of CBT-I on cognitive outcomes. RESULTS: The mean age of the sample was 60 years, 77% were women, and breast cancer was the most common diagnosis (41%). The treatment group reported an 11.35-point reduction in insomnia severity, compared with a 2.67-point reduction in the waitlist control group (P < .001). The treatment group had a greater overall improvement than the waitlist control on perceived cognitive impairment (P < .001; d = 0.75), cognitive abilities (P < .001; d = 0.92), and impact on quality of life (P < .001; d = 1.01). These improvements were maintained at follow-up. Change in insomnia symptoms fully mediated the effect of CBT-I on subjective cognitive outcomes. CONCLUSION: Treating insomnia with CBT-I produces clinically meaningful and durable improvements in CRCI. There is an urgent need increase access to evidence-based treatment for insomnia in cancer centers and the community.

Perceived Executive Functioning Deficits After Diagnosis in Women with Non-Metastatic Breast Cancer Prior to Adjuvant Therapies.

BACKGROUND: Perceived deficits in executive functioning are among the many difficulties that women diagnosed with breast cancer experience. This study assessed the presence of perceived deficits in executive functioning among women with breast cancer prior to systemic treatment and radiation and associations between perceived deficits in executive function and comorbid fatigue, sleep, and mood disturbance. METHOD: Participants were recruited following their breast cancer diagnosis and assessed using the Behavior Rating Inventory of Executive Function for Adults (BRIEF-A), subjective and objective measures of sleep duration and efficiency, and self-report measures of insomnia severity, sleep quality, fatigue, and mood disturbance. Hierarchical regression was used to examine associations between symptoms, adjusting for age and education. RESULTS: The final sample included 92 women with a mean age of 60.7 years and 13.5 years of education. Thirteen percent of participants reported global executive dysfunction. After partitioning out variability from other independent variables, fatigue (p = < .001), perceived sleep quality (p = .030), and symptoms of insomnia (p = .008) accounted for 13.3%, 5.7%, and 8.5% of unique variance in perceived executive functioning, respectively. Emotional fatigue was most strongly associated with perceived deficits in executive functioning. Neither subjective or objective sleep duration or efficiency was associated with perceived deficits in executive functioning. CONCLUSION: Fatigue, particularly emotional fatigue, insomnia, and poor sleep quality had the strongest associations with perceived deficits in executive functioning. Sleep interventions and fatigue management strategies may prove useful for women who seek to improve their perceived executive functioning.

Novel Therapies for the Treatment of HER2-Positive Advanced Breast Cancer: A Canadian Perspective.

The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, we can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane. In the second-line setting, clinical trials show that trastuzumab deruxtecan (T-DXd) is a highly effective option, resulting in a shift from trastuzumab emtansine (T-DM1) as the previous standard of care. Moreover, we now have data for patients with brain metastases to show that tucatinib + trastuzumab + capecitabine can improve survival in this higher-risk group and be an effective regimen for all patients in the third-line setting. Finally, we have a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes. This review paper discusses the current treatment options and presents a practical treatment sequencing algorithm in the context of the Canadian landscape.

Rationale and protocol for a randomized waitlist controlled trial of videoconference delivered cognitive behaviour therapy for insomnia (CBT-I) to improve perceived cognitive impairment (PCI) among cancer survivors.

Perceived cognitive impairment (PCI) and sleep disturbances (such as insomnia) are commonly reported barriers preventing cancer survivors from resuming normal functioning. Cognitive-behaviour therapy for insomnia (CBT-I) is the treatment of choice for insomnia among cancer survivors. Literature suggests that treatment with CBT-I may lead to an improvement in PCI, but this needs to be tested in a sample of patients with PCI at study entry with cognitive impairments as the primary study outcome. Here we describe the design of a clinical trial to evaluate the efficacy of videoconference-delivered CBT-I for the improvement of PCI among cancer survivors. This project is a randomized waitlist-controlled trial with a recruitment target of 124 adult cancer survivors (solid tumors and hematological malignancies) who have completed primary treatment at least 6 months prior, report PCI and meet criteria for insomnia disorder. Participants will complete assessments at baseline, 4 weeks (mid-treatment), 8 weeks (post treatment), and 3 and 6 months post-treatment. The primary outcome is the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog). Treatment of PCI in cancer patients is a priority for clinicians, researchers, and patients. This research will increase our understanding of the mechanisms of cognitive impairment associated with cancer, and potentially expand currently available treatment options.

Evaluating the experience of rural individuals with prostate and breast cancer participating in research via telehealth.

INTRODUCTION: Studies that use objective assessments often only recruit individuals in the geographic region in which the study is being conducted, because the assessments require that the researcher and participant be face to face. This limits the number and variety of individuals who can participate. Telehealth is one approach that could be used to increase sample size and representativeness. The present analysis aims to evaluate the experience of individuals diagnosed with breast or prostate cancer, who participated by telehealth in studies investigating the effects of cancer treatment on sleep and cognition. Specifically, this study aimed to highlight potential benefits of using telehealth and identify ways to improve the process for future studies and assessments. METHODS: Telephone interviews were conducted with 20 individuals with cancer who participated via telehealth in a larger study investigating the effects of cancer treatment on sleep and cognition; 12 individuals had breast cancer and 8 individuals had prostate cancer. Participants were organized into the four regional health authorities of Newfoundland and Labrador: Eastern, Western, Central, and Grenfell-Labrador. Participants of varying ages and communities were purposively selected. Participants were interviewed about their experience participating in the study via telehealth and invited to offer suggestions for how to improve the process. Interview transcripts were coded using a thematic analysis approach. Demographic information was used to characterize the sample. RESULTS: Including telehealth as an option in the overall study allowed for a 55% sample size increase for participants with breast cancer, and a 45% sample size increase for participants with prostate cancer. Participants reported an overall positive experience (70% reported the experience as good and/or great), with telehealth allowing for greater convenience, more personable interactions, increased access, and an otherwise unavailable opportunity to help others and themselves. Identified areas for improvement were sound quality, and better access for those who still face barriers of commuting to telehealth locations. Inter-rater reliability yielded a 92% agreement. CONCLUSIONS: For studies and assessments requiring face-to-face contact, telehealth is clearly a feasible option for improving research representativeness and access for individuals residing in rural areas. Future research should make use of telehealth services, to give a voice to rural individuals who are too often left out.

Choosing Wisely Canada cancer list: ten low-value or harmful practices that should be avoided in cancer care.

PURPOSE: Choosing Wisely Canada, modeled after Choosing Wisely in the United States, is intended to identify low-value or potentially harmful practices relevant to the Canadian health care environment. Our objective was to use multidisciplinary, pan-Canadian, physician-based consensus to identify a list of low-value or harmful cancer practices frequently used in Canada. METHODS: A Task Force convened by the Canadian Partnership Against Cancer included physician representation from the Canadian Society of Surgical Oncology, Canadian Association of Medical Oncologists, and Canadian Association of Radiation Oncology, and an expert advisor. The methodology included four phases: identify potentially relevant items, develop a long list, refine and reduce the long list to a short list, and select and endorse a final list. A framework-driven consensus process and a series of electronic surveys and voting processes were used to capture consensus. RESULTS: Sixty-six potentially relevant cancer-related practices were identified. The long list (41 practices) was reduced to a short list of 19 practices. Of the 10 practices on the final list, five are completely new, and five are revisions or adaptations of practices from previous US society lists. Six of the 10 involve multiple disease sites, and four are disease-site specific. One relates to diagnosis, six relate to treatment, two relate to surveillance/survivorship, and one practice spans the cancer care continuum. CONCLUSION: The cancer list was developed in partnership with the Canadian Society of Surgical Oncology, Canadian Association of Medical Oncologists, and Canadian Association of Radiation Oncology. Using knowledge translation and exchange efforts, this list should empower patients with cancer and physicians to assist in a targeted conversation about the appropriateness and quality of individual patient care.

Outcomes assessment of a pharmacist-directed seamless care program in an ambulatory oncology clinic.

The primary goal of seamless care is improved patient outcomes and improved standards of care for patients with cancer. The pharmacy service of the Newfoundland Cancer Treatment and Research Foundation conducted a randomized control study that measured clinical and humanistic outcomes of a pharmacist-directed seamless care program in an ambulatory oncology clinic. This article focuses on the intervention group, particularly the identification of drug-related problems (DRPs) and utilization of health care services as well the satisfaction of 3 types of health professionals with the services provided by the pharmacist-directed seamless care program. Overall, the seamless care pharmacist (SCP) identified an average of 3.7 DRPs per intervention patient; the most common DRP reported was a patient not receiving or taking a drug therapy for which there is an indication. The SCP identified more DRPs in patients receiving adjuvant treatment compared to those receiving palliative treatment. On average, family physicians, oncology nurses, and hospital pharmacists were satisfied with the SCP intervention indicating that they agreed the information collected and distributed by the SCP was useful to them. Pharmacist-directed seamless care services in an ambulatory oncology clinic have a significant impact on clinical outcomes and processes of patient care. The presence of a SCP can help identify and resolve DRPs experienced by patients in an outpatient oncology clinic, ensuring that patients are receiving the highest standard of care.

Use of bisphosphonates in metastatic breast cancer: single institution review at the Dr. H. Bliss Murphy Cancer Centre.

PURPOSE: Bone metastases occur in 65-75% of patients with metastatic breast cancer. These patients are at risk of developing skeletal-related events (SREs). SREs are defined as any pathological fracture, spinal cord compression, hypercalcemia, and surgery or radiation required for treatment of bone metastases. Bisphosphonates are used to prevent the development of SREs. The purpose of this study is to review the incidence of SREs in metastatic breast cancer patients with bony disease in Newfoundland and Labrador and to determine if there is an association between SREs and the type of bisphosphonate therapy given. METHODS: This retrospective chart review includes all metastatic breast cancer patients with bony disease treated at the Dr. H. Bliss Murphy Cancer Centre from 2008 to 2010. Patient demographics, treatment received, and treatment changes were collected. Patients at the Centre received bisphosphonate, pamidronate or zolendronic acid to prevent SREs. The prescribing pattern of bisphosphonates was collected. The occurrences of SREs were then compared to the type of treatment received. RESULTS: Sixty-five patients with breast cancer and bony metastasis were identified using the provincial tumor registry, three patients were excluded from the review as their charts could not be located. Following the initial diagnosis of bone metastasis, 8 patients (12.7%) were started on zolendronic acid, 50 patients (80.6%) were started on pamidronate, and 4 (6.4%) received no treatment. Six patients (75%) on zolendronic acid experienced one SRE; however, none experienced multiple SREs. Thirty-one patients (62%) on pamidronate experienced one SRE, and ten (20%) had multiple SREs. Of the 31 patients on pamidronate with an SRE, 4 (12.9%) were switched to zolendronic acid. Three of the four (75%) had multiple SREs despite treatment changes. Of the six patients on zolendronic acid with SREs, none were switched to pamidronate. CONCLUSION: Our results show that the majority of patients with breast cancer, who develop bony metastases in Newfoundland and Labrador, are initially treated with the bisphosphonate, pamidronate. Over 60% of these patients experienced at least one SRE, and 20% had more than two SREs. A small proportion of the patients were initially started on zolendronic acid, and this group had better outcomes with fewer SREs and none had more than two SREs. It appears that zolendronic acid is superior to pamidronate in preventing SREs; however, zolendronic acid is being used primarily as second-line in Newfoundland and Labrador.

Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial.

BACKGROUND: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. METHODS: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. FINDINGS: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. INTERPRETATION: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. FUNDING: Sanofi.

Access to cancer drugs in Canada: looking beyond coverage decisions.

OBJECTIVE: To examine variation in patients' access to a set of cancer drugs through publicly funded provincial drug programs. DATA SOURCES/STUDY DESIGN: We surveyed provincial drug program managers about their highest-expenditure intravenous and oral cancer drugs. We then investigated whether the same cancer drugs account for the highest expenditures across the provincial programs. We also compared the rates at which these drugs are accessed through these programs. PRINCIPAL FINDINGS: While there is moderate consistency in the selection of cancer drugs that account for the highest provincial expenditures, considerable differences were found in the rates at which some drugs are accessed across provincial programs. CONCLUSIONS: The study demonstrates the existence of interprovincial variation in publicly funded access to cancer drugs even after these drugs have been approved for public coverage.

Adjuvant targeted therapy in early breast cancer.

For this review, the authors appraised the evidence for adjuvant trastuzumab therapy in early breast cancer. There was level 1 evidence to support the routine use of 1 year of adjuvant trastuzumab in conjunction with chemotherapy for women with human epidermal growth factor receptor 2 (HER-2)-positive early breast cancer. The relative benefits of concurrent versus sequential administration remained unclear; however concurrent administration permitted the earliest possible intervention with trastuzumab with possible superiority. There was evidence to support the use of trastuzumab in both lymph node-positive and high-risk lymph node-negative patients, and preliminary data suggested that all patient subgroups that were eligible for the trials benefit equally from trastuzumab. Adjuvant trastuzumab was associated with a risk of cardiotoxicity, the long-term impact of which remains largely unknown. Routine cardiac risk assessment considering left ventricular ejection fraction, age, and prior history of cardiac events is recommended along with the selection of trastuzumab-based regimens that minimize cardiotoxicity. Trastuzumab acquisition costs for 1 year of therapy were the largest component of treatment costs.

Selection of adjuvant chemotherapy for treatment of node-positive breast cancer.

Over the past two decades, several studies have suggested that regimens that contain anthracyclines are more effective than those that do not. A meta-analysis by the 2005 Early Breast Cancer Trialists' Collaborative Group confirmed that about 6 months of anthracycline-based polychemotherapy in the adjuvant setting reduced the yearly death rate from breast cancer by about 38% for women younger than 50 years and by 20% for women aged 50-69 years. Although this meta-analysis found that survival was better with regimens that contain anthracycline than with regimens based on cyclophosphamide, methotrexate, and fluorouracil, the best use of anthracycline-based regimens remains unclear. Adjuvant regimens in use can be categorised into three groups: standard-dose anthracycline; escalated-dose epirubicin; and anthracyclines and taxanes. The duration of treatment and combination of dose and drugs varies between these three categories. We reviewed the three types of regimen to establish which provide a better outcome in terms of safety, efficacy, cost, and convenience to patients. We found that both escalated-dose epirubicin and anthracycline-taxane regimens were most effective in terms of disease-free survival and overall survival. Of the specific anthracycline-based regimens, the docetaxel, doxorubicin, and cyclophosphamide regimen (TAC); the fluorouracil, 100 mg epirubicin, and cyclophosphamide regimen (FEC100); and the cyclophosphamide, epirubicin, and fluorouracil regimen (CEF) produced the greatest proportional decreases in 5-year death rate.