Developing Policy Infrastructure to Guide Genomics-Informed Oncology Nursing in Canada: An Interpretive Descriptive Study.

BACKGROUND: Genomic technologies such as genetic testing and precision treatments are rapidly becoming routine in oncology care, and nurses play an increasingly important role in supporting the growing demands for genomics-informed healthcare. Policy infrastructure such as competencies, standards, scope of practice statements, and education and curriculum frameworks are urgently needed to guide these practice and education changes. PURPOSE: This study is part of a larger three-phase project to develop recommendations and catalyze action for genomics-informed oncology nursing education and practice for the Canadian Association of Nurses in Oncology and the Canadian Association of Schools of Nursing. This phase aimed to enhance understanding of policy needs and action drivers for genomics-informed oncology nursing education and practice through the perspectives of Canadian oncology nurses and patient partners. METHODS: Interpretive description methodology guided the study. Twenty semi-structured virtual interviews were conducted; 17 with oncology nurses in various domains of practice, and three with patient partner representatives. Data collection and analysis occurred concurrently. RESULTS: Our analysis identified three themes: 1) nurses and patients recognize that it is time for action, 2) nurses and patients see advantages to executing intentional, strategic, and collaborative policy development, and 3) leadership and advocacy are required to drive action. CONCLUSION: Nursing policy infrastructure is required to increase genomic literacy, support nurses in providing safe patient care, and establish clear roles, responsibilities, and accountabilities within the interdisciplinary team. Strong leadership and advocacy at the practice, organizational, and systems levels are vital to accelerating action.

The Canadian Landscape of Genetics and Genomics in Nursing: A Policy Document Analysis.

BACKGROUND: Genetics and genomics (GG) are transforming approaches to healthcare in Canada and around the globe. Canadian nurses must be prepared to integrate GG in their practice, but modest research in this area suggests that Canadian nurses have limited GG competency. Countries that have integrated GG across nursing provided guidance to nurses about the practice implications of GG through regional nursing policy documents. These documents propelled action to integrate GG across nursing. Little is known about the GG content in the nursing policy document infrastructure in Canada. PURPOSE: This study aimed to examine the guidance for GG-informed nursing practice as provided by Canadian nursing organizations in official professional documents. METHODS: Qualitative document analysis was used. A hybrid inductive/deductive analysis approach was used to analyze findings within the diffusion of innovation theory framework. RESULTS: There is an overall lack of depth and breadth of Canadian nursing documents that include content related to GG. Of the (n = 37) documents analyzed, four themes were generated including (a) GG guidance in nursing education; (b) regulators' requirements for foundational GG knowledge, (c) Canadian Nurses Association (CNA) as an early catalyst to GG integration; and (d) early adopters in speciality practice. CONCLUSION: There are opportunities to enhance the guidance available to Canadian nurses for the application of GG, through documents of nursing professional associations, nursing education accreditation organizations, and regulatory bodies. Findings suggest oncology and perinatal nurses are the early adopters which is an important consideration in future strategies to implement GG into Canadian nursing.

Psychological and health behaviour outcomes following multi-gene panel testing for hereditary breast and ovarian cancer risk: a mini-review of the literature.

INTRODUCTION: Knowledge of the genetic mechanisms driving hereditary breast and ovarian cancer (HBOC) has recently expanded due to advances in gene sequencing technologies. Genetic testing for HBOC risk now involves multi-gene panel testing, which includes well characterized high-penetrance genes (e.g. BRCA1 and BRCA2), as well as moderate- and low-penetrance genes. Certain moderate and low penetrance genes are associated with limited data to inform cancer risk estimates and clinical management recommendations, which create new sources of genetic and clinical uncertainty for patients. PURPOSE: The aim of this review is to evaluate the psychological and health behaviour outcomes associated with multi-gene panel testing for HBOC risk. The search was developed in collaboration with an Information Specialist (Princess Margaret Cancer Centre) and conducted in the following databases: MEDLINE, EMBASE, EMCare, PsycINFO, Epub Ahead of Publication. RESULTS: Similar to the BRCA1/2 literature, individuals with a pathogenic variant (PV) reported higher levels of testing-related concerns and cancer-specific distress, as well as higher uptake of prophylactic surgery in both affected and unaffected individuals compared to those with variant of uncertain significance (VUS) or negative result. A single study demonstrated that individuals with a PV in a moderate penetrance gene reported higher rates of cancer worry, genetic testing concerns and cancer-related distress when compared to women with high penetrance PV. Analysis of cancer screening and prevention outcomes based upon gene penetrance were limited to two studies, with conflicting findings. CONCLUSION: The findings in this review emphasize the need for studies examining psychological and health behavior outcomes associated with panel testing to include between group differences based upon both variant pathogenicity and gene penetrance. Future studies evaluating the impact of gene penetrance on patient-reported and clinical outcomes will require large samples to be powered for these analyses given that a limited number of tested individuals are found to have a PV.

Psychosocial Interventions for Women with a BRCA1 or BRCA2 Mutation: A Scoping Review.

This scoping review aimed to explore the effectiveness of psychological and psychoeducational interventions for BRCA mutation carriers. Four electronic bibliographic databases were searched. After review, 23 articles that described or assessed forms of an additional psychosocial intervention for individuals with a BRCA mutation were identified and included. Intervention types discussed in the articles were telephone-based peer-to-peer counselling (5), online communities (4), in-person group counselling (8), and one-day sessions (6). Outcomes investigated within the articles included psychosocial outcomes (18), satisfaction (8), health behaviours (7), and knowledge (5). The included studies suggested that telephone-based peer-to-peer counselling and online communities improve patient knowledge and psychosocial functioning and can overcome challenges such as scheduling and travel associated with in-person support groups, but may have challenges with recruitment and retainment of participants. Group in-person education sessions satisfied the need amongst BRCA1/2 carriers in terms of accessing necessary information regarding cancer risk assessment and management; however, the impact of group education sessions on psychological outcomes was variable across the included studies. Overall, all the forms of intervention described in this scoping review were well-received by participants; some have been shown to reduce distress, depression, and anxiety.

Quality of life drives patients' preferences for secondary findings from genomic sequencing.

There is growing impetus to include measures of personal utility, the nonmedical value of information, in addition to clinical utility in health technology assessment (HTA) of genomic tests such as genomic sequencing (GS). However, personal utility and clinical utility are challenging to define and measure. This study aimed to explore what drives patients' preferences for hypothetically learning medically actionable and non-medically actionable secondary findings (SF), capturing clinical and personal utility; this may inform development of measures to evaluate patient outcomes following return of SF. Semi-structured interviews were conducted with adults with a personal or family cancer history participating in a trial of a decision aid for selection of SF from genomic sequencing (GS) ( www.GenomicsADvISER.com ). Interviews were analyzed thematically using constant comparison. Preserving health-related and non-health-related quality of life was an overarching motivator for both learning and not learning SF. Some participants perceived that learning SF would help them "have a good quality of life" through informing actions to maintain physical health or leading to psychological benefits such as emotional preparation for disease. Other participants preferred not to learn SF because results "could ruin your quality of life," such as by causing negative psychological impacts. Measuring health-related and non-health-related quality of life may capture outcomes related to clinical and personal utility of GS and SF, which have previously been challenging to measure. Without appropriate measures, generating and synthesizing evidence to evaluate genomic technologies such as GS will continue to be a challenge, and will undervalue potential benefits of GS and SF.

The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

OPINION STATEMENT: Concurrent chemoradiotherapy (CRT) with high-dose (100 mg/m2), single-agent cisplatin is considered the standard of care for locoregionally advanced head and neck cancer (LAHNC). Poor compliance often due to significant treatment-related toxicities observed during CRT regimen has stimulated research efforts to examine for evidence of the optimal cumulative cisplatin dose and schedule. The findings from this systematic literature review demonstrate that there are insufficient prospective, randomized controlled data to determine the optimal total dose (and schedule) of cisplatin to administer concomitantly with radiotherapy in the treatment of LAHNC. Given the clinical challenges associated with administering concurrent CRT with single-agent high-dose cisplatin, as well as the long-term toxicities accompanying this treatment, an examination of the available literature for evidence of dose efficacy is of continued clinical interest. Moving forward, it is critical that researchers include complete descriptions of key disease and treatment variables (i.e. treatment compliance and HPV status) to inform and strengthen clinical decisions. The substantial heterogeneity of LAHNC has led to the focus of recent research efforts to risk-stratify using a combination of clinical and molecular markers (e.g. HPV status). Thus, the optimal total dose (and schedule) of cisplatin may need to be modified to reflect the specific characteristics of the individual patient subpopulations being treated. At present, CRT remains the standard of care for LAHNC, but this field is rapidly evolving. National and international clinical trials are ongoing to evaluate treatment de-intensification in favourable risk patient subsets and treatment intensification in poor-risk patient subsets, these will provide evidence-based guidance to individualize therapy with the ultimate goal of improving patient outcomes.

Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial.

PURPOSE: Women with a BRCA1 or BRCA2 mutation are at high risk for breast cancer and must make important decisions about breast cancer prevention and screening. In the current study, we report a multisite, randomized, controlled trial evaluating the effectiveness of a decision aid for breast cancer prevention in women with a BRCA mutation with no previous diagnosis of cancer. METHODS: Within 1 month of receiving a positive BRCA result, women were randomized to receive either usual care (control group) or decision aid (intervention group). Participants were followed at 3, 6, and 12 months; were asked about preventive measures; and completed standardized questionnaires assessing decision making and psychosocial functioning. RESULTS: One hundred fifty women were randomized. Mean cancer-related distress scores were significantly lower in the intervention group compared with the control group at 6 months (P = 0.01) and at 12 months postrandomization (P = 0.05). Decisional conflict scores declined over time for both groups and at no time were there statistical differences between the two groups. CONCLUSION: The decision aid for breast cancer prevention in women with a BRCA1 or BRCA2 mutation is effective in significantly decreasing cancer-related distress within the year following receipt of positive genetic test results.Genet Med 19 3, 330-336.

Randomized feasibility study of de-escalated (every 12 wk) versus standard (every 3 to 4 wk) intravenous pamidronate in women with low-risk bone metastases from breast cancer.

OBJECTIVES: Despite substantial variability in individual risk of skeletal complications, patients with metastatic bone disease are treated with bisphosphonates at the same dose and dosing interval. This study assessed the feasibility of conducting a randomized trial of less frequent bisphosphonate administration in women with breast cancer and low-risk bone metastases. METHODS: A randomized feasibility study was conducted. Patients receiving intravenous bisphosphonates for ≥3 months and with low-risk baseline serum C-telopeptide (CTx) levels (<600 ng/L) were assigned to pamidronate 90 mg intravenously every 3 to 4 weeks (control) or every 12 weeks (de-escalated). CTx, bone alkaline phosphatase, and pain scores (Brief Pain Inventory and Functional Assessment of Cancer Therapy-Bone Pain) were collected every 12 weeks for 48 weeks. RESULTS: Fifty-four patients were approached, 44 consented, and 38 were randomized. Median age was 55 (range, 29 to 77) and median baseline CTx was 163 ng/L (range, 10 to 526). Fourteen control group participants (73.7%) and 13 de-escalated group participants (68.4%) maintained CTx in the low-risk range (P=0.64). All patients changing to higher-risk range had progressive extraskeletal disease. Compared with the control group, there was a time-dependent increase in CTx in the de-escalated group. There were no significant differences in bone alkaline phosphatase, Brief Pain Inventory, or Functional Assessment of Cancer Therapy-Bone Pain. CONCLUSIONS: It is feasible to conduct randomized trials of de-escalated pamidronate in low-risk women treated with ≥3 months of prior bisphosphonate therapy. De-escalated scheduling satisfied our predefined definition of noninferiority compared with 3- to 4-weekly treatment. Larger trials should assess whether increasing CTx levels with de-escalated therapy lead to higher rates of skeletal complications.

Management of small HER2 overexpressing tumours.

Overexpression of the human epidermal growth factor receptor 2 (HER2) is found in 10-20 % of breast cancers and is associated with a worse prognosis. Several large studies have established the addition of trastuzumab to chemotherapy as the gold standard in early breast cancer that overexpresses HER2. Little is known about the role of such adjuvant treatment in node-negative subcentimeter tumours ('small tumours', pT1a/b) because these patients were generally excluded from the pivotal trials. Only the BCIRG006 study published in 2011 included such tumours if high-risk features were present. Here we review the literature of small HER2-positive tumours and present a meta-analysis of retrospective studies confirming a worse outcome in terms of disease-free survival (hazard ratio 2.6, p < 0.001) and a trend for higher odds of distant recurrence at 5 years (odds ratio [OR] 2.51, p = 0.11). We discuss these findings in the light of the increased risk of grade 3 and 4 cardiac toxicity (OR 7.6, p < 0.001) and other adverse events associated with the use of trastuzumab. Such treatment may well be a valuable option in selected patients with high-risk features but physicians should exercise caution given the small absolute benefits of adjuvant chemotherapy and trastuzumab for patients with small HER2-overexpressing tumours.

Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Aromatase inhibitors are associated with consistent improvements in disease-free survival but not in overall survival. We conducted a literature-based meta-analysis of randomized trials to examine whether the relative toxicity of aromatase inhibitors compared with tamoxifen may explain this finding. METHODS: We conducted a systematic review to identify randomized controlled trials that compared aromatase inhibitors and tamoxifen as primary adjuvant endocrine therapy in postmenopausal women by searching MEDLINE, EMBASE, and databases of the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium. Odds ratios (ORs), 95% confidence intervals (CIs), absolute risks, and the number needed to harm associated with one adverse event were computed for prespecified serious adverse events including cardiovascular disease, cerebrovascular disease, bone fractures, thromboembolic events, endometrial carcinoma and other second cancers not including new breast cancer. All statistical tests were two-sided. RESULTS: Seven trials enrolling 30,023 patients met the inclusion criteria. Longer duration of aromatase inhibitor use was associated with increased odds of developing cardiovascular disease (OR = 1.26, 95% CI = 1.10 to 1.43, P < .001; number needed to harm = 132) and bone fractures (OR = 1.47, 95% CI = 1.34 to 1.61, P < .001; number needed to harm = 46), but a decreased odds of venous thrombosis (OR = 0.55, 95% CI = 0.46 to 0.64, P < .001; number needed to harm = 79) and endometrial carcinoma (OR = 0.34, 95% CI = 0.22 to 0.53, P < .001; number needed to harm = 258). Five years of aromatase inhibitors was associated with a non-statistically significant increased odds of death without recurrence compared with 5 years of tamoxifen alone or tamoxifen for 2-3 years followed by an aromatase inhibitor for 2-3 years (OR = 1.11, 95% CI = 0.98 to 1.26, P = .09). CONCLUSIONS: The cumulative toxicity of aromatase inhibitors when used as up-front treatment may explain the lack of overall survival benefit despite improvements in disease-free survival. Switching from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the best balance between efficacy and toxicity.