Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study.

OBJECTIVE: To evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis. DESIGN: Cohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857). SETTING: North-East London Cancer Network (NELCN) population. POPULATION/SAMPLE: Women with high-grade non-mucinous epithelial OC. METHODS: A more detailed DA was developed using patient and stakeholder input following the principles/methodology of IPDAS (International Patients Decision Aids Standards). Unselected patients attending oncology clinics evaluated both a pre-existing short and a new long DA version and then underwent mainstreaming genetic testing by a cancer clinician. Appropriate inferential descriptive and regression analyses were undertaken. MAIN OUTCOME MEASURES: Satisfaction, readability, understanding, emotional well-being and preference for long/short DA. RESULTS: The mean age of patients was 66 years (interquartile range 11), and 85% were White British ethnicity. Of the participants, 74% found DAs helpful/useful in decision-making. Women reported higher levels of satisfaction (86% versus 58%, p < 0.001), right amount of information provided (76.79% versus49.12%, p < 0.001) and improved understanding (p < 0.001) with the long DA compared with the short DA. There was no statistically significant difference in emotional outcomes (feeling worried/concerned/reassured/upset) between 'short' and 'long' DA; 74% of patients preferred the long DA and 24% the short DA. Patients undergoing treatment (correlation coefficient (coef) = 0.603; 95% CI 0.165-1.041, p = 0.007), those with recurrence (coef = 0.493; 95% CI 0.065-0.92, p = 0.024) and older women (coef = 0.042; 95% CI 0.017-0.066, p = 0.001) preferred the short DA. Ethnicity did not affect outcomes or overall preference for long/short DA. CONCLUSIONS: A longer DA in OC patients has higher satisfaction without increasing emotional distress. Older women and those undergoing treatment/recurrence prefer less extensive information, whereas those in remission preferred a longer DA.

Characteristics of Convex Skin Barriers and Clinical Application: Results of an International Consensus Panel.

Regulatory bodies do not set parameters for measuring certain ostomy product characteristics. As a result, each manufacturer has a different way of measuring specific convex skin barrier characteristics that may create confusion among clinicians when selecting a product. In order to alleviate this confusion and encourage consistency in reporting product characteristics, an international meeting of clinicians with expertise in the care of persons living with an ostomy was convened. The goal of the meeting was to define and establish consistency in convex skin barrier characteristics and their clinical application of the product based on these characteristics. Twelve nurse panelists from 11 countries reviewed, discussed, and reached consensus on a group of proposed statements designed to provide standard definitions of convex skin barrier characteristics and clinically relevant application. The group reached consensus on 5 characteristics of convex skin barriers: depth, compressibility, flexibility, slope, and tension location. These statements provide a basis for quantifying the most clinically relevant characteristics of convex skin barriers and a framework for their application in clinical practice.

Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51-62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51-71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Evaluation of a Novel Ostomy Barrier Ring with Assisted Flow for Individuals with an Ileostomy.

OBJECTIVE: To determine the performance and user experience of a novel ostomy barrier ring over a 4-week period. METHODS: This single-arm investigation conducted across three clinical sites included 25 adult participants with an ileostomy for 3 months or longer. The participants used their standard ostomy pouching appliance along with a novel barrier ring for a period of 4 weeks. Skin condition was assessed using the Ostomy Skin Tool. Change in skin condition over the study period was recorded for each participant. The participants' experience in using the novel barrier ring was measured using a five-point Likert-type scale. RESULTS: Twenty of the 25 participants (80%) completed the trial. Of those participants, the median Ostomy Skin Tool score at both the beginning (range, 0-8) and end was 0 (range, 0-6). In terms of skin condition, 7 participants experienced an improvement in skin condition, 11 experienced no change, and 2 got worse. A median score of 5 out of 5 was recorded for all questions relating to user experience. CONCLUSIONS: Although not statistically significant, there was a clear trend toward improvements in peristomal skin condition using the novel barrier ring, even for participants who were already using a barrier ring. User feedback was positive with respect to comfort, device handling, and the perception of the device's ability to protect the skin. Further, most participants who already used a barrier ring indicated that the novel barrier ring would result in a longer wear time.

Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer.

PURPOSE: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHODS: Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULTS: A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/ß estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION: At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

Five-year outcome for women randomised in a phase III trial comparing doxorubicin and cyclophosphamide with doxorubicin and docetaxel as primary medical therapy in early breast cancer: an Anglo-Celtic Cooperative Oncology Group study.

To compare the long-term outcome of women with primary or locally advanced breast cancer randomised to receive either doxorubicin and cyclophosphamide (AC) or doxorubicin and docetaxel (AD) as primary chemotherapy. Eligible patients with histologic-proven breast cancer with primary tumours > or = 3 cm, inflammatory or locally advanced disease, and no evidence of distant metastases, were randomised to receive a maximum of 6 cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) i/v or doxorubicin (50 mg/m(2)) plus docetaxel (75 mg/m(2)) i/v every 3 weeks, followed by surgery on completion of chemotherapy. Clinical and pathologic responses have previously been reported. Time to relapse, site of relapse, and all-cause mortality were recorded. This updated analysis compares long-term disease-free (DFS) and overall survival (OS) using stratified log rank methods. A total of 363 patients were randomised to AC (n = 181) or AD (n = 182). A complete pathologic response was observed in 16% for AC and 12% for AD (P = 0.43). The number of patients with positive axillary nodes at surgery with AC was 61% and AD 66% (P = 0.36). At a median follow-up of 99 months there is no significant difference between the two groups for DFS (P = 0.20) and OS (P = 0.24). Deaths were due to metastatic breast cancer in 96% of patients. Our data do not support a clinical benefit for simultaneous administration of AD compared with AC. However, the data do not exclude a smaller benefit than the study was powered to detect and are consistent with an increase in both disease-free and overall survival of about 5% for AD compared with AC. Outcome is consistent with the pathologic complete response following surgery.

Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study.

PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.

Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS).

PURPOSE: In experimental systems, interference with coagulation can affect tumor biology. Furthermore, it has been suggested that low molecular weight heparin therapy may prolong survival in patients with cancer. The primary aim of this study was to assess survival at 1 year of patients with advanced cancer. PATIENTS AND METHODS: Patients with advanced malignancy (N = 385) were randomly assigned to receive either a once-daily subcutaneous injection of dalteparin (5,000 IU), a low molecular weight heparin, or placebo for 1 year. RESULTS: The Kaplan-Meier survival estimates at 1, 2, and 3 years after randomization for patients receiving dalteparin were 46%, 27%, and 21%, respectively, compared with 41%, 18%, and 12%, respectively, for patients receiving placebo (P =.19). In an analysis not specified a priori, survival was examined in a subgroup of patients (dalteparin, n = 55; and placebo, n = 47) who had a better prognosis and who were alive 17 months after randomization. In these patients, Kaplan-Meier survival estimates at 2 and 3 years from randomization were significantly improved for patients receiving dalteparin versus placebo (78% v 55% and 60% v 36%, respectively, P =.03). The rates of symptomatic venous thromboembolism were 2.4% and 3.3% for dalteparin and placebo, respectively, with bleeding rates of 4.7% and 2.7%, respectively. CONCLUSION: Dalteparin administration did not significantly improve 1-year survival rates in patients with advanced malignancy. However, the observed improved survival in a subgroup of patients with a better prognosis suggests a potential modifying effect of dalteparin on tumor biology.