Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients

Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.Subject terms: Breast cancer, Translational research, Predictive markers, Breast cancer     

Entering a World with No Future: A phenomenological study describing the embodied experience of time when living with severe incurable disease

Scand J Caring Sci; 2013; 27; 165–174 A phenomenological study describing the embodied experience of time when living with severe incurable disease This article presents findings from a phenomenological study exploring experience of time by patients living close to death. The empirical data consist of 26 open‐ended interviews from 23 patients living with severe incurable disease receiving palliative care in Norway. Three aspects of experience of time were revealed as prominent: (i) Entering a world with no future; living close to death alters perception of and relationship to time. (ii) Listening to the rhythm of my body, not looking at the clock; embodied with severe illness, it is the body not the clock that structures and controls the activities of the day. (iii). Receiving time, taking time; being offered – not asked for – help is like receiving time that confirms humanity, in contrast to having to ask for help which is like taking others time and thereby revealing own helplessness. Experience of time close to death is discussed as an embodied experience of inner, contextual, relational dimensions in harmony and disharmony with the rhythm of nature, environment and others. Rhythms in harmony provide relief, while rhythms in disharmony confer weakness and limit time.     

Translation of the Manchester Clinical Supervision Scale (MCSS) into Danish and a preliminary psychometric validation

A central challenge for empirical research of clinical supervision is how to measure the effectiveness of clinical supervision. The Manchester Clinical Supervision Scale (MCSS) measures supervisees' perception of the effectiveness of clinical supervision. The aims of this paper were to account for the translation of the MCSS from English into Danish and to present a preliminary psychometric validation of the Danish version of the scale. Methods included a formal translation/back‐translation procedure and statistical analyses. The sample consisted of MCSS scores from 139 Danish mental health nursing staff members. The total MCSS score had good internal consistency, but the analyses identified a number of reliability and consistency issues. The results were compared with other translations of the MCSS and with the reduced version of the MCSS, the MCSS‐26. The discussion indicated that MCSS theoretically refers to a broad conception of supervision, which includes supervision practices ranging from highly formalized events to more frequent ad hoc sessions. The MCSS's intention to measure perceptions of supervisees from this variety of practices may be problematic, and it is suggested that a further reduction of the type of practices MCSS currently aims at measuring could be beneficial.     

Relevance of neoadjuvant and adjuvant treatment for patients with resectable liver metastases of colorectal carcinoma

Background: Excellent results after resection of colorectal liver metastases are associated with a high rate of recurrence. Influenced by positive results of palliative and adjuvant treatment in advanced cancer, various chemotherapy regimens were evaluated to improve long-term results. Methods: The databases Medline and Cancerlit (1982–1998) gave information about 675 patients who were treated either by means of systemic, intra-arterial, intraportal or intraperitoneal administration before or after liver resection. Results: In general, the feasibility of an adjuvant treatment was tested. Proof has been furnished for the practicability of systemic and arterial therapy and for immunotherapy after liver resection whereas, for peritoneal and portal treatment, further studies are necessary. In a few non-randomised trials, it has been possible to discern a trend towards an improvement due to adjuvant postoperative therapy using historical or matched-pair control groups. Until now, only one of five randomised studies has been published. Six months of postoperative adjuvant intra-arterial treatment using 5-fluorouracil (1000 mg/m² for 5 days every 28 days) and folinic acid (200 mg/m² for 5 days every 28 days) was compared with observation only. Neither in the intention-to-treat nor in the as-treated analysis was median survival time (34.5 months versus 40.8 months and 39.7 months versus 44.8 months, respectively) significantly increased. As neoadjuvant treatment was successful in primary non-resectable patients, this approach is now being tested in resectable patients. Conclusion: Despite several theoretical reasons for post- or preoperative treatment in resectable patients, every approach should be tested using of controlled studies. Received: 2 March 1999 Accepted: 28 June 1999     

Unstable versus stable uncemented femoral stems: a radiological study of periprosthetic bone changes in two types of uncemented stems with different concepts of fixation

Introduction Uncemented stems in total hip arthroplasty (THA) are used increasingly often because they are believed to offer a reliable long-term fixation. However, periprosthetic bone remodelling has been a worrying issue. A proximal demineralization has been noted in femurs with well-fixed stems, and it has been explained as by-passing of mechanical forces along the fixed implant (stress-shielding). Aseptic loosening has been a major problem in several uncemented series with earlier designs. The objective for this study was to investigate how the host bone adapts to a loose stem compared with a well-fixed stem after a long time.Materials and methods An investigation with dual-energy X-ray absorptiometry (DEXA), scintimetry and radiological assessment was carried out in 20 patients 8 years after a THA for arthrosis with two different uncemented stems. Ten patients received a stem coated with polytetrafluoroethylene (Anaform); all prostheses showed migration and were considered unstable. Ten patients received a hydroxyapatite-coated stem (Bi-Metric); no prosthesis migrated.Results Different remodelling patterns were seen. In the unstable group, the periprosthetic bone mineral density (BMD) was significantly reduced along the entire stem, while in the stable group only proximal bone loss was seen. The scintigraphic uptake was increased under the stem tip in both groups, and among unstable stems uptake was also increased in the calcar region.Conclusion The assessment of periprosthetic bone remodelling after uncemented THA with long-term observation shows a different host-bone response in stable versus unstable femoral implants. Prior to a femoral revision, measurement of the BMD could be beneficial; it may guide the surgeon when deciding which surgical technique to use.