The addition of bevacizumab to standard chemotherapy in breast cancer : which patient benefits the most?

Bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor, is an effective and well-tolerated treatment option for patients with breast cancer. Bevacizumab has demonstrated a gain in progression-free survival and a trend towards an overall survival benefit in various subgroups of breast cancer. Given the lack of a predictive biomarker, we performed a literature search with regard to efficacy and tolerability of bevacizumab in different subgroups of breast cancer patients and in different settings. In the metastatic setting, the efficacy of bevacizumab has been most extensively studied and demonstrated in patients with triple-negative breast cancer, the most difficult-to-treat population among patients with advanced disease and also the group with the biggest need for new treatment options. Overall, bevacizumab is well tolerated with very few serious adverse events. Bevacizumab is also an active and feasible treatment option for patients above 70 years of age

Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports

Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an inhibitory molecule typically expressed on T cells. Blockade of CTLA-4 induces an overall activation of T cells, including an immune-mediated anti-tumour response. Unfortunately, this broad T cell stimulation also causes immune-related adverse events (irAEs), such as dermatitis, colitis, hepatitis and hypophysitis. Ipilimumab is currently available in Belgium as a second line of treatment for patients with advanced melanoma, and is used at a dose of 3 mg/kg of body weight, although higher doses were previously used (up to 10 mg/kg). We performed a retrospective analysis to identify melanoma patients treated with ipilimumab at the Ghent University Hospital between 2010 and 2013. Data on symptoms, stage and timing of ipilimumab, response and adverse events were collected with a special attention to endocrine disturbances, going from a limited involvement of one endocrine axis to development of a hypophysitis. We identified a total of 39 patients with stage III (No. = 7) or stage IV (No. = 32) melanoma, who received a dose of 3 (No. = 31) or 10 (No. = 8) mg/kg. Six patients developed a severe form of irAEs, including one case of colitis (2 %), one case of sarcoidosis (2 %) and 4 cases (10 %) of hypophysitis. Hypophysitis developed between the second and fourth cycle of ipilimumab administration and was independent of the dose used. We describe four cases of involvement of the pituitary gland during treatment with ipilimumab. When managed with vigilant monitoring and high-dose corticosteroids, the acute symptoms resolve, but lifelong hormone substitution therapy can be necessary. Involvement of the pituitary axes is a severe side effect of treatment with ipilimumab with an urgent need for the correct medical intervention

Contrast-enhanced ultrasonography in hepatosplenic sarcoidosis

We report a case of a 38-year-old woman with atypical pain in the left lower hemi-abdomen. On abdominal B-mode ultrasonography the liver was normal; the spleen showed multiple subcentimetric hypoechoic nodules. A multidetector CT-examination revealed multiple small low-attenuation nodules in the liver and the spleen, suggestive for metastatic disease. Contrast-enhanced ultrasound (CEUS) revealed two hypoechoic nodules in the liver that were visible in the portal phase and disappeared in the late phase. The focal splenic lesions were visible as irregular hypo-enhancing nodules. An MRI examination, including T1, T2 and contrast-enhanced images, could not confirm the exact nature of the lesions. A core biopsy of a splenic nodule yielded non-caseating epithelioid cell granulomas. Different complementary examinations were normal and hepatosplenic sarcoidosis was diagnosed. The pain in the left lower hemi-abdomen was ascribed to irritable bowel syndrome

Quality of life and symptom intensity over time in people with cancer receiving palliative care : results from the international European Palliative Care Cancer Symptom study

Background People with advanced cancer experience multiple symptoms during their illness trajectory, which can fluctuate in intensity. Aim To describe the course of self-reported quality of life, emotional functioning, physical functioning and symptom intensity over time in cancer patients receiving palliative care. Design Longitudinal study with monthly assessments, using the EORTC QLQ-C15-PAL. Data were analysed (1) prospectively, from baseline to >= 8-month follow-up; and (2) retrospectively, by taking death as index date and comparing results from three cross-sectional subsamples at different stages of illness (time to death >= 6, 5-3 and 2-0 months). Linear mixed models were calculated. Setting/participants A total of 1739 patients (mean age 66, 50% male) from 30 palliative care centers in 12 countries were included. Results In prospective analyses, quality of life, functioning and symptoms-except nausea/vomiting-remained generally stable over time. In retrospective analyses, patients 2-0 months before death reported significantly lower quality of life and physical functioning scores than those 5-3 months before death, who in turn scored lower than those >= 6 months before death, suggesting progressive decline. Emotional functioning remained initially unchanged, but decreased in the last months. Pain, fatigue and appetite loss showed a stable increase in intensity towards death. Dyspnea, insomnia and constipation increased from 5-3 to 2-0 months before death. Nausea/vomiting only increased when comparing those >= 6 months before death with those 2-0 months before death. Conclusion While the prospective approach showed predominantly stable patterns for quality of life, functioning and symptom severity throughout study duration, retrospective analyses indicated that deterioration was already apparent before the terminal phase and accelerated close to death. Our findings support the importance of early symptom identification and treatment in this population, and highlight the need for further studies to explore what characterizes those with either lower or higher symptom burden at different time points towards death

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

Introduction: Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods: Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results: Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70-0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59-0.82], P = 0.042) as isolated test. Conclusions: We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation

'A palliative end-stage COPD patient does not exist' : a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD

Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers' education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients' disease insight and training PHC nurses in care for end-stage COPD

Development of a complex intervention for early integration of palliative home care into standard care for end-stage COPD patients : a phase 0-I study

Background : Research suggests that palliative home care should be integrated early into standard care for end-stage COPD patients. Patients also express the wish to be cared for and to die at home. However, a practice model for early integration of palliative home care (PHC) into standard care for end-stage COPD has not been fully developed. Aim : To develop an intervention for early integration of PHC into standard care for end-stage COPD patients. Methods : We conducted a Phase 0-I study according to the Medical Research Council Framework for the development of complex interventions. Phase 0 aimed to identify the inclusion criteria and key components of the intervention by way of an explorative literature search of interventions, expert consultations, and seven focus groups with general practitioners and community nurses on perceived barriers to and facilitators of early integrated PHC for COPD. In Phase 1, the intervention, its inclusion criteria and its components were developed and further refined by an expert panel and two expert opinions. Results : Phase 0 resulted in identification of inclusion criteria and components from existing interventions, and barriers to and facilitators of early integration of PHC for end-stage COPD. Based on these findings, a nurse-led intervention was developed in Phase I consisting of training for PHC nurses in symptom recognition and physical therapy exercises for end-stage COPD, regular visits by PHC nurses at the patients' homes, two information leaflets on selfmanagement, a semi-structured protocol and follow-up plan to record the outcomes of the home visits, and integration of care by enabling collaboration and communication between home and hospital-based professional caregivers. Conclusion : This Phase 0-I trial succeeded in developing a complex intervention for early integration of PHC for end-stage COPD. The use of three methods in Phase 0 gave reliable data on which to base inclusion criteria and components of the intervention. The preliminary effectiveness, feasibility and acceptability of the intervention will be subsequently tested in a Phase II study