Improving Palliative Care for Cancer

British Journal of Cancer (2002) 87, 1481–1481. doi:10.1038/sj.bjc.6600646 www.bjcancer.co

Clinician estimates of prognosis: accuracy and impact-a retrospective inpatient hospice study

Objective: To evaluate the accuracy and impact of clinicians’ estimates of prognosis (CEP) in patients referred for hospice inpatient care. Methods: Retrospective review of 12 months’ referrals to a London hospice unit. Data extracted included date of referral, admission and death and CEP. Results: N=383. Mean age 72 years (range 24–101). CEP accuracy: Median survival where CEP was ‘days’ (n=141) was 7 days (0–164); CEP ‘weeks’ (n=167) was 14 days (1–538); CEP ‘months’ (n=75) was 32 days (2–507). Kaplan-Meier survival curves showed significant difference between CEP of ‘months’ and ‘weeks’ (p<0.0001); ‘months’ and ‘days’ (p<0.0001); but not ‘days’ and ‘weeks’ (p=0.1). CEP impact: admission waiting time increased with increasing CEP: CEP ‘days’ (n=105) median 1 day (0–14); CEP ‘weeks’ (n=154) median 2 days (0–46); CEP ‘months’ (n=69) median 3 days (0–46). No significant difference was demonstrated in the number of discharge planning conversations between groups (0.9/patient). Conclusions: CEP was accurate in over half of the cases but did not adequately discriminate between those with prognoses of days or weeks. CEP may affect the prioritisation given to patients by hospices. Inaccurate CEP on referral forms may influence other aspects of care; however, further research is needed

THE ROLE OF THE DNA DAMAGE AND REPAIR PATHWAYS IN THE EFFICACY OF ONCOLYTIC ADENOVIRUS FOR OVARIAN CANCER

PhDDefects within the DNA damage response (DDR) pathways are common in human malignancies. This is especially true in high-grade serous ovarian cancer (HGSOC) where defects within the Homologous Recombination (HR) pathway may be present in up to 50% of tumours. Oncolytic adenovirus is a potential novel therapy for human malignancies. These viruses infect malignant cells and multiply selectively within them causing cell death and release of mature virions. Here, I have investigated the role of the DDR in determining the efficacy of the E1A-CR2 deleted adenovirus type 5 (Ad5) vector, dl922-947, in ovarian cancer. I show that infection with dl922-947 stimulates a robust DDR within the host cell, which the virus manipulates in order to ensure optimal viral replication. In a panel of HGSOC cell lines, the extent of overreplication of genomic DNA and the degree of genomic damage following infection with dl922-947 was shown to correlate closely with viral efficacy. Functional HR, however, promoted viral DNA replication and augmented overall anti-cancer efficacy. Mechanistically, both BRCA2 and RAD51 localised to viral replication centres within the infected cell nucleus. RAD51 co-localisation was also demonstrated in cells with defective HR and occurred independently of BRCA2. In addition, a direct interaction was identified between RAD51 and adenovirus E2 DNA binding protein. Using functional assays of HR competence, I show that Ad5 infection does not alter cellular ability to repair DNA double-strand break damage via HR. These data suggest that oncolytic adenoviral therapy may be most clinically relevant in tumours with intact HR function. Using a high-throughput siRNA DNA repair screen, potential novel targets have been identified that can increase the efficacy of dl922-947 (for example: NONO) and also result in increased resistance (RPA). These results highlight the complex interplay between adenovirus and host cell. Further understanding of these pathways is vital to increase efficacy, develop biomarkers and improve patient selection into clinical trials for these therapies.Medical Research Counci

Interventions for sexual dysfunction following treatments for cancer in women

BACKGROUND: The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life, including sexual function, in those affected by cancer. Sexual dysfunction is a potential long-term complication of many cancer treatments. This includes treatments that have a direct impact on the pelvic area and genitals, and also treatments that have a more generalised (systemic) impact on sexual function.This is an update of the original Cochrane review published in Issue 4, 2007, on interventions for treating sexual dysfunction following treatments for cancer for men and women. Since publication in 2007, there has been an increase in the number of trials for both men and women and this current review critiques only those for women. A review in press will present those for men. OBJECTIVES: To evaluate the effectiveness of interventions for treating sexual dysfunction in women following treatments for cancer. To assess adverse events associated with interventions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, Dissertation Abstracts and the NHS Research Register. The searches were originally run in January 2007 and we updated these to September 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed the effectiveness of a treatment for sexual dysfunction. The trial participants were women who had developed sexual dysfunction as a consequence of a cancer treatment. We sought evaluations of interventions that were pharmaceutical, mechanical, psychotherapeutic, complementary or that involved physical exercise. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed trial quality. We considered meta-analysis for trials with comparable key characteristics. MAIN RESULTS: Since the original version of this review we have identified 11 new studies in women. The one study identified in the earlier version of this review was excluded in this update as it did not meet our narrower inclusion criteria to include only interventions for the treatment, not prevention, of sexual dysfunction.In total 1509 female participants were randomised across 11 trials. All trials explored interventions following treatment either for gynaecological or breast cancer. Eight trials evaluated a psychotherapeutic or psycho-educational intervention. Two trials evaluated a pharmaceutical intervention and one pelvic floor exercises. All involved heterosexual women. Eight studies were at a high risk of bias as they involved a sample of fewer than 50 participants per trial arm. The trials varied not only in intervention content but in outcome measurements, thereby restricting combined analysis. In the trials evaluating a psychotherapeutic intervention the effect on sexual dysfunction was mixed; in three trials benefit was found for some measures of sexual function and in five trials no benefit was found. Evidence from the other three trials, two on different pharmaceutical applications and one on exercise, differed and was limited by small sample sizes. Only the trial of a pH-balanced vaginal gel found significant improvements in sexual function. The trials of pharmaceutical interventions measured harm: neither reported any. Only one psychological intervention trial reported that no harm occurred because of the intervention; the other trials of psychological support did not measure harm. AUTHORS' CONCLUSIONS: Since the last version of this review, the new studies do not provide clear information on the impact of interventions for sexual dysfunction following treatments for cancer in women. The sexual dysfunction interventions in this review are not representative of the range that is available for women, or of the wider range of cancers in which treatments are known to increase the risk of sexual problems. Further evaluations are needed

Drug therapy for delirium in terminally ill adult patients.

BACKGROUND: Delirium is a syndrome characterised by a disturbance of consciousness (often fluctuating), cognition and perception. In terminally ill patients it is one of the most common causes of admission to clinical care. Delirium may arise from any number of causes and treatment should be directed at addressing these causes rather than the symptom cluster. In cases where this is not possible, or treatment does not prove successful, the use of drug therapy to manage the symptoms may become necessary. This is an update of the review published on 'Drug therapy for delirium in terminally ill adult patients' in The Cochrane Library 2004, Issue 2 ( Jackson 2004). OBJECTIVES: To evaluate the effectiveness of drug therapies to treat delirium in adult patients in the terminal phase of a disease. SEARCH METHODS: We searched the following sources: CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to 2012), EMBASE (1980 to 2012), CINAHL (1982 to 2012) and PSYCINFO (1990 to 2012). SELECTION CRITERIA: Prospective trials with or without randomisation or blinding involving the use of drug therapies for the treatment of delirium in adult patients in the terminal phase of a disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality using standardised methods and extracted trial data. We collected outcomes related to efficacy and adverse effects. MAIN RESULTS: One trial met the criteria for inclusion. In the 2012 update search we retrieved 3066 citations but identified no new trials. The included trial evaluated 30 hospitalised AIDS patients receiving one of three agents: chlorpromazine, haloperidol and lorazepam. The trial under-reported key methodological features. It found overall that patients in the chlorpromazine group and those in the haloperidol group had fewer symptoms of delirium at follow-up (to below the diagnostic threshold using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and that both were equally effective (at two days mean difference (MD) 0.37; 95% confidence interval (CI) -4.58 to 5.32; between two and six days MD -0.21; 95% CI -5.35 to 4.93). Chlorpromazine and haloperidol were found to be no different in improving cognitive status in the short term (at 48 hours) but at subsequent follow-up cognitive status was reduced in those taking chlorpromazine. Improvements from baseline to day two for patients randomised to lorazepam were not apparent. All patients on lorazepam (n = 6) developed adverse effects, including oversedation and increased confusion, leading to trial drug discontinuation. AUTHORS' CONCLUSIONS: There remains insufficient evidence to draw conclusions about the role of drug therapy in the treatment of delirium in terminally ill patients. Thus, practitioners should continue to follow current clinical guidelines. Further research is essential

Insight Report: “Innovative, automated use of real-world healthcare data to improve outcomes for patients with ovarian cancer” project online public involvement session

A summary of the insights gathered from a public involvement discussion involving patients and cares with lived experience of ovarian cancer and their views on a health data project “Innovative, automated use of real-world healthcare data to improve outcomes for patients with ovarian cancer