A Study of Pazopanib Safety and Efficacy in Patients With Advanced Clear Cell Renal Cell Carcinoma and ECOG Performance Status 2 (Pazo2): An Open label, Multicentre, Single Arm, Phase II Trial.

AIM: Patients with advanced renal cell carcinoma and poor performance status (PS≥2) are often deemed unsuitable for treatment. The Pazo2 trial aimed to assess tolerability and efficacy of pazopanib as first-line treatment in renal cancer patients with ECOG PS2. METHODS: Pazo2 was a prospective, single arm, open label, multicentre, phase II trial, conducted in 26 UK centres. Eligible patients were aged ≥18 years, with advanced or metastatic renal cancer and a clear cell component (aRCC), measurable disease as per RECIST Criteria 1.1, and ECOG PS2. Co-primary outcomes, assessed at 6-months after patients entered the trial, were tolerability, defined as the proportion of patients who did not develop "intolerable" adverse events, and efficacy, defined as the proportion of all patients who were progression-free and alive. RESULTS: Between February 21, 2013 and August 12, 2016, 75 patients were registered. Median age was 68.6 years (IQR 64.6-76.0), 100% ECOG PS2, 62.7% 'poor risk' (International Metastatic Renal-Cell Carcinoma Database Consortium). Of the 65 evaluable patients, 70.8% (95% CI: 58.8, 80.4) did not develop "intolerable" adverse events and 56.9% (95% CI: 44.8, 68.2) were still alive and progression-free 6 months after starting pazopanib. Twenty-seven patients developed serious adverse events deemed to be related to pazopanib. CONCLUSION: These data suggests that pazopanib is tolerated and effective in aRCC patients with PS2 and represents a treatment option for patients who cannot receive or tolerate immune checkpoint inhibitors.

Evaluating process and effectiveness of a low-intensity CBT intervention for women with gynaecological cancer (the EPELIT Trial).

Background: Improving survival from gynaecological cancers is creating an increasing clinical challenge for long-term distress management. Psychologist-led interventions for cancer survivors can be beneficial, but are often costly. The rise of the Psychological Wellbeing Practitioner (PWP) workforce in the UK might offer a cheaper, but equally effective, intervention delivery method that is more sustainable and accessible. We aimed to test the effectiveness of a PWP co-facilitated intervention for reducing depression and anxiety, quality of life and unmet needs. Methods: We planned this trial using a pragmatic, non-randomised controlled design, recruiting a comparator sample from a second clinical site. The intervention was delivered over six-weekly sessions; data were collected from participants at baseline, weekly during the intervention, and at one-week and three-month follow-up. Logistical challenges meant that we only recruited 8 participants to the intervention group, and 26 participants to the control group. Results: We did not find significant, between-group differences for depression, quality of life or unmet needs, though some differences at follow-up were found for anxiety ( p<.001). Analysis of potential intervention mediator processes indicated the potential importance of self-management self-efficacy. Low uptake into the psychological intervention raises questions about (a) patient-driven needs for group-based support, and (b) the sustainability of this intervention programme. Conclusions: This study failed to recruit to target; the under-powered analysis likely explains the lack of significant effects reported, though some trends in the data are of interest. Retention in the intervention group, and low attrition in the control group indicate acceptability of the intervention content and trial design; however a small baseline population rendered this trial infeasible in its current design. Further work is required to answer our research questions, but also, importantly, to address low uptake for psychological interventions in this group of cancer survivors. Trial registration: ClinicalTrials.gov, NCT03553784 (registered 14 June 2018).

An increasing number of people are surviving for longer time periods following treatment for gynaecological cancer and this means we need to change how we care for and support a growing cancer survivor population. Psychological distress and poor quality of life are common in people affected by cancer, and these do not always improve once treatment ends. Providing psychological support can be expensive, which means that not everyone who wants it can access it. Psychological Wellbeing Practitioners (PWPs) have been introduced in UK health care. This workforce might offer an alternative for providing psychological support to a greater number of cancer survivors. We aimed to test how good a PWP co-delivered intervention is at improving depression, anxiety and quality of life in people who had been treated for gynaecological cancer. The intervention was delivered to small groups of patients over six weekly sessions. We compared those who received the intervention with a similar patient group who did not have access to the same psychological support from a different hospital. Participants reported their psychological wellbeing and quality of life at the point of recruitment, weekly for six weeks, and then at follow-up time-points one week and three months later. Because of low interest in the group intervention we did not recruit to target. Only 8 participants took part in the intervention, and we recruited only 26 participants in the control group. This means we can't have full confidence in our results. Nonetheless, the findings indicate that this intervention was helpful for improving participants' anxiety levels. Further trials, which recruit a larger number of cancer survivors, are needed to answer our research questions. However, this trial indicates acceptability and potential benefit. We also need to undertake research to understand why so few cancer survivors wanted to take part in this group-based intervention.

Universal BRCA1/BRCA2 Testing for Ovarian Cancer Patients is Welcomed, but with Care: How Women and Staff Contextualize Experiences of Expanded Access.

Decreasing costs of genetic testing and advances in treatment for women with cancer with germline BRCA1/BRCA2 mutations have heralded more inclusive genetic testing programs. The Genetic Testing in Epithelial Ovarian Cancer (GTEOC) Study, investigates the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (universal genetic testing or UGT). Study participants and staff were interviewed to: (i) assess the impact of UGT (ii) integrate patients' and staff perspectives in the development of new UGT programs. Semi-structured interviews were conducted with twelve GTEOC Study participants and five members of staff involved in recruiting them. The transcripts were transcribed verbatim and analyzed using Interpretative Phenomenological Analysis. There are two super-ordinate themes: motivations and influences around offers of genetic testing and impacts of genetic testing in ovarian cancer patients. A major finding is that genetic testing is contextualized within the broader experiences of the women; the impact of UGT was minimized in comparison with the ovarian cancer diagnosis. Women who consent to UGT are motivated by altruism and by their relatives' influence, whilst those who decline are often considered overwhelmed or fearful. Those without a genetic mutation are usually reassured by this result, whilst those with a genetic mutation must negotiate new uncertainties and responsibilities towards their families. Our findings suggest that UGT in this context is generally acceptable to women. However, the period shortly after diagnosis is a sensitive time and some women are emotionally overburdened. UGT is considered a 'family affair' and staff must acknowledge this.

Analytical expressions for the log-amplitude correlation function of a plane wave through anisotropic atmospheric refractive turbulence.

The effect of anisotropic Kolmogorov turbulence on the log-amplitude correlation function for plane-wave fields is investigated using analysis, numerical integration, and simulation. A new analytical expression for the log-amplitude correlation function is derived for anisotropic Kolmogorov turbulence. The analytic results, based on the Rytov approximation, agree well with a more general wave-optics simulation based on the Fresnel approximation as well as with numerical evaluations, for low and moderate strengths of turbulence. The new expression reduces correctly to previously published analytic expressions for isotropic turbulence. The final results indicate that, as asymmetry becomes greater, the Rytov variance deviates from that given by the standard formula. This deviation becomes greater with stronger turbulence, up to moderate turbulence strengths. The anisotropic effects on the log-amplitude correlation function are dominant when the separation of the points is within the Fresnel length. In the direction of stronger turbulence, there is an enhanced dip in the correlation function at a separation close to the Fresnel length. The dip is diminished in the weak-turbulence axis, suggesting that energy redistribution via focusing and defocusing is dominated by the strong-turbulence axis. The new analytical expression is useful when anisotropy is observed in relevant experiments.