TPS5635
Background: Patients with advanced gynaecological cancers who are approaching end of life (EOL) have a high symptom burden and following several prior lines of therapy, a low likelihood of ...response to further anti-cancer treatment. Despite this, 20-30% of women with gynecological cancer received chemotherapy in the last 30 days of life, with potentially detrimental effects on health and quality of life. Little is known about patients' and carers' perceptions and preferences in this phase of illness. Eliciting patient’s values and preferences for EOL care and shared decision-making are central elements of GCIG SB-001/NSGO-CTU-PEACE with the aim of improving patient-centered EOL care. The primary aim of PEACE is to assess the feasibility of collecting data on patient satisfaction towards EOL. Secondary aims include collecting data on patient and carer satisfaction with care, as well as prospective collection of details of their care. Methods: PEACE will prospectively enroll patients in Norway and Australia. Key eligibility criteria include: Patients with gynaecological cancer at an advanced stage with a predicted life expectancy of approximately 4 months. Patients may be on anti-cancer treatment or may be under observation/palliative care. In addition, the patient must be able (both physically and cognitively) to complete patient-reported outcome measures independently. The study will also include an appointed carer (not mandatory). Patient and carer satisfaction with care and the importance of domains of care will be assessed with the CANHELP-Lite individualized (Canadian Health Care Evaluation Project) instrument and FACIT (Functional Assessment of Chronic Illness Therapy). Carer’s perception of the bereavement period and the quality of the patient’s death will be assessed with the CANHELP lite bereavement and the Quality of Death and Dying questionnaire. The study will prospectively collect data on EOL treatment. Patient and carer satisfaction with care and quality of the dying process will be summarized by standard descriptive statistical measures. A sample size of 65 patients would have at least 80% power with 95% confidence to rule out a 60% completion rate in favour of the more interesting 75% rate. Assuming a 10% drop-out rate, PEACE will enrol 73 patients. Enrolment commenced in December 2022. ClinicalTrials.gov Identifier: NCT05142150 Clinical trial information: NCT05142150 .
Background
Cancer patients have increased morbidity and mortality from COVID‐19, but may respond poorly to vaccination. The Evaluation of COVID‐19 Vaccination Efficacy and Rare Events in Solid Tumors ...(EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS‐CoV‐2 community‐transmission setting, allows determination of vaccine response with minimal interference from infection.
Methods
Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID‐19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre‐second vaccine dose and at 1, 3 (primary endpoint), and 6 months post‐second dose. SARS‐CoV‐2 anti‐spike‐RBD (S‐RBD) and anti‐nucleocapsid IgG antibodies were measured.
Results
Ninety‐six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID‐19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p = .12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose.
Conclusion
Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS‐CoV‐2 infection amplifies S‐RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID‐naïve population in studying vaccine immunogenicity.
This study prospectively compared the antibody response to COVID‐19 vaccination between cancer patients and healthy controls in a population with very low COVID‐19 prevalence. Serology was not effective at detecting all cases of prior SARS‐COV‐2 infection (resulting in natural immunity), underlining the value of measuring vaccine‐induced immune responses in a COVID‐naïve cohort. The majority of cancer patients and all controls were seropositive after two vaccinations.
Background: Capecitabine and i.v. vinorelbine are both active in metastatic breast cancer with non‐overlapping toxicities. This study examined the efficacy and safety of the combination of these ...agents in patients with pretreated metastatic breast cancer.
Methods: Patients previously treated for breast cancer, maximum of one prior metastatic regimen, received capecitabine 1000 mg/m2 b.d. for days 1–14 and vinorelbine 25 mg/m2 i.v. days 1 and 8 every 21 days. All patients had measurable disease and adequate baseline organ function. The primary endpoint was response and secondary endpoints time to progression, duration of response, survival and safety.
Results: Twenty‐two patients (median age 56 years) received a median of six cycles. All patients had received anthracyclines and 64% taxanes. Objective responses were seen in 7/21 (33%, 95% confidence interval CI 18–57%), with two complete responses; stable disease was seen in 5/21 (24%, 95% CI 8–42%). Median duration of response was 6.9 months (95% CI 4.7–13.1), time to progression was 5.8 months (95% CI 2.8–6.8) and survival was 13.5 months (95% CI 6.9–19.9). The median dose intensity of vinorelbine was 75% of the intended dose and of capecitabine 85% of intended dose. The main toxicity was myelosuppression including 16 episodes of G3–4 neutropenia in 11 patients (50%). Other toxicities were generally mild to moderate.
Conclusion: The combination of capecitabine and i.v. vinorelbine is active and well tolerated in patients with pretreated metastatic breast cancer. The recent availability of oral vinorelbine provides an opportunity to explore a fully oral combination.
Observational studies of the Mediterranean diet suggest cognitive benefits, potentially reducing dementia risk.
We performed the first published review to our knowledge of randomized controlled ...trials (RCTs) investigating Mediterranean diet effects on cognition or brain morphology and function, with an additional focus on intervention diet quality and its relation to “traditional” Mediterranean dietary patterns.
We searched 9 databases from inception (final update December 2017) for RCTs testing a Mediterranean compared with alternate diet for cognitive or brain morphology and function outcomes.
Analyses were based on 66 cognitive tests and 1 brain function outcome from 5 included studies (n = 1888 participants). The prescribed Mediterranean diets varied considerably between studies, particularly with regards to quantitative food advice. Only 8/66 (12.1%) of individual cognitive outcomes at trial level significantly favored a Mediterranean diet for cognitive performance, with effect sizes (ESs) ranging from small (0.32) to large (1.66), whereas 2 outcomes favored controls. Data limitations precluded a meta-analysis. Of 8 domain composite cognitive scores from 2 studies, the 3 (Memory, Frontal, and Global function) from PREDIMED (PREvención con DIeta MEDiterránea) were significant, with ESs ranging from 0.39 to 1.29. A posttest comparison at a second PREDIMED site found that the Mediterranean diet modulates the effect of several genotypes associated with dementia risk for some cognitive outcomes, with mixed results. Finally, the risk of low-plasma brain-derived neurotrophic factor was reduced by 78% (OR = 0.22; 95% CI: 0.05, 0.90) in those who consumed a Mediterranean diet compared to control diet at 3 y in this trial. There was no benefit of the Mediterranean diet for incident cognitive impairment or dementia.
Five RCTs of the Mediterranean diet and cognition have been published to date. The data are mostly nonsignificant, with small ESs. However, the significant improvements in cognitive domain composites in the most robustly designed study warrant additional research.
IMPORTANCE: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical ...cystectomy for bladder cancer. OBJECTIVES: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021. INTERVENTIONS: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169). MAIN OUTCOMES AND MEASURES: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center. RESULTS: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women 21%; 107 34% received neoadjuvant chemotherapy; 282 89% underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days 95% CI, 0.50-3.85; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, –6.5% 95% CI, –11.4% to –1.4%) and wound complications (5.6% vs 16.0%; difference, –11.7% 95% CI, –18.6% to –4.6%) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, –0.07 95% CI, –0.11 to –0.03; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 95% CI, 0.15-0.73; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 95% CI, 0.09-0.68; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 18% vs 25/156 16% after robotic and open surgery, respectively) and overall mortality (23/161 14.3% vs 23/156 14.7%), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1). CONCLUSIONS AND RELEVANCE: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain. TRIAL REGISTRATION: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410
Background:
3,4-methylenedioxymethamphetamine (MDMA) therapy has qualities that make it potentially well suited for patients with addictions, but this has never been explored in a research study. We ...present data from the Bristol Imperial MDMA in Alcoholism (BIMA) study. This is the first MDMA addiction study, an open-label safety and tolerability proof-of-concept study investigating the potential role for MDMA therapy in treating patients with alcohol use disorder (AUD).
Aims:
This study aimed to assess if MDMA-assisted psychotherapy can be delivered safely and can be tolerated by patients with AUD post detoxification. Outcomes regarding drinking behaviour, quality of life and psychosocial functioning were evaluated.
Methods:
Fourteen patients with AUD completed a community alcohol detoxification and received an eight-week course of recovery-based therapy. Participants received two sessions with MDMA (187.5 mg each session). Psychological support was provided before, during and after each session. Safety and tolerability were assessed alongside psychological and physiological outcome measures. Alcohol use behaviour, mental well-being and functioning data were collected for nine months after alcohol detoxification.
Results:
MDMA treatment was well tolerated by all participants. No unexpected adverse events were observed. Psychosocial functioning improved across the cohort. Regarding alcohol use, at nine months post detox, the average units of alcohol consumption by participants was 18.7 units per week compared to 130.6 units per week before the detox. This compares favourably to a previous observational study (the ‘Outcomes’ study) by the same team with a similar population of people with AUD.
Conclusions:
This study provides preliminary support for the safety and tolerability of a novel intervention for AUD post detox. Further trials to examine better the therapeutic potential of this approach are now indicated.
Approximately half of men in a contemporary UK cohort reported that they either leaked urine or used pads for urine leakage or both at 1 yr after radical prostatectomy (RP). The majority of those ...wearing pads needed only 1 pad per day, and only one in ten men considered urine leakage a moderate or big problem. Among men who did not need medication for erections before RP, 17% reported that they were able to achieve erections, with or without medication, at 1 yr after surgery.
Radical prostatectomy (RP) is an established treatment for localised prostate cancer that can have a significant impact on urinary and sexual function, with recovery over time. Our aim was to describe functional recovery in the first year after RP, reporting descriptive outcomes alongside validated patient-reported outcome measure scores (Expanded Prostate Cancer Index Composite, EPIC-26).
Men undergoing RP between September 2015 and November 2019 completed EPIC-26 at baseline and 1, 3, 6, and 12 mo.
Overall, 2030 men consented to participation, underwent RP, and completed EPIC-26. At baseline, 97% were pad-free (1928/1996; 95% confidence interval CI 96–97%) and 77% were leak-free and pad-free (1529/1996; 95% CI 75–78), with a median EPIC-26 incontinence domain score of 100 (interquartile range IQR 86–100). At 12 mo, 65% were pad-free (904/1388; 95% CI 63–68%) and 42% were leak-free and pad-free (583/1388; 95% CI 39–45%), with a median EPIC-26 score of 76 (IQR 61–100). While one in three men reported wearing a pad at 12 mo, fewer than one in ten men needed more than 1 pad/d. At baseline, 1.9% reported a “moderate or big problem” with urine leakage, which increased to 9.7% at 12 mo. At baseline, the median sexual domain score among 1880 men was 74 (IQR 43–92) and 52% had erections sufficient for intercourse without medication (975/1880; 95% CI 50–54%). Among these 975 men, 630 responded at 12 mo, of whom 17% reported sufficient erections for intercourse (105/630; 95% CI 14–20%), without medication in 6% (37/630; 95% CI 4–8%) and needing medication in 11% (68/630; 95% CI 9–13%); the median EPIC-26 domain score was 26 (IQR 13–57).
Reporting of functional outcomes after RP in terms of easily understood concepts such as pad-free and leak-free status, and erections with and with medication, alongside the classical report using EPIC-26 domain scores, increases the understanding of RP recovery patterns over the first year.
At 12 months after surgery for prostate cancer, one in ten men reported a moderate or big problem with urine leakage and one in five men reported sufficient erections.
IMPORTANCE: The value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is ...unclear. OBJECTIVES: To compare the cost-effectiveness of iRARC with that of ORC. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023. INTERVENTIONS: Patients were randomized to receive either iRARC (n = 169) or ORC (n = 169). MAIN OUTCOMES AND MEASURES: Costs of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion. RESULTS: A total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% 95% CI, 0.42%-12.28%), and readmissions to hospital (14.56% 95% CI, 5.00%-24.11%), but increases in theater time (31.35 95% CI, 13.67-49.02 minutes). The additional cost of iRARC per patient was £1124 (95% CI, −£576 to £2824 US $1622 (95% CI, −$831 to $4075)) with an associated gain in quality-adjusted life-years of 0.01124 (95% CI, 0.00391-0.01857). The incremental cost-effectiveness ratio was £100 008 (US $144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status. CONCLUSIONS AND RELEVANCE: In this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03049410
PDF
