Social Characteristics of Culturally and Linguistically Diverse Cancer Patients Enrolled in Early Phase Clinical Trials in South Western Sydney.

INTRODUCTION: Early phase clinical trials (EPCTs) enable access to novel therapies for patients who have exhausted standard of care treatment and contribute a crucial role in drug development and research. Culturally and linguistically diverse (CALD) or socially disadvantaged patients have notably lower rates of participation in these trials. We aimed to characterise the social and cultural demographics of patients enrolled on an EPCT in South Western Sydney. METHODS: We conducted a 10-year retrospective review of patients enrolled on a EPCT at Liverpool Hospital. CALD patients were defined as those born overseas or whose preferred language was other than English. The patient residential address was used to calculate distance travelled, and the Index of Relative Socioeconomic Disadvantage (IRSD) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) scores were calculated and used as a surrogate for socioeconomic status (SES). RESULTS: Our study included 233 patients across 39 EPCTs. Ninety-one patients (39%) were identified as CALD. The median IRSD and IRSAD scores were 941 and 944, respectively, with 62.7-67.4% of patients residing in an area with greater disadvantage compared to the median of Australia. The median distance travelled was 17 kilometres with only 12% of participants travelling more than 50 km. CALD patients were more likely to reside in an area of low SES (OR 3.4, 95% CI: 1.8-6.5, p < 0.01) and travelled shorter median distances (10 vs. 23 km) when compared to non-CALD patients. CONCLUSION: Our study cohort contained a lower proportion of CALD patients and a higher SES than what we might have expected from our local population. Furthermore, there was a trend toward greater SES disadvantage (lower IRSD/IRSAD scores) for the CALD population. This study provides novel Australian data to support the underrepresentation of culturally diverse or disadvantaged patients on EPCTs. Future efforts should be made to reduce barriers to participation and improve equity in clinical trial participation.

Melanoma: An immunotherapy journey from bench to bedside.

Melanoma gave science a window into the role immune evasion plays in the development of malignancy. The entire spectrum of immune focused anti-cancer therapies has been subjected to clinical trials in this disease, with limited success until the immune checkpoint blockade era. That revolution launched first in melanoma, heralded a landscape change throughout cancer that continues to reverberate today.

Symptomatic treatment of children with anti-NMDAR encephalitis.

AIM: We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHOD: A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti-NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome. RESULTS: Only two out of 27 patients were white, whereas 16 out of 27 patients were from the Pacific Islands/New Zealand Maori. The mean duration of admission was 69 days (10-224d) and 48% of patients (13/27) needed treatment in an intensive care setting. A mean of eight medications per patient was used for symptomatic management. Symptoms treated were agitation (n=25), seizures (n=24), movement disorders (n=23), sleep disruption (n=17), psychiatric symptoms (n=10), and dysautonomia (n=four). The medications used included five different benzodiazepines (n=25), seven anticonvulsants (n=25), eight sedatives and sleep medications (n=23), five antipsychotics (n=12), and five medications for movement disorders (n=10). Sedative and sleep medications other than benzodiazepines were the most effective, with a mean benefit of 67.4% per medication and a mean adverse effect-benefit ratio of 0.04 per medication. Antipsychotic drugs were used for a short duration (median 9d), and had the poorest mean benefit per medication of 35.4% and an adverse effect-benefit ratio of 2.0 per medication. INTERPRETATION: Long-acting benzodiazepines, anticonvulsants, and clonidine can treat multiple symptoms. Patients with anti-NMDAR encephalitis appear vulnerable to antipsychotic-related adverse effects. Pacific Islanders appear to have a vulnerability to anti-NMDAR encephalitis in our region.

Chronic kidney disease and the risk of stroke: a systematic review and meta-analysis.

BACKGROUND: People with chronic kidney disease (CKD) have an increased risk of stroke but the magnitude of increased risk and the independent effects of glomerular filtration rate (GFR) and albuminuria are unclear. We aimed to quantify the association between the independent and combined effects of GFR and albuminuria on stroke risk. METHODS: We searched MEDLINE and EMBASE (February 2014) for cohort studies or randomized controlled trials (RCTs) which reported stroke incidence in adults with a baseline measurement of GFR and/or albuminuria. We extracted study and participant characteristics, risk of bias and relative risks (RR, with confidence interval; CI) of stroke associated with GFR and/or quantity of albuminuria, synthesized data using random effects meta-analysis and explored heterogeneity using meta-regression. RESULTS: We identified 83 studies; 63 cohort studies (2 085 225 participants) and 20 RCTs (168 516 participants) reporting 30 392 strokes. There was an inverse linear relationship between GFR and risk of stroke, with risk of stroke increasing 7% (RR: 1.07, CI: 1.04-1.09) for every 10 mL/min/1.73 m(2) decrease in GFR. A 25 mg/mmol increase in albumin-creatinine ratio was associated with a 10% increased risk of stroke (RR: 1.10, 95% CI: 1.01-1.20). The effect of albuminuria was independent of GFR. Results were not different across subtypes of stroke, sex and varying prevalence of cardiovascular risk factors. CONCLUSIONS: Stroke risk increases linearly and additively with declining GFR and increasing albuminuria. CKD staging may also be a useful clinical tool for identifying people who may benefit most from interventions to reduce cardiovascular risk.

The impact of brain cancer care coordinators on healthcare utilization and outcomes in patients with glioblastoma.

Background: Cancer care coordinators (CCCs) are recognized as having an important role in patients' and carers' cancer journey. However, there are no studies investigating the impact of CCCs on quantitative outcomes. We performed a retrospective cohort study investigating the impact of brain cancer care coordinators (BCCCs) on health service resource use and survival in patients with glioblastoma. Methods: All patients diagnosed with glioblastoma between 2012 and 2019 in Hunter New England Local Health District, Australia (HNELHD) were included and the patients were divided into 2 cohorts: before and after the introduction of the BCCC. Any patient diagnosed in 2016, during the introduction of the BCCC, were excluded. The main outcomes assessed were overall survival, health service resource use, odds of being admitted to hospital after the emergency presentation, and cost-offset analysis to examine the economic implications of BCCCs. Results: A total of 187 patients were included. There were no significant differences in overall survival between the 2 groups (mOS 12.0 vs 11.16 months, HR 0.95). However, there was a reduction in the number of ED presentations and admissions. This was associated with a 24% reduction in aggregate length of stay with the BCCC. There was no statistically significant difference in mean patient costs, however our hospital may have saved over AUD$500 000 with BCCCs. Conclusions: The introduction of BCCC did not improve survival but appeared to be associated with reduced health resource utilization. This study provides economic justification, in addition to the established quality of life improvements, to support the presence of BCCCs.

Comparison of Prognostic Scores in Early Phase Clinical Trials: A 10-year Single Centre Australian Experience.

BACKGROUND/AIM: Early phase clinical trials (EPCTs) assess the tolerability of novel anti-cancer therapeutics in patients with advanced malignancy. Patient selection is important given the modest clinical benefit and time commitments for trials. Prognostic scores have been developed to facilitate identification of high-risk patients. This study aimed to compare five prognostic scores to predict survival for patients on an EPCT. PATIENTS AND METHODS: We performed a retrospective review of patients enrolled in EPCT at Liverpool Hospital, Sydney, from 2013 to 2023. Demographic, biochemical, and survival data were collected from electronic medical records. The score from five prognostic scoring systems (Royal Marsden hospital, MD Anderson Cancer centre, Gustave Roussy Immune, MD Anderson Immune Checkpoint Inhibitor and Princess Margaret Hospital Index) were calculated. Overall survival was measured using the Kaplan-Meier method and predictive discrimination was assessed using Harrell's c-index. RESULTS: A total of 218 patients across 36 EPCTs were included. The median overall survival was 9.8 months with 22% of patients dying in less than 90 days. Seventeen to thirty-four percent of patients were categorised as high-risk. The MDACC score obtained the highest predictability for overall survival for the whole cohort (c-index=0.67, 95%CI=0.62-0.72) and the immunotherapy-based cohort (c-index= 0.65, 95%CI=0.59-0.71). However, all scores performed similarly with a significant overlap in the confidence intervals. CONCLUSION: Our retrospective audit confirms the utility of prognostic scores to predict survival in an Australian EPCT cohort, with similar predictive discrimination across various scoring systems. Integration of these prognostic tools into EPCT screening processes may optimise benefits and reduce risks associated with EPCTs.