Utility of 30-day mortality as a quality metric for palliative radiation treatment: A population-based analysis from Queensland, Australia.

INTRODUCTION: Palliative radiotherapy (PRT) is frequently used to treat symptoms of advanced cancer, however benefits are questionable when life expectancy is limited. The 30-day mortality rate after PRT is a potential quality indicator, and results from a recent meta-analysis suggest a benchmark of 16% as an upper limit. In this population-based study from Queensland, Australia, we examined 30-day mortality rates following PRT and factors associated with decreased life expectancy. METHODS: Retrospective population data from Queensland Oncology Repository was used. Study population data included 22,501 patients diagnosed with an invasive cancer who died from any cause between 2008 and 2017 and had received PRT. Thirty-day mortality rates were determined from the date of last PRT fraction to date of death. Cox proportional hazards models were used to identify factors independently associated with risk of death within 30 days of PRT. RESULTS: Overall 30-day mortality after PRT was 22.2% with decreasing trend in more recent years (P = 0.001). Male (HR = 1.20, 95% CI = 1.13-1.27); receiving 5 or less radiotherapy fractions (HR = 2.97, 95% CI = 2.74-3.22 and HR = 2.17, 95% CI = 2.03-2.32, respectively) and receiving PRT in a private compared to public facility (HR = 1.61, 95% CI = 1.51-1.71) was associated with decreased survival. CONCLUSION: The 30-day mortality rate in Queensland following PRT is higher than expected and there is scope to reduce unnecessarily protracted treatment schedules. We encourage other Australian and New Zealand centres to examine and report their own 30-day mortality rate following PRT and would support collaboration for 30-day mortality to become a national and international quality metric for radiation oncology centres.

Defining the expected 30-day mortality for patients undergoing palliative radiotherapy: A meta-analysis.

BACKGROUND: The expected 30-day mortality rate for patients treated with palliative radiationisnotestablished. The primary objective of this study is todefinetheproportion of patientswith advanced cancerwho diewithin 30-daysofpalliative radiotherapy(PR). Additionally, we explored the short term survival of patient subgroups undergoing PR treatment. METHODS: We searched MEDLINE, CINAHL, Embase and Cochrane Database of Systematic Reviews from January 1st 1980 to June 26, 2020. We included PUBMED's related search and reference lists to further identify articles. A meta-analysis of these research studies and reviews was performed. Published and unpublished English language randomized controlled trials, observational or prospective studies, and systematic reviews that reported 30-day mortality for patients with advanced cancer who received PR were eligible. Data extraction was done by two independent authors and included study quality indicators. To improve distribution and variance, all proportions were transformed using logit transformation. A random-effects model was used to pool data, using Der Simonian and Laird method of estimation where possible and appropriate. RESULTS: The data from 42 studies contributing 88,516 patients with advanced cancer who received PR were evaluated. The summary proportion of mortality in patients with advanced cancer within 30 days of receiving PR was 16% (95% CI = 14% to 18%). We found substantial heterogeneity in our data (I2 = 98.76%, p < 0.001), hence we applied subgroup analysis to identify potential moderating factors. We found a higher 30-day mortality rate after PR in the following groups: multiple treatment sites (QM(1) = 9.54, p = 0.002), hepatobiliary primary (QM(1) = 24.20, p < 0.001), inpatient status (QM(1) = 92.27, p < 0.001), Eastern Cooperative Oncology Group performance status (ECOG) 3-4 (QM(1) = 8.70, p = 0.003), United States (U.S.) patients (QM(1) = 28.70, p < 0.001) among others. CONCLUSIONS: We found that 16% of patients with advanced cancer receiving PR die within 30 days of treatment. Our findingcan be used asabenchmarktoestablishaglobal quality metric for radiation oncology practice audits.

Cranial irradiation in juvenile mice leads to early and sustained defects in the stem and progenitor cell pools and late cognitive impairments.

Cranial irradiation is used in combination with other therapies as a treatment for brain tumours and is thought to contribute to long-term cognitive deficits. Several rodent models have demonstrated that these cognitive deficits may be correlated with damage to neural progenitor cells in the subventricular zone (SVZ) and dentate gyrus (DG), the two neurogenic niches of the brain. Studies in rodent models typically assess the proliferating progenitor population, but rarely investigate the effect of cranial irradiation on the neural stem cell pool. Further, few studies evaluate the effects in juveniles, an age when children typically receive this treatment. Herein, we examine the cellular and behavioural effects of juvenile cranial irradiation on stem and progenitor populations in the two neurogenic regions of the brain and assess cognitive outcomes. We found regionally distinct effects of cranial irradiation in the juvenile brain. In the SVZ, we observed a defect in the stem cell pool and a concomitant decrease in proliferating cells that were maintained for at least one week. In the DG, a similar defect in the stem cell pool and proliferating cells was observed and persisted in the stem cell population. Finally, we demonstrated that cranial irradiation resulted in late cognitive deficits. This study demonstrates that juvenile cranial irradiation leads to regionally distinct defects in the stem and progenitor populations, and late cognitive deficits, which may be important factors in determining therapeutic targets and timing of interventions following cranial irradiation.

Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury.

The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models.