Potentially burdensome care at the end-of-life for cancer decedents: a retrospective population-wide study.

BACKGROUND: Variation persists in the quality of end-of-life-care (EOLC) for people with cancer. This study aims to describe the characteristics of, and examine factors associated with, indicators of potentially burdensome care provided in hospital, and use of hospital services in the last 12 months of life for people who had a death from cancer. METHOD: A population-based retrospective cohort study of people aged ≥ 20 years who died with a cancer-related cause of death during 2014-2019 in New South Wales, Australia using linked hospital, cancer registry and mortality records. Ten indicators of potentially burdensome care were examined. Multinominal logistic regression examined predictors of a composite measure of potentially burdensome care, consisting of > 1 ED presentation or > 1 hospital admission or ≥ 1 ICU admission within 30 days of death, or died in acute care. RESULTS: Of the 80,005 cancer-related deaths, 86.9% were hospitalised in the 12 months prior to death. Fifteen percent had > 1 ED presentation, 9.9% had > 1 hospital admission, 8.6% spent ≥ 14 days in hospital, 3.6% had ≥ 1 intensive care unit admission, and 1.2% received mechanical ventilation on ≥ 1 occasion in the last 30 days of life. Seventeen percent died in acute care. The potentially burdensome care composite measure identified 20.0% had 1 indicator, and 10.9% had ≥ 2 indicators of potentially burdensome care. Compared to having no indicators of potentially burdensome care, people who smoked, lived in rural areas, were most socially economically disadvantaged, and had their last admission in a private hospital were more likely to experience potentially burdensome care. Older people (≥ 55 years), females, people with 1 or ≥ 2 Charlson comorbidities, people with neurological cancers, and people who died in 2018-2019 were less likely to experience potentially burdensome care. Compared to people with head and neck cancer, people with all cancer types (except breast and neurological) were more likely to experience ≥ 2 indicators of potentially burdensome care versus none. CONCLUSION: This study shows the challenge of delivering health services at end-of-life. Opportunities to address potentially burdensome EOLC could involve taking a person-centric approach to integrate oncology and palliative care around individual needs and preferences.

Variations in breast cancer histology and treatment patterns between the major ethnic groups of South West Sydney.

Studies in the United States and United Kingdom have demonstrated ethnic variations in breast cancer receptor status, histology, and treatment access. This study aimed to investigate whether ethnicity variation similarly exists in Australia. Patients diagnosed with breast cancer between 2006 and 2011 across all public hospitals in the South Western Sydney Local Health District were identified and patient data collected retrospectively. Logistic regression analysis was used to measure the association between various biologic and treatment parameters and ethnicity. Ethnicity was found to have an influence on age of diagnosis, histology, treatment utilization, and recurrence in breast cancer patients.

Safety and efficacy of progressive resistance training in breast cancer: a systematic review and meta-analysis.

The purpose of this study was to assess the safety and efficacy of progressive resistance training (PRT) in breast cancer. Randomized controlled trials (RCTs) published to November 2013 that reported on the effects of PRT (>6 weeks) on breast cancer-related lymphedema (BCRL) (incidence/exacerbation, arm volume, and symptom severity), physical functioning (upper and lower body muscular strength), and health-related quality of life (HRQoL) in breast cancer patients were included. Of 446 citations retrieved, 15 RCTs in 1,652 patients were included and yielded five studies on BCRL incidence/exacerbation (N = 647), four studies on arm volume (N = 384) and BCRL symptom severity (N = 479), 11 studies on upper body muscular strength (N = 1,252), nine studies on lower body muscular strength (N = 1,079), and seven studies on HRQoL (N = 823). PRT reduced the risk of BCRL versus control conditions [OR = 0.53 (95% CI 0.31-0.90); I2 = 0%] and did not worsen arm volume or symptom severity (both SMD = -0.07). PRT significantly improved upper [SMD = 0.57 (95% CI 0.37-0.76); I2 = 58.4%] and lower body muscular strength [SMD = 0.48 (95% CI 0.30-0.67); I2 = 46.7%] but not HRQoL [SMD = 0.17 (95% CI -0.03 to 0.38); I2 = 47.0%]. The effect of PRT on HRQoL became significant in our sensitivity analysis when two studies conducted during adjuvant chemotherapy [SMD = 0.30 (95% CI 0.04-0.55), I2 = 37.0%] were excluded. These data indicate that PRT improves physical functioning and reduces the risk of BCRL. Clinical practice guidelines should be updated to inform clinicians on the benefits of PRT in this cohort.

Survival of patients who had cancer diagnosed through an emergency hospital admission: A retrospective matched case-comparison study in Australia.

BACKGROUND: Individuals diagnosed with cancer via emergency admission are likely to have poor outcomes. This study aims to identify cancer diagnosed through an emergency hospital admission and examine predictors associated with mortality within 12-months. METHOD: A population-based retrospective 1:1 propensity-matched case-comparison study of people who had an emergency versus a planned hospital admission with a principal diagnosis of cancer during 2013-2020 in New South Wales, Australia using linked hospital, cancer registry and mortality records. Conditional logistic regression examined predictors of mortality at 12-months. RESULTS: There were 28,502 matched case-comparisons. Individuals who had an emergency admission were four times more likely to die within 12-months (Odds Ratio (OR) 3.93; 95 % confidence interval (CI) 3.75-4.13) compared to individuals who had a planned admission for cancer. Older individuals, diagnosed with lung (OR 1.89; 95 %CI 1.36-2.63) or digestive organ, excluding colorectal (OR1.78; 95 %CI 1.30-2.43) cancers, where the degree of spread was metastatic (OR 3.61; 95 %CI 2.62-4.50), who had a mental disorder diagnosis (OR 2.08; 95 %CI 1.89-2.30), lived in rural (OR 1.27; 95 %CI 1.17-1.37) or more disadvantaged neighbourhoods had a higher likelihood of death within 12-months following an unplanned admission compared to referent groups. Females (OR 0.87; 95 %CI 0.81-0.93) had an 13 % lower likelihood of mortality within 12-months compared to males. CONCLUSIONS: While some emergency cancer admissions are not avoidable, the importance of preventive screening and promotion of help-seeking for early cancer symptoms should not be overlooked as mechanisms to reduce emergency admissions related to cancer and to improve cancer survival.

DAta Linkage to Enhance Cancer Care (DaLECC): Protocol of a Large Australian Data Linkage Study.

Cancer is a leading cause of global morbidity and mortality, accounting for 250 Disability-Adjusted Life Years and 10 million deaths in 2019. Minimising unwarranted variation and ensuring appropriate cost-effective treatment across primary and tertiary care to improve health outcomes is a key health priority. There are few studies that have used linked data to explore healthcare utilisation prior to diagnosis in addition to post-diagnosis patterns of care. This protocol outlines the aims of the DaLECC project and key methodological features of the linked dataset. The primary aim of this project is to explore predictors of variations in pre- and post-cancer diagnosis care, and to explore the economic and health impact of any variation. The cohort of patients includes all South Australian residents diagnosed with cancer between 2011 and 2020, who were recorded on the South Australian Cancer Registry. These cancer registry records are being linked with state and national healthcare databases to capture health service utilisation and costs for a minimum of one-year prior to diagnosis and to a maximum of 10 years post-diagnosis. Healthcare utilisation includes state databases for inpatient separations and emergency department presentations and national databases for Medicare services and pharmaceuticals. Our results will identify barriers to timely receipt of care, estimate the impact of variations in the use of health care, and provide evidence to support interventions to improve health outcomes to inform national and local decisions to enhance the access and uptake of health care services.

Standardising Breast Radiotherapy Structure Naming Conventions: A Machine Learning Approach.

In progressing the use of big data in health systems, standardised nomenclature is required to enable data pooling and analyses. In many radiotherapy planning systems and their data archives, target volumes (TV) and organ-at-risk (OAR) structure nomenclature has not been standardised. Machine learning (ML) has been utilised to standardise volumes nomenclature in retrospective datasets. However, only subsets of the structures have been targeted. Within this paper, we proposed a new approach for standardising all the structures nomenclature by using multi-modal artificial neural networks. A cohort consisting of 1613 breast cancer patients treated with radiotherapy was identified from Liverpool & Macarthur Cancer Therapy Centres, NSW, Australia. Four types of volume characteristics were generated to represent each target and OAR volume: textual features, geometric features, dosimetry features, and imaging data. Five datasets were created from the original cohort, the first four represented different subsets of volumes and the last one represented the whole list of volumes. For each dataset, 15 sets of combinations of features were generated to investigate the effect of using different characteristics on the standardisation performance. The best model reported 99.416% classification accuracy over the hold-out sample when used to standardise all the nomenclatures in a breast cancer radiotherapy plan into 21 classes. Our results showed that ML based automation methods can be used for standardising naming conventions in a radiotherapy plan taking into consideration the inclusion of multiple modalities to better represent each volume.

Clinicians' attitudes to oncology clinical practice guidelines and the barriers and facilitators to adherence: a mixed methods study protocol.

INTRODUCTION: Clinical practice guidelines (CPGs) are designed to reduce inappropriate clinical variation and improve the quality of care. Barriers to CPGs include a lack of awareness of CPGs, access to them, time pressures and concerns regarding the evidence underpinning CPG development, implementation and dissemination. The objectives of this study are to assess clinicians' attitudes to CPGs for cancer treatment and the perceived barriers to and facilitators of CPG adherence in order to inform the implementation of cancer treatment CPGs. METHODS AND ANALYSIS: A mixed methods study will be conducted using a three-phase, sequential design, with each phase informing the next. In phase 1, a qualitative study using recorded interviews will investigate clinicians' attitudes to CPGs for cancer treatment and perceptions of barriers and facilitators to CPG adherence (n=30); interview transcripts will be analysed thematically. In phase 2, a survey will quantify the frequency of attitudes, barriers and facilitators identified in phase 1, in a broader clinical sample (n=200). In phase 3, a workshop forum will be held to facilitate discussions examining the implications of phase 1 and 2 findings for cancer CPG implementation strategies (n=40) leading to recommendations for improvements to practice. The workshop discussion will be recorded, and the transcript will be analysed thematically. ETHICS AND DISSEMINATION: This study has received ethics approval in New South Wales, Australia (2019/ETH11722, #52019568810127). Study findings will be published in peer-reviewed journals and will form part of a doctoral thesis and be presented at national and international conferences.

Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews.

BACKGROUND: Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents. METHODS: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (International Prospective Register of Systematic Reviews CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes based on statistical significance, study quality, and size. RESULTS: From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone, and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade arterial thromboembolism for trastuzumab, and all-grade arterial thromboembolism for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction decline or congestive heart failure for bevacizumab and trastuzumab, and all-grade left ventricular ejection fraction decline/congestive heart failure for pazopanib and sunitinib; and all-grade corrected QT interval prolongation for vandetanib. CONCLUSIONS: Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.

Quantification of cardiac subvolume dosimetry using a 17 segment model of the left ventricle in breast cancer patients receiving tangential beam radiotherapy.

PURPOSE: Subacute changes following breast radiotherapy have been demonstrated in discrete areas of the left ventricle (LV), with recent guidelines being developed to help determine dose to subvolumes of the LV. This study aims to determine doses to the 17 segments of the LV as per the American Heart Association (AHA) and other cardiac subvolumes, and to correlate mean heart (MHD) dose with various subvolume dosimetric indices. These results may direct focus to specific left ventricular segments in studies of radiation-related heart disease incorporating surveillance imaging, help to determine more precise dose response relationships, and potentially aid prediction of late radiation effects. METHODS AND MATERIALS: The heart and cardiac subvolumes of 29 patients treated with tangential radiotherapy for left breast cancer were contoured. Delineation of cardiac subvolumes (cardiac chambers, cardiac valves and the 17 segments of the LV) was undertaken using a novel contouring method on planning CT data reformatted into the cardiac axis. Individual segments were then combined to determine doses to the basal, mid and apical left ventricular regions, and the anterior, septal, inferior and lateral ventricular walls. Radiotherapy doses (including maximum, mean, D1cc, V25) were determined. Correlation analyses were performed between MHD and various substructure dosimetric indices. RESULTS: Twenty five patients received tangential breast free breathing radiotherapy alone, and four patients received regional nodal irradiation including the internal mammary chain with deep inspiration breath hold (DIBH). For patients receiving breast only radiation, the median mean heart radiation dose was 2.62 Gy (range 1.52-3.90 Gy), and a heterogeneous dose distribution to the LV was noted, with the apical region receiving the highest median mean dose (14.99 Gy) compared with the mid and basal regions (3.10 Gy and 1.51 Gy respectively). The anterior LV wall received the highest median mean dose (9.21 Gy) with the remaining walls receiving similar mean doses (range 1.79-3.05 Gy). The anterior LV apical segment (segment 13) and apex (segment 17) received the highest individual median mean segment doses (26.73 Gy and 30.02 Gy respectively). Apical segments received the highest median mean doses (segments 13, 14, 15, 16), followed by the mid anterior (segment 7) and anteroseptal (segment 8) segments. Segments receiving the highest doses remained unchanged between the DIBH cohort and free breathing cohort. MHD showed a high correlation with the anterior wall r = 0.71, p < 0.05 and entire left ventricle r = 0.82, p < 0.05, but correlations varied from weak to high when MHD was correlated with segments receiving highest doses (range r = 0.43-0.76), p < 0.05. CONCLUSIONS: In the setting of breast cancer radiotherapy, there are substantial RT dose variations within specific LV segments, with mid and apical anterior ventricular segments (segments 7, 13) and the apical region of the LV (segments 13, 14, 15, 16, 17) being consistently exposed to the highest radiation doses. Determining segmental and regional RT doses to the left ventricle may help guide focus in diagnostic cardiology in the post radiotherapy setting.

What is multidisciplinary cancer care like in practice? a protocol for a mixed-method study to characterise ambulatory oncology services in the Australian public sector.

INTRODUCTION: An understanding of the real-world provision of oncology outpatient services can help maintain service quality in the face of escalating demand and tight budgets, by informing the design of interventions that improve the effectiveness or efficiency of provision. The aims of this study are threefold. First, to develop an understanding of cancer services in outpatient clinics by characterising the organisation and practice of multidisciplinary care (MDC). Second, to explore the key areas of: (a) clinical decision-making and (b) engagement with patients' supportive needs. Third, to identify barriers to, and facilitators of, the delivery of quality care in these settings. METHODS AND ANALYSIS: A suite of mixed-methods studies will be implemented at six hospitals providing cancer outpatient clinics, with a staged roll-out. In Stage One, we will examine policies, use unstructured observations and undertake interviews with key health professionals to characterise the organisation and delivery of MDC. In Stage Two, observations of practice will continue, to deepen our understanding, and to inform two focused studies. The first will explore decision-making practices and the second will examine how staff engage with patients' needs; both studies involve interviews, to complement observation. As part of the study of supportive care, we will examine the implications of an introduction of patient-reported measures (PRMs) into care, adding surveys to interviews before and after PRMs roll-out. Data analysis will account for site-specific and cross-site issues using an adapted Qualitative Rapid Appraisal, Rigorous Analysis approach. Quantitative data from clinician surveys will be statistically analysed and triangulated with the related qualitative study findings. ETHICS AND DISSEMINATION: Ethical approval was granted by South Eastern Sydney Local Health District Human Research Ethics Committee (no. 18/207). Findings will be shared with participating hospitals and widely disseminated through publications and presentations.

Testing criterion-based benchmarking for the appropriate use of radiotherapy.

INTRODUCTION: Planning for radiotherapy (RT) services requires information on the proportion of patients who should be given radiotherapy. Criterion-Based Benchmark (CBB) has been proposed in Canada to estimate the proportion of cancer patients who should be treated with radiotherapy. The aim of this study was to assess CBB in a health system outside of Canada. METHODS: Radiotherapy data for all new cases of cancer in New South Wales (NSW), and the Australian Capital Territory (ACT) Australia in 2004-06 and were linked to Central Cancer Registry records. Road distances between patient residence and the nearest RT centre were calculated. Local Government Areas (LGAs) with public radiotherapy departments were selected as CBB LGAs if they met the following criteria: 1. Patients make no direct payment for radiotherapy. 2. All RT is provided by site-specialised radiation oncologists in multi-disciplinary centres. 3. Radiation oncologists receive salary for their service. 4. More than 75% of patients live within 30 km from the nearest RT, and 5. Patients' waiting times were <4 weeks. RESULTS: 25,383 (26%) out of 98,000 eligible patients in NSW and ACT received radiotherapy in the study period as part of their initial treatment. An average of 31% of patients in the CBB LGAs received radiotherapy compared to an average of 26% in all LGAs during the study period. DISCUSSION: NSW-ACT RT utilisation for selected tumour sites was 7-16% higher in the CBB LGAs than in all LGAs, but was still 30-65% below the estimated optimal radiotherapy utilisation rates and differed significantly from Canadian CBBs. CBB is based on the assumption that there is perfect service delivery in some parts of the health service that can be used to benchmark the whole service. It may be applicable in well-resourced publicly-funded services in Canada, but the CBB approach may not be reproducible in other jurisdictions.

Evaluation of traditional and novel echocardiographic methods of cardiac diastolic dysfunction post radiotherapy in breast cancer.

BACKGROUND: To investigate alterations in left ventricular (LV) diastolic function using traditional and novel echocardiographic parameters, following radiation therapy (RT) in breast cancer patients in the acute setting. METHODS: 40 chemotherapy-naïve women with left-sided breast cancer undergoing RT were prospectively recruited. A comprehensive transthoracic echocardiogram (TTE) was performed at baseline, during RT and 6weeks post-RT. Traditional echocardiographic diastolic parameters and diastolic strain rate were measured and analysed. The relationship between alterations in diastolic parameters, changes in global longitudinal systolic strain (GLS) and radiation dose were investigated. RESULTS: Traditional diastolic parameters remained largely unchanged; however diastolic strain parameters, E-Sr and A-Sr were significantly reduced 6weeks post-RT [Longitudinal E-Sr (s-1) 1.47+/-0.32 vs 1.29+/-0.27*; Longitudinal A-Sr (s-1) 1.19+/-0.31 vs 1.03+/-0.24*; *p<0.05 vs baseline]. When patients were divided by a reduction ≥10% versus <10% in GLS post-RT, a greater reduction in both traditional diastolic and diastolic strain parameters was observed in the group with >10% reduction in systolic function as evaluated by GLS. When patients were divided by mean v30 dose, a greater % change in E-Sr was noted in those receiving more than mean V30 dose. CONCLUSION: Diastolic dysfunction was only evident acutely, post-RT with the use of newer methods like strain analysis. A significant reduction in diastolic function was seen in the patient subgroup with ≥10% reduction in systolic function, enhancing the notion of diastolic function as a potential indicator for systolic dysfunction. Future longitudinal studies are required to determine the specific prognostic value of these observations.

The population benefit of radiotherapy for gynaecological cancer: Local control and survival estimates.

BACKGROUND: The population benefit of radiotherapy for gynaecological cancer (GC) if evidence-based guidelines were routinely followed is not known. This study's aim was to address this. METHODS: Decision trees were utilised to estimate benefit. Radiotherapy alone (RT) benefit was the absolute proportional benefit of radiotherapy over no radiotherapy for radical indications, and over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemotherapy and RT over RT alone. Citation databases were systematically queried for the highest level of evidence defining 5-year Local Control (LC), and 2-year and 5-year Overall Survival (OS) benefit. Meta-analysis was performed if there were multiple sources of the same evidence level. Deterministic and probabilistic sensitivity analysis was performed. FINDINGS: Guidelines supported 22 radiotherapy indications, of which 8 were for CRT. 21% of all GC had an adjuvant or curative radiotherapy indication. The absolute estimated population-based 5-year LC and OS benefits of RT, if all patients were treated according to guidelines, were: endometrial cancer LC 5.7% (95% CI (3.5%,8.2%)), OS 2.3% (1.2%,3.4%), ovarian cancer (nil), vulval cancer LC 10.0% (1.6%,18.2%), OS 8.5% (0.5%,15.9%). Combined with prior estimates for cervical cancer, RT benefits for all GC were LC 9.0% (7.8%,10.3%), OS 4.6% (3.8%,5.4%). The incremental benefit of CRT for all GC was LC 0.7% (0.4%,0.9%), OS 0.5% (0.2%,0.8%). Benefits were distinct from the contribution of other modalities. The model was robust in sensitivity analysis. Most radiotherapy benefit was irreplaceable by other modalities. INTERPRETATION: Radiotherapy provides important and irreplaceable LC and OS benefits for GC when optimally utilised. The population model provided a robust means for estimating this benefit.