RESUMEN

In resource-limited settings where vital registration and medical death certificates are unavailable or incomplete, verbal autopsy (VA) is often used to attribute causes of death (CoD) and prioritize resource allocation and interventions. We aimed to determine the CoD concordance between InterVA and CHAMPS's method. The causes of death (CoDs) of children <5 were determined by two methods using data from seven low- and middle-income countries (LMICs) enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. The first CoD method was from the DeCoDe panel using data from Minimally Invasive Tissue Sampling (MITS), whereas the second method used Verbal Autopsy (VA), which utilizes the InterVA software. This analysis evaluated the agreement between the two using Lin's concordance correlation coefficient. The overall concordance of InterVA4 and DeCoDe in assigning causes of death across surveillance sites, age groups, and causes of death was poor (0.75 with 95% CI: 0.73-0.76) and lacked precision. We found substantial differences in agreement by surveillance site, with Mali showing the lowest and Mozambique and Ethiopia the highest concordance. The InterVA4 assigned CoD agrees poorly in assigning causes of death for U5s and stillbirths. Because VA methods are relatively easy to implement, such systems could be more useful if algorithms were improved to more accurately reflect causes of death, for example, by calibrating algorithms to information from programs that used detailed diagnostic testing to improve the accuracy of COD determination.

RESUMEN

This study explores the variation in specialist physician fees and examines whether the variation can be attributed to patient risk factors, variation between physicians, medical specialties, or other factors. We use health insurance claims data from a large private health insurer in Australia. Although Australia has a publicly funded health system that provides universal health coverage, about 44 % of the population holds private health insurance. Specialist physician fees in the private sector are unregulated; physicians can charge any price they want, subject to market forces. We examine the variation in fees using two price measures: total fees charged and out-of- pocket payments. We follow a two-stage method of removing the influence of patient risk factors by computing risk-adjusted prices at patient-level, and aggregating the adjusted prices over all claims made by each physician to arrive at physician-level average prices. In the second stage, we use variance-component models to analyse the variation in the physician-level average prices. We find that patient risk factors account for a small portion of the variance in fees and out-of-pocket payments. Physician-specific variation accounts for the bulk of the vari- ance. The results underscore the importance of understanding physician characteristics in formulating policy efforts to reduce fee variation.

Asunto(s)

RESUMEN

BACKGROUND: New medical devices are frequently introduced at the point of care, and nursing competence in their management is critical for safe patient care. Industry vendors often provide on-the-job in-services for new devices within the constraints of clinical priorities, yet these in-services are not usually monitored or systematically coordinated with stakeholders. METHOD: This project employed quick response (QR) codes and best practices in instructional design in a partnership with vendors to develop and evaluate the impact of an in-service for a new medical device on nursing competence. An online survey measured usefulness, knowledge, and the change in self-perceived competence. DISCUSSION: A total of 536 nurses participated, and 91.2% correctly answered five or six of six questions about device management. The proportion of nurses rating their competence as no experience decreased from 21.2% to 4.5%, and ratings for can do independently/competent increased from 37.6% to 60.2%. CONCLUSION: The use of QR codes offers novel solutions to evaluate how structured, on-the-job education can positively impact nursing practice around medical devices. [J Contin Educ Nurs. 2024;55(9):425-432.].

Asunto(s)

RESUMEN

PURPOSE: Test whether a well-grounded KBP model trained on moderately hypo-fractionated prostate treatments can be used to satisfactorily drive the optimization of SBRT prostate treatments. MATERIALS AND METHODS: A KBP model (SBRT-model) was developed, trained and validated using the first forty-seven clinically treated VMAT SBRT prostate plans (42.7 Gy/7fx or 36.25 Gy/5fx). The performance and robustness of this model were compared against a high-quality KBP-model (ST-model) that was already clinically adopted for hypo-fractionated (70 Gy/28fx and 60 Gy/20fx) prostate treatments. The two models were compared in terms of their predictions robustness, and the quality of their outcomes were evaluated against a set of reference clinical SBRT plans. Plan quality was assessed using DVH metrics, blinded clinical ranking, and a dedicated Plan Quality Metric algorithm. RESULTS: The plan libraries of the two models were found to share a high degree of anatomical similarity. The overall quality (APQM%) of the plans obtained both with the ST- and SBRT-models was compatible with that of the original clinical plans, namely (93.7 ± 4.1)% and (91.6 ± 3.9)% vs (92.8.9 ± 3.6)%. Plans obtained with the ST-model showed significantly higher target coverage (PTV V95%): (97.9 ± 0.8)% vs (97.1 ± 0.9)% (p < 0.05). Conversely, plans optimized following the SBRT-model showed a small but not-clinically relevant increase in OAR sparing. ST-model generally provided more reliable predictions than SBRT-model. Two radiation oncologists judged as equivalent the plans based on the KBP prediction, which was also judged better that reference clinical plans. CONCLUSION: A KBP model trained on moderately fractionated prostate treatment plans provided optimal SBRT prostate plans, with similar or larger plan quality than an embryonic SBRT-model based on a limited number of cases.

Asunto(s)

RESUMEN

BACKGROUND: Diagnostic autopsy is the most reliable approach to definitively ascertain the cause of death and evaluate the accuracy of antemortem clinical diagnoses. Identifying diagnostic discrepancies is vital to understanding common gaps in antemortem clinical diagnoses and modifying antemortem diagnostic approaches to increase the accuracy of clinical diagnosis. The objective of this study was to determine the frequency of diagnostic discrepancies between antemortem clinical diagnoses and postmortem autopsies on lung pathologies and to understand the reasons for diagnostic discrepancies among cases included in Child Health and Mortality Prevention Surveillance (CHAMPS) in Ethiopia. METHODS: A clinical case series study of deaths among children under-five in the CHAMPS study at three sites in Ethiopia between October 2019 and April 2022 was conducted. The antemortem clinical diagnoses and postmortem pathological diagnoses of the lung were compared for each case. Two senior physicians assessed the findings for both agreement and disagreement. McNemar's test was used to assess for statistically significant differences between antemortem and postmortem diagnoses. RESULTS: Seventy-five cases were included (73.3% male). Over half (54.7%) died between the 1st and 7th day of life. Sepsis (66.7%), pneumonia (6.7%), and meconium aspiration syndrome (5.0%) were the most common immediate causes of death. Half (52%) of cases were correctly diagnosed antemortem. The magnitude of diagnostic discrepancy was 35% (95% CI: 20-47%). The most common contributing factors to diagnostic discrepancy were gaps in knowledge (22/75, 35.5%) and problems in consultation and teamwork (22/75, 35.5%). CONCLUSIONS: Misdiagnoses were common among young children who died with positive lung pathology findings. In-service education initiatives and multidisciplinary collaboration are needed to mitigate high rates of diagnostic discrepancies among young children to potentially prevent future deaths.

Asunto(s)

RESUMEN

Traditionally, in many countries general practices have been privately-owned independent small businesses. However, the last three decades has seen the rise of large corporate medical groups defined as private companies which are able to have non-GP shareholders and with branches across many locations. The greater prominence of profit motives may have implications for costs, access to care and quality of care. We estimate that 45% of GPs in Australia worked in a practice that was a private company, and within this group over one third (19.9% of total) worked in a corporate medical group (a private company with 10 or more practice locations). We examine the association between being in a corporate medical group and 19 outcomes classified into five groups: GP wellbeing, workload, patient access, organizational efficiency, and service quality. GPs who worked in such groups were more likely to be older, qualified overseas, and to have a conscientious personality. There was mixed evidence on GPs wellbeing, with GPs in corporate medical groups reporting a higher turnover of GPs but similar levels of job satisfaction. GP workload was similar in terms of hours worked and after hours work but they reported a lower work-life balance. Patient access was better in terms of lower fees charged to patients but there was weak evidence that patients waited longer. GPs in corporate medical groups reported higher organisational efficiency because GPs spent less time spent on administration and management, had more nurses per GP, but despite this GPs were more likely to undertake tasks someone less qualified could do suggesting that nurses were complements not substitutes. There were no differences in service quality (teaching, patient complaints, consultation length, patients seen per hour). Corporate medical groups have become a substantial part of primary care provision in Australia. There is evidence they are more efficient, patient access is better with lower out of pocket costs and there are no differences in our measures service quality, but concerns remain about GP's wellbeing and work-life balance. Further research is needed on continuity of care and patient reported experiences and health outcomes.

Asunto(s)

RESUMEN

Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated with improved OS in both univariate (p = 0.022; 26.3 months vs 10.2 months) and multivariate analysis (p = 0.011, HR 0.49, 95% CI [0.29, 0.85]). PFS did not reach significance (univariate, p = 0.12, 8.2 months vs 5.1 months). Eleven patients developed endocrine irAEs. HLA-DRB4 was the predominant genotype among these patients (9/11, 81.8%). Cumulative incidence of endocrine irAEs was higher in patients with HLA-DRB4 (p = 0.0139). Our study is the first to suggest that patients with metastatic NSCLC patients on ICI therapy with HLA-DRB4 genotype experience improved survival outcomes. Patients with HLA-DRB4 had the longest median OS (26.3 months). Additionally, we found a correlation between HLA-DRB4 and the occurrence of endocrine irAEs.

Asunto(s)

RESUMEN

BACKGROUND: Alcohol-related harm (ARH) is a significant public health concern affecting young individuals, particularly those involved in alcohol-related police incidents resulting in hospitalisation. However, the impact of alcohol on young victims remains under researched. This study aimed to identify the characteristics of offenders and victims involved in these incidents, analyse the types of offences, and understand the under-ascertainment of ARH in hospital records. METHODS: A retrospective longitudinal study of 12-24-year-olds born between 1980 and 2005 was conducted using linked data from hospital admissions, emergency department presentations, and police incident records. Alcohol-related incidents were identified based on the attending officers' opinions in the Western Australia Police's Incident Management System (IMS). Logistic and log-binomial regression were utilised to analyse the factors associated with victimisation and under-ascertainment of ARH. RESULTS: Our study included 22,747 individuals (11,433 victims and 11,314 offenders) involved in alcohol-related police incidents, with a small majority of victims being female (53%, n = 6,074) and a large majority of offenders being male (84.3%, n = 9,532). Most victims did not receive a diagnosis of ARH (71%, n = 760). Women were 10 times more likely to have been a victim in ARH police incidents and 2 times more likely to have an undiagnosed alcohol-related hospital admission than men. Victims and offenders predominantly came from disadvantaged areas and major cities. Aboriginal individuals were overrepresented as both offenders and victims. A significant proportion of individuals experienced emergency department presentations or hospital admissions, with head injuries being the most common. Assault causing bodily harm was the most prevalent offence resulting in hospitalisation (66%, n = 2,018). CONCLUSIONS: There is a noteworthy disparity between the quantity of hospital admissions attributed to alcohol-related incidents and the number of cases that are formally classified as ARH in the hospital system. This disparity highlights a more profound issue of substantial under-ascertainment or inadequate identification of ARH than previously acknowledged. Our findings justify the prioritisation of prevention strategies, beyond improvement in the documentation of alcohol-related hospitalisation. Considering the scale of the problem, and the underestimation of the burden of alcohol-related hospitalisation, a proportional increase in investment is necessary to achieve population-level reductions in ARH.

Asunto(s)

RESUMEN

Risk attitude is known to influence physicians' decision-making under uncertainty. Research on the risk attitudes of physicians is therefore important in facilitating a better understanding of physicians' decisions. However, little is known about the stability of physicians' risk attitudes across domains. Using five waves of data from a prospective panel study of Australian physicians from 2013 to 2017, we explored the stability of risk attitudes over a four-year period and examined the association between negative life events and risk attitudes among 4417 physicians. Further, we tested the stability of risk attitude across three domains most relevant to a physician's career and clinical decision-making (financial, career and clinical). The results showed that risk attitude was stable over time at both the mean and individual levels but the correlation between domains was modest. There were no significant associations between negative life events and risk attitude changes in all three domains. These findings suggest that risk attitude can be assumed to be constant but domain-specificity needs to be considered in analyses of physician decision-making.

Asunto(s)

RESUMEN

The Australian government, through Medicare, defines the type of medical specialist services it covers and subsidizes, but it does not regulate prices. Specialists in private practice can charge more than the fee listed by Medicare depending on what they feel 'the market will bear'. This can sometimes result in high and unexpected out-of-pocket (OOP) payments for patients. To reduce pricing uncertainty and 'bill shock' faced by consumers, the government introduced a price transparency website in December 2019. It is not clear how effective such a website will be and whether specialists and patients will use it. The aim of this qualitative study was to explore factors influencing how specialists set their fees, and their views on and participation in price transparency initiatives. We conducted 27 semi-structured interviews with surgical specialists. We analysed the data using thematic analysis and responses were mapped to the Theoretical Domains Framework and the Capability, Opportunity, Motivation and Behavior model. We identified several patient, specialist and system-level factors influencing fee setting. Patient-level factors included patient characteristics, circumstance, complexity, and assumptions regarding perceived value of care. Specialist-level factors included perceived experience and skills, ethical considerations, and gendered-behavior. System-level factors included the Australian Medical Association recommended price list, practice costs, and supply and demand factors including perceived competition and practice location. Specialists were opposed to price transparency websites and lacked motivation to participate because of the complexity of fee setting, concerns over unintended consequences, and feelings of frustration they were being singled out. If price transparency websites are to be pursued, specialists' lack of motivation to participate needs to be addressed.

Asunto(s)

RESUMEN

We examine the impact of changes to a national physician fee schedule on total medical expenditures, the volume of services, and fees charged. In our context, changes to the fee schedule were designed to promote value-based health care, and so included different types of changes to subsidised medical services, including changes to fees. Using claims data from a sample of doctors linked to a physician survey, we use difference-in-difference methods with a staggered adoption design to compare medical services which were affected with those which were not. We show that medical expenditures and the volume of affected services fell, though there is uncertainty about the magnitude of the fall. For GPs, we find evidence of increases in expenditures and fees and an increase in fees for some services provided by specialists.

Asunto(s)

RESUMEN

Background: Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). Methods: Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. Results: We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). Conclusions: Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs.

RESUMEN

Despite their low cost, the use of email invitations to distribute surveys to medical practitioners have been associated with lower response rates. This research compares the difference in response rates from using email approach plus online completion rather than a mailed invitation letter plus a choice of online or paper completion. A parallel randomised controlled trial was conducted during the 11th annual wave of the nationally representative Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey of doctors. The control group was invited using a mailed paper letter (including a paper survey plus instructions to complete online) and three mailed paper reminders. The intervention group was approached in the same way apart from the second reminder when they were approached by email only. The primary outcome is the response rate and the statistical analysis was blinded. 18,247 doctors were randomly allocated to the control (9,125) or intervention group (9,127), with 9,108 and 9,107 included in the analysis. Using intention to treat analysis, the response rate in the intervention group was 35.92% compared to 37.59% in the control group, a difference of -1.66 percentage points (95% CI: -3.06 to -0.26). The difference was larger for General Practitioners (-2.76 percentage points, 95% CI: -4.65 to -0.87) compared to other specialists (-0.47 percentage points, 95% CI: -2.53 to 1.60). For those who supplied an email address, the average treatment effect on the treated was higher at -2.63 percentage points (95% CI: -4.50 to -0.75) for all physicians, -3.17 percentage points (95% CI: -5.83 to -0.53) for General Practitioners, and -2.1 percentage points (95% CI: -4.75 to 0.56) for other specialists. For qualified physicians, using email to invite participants to complete a survey leads to lower response rates compared to a mailed letter. Lower response rates need to be traded off with the lower costs of using email rather than mailed letters.

Asunto(s)

RESUMEN

INTRODUCTION: The standard of care for imaging of breast pathology has historically been mammography and sonography. MRI is a modern adjunct in the surgeon's toolkit. We looked to examine the differences in imaging modalities and their ability to predict the size in relation to the pathologic size after excision with focus on pathologic subtypes. METHODS: We analyzed patient records across a 4-year period from 2017 to 2021 who were treated surgically for breast cancer at our facility. We used a retrospective chart review to collect measurements that were recorded of the tumors by the radiologist for available mammography, ultrasound, and MRI which were compared to pathology report measurements of the final specimens. We subdivided the results by pathologic subtypes including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS). RESULTS: 658 total patients met criteria for analysis. Mammography overestimated specimens with DCIS by 1.93 mm (P = .15), US underestimated by .56 (.55), and MRI overestimated by 5.77 mm (P < .01). There was no statistically significant difference in any modalities with IDC. With specimens of ILC, all 3 imaging modalities underestimated tumor size, with only US being significant. DISCUSSION: Mammography and MRI consistently overestimated tumor size with the exception of ILC while US underestimated tumor size on all pathologic subtypes. MRI significantly overestimated tumor size in DCIS by 5.77 mm. Mammography was the most accurate imaging modality for all pathologic subtypes and never had a statistically significant difference from actual tumor size.

Asunto(s)

RESUMEN

OBJECTIVES: Personality differences between doctors and patients can affect treatment outcomes. We examine these trait disparities, as well as differences across medical specialities. DESIGN: Retrospective, observational statistical analysis of secondary data. SETTING: Data from two data sets that are nationally representative of doctors and the general population in Australia. PARTICIPANTS: We include 23 358 individuals from a representative survey of the general Australian population (with subgroups of 18 705 patients, 1261 highly educated individuals and 5814 working in caring professions) as well as 19 351 doctors from a representative survey of doctors in Australia (with subgroups of 5844 general practitioners, 1776 person-oriented specialists and 3245 technique-oriented specialists). MAIN OUTCOME MEASURES: Big Five personality traits and locus of control. Measures are standardised by gender, age and being born overseas and weighted to be representative of their population. RESULTS: Doctors are significantly more agreeable (a: standardised score -0.12, 95% CIs -0.18 to -0.06), conscientious (c: -0.27 to -0.33 to -0.20), extroverted (e: 0.11, 0.04 to 0.17) and neurotic (n: 0.14, CI 0.08 to 0.20) than the general population (a: -0.38 to -0.42 to -0.34, c: -0.96 to -1.00 to -0.91, e: -0.22 to -0.26 to -0.19, n: -1.01 to -1.03 to -0.98) or patients (a: -0.77 to -0.85 to -0.69, c: -1.27 to -1.36 to -1.19, e: -0.24 to -0.31 to -0.18, n: -0.71 to -0.76 to -0.66). Patients (-0.03 to -0.10 to 0.05) are more open than doctors (-0.30 to -0.36 to -0.23). Doctors have a significantly more external locus of control (0.06, 0.00 to 0.13) than the general population (-0.10 to -0.13 to -0.06) but do not differ from patients (-0.04 to -0.11 to 0.03). There are minor differences in personality traits among doctors with different specialities. CONCLUSIONS: Several personality traits differ between doctors, the population and patients. Awareness about differences can improve doctor-patient communication and allow patients to understand and comply with treatment recommendations.

Asunto(s)

RESUMEN

BACKGROUND AND PURPOSE: Clinical knowledge-based planning (KBP) models dedicated to prostate radiotherapy treatment may require periodical updates to remain relevant and to adapt to possible changes in the clinic. This study proposes a paired comparison of two different update approaches through a longitudinal analysis. MATERIALS AND METHODS: A clinically validated KBP model for moderately hypofractionated prostate therapy was periodically updated using two approaches: one was targeted at achieving the biggest library size (Mt), while the other one at achieving the highest mean sample quality (Rt). Four subsequent updates were accomplished. The goodness, robustness and quality of the outcomes were measured and compared to those of the common ancestor. Plan quality was assessed through the Plan Quality Metric (PQM) and plan complexity was monitored. RESULTS: Both update procedures allowed for an increase in the OARs sparing between +3.9 % and +19.2 % compared to plans generated by a human planner. Target coverage and homogeneity slightly reduced [-0.2 %;-14.7 %] while plan complexity showed only minor changes. Increasing the sample size resulted in more reliable predictions and improved goodness-of-fit, while increasing the mean sample quality improved the outcomes but slightly reduced the models reliability. CONCLUSIONS: Repeated updates of clinical KBP models can enhance their robustness, reliability and the overall quality of automatically generated plans. The periodical expansion of the model sample accompanied by the removal of the unacceptable low quality plans should maximize the benefits of the updates while limiting the associated workload.

Asunto(s)

RESUMEN

BACKGROUND: Lynch syndrome (LS) is a cancer predisposition syndrome affecting more than 1 in every 300 individuals worldwide. Clinical genetic testing for LS can be life-saving but is complicated by the heavy burden of variants of uncertain significance (VUS), especially missense changes. RESULT: To address this challenge, we leverage a multiplexed analysis of variant effect (MAVE) map covering >94% of the 17,746 possible missense variants in the key LS gene MSH2. To establish this map's utility in large-scale variant reclassification, we overlay it on clinical databases of >15,000 individuals with LS gene variants uncovered during clinical genetic testing. We validate these functional measurements in a cohort of individuals with paired tumor-normal test results and find that MAVE-based function scores agree with the clinical interpretation for every one of the MSH2 missense variants with an available classification. We use these scores to attempt reclassification for 682 unique missense VUS, among which 34 scored as deleterious by our function map, in line with previously published rates for other cancer predisposition genes. Combining functional data and other evidence, ten missense VUS are reclassified as pathogenic/likely pathogenic, and another 497 could be moved to benign/likely benign. Finally, we apply these functional scores to paired tumor-normal genetic tests and identify a subset of patients with biallelic somatic loss of function, reflecting a sporadic Lynch-like Syndrome with distinct implications for treatment and relatives' risk. CONCLUSION: This study demonstrates how high-throughput functional assays can empower scalable VUS resolution and prospectively generate strong evidence for variant classification.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Asunto(s)

RESUMEN

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Asunto(s)