Economic Evaluations of Obesity-Targeted Sugar-Sweetened Beverage (SSB) Taxes-A Review to Identify Methodological Issues.

INTRODUCTION: Economic evaluations of public health interventions like sugar-sweetened beverage (SSB) taxes face difficulties similar to those previously identified in other public health areas. This stems from challenges in accurately attributing effects, capturing outcomes and costs beyond health, and integrating equity effects. This review examines how these challenges were addressed in economic evaluations of SSB taxes. METHODS: A systematic review was conducted to identify economic evaluations of SSB taxes focused on addressing obesity in adults, published up to February 2021. The methodological challenges examined include measuring effects, valuing outcomes, assessing costs, and incorporating equity. RESULTS: Fourteen economic evaluations of SSB taxes were identified. Across these evaluations, estimating SSB tax effects was uncertain due to a reliance on indirect evidence that was less robust than evidence from randomised controlled trials. Health outcomes, like quality-adjusted life years, along with a healthcare system perspective for costs, dominated the evaluations of SSB taxes, with a limited focus on broader non-health consequences. Equity analyses were common but employed significantly different approaches and exhibited varying degrees of quality. CONCLUSION: Addressing the methodological challenges remains an issue for economic evaluations of public health interventions like SSB taxes, suggesting the need for increased attention on those issues in future studies. Dedicated methodological guidelines, in particular addressing the measurement of effect and incorporation of equity impacts, are warranted.

Discrete Event Simulation to Incorporate Infusion Wait-Time When Assessing Cost-Effectiveness of a Chimeric-Antigen Receptor T Cell Therapy.

OBJECTIVES: The main objective was to use discrete event simulation to model the impact of wait-time, defined as the time between leukapheresis and chimeric antigen receptor (CAR-T) infusion, when assessing the cost-effectiveness of tisagenlecleucel in young patients with relapsed/refractory acute lymphoblastic leukemia. METHODS: The movement of patients through the model was determined by parametric time-to-event distributions, with the competing risk of an event determining the costs and quality-adjusted life-years (QALYs) assigned. Cost-effectiveness was expressed using the incremental cost-effectiveness ratio (ICER) for tisagenlecleucel compared with chemotherapy over the lifetime. RESULTS: The base case generated a total of 5.79 QALYs and $622 872 for tisagenlecleucel and 1.19 QALYs and $181 219 for blinatumomab, resulting in an ICER of $96 074 per QALY. An increase in mean CAR-T wait-time to 6.20 months reduced the benefit and costs of tisagenlecleucel to 2.78 QALYs and $294 478 because of fewer patients proceeding to infusion, reducing the ICER to $71 112 per QALY. Alternatively, when the cost of tisagenlecleucel was assigned pre-infusion in sensitivity analysis, the ICER increased with increasing wait-time. CONCLUSIONS: Under a payment arrangement where CAR-T cost is incurred post-infusion, the loss of benefit to patients is not reflected in the ICER. This may be misguiding to decision makers, where cost-effectiveness ratios are used to guide resource allocation. discrete event simulation is an important tool for economic modeling of CAR-T as it is amenable to capturing the impact of wait-time, facilitating better understanding of factors affecting service delivery and consequently informed decision making to deliver faster access to CAR-T for patients.

Healthcare Resource Utilization and Cost Associated with Allogeneic Hematopoietic Stem Cell Transplantation: A Scoping Review.

This scoping review summarizes the evidence regarding healthcare resource utilization (HRU) and costs associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study was conducted in accordance with the Joanne Briggs Institute methodology for scoping reviews. The PubMed, Embase, and Health Business Elite Electronic databases were searched, in addition to grey literature. The databases were searched from inception up to November 2022. Studies that reported HRU and/or costs associated with adult (≥18 years) allo-HSCT were eligible for inclusion. Two reviewers independently screened 20% of the sample at each of the 2 stages of screening (abstract and full text). Details of the HRU and costs extracted from the study data were summarized, based on the elements and timeframes reported. HRU measures and costs were combined across studies reporting results defined in a comparable manner. Monetary values were standardized to 2022 US Dollars (USD). We identified 43 studies that reported HRU, costs, or both for allo-HSCT. Of these studies, 93.0% reported on costs, 81.4% reported on HRU, and 74.4% reported on both. HRU measures and cost calculations, including the timeframe for which they were reported, were heterogeneous across the studies. Length of hospital stay was the most frequently reported HRU measure (76.7% of studies) and ranged from a median initial hospitalization of 10 days (reduced-intensity conditioning [RIC]) to 73 days (myeloablative conditioning). The total cost of an allo-HSCT ranged from $63,096 (RIC) to $782,190 (double umbilical cord blood transplantation) at 100 days and from $69,218 (RIC) to $637,193 at 1 year (not stratified). There is heterogeneity in the reporting of HRU and costs associated with allo-HSCT in the literature, making it difficult for clinicians, policymakers, and governments to draw definitive conclusions regarding the resources required for the delivery of these services. Nevertheless, to ensure that access to healthcare meets the necessary high cost and resource demands of allo-HSCT, it is imperative for clinicians, policymakers, and government officials to be aware of both the short- and long-term health resource requirements for this patient population. Further research is needed to understand the key determinants of HRU and costs associated with allo-HSCT to better inform the design and delivery of health care for HSCT recipients and ensure the quality, safety, and efficiency of care.

An Economic Analysis of SC24 in Canada: A Randomized Study of SBRT Compared With Conventional Palliative RT for Spinal Metastases.

PURPOSE: The Canadian Cancer Trials Group (CCTG) Symptom Control 24 protocol (SC.24) was a multicenter randomized controlled phase 2/3 trial conducted in Canada and Australia. Patients with painful spinal metastases were randomized to either 24 Gy/2 stereotactic body radiation therapy (SBRT) or 20 Gy/5 conventional external beam radiation therapy (CRT). The study met its primary endpoint and demonstrated superior complete pain response rates at 3 months following SBRT (35%) versus CRT (14%). SBRT planning and delivery is resource intensive. Given its benefits in SC.24, we performed an economic analysis to determine the incremental cost-effectiveness of SBRT compared with CRT. METHODS AND MATERIALS: The trial recruited 229 patients. Cost-effectiveness was assessed using a Markov model taking into account observed survival, treatments costs, retreatment, and quality of life over the lifetime of the patient. The EORTC-QLU-C10D was used to determine quality of life values. Transition probabilities for outcomes were from available patient data. Health system costs were from the Canadian health care perspective and were based on 2021 Canadian dollars (CAD). The incremental cost-effectiveness ratio (ICER) was expressed as the ratio of incremental cost to quality-adjusted life years (QALY). The impact of parameter uncertainty was investigated using deterministic and probabilistic sensitivity analyses. RESULTS: The base case for SBRT compared with CRT had an ICER of $9,040CAD per QALY gained. Sensitivity analyses demonstrated that the ICER was most sensitive to variations in the utility assigned to "No local failure" ($5,457CAD to $241,051CAD per QALY), adopting low and high estimates of utility and the cost of the SBRT (ICERs ranging from $7345-$123,361CAD per QALY). It was more robust to variations in assumptions around survival and response rate. CONCLUSIONS: SBRT is associated with higher upfront costs than CRT. The ICER shows that, within the Canadian health care system, SBRT with 2 fractions is likely to be more cost-effective than CRT.

The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.

BACKGROUND: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown. STUDY DESIGN: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial. ENDPOINTS: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness. ELIGIBILITY CRITERIA: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT. PATIENTS AND METHODS: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707).

An analysis of the resource use and costs of febrile neutropenia events in pediatric cancer patients in Australia.

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.

Education messages and strategies to inform the public, potential screening candidates and healthcare providers about lung cancer screening: A systematic review.

International lung cancer screening (LCS) trials, using low-dose computed tomography, have demonstrated clinical effectiveness in reducing mortality from lung cancer. This systematic review aims to synthesise the key messages and strategies that could be successful in increasing awareness and knowledge of LCS, and ultimately increase uptake of screening. Studies were identified via relevant database searches up to January 2022. Two authors evaluated eligible studies, extracted and crosschecked data, and assessed quality. Results were synthesised narratively. Of 3205 titles identified, 116 full text articles were reviewed and 22 studies met the inclusion criteria. Twenty studies were conducted in the United States. While the study findings were heterogenous, key messages mentioned across multiple studies were about: provision of information on LCS and the recommendations for LCS (n = 8); benefits and harms of LCS (n = 6); cost of LCS and insurance coverage for participants (n = 6) and eligibility criteria (n = 5). To increase knowledge and awareness, evidence from awareness campaigns suggests that presenting information about eligibility and the benefits and harms of screening, may increase screening intention and uptake. Evidence from behavioural studies suggests that campaigns supporting engagement with platforms such as educational videos and digital awareness campaigns might be most effective. Group based learning appears to be most suited to increasing health professionals' knowledge. This systematic review found a lack of consistent evidence to demonstrate which strategies are most effective for increasing participant healthcare professional and community awareness and education about LCS.

Cost-Effectiveness of Single Versus Multifraction SABR for Pulmonary Oligometastases: The SAFRON II Trial.

PURPOSE: The use of stereotactic ablative body radiation therapy (SABR) in advanced cancer care is increasing, yet the cost-effectiveness of single-fraction (SF) versus multifraction (MF) SABR in pulmonary oligometastases is unknown. METHODS: A prespecified cost-effectiveness analysis was conducted of the Trans Tasman Radiation Oncology Group 13.01 - SAFRON II - randomized trial comparing SF with MF SABR in 87 patients with 133 pulmonary oligometastases. A partitioned survival model assessed costs and quality-adjusted life-years (QALY) over the within-trial period (4 years) and longer-term (10 years). Costs reflected a societal perspective, expressed in Australian dollars (A$) using 2020 prices and were estimated using patient level data on health care utilization for radiation therapy (including patient time), post-radiation systemic therapy and treatment of adverse effects. Quality of life was assessed using the EuroQoL EQ-5D-5L. The incremental cost-effectiveness ratio (ICER) was expressed as the cost per QALY gained for SF versus MF SABR, with uncertainty assessed using deterministic and probabilistic sensitivity analyses. RESULTS: SF cost less than MF for initial therapy (difference of A$1194/patient). Mean time to initiation of systemic drug therapy did not differ between arms (P = .94). Numerical differences in survival favoring SF resulted in greater overall health care use for the within-trial period. The within-trial ICER was A$15,821/QALY and A$23,265/QALY over the longer term. Results were most sensitive to the cost of postprogression therapies and utility values. The sensitivity analysis indicated that SF SABR has a 97% probability of being cost-effective at a willingness-to-pay of A$50,000/QALY. CONCLUSIONS: SF has lower initial costs and is highly likely to be cost-effective. Time to initiation of systemic therapy associated with disease progression is highly patient relevant and is a major driver of cost-effectiveness. Comparisons for SF SABR with nonradiation therapy approaches to the treatment of pulmonary oligometastases warrant further investigation.

Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia.

BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children's Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children's general and cancer-related health-related quality of life (HRQoL) and parents' emotional well-being. METHODS: Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. RESULTS: Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1-213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children's HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. CONCLUSIONS: It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL.

The SCRIPT trial: study protocol for a randomised controlled trial of a polygenic risk score to tailor colorectal cancer screening in primary care.

BACKGROUND: Polygenic risk scores (PRSs) can predict the risk of colorectal cancer (CRC) and target screening more precisely than current guidelines using age and family history alone. Primary care, as a far-reaching point of healthcare and routine provider of cancer screening and risk information, may be an ideal location for their widespread implementation. METHODS: This trial aims to determine whether the SCRIPT intervention results in more risk-appropriate CRC screening after 12 months in individuals attending general practice, compared with standard cancer risk reduction information. The SCRIPT intervention consists of a CRC PRS, tailored risk-specific screening recommendations and a risk report for participants and their GP, delivered in general practice. Patients aged between 45 and 70 inclusive, attending their GP, will be approached for participation. For those over 50, only those overdue for CRC screening will be eligible to participate. Two hundred and seventy-four participants will be randomised to the intervention or control arms, stratified by general practice, using a computer-generated allocation sequence. The primary outcome is risk-appropriate CRC screening after 12 months. For those in the intervention arm, risk-appropriate screening is defined using PRS-derived risk; for those in the control arm, it is defined using family history and national screening guidelines. Timing, type and results of the previous screening are considered in both arms. Objective health service data will capture screening behaviour. Secondary outcomes include cancer-specific worry, risk perception, predictors of CRC screening behaviour, screening intentions and health service use at 1, 6 and 12 months post-intervention delivery. DISCUSSION: This trial aims to determine whether a PRS-derived personalised CRC risk estimate delivered in primary care increases risk-appropriate CRC screening. A future population risk-stratified CRC screening programme could incorporate risk assessment within primary care while encouraging adherence to targeted screening recommendations. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12621000092897p. Registered on 1 February 2021.

Preferences for HIV Testing Services and HIV Self-Testing Distribution Among Migrant Gay, Bisexual, and Other Men Who Have Sex With Men in Australia.

Background: In Australia, undiagnosed HIV rates are much higher among migrant gay, bisexual, or other men who have sex with men (GBMSM) than Australian-born GBMSM. HIV self-testing is a promising tool to overcome barriers to HIV testing and improve HIV testing uptake among migrant GBMSM. We compared the preferences for HIV testing services, including HIV self-testing, among migrant and Australian-born GBMSM. Methods: Preferences were assessed via two discrete choice experiments (DCEs). Participants were recruited between December 2017 and January 2018 using online and offline advertising and randomly assigned to complete one of two online DCE surveys. Migrant GBMSM were classified as being born in a country with a reciprocal healthcare agreement (RHCA) with Australia (providing free or subsided health care) or not. Latent class analysis and mixed logit models were used to explore heterogeneity in preferences. Findings: We recruited 1,606 GBMSM, including 583 migrant men of whom 419 (72%) were born in non-RHCA countries. Most participants preferred a free or cheap oral test with higher accuracy and a shorter window period to facilitate early detection of infections. Cost was more important for men born in non-RHCA countries than for men from RHCA countries or Australia. All groups preferred accessing kits through online distributers or off the shelf purchasing from pharmacies. Men born in RHCA countries least preferred accessing HIV self-testing kits from a medical clinic, while more than half of men from non-RHCA countries most preferred sourcing kits from a clinic. Sex-on-premises venues were the least preferred location to access test kits among all groups. In addition, two latent class analyses explored heterogeneity in preferences among men from non-RHCA countries and we found four latent classes for HIV testing services and two latent classes for HIVST distribution. Interpretation: Our findings emphasise the need for high-performing and low-cost HIV self-testing kits that are accessible from a variety of distribution points as a component of Australia's HIV response, especially for those who do not have access to free or subsidised health care in Australia.

GUIDE: a randomised non-comparative phase II trial of biomarker-driven intermittent docetaxel versus standard-of-care docetaxel in metastatic castration-resistant prostate cancer (clinical trial protocol).

Objective: To determine the efficacy and safety of intermittent docetaxel chemotherapy guided by circulating methylated glutathione S-transferase Pi-1 (mGSTP1) in men with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods: GUIDE (NCT04918810) is a randomised, two-arm, non-comparative phase-2 trial recruiting 120 patients at six Australian centres. Patients with Prostate Cancer Working Group-3 defined metastatic CRPC who are commencing docetaxel 75 mg/m2 q3w will be pre-screened for detectable mGSTP1 at baseline ± following two cycles of treatment. Those with detectable plasma mGSTP1 at baseline that becomes undetectable after two cycles of chemotherapy will be eligible for GUIDE. Prior to Cycle 4 of docetaxel, these patients are randomised 2:1 to one of two treatment arms: Arm A (cease docetaxel and reinstitute if mGSTP1 becomes detectable) or Arm B (continue docetaxel 75 mg/m2 q3w in accordance with clinician's usual practice). The primary endpoint is radiographic progression-free survival. Secondary endpoints include time on treatment holidays, safety, patient-reported outcomes, overall survival, health resource use, and cost associated with treatment. Enrolment commenced November 2021. Results and Conclusion: The results of this trial will generate data on the clinical utility of mGSTP1 as a novel biomarker to guide treatment de-escalation in metastatic CRPC.

LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study.

INTRODUCTION: Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsies METHODS AND ANALYSIS: This study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library preparation and targeted capture will be performed using the TruSight Tumor 170 (TST170) kit and samples sequenced on NextSeq 550 (Illumina) using NextSeq V.2.5 hi output reagents, according to the manufacturer's instructions. Data analysis will be performed using the Illumina BaseSpace TST170 app v1.02 and a custom tertiary pipeline, implemented within the Clinical Genomics Workspace software platform from PierianDx (also refer to section 3.2). Primary outcomes for the study will be the number of patients enrolled and the number of patients who complete molecular screening. Secondary outcomes will include the proportion of screened patients enrolled; proportion of patients who complete molecular screening; the turn-around time of molecular screening; and the value of a brain tumour specific multi-disciplinary tumour board, called the molecular tumour advisory panel as measured by the proportion of patients in whom the treatment recommendation was refined compared with the recommendations from the automated bioinformatics platform of the reference laboratory testing. ETHICS AND DISSEMINATION: The study was approved by the lead Human Research Ethics Committee of the Sydney Local Health District: Protocol No. X19-0383. The study will be conducted in accordance with the principles of the Declaration of Helsinki 2013, guidelines for Good Clinical Practice and the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2007, updated 2018 and as amended periodically). Results will be disseminated using a range of media channels including newsletters, social media, scientific conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12620000087954; Pre-results.

Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital.

BACKGROUND: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. METHOD: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. RESULTS: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. CONCLUSION: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program.

Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation.

PURPOSE: Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion. METHODS: EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate-ICECaP-database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS: Data for 10,350 patients were analyzed from 15 radiation therapy-based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall's tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION: EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy-based trials.

A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol.

BACKGROUND: Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. OBJECTIVES AND METHODS: The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. OUTCOME AND SIGNIFICANCE: This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.