Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Colorectal cancer survivors' experiences and views of shared and telehealth models of survivorship care: A qualitative study.

OBJECTIVES: The number of colorectal cancer (CRC) survivors is increasing and current models of survivorship care are unsustainable. There is a drive to implement alternative models of care including shared care between general practitioners (GPs) and hospital-based providers. The primary objective of this study was to explore perspectives on facilitators and barriers to shared care. The secondary objective was to explore experiences of telehealth-delivered care. METHOD: Qualitative data were collected via semi-structured interviews with participants in the Shared Care for Colorectal Cancer Survivors (SCORE) randomised controlled trial. Interviews explored patient experiences of usual and shared survivorship care during the SCORE trial. In response to the COVID pandemic, participant experiences of telehealth appointments were also explored. Interviews were recorded and transcribed for thematic analysis. RESULTS: Twenty survivors of CRC were interviewed with an even number in the shared and usual care arms; 14 (70%) were male. Facilitators to shared care included: good relationships with GPs; convenience of GPs; good communication between providers; desire to reduce public health system pressures. Barriers included: poor communication between clinicians; inaccessibility of GPs; beliefs about GP capacity; and a preference for follow-up care with the hospital after positive treatment experiences. Participants also commonly expressed a preference for telehealth-based follow-up when there was no need for a clinical examination. CONCLUSIONS: This is one of few studies that have explored patient experiences with shared and telehealth-based survivorship care. Findings can guide the implementation of these models, particularly around care coordination, communication, preparation, and personalised pathways of care.

A systematic review of economic evaluations for RPE65-mediated inherited retinal disease including HTA assessment of broader value.

OBJECTIVE: To summarize the key methodological challenges identified by health technology assessment (HTA) agencies assessing gene therapy (GT) and consideration of broad elements of value. METHOD: Economic evaluations (EEs) of voretigene neparvovec (VN) in RPE65-mediated inherited retinal disease (IRD) published in English were selected. HTA evaluations from Australia, Canada, Ireland, Scotland, England, and the United States were reviewed. An existing methodological framework was used to identify the challenges and considerations. RESULTS: Eight unique EEs were identified of which six were evaluated by HTA agencies. Incremental cost-effectiveness ratios ranged from $68,951 to $643,813 per quality-adjusted life-years (QALY) gained (healthcare perspective) and dominant to $480,130 per QALY gained (societal perspective). The key challenges were the lack of validated surrogate outcome, utility values and indirect costs from IRD patients, and limited evidence of the long-term treatment effect. Two HTA agencies reviewed a range of novel broader elements of value and whether they were associated with VN while other agencies discussed some elements of broader value. Caregiver disutility was included in some, but not all, evaluations. CONCLUSION: The methodological challenges were consistent with innovative interventions for rare diseases and managed using standard methods. Broader value was important to decision-makers but inconsistently applied across agencies. Possible reasons are limitations in the evidence available of the broader benefits that VN offers and how to incorporate these within an EE. A need exists for greater guidance and consistency across jurisdictions regarding the consideration of broader value that considers latest best practice.

Preferences for a polygenic test to estimate cancer risk in a general Australian population.

PURPOSE: There is significant interest in the use of polygenic risk score (PRS) tests to improve cancer risk assessment and stratified prevention. Our current understanding of preferences regarding different aspects of this novel testing approach is limited. This study examined which attributes of a PRS test most influence the likelihood of testing. METHODS: A discrete choice experiment was developed to elicit preferences for different aspects of a PRS test by surveying an online sample of the Australian population. Preferences were assessed using mixed logistic regression, latent class analysis, and marginal willingness to pay. RESULTS: The 1002 surveyed respondents were more likely to choose a PRS test that was more accurate, tested for multiple cancer types, and enabled cancer risk reduction through lifestyle modification, screening, or medication. There was also a preference for testing through a primary care physician rather than online or through a genetic specialist. A test that did not impact life insurance eligibility or premiums was preferred over the one that did. CONCLUSION: This study found that the Australian population prefer a PRS test that is highly accurate, tests for multiple cancers, has noninvasive risk reduction measures, and is performed through primary care.

A Systematic Review of Health Technology Assessments of Chimeric Antigen Receptor T-Cell Therapies in Young Compared With Older Patients.

OBJECTIVES: The objective of this review was to identify sources of variability in cost-effectiveness analyses of chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel and axicabtagene ciloleucel, evaluated by health technology assessment (HTA) agencies, focusing on young compared with older patients. METHODS: HTA evaluations in pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL) were included from Australia, Canada, England, Norway, and the United States. Key clinical evidence, economic approach, and outcomes (costs, quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratios) were summarized. RESULTS: Fourteen HTA evaluations were identified (5 ALL, 9 DLBCL [4 tisagenlecleucel, 5 axicabtagene]). Analyses were naive comparisons of prospective single-arm studies for the CAR-Ts with retrospective cohort studies for the comparators. Key clinical evidence and economic model approaches were generally consistent by CAR-T and indication, although outcomes varied. Notably, incremental QALYs varied substantially in ALL (3.67-10.6 QALYs gained), whereas variation in DLBCL was less (1.21-1.97 [tisagenlecleucel], 1.97-3.40 [axicabtagene]). Discounting of costs and outcomes varied, with the highest QALYs generated for tisagenlecleucel in ALL (10.95) associated with the lowest discount rate (1.5%) and vice versa (4.97 QALYs; 5% discount rate). The approach to extrapolation of overall survival data varied, even where the same empirical data were used. CONCLUSION: Modeled, long-term treatment benefit in young patients may be associated with greater uncertainty compared with adults because of potential life-long benefits with cell and gene therapies. This reflects the methodological challenges identified by HTA agencies associated with single-arm, short-term studies.

Cost-effectiveness of home-based care of febrile neutropenia in children with cancer.

INTRODUCTION: Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. METHODS: A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). FINDINGS: The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. CONCLUSION: Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.

Family, healthcare professional, and societal preferences for the treatment of infantile spinal muscular atrophy: A discrete choice experiment.

AIM: To understand the factors that most influence decision-making in the treatment of infantile spinal muscular atrophy (SMA). METHOD: A discrete choice experiment was conducted among parents of people with SMA (parents), healthcare professionals (HCPs), and members of the Australian general population (GenPop). Respondents were asked to accept/reject treatment for an infant newly diagnosed with SMA in eight hypothetical scenarios, characterized by different combinations of the attributes of the treatment offered. The results were analyzed using probability analysis. RESULTS: Completed responses were provided from 1113 individuals (1024 GenPop, 21 parents, 68 HCPs). Respondents were more likely to accept treatments that improved functioning and mobility. Treatments with higher costs, invasive delivery, and risks of adverse events were accepted less often. Cost most affected treatment choices by HCPs and GenPop, while change in mobility and mode of administration were most influential for parents. INTERPRETATION: These results highlight the importance of understanding value for money and clinical impact in affecting treatment choice, which are crucial for effective planning of healthcare and the successful implementation of treatment programmes for SMA. What this paper adds Spinal muscular atrophy (SMA) treatments with a higher chance of improving functioning and mobility are preferred by the general population, parents, and healthcare professionals. Treatments with higher costs, invasive delivery, and risk of adverse events are less preferred. Willingness to pay for SMA treatments increases with impact on functioning.

Understanding decisions to participate in genomic medicine in children's cancer care: A comparison of what influences parents, health care providers, and the general community.

BACKGROUND: The emerging role of genomically guided precision medicine in pediatric cancer care presents significant clinical, practical, and ethical challenges. We investigated the factors that influence decision-making in genomic medicine from the perspective of different stakeholders in the context of difficult-to-treat childhood cancer. METHODS: Health care providers (HCPs), parents of childhood cancer survivors, and general community members completed an online discrete choice experiment survey. Respondents considered whether to recommend (HCPs) or choose (parents/community) a genomically guided approach to pediatric cancer treatment. Respondents completed eight choice questions varying by survival benefit, prognosis, likelihood of finding a target, quality of life (QoL), HCP/parent preference, need for biopsy, cost, and who pays. Data were analyzed using a probability regression model, with findings expressed as relative importance, stated importance, and marginal willingness to pay (mWTP). RESULTS: One hundred twenty-six HCPs, 130 parents, and 531 community members participated. The probability of recommending/choosing genomically guided treatment increased significantly with better prognosis, survival benefit, improvements in QoL, and decision-making partner support. It decreased with increasing costs and if parents paid for treatment. HCPs were more responsive to all factors but were most influenced by survival outcomes, and parents and community members by QoL. In contrast to these forced choice preference results, HCPs stated they were most influenced by QoL and community members by survival. CONCLUSION: Our findings support the primacy of QoL in genomic decision-making, with some differences across stakeholders in the other factors influencing decision-making. These findings emphasize the need for high-quality information giving and communication to support genomic medicine choices.

Long-term health-related quality of life in young childhood cancer survivors and their parents.

PURPOSE: Few studies have investigated the health-related quality of life (HRQoL) of young childhood cancer survivors and their parents. This study describes parent and child cancer survivor HRQoL compared to population norms and identifies factors influencing child and parent HRQoL. METHODS: We recruited parents of survivors who were currently <16 years, and >5 years postdiagnosis. Parents reported on their child's HRQoL (Kidscreen-10), and their own HRQoL (EQ-5D-5L). Parents rated their resilience and fear of cancer recurrence and listed their child's cancer-related late effects. RESULTS: One hundred eighty-two parents of survivors (mean age = 12.4 years old and 9.7 years postdiagnosis) participated. Parent-reported child HRQoL was significantly lower than population norms (48.4 vs. 50.7, p < .009). Parents most commonly reported that their child experienced sadness and loneliness (18.1%). Experiencing more late effects and receiving treatments other than surgery were associated with worse child HRQoL. Parents' average HRQoL was high (0.90) and no different to population norms. However 38.5% of parents reported HRQoL that was clinically meaningfully different from perfect health, and parents experienced more problems with anxiety/depression (43.4%) than population norms (24.7%, p < .0001). Worse child HRQoL, lower parent resilience, and higher fear of recurrence was associated with worse parent HRQoL. CONCLUSIONS: Parents report that young survivors experience small but significant ongoing reductions in HRQoL. While overall mean levels of HRQoL were no different to population norms, a subset of parents reported HRQoL that was clinically meaningfully different from perfect health. Managing young survivors' late effects and improving parents' resilience through survivorship may improve HRQoL in long-term survivorship.

Managing low-risk febrile neutropenia in children in the time of COVID-19: What matters to parents and clinicians.

AIM: The Australian 'There is no place like home' project is implementing a paediatric low-risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID-19) pandemic on programme implementation. METHODS: Paediatric oncology, infectious diseases and emergency medicine health-care workers and parent/carers were surveyed to explore the impact of the COVID-19 pandemic on home-based FN care. Online surveys were distributed nationally to health-care workers involved in care of children with FN and to parents or carers of children with cancer. RESULTS: Surveys were completed by 78 health-care workers and 32 parents/carers. Overall, 95% of health-care workers had confidence in the safety of home-based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre-pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home-based FN care. Among both groups, increased telehealth access and acceptance of home-based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re-direction of resources due to COVID-19 and challenges in implementing change during a crisis were potential barriers. CONCLUSION: There is strong clinician and parent/carer support for home-based management of low-risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home-based treatments and opportunities exist to leverage these to refine the low-risk FN programme.

The Preferred Qualities of Human Immunodeficiency Virus Testing and Self-Testing Among Men Who Have Sex With Men: A Discrete Choice Experiment.

OBJECTIVES: Human immunodeficiency virus self-testing (HIVST) is a promising approach to improve HIV testing coverage. We aimed to understand HIV testing preferences of men who have sex with men (MSM) to optimize HIVST implementation. METHODS: Discrete choice experiments (DCEs) were conducted among HIV-negative MSM living in Australia and aged ≥18 years. Men completed 1 of 2 DCEs: DCETest for preferred qualities of HIV testing (price, speed, window period, test type, and collector of specimen) and DCEKits for preferred qualities of HIVST kits (price, location of access, packaging, and usage instructions). Latent class conditional logit regression was used to explore similarities (or "classes") in preference behavior. RESULTS: Overall, the study recruited 1606 men: 62% born in Australia, who had an average age of 36.0 years (SD 11.7), and a self-reported median of 4 (interquartile range 2-8) sexual partners in the last 6 months. The respondents to DCETest was described by 4 classes: "prefer shorter window period" (36%), "prefer self-testing" (27%), "prefer highly accurate tests" (22%), and "prefer low prices" (15%). Respondents to DCEKits were described by 4 classes: "prefer low prices" (48%), "prefer retail access (from pharmacy or online stores)" (29%), "prefer access at sex venues" (15%), and "prefer to buy from healthcare staff" (12%). Preferences varied by when someone migrated to Australia, age, frequency of testing, and number of sexual partners. CONCLUSION: A subset of MSM, particularly infrequent testers, value access to HIVST. Expanding access to HIVST kits through online portals and pharmacies and at sex venues should be considered.

Assessing health-related quality of life in cancer survivors: factors impacting on EORTC QLU-C10D-derived utility values.

PURPOSE: To investigate the factors influencing EORTC QLQ-C30-derived EORTC QLU-C10D utility values across five cancer types (non-Hodgkin lymphoma, multiple myeloma, colorectal, thyroid, and prostate cancer) and a general population sample. METHODS: Data from the Dutch population-based patient-reported outcomes following initial treatment and long-term evaluation of survivorship (PROFILES) registry collected between 2009 and 2012 were used. EORTC QLQ-C30 data were used to estimate utility values by applying the EORTC QLU-C10D instrument using Australian utility weights. Regression analyses were conducted, within and across cancer type, to examine the factors influencing utility values, including patient- and cancer-specific factors, as well as the EORTC QLQ-C30 scale/item scores. RESULTS: The mean utility value for the total cancer sample was 0.791 (SD 0.201), significantly lower than that from the general population (0.865, SD 0.165). Multiple myeloma patients had the lowest utility value at 0.663 (SD 0.244). Physical functioning, pain and nausea and vomiting were the health-related quality of life (HRQoL) domains with the greatest impact on utility values; cognitive functioning and dyspnea had the lowest impact. Of the demographic and clinical factors, unemployment for reasons other than retirement, age older than 75 years, number of comorbidities, and experience of symptoms all had a statistically significant negative impact on utility values. CONCLUSIONS: This study is one of the first to apply the EORTC QLU-C10D to a heterogeneous group of cancer patients. Results can be used to more efficiently target care towards factors influencing HRQoL. Furthermore, it enhances our understanding of how the EORTC QLU-C10D performs across cancer types, supporting its use in cost-utility analyses.

My mind is made up: Cancer concern and women's preferences for contralateral prophylactic mastectomy.

The fear of cancer recurrence is cited as a motivator of women's preferences between routine monitoring and contralateral prophylactic mastectomy (CPM) as methods of managing ongoing breast cancer risk. We conducted a discrete choice experiment among a general community sample of women who completed 12 hypothetical choices between routine monitoring and CPM described by aspects of treatment efficacy, safety, cost and involvement in decision-making. Respondents also completed a modified cancer worry question to assess cancer concern. Approximately 57.5% of 464 women always chose one option, typically routine monitoring. The majority (71.5%) reported being concerned about cancer recurrence when completing choice tasks. Latent class analysis identified three groups: preferred routine monitoring; preferred CPM; and "traders" (willing to swap between options). Among traders, women were less likely to choose an option associated with higher risk of recurrence. Women were more likely to choose options associated with less-intrusive monitoring methods and where they were involved in decision-making. Women concerned about cancer recurrence were more likely to choose CPM over monitoring. This study shows that women's preferences about how to manage breast cancer recurrence risk reflect the importance of the associated health effects, experience of care and attitudes to cancer recurrence.

Reviewing the cost-effectiveness of long-acting reversible contraceptive methods in an Australian context.

BACKGROUND: Relative to the oral contraceptive pill, uptake of long-acting reversible contraceptive methods (LARCs) in Australia continues to be lower than might be suggested by the evidence on their clinical and economic benefits. AIM: To undertake a critical appraisal of published economic evaluations of LARCs to assess the generalisability of their results to the Australian healthcare context. MATERIALS AND METHODS: A search of the literature was conducted to identify studies of economic evaluations of LARCs using the Medline, Embase and PubMed databases. The quality of the studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: A total of 1009 citations were screened, from which 20 papers, typically reporting the cost per pregnancy avoided, were reviewed. The overall quality of the studies varied but was generally poor (average score of 62/100). To aid comparisons, results have been grouped under the headings IUS (all hormonal intrauterine systems), IUDs (all non-hormonal intrauterine devices), injectables (all contraceptive injections) and implants (all subdermal contraceptive implants). Overall, the results indicated that LARCs were more effective and less costly than oral contraceptives. CONCLUSIONS: Despite evidence that LARCs represent value for money, limitations in study quality and approaches must be taken into account when applying these results to Australia. Differences in healthcare settings aside, LARCs may also have benefits beyond their effect on pregnancy that might be captured in broader analyses, such as cost-benefit analyses using willingness to pay methods. These would capture benefits beyond health, which seem to be particularly relevant to contraception.

Tell me once, tell me soon: parents' preferences for clinical genetics services for congenital heart disease.

PURPOSE: As the molecular basis of congenital heart disease (CHD) comes into sharper focus, cardiac genetics services are likely to play an increasingly important role. This study aimed to identify parents' preferences for, and willingness to participate in, clinical genetics services for CHD. METHODS: A discrete choice experiment was developed to assess parents' preferences for pediatric cardiogenetics services based on four attributes: appointment format, health professionals involved, waiting time, and information format. Data were analyzed using a mixed logit model. RESULTS: One hundred parents with a living child diagnosed with CHD requiring surgical intervention between 2000 and 2009 completed the discrete choice experiment. Parents expressed a clear preference for cardiac genetics services featuring (i) a single appointment, (ii) the presence of a clinical geneticist and a genetic counselor, (iii) both verbal (oral) and Web-based information about CHD and genetics, and (iv) availability of an appointment within 2 weeks. If offered such conditions, 93% of respondents indicated that they would attend. The choice of service was most strongly influenced by the presence of both a clinical geneticist and a genetic counselor. CONCLUSION: Parents of children with CHD favor a single, timely genetics appointment with both a geneticist and a genetic counselor present. If appointments offered match these preferences, uptake is likely to be high.

TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

Comparing the cost of preparing matched unrelated donor and TCR α+ ß+ /CD19+ depleted donor material for pediatric hematopoietic stem cell transplants in Australia.

Use of TCR α+ ß+ /CD19+ depletion in a pediatric setting has improved the utility of haploidentical donor material, resulting in better rates of engraftment, lower rates of graft vs host disease (GVHD), and improved transplant-related mortality. There are currently no data available on the costs of TCR α+ ß+ /CD19+ depletion. This study assessed the costs of acquiring and preparing TCR α+ ß+ /CD19+ depleted haploidentical donor cells in comparison with matched unrelated donor (MUD) products for use in pediatric patients in Australia. Data from four pediatric transplant centers were used to estimate the resources required for donor work-up, graft acquisition, and laboratory procedures for graft preparation. Information on MUD work-up and graft acquisition was also acquired from these sites and from the national coordinating donor center in Australia. Australian-specific prices and fees were used to estimate total average costs for each transplant type, converted to USD. Preparation of graft material (including work-up, acquisition, and laboratory processes) costs USD 28 963 for TCR α+ ß+ /CD19+ depleted haploidentical grafts and USD 27 297 for MUD grafts. The estimated difference of USD 1666 is largely attributed to the process and consumables to perform TCR α+ ß+ /CD19+ depletion. Given the potential for recipients of TCR α+ ß+ /CD19+ depleted grafts to require minimal GVHD prophylaxis and experience less transplant-related morbidity and mortality, use of TCR α+ ß+ /CD19+ depletion appears favorable despite the higher initial cost. Research is currently ongoing to assess the clinical effectiveness and potential cost-effectiveness of TCR α+ ß+ /CD19+ depletion over a patients' lifetime.

Predicting Infectious ComplicatioNs in Children with Cancer: an external validation study.

BACKGROUND: The aim of this study was to validate the 'Predicting Infectious ComplicatioNs in Children with Cancer' (PICNICC) clinical decision rule (CDR) that predicts microbiologically documented infection (MDI) in children with cancer and fever and neutropenia (FN). We also investigated costs associated with current FN management strategies in Australia. METHODS: Demographic, episode, outcome and cost data were retrospectively collected on 650 episodes of FN. We assessed the discrimination, calibration, sensitivity and specificity of the PICNICC CDR in our cohort compared with the derivation data set. RESULTS: Using the original variable coefficients, the CDR performed poorly. After recalibration the PICNICC CDR had an area under the receiver operating characteristic (AUC-ROC) curve of 0.638 (95% CI 0.590-0.685) and calibration slope of 0.24. The sensitivity, specificity, positive predictive value and negative predictive value of the PICNICC CDR at presentation was 78.4%, 39.8%, 28.6% and 85.7%, respectively. For bacteraemia, the sensitivity improved to 85.2% and AUC-ROC to 0.71. Application at day 2, taking into consideration the proportion of MDI known (43%), further improved the sensitivity to 87.7%. Length of stay is the main contributor to cost of FN treatment, with an average cost per day of AUD 2183 in the low-risk group. CONCLUSIONS: For prediction of any MDI, the PICNICC rule did not perform as well at presentation in our cohort as compared with the derivation study. However, for bacteraemia, the predictive ability was similar to that of the derivation study, highlighting the importance of recalibration using local data. Performance also improved after an overnight period of observation. Implementation of a low-risk pathway, using the PICNICC CDR after a short period of inpatient observation, is likely to be safe and has the potential to reduce health-care expenditure.

Community preferences in general practice: important factors for choosing a general practitioner.

BACKGROUND: Understanding the important factors for choosing a general practitioner (GP) can inform the provision of consumer information and contribute to the design of primary care services. OBJECTIVE: To identify the factors considered important when choosing a GP and to explore subgroup differences. DESIGN: An online survey asked about the respondent's experience of GP care and included 36 questions on characteristics important to the choice of GP. PARTICIPANTS: An Australian population sample (n = 2481) of adults aged 16 or more. METHODS: Principal components analysis identified dimensions for the creation of summated scales, and regression analysis was used to identify patient characteristics associated with each scale. RESULTS: The 36 questions were combined into five scales (score range 1-5) labelled: care quality, types of services, availability, cost and practice characteristics. Care quality was the most important factor (mean = 4.4, SD = 0.6) which included questions about technical care, interpersonal care and continuity. Cost (including financial and time cost) was also important (mean = 4.1, SD = 0.6). The least important factor was types of services (mean = 3.3, SD = 0.9), which covered the range of different services provided by or co-located with the practice. Frequent GP users and females had higher scores across all 5 scales, while the importance of care quality increased with age. CONCLUSIONS: When choosing a GP, information about the quality of care would be most useful to consumers. Respondents varied in the importance given to some factors including types of services, suggesting the need for a range of alternative primary care services.