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"Alexander, Marliese"
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Trends in primary care blood tests prior to lung and colorectal cancer diagnosis—A retrospective cohort study using linked Australian data
2024
Abnormal results in common blood tests may occur several months before lung cancer (LC) and colorectal cancer (CRC) diagnosis. Identifying early blood markers of cancer and distinct blood test signatures could support earlier diagnosis in general practice.
Using linked Australian primary care and hospital cancer registry data, we conducted a cohort study of 855 LC and 399 CRC patients diagnosed between 2001 and 2021. Requests and results from general practice blood tests (six acute phase reactants [APR] and six red blood cell indices [RBCI]) were examined in the 2 years before cancer diagnosis. Poisson regression models were used to estimate monthly incidence rates and examine pre-diagnostic trends in blood test use and abnormal results prior to cancer diagnosis, comparing patterns in LC and CRC patients.
General practice blood test requests increase from 7 months before CRC and 6 months before LC diagnosis. Abnormalities in many APR and RBCI tests increase several months before cancer diagnosis, often occur prior to or in the absence of anaemia (in 51% of CRC and 81% of LC patients with abnormalities), and are different in LC and CRC patients.
This study demonstrates an increase in diagnostic activity in Australian general practice several months before LC and CRC diagnosis, indicating potential opportunities for earlier diagnosis. It identifies blood test abnormalities and distinct signatures that are early markers of LC and CRC. If combined with other pre-diagnostic information, these blood tests have potential to support GPs in prioritising patients for cancer investigation of different sites to expedite diagnosis.
Journal Article
Healthcare professionals' and consumers' knowledge, attitudes, perspectives, and education needs in oncology pharmacogenomics: A systematic review
2023
Clinical implementation of pharmacogenomic (PGx)‐guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.
Journal Article
Safety and adherence to medications and self-care advice in oncology (SAMSON): pilot randomised controlled trial protocol
by
Dang, Thu Ha
,
Quinn, Steve
,
Brooks, Sally L
in
Antineoplastic Agents - adverse effects
,
Antineoplastic Agents - therapeutic use
,
Australia
2024
IntroductionWith the increasing use of oral anti-cancer medicines (OAMs), research demonstrating the magnitude of the medication non-adherence problem and its consequences on treatments’ efficacy and toxicity is drawing more attention. Mobile phone interventions may be a practical solution to support patients taking OAMs at home, yet evidence to inform the efficacy of these interventions is lacking. The safety and adherence to medications and self-care advice in oncology (SAMSON) pilot randomised control trial (RCT) aims to evaluate the acceptability, feasibility and potential efficacy of a novel digital solution to improve medication adherence (MA) among people with cancer.Methods and analysisThis is a two-arm, 12-week, pilot RCT aiming to enrol 50 adults with haematological, lung or melanoma cancers at an Australian metropolitan specialised oncology hospital, who are taking oral anti-cancer medicines. Participants will be randomised (1:1 allocation ratio) to either the intervention group (SAMSON solution) or the control group (usual care). The primary outcomes are the acceptability and feasibility of SAMSON. The secondary outcomes are MA, toxicity self-management, anxiety and depressive symptoms, health-related quality of life, and parameters relating to optimal intervention strategy. Quantitative data will be analysed on a modified intention-to-treat basis.SummaryWhile multicomponent interventions are increasingly introduced, SAMSON incorporates novel approaches to the solution. SAMSON provides a comprehensive, patient-centred, digital MA intervention solution with seamless integration of a mobile platform with clinical consultations that are evidence-based, theory-based, co-designed and rigorously tested. The pilot trial will determine whether this type of intervention is feasible and acceptable in oncology and will provide a foundation for a future full-scale RCT.Ethics and disseminationPrimary ethics approvals were received from Peter MacCallum Cancer Centre and Swinburne University of Technology Human Research Ethics Committees (HREC/95332/PMCC and 20237273–15836). Results will be disseminated via peer-reviewed publications and presentations at international and national conferences.Trial registration numberThe protocol has been prospectively registered on the Australian New Zealand Clinical Trials Registry with trial registration number (ACTRN12623000472673).
Journal Article
A systematic review of knowledge, attitude and practice of pharmacogenomics in pediatric oncology patients
2023
Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence‐based guidelines. This systematic review aims to understand enablers and barriers to pharmacogenomics implementation in pediatric oncology by assessing the knowledge, attitudes, and practice of healthcare professionals and consumers. Medline, Embase, Emcare, and PsycINFO database searches identified 146 relevant studies of which only three met the inclusion criteria. These studies reveal that consumers were concerned with pharmacogenomic test costs, insurance discrimination, data sharing, and privacy. Healthcare professionals possessed mostly positive attitudes toward pharmacogenomic testing yet identified lack of experience and training as barriers to implementation. Education emerged as the key enabler, reported in all three studies and both healthcare professionals and consumer groups. However, despite the need for education, no studies utilizing a pediatric oncology consumer or healthcare professional group have reported on the implementation or analysis of a pharmacogenomic education program in pediatric oncology. Increased access to guidelines, expert collaborations and additional guidance interpreting results were further enablers established by healthcare professionals. The themes identified mirror those reported in broader pediatric genetic testing literature. As only a small number of studies met inclusion criteria for this review, further research is warranted to elicit implementation determinants and advance pediatric pharmacogenomics.
Journal Article
Phenoconversion of CYP3A4, CYP2C19 and CYP2D6 in Pediatrics, Adolescents and Young Adults With Lymphoma: Rationale and Design of the PEGASUS Study
2025
Phenoconversion is the discrepancy between genotype‐predicted phenotype and clinical phenotype, due to nongenetic factors. In oncology patients, the impact of phenoconversion on drug selection, efficacy, toxicity, and treatment outcomes is unknown. This study will assess acceptability and feasibility of investigating phenoconversion using probe medications in a pediatric and adolescent and young adult (AYA) oncology population. This prospective, single‐arm, single‐blind, nonrandomized feasibility study, will enroll individuals aged 6–25 years with a new diagnosis of Hodgkin Lymphoma or Non‐Hodgkin Lymphoma. Genotyping will be performed at baseline using whole genome sequencing or targeted panel testing. Longitudinal phenotyping will be conducted throughout the cancer treatment using exogenous oral enzyme‐specific probes, specifically subtherapeutic dextromethorphan (CYP2D6) and omeprazole (CYP2C19, CYP3A4) for enzyme activity assessment. The primary outcome measure will be the proportion of patients who consent to the study and successfully complete baseline and at least two longitudinal time points with valid probe drug metabolic ratio measurements. Secondary outcomes include classification of clinical phenotypes based on probe drug metabolic ratios, probe drug safety, barriers to consent, acceptability of pharmacogenomic and phenoconversion testing, longitudinal genotype/phenotype concordance, inflammatory profiles, and patient and disease factors influencing phenoconversion. The trial has received ethics approval (2023/ETH1954) and is registered at ClinicalTrials.gov (NCT06383338). Findings will be disseminated through peer‐reviewed publications and professional conferences, providing critical insights to advance the understanding of phenoconversion in oncology from pediatrics to adults. These results will help shape future research and drive the implementation of more personalized precision medicine strategies for all people with cancer.
Journal Article
Pharmacogenetic‐guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A128) chemotherapies for patients with cancer (PACIFIC‐PGx): A multicenter clinical trial
2024
PACIFIC‐PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype‐guided dosing on severe fluoropyrimidine (FP) and irinotecan‐related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis). DPYD genotyping identified 96% (n = 443/462) Wild‐Type, 4% (n = 19/462) Intermediate Metabolizers (50% dose reduction), and 0% Poor Metabolizers. UGT1A1 genotyping identified 52% (n = 26/50) Wild‐Type, 40% (n = 20/50) heterozygous, and 8% (n = 4/50) homozygous (30% dose reduction). Key demographics for the FP/irinotecan safety cohorts included: age range 23–89/34–74 years, male 56%/73%, Caucasian 83%/73%, lower gastrointestinal cancer 50%/57%. Genotype results were reported prior to cycle‐1 (96%), average 5–7 days from sample collection. PGx‐dosing for DPYD variant allele carriers reduced high‐grade toxicities compared to historic controls (7% vs. 39%; OR = 0.11, 95% CI 0.01–0.97, p = 0.024). High‐grade toxicities among Wild‐Type were similar (14% vs. 14%; OR = 0.99, 95% CI 0.64–1.54, p = 0.490). PGx‐dosing reduced FP‐related hospitalizations (−22%) and deaths (−3.7%) compared to controls. There were no high‐grade toxicities or hospitalizations for UGT1A1*28 homozygotes. PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings.
Journal Article
Investigation of Intervention Solutions to Enhance Adherence to Oral Anticancer Medicines in Adults: Overview of Reviews
by
Forkan, Abdur Rahim Mohammad
,
Dang, Thu Ha
,
Jayaraman, Prem Prakash
in
Breast cancer
,
Cancer therapies
,
Intervention
2022
Adherence to anticancer medicines is critical for the success of cancer treatments; however, nonadherence remains challenging, and there is limited evidence of interventions to improve adherence to medicines in patients with cancer.
This overview of reviews aimed to identify and summarize available reviews of interventions to improve adherence to oral anticancer medicines in adult cancer survivors.
A comprehensive search of 7 electronic databases was conducted by 2 reviewers who independently conducted the study selection, quality assessment using the A Measurement Tool to Assess Systematic Reviews 2, and data extraction. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 checklist was adapted to report the results.
A total of 29 reviews were included in the narrative synthesis. The overall quality of the systematic reviews was low. The 4 main strategies to promote adherence were focused on education, reminders, behavior and monitoring, and multicomponent approaches. Digital technology-based interventions were reported in most reviews (27/29, 93%). A few interventions applied theories (10/29, 34%), design frameworks (2/29, 7%), or engaged stakeholders (1/29, 3%) in the development processes. The effectiveness of interventions was inconsistent between and within reviews. However, interventions using multiple strategies to promote adherence were more likely to be effective than single-strategy interventions (12/29, 41% reviews). Unidirectional communication (7/29, 24% reviews) and technology alone (11/29, 38% reviews) were not sufficient to demonstrate improvement in adherence outcomes. Nurses and pharmacists played a critical role in promoting patient adherence to oral cancer therapies, especially with the support of digital technologies (7/29, 24% reviews).
Multicomponent interventions are potentially effective in promoting patient adherence to oral anticancer medicines. The seamless integration of digital solutions with direct clinical contacts is likely to be effective in promoting adherence. Future research for developing comprehensive digital adherence interventions should be evidence-based, theory-based, and rigorously evaluated.
Journal Article
Patient and healthcare professional acceptability of pharmacogenetic screening for DPYD and UGT1A1: A cross sectional survey
2023
This study explored the acceptability of a novel pharmacist‐led pharmacogenetics (PGx) screening program among patients with cancer and healthcare professionals (HCPs) taking part in a multicenter clinical trial of PGx testing (PACIFIC‐PGx ANZCTR:12621000251820). Medical oncologists, oncology pharmacists, and patients with cancer from across four sites (metropolitan/regional), took part in an observational, cross‐sectional survey. Participants were recruited from the multicenter trial. Two study‐specific surveys were developed to inform implementation strategies for scaled and sustainable translation into routine clinical care: one consisting of 21 questions targeting HCPs and one consisting of 17 questions targeting patients. Responses were collected from 24 HCPs and 288 patients. The 5‐to‐7‐day PGx results turnaround time was acceptable to HCP (100%) and patients (69%). Most HCPs (92%) indicated that it was appropriate for the PGx clinical pharmacist to provide results to patients. Patients reported equal preference for receiving PGx results from a doctor/pharmacist. Patients and HCPs highly rated the pharmacist‐led PGx service. HCPs were overall accepting of the program, with the majority (96%) willing to offer PGx testing to their patients beyond the trial. HCPs identified that lack of financial reimbursements (62%) and lack of infrastructure (38%) were the main reasons likely to prevent/slow the implementation of PGx screening program into routine clinical care. Survey data have shown overall acceptability from patients and HCPs participating in the PGx Program. Barriers to implementation of PGx testing in routine care have been identified, providing opportunity to develop targeted implementation strategies for scaled translation into routine practice.
Journal Article
Light-enhanced cognitive behavioural therapy for sleep and fatigue: study protocol for a randomised controlled trial during chemotherapy for breast cancer
by
Francis, Prudence A.
,
Wiley, Joshua F.
,
Little, Ruth
in
Administration, Intravenous
,
Adult
,
Aged
2020
Background
Women with breast cancer experience a significantly higher prevalence of sleep disturbance and insomnia than the general population. The experience of persistent sleep disturbance places these women at a higher risk of psychological and physical morbidity and a reduced quality of life. Treatment for sleep in this population is not part of routine care and is often managed inadequately. This randomised controlled trial will examine the combined effects of cognitive behavioural therapy (CBT) and bright light therapy (BLT) on the symptoms of insomnia, fatigue and mental health.
Method/design
Women diagnosed with breast cancer who receive intravenous chemotherapy treatment at a quaternary referral metropolitan cancer centre in Melbourne, Australia, will be recruited. Recruitment will occur after diagnosis and prior to completion of chemotherapy. Eligible women will be randomised to the combined CBT and BLT intervention (CBT+) or relaxation audio-enhanced treatment as usual (TAU+). The CBT+ group will receive one face-to-face session on sleep strategies, one subsequent telephone call, and seven email packages containing CBT-based information and strategies. CBT+ participants will also wear Luminette® light glasses for 20 min each morning for the 6-week duration of the intervention. Women in TAU+ will receive two relaxation audio tracks via email. Outcomes will be measured at multiple points throughout the 6 weeks. Primary outcomes will be symptoms of insomnia and sleep efficiency, measured using the Insomnia Severity Index and a self-reported sleep diary. Secondary outcomes include objective measures of sleep assessed using the ActiGraph wGT3X-BT, and sleep-related complaints, fatigue and mental health, all assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). Data will also be collected on potential treatment moderators and mechanisms and adherence to treatment. There will be 3-month follow-up measurements of insomnia symptoms, fatigue, sleep-related impairment, sleep disturbance, depression and anxiety.
Discussion
This is the first randomised controlled trial to combine CBT and BLT for the treatment of sleep disturbance in women with breast cancer. This novel design addresses the multiple causal factors for sleep complaints in this population. Results from this trial will advance knowledge in this field and may have important clinical implications for how best to treat sleep disturbance and insomnia in this population. If effective, the largely email-based format of the intervention would allow for relatively easy translation.
Trial Registration
Australian New Zealand Clinical Trials Registry (ANZCTR),
ACTRN12618001255279
. Retrospectively registered on 25 July 2018.
Journal Article
Effects of clinical and socioeconomic factors on Medicare and patient costs for colorectal cancer in Australia: a retrospective multivariate regression analysis
2024
ObjectiveWe study how clinical and socioeconomic factors influence colorectal cancer (CRC) costs for patients and Medicare in Australia. The study seeks to extend the limited Australian literature on CRC costs by analysing comprehensive patient-level medical services and pharmaceutical cost data.Design, setting and participantsUsing the Victorian Cancer Registry, we identified all patients in Victoria who were diagnosed with CRC from 2010 to 2019 and extracted their linked 2010–2021 Medicare data. This data includes expenses from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule services. We examined variables such as disease stage, CRC type, molecular profile, metastasis status and demographics (eg, age, birth country, socioeconomic level via the SEIFA index, and native language). We applied descriptive and log-linear multivariate regression analyses to explore patient and Medicare costs related to CRC treatment.ResultsCosts significantly rise with advanced cancer stages, especially on medication costs. Patients’ average out-of-pocket (OOP) expenses are roughly $A441 per year. Key cost influencers are gender, age and socioeconomic status. On average, males incur 13.5% higher annual costs, a significantly larger OOP expense, than females. Compared with patients aged 50 or below, there is a 7.1% cost increase for individuals aged 50–70 and an 8.8% decrease post-70, likely reflecting less intensive treatment for the elderly. Socioeconomic factors show a clear gradient. Wealthier areas experience higher costs, especially among native English speakers. Costs also vary based on cancer’s anatomical location and specific genetic mutations.ConclusionThe research highlights that CRC treatment expenses for patients and Medicare differ considerably due to factors such as diagnostic stage, demographics, anatomical location of the tumour and mutations. These cost variations lead to concerns about healthcare equality and decision-making autonomy. Policymakers may need to focus on early detection, increased support for advanced-stage patients, gender-sensitive healthcare, and equitable access to treatment across different socioeconomic groups.
Journal Article