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BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.
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Edad de Inicio , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Estudios Prospectivos , Adenocarcinoma/terapia , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/mortalidadRESUMEN
Despite being eligible, only 26 patients with primary brain cancer became organ donors from 2009 to 2018 in Australia. We describe two patients with high grade gliomas who successfully donated their organs after obtaining first-person consent in the outpatient setting by careful multidisciplinary planning and an elective intensive care unit admission for organ donation. Barriers and facilitators were examined based on these experiences and suggestions for future practices are explored. The recommended practices include: 1. Systematic incorporation of organ donation into advance care planning. 2. Integrating organ donation organisation coordinators into advance care planning. 3. Standardization of donor care and clear communication and collaboration between treatment teams. 4. Support and involvement of the medical treatment decision maker. 5. Identification of clinical triggers for admission to hospital and intensive care unit. These two cases illustrate that with careful coordination and involvement from a multidisciplinary team, successful organ transplantation outcomes are possible.
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Clinical trials play a crucial role in generating evidence about healthcare interventions and improving outcomes for current and future patients. For individual trial participants, however, there are inevitably trade-offs involved in clinical trial participation, given that trials have traditionally been designed to benefit future patient populations rather than to offer personalised care. Failure to understand the distinction between research and clinical care and the likelihood of benefit from participation in clinical trials has been termed the 'therapeutic misconception'. The evolution of the clinical trials landscape, including greater integration of clinical trials into healthcare and development of novel trial methodologies, may reinforce the significance of the therapeutic misconception and other forms of misunderstanding while at the same time (paradoxically) challenging its salience. Using cancer clinical trials as an exemplar, we describe how methodological changes in early- and late-phase clinical trial designs, as well as changes in the design and delivery of healthcare, impact upon the therapeutic misconception. We suggest that this provides an impetus to re-examine the ethics of clinical research, particularly in relation to trial access, participant selection, communication and consent, and role delineation.
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Neoplasias , Malentendido Terapéutico , Humanos , Consentimiento Informado , Neoplasias/terapia , Comunicación , PredicciónRESUMEN
Objective High-quality end-of-life care involves addressing patients' physical, psychosocial, cultural and spiritual needs. Although the measurement of the quality of care associated with dying and death is an important component of health care, there is a lack of evidence-based, systematic processes to examine the quality of dying and death of patients in hospital settings. Our purpose was to develop a systematic appraisal framework (QualDeath) for reviewing the quality of dying and death for patients with advanced cancer. The objectives were to: (1) explore the evidence regarding existing tools and processes related to appraisal of end-of-life care; (2) examine existing practices related to appraisal of quality of dying and death in hospital settings; and (3) develop QualDeath with consideration of potential acceptability and feasibility factors. Methods A co-design multiple methods approach was used. For objective 1, a rapid literature review was undertaken; for objective 2 we carried out semi-structured interviews and focus groups with key stakeholders in four major teaching hospitals; and for objective 3 we interviewed key stakeholders and held workshops with the project team to reach consensus. Results We developed QualDeath, a framework to assist hospital administrators and clinicians to systematically and retrospectively review the quality of dying and death for patients expected to die from advanced cancer. It offers four levels of potential implementation for hospitals to select from and incorporates medical record review, multidisciplinary meetings, quality of end-of-life care surveys and bereavement interviews with family carers. Conclusions The QualDeath framework provides hospitals with recommendations to formalise processes to evaluate end-of-life care. Although QualDeath was underpinned by several research methods, further research is needed to rigorously explore its impact and test its feasibility.
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Cuidados Paliativos al Final de la Vida , Neoplasias , Cuidado Terminal , Humanos , Estudios Retrospectivos , Cuidado Terminal/métodos , Hospitales , Neoplasias/terapiaRESUMEN
BACKGROUND: Despite global support, there remain gaps in the integration of early palliative care into cancer care. The methods of implementation whereby evidence of benefits of palliative care is translated into practice deserve attention. AIM: To identify implementation frameworks utilised in integrated palliative care in hospital-based oncology services and to describe the associated enablers and barriers to service integration. DESIGN: Systematic review with a narrative synthesis including qualitative, mixed methods, pre-post and quasi experimental designs following the guidance by the Centre for Reviews and Dissemination (PROSPERO registration CRD42021252092). DATA SOURCES: Six databases searched in 2021: EMBASE, EMCARE, APA PsycINFO, CINAHL, Cochrane Library and Ovid MEDLINE searched in 2023. Included were qualitative or quantitative studies, in English language, involving adults >18 years, and implementing hospital-based palliative care into cancer care. Critical appraisal tools were used to assess the quality and rigour. RESULTS: Seven of the 16 studies explicitly cited the use of frameworks including those based on RE-AIM, Medical Research Council evaluation of complex interventions and WHO constructs of health service evaluation. Enablers included an existing supportive culture, clear introduction to the programme across services, adequate funding, human resources and identification of advocates. Barriers included a lack of communication with the patients, caregivers, physicians and palliative care team about programme goals, stigma around the term 'palliative', a lack of robust training, or awareness of guidelines and undefined staff roles. CONCLUSIONS: Implementation science frameworks provide a method to underpin programme development and evaluation as palliative care is integrated within the oncology setting.
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Background: The global COVID-19 pandemic disproportionately affected certain populations and its management differed between countries. This national study describes characteristics and outcomes of COVID-19 in patients with cancer in Australia. Methods: We performed a multicentre cohort study of patients with cancer and COVID-19 from March 2020 to April 2022. Data were analysed to determine varying characteristics between cancer types and changes in outcomes over time. Multivariable analysis was performed to determine risk factors associated with oxygen requirement. Findings: 620 patients with cancer from 15 hospitals had confirmed COVID-19. There were 314/620 (50.6%) male patients, median age 63.5 years (IQR 50-72) and majority had solid organ tumours (392/620, 63.2%). The rate of COVID-19 vaccination (≥1 dose) was 73.4% (455/620). Time from symptom onset to diagnosis was median 1 day (IQR 0-3), patients with haematological malignancy had a longer duration of test positivity. Over the study period, there was a significant decline in COVID-19 severity. Risk factors associated with oxygen requirement included male sex (OR 2.34, 95% CI 1.30-4.20, p = 0.004), age (OR 1.03, 95% CI 1.01-1.06, p = 0.005); not receiving early outpatient therapy (OR 2.78, 95% CI 1.41-5.50, p = 0.003). Diagnosis during the omicron wave was associated with lower odds of oxygen requirement (OR 0.24, 95% CI 0.13-0.43, p < 0.0001). Interpretation: Outcomes from COVID-19 in patients with cancer in Australia over the pandemic have improved, potentially related to changing viral strain and outpatient therapies. Funding: This study was supported by research funding from MSD.
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Many factors influence patients' decisions to participate in clinical trials. For many, the primary motivation is the possibility that they might derive some benefit from participation. This is particularly true for patients with limited treatment options, such as patients with advanced cancer. While this is not surprising, it is potentially problematic if patients fail to recognise the distinction between research and clinical care (a phenomenon known as the 'therapeutic misconception'). This is becoming increasingly problematic as clinical trial designs become more complex, as clinical trials become more embedded in routine clinical care, and as trials are increasingly used by patients and clinicians to access new diagnostic platforms and therapies. We outline some of these recent trends, focusing on the cancer clinical trials landscape as this provides a good case study of the phenomenon. We conclude by making preliminary suggestions that changes to the consent process, perhaps using 'dynamic consent' platforms, might help to mitigate the therapeutic misconception and note the need for further research to guide strategies for improving communication and decision-making.
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Neoplasias , Malentendido Terapéutico , Humanos , Consentimiento Informado , ComunicaciónRESUMEN
Background: Despite robust evidence for the integration of early palliative care for patients with advanced cancer, many patients still access this approach to care late. Communication about the introduction of Early Palliative Care is an important skill of healthcare providers working in this setting. In the context of limited community understanding about palliative care, patients and their families may express fear or negative reactions to its early introduction. Health professionals may lack the confidence or skill to describe the role and benefits of early palliative care. Aim: This study sought to explore clinicians' perspectives on communication about referral to early palliative care, specifically identifying facilitators in undertaking this communication task. Methods: An exploratory qualitative study set within a tertiary oncology service in Victoria, Australia. Semi-structured interviews were conducted with purposively sampled oncology clinicians exploring their perspectives on communication about referral to early palliative care. A reflexive thematic analysis was undertaken by two researchers, including both latent and semantic coding relevant to the research question. Reporting of the research was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results: Twelve oncology clinicians (58% female, with 67% > 15 years clinical experience) from medical oncology, surgical oncology, and haematology participated. The artful navigation of communication about early palliative care was characterised by the need for a 'spiel' involving the adoption of a series of strategies or 'tactics' when introducing this service. These themes included: 1) Using carefully selected and rehearsed language; 2) Framing in terms of symptom control; 3) Framing as additive to patient care; 4) Selling the service benefits of early palliative care; 5) Framing acceptance of referral as an altruistic act; and 6) Adopting a phased approach to delivering information about palliative care. Implications: This study highlights the wide ranging and innovative communication strategies and skills required by health professionals to facilitate referral to early palliative care for cancer patients and their families. Future focus on upskilling clinicians around communication of this topic will be important to ensure successful implementation of models of early palliative care in routine cancer care.
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BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).
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Antineoplásicos , Quimioterapia Adyuvante , ADN Tumoral Circulante , Neoplasias del Colon , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Australia , Quimioterapia Adyuvante/métodos , ADN Tumoral Circulante/análisis , ADN Tumoral Circulante/sangre , Neoplasias del Colon/sangre , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Supervivencia sin Enfermedad , Fluorouracilo/uso terapéutico , Humanos , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Oxaliplatino/uso terapéuticoRESUMEN
BACKGROUND: To perform virtual re-executions of a breast cancer clinical trial with a time-to-event outcome to demonstrate what would have happened if the trial had used various Bayesian adaptive designs instead. METHODS: We aimed to retrospectively "re-execute" a randomised controlled trial that compared two chemotherapy regimens for women with metastatic breast cancer (ANZ 9311) using Bayesian adaptive designs. We used computer simulations to estimate the power and sample sizes of a large number of different candidate designs and shortlisted designs with the either highest power or the lowest average sample size. Using the real-world data, we explored what would have happened had ANZ 9311 been conducted using these shortlisted designs. RESULTS: We shortlisted ten adaptive designs that had higher power, lower average sample size, and a lower false positive rate, compared to the original trial design. Adaptive designs that prioritised small sample size reduced the average sample size by up to 37% when there was no clinical effect and by up to 17% at the target clinical effect. Adaptive designs that prioritised high power increased power by up to 5.9 percentage points without a corresponding increase in type I error. The performance of the adaptive designs when applied to the real-world ANZ 9311 data was consistent with the simulations. CONCLUSION: The shortlisted Bayesian adaptive designs improved power or lowered the average sample size substantially. When designing new oncology trials, researchers should consider whether a Bayesian adaptive design may be beneficial.
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Neoplasias de la Mama , Teorema de Bayes , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Proyectos de Investigación , Estudios Retrospectivos , Tamaño de la MuestraRESUMEN
BACKGROUND: Prior to 2020, the use of telehealth in cancer care was limited, but COVID-19 necessitated its rapid and widespread adoption into routine care delivery. This study aimed to evaluate perceptions of telehealth through a dyadic exploration of matched cancer patient- and clinician-reported acceptability data and to explore factors that may predict greater suitability for telehealth. METHODS: A prospective, cross-sectional, exploratory survey study assessed (matched) patient- and clinician-reported perceptions of telehealth consultations occurring at a metropolitan, tertiary-based cancer centre in Victoria, Australia. RESULTS: One-hundred and fifty-five matched patient- and clinician-reported data were included. High rates of acceptability with telehealth were reported by patients (93%) and clinicians (91%), who mostly shared concordant views (86%). Factors significantly associated with increased acceptability for telehealth, included, for clinicians, greater familiarity with the patient (OR 8.20, 95% CI: 1.50-45.06, p = 0.02), and younger patient age (OR 1.06, 95% CI: 0.99-1.13, p = 0.05), and for patients was earlier stage disease (≤stage III) (OR 5.29, 95% CI: 1.08-25.82, p = 0.04). Lower acceptability for telehealth according to clinicians was associated with poorer patient performance status (OR 0.04, 95% CI 1.00-1.08, p = 0.04) and for patients with the need for an interpreter (0R 0.06, 95% CI: 0.008-0.51, p = 0.009). CONCLUSION: While overall telehealth is acceptable in cancer care, our findings raise important implications for future service development, notably that it may be less optimal for patients with higher complexity of need-including those with more advanced disease, poorer performance status, those less well known to treating clinicians and those identified to have additional language barriers.
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COVID-19 , Neoplasias , Telemedicina , Australia/epidemiología , COVID-19/epidemiología , Estudios Transversales , Humanos , Neoplasias/epidemiología , Neoplasias/terapia , Estudios ProspectivosRESUMEN
OBJECTIVE: The COVID-19 pandemic has accelerated the rapid expansion of telehealth, affording opportunities to study its impact on oncology care. Our qualitative study explored physician and patient perspectives of telehealth in cancer care. METHODS: Semistructured interviews were conducted with seven physicians and eleven patients, recruited from an Australian hospital oncology department. Two authors independently coded the transcripts with emerging themes identified and refined iteratively in a thematic analysis. RESULTS: Telehealth offered broadened possibilities by allowing continuity of care in the pandemic and revealing advantages of convenience in consultations. It also highlighted core elements of in-person care that were unavailable. These included the information communicated through formal and informal physical examination, the collaboration between patient and physician in shaping outcomes and building rapport and the confidence in decisions made and physician performance. While patients and physicians envisioned the continuation of telehealth postpandemic, logistical steps are necessary to address these challenges. CONCLUSION: This study highlights the unprecedented opportunities that telehealth presents in widening access to oncology care and simultaneously reveals that it cannot always reach equivalence in quality of care. Further research is required to identify when and for whom telehealth is most acceptable as future care models are considered.
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COVID-19 , Telemedicina , Australia , Humanos , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization. METHODS: Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99mTc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants. RESULTS: Analysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CLSN38. Only UGT1A3_c.31 T > C and ABCB1_c.3435C > T were included in the final model, whereby CLSN38 reduced from 76.8 to 55.1%. CONCLUSION: The identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance.
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Neoplasias Colorrectales/tratamiento farmacológico , Glucuronosiltransferasa/genética , Irinotecán/farmacocinética , Hígado/metabolismo , Inhibidores de Topoisomerasa I/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Australia , Neoplasias Colorrectales/patología , Genotipo , Humanos , Irinotecán/uso terapéutico , Hígado/diagnóstico por imagen , Modelos Biológicos , Metástasis de la Neoplasia , Farmacogenética , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Inhibidores de Topoisomerasa I/uso terapéuticoRESUMEN
Australia, like many other nations, continues to become more culturally and linguistically diverse. Medical interpreters play a key role in bridging the linguistic gap between healthcare professionals (HCPs) and patients. Little research exists from the HCP's perspective about working with interpreters. This study aimed to explore the views of HCPs regarding working with interpreters in a cancer setting. This exploratory study utilised a cross-sectional, qualitative design, involving focus groups and semi-structured interviews. HCPs from the Oncology and Palliative Care units were invited to participate and were asked about their experiences of working with interpreters in a cancer setting. Interviews were audio-recorded and transcribed. An inductive thematic analysis of qualitative data derived an understanding of attitudes and beliefs which may affect the way in which HCPs interact with interpreters and patients. Twenty-five participants were recruited. Five key themes emerged from the data: (1) communication practices and preferences, (2) training and supports, (3) alternative methods for translation, (4) challenges faced by HCPs and interpreters, and (5) limitations of translation. Communication with non-English-speaking patients using interpreters could be significantly improved with further training and support for both HCPs and interpreters, and a greater appreciation for the challenges each party faces.
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Personal de Salud , Neoplasias , Estudios Transversales , Atención a la Salud , Grupos Focales , Humanos , Neoplasias/terapia , Investigación CualitativaRESUMEN
BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is highly lethal. Combination chemotherapy regimens improve overall survival (OS). Historically, only one-third of mPDAC patients in Victoria received chemotherapy. AIM: To describe current Australian chemotherapy utilisation and outcomes in patients with mPDAC using the multi-site PURPLE (Pancreatic cancer: Understanding Routine Practice and Lifting End Results) registry. METHODS: PURPLE collects longitudinal data on consecutive patients with pancreatic cancer seen since January 2016. Data were collated for patients with mPDAC from six Victorian sites, and analysed descriptively. RESULTS: Three hundred and sixty-three patients with mPDAC were identified. Median age was 70 years (range 20-94 years). First-line chemotherapy was administered in 195 (54%) patients. Prevalent regimens included gemcitabine-nab-paclitaxel (71%), gemcitabine alone (10%) and FOLFIRINOX (6%). Sixty-two of 195 (32%) patients who received first line treatment have proceeded to second-line chemotherapy. Chemotherapy-treated patients were younger (69 versus 73 years; P < 0.01), with better Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1 89 vs 66%; P < 0.01) and lower median Charlson comorbidity index (3 vs 4; P < 0.01) compared with untreated patients. Median OS of the entire cohort from diagnosis of metastases was 5.1 months. Median OS was 9.3 months in the chemotherapy treated patients, and 2.5 months in chemotherapy-untreated patients (P < 0.01). CONCLUSIONS: A substantial proportion of patients with mPDAC still do not receive active treatment, which may in part by explained by age, poor performance status and comorbidity. Gemcitabine-nab-paclitaxel was the preferred first-line chemotherapy regimen. Median OS for treated patients in this cohort was comparable to that of recent published clinical trials.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Victoria/epidemiología , Adulto JovenRESUMEN
Background: Recreational physical activity (RPA) is associated with improved survival after breast cancer (BC) in average-risk women, but evidence is limited for women who are at increased familial risk because of a BC family history or BRCA1 and BRCA2 pathogenic variants (BRCA1/2 PVs). Methods: We estimated associations of RPA (self-reported average hours per week within 3 years of BC diagnosis) with all-cause mortality and second BC events (recurrence or new primary) after first invasive BC in women in the Prospective Family Study Cohort (n = 4610, diagnosed 1993-2011, aged 22-79 years at diagnosis). We fitted Cox proportional hazards regression models adjusted for age at diagnosis, demographics, and lifestyle factors. We tested for multiplicative interactions (Wald test statistic for cross-product terms) and additive interactions (relative excess risk due to interaction) by age at diagnosis, body mass index, estrogen receptor status, stage at diagnosis, BRCA1/2 PVs, and familial risk score estimated from multigenerational pedigree data. Statistical tests were 2-sided. Results: We observed 1212 deaths and 473 second BC events over a median follow-up from study enrollment of 11.0 and 10.5 years, respectively. After adjusting for covariates, RPA (any vs none) was associated with lower all-cause mortality of 16.1% (95% confidence interval [CI] = 2.4% to 27.9%) overall, 11.8% (95% CI = -3.6% to 24.9%) in women without BRCA1/2 PVs, and 47.5% (95% CI = 17.4% to 66.6%) in women with BRCA1/2 PVs (RPA*BRCA1/2 multiplicative interaction P = .005; relative excess risk due to interaction = 0.87, 95% CI = 0.01 to 1.74). RPA was not associated with risk of second BC events. Conclusion: Findings support that RPA is associated with lower all-cause mortality in women with BC, particularly in women with BRCA1/2 PVs.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Ejercicio Físico , Predisposición Genética a la Enfermedad , Terapia Recreativa , Adulto , Factores de Edad , Anciano , Causas de Muerte , Ejercicio Físico/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Genes BRCA1 , Genes BRCA2 , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/genética , Modelos de Riesgos Proporcionales , Terapia Recreativa/estadística & datos numéricos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Current international consensus is that 'early' referral to palliative care services improves cancer patient and family carer outcomes. In practice, however, these referrals are not routine. An approach which directly addresses identified barriers to early integration of palliative care is required. This protocol details a trial of a standardized model of early palliative care (Care Plus) introduced at key defined, disease-specific times or transition points in the illness for people with cancer. Introduced as a 'whole of system' practice change for identified advanced cancers, the key outcomes of interest are population health service use change. The aims of the study are to examine the effect of Care Plus implementation on (1) acute hospitalisation days in the last 3 months of life; (2) timeliness of access to palliative care; (3) quality and (4) costs of end of life care; and (5) the acceptability of services for people with advanced cancer. METHODS: Multi-site stepped wedge implementation trial testing usual care (control) versus Care Plus (practice change). The design stipulates 'control' periods when usual care is observed, and the process of implementing Care Plus which includes phases of planning, engagement, practice change and evaluation. During the practice change phase, all patients with targeted advanced cancers reaching the transition point will, by default, receive Care Plus. Health service utilization and unit costs before and after implementation will be collated from hospital records, and state and national health service administrative datasets. Qualitative data from patients, consumers and clinicians before and after practice change will be gathered through interviews and focus groups. DISCUSSION: The study outcomes will detail the impact and acceptability of the standardized integration of palliative care as a practice change, including recommendations for ongoing sustainability and broader implementation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12619001703190 . Registered 04 December 2019.
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Neoplasias , Cuidados Paliativos , Australia , Hospitalización , Hospitales , Humanos , Neoplasias/terapia , Evaluación de Resultado en la Atención de Salud , Medicina EstatalRESUMEN
PURPOSE: Irinotecan (IR) displays significant PK/PD variability. This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response). METHODS: Eligible patients (pts) suitable for Irinotecan-based therapy. At baseline: (i) PGs: blood analyzed by the Affymetrix-DMET™-Plus-Array (1936 variants: 1931 single nucleotide polymorphisms [SNPs] and 5 copy number variants in 225 genes, including 47 phase I, 80 phase II enzymes, and membrane transporters) and Sanger sequencing (variants in HNF1A, Topo-1, XRCC1, PARP1, TDP, CDC45L, NKFB1, and MTHFR), (ii) HNI: pts given IV 250 MBq-99mTc-IDA, data derived for hepatic extraction/excretion parameters (CLHNI, T1/2-HNI, 1hRET, HEF, Td1/2). In cycle 1, blood was taken for IR analysis and PK parameters were derived by non-compartmental methods. Associations were evaluated between HNI and PGs, with IR PK, toxicity, objective response rate (ORR) and progression-free survival (PFS). RESULTS: N = 31 pts. The two most significant associations between PK and PD with gene variants or HNI parameters (P < 0.05) included: (1) PK: SN38-Metabolic Ratio with CLHNI, 1hRET, (2) Grade 3+ diarrhea with SLC22A2 (rs 316019), GSTM5 (rs 1296954), (3) Grade 3+ neutropenia with CLHNI, 1hRET, SLC22A2 (rs 316019), CYP4F2 (rs2074900) (4) ORR with ALDH2 (rs 886205), MTHFR (rs 1801133). (5) PFS with T1/2-HNI, XDH (rs 207440), and ABCB11 (rs 4148777). CONCLUSIONS: Exploratory associations were observed between Irinotecan PK/PD with hepatic functional imaging and extensive pharmacogenomics. Further work is required to confirm and validate these findings in a larger cohort of patients. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY (ANZCTR) NUMBER: ACTRN12610000897066, Date registered: 21/10/2010.
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Neoplasias Colorrectales/tratamiento farmacológico , Irinotecán/farmacocinética , Irinotecán/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Australia , Neoplasias Colorrectales/genética , Femenino , Genotipo , Humanos , Hígado/efectos de los fármacos , Masculino , Persona de Mediana Edad , Farmacogenética/métodos , Polimorfismo de Nucleótido Simple/genética , Supervivencia sin ProgresiónRESUMEN
Background: This study examined why women and doctors screen for ovarian cancer (OC) contrary to guidelines. Methods: Surveys, based on the Theoretical Domains Framework, were sent to women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer and family physicians and gynecologists who organized their screening. Results: Of 1264 Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer women, 832 (65.8%) responded. In the past 2 years, 126 (15.1%) had screened. Most of these (n = 101, 80.2%) would continue even if their doctor told them it is ineffective. For women, key OC screening motivators operated in the domains of social role and goals (staying healthy for family, 93.9%), emotion and reinforcement (peace of mind, 93.1%), and beliefs about capabilities (tests are easy to have, 91.9%). Of 531 clinicians 252 (47.5%) responded; a minority (family physicians 45.8%, gynecologists 16.7%) thought OC screening was useful. For gynecologists, the main motivators of OC screening operated in the domains of environmental context (lack of other screening options, 27.6%), and emotion (patient peace of mind, 17.2%; difficulty discontinuing screening, 13.8%). For family physicians,, the strongest motivators were in the domains of social influence (women ask for these tests, 20.7%), goals (a chance these tests will detect cancer early, 16.4%), emotion (patient peace of mind, 13.8%), and environmental context (no other OC screening options, 11.2%). Conclusion: Reasons for OC screening are mostly patient driven. Clinician knowledge and practice are discordant. Motivators of OC screening encompass several domains, which could be targeted in interventions to reduce inappropriate OC screening.
Asunto(s)
Ginecología , Motivación , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/psicología , Médicos de Familia , Procedimientos Innecesarios/estadística & datos numéricos , Adulto , Anciano , Actitud Frente a la Salud , Australia , Neoplasias de la Mama , Femenino , Genes BRCA1 , Genes BRCA2 , Adhesión a Directriz/estadística & datos numéricos , Ginecología/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/genética , Prioridad del Paciente/psicología , Prioridad del Paciente/estadística & datos numéricos , Médicos de Familia/psicología , Médicos de Familia/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos , Ultrasonografía/estadística & datos numéricosRESUMEN
BACKGROUND: Being a parent alongside a cancer diagnosis presents unique challenges. It is unclear to what degree parenting considerations feature in routine care and how doctors approach treatment decision discussions. OBJECTIVE: To explore doctor perspectives regarding patients with cancer who have dependent children. METHODOLOGY: Focus groups and interviews conducted to ascertain doctor views. Responses were audio-recorded, transcribed and thematically analysed. RESULTS: Twenty-eight doctors participated: medical oncology (7), haematology (10), palliative care (8), and psycho-oncology (3). Participants observed cancer impacted upon parenting across several domains: psycho-social, practical, and family implications. Having dependent children was perceived to influence the patient experience and decision-making by patients and clinicians. Participants identified this cohort as emotionally demanding to care for with a range of psychological effects identified for doctors, particularly in highly challenging circumstances (single-parent and non-English speaking families, scenarios involving communication difficulties). CONCLUSION: Participants recognised the presence of dependent children to profoundly influence the experience of being both a parent and a patient with cancer. Identifying patients with parental responsibilities was noted as relevant for management at diagnosis through to death. Greater understanding of doctors' experiences providing care for this cohort may inform the development of resources to assist doctors and their patients.