eviQ Cancer Treatments Online: Providing evidence-based information to improve cancer patient outcomes.

AIM: To understand the current usage of eviQ Cancer Treatments Online (www.eviQ.org.au), an Australian, open-access website providing evidence-based and consensus-driven cancer treatment protocols and information, and the extent to which it is meeting its intended outcomes and providing value to its users. METHODS: A mixed-method evaluation was conducted in 2020-2022 which included a review of key program documentation and website usage data, and delivery of a focused online survey to its users. RESULTS: In 2022, 329 clinicians representing all Australian states and territories contributed to eviQ content development and review. eviQ content continues to grow with a 15.2% increase in total content from 2019 to 2022.  eviQ website users continue to grow with 90,000 total monthly users in 2022, representing a 166% increase from 2018. The proportion of international users compared to Australian users continues to grow with 57% of total users in Australia and 43% international in 2022. Of 466 survey responses, the most cited reason for eviQ use was for information on side effects/toxicity (67%). Ninety-three percent (93%) of respondents either agreed or strongly agreed that eviQ contributed to both health professionals providing the best evidence-based treatment and care and improving the standardization of treatment and care provided. CONCLUSION:  eviQ is embedded in Australian clinical practice, highly valued, and relied upon by users. Users agree that eviQ has a positive impact on patients by supporting the delivery of evidence-based treatment and that eviQ contributed to patients' improved health outcomes and quality of life. eviQ's increasing international usage should be explored.

End-to-end prognostication in colorectal cancer by deep learning: a retrospective, multicentre study.

BACKGROUND: Precise prognosis prediction in patients with colorectal cancer (ie, forecasting survival) is pivotal for individualised treatment and care. Histopathological tissue slides of colorectal cancer specimens contain rich prognostically relevant information. However, existing studies do not have multicentre external validation with real-world sample processing protocols, and algorithms are not yet widely used in clinical routine. METHODS: In this retrospective, multicentre study, we collected tissue samples from four groups of patients with resected colorectal cancer from Australia, Germany, and the USA. We developed and externally validated a deep learning-based prognostic-stratification system for automatic prediction of overall and cancer-specific survival in patients with resected colorectal cancer. We used the model-predicted risk scores to stratify patients into different risk groups and compared survival outcomes between these groups. Additionally, we evaluated the prognostic value of these risk groups after adjusting for established prognostic variables. FINDINGS: We trained and validated our model on a total of 4428 patients. We found that patients could be divided into high-risk and low-risk groups on the basis of the deep learning-based risk score. On the internal test set, the group with a high-risk score had a worse prognosis than the group with a low-risk score, as reflected by a hazard ratio (HR) of 4·50 (95% CI 3·33-6·09) for overall survival and 8·35 (5·06-13·78) for disease-specific survival (DSS). We found consistent performance across three large external test sets. In a test set of 1395 patients, the high-risk group had a lower DSS than the low-risk group, with an HR of 3·08 (2·44-3·89). In two additional test sets, the HRs for DSS were 2·23 (1·23-4·04) and 3·07 (1·78-5·3). We showed that the prognostic value of the deep learning-based risk score is independent of established clinical risk factors. INTERPRETATION: Our findings indicate that attention-based self-supervised deep learning can robustly offer a prognosis on clinical outcomes in patients with colorectal cancer, generalising across different populations and serving as a potentially new prognostic tool in clinical decision making for colorectal cancer management. We release all source codes and trained models under an open-source licence, allowing other researchers to reuse and build upon our work. FUNDING: The German Federal Ministry of Health, the Max-Eder-Programme of German Cancer Aid, the German Federal Ministry of Education and Research, the German Academic Exchange Service, and the EU.

Development of a novel and more holistic approach for assessing impact in health and medical research: the Research Impact Assessment Framework.

Considered investment in health and medical research (HMR) is critical for fostering a healthcare system that is sustainable, effective, responsive, and innovative. While several tools exist to measure the impact of research, few assess the research environment that nurtures and supports impactful research and the strategic alignment of research with societal needs. This perspective article discusses the limitations of existing assessment tools and presents a novel Research Impact Assessment Framework designed to enable more strategic and targeted investment towards HMR, having the potential for significant public benefit.

Transformer-based biomarker prediction from colorectal cancer histology: A large-scale multicentric study.

Deep learning (DL) can accelerate the prediction of prognostic biomarkers from routine pathology slides in colorectal cancer (CRC). However, current approaches rely on convolutional neural networks (CNNs) and have mostly been validated on small patient cohorts. Here, we develop a new transformer-based pipeline for end-to-end biomarker prediction from pathology slides by combining a pre-trained transformer encoder with a transformer network for patch aggregation. Our transformer-based approach substantially improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms. After training and evaluating on a large multicenter cohort of over 13,000 patients from 16 colorectal cancer cohorts, we achieve a sensitivity of 0.99 with a negative predictive value of over 0.99 for prediction of microsatellite instability (MSI) on surgical resection specimens. We demonstrate that resection specimen-only training reaches clinical-grade performance on endoscopic biopsy tissue, solving a long-standing diagnostic problem.

Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare.

Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Comprehensive analyses of the health economic, policy, ethical, legal, implementation and workforce implications of incorporating genomics in the Australian context have informed evidence-based change in policy and practice, resulting in national government funding and equity of access for a range of genomic tests. Simultaneously, Australian Genomics has built national skills, infrastructure, policy, and data resources to enable effective data sharing to drive discovery research and support improvements in clinical genomic delivery.

Oncomicrobial Community Profiling Identifies Clinicomolecular and Prognostic Subtypes of Colorectal Cancer.

BACKGROUND & AIMS: Dysbiosis of gut microbiota is linked to the development of colorectal cancer (CRC). However, microbiota-based stratification of CRC tissue and how this relates to clinicomolecular characteristics and prognosis remains to be clarified. METHODS: Tumor and normal mucosa from 423 patients with stage I to IV CRC were profiled by bacterial 16S rRNA gene sequencing. Tumors were characterized for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), APC, BRAF, KRAS, PIK3CA, FBXW7, SMAD4, and TP53 mutations, subsets for chromosome instability (CIN), mutation signatures, and consensus molecular subtypes (CMS). Microbial clusters were validated in an independent cohort of 293 stage II/III tumors. RESULTS: Tumors reproducibly stratified into 3 oncomicrobial community subtypes (OCSs) with distinguishing features: OCS1 (Fusobacterium/oral pathogens, proteolytic, 21%), right-sided, high-grade, MSI-high, CIMP-positive, CMS1, BRAF V600E, and FBXW7 mutated; OCS2 (Firmicutes/Bacteroidetes, saccharolytic, 44%), and OCS3 (Escherichia/Pseudescherichia/Shigella, fatty acid ß-oxidation, 35%) both left-sided and exhibiting CIN. OCS1 was associated with MSI-related mutation signatures (SBS15, SBS20, ID2, and ID7) and OCS2 and OCS3 with SBS18 related to damage by reactive oxygen species. Among stage II/III patients, OCS1 and OCS3 both had poorer overall survival compared with OCS2 for microsatellite stable tumors (multivariate hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.15-2.99; P = .012; and HR, 1.52; 95% CI 1.01-2.29; P = .044, respectively) and left-sided tumors (multivariate HR, 2.66; 95% CI, 1.45-4.86; P = .002; and HR, 1.76; 95% CI, 1.03-3.02; P = .039, respectively). CONCLUSIONS: OCS classification stratified CRCs into 3 distinct subgroups with different clinicomolecular features and outcomes. Our findings provide a framework for a microbiota-based stratification of CRC to refine prognostication and to inform the development of microbiota-targeted interventions.

Colon and rectal cancer treatment patterns and their associations with clinical, sociodemographic and lifestyle characteristics: analysis of the Australian 45 and Up Study cohort.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer globally and the second leading cause of cancer death. We examined colon and rectal cancer treatment patterns in Australia. METHODS: From cancer registry records, we identified 1,236 and 542 people with incident colon and rectal cancer, respectively, diagnosed during 2006-2013 in the 45 and Up Study cohort (267,357 participants). Cancer treatment and deaths were determined via linkage to routinely collected data, including hospital and medical services records. For colon cancer, we examined treatment categories of "surgery only", "surgery plus chemotherapy", "other treatment" (i.e. other combinations of surgery/chemotherapy/radiotherapy), "no record of cancer-related treatment, died"; and, for rectal cancer, "surgery only", "surgery plus chemotherapy and/or radiotherapy", "other treatment", and "no record of cancer-related treatment, died". We analysed survival, time to first treatment, and characteristics associated with treatment receipt using competing risks regression. RESULTS: 86.4% and 86.5% of people with colon and rectal cancer, respectively, had a record of receiving any treatment ≤2 years post-diagnosis. Of those treated, 93.2% and 90.8% started treatment ≤2 months post-diagnosis, respectively. Characteristics significantly associated with treatment receipt were similar for colon and rectal cancer, with strongest associations for spread of disease and age at diagnosis (p<0.003). For colon cancer, the rate of "no record of cancer-related treatment, died" was higher for people with distant spread of disease (versus localised, subdistribution hazard ratio (SHR)=13.6, 95% confidence interval (CI):5.5-33.9), age ≥75 years (versus age 45-74, SHR=3.6, 95%CI:1.8-7.1), and visiting an emergency department ≤1 month pre-diagnosis (SHR=2.9, 95%CI:1.6-5.2). For rectal cancer, the rate of "surgery plus chemotherapy and/or radiotherapy" was higher for people with regional spread of disease (versus localised, SHR=5.2, 95%CI:3.6-7.7) and lower for people with poorer physical functioning (SHR=0.5, 95%CI:0.3-0.8) or no private health insurance (SHR=0.7, 95%CI:0.5-0.9). CONCLUSION: Before the COVID-19 pandemic, most people with colon or rectal cancer received treatment ≤2 months post-diagnosis, however, treatment patterns varied by spread of disease and age. This work can be used to inform future healthcare requirements, to estimate the impact of cancer control interventions to improve prevention and early diagnosis, and serve as a benchmark to assess treatment delays/disruptions during the pandemic. Future work should examine associations with clinical factors (e.g. performance status at diagnosis) and interdependencies between characteristics such as age, comorbidities, and emergency department visits.

The predicted effect and cost-effectiveness of tailoring colonoscopic surveillance according to mismatch repair gene in patients with Lynch syndrome.

PURPOSE: Lynch syndrome-related colorectal cancer (CRC) risk substantially varies by mismatch repair (MMR) gene. We evaluated the health impact and cost-effectiveness of MMR gene-tailored colonoscopic surveillance. METHODS: We first estimated sex- and MMR gene-specific cumulative lifetime risk of first CRC without colonoscopic surveillance using an optimization algorithm. Next, we harnessed these risk estimates in a microsimulation model, "Policy1-Lynch," and compared 126 colonoscopic surveillance strategies against no surveillance. RESULTS: The most cost-effective strategy was 3-yearly surveillance from age 25 to 70 years (pathogenic variants [path_] in MLH1 [path_MLH1], path_MSH2) with delayed surveillance for path_MSH6 (age 30-70 years) and path_PMS2 (age 35-70 years) heterozygotes (incremental cost-effectiveness ratio = Australian dollars (A) $8,833/life-year saved). This strategy averted 60 CRC deaths (153 colonoscopies per death averted) over the lifetime of 1000 confirmed patients with Lynch syndrome (vs no surveillance). This also reduced colonoscopies by 5% without substantial change in health outcomes (vs nontailored 3-yearly surveillance from 25-70 years). Generally, starting surveillance at age 25 (vs 20) years was more cost-effective with minimal effect on life-years saved and starting 5 to 10 years later for path_MSH6 and path_PMS2 heterozygotes (vs path_MLH1 and path_MSH2) further improved cost-effectiveness. Surveillance end age (70/75/80 years) had a minor effect. Three-yearly surveillance strategies were more cost-effective (vs 1 or 2-yearly) but prevented 3 fewer CRC deaths. CONCLUSION: MMR gene-specific colonoscopic surveillance would be effective and cost-effective.

Antibiotic exposure within six months before systemic therapy was associated with lower cancer survival.

OBJECTIVES: The objective of the study was to quantify associations between cancer survival and antibiotic exposure before systemic anticancer therapy. STUDY DESIGN AND SETTING: This population-based cohort study compares cause-specific survival according to antibiotic exposure before non-immune checkpoint inhibitor (ICI) systemic therapy in patients diagnosed with single primary cancers in New South Wales between 2013 and 2016. Proportional hazards regression was used to control for confounding, with no antibiotic exposure in the six months before non-ICI systemic therapy serving as the comparator. RESULTS: After adjusting for tumour spread, cancer site, age, sex and comorbidity, people having antibiotic exposure within 180 days before non-ICI systemic therapy had poorer cancer survival (hazard ratios ranging from 1.21 [95% confidence interval: 1.06-1.39] to 1.58 [1.34-1.87]) for shorter periods since antibiotic exposure (P < .0001). Similarly, poorer survival trends applied for localized and metastatic cancer. Of six prevalent cancers studied, lung and breast primaries showed the strongest associations of lower survival with prior antibiotic exposure. CONCLUSION: Antibiotic exposure within 180 days before non-ICI systemic cancer treatment is associated with poorer survival. If confirmed in other studies, it provides another reason for vigilant antibiotic stewardship.

The complexities, coordination, culture and capacities that characterise the delivery of oncology services in the common areas of ambulatory settings.

BACKGROUND: Relatively little is understood about real-world provision of oncology care in ambulatory outpatient clinics (OPCs). This study aimed to: 1) develop an understanding of behaviours and practices inherent in the delivery of cancer services in OPC common areas by characterising the organisation and implementation of this care; and 2) identify barriers to, and facilitators of, the delivery of this care in OPC common areas. METHODS: A purpose-designed ethnographic study was employed in four public hospital OPCs. Informal field scoping activities were followed by in-situ observations, key informant interviews and document review. A view of OPCs as complex adaptive systems was used as a scaffold for the data collection and interpretation, with the intent of understanding 'work as done'. Data were analysed using an adapted "Qualitative Rapid Appraisal, Rigorous Analysis" approach. RESULTS: Field observations were conducted over 135 h, interviews over 6.5 h and documents were reviewed. Analysis found six themes. Staff working in OPCs see themselves as part of small local teams and as part of a broader multidisciplinary care team. Professional role boundaries could be unclear in practice, as duties expanded to meet demand or to stop patients "falling through the cracks." Formal care processes in OPCs were supported by relationships, social capital and informal, but invaluable, institutional expertise. Features of the clinic layout, such as the proximity of departments, affected professional interactions. Staff were aware of inter- and intra-service communication difficulties and employed strategies to minimise negative impacts on patients. We found that complexity, coordination, culture and capacity underpin the themes that characterise this care provision. CONCLUSIONS: The study advances understanding of how multidisciplinary care is delivered in ambulatory settings and the factors which promote or inhibit effective care practice. Time pressures, communication challenges and competing priorities can pose barriers to care delivery. OPC care is facilitated by: self-organisation of participants; professional acumen; institutional knowledge; social ties and relationships between and within professional groups; and commitment to patient-centred care. An understanding of the realities of 'work-as-done' may help OPCs to sustain high-quality care in the face of escalating service demand.

Evaluating genetic and genomic tests for heritable conditions in Australia: lessons learnt from health technology assessments.

The Medical Services Advisory Committee (MSAC) is an independent non-statutory committee established by the Australian government to provide recommendations on public reimbursement of technologies and services, other than pharmaceuticals. MSAC has established approaches for undertaking health technology assessment (HTA) of investigative services and codependent technologies. In 2016, MSAC published its clinical utility card (CUC) Proforma, an additional tool to guide assessments of genetic testing for heritable conditions. We undertook a review and narrative synthesis of information extracted from all MSAC assessments of genetic testing for heritable conditions completed since 2016, regardless of the HTA approach taken. Ten assessments met our inclusion criteria, covering a range of testing methods (from gene panels to whole-exome sequencing) and purposes (including molecular diagnosis, genetic risk assessment, identification of congenital anomaly syndromes, and carrier screening). This analysis identified a range of methodological and policy challenges such as how to incorporate patient and societal preferences for the health and non-health outcomes of genomic testing, how best to capture the concept of co-production of utility, and how to engage clinicians as referrers for genomics tests whilst at the same time ensuring equity of access to a geographically dispersed population. A further challenge related to how qualitative assessments of patient and community needs influenced the evidence thresholds against which decisions were made. These concepts should be considered for incorporation within the value assessment frameworks used by HTA agencies around the world.

Providing outpatient cancer care for CALD patients: a qualitative study.

OBJECTIVE: There have been few descriptions of how outpatient cancer care is provided to patients from culturally and linguistically diverse (CALD) communities. As populations who experience disparities in cancer care access and outcomes, deeper understanding is needed to help identify those factors which can shape the receipt of multidisciplinary care in ambulatory settings. This paper reports on data collected and analysed as part of a multicentre characterisation of care in Australian public hospital cancer outpatient clinics (OPCs). RESULTS: Analysis of data from our ethnographic study of four OPCs identified three themes: "Identifying CALD patient language-related needs"; "Capacity and resources to meet CALD patient needs", and "Making it work for CALD communities." The care team comprises not only clinicians but also families and non-clinical staff; OPCs serve as "touchpoints" facilitating access to a range of therapeutic services. The findings highlight the potential challenges oncology professionals negotiate in providing care to CALD communities and the ways in which clinicians adapt their practices, formulate strategies and use available resources to support care delivery.

Queensland Genomics: an adaptive approach for integrating genomics into a public healthcare system.

The establishment of genomics in health care systems has been occurring for the past decade. It is recognised that implementing genomics within a health service is challenging without a system-wide approach. Globally, as clinical genomics implementation programs have matured there is a growing body of information around program design and outcomes. Program structures vary depending on local ecosystems including the health system, politics and funding availability, however, lessons from other programs are important to the design of programs in different jurisdictions. Here we describe an adaptive approach to the implementation of genomics into a publicly funded health care system servicing a population of 5.1 million people. The adaptive approach enabled flexibility to facilitate substantial changes during the program in response to learnings and external factors. We report the benefits and challenges experienced by the program, particularly in relation to the engagement of people and services, and the design of both individual projects and the program as a whole.

Challenges in valuing and paying for combination regimens in oncology: reporting the perspectives of a multi-stakeholder, international workshop.

BACKGROUND: It is increasingly common for two or more treatments for cancer to be combined as a single regimen. Determining value and appropriate payment for such regimens can be challenging. This study discusses these challenges, and possible solutions. METHODS: Stakeholders from around the world attended a 2-day workshop, supported by a background paper. This study captures key outcomes from the discussion, but is not a consensus statement. RESULTS: Workshop attendees agreed that combining on-patent treatments can result in affordability and value for money challenges that delay or deny patient access to clinically effective treatments in many health systems. Options for addressing these challenges include: (i) Increasing the value of combination therapies through improved clinical development; (ii) Willingness to pay more for combinations than for single drugs offering similar benefit, or; (iii) Aligning the cost of constituent therapies with their value within a regimen. Workshop attendees felt that (i) and (iii) merited further discussion, whereas (ii) was unlikely to be justifiable. Views differed on the feasibility of (i). Key to (iii) would be systems allowing different prices to apply to different uses of a drug. CONCLUSIONS: Common ground was identified on immediate actions to improve access to combination regimens. These include an exploration of the legal challenges associated with price negotiations, and ensuring that pricing systems can support implementation of negotiated prices for specific uses. Improvements to clinical development and trial design should be pursued in the medium and longer term.

Extrapolation of Survival Curves Using Standard Parametric Models and Flexible Parametric Spline Models: Comparisons in Large Registry Cohorts with Advanced Cancer.

BACKGROUND: It is often important to extrapolate survival estimates beyond the limited follow-up times of clinical trials. Extrapolated survival estimates can be highly sensitive to model choice; thus, appropriate model selection is crucial. Flexible parametric spline models have been suggested as an alternative to standard parametric models; however, their ability to extrapolate is not well understood. AIM: To determine how well standard parametric and flexible parametric spline models predict survival when fitted to registry cohorts with artificially right-censored follow-up times. METHODS: Adults with advanced breast, colorectal, small cell lung, non-small cell lung, or pancreatic cancer with a potential follow-up time of 10 y were selected from the SEER 1973-2015 registry data set. Patients were classified into 15 cohorts by cancer and age group at diagnosis (18-59, 60-69, 70+ y). Follow-up times for each cohort were right censored at 20%, 35%, and 50% survival. Standard parametric models (exponential, Weibull, Gompertz, log-logistic, log-normal, generalized gamma) and spline models (proportional hazards, proportional odds, normal/probit) were fitted to the 10-y data set and the 3 right-censored data sets. Predicted 10-y restricted mean survival time and percentage surviving at 10 y were compared with the observed values. RESULTS: Across all data sets, the spline odds and spline normal models most frequently gave accurate predictions of 10-y survival outcomes. Visually, spline models tended to demonstrate better fit to the observed hazard functions than standard parametric models, both in the censored and 10-y data. CONCLUSIONS: In these cohorts, where there was little uncertainty in the observed data, the spline models performed well when extrapolating beyond the observed data. Spline models should be routinely included in the set of models that are fitted when extrapolating cancer survival data.

Implementing gene curation for hereditary cancer susceptibility in Australia: achieving consensus on genes with clinical utility.

BACKGROUND: The strength of evidence supporting the validity of gene-disease relationships is variable. Hereditary cancer has the additional complexity of low or moderate penetrance for some confirmed disease-associated alleles. METHODS: To promote national consistency in interpretation of hereditary cancer/tumour gene test results, we requested opinions of representatives from Australian Family Cancer Clinics regarding the clinical utility of 157 genes initially collated for a national research project. Viewpoints were sought by initial survey, face-to-face workshop and follow-up survey. Subsequent review was undertaken by the eviQ Cancer Genetics Reference Committee, a national resource providing evidence-based and consensus-driven cancer treatment protocols. RESULTS: Genes were categorised by clinical actionability as: relevant for testing on presentation of common cancer/tumour types (n=45); relevant for testing in the context of specific rare phenotypes (n=74); insufficient clinical utility (n=34) or contentious clinical utility (n=3). Opinions for several genes altered during the study time frame, due to new information. CONCLUSION: Through an iterative process, consensus was achieved on genes with clinical utility for hereditary cancer/tumour conditions in the Australian setting. This study highlighted need for regular review of gene-disease lists, a role assumed in Australia for hereditary cancer/tumour predisposition genes by the eviQ Cancer Genetics Reference Committee.

Pathways to a cancer-free future: a protocol for modelled evaluations to minimise the future burden of colorectal cancer in Australia.

INTRODUCTION: With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods. METHODS AND ANALYSIS: Pathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged <50 years; increasing screening participation in the general and Aboriginal and Torres Strait Islander populations; alternative screening technologies and modalities; and changes to follow-up surveillance protocols. Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments. ETHICS AND DISSEMINATION: Ethics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers.

Diagnostic and health service pathways to diagnosis of cancer-registry notified cancer of unknown primary site (CUP).

BACKGROUND: Cancer of unknown primary (CUP) is a late-stage malignancy with poor prognosis, but we know little about what diagnostic tests and procedures people with CUP receive prior to diagnosis. The purpose of this study was to determine how health service utilisation prior to diagnosis for people with cancer-registry notified CUP differs from those notified with metastatic cancer of known primary. METHODS: We identified people with a cancer registry notification of CUP (n = 327) from the 45 and Up Study, a prospective cohort of 266,724 people ≥45 years in New South Wales, Australia, matched with up to three controls with a diagnosis of metastatic cancer of known primary (n = 977). Baseline questionnaire data were linked to population health data to identify all health service use, diagnostic tests, and procedures in the month of diagnosis and 3 months prior. We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After adjusting for age and educational attainment, people with a cancer-registry notified CUP diagnosis were more likely to be an aged care resident (OR = 2.78, 95%CI 1.37-5.63), have an emergency department visit (OR = 1.65, 95%CI 1.23-2.21), serum tumor marker tests (OR = 1.51, 95%CI 1.12-2.04), or a cytology test without immunohistochemistry (OR = 2.01, 95%CI 1.47-2.76), and less likely to have a histopathology test without immunohistochemistry (OR = 0.43, 95%CI 0.31-0.59). Neither general practitioner, specialist, allied health practitioner or nurse consultations, hospitalisations, nor imaging procedures were associated with a CUP diagnosis. CONCLUSIONS: The health service and diagnostic pathway to diagnosis differs markedly for people notified with CUP compared to those with metastatic cancer of known primary. While these differences may indicate missed opportunities for earlier detection and appropriate management, for some patients they may be clinically appropriate.

Tumour infiltrating lymphocyte status is superior to histological grade, DNA mismatch repair and BRAF mutation for prognosis of colorectal adenocarcinomas with mucinous differentiation.

Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p < 0.001). TIL status was a strong independent predictor of DFS in mucinous/mucinous component tumours (HR 0.40, 95% CI 0.23-0.67; p < 0.001), and a superior predictor of prognosis compared with histological grade, MMR and BRAF mutation. Mucinous component and mucinous stage II/III CRCs exhibit clinico-molecular resemblances, with histological grade and BRAF mutation lacking prognostic value. Prognosis for these tumours was instead strongly associated with TIL status, with the most favourable outcomes in TIL-high dMMR tumours, whilst TIL-low tumours had poor outcomes irrespective of MMR status.

What are the attitudes of health professionals regarding patient reported outcome measures (PROMs) in oncology practice? A mixed-method synthesis of the qualitative evidence.

BACKGROUND: The adoption of Patient Reported Outcome Measures (PROMs) in cancer care has been widely advocated, but little is known about the evidence for the implementation of PROMs in practice. Qualitative research captures the perspectives of health professionals as end-users of PROMs and can be used to inform adoption efforts. This paper presents a systematic review and synthesis of qualitative research conducted to address the question: What are the attitudes of health professionals towards PROMs in oncology, including any barriers and facilitators to the adoption of PROMS, reported in qualitative evidence? METHODS: Systematic searches of qualitative evidence were undertaken in four databases and reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published in English between 1998 and 2018, which reported qualitative findings about the attitudes of health professionals working in oncology towards PROMs were eligible. Studies were assessed using the Critical Appraisal Skills Programme's Qualitative Research Checklist. A sentiment analysis was conducted on primary text to examine the polarity (neutral, positive or negative) of health professionals' views of PROMs. Qualitative meta-synthesis was conducted using a constant comparative analysis. RESULTS: From 1227 articles after duplicates were removed, with 1014 excluded against the screening criteria, 213 full text articles remained and were assessed; 34 studies met the inclusion criteria and were included. The majority of studies were of good quality. Sentiment analysis on primary text demonstrated an overall positive polarity from the expressed opinions of health professionals. The meta-synthesis showed health professionals' attitudes in four domains: identifying patient issues and needs using PROMs; managing and addressing patient issues; the care experience; and the integration of PROMs into clinical practice. CONCLUSIONS: From the accounts of health professionals, the fit of PROMs with existing practice, how PROMs are valued, capacity to respond to PROMs and the supports in place, formed the key factors which may impede or promote adoption of PROMs in routine practice. To assist policy-makers and services involved in implementing these initiatives, further evidence is required about the relationship between PROMs data collection and corresponding clinical actions. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019119447, 6th March, 2019.