Examining the impact of the time before diagnosis and treatment in colorectal cancer using a linked Victorian dataset and dose-response meta-analysis.

© 2024 Allison Fiona DrosdowskyColorectal cancer is the fourth most common cancer in Australia, and despite a national screening program, is largely diagnosed symptomatically through the primary healthcare system. A frequent target for policy and intervention is reducing the time it takes to diagnose and treat cancer. However, researching this time, and specifically the relationship between time and health-related outcomes, is difficult. This thesis aims to: 1) To characterise statistical and methodological issues in research examining associations between time intervals before diagnosis and initial treatment and health-related outcomes in colorectal cancer to provide guidance for future research. 2) To examine associations between the time before diagnosis and initial treatment and health-related outcomes in colorectal cancer. 3) To examine the lengths of intervals in the time before diagnosis and initial treatment and associations between sociodemographic, disease-specific and health care utilisation characteristics and these intervals. Aim one was met using a systematic review of methodological considerations. In total, 130 papers were included, and several methodological problems were identified. A set of recommendations for future research was produced, including avoiding artificial categorisation of intervals, ensuring bias has not been introduced due to out-of-sequence use of key events and increased use of theoretical frameworks to detect and reduce bias. These recommendations guided aim two which was addressed through meta-analysis and analysis of a novel linked data resource. The time before diagnosis was delineated into key intervals that cover specific processes or engagement with specific components of the healthcare system. Aim two then assessed the association between these intervals and health-related outcomes, overall survival, and stage of disease. Data from the systematic review was synthesised using a novel meta-analytic technique, dose response meta-analysis, to enable non-linear associations to be examined. Evidence from the Australian setting was produced by linking cancer clinical registry data with general practice electronic medical record and hospital administrative data to follow a cohort of colorectal cancer patients through the healthcare system. Findings from both pieces of work demonstrated the waiting time paradox, or poorer outcomes for patients with both short and long times, for diagnostic and treatment intervals with both survival and stage. This is the first time this has been shown both in a meta-analysis, and in Australian data. Finally, aim three was met through the same linked data resource, with a focus on examining if any characteristics were associated with interval length. While few patient sociodemographic characteristics were associated with interval length for any intervals examined, disease and medical system factors were. This suggests that broad improvements to the overall efficient functioning of the healthcare system are likely to improve timeliness. Overall, this thesis contributed novel evidence surrounding the association between times to diagnosis and treatment and health-related outcomes in colorectal cancer. This can assist with the timely diagnosis of colorectal cancer as it provides further evidence of longer times leading to poorer outcomes and identifies areas for intervention in the diagnostic and treatment pathways, such as implementing recommended maximum lengths of intervals along the diagnostic and treatment pathway

A systematic review of methodological considerations in time to diagnosis and treatment in colorectal cancer research

Research focusing on timely diagnosis and treatment of colorectal cancer is necessary to improve outcomes for people with cancer. Previous attempts to consolidate research on time to diagnosis and treatment have noted varied methodological approaches and quality, limiting the comparability of findings. This systematic review was conducted to comprehensively assess the scope of methodological issues in this field and provide recommendations for future research. Eligible articles had to assess the role of any interval up to treatment, on any outcome in colorectal cancer, in English, with no limits on publication time. Four databases were searched (Ovid Medline, EMBASE, EMCARE and PsycInfo). Papers were screened by two independent reviewers using a two-stage process of title and abstract followed by full text review. In total, 130 papers were included and had data extracted on specific methodological and statistical features. Several methodological problems were identified across the evidence base. Common issues included arbitrary categorisation of intervals (n = 107, 83%), no adjustment for potential confounders (n = 65, 50%), and lack of justification for included covariates where there was adjustment (n = 40 of 65 papers that performed an adjusted analysis, 62%). Many articles introduced epidemiological biases such as immortal time bias (n = 37 of 80 papers that used survival as an outcome, 46%) and confounding by indication (n = 73, 56%), as well as other biases arising from inclusion of factors outside of their temporal sequence. However, determination of the full extent of these problems was hampered by insufficient reporting. Recommendations include avoiding artificial categorisation of intervals, ensuring bias has not been introduced due to out-of-sequence use of key events and increased use of theoretical frameworks to detect and reduce bias. The development of reporting guidelines and domain-specific risk of bias tools may aid in ensuring future research can reliably contribute to recommendations regarding optimal timing and strengthen the evidence base

Psychological distress, quality of life, symptoms and unmet needs of colorectal cancer survivors near the end of treatment

Purpose This study investigated psychological morbidity, quality of life (QoL), colorectal cancer (CRC)-specific symptoms and supportive care needs in a CRC population at the end of treatment (EOT). Methods CRC survivors (n = 152) completed a post-treatment baseline questionnaire as part of a multisite supportive care randomised controlled trial (SurvivorCare). CRC survivors had completed treatment with curative intent within 0 to 6 months. Measures are as follows: Brief Symptom Inventory 18 (BSI-18) (psychological morbidity), EORTC QLQ-C30 and QLQ-CR29 (QoL and CRC-specific symptoms and problems) and Cancer Survivors' Unmet Needs (CaSUN) measure with a simplified response format (unmet needs). Linear regression models were used to compare participants' QoL with a general population sample. Correlation analysis examined associations between psychological morbidity, QoL and CRC-specific symptoms and problems. Results Average participant age was 64 years, and 51 % were male. The majority (68 %) had stage 3 disease. In comparison to population norms, CRC survivors had lower depression and anxiety scores (47.4 and 45.6, respectively) but higher somatisation, and lower role, cognitive and social functioning (p < 0.001). CRC survivors had higher fatigue, nausea/vomiting, appetite loss, diarrhoea and financial problems (all p < 0.001), as well as pain (p = 0.002) and constipation (p = 0.019). CRC-specific psychological scores were positively correlated with all three BSI domain scores, and pain and fatigue symptom scores on the QLQ-C30 while negatively correlated with all five functional scales of the QLQ-C30. Conclusions CRC survivors reported good mental health at EOT. Role and social functioning were impaired compared to population norms, possibly related to physical symptoms. Implications for Cancer Survivors Findings may help guide consultations with patients and inform the design of more tailored supportive care interventions. Trial registration: ACTRN1261000020701

Defining the supportive care needs and psychological morbidity of patients with functioning versus nonfunctioning neuroendocrine tumors: Protocol for a phase 1 trial of a nurse-led online and phone-based intervention

&copy; 2019 Journal of Medical Internet Research. All rights reserved. Background: Online information resources and support have been demonstrated to positively influence the well-being of people diagnosed with cancer. This has been explored in past literature for more common cancers; however, for rare cancers, such as neuroendocrine tumors (NETs), there are little to no support or resources available. Despite relatively good prognoses, the quality of life (QoL) of patients with NETs is significantly lower compared with samples of mixed cancer patients and the general population. Patients with NETs also typically report unclear and difficult pathways of disease management and treatment, given the heterogeneity of the diagnosis. There is a vital need to improve the availability of disease-specific information for this patient group and provide supportive care that is tailored to the unique needs of the NET patient population. Objective: This study described the protocol of a study aimed to better understand the outcomes and experiences of patients diagnosed with NETs and to develop and pilot test a nurse-led online and phone-based intervention that will provide tailored supportive care targeted to NET subgroups (functioning vs nonfunctioning). Methods: This is a multisite cohort with 3 phases, incorporating both quantitative and qualitative data collection. Phase 1 is a mixed methods prospective cohort study of NET patients identifying differences in patient experiences and priority of needs between NET subgroups. Phase 2 utilizes results from phase 1 to develop an online and nurse-led phone-based intervention. Phase 3 is to pilot test and evaluate the intervention\u27s acceptability, appropriateness, and feasibility. Results: Currently, the project is progressing through phase 1 and has completed recruitment. A total of 138 participants have been recruited to the study. To date, patient-reported outcome data from 123 participants at baseline and 87 participants at 6-month follow-up have been collected. Of these, qualitative data from semistructured interviews from 35 participants have also been obtained. Phase 2 and phase 3 of the project are yet to be completed. Conclusions: Limited research for patients with NETs suggests that QoL and patient experiences are significantly impaired compared with the general population. Furthermore, past research has failed to delineate how the clinical variability between those with functioning and nonfunctioning NETs impacts patient supportive care needs. This study will improve on the availability of disease-specific information as well as informing the design of a nurse-led online and phone-based supportive care intervention tailored for the unique needs of the NET patient population. International Registered Report Identifier (IRRID): DERR1-10.2196/14361