Acceptability and appropriateness of a clinical pathway for managing anxiety and depression in cancer patients: a mixed methods study of staff perspectives.

BACKGROUND: Clinical pathways (CPs) can improve health outcomes, but to be sustainable, must be deemed acceptable and appropriate by staff. A CP for screening and management of anxiety and depression in cancer patients (the ADAPT CP) was implemented in 12 Australian oncology services for 12 months, within a cluster randomised controlled trial of core versus enhanced implementation strategies. This paper compares staff-perceived acceptability and appropriateness of the ADAPT CP across study arms. METHODS: Multi-disciplinary lead teams at each service tailored, planned, championed and implemented the CP. Staff at participating services, purposively selected for diversity, completed a survey and participated in an interview prior to implementation (T0), and at midpoint (6 months: T1) and end (12 months: T2) of implementation. Interviews were recorded, transcribed and thematically analysed. RESULTS: Seven metropolitan and 5 regional services participated. Questionnaires were completed by 106, 58 and 57 staff at T0, T1 and T2 respectively. Eighty-eight staff consented to be interviewed at T0, with 89 and 76 at T1 and T2 (response rates 70%, 66% and 57%, respectively). Acceptability/appropriateness, on the quantitative measure, was high at T0 (mean of 31/35) and remained at that level throughout the study, with no differences between staff from core versus enhanced services. Perceived burden was relatively low (mean of 11/20) with no change over time. Lowest scores and greatest variability pertained to perceived impact on workload, time and cost. Four major themes were identified: 1) Mental health is an important issue which ADAPT addresses; 2) ADAPT helps staff deliver best care, and reduces staff stress; 3) ADAPT is fit for purpose, for both cancer care services and patients; 4) ADAPT: a catalyst for change. Opposing viewpoints are outlined. CONCLUSIONS: This study demonstrated high staff-perceived acceptability and appropriateness of the ADAPT CP with regards to its focus, evidence-base, utility to staff and patients, and ability to create change. However, concerns remained regarding burden on staff and time commitment. Strategies from a policy and managerial level will likely be required to overcome the latter issues. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347. https://www.anzctr.org.au/

Comparison of implementation strategies to influence adherence to the clinical pathway for screening, assessment and management of anxiety and depression in adult cancer patients (ADAPT CP): Study protocol of a cluster randomised controlled trial

© 2018 The Author(s). Background: Health service change is difficult to achieve. One strategy to facilitate such change is the clinical pathway, a guide for clinicians containing a defined set of evidence-based interventions for a specific condition. However, optimal strategies for implementing clinical pathways are not well understood. Building on a strong evidence-base, the Psycho-Oncology Co-operative Research Group (PoCoG) in Australia developed an evidence and consensus-based clinical pathway for screening, assessing and managing cancer-related anxiety and depression (ADAPT CP) and web-based resources to support it - staff training, patient education, cognitive-behavioural therapy and a management system (ADAPT Portal). The ADAPT Portal manages patient screening and prompts staff to follow the recommendations of the ADAPT CP. This study compares the clinical and cost effectiveness of two implementation strategies (varying in resource intensiveness), designed to encourage adherence to the ADAPT CP over a 12-month period. Methods: This cluster randomised controlled trial will recruit 12 cancer service sites, stratified by size (large versus small), and randomised at site level to a standard (Core) versus supported (Enhanced) implementation strategy. After a 3-month period of site engagement, staff training and site tailoring of the ADAPT CP and Portal, each site will "Go-live", implementing the ADAPT CP for 12 months. During the implementation phase, all eligible patients will be introduced to the ADAPT CP as routine care. Patient participants will be registered on the ADAPT Portal to complete screening for anxiety and depression. Staff will be responsible for responding to prompts to follow the ADAPT CP. The primary outcome will be adherence to the ADAPT CP. Secondary outcomes include staff attitudes to and experiences of following the ADAPT CP, using the ADAPT Portal and being exposed to ADAPT implementation strategies, collected using quantitative and qualitative methods. Data will be collected at T0 (baseline, after site engagement), T1 (6 months post Go-live) and T2 (12 months post Go-live). Discussion: This will be the first cluster randomised trial to establish optimal levels of implementation effort and associated costs to achieve successful uptake of a clinical pathway within cancer care. Trial registration: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN1261700041134

Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection.

BACKGROUND: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. METHODS: DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. RESULTS: The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. CONCLUSIONS: Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users

Primary pancreatic lymphoma – pancreatic tumours that are potentially curable without resection, a retrospective review of four cases

BACKGROUND: Primary pancreatic lymphomas (PPL) are rare tumours of the pancreas. Symptoms, imaging and tumour markers can mimic pancreatic adenocarcinoma, but they are much more amenable to treatment. Treatment for PPL remains controversial, particularly the role of surgical resection. METHODS: Four cases of primary pancreatic lymphoma were identified at Prince of Wales Hospital, Sydney, Australia. A literature review of cases of PPL reported between 1985 and 2005 was conducted, and outcomes were contrasted. RESULTS: All four patients presented with upper abdominal symptoms associated with weight loss. One case was diagnosed without surgery. No patients underwent pancreatectomy. All patients were treated with chemotherapy and radiotherapy, and two of four patients received rituximab. One patient died at 32 months. Three patients are disease free at 15, 25 and 64 months, one after successful retreatment. Literature review identified a further 103 patients in 11 case series. Outcomes in our series and other series of chemotherapy and radiotherapy compared favourably to surgical series. CONCLUSION: Biopsy of all pancreatic masses is essential, to exclude potentially curable conditions such as PPL, and can be performed without laparotomy. Combined multimodality treatment, utilising chemotherapy and radiotherapy, without surgical resection is advocated but a cooperative prospective study would lead to further improvement in treatment outcomes

Large-scale mass wasting in the western Indian Ocean constrains onset of East African rifting

Faulting and earthquakes occur extensively along the flanks of the East African Rift System, including an offshore branch in the western Indian Ocean, resulting in remobilization of sediment in the form of landslides. To date, constraints on the occurrence of submarine landslides at margin scale are lacking, leaving unanswered a link between rifting and slope instability. Here, we show the first overview of landslide deposits in the post-Eocene stratigraphy of the Tanzania margin and we present the discovery of one of the biggest landslides on Earth: the Mafia mega-slide. The emplacement of multiple landslides, including the Mafia mega-slide, during the early-mid Miocene is coeval with cratonic rifting in Tanzania, indicating that plateau uplift and rifting in East Africa triggered large and potentially tsunamigenic landslides likely through earthquake activity and enhanced sediment supply. This study is a first step to evaluate the risk associated with submarine landslides in the region

Accurate isolation and detection of circulating tumor cells using enrichment-free multiparametric high resolution imaging

IntroductionThe reliable and accurate detection of rare circulating tumor cells (CTCs) from cancer patient blood samples promises advantages in both research and clinical applications. Numerous CTC detection methods have been explored that rely on either the physical properties of CTCs such as density, size, charge, and/or their antigen expression profiles. Multiple factors can influence CTC recovery including blood processing method and time to processing. This study aimed to examine the accuracy and sensitivity of an enrichment-free method of isolating leukocytes (AccuCyte® system) followed by immunofluorescence staining and high-resolution imaging (CyteFinder® instrument) to detect CTCs.MethodHealthy human blood samples, spiked with cancer cells from cancer cell lines, as well as blood samples obtained from 4 subjects diagnosed with cancer (2 pancreatic, 1 thyroid, and 1 small cell lung) were processed using the AccuCyte-CyteFinder system to assess recovery rate, accuracy, and reliability over a range of processing times.ResultsThe AccuCyte-CyteFinder system was highly accurate (95.0%) at identifying cancer cells in spiked-in samples (in 7.5 mL of blood), even at low spiked-in numbers of 5 cells with high sensitivity (90%). The AccuCyte-CyteFinder recovery rate (90.9%) was significantly higher compared to recovery rates obtained by density gradient centrifugation (20.0%) and red blood cell lysis (52.0%). Reliable and comparable recovery was observed in spiked-in samples and in clinical blood samples processed up to 72 hours post-collection. Reviewer analysis of images from spiked-in and clinical samples resulted in high concordance (R-squared value of 0.998 and 0.984 respectively).DiscussionThe AccuCyte-CyteFinder system is as an accurate, sensitive, and clinically practical method to detect and enumerate cancer cells. This system addresses some of the practical logistical challenges in incorporating CTCs as part of routine clinical care. This could facilitate the clinical use of CTCs in guiding precision, personalized medicine

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium

PURPOSE The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor