Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

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.).

A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6.

BACKGROUND: In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC). OBJECTIVES: To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (groups 1 and 2), fixed-dose cemiplimab in mCSCC (group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (group 6). METHODS: Patients received cemiplimab (3 mg/kg intravenously every 2 weeks [groups 1 and 2]) or cemiplimab (350 mg intravenously [groups 3 and 6]) every 3 weeks. The primary end point was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments. RESULTS: At 42.5 months, ORR for groups 1-3 (n = 193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for group 6 (n = 165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were groups 1-3: 31.1% and group 6: 34.5%. LIMITATIONS: Nonrandomized study, nonsurvival primary end point. CONCLUSION: EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC.

Immune checkpoint inhibitor therapy for advanced cutaneous squamous cell carcinoma in Australia: a retrospective real world cohort study.

OBJECTIVES: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. STUDY DESIGN: Retrospective observational study; review of patient records in fifteen Australian institutions. SETTING, PARTICIPANTS: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. MAIN OUTCOME MEASURES: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival. RESULTS: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths. CONCLUSION: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.

Chemoradiotherapy with concurrent durvalumab for the palliative treatment of oligometastatic oesophageal and gastrooesophageal carcinoma with dysphagia: a single arm phase II clinical trial (PALEO, sponsored by the Australasian Gastro-Intestinal Trials Group).

BACKGROUND: Oesophageal and gastrooesophageal junction (GOJ) carcinoma frequently present with dysphagia and de novo metastatic disease. There is scope to improve treatment paradigms to both address symptoms and improve survival. One method is integrating immune checkpoint inhibition with novel treatment combinations. METHODS: PALEO is a single arm, phase II clinical trial in patients with previously untreated, oligometastatic or locoregionally advanced oesophageal or GOJ carcinoma and dysphagia. PALEO is sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG). Participants receive 2 weeks of therapy with concurrent hypofractionated radiotherapy of 30Gy in 10 fractions to the primary tumour, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m2 and durvalumab 1500 mg q4 weekly, followed by durvalumab monotherapy continuing at 1500 mg q4weekly until disease progression, unacceptable toxicity or 24 months of therapy. A single metastasis is treated with stereotactic radiotherapy of 24Gy in 3 fractions in week 7. The trial primary endpoint is the progression free survival rate at 6 months. Secondary endpoints include duration of dysphagia relief, nutritional status change, quality of life, response rate, toxicity, progression free survival and overall survival. The tertiary endpoint is prediction of outcome based on biomarkers identified from patient serial blood samples collected pre- and post-radiotherapy. DISCUSSION: This unique investigator-initiated clinical trial is designed to simultaneously address the clinically relevant problems of dysphagia and distant disease control. The overarching aims are to improve patient nutrition, quality of life and survival with low toxicity therapy. AGITG PALEO is a multidisciplinary collaboration and will add to the understanding of the relationship between radiotherapy and the anti-tumour immune response. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12619001371189 , registered 8 October 2019.

Business as unusual: medical oncology services adapt and deliver during COVID-19.

BACKGROUND: The COVID-19 pandemic has challenged cancer care globally, introducing resource limitations and competing risks into clinical practice. AIMS: To describe the COVID-19 impact on medical oncology care provision in an Australian setting. METHODS: Calvary Mater Newcastle and Newcastle Private Hospital medical oncology data from 1 February to 31 April 2019 versus 2020 were retrospectively analysed. RESULTS: Three hundred and sixty-four inpatient admissions occurred in 2020, 21% less than in 2019. Total inpatient days decreased by 22% (2842 vs 2203). April was most impacted (36% and 44% fewer admissions and inpatient days respectively). Mean length of stay remained unchanged (6.4 vs 6.2 days, P = 0.7). In all, 5072 outpatient consultations were conducted, including 417 new-patient consultations (4% and 6% increase on 2019 respectively). Telephone consultations (0 vs 1380) replaced one-quarter of face-to-face consultations (4859 vs 3623, -25%), with minimal telehealth use (6 vs 69). Day Treatment Centre encounters remained stable (3751 vs 3444, -8%). The proportion of new patients planned for palliative treatment decreased (35% vs 28%, P = 0.04), observation increased (16% vs 23%, P = 0.04) and curative intent treatment was unchanged (both 41%). Recruiting clinical trials decreased by one-third (45 vs 30), two trials were activated (vs 5 in 2019) and 45% fewer patients consented to trial participation (62 vs 34). CONCLUSION: Our medical oncology teams adapted rapidly to COVID-19 with significant changes to care provision, including fewer hospital admissions, a notable transition to telephone-based outpatient clinics and reduced clinical trial activity. The continuum of care was largely defended despite pandemic considerations and growing service volumes.

ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours.

BACKGROUND: Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are "wild type"). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a "quadruple wild type" tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent. METHODS AND DESIGN: ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with "quadruple wild type" or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer. DISCUSSION: This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the "quadruple wild type", which may 'superselect' for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12612000901808 , registered 16 August 2012.

Impact of regular aspirin use on overall and cancer-specific survival in patients with colorectal cancer harboring a PIK3CA mutation.

BACKGROUND: Recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer (CRC) patients harboring PIK3CA mutations. However, the number of PIK3CA-mutated CRC patients examined in these studies was modest. Our collaborative study aims to validate the association between regular aspirin use and survival in patients with PIK3CA-mutated CRC. PATIENTS AND METHODS: Patients with PIK3CA-mutated CRC were identified at Moffitt Cancer Center (MCC) in the United States and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data and survival data were available. At MCC, PIK3CA mutations were identified by targeted exome sequencing using the Illumina GAIIx Next Generation Sequencing platform. At RMH, Sanger sequencing was utilized. Multivariate survival analyses were conducted using Cox logistic regression. RESULTS: From a cohort of 1487 CRC patients, 185 patients harbored a PIK3CA mutation. Median age of patients with PIK3CA-mutated tumors was 72 years (range: 34-92) and median follow up was 54 months. Forty-nine (26%) patients used aspirin regularly. Regular aspirin use was not associated with improved overall survival (multivariate HR 0.96, p = 0.86). There was a trend towards improved cancer-specific survival (multivariate HR 0.60, p = 0.14), but this was not significant. CONCLUSIONS: Despite examining a large number of patients, we did not confirm that regular aspirin use was associated with statistically significant improvements in survival in PIK3CA-mutated CRC patients. Prospective evaluation of this relationship is warranted.

How the 'Health Leader-as-Coach' benefits health leaders, their teams, peers, organisation and the system.

One of the main ways in which health leaders at all levels can be developed on a daily basis has been neglected by clinical leadership research, and by the research community generally, relating to the leader consciously using evidence-based coaching skills to positively impact their direct reports, team members, peers, organisations and the wider system in the context of their vocational role, as 'Leader-as-Coach'.This paper summarises the research on the role of 'Leader-as-Coach', and translates the learning from this into the practice of clinical leadership development.Line managers are increasingly expected to use a coaching approach and are in an ideal position to do so. While there are many similarities with professional external coaching, the behaviours of the 'Leader-as-Coach' are also not identical and multiple ethical issues can arise.There is no consistent academic definition to describe the behaviours of coaching in the context of a leader's vocational role, nor yet specific competencies for training or supervision purposes.The outcomes are summarised from the known literature in this field. Individual and system challenges are then discussed and conclusions are drawn about what this research means in practice for clinical leaders and their systems.

Esophageal chemoradiotherapy with concurrent nivolumab: Pilot results in the palliative treatment of oligometastatic disease.

AIMS: Many patients diagnosed with esophageal cancer have dysphagia from their primary tumor and de novo metastatic disease. The purpose of this study was to test the safety and efficacy of nivolumab given concurrently with hypofractionated chemoradiotherapy to patients with oligometastatic and obstructing esophageal tumors. METHODS: Patients were enrolled in a planned single-arm, phase 2 clinical trial. Eligible participants had previously untreated oligometastatic (≤5 metastases on fludeoxyglucose-18 positron emission tomography scan outside the primary tumor radiotherapy field) esophageal or gastroesophageal carcinoma, dysphagia, and Eastern Cooperative Oncology Group performance status 0-1. Treatment was with 2 weeks of concurrent hypofractionated radiotherapy (30 Gy/10#) to the primary tumor, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m2, and q2weekly nivolumab 240 mg, followed by nivolumab 480 mg continuing q4weekly until disease progression or 24 months total. A single metastasis was treated with stereotactic radiotherapy (SBRT) (24 Gy/3#) in week 7. RESULTS: Five patients were recruited before trial closure to new participants for logistical reasons. Existing participants continued treatment per protocol as a pilot study at one center. All five patients completed chemoradioimmunotherapy and SBRT. All patients derived an improvement in their dysphagia. Two patients completed 24 months of nivolumab without disease progression. Grade 3 adverse events (AEs) occurred in 3 patients, however, there were no grade 4 AEs, AEs due to SBRT, or AEs of special interest as defined by the protocol. CONCLUSION: Pilot results from five patients at one center found that treatment was well tolerated and effective for dysphagia relief. The efficacy of hypofractionated chemoradiotherapy with concurrent checkpoint inhibition should be tested in a multicentre study.

Psychologically informed leadership coaching positively impacts the mental well-being of 80 senior doctors, medical and public health leaders.

INTRODUCTION: Senior doctors, medical and public health leaders frequently experience poor levels of mental well-being. The aim was to investigate whether psychologically informed leadership coaching impacted on the mental well-being of 80 UK-based senior doctors, medical and public health leaders. METHODS: A pre-post study was undertaken during 2018-2022 of 80 UK senior doctors, medical and public health leaders. Before and after measures of mental well-being were measured using the Short Warwick-Edinburgh Mental Well-Being Scale. The age range was 30-63 years (mean 44.5, mode and median, 45.0). Thirty-seven participants were male (46.3%). The proportion of non-white ethnicity was 21.3%.Participants undertook an average of 8.7 hours of bespoke 1:1 psychologically informed leadership coaching. RESULTS: The mean well-being score before the intervention was 21.4 (SD=3.28). The mean well-being score after the intervention increased to 24.5 (SD=3.38). A paired samples t-test found that the increase in metric well-being scores after the intervention was statistically significant (t=-9.52, p<0.001; Cohen's d=3.14).The mean improvement was+17.4% (median 115.8%, mode 100, range -17.7% to+202.4%). This was observed particularly in two subdomains. CONCLUSION: Psychologically informed leadership coaching may be an effective way to improve mental well-being outcomes in senior doctors, medical and public heath leaders. The contribution of psychologically informed coaching is currently limited in medical leadership development research.

Implementing Smoking Cessation Interventions for Tobacco Users Within Oncology Settings: A Systematic Review.

Importance: Patients with cancer who continue to smoke tobacco experience greater treatment-related complications, higher risk of secondary cancers, and greater mortality. Despite research to improve smoking cessation care within clinical oncology, implementation of proposed interventions within routine care remains challenging. Objective: To identify and recommend implementation strategies for smoking cessation interventions associated with improved screening, advice-giving, and referral for tobacco users recently diagnosed with cancer, as well as shifting smoking behaviors and attitudes in this patient population. Evidence Review: MEDLINE, CINAHL, Embase, and PsycINFO databases, as well as Google Scholar, were searched for articles published before September 7, 2020, using terms related to cancer, smoking cessation, and implementation science. Outcomes of interest were study characteristics, implementation strategies, and outcome measures (screening, advice, referral, abstinence rates, and attitudes). The Cochrane Risk of Bias Tool for randomized and nonrandomized studies was used to assess bias. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and Synthesis Without Meta-analysis (SWiM) guideline. Implementation strategies were categorized according to Expert Recommendations for Implementing Change (ERIC) study taxonomy. A systematic analysis was conducted focusing on studies with low or moderate risk of bias due to high heterogeneity in outcome measurement. Findings: In total, 6047 records were screened, yielding 43 articles (10 randomized clinical trials and 33 nonrandomized studies). Four strategies were associated with improved screening, advice-giving, and referral: (1) supporting clinicians, (2) training implementation stakeholders (including clinicians), (3) changing the infrastructure, and (4) developing stakeholder interrelationships. Conclusions and Relevance: In this systematic review, supporting clinicians by providing cessation care through a trained tobacco specialist was identified as important for achieving short-term abstinence and changing attitudes among patients with cancer. Combined with a theoretical framework and stakeholder involvement, these strategies provide the basis for successful implementation of cessation support; this systematic review serves as an illustration of the methodological application and synthesis of implementation studies and other medical conditions more generally.

A workplace Acceptance and Commitment Therapy (ACT) intervention for improving healthcare staff psychological distress: A randomised controlled trial.

The levels of psychological distress and burnout among healthcare staff are high, with negative implications for patient care. A growing body of evidence indicates that workplace programmes based on Acceptance and Commitment Therapy (ACT) are effective for improving employees' general psychological health. However, there is a paucity of research examining the specific psychological and/or behavioural processes through which workplace ACT programmes transmit their beneficial effects. The aim of this randomised controlled trial was to investigate the outcomes and putative processes of change in a 4-session ACT training programme designed to reduce psychological distress among healthcare staff (n = 98). Ninety-eight employees of a healthcare organisation were randomly allocated to the ACT intervention or to a waiting list control group. Study measures were administered on four occasions (baseline, mid-intervention, post-intervention, and follow-up) over a three-month evaluation period. Results showed that the ACT intervention led to a significant decrease in symptoms of psychological distress and a less pronounced reduction in burnout. These effects were mediated primarily via an improvement in mindfulness skills and values-based behaviour and moderated by participants' initial levels of distress. At four-week post-intervention, 48% of participants who received the ACT intervention showed reliable improvements in psychological distress, with just under half of the aforementioned improvements (46.15%) meeting criteria for clinically significant change. The results advance ACT as an effective stress management intervention for healthcare staff. The findings should be confirmed in a large scale randomised controlled trial with longer follow-up and cost-effectiveness analyses.

Phase I trial of hypofractionated chemoradiotherapy in the palliative management of esophageal and gastro-esophageal cancer.

BACKGROUND: Many patients with incurable esophageal cancer (ECa) present with dysphagia as their predominant symptom. Currently there is no consensus on how best to initially manage this scenario with multiple therapeutic options available. We aimed to assess the safety and efficacy of using hypofractionated radiotherapy given over a progressively shorter timeframe with concurrent carboplatin and paclitaxel in the management of patients with ECa and dysphagia. METHODS: In this phase I trial we enrolled patients with histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus or the gastro-esophageal junction with symptomatic dysphagia from local disease and not for curative treatment. Patients needed to be 18 years or older, have an ECOG performance status of 0-2 and be suitable to receive carboplatin and paclitaxel chemotherapy. Patients were placed in four progressively shorter radiation schedules culminating in 30 Gy in 10 fractions in a step wise manner, all with concurrent carboplatin AUC 2 and paclitaxel 50 mg/m2 chemotherapy delivered weekly with the radiation therapy. The primary endpoint was the development of the dose limiting toxicities (DLTs) esophageal perforation or febrile neutropenia. Secondary endpoints were relief of dysphagia, time to improvement of dysphagia, dysphagia progression free survival and overall survival. RESULTS: Eighteen patients were enrolled in the study between October 2014 and March 2019. There were no DLTs experienced during the trial. The most common grade 3 + acute toxicity experienced by patients were nausea and vomiting (both in 4/18 patients). The most common radiation specific acute toxicity experienced was esophagitis with 67% of patients experiencing grade 1-2 symptoms. All patients experienced improvement in dysphagia. The median time to dysphagia improvement was 3 weeks from the start of chemoradiotherapy (CTRT) (range 2-10 weeks). The median dysphagia free survival was 5.8 months with a median overall survival of 8.9 months. CONCLUSION: Hypofractionated palliative CTRT with 30 Gy/10# of radiation therapy with concurrent weekly carboplatin and paclitaxel chemotherapy is well tolerated and provides a good response in improvement of dysphagia. Further studies need to be undertaken which provide both symptomatic improvement in the primary tumor but also control of the metastatic burden in these patients. CLINICAL TRIAL REGISTRATION: This trial was prospectively registered with www.anzctr.org.au Identifier: ACTRN12614000821695.

Building staff capability, opportunity, and motivation to provide smoking cessation to people with cancer in Australian cancer treatment centres: development of an implementation intervention framework for the Care to Quit cluster randomised controlled trial.

Few rigorous studies provide a clear description of the methodological approach of developing an evidence-based implementation intervention, prior to implementation at scale. This study describes the development, mapping, rating, and review of the implementation strategies for the Care to Quit smoking cessation trial, prior to application in nine cancer services across Australia. Key stakeholders were engaged in the process from conception through to rating, reviewing and refinement of strategies and principles. An initial scoping review identified 21 barriers to provision of evidence-based smoking cessation care to patients with cancer, which were mapped to the Theoretical Domains Framework and Behaviour Change Wheel (BCW) to identify relevant intervention functions. The mapping identified 26 relevant behaviour change techniques, summarised into 11 implementation strategies. The implementation strategies were rated and reviewed against the BCW Affordability, Practicality, Effectiveness and cost-effectiveness, Acceptability, Side-effects/safety, and Equity criteria by key stakeholders during two interactive workshops to facilitate a focus on feasible interventions likely to resonate with clinical staff. The implementation strategies and associated intervention tools were then collated by form and function to provide a practical guide for implementing the intervention. This study illustrates the rigorous use of theories and frameworks to arrive at a practical intervention guide, with potential to inform future replication and scalability of evidence-based implementation across a range of health service settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s10742-022-00288-6.

Psychometric properties of leadership scales for health professionals: a systematic review.

BACKGROUND: The important role of leaders in the translation of health research is acknowledged in the implementation science literature. However, the accurate measurement of leadership traits and behaviours in health professionals has not been directly addressed. This review aimed to identify whether scales which measure leadership traits and behaviours have been found to be reliable and valid for use with health professionals. METHODS: A systematic review was conducted. MEDLINE, EMBASE, PsycINFO, Cochrane, CINAHL, Scopus, ABI/INFORMIT and Business Source Ultimate were searched to identify publications which reported original research testing the reliability, validity or acceptability of a leadership-related scale with health professionals. RESULTS: Of 2814 records, a total of 39 studies met the inclusion criteria, from which 33 scales were identified as having undergone some form of psychometric testing with health professionals. The most commonly used was the Implementation Leadership Scale (n = 5) and the Multifactor Leadership Questionnaire (n = 3). Of the 33 scales, the majority of scales were validated in English speaking countries including the USA (n = 15) and Canada (n = 4), but also with some translations and use in Europe and Asia, predominantly with samples of nurses (n = 27) or allied health professionals (n = 10). Only two validation studies included physicians. Content validity and internal consistency were evident for most scales (n = 30 and 29, respectively). Only 20 of the 33 scales were found to satisfy the acceptable thresholds for good construct validity. Very limited testing occurred in relation to test-re-test reliability, responsiveness, acceptability, cross-cultural revalidation, convergent validity, discriminant validity and criterion validity. CONCLUSIONS: Seven scales may be sufficiently sound to be used with professionals, primarily with nurses. There is an absence of validation of leadership scales with regard to physicians. Given that physicians, along with nurses and allied health professionals have a leadership role in driving the implementation of evidence-based healthcare, this constitutes a clear gap in the psychometric testing of leadership scales for use in healthcare implementation research and practice. TRIAL REGISTRATION: This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (see Additional File 1) (PLoS Medicine. 6:e1000097, 2009) and the associated protocol has been registered with the PROSPERO International Prospective Register of Systematic Reviews (Registration Number CRD42019121544 ).

Group-based acceptance and commitment therapy interventions for improving general distress and work-related distress in healthcare professionals: A systematic review and meta-analysis.

BACKGROUND: A large proportion of the healthcare workforce reports significant distress and burnout, which can lead to poor patient care. Several psychological interventions, such as Acceptance and Commitment Therapy (ACT), have been applied to improve general distress and work-related distress in healthcare professionals (HCPs). However, the overall efficacy of ACT in this context is unknown. This review and meta-analysis aimed to: 1) test the pooled efficacy of ACT trials for improving general distress and reducing work-related distress in HCPs; 2) evaluate the overall study quality and risk of bias; and 3) investigate potential moderators of intervention effectiveness. METHOD: Four databases (Ovid MEDLINE, EMBASE, PsycINFO, CINHAL) were searched, with 22 pre-post design and randomised controlled trial (RCTs) studies meeting the inclusion criteria. 10 RCTs studies were included in the meta-analysis. RESULTS: Two random effects meta-analyses on general distress and work-related distress found that ACT outperformed pooled control conditions with a small effect size for general distress at post-intervention (g = 0.394, CIs [.040; .748]) and for work-related distress (g = 0.301, CIs [.122; .480]) at follow-up. However, ACT was more effective than controls. The number of treatment sessions was a moderator of intervention efficacy for general distress. ACT process measures (psychological flexibility) did not show significantly greater improvements in those who received the intervention. LIMITATIONS: The methodological quality of studies was poor and needs to be improved. CONCLUSIONS: Overall, ACT interventions are effective in improving general distress and work-related distress in HCPs. These findings have implications for policymakers, healthcare organisations and clinicians.

Care to Quit: a stepped wedge cluster randomised controlled trial to implement best practice smoking cessation care in cancer centres.

BACKGROUND: Cigarette smoking in people with cancer is associated with negative treatment-related outcomes including increased treatment toxicity and complications, medication side effects, decreased performance status and morbidity. Evidence-based smoking cessation care is not routinely provided to patients with cancer. The purpose of this study is to determine the effectiveness of a smoking cessation implementation intervention on abstinence from smoking in people diagnosed with cancer. METHODS: A stepped wedge cluster randomised design will be used. All sites begin in the control condition providing treatment as usual. In a randomly generated order, sites will move to the intervention condition. Based on the Theoretical Domains Framework, implementation of Care to Quit will include (i) building the capability and motivation of a critical mass of key clinical staff and identifying champions; and (ii) identifying and implementing cessation care models/pathways. Two thousand one hundred sixty patients with cancer (diagnosed in the prior six months), aged 18+, who report recent combustible tobacco use (past 90 days or in the 30 days prior to cancer diagnosis) and are accessing anti-cancer therapy, will be recruited at nine sites. Assessments will be conducted at baseline and 7-month follow-up. The primary outcome will be 6-month abstinence from smoking. Secondary outcomes include biochemical verification of abstinence from smoking, duration of quit attempts, tobacco consumption, nicotine dependence, provision and receipt of smoking cessation care, mental health and quality of life and cost effectiveness of the intervention. DISCUSSION: This study will implement best practice smoking cessation care in cancer centres and has the potential for wide dissemination. TRIAL REGISTRATION: The trial is registered with ANZCTR (www.anzctr.org.au): ACTRN ( ACTRN12621000154808 ) prior to the accrual of the first participant and will be updated regularly as per registry guidelines.

Promoting colorectal cancer screening: a systematic review and meta-analysis of randomised controlled trials of interventions to increase uptake.

Colorectal cancer (CRC) represents a global public health concern. CRC screening is associated with significant reductions in CRC incidence and mortality, however, uptake is suboptimal. This systematic review and meta-analysis of randomised controlled trials explored the effectiveness of interventions designed to increase screening uptake, plus the impact of various moderators. Data from 102 studies including 1.94 million participants were analysed. Results showed significant benefit of all interventions combined (OR, 1.49, 95% CI: 1.43, 1.56, p < 0.001). The effects were similar in studies using objective versus self-reported uptake measures and lower in studies judged to be at high risk of bias. Moderator analyses indicated significant effects for aspects of behaviour (effects lower for studies on non-endoscopic procedures), and intervention (effects higher for studies conducted in community settings, in healthcare systems that are not free, and that use reminders, health-professional providers, paper materials supplemented with in-person or phone contact, but avoid remote contact). Interventions that included behaviour change techniques targeting social support (unspecified or practical), instructions or demonstration of the behaviour, and that added objects to the environment produced stronger effects. The way in which findings can inform interventions to improve CRC screening uptake is discussed.

Gastrostomy dependency trends over 15 years of patients at a large tertiary referral center following the insertion of a prophylactic gastrostomy for chemoradiation for mucosal head and neck cancer.

AIM: The routine use of prophylactic percutaneous endoscopic gastrostomy (PEG) tubes for nutrition support during radical chemoradiation for head and neck cancer has been suggested to result in PEG dependency. This research aimed to determine the rates of gastrostomy dependency at the Calvary Mater Newcastle (CMN) where PEGs are routinely used and to identify potentially modifiable risk factors. METHODS: All patients with head and neck cancer planned for curative chemoradiation with a prophylactic PEG inserted were included in this review. Medical records of 250 patients treated between 2000 and 2015 were examined. RESULTS: Overall, eight patients (3%) were unable to wean. At 12 months following treatment, 16 patients (6%) still required PEG tubes for feeding. A greater T extent (T4 or synchronous head and neck tumors) and number of days Nil By Mouth (NBM) remained as significant independent risk factors for PEG dependency at 12 months (Textent OR 6.96 P < .001; NBM OR 1.01 P = .004) and overall (Textent OR8.04 P = .02; NBM OR1.01 P = .001). Associations with NBM were investigated, which demonstrated that patients had less NBM days with intensity-modulated radiation therapy (IMRT) (ß-13.3, P = .007) and seeing a speech pathologist during treatment (ß-11.9, P = .026). More NBM days were associated with tumors with greater T extent (ß+22; P < .001). CONCLUSION: The routine use of prophylactic PEGs has not resulted in significant rates of PEG dependency at the CMN. Seeing a speech pathologist during treatment and IMRT may decrease time NBM, which was identified as a potentially modifiable risk factor for PEG dependency.

Cluster randomized controlled trial of volitional and motivational interventions to improve bowel cancer screening uptake: A population-level study.

OBJECTIVES: Colorectal cancer (CRC) is a leading cause of cancer death worldwide, although effective uptake of bowel cancer screening is below 60% in England. This trial investigated the influence of volitional and motivational interventions and their combination on increasing guaiac fecal occult blood testing (gFOBT) screening uptake. METHOD: In total, 34,633 participants were recruited (via North-East of England bowel cancer screening hub) into a 2×2 factorial cluster randomized controlled trial. Social norm-based motivational intervention (SNA); Implementation intention-based Volitional Help Sheet (VHS); Combined intervention (SNA+VHS); Treatment as usual control. Screening rate (gFOBT kit return rate within 8 weeks of invitation) was the primary outcome. RESULTS: Screening kits were returned by 60% of participants (N=20,847/34,633). A substantial imbalance was observed in participant characteristics, participants in the combined intervention group were younger and more likely to be first time invitees. Adjusted analyses found insufficient evidence that any of the interventions were different to control (Combined: OR = 1.18, 95% CI 0.97-1.44; SNA alone: OR=0.93; 95% CI: 0.76-1.15; VHS alone OR= 0.88; 95% CI: 0.75-1.03). Subgroup analyses demonstrated a significant beneficial effect of the combined intervention in the youngest age group compared to control (OR = 1.27; 95% CI: 1.05-1.54). CONCLUSIONS: The study did not support any benefit of either VHS or SNA interventions alone on bowel cancer screening uptake. The combined SNA+VHS intervention was significantly different from control only in the youngest age group in adjusted analyses. However, the magnitude of effect in the youngest age group suggests that further testing of VHS plus SNA interventions in carefully targeted populations may be warranted.