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BACKGROUND AND OBJECTIVES: Bio-medical image segmentation models typically attempt to predict one segmentation that resembles a ground-truth structure as closely as possible. However, as medical images are not perfect representations of anatomy, obtaining this ground truth is not possible. A surrogate commonly used is to have multiple expert observers define the same structure for a dataset. When multiple observers define the same structure on the same image there can be significant differences depending on the structure, image quality/modality and the region being defined. It is often desirable to estimate this type of aleatoric uncertainty in a segmentation model to help understand the region in which the true structure is likely to be positioned. Furthermore, obtaining these datasets is resource intensive so training such models using limited data may be required. With a small dataset size, differing patient anatomy is likely not well represented causing epistemic uncertainty which should also be estimated so it can be determined for which cases the model is effective or not. METHODS: We use a 3D probabilistic U-Net to train a model from which several segmentations can be sampled to estimate the range of uncertainty seen between multiple observers. To ensure that regions where observers disagree most are emphasised in model training, we expand the Generalised Evidence Lower Bound (ELBO) with a Constrained Optimisation (GECO) loss function with an additional contour loss term to give attention to this region. Ensemble and Monte-Carlo dropout (MCDO) uncertainty quantification methods are used during inference to estimate model confidence on an unseen case. We apply our methodology to two radiotherapy clinical trial datasets, a gastric cancer trial (TOPGEAR, TROG 08.08) and a post-prostatectomy prostate cancer trial (RAVES, TROG 08.03). Each dataset contains only 10 cases each for model development to segment the clinical target volume (CTV) which was defined by mul

In the supplementary material to this paper we noted some errors in supplementary Online Resource 4: (a) The title ‘CHEERS checklist’ should be deleted and replaced with ‘CHEERS checklist and adapted scoring criteria’. (b) We should have cited the following two references: Lynch et al., 2019 and Husereau et al., 2013 in the title: • D. Husereau, M. Drummond, S. Petrou, C. Carswell, D. Moher, D. Greenberg, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS)–explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value in Health, 16 (2) (2013), pp. 231-250 • M. Lynch, R. De Abreu Lourenco, M. Flattery, M. Haas. Reviewing the cost-effectiveness of long-acting reversible contraceptive methods in an Australian context. Aust. N. Zeal. J. Obstet. Gynaecol., 59 (2019), pp. 21-35 (c) In Row 7 (Comparators), the example offered ‘e.g. IUS is used rather than LNG-IUS20 or Mirena’ should be disregarded because ‘LNG-IUS20 or Mirena’ was included in error and was not relevant to this paper. The authors would like to apologise for any inconvenience caused.

PURPOSE: The TOPGEAR phase 3 trial hypothesized that adding preoperative chemoradiation therapy (CRT) to perioperative chemotherapy will improve survival in patients with gastric cancer. Owing to the complexity of gastric irradiation, a comprehensive radiation therapy quality assurance (RTQA) program was implemented. Our objective is to describe the RTQA methods and outcomes. METHODS AND MATERIALS: RTQA was undertaken in real time before treatment for the first 5 patients randomized to CRT from each center. Once acceptable quality was achieved, RTQA was completed for one-third of subsequent cases. RTQA consisted of evaluating (1) clinical target volume and organ-at-risk contouring and (2) radiation therapy planning parameters. Protocol violations between high- (20+ patients enrolled) and low-volume centers were compared using the Fisher exact test. RESULTS: TOPGEAR enrolled 574 patients, of whom 286 were randomized to receive preoperative CRT and 203 (71%) were included for RTQA. Of these, 67 (33%) and 136 (67%) patients were from high- and low-volume centers, respectively. The initial RTQA pass rate was 72%. In total, 28% of cases required resubmission. In total, 200 of 203 cases (99%) passed RTQA before treatment. Cases from low-volume centers required resubmission more often (44/136 [33%] vs 13/67 [18%]; P = .078). There was no change in the proportion of cases requiring resubmission over time. Most cases requiring resubmission had multiple protocol violations. At least 1 aspect of the clinical target volume had to be adjusted in all cases. Inadequate coverage of the duodenum was most common (53% major violation, 25% minor violation). For the remaining cases, the resubmission process was triggered secondary to poor contour/plan quality. CONCLUSIONS: In a large multicenter trial, RTQA is feasible and effective in achieving high-quality treatment plans. Ongoing education should be performed to ensure consistent quality during the entire study period.

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Background Evidence-based clinical practice guidelines recommend discussion by a multidisciplinary team (MDT) to review and plan the management of patients for a variety of cancers. However, not all patients diagnosed with cancer are presented at an MDT. Objectives (1) To identify the factors (barriers and enablers) influencing presentation of all patients to, and the perceived value of, MDT meetings in the management of patients with pancreatic cancer and; (2) to identify potential interventions that could overcome modifiable barriers and enhance enablers using the theoretical domains framework (TDF). Methods Semistructured interviews were conducted with radiologists, surgeons, medical and radiation oncologists, gastroenterologists, palliative care specialists and nurse specialists based in New South Wales and Victoria, Australia. Interviews were conducted either in person or via videoconferencing. All interviews were recorded, transcribed verbatim, deidentified and data were thematically coded according to the 12 domains explored within the TDF. Common belief statements were generated to compare the variation between participant responses. Results In total, 29 specialists were interviewed over a 4-month period. Twenty-two themes and 40 belief statements relevant to all the TDF domains were generated. Key enablers influencing MDT practices included a strong organisational focus (social/professional role and identity), beliefs about the benefits of an MDT discussion (beliefs about consequences), the use of technology, for example, videoconferencing (environmental context and resources), the motivation to provide good quality care (motivation and goals) and collegiality (social influences). Barriers included: absence of palliative care representation (skills), the number of MDT meetings (environmental context and resources), the cumulative cost of staff time (beliefs about consequences), the lack of capacity to discuss all patients within the allotted time (beliefs a

Background: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival. Method(s): Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. Result(s): 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy +/- chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96). Conclusion(s): Capture of a concise data set has enabled quality of care to be assessed.Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc.

INTRODUCTION: Obtaining tissue diagnosis for lung cancer can sometimes be difficult and unsafe. We evaluated outcomes of biopsy-confirmed versus radiologically-diagnosed lung cancer treated with stereotactic body radiotherapy (SBRT). METHODS: A single-institutional retrospective cohort of lung cancer patients treated with SBRT between February 2014 and October 2018. Outcomes of interest were: local failure (LF), distant failure (DF), and overall survival (OS). Probability of LF, DF, and OS were estimated using the Kaplan-Meier method. Differences in outcomes between biopsy-confirmed versus radiologically-diagnosed lung cancer were evaluated using the log-rank test. RESULTS: Sixty-five lung lesions in 61 patients were treated with SBRT. Mean age was 75.6 years. Twenty-seven patients (44.3%) were ECOG 2-3. Thirty-nine patients (64%) were radiologically-diagnosed. There were five cases of LF observed at median of 12.8 months post-SBRT and 12-month LF-free survival was 96% (95% CI, 86-99%), with no differences between groups (p = 0.1). Sixteen patients developed DF, with 12-month DF-free survival of 84% (95% CI, 71-91%), and no difference between groups (p = 0.06). Sixteen deaths were reported at a median of 12.5 months post-SBRT, with 12-month OS of 85% (95% CI, 73-92%), and no differences between study groups (p = 0.5). No grade 3 toxicities were reported. CONCLUSION: The oncological outcomes were similar in patients with early lung cancer treated with SBRT with or without biopsy-confirmation. In situations where tissue diagnosis is not feasible or unsafe, it is not unreasonable to offer SBRT based on clinical and radiological suspicion following multidisciplinary discussions.

INTRODUCTION: Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand. METHODS AND ANALYSIS: Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight. ETHICS AND DISSEMINATION: The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.

BACKGROUND: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. METHODS: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier: NCT04460352.

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 Octobe

BACKGROUND: Incontinence-associated dermatitis is a common, under-recognized painful skin condition associated with poorer quality of life, increased nurse workloads, and costs. OBJECTIVE: To systematically review economic evidence for the prevention and treatment of incontinence-associated dermatitis. DESIGN: Systematic review of quantitative research. DATA SOURCES: PubMed, MEDLINE, EMBASE, Cochrane Library, York Centre for Reviews and Dissemination database, Econlit, Tufts' Cost-Effectiveness Analysis Registry, and Web of Science. REVIEW METHODS: A comprehensive search for studies on resource use (costs), health outcomes, and cost-effectiveness of interventions for incontinence-associated dermatitis was conducted. Screening, data extraction, and initial quality assessment were conducted independently by two reviewers, with disagreements/queries regarding quality settled through consensus with the larger team. Quality evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist and results narratively arranged. FINDINGS: Seventeen studies (10 for prevention, one for treatment and six for both prevention and treatment) included. All studies measured resource use from a healthcare provider perspective; 14 quantified resources in monetary terms. Considerable variation existed in the resource use data primarily due to differences in the type of resources counted, selected time horizons, valuation methods, and reporting approaches. Ten studies provided evidence of their intervention to be cost saving (or at least cost avoiding). Five studies on barrier products provided evidence to be cost saving: three for prevention, one for treatment, and one for both prevention and treatment. Two studies of cleanser and barrier products provided evidence to be cost saving for the prevention and treatment of incontinence-associated dermatitis. One study found a cleanser to be a cost saving preventative intervention. One bowel management system was found t