Outcomes of multimodal therapy in a large series of patients with anaplastic thyroid cancer.

BACKGROUND: The role of radiotherapy (RT) in the treatment of patients with anaplastic thyroid cancer (ATC) for local tumor control is critical because mortality often is secondary to complications of tumor volume rather than metastatic disease. Herein, the authors report the long-term outcomes of RT for patients with ATC. METHODS: A total of 104 patients with histologically confirmed ATC were identified who presented to the study institution between 1984 and 2017 and who received curative-intent or postoperative RT. Locoregional progression-free survival (LPFS), overall survival (OS), and distant metastasis-free survival were assessed. RESULTS: The median age of the patients was 63.5 years. The median follow-up was 5.9 months (interquartile range, 2.7-17.0 months) for the entire cohort and 10.6 months (interquartile range, 5.3-40.0 months) for surviving patients. Thirty-one patients (29.8%) had metastatic disease prior to the initiation of RT. Concurrent chemoradiation was administered in 99 patients (95.2%) and 53 patients (51.0%) received trimodal therapy. Systemic therapy included doxorubicin (73.7%), paclitaxel with or without pazopanib (24.3%), and other systemic agents (2.0%). The 1-year OS and LPFS rates were 34.4% and 74.4%, respectively. On multivariate analysis, RT ≥60 Gy was associated with improved LPFS (hazard ratio [HR], 0.135; P = .001) and improved OS (HR, 0.487; P = .004), and trimodal therapy was associated with improved LPFS (HR, 0.060; P = .017). The most commonly observed acute grade 3 adverse events included dermatitis (20%) and mucositis (13%), with no grade 4 subacute or late adverse events noted (adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: RT appears to demonstrate a dose-dependent, persistent LPFS and OS benefit in patients with locally advanced ATC with an acceptable toxicity profile. Aggressive RT should be strongly considered for the treatment of patients with ATC as part of a trimodal treatment approach.

Proton Radiotherapy for Recurrent or Metastatic Head and Neck Cancers with Palliative Quad Shot.

PURPOSE: Some patients with previously treated, unresectable, recurrent or metastatic head and neck malignancies are not amenable to curative-intent treatment. Here, we investigated the quad-shot (RTOG 8502) regimen of hypofractionated proton radiotherapy (RT) in that patient population. MATERIALS AND METHODS: From 2013 to 2015, 26 patients with recurrent or metastatic cancers were treated with palliative proton RT to the head and neck with quad shot (3.7 Gy twice daily for 2 days). Patient characteristics and survival data were reviewed. RESULTS: Seventeen (65%) patients received ≥ 3 quad-shot cycles and 23 (88%) had prior head and neck RT. Overall palliative response was 73% (n = 19). The most common presenting symptom was pain (50%; n = 13), which improved in 85% (n = 22) of all patients. The overall grade-1 acute-toxicity rate was 58% (n = 15), and no acute grade 3 to 5 toxicities were observed. CONCLUSIONS: The proton quad-shot regimen demonstrates favorable palliative response and toxicity profile, even in patients that received prior RT.

Inhibition of non-homologous end joining in Fanconi Anemia cells results in rescue of survival after interstrand crosslinks but sensitization to replication associated double-strand breaks.

When Fanconi Anemia (FA) proteins were depleted in human U2OS cells with integrated DNA repair reporters, we observed decreases in homologous recombination (HR), decreases in mutagenic non-homologous end joining (m-NHEJ) and increases in canonical NHEJ, which was independently confirmed by measuring V(D)J recombination. Furthermore, depletion of FA proteins resulted in reduced HR protein foci and increased NHEJ protein recruitment to replication-associated DSBs, consistent with our observation that the use of canonical NHEJ increases after depletion of FA proteins in cycling cells. FA-depleted cells and FA-mutant cells were exquisitely sensitive to a DNA-PKcs inhibitor (DNA-PKi) after sustaining replication-associated double strand breaks (DSBs). By contrast, after DNA interstrand crosslinks, DNA-PKi resulted in increased survival in FA-deficient cells, implying that NHEJ is contributing to lethality after crosslink repair. Our results suggest FA proteins inhibit NHEJ, since repair intermediates from crosslinks are rendered lethal by NHEJ. The implication is that bone marrow failure in FA could be triggered by naturally occurring DNA crosslinks, and DNA-PK inhibitors would be protective. Since some sporadic cancers have been shown to have deficiencies in the FA-pathway, these tumors should be vulnerable to NHEJ inhibitors with replication stress, but not with crosslinking agents, which could be tested in future clinical trials.

A randomised controlled trial of an intervention to increase the implementation of a healthy canteen policy in Australian primary schools: study protocol.

BACKGROUND: The implementation of healthy school canteen policies has been recommended as a strategy to help prevent unhealthy eating and excessive weight gain. Internationally, research suggests that schools often fail to implement practices consistent with healthy school canteen policies. Without a population wide implementation, the potential benefits of these policies will not be realised. The aim of this trial is to assess the effectiveness of an implementation intervention in increasing school canteen practices consistent with a healthy canteen policy of the New South Wales (NSW), Australia, government known as the 'Fresh Tastes @ School NSW Healthy School Canteen Strategy'. METHODS/DESIGN: The parallel randomised trial will be conducted in 70 primary schools located in the Hunter region of New South Wales, Australia. Schools will be eligible to participate if they are not currently meeting key components of the healthy canteen policy. Schools will be randomly allocated after baseline data collection in a 1:1 ratio to either an intervention or control group using a computerised random number function in Microsoft Excel. Thirty-five schools will be selected to receive a multi-component intervention including implementation support from research staff, staff training, resources, recognition and incentives, consensus and leadership strategies, follow-up support and implementation feedback. The 35 schools allocated to the control group will not receive any intervention support as part of the research trial. The primary outcome measures will be i) the proportion of schools with a canteen menu that does not contain foods or beverages restricted from regular sale ('red' and 'banned' items) and ii) the proportion of schools where healthy canteen items ('green' items) represent the majority (>50%) of products listed on the menu. Outcome data will be collected via a comprehensive menu audit, conducted by dietitians blind to group allocation. Intervention effectiveness will be assessed using logistic regression models adjusting for baseline values. DISCUSSION: The proposed trial will represent a novel contribution to the literature, being the first randomised trial internationally to examine the effectiveness of an intervention to facilitate implementation of a healthy canteen policy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000311752.

Validity of a self-report survey tool measuring the nutrition and physical activity environment of primary schools.

BACKGROUND: Valid tools measuring characteristics of the school environment associated with the physical activity and dietary behaviours of children are needed to accurately evaluate the impact of initiatives to improve school environments. The aim of this study was to assess the validity of Principal self-report of primary school healthy eating and physical activity environments. METHODS: Primary school Principals (n = 42) in New South Wales, Australia were invited to complete a telephone survey of the school environment; the School Environment Assessment Tool - SEAT. Equivalent observational data were collected by pre-service teachers located within the school. The SEAT, involved 65 items that assessed food availability via canteens, vending machines and fundraisers and the presence of physical activity facilities, equipment and organised physical activities. Kappa statistics were used to assess agreement between the two measures. RESULTS: Almost 70% of the survey demonstrated moderate to almost perfect agreement. Substantial agreement was found for 10 of 13 items assessing foods sold for fundraising, 3 of 6 items assessing physical activity facilities of the school, and both items assessing organised physical activities that occurred at recess and lunch and school sport. Limited agreement was found for items assessing foods sold through canteens and access to small screen recreation. CONCLUSIONS: The SEAT provides researchers and policy makers with a valid tool for assessing aspects of the school food and physical activity environment.

Effectiveness of a multi-strategy intervention in increasing the implementation of vegetable and fruit breaks by Australian primary schools: a non-randomized controlled trial.

BACKGROUND: Limited evidence exists describing the effectiveness of strategies in facilitating the implementation of vegetable and fruit programs by schools on a population wide basis. The aim of this study was to examine the effectiveness of a multi-strategy intervention in increasing the population-wide implementation of vegetable and fruit breaks by primary schools and to determine if intervention effectiveness varied by school characteristics. METHODS: A quasi-experimental study was conducted in primary schools in the state of New South Wales, Australia. All primary schools in one region of the state (n = 422) received a multi-strategy intervention. A random sample of schools (n = 406) in the remainder of the state served as comparison schools. The multi-strategy intervention to increase vegetable and fruit breaks involved the development and provision of: program consensus and leadership; staff training; program materials; incentives; follow-up support; and implementation feedback. Comparison schools had access to routine information-based Government support. Data to assess the prevalence of vegetable and fruit breaks were collected by telephone from Principals of the intervention and comparison schools at baseline (2006-2007) and 11 to 15 months following the commencement of the intervention (2009-2010). GEE analysis was used to examine the change in the prevalence of vegetable and fruit breaks in intervention schools compared to comparison schools. RESULTS: At follow-up, prevalence of vegetable and fruit breaks increased significantly in both intervention (50.3% to 82.0%, p < 0.001) and comparison (45.4% to 60.9% p < 0.001) schools. The increase in prevalence in intervention schools was significantly larger than among comparison schools (OR 2.36; 95% CI 1.60-3.49, p <0.001). The effect size was similar between schools regardless of the rurality or socioeconomic status of school location, school size or government or non-government school type. CONCLUSION: The findings suggest that a multi-strategy intervention can significantly increase the implementation of vegetable and fruit breaks by a large number of Australian primary schools.

Process and impact evaluation of the Romp & Chomp obesity prevention intervention in early childhood settings: lessons learned from implementation in preschools and long day care settings.

BACKGROUND: The Romp & Chomp controlled trial, which aimed to prevent obesity in preschool Australian children, was recently found to reduce the prevalence of childhood overweight and obesity and improve children's dietary patterns. The intervention focused on capacity building and policy implementation within various early childhood settings. This paper reports on the process and impact evaluation of this trial and the lessons learned from this complex community intervention. METHODS: Process data was collected throughout and audits capturing nutrition and physical activity-related environments and practices were completed postintervention by directors of Long Day Care (LDC) centers (n = 10) and preschools (n = 41) in intervention and comparison (n = 161 LDC and n = 347 preschool) groups. RESULTS: The environmental audits demonstrated positive impacts in both settings on policy, nutrition, physical activity opportunities, and staff capacity and practices, although results varied across settings and were more substantial in the preschool settings. Important lessons were learned in relation to implementation of such community-based interventions, including the significant barriers to implementing health-promotion interventions in early childhood settings, lack of engagement of for-profit LDC centers in the evaluation, and an inability to attribute direct intervention impacts when the intervention components were delivered as part of a health-promotion package integrated with other programs. CONCLUSIONS: These results provide confidence that obesity prevention interventions in children's settings can be effective; however, significant efforts must be directed toward developing context-specific strategies that invest in policies, capacity building, staff support, and parent engagement. Recognition by funders and reviewers of the difficulties involved in implementing and evaluating such complex interventions is also critical to strengthening the evidence base on the effectiveness of such public health approaches to obesity prevention.

Assessing the intake of obesity-related foods and beverages in young children: comparison of a simple population survey with 24 hr-recall.

BACKGROUND: With an increasing focus on obesity prevention there is a need for simple, valid tools to assess dietary indicators that may be the targets of intervention programs. The objective of this study was to determine the relative validity of previous day dietary intake using a newly developed parent-proxy questionnaire (EPAQ) for two to five year old children. METHODS: A convenience sample of participants (n = 90) recruited through preschools and the community in Geelong, Australia provided dietary data for their child via EPAQ and interviewer-administered 24-hour dietary recall (24 hr-recall). Comparison of mean food and beverage group servings between the EPAQ and 24 hr-recall was conducted and Spearman rank correlations were computed to examine the association between the two methods. RESULTS: Mean servings of food/beverage groups were comparable between methods for all groups except water, and significant correlations were found between the servings of food and beverages using the EPAQ and 24-hr recall methods (ranging from 0.57 to 0.88). CONCLUSION: The EPAQ is a simple and useful population-level tool for estimating the intake of obesity-related foods and beverages in children aged two to five years. When compared with 24-hour recall data, the EPAQ produced an acceptable level of relative validity and this short survey has application for population monitoring and the evaluation of population-based obesity prevention interventions for young children.

Association between the family environment and television viewing in Australian children.

AIM: To describe the time children spend watching television (TV) and to assess associations between TV viewing time, the family environment and weight status. METHODS: Parents reported the amount of time children watched TV/video both for 'the previous school day' and 'usually' and described aspects of the family environment influencing TV access as part of a large cross-sectional study in the Barwon South-western region of Victoria, Australia. Child weight status was based on measured height and weight. All data were collected in 2003/2004. RESULTS: A total of 1926 children aged 4-12 years participated. Parent-reported mean +/- SE TV time for the previous school day was 83 +/- 1.5 min. Children who lived in a family with tight rules governing TV viewing time (22%), or who never watched TV during dinner (33%), or had only one TV in the household (23%) or had no TV in their bedroom (81%) had significantly less TV time than their counterparts. Overweight or obese children had more TV time than healthy weight children 88 +/- 2.9 versus 82 +/- 1.7 min per day (P=0.04). They were also more likely to live in a household where children had a TV in their bedroom than healthy weight children (25% vs. 17%, P<0.001). CONCLUSION: Strategies to reduce TV time should be included as part of broader strategies to prevent childhood obesity. They should include messages to parents about not having a TV in children's bedrooms, encouraging family rules restricting TV viewing, and not having the TV on during dinner.