Impact of a contouring atlas on radiographer inter-observer variation in male pelvis radiotherapy.

PURPOSE/OBJECTIVE: To determine the impact of a MR-based contouring atlas for male pelvis radiotherapy delineation on inter-observer variation to support radiographer led real-time magnetic resonance image guided adaptive radiotherapy (MRgART). MATERIAL/METHODS: Eight RTTs contoured 25 MR images in the Monaco treatment planning system (Monaco 5.40.01), from 5 patients. The prostate, seminal vesicles, bladder, and rectum were delineated before and after the introduction of an atlas developed through multi-disciplinary consensus. Inter-observer contour variations (volume), time to contour and observer contouring confidence were determined at both time-points using a 5-point Likert scale. Descriptive statistics were used to analyse both continuous and categorical variables. Dice similarity coefficient (DSC), Dice-Jaccard coefficient (DJC) and Hausdorff distance were used to calculate similarity between observers. RESULTS: Although variation in volume definition decreased for all structures among all observers post intervention, the change was not statistically significant. DSC and DJC measurements remained consistent following the introduction of the atlas for all observers. The highest similarity was found in the bladder and prostate whilst the lowest was the seminal vesicles. The mean contouring time for all observers was reduced by 50% following the introduction of the atlas (53 to 27 minutes, p=0.01). For all structures across all observers, the mean contouring confidence increased significantly from 2.3 to 3.5 out of 5 (p=0.02). CONCLUSION: Although no significant improvements were observed in contour variation amongst observers, the introduction of the consensus-based contouring atlas improved contouring confidence and speed; key factors for a real-time RTT-led MRgART.

Geometric distortion caused by metallic femoral head prosthesis in prostate cancer imaging on an MR Linac: in-vivo measurements of spatial deformation.

OBJECTIVES: Metallic implants cause artefacts and distortion on MRI. To ensure accurate dose delivery and plan adaptation on an MR Linac, there is a need to evaluate distortion caused. METHODS: Participants were imaged on an MR Linac (Elekta Unity, Elekta AB Stockholm). Three sequences were evaluated. Two vendor supplied (T2W TSE 3D), and one T2W TSE 3D optimized to reduce metal artefact distortions. Images were rigidly registered to CT images by a single observer, using bony anatomy. Three coronal and three axial images were selected, and six paired, adjacent, bony landmarks were identified on each slice. Images bisecting treatment isocentre were included. Difference between landmark coordinates was taken to be measure of distortion. RESULTS: Five observers participated. Thirty six pairs of bony landmarks were identified. Median difference in position of landmarks was ≤3 mm (range 0.3-4.4 mm). One-way analysis of variance (ANOVA) between observer means showed no significant variation between sequences or patients (P = 1.26 in plane, P = 0.11 through plane). Interobserver intra class correlation (ICC) was 0.70 in-plane and 0.78 through-plane. Intra-observer ICC for three observers was 0.76, 0.81, 0.83, showing moderate to good reliability on this small cohort. CONCLUSIONS: This in-vivo feasibility study suggests distortion due to metallic hip prosthesis is not an obstacle for pelvic radiotherapy on an MR Linac. Research on the impact on plan quality is warranted. ADVANCES IN KNOWLEDGE: This work supports feasibility of treating patients with metallic hip prosthesis on an MR Linac.

Feasibility of using a dual isocentre technique for treating cervical cancer on the 1.5 T MR-Linac.

Objective.Patients treated for cervical cancer exhibit large inter and intra-fraction anatomical changes. The Unity MR-Linac (MRL) can image these patients with MR prior to and during treatment which enables daily plan adaptation. However, the MRL has a limited treatment field in the sup/inf direction of 22 cm which can restrict the treatment of patients who require longer treatment fields. Here we explore potential adaptive workflows in combination with a dual isocentre approach, to widen the range of cervix patients that can benefit from this treatment.Approach.Ten cervical cancer patients were retrospectively planned with a dual isocentre technique to deliver 45 Gy in 25 fractions. 5 node-negative and 5 node-positive patients were planned using the EMBRACE II protocol. A 2 cm overlap region between the two isocentres was positioned entirely in the nodal region. A treatment workflow was simulated to account for inter-fraction anatomical change. Isocentre shifts of 3 and 6 mm were applied to investigate the effect of intra-fraction motion.Main results.Dual isocentre adapted plans ensured significantly better coverage than non-adapted (recalculated) plans with a larger benefit seen for the node-negative cases. The difference to the reference plan for the V4275 cGy to the ITV was -0.8 cGy and -8.2 cGy for the adapted and recalculated plans respectively. Movements superiorly did not affect the coverage of the ITV by more than 1%, but shifting it inferiorly caused the ITV coverage on the plan to reduce by ∼2.4% per mm.Significance.A dual isocentre technique for cervical cancer treatments and adaptive workflows have been demonstrated to recover the required plan quality for inter-fraction changes. This illustrates the feasibility of a dual isocentre technique for the MRL.

The impact of an educational tool in cervix image registration across three imaging modalities.

OBJECTIVES: Accurate image registration is vital in cervical cancer where changes in both planning target volume (PTV) and organs at risk (OARs) can make decisions regarding image registration complicated. This work aims to determine the impact of a dedicated educational tool compared with experience gained in MR-guided radiotherapy (MRgRT). METHODS: 10 therapeutic radiographers acted as observers and were split into two groups based on previous experience with MRgRT and Monaco treatment planning system. Three CBCT-CT, three MR-CT and two MR-MR registrations were completed per patient by each observer. Observers recorded translations, time to complete image registration and confidence. Data were collected in two phases; prior to and following the introduction of a cervix registration guide. RESULTS: No statistically significant differences were noted between imaging modalities. Each group was assessed independently pre- and post-education, no statistically significant differences were noted in either CBCT-CT or MR-CT imaging. Group 1 MR-MR imaging showed a statistically significant reduction in interobserver variability (p=0.04), in Group 2, the result was not statistically significant (p=0.06). Statistically significant increases in confidence were seen in all three modalities (p≤0.05). CONCLUSIONS: At The Christie NHS Foundation Trust, radiographers consistently registered images across three different imaging modalities regardless of their previous experience. The implementation of an image registration guide had limited impact on inter- and intraobserver variability. Radiographers' confidence showed statistically significant improvements following the use of the registration manual. ADVANCES IN KNOWLEDGE: This work helps evaluate training methods for novel roles that are developing in MRgRT.

Evaluation of the palliative radiotherapy pathway in a single institute: Can an MR Linac improve efficiency?

BACKGROUND: Palliative radiotherapy (RT) is effectively used to relieve cancer related symptoms. The demand for these services is increasing worldwide. Rapid response clinics have been developed as a means to streamline the palliative RT radiotherapy process and increase efficiency and improve patient experiences. Key components to successful rapid response palliative RT are access to care, streamlined services and innovation. To successfully implement a rapid response RT programme, it is essential to identify gaps between currently provided care and ideal or enhanced care. The aims of this work are to audit the current palliative RT workflow at our institution both prior to and during the coronavirus pandemic. This work reports the impact of covid-19 on rate of palliative RT referrals and proposes a radiographer led, MR guided rapid response workflow to reduce wait times METHODS: A retrospective audit of palliative radiotherapy booking forms was completed over a two yearperiod (2019-2020) to assess the current pathway both prior to and during the covid-19 pandemic. This audit identified patients who had received urgent/emergency spinal RT in the specified timeframe. Further data on these patients was collected using departmental oncology information systems to form a detailed analysis of the pathway and wait times. Data was recorded and analysed using Microsoft Excel. RESULTS: A total of 813 patients met the inclusion criteria for this audit. Data was reported for 2019 and 2020 separately to determine any significant impact caused by the covid-19 pandemic. In 2020 there was an 11.5% increase in referrals for palliative radiotherapy with an equal portion (81%) of total referrals in each year being for single fractions. Timelines from referral to treatment delivery were reported, with those patients receiving same day single fraction RT palliative radiotherapy undergoing further analysis to determine the amount of time spent in the department. Mean wait time for these patients was 5 hours and 20 minutes in 2019 but increased by 20.9% in 2020. CONCLUSIONS: The increasing demand for palliative RT due to rising global cancer rates and extended life expectancy due to advanced systemic treatments may lead to increased wait times. An increase in both referrals and mean wait time was seen during the covid-19 pandemic. Improving efficiency and access to care is essential for this population. The MR Linac could play a role in streamlining palliative RT workflows due to its ability to employ a scan, plan and treat model in a single session. This work forms preliminary support for the development of a trial one stop palliative program on the MR Linac.

Failure to Provide Adequate Palliative Care May Be Medical Neglect.

Doctors are required to notify Child Protective Services (CPS) if parents do not provide appropriate medical care for their children. But criteria for reporting medical neglect are vague. Which treatments properly fall within the realm of shared decision-making in which parents can decide whether to accept doctors' recommendations? Which treatments are so clearly in the child's interest that it would be neglectful to refuse them? When to report medical neglect concerns to CPS may be controversial. It would seem inhumane to allow a child to suffer because of parental refusal to administer proper analgesia. In this ethics rounds, we present a case of an adolescent with chronic pain who is terminally ill. Her parents were not adherent to recommended analgesia regimens. Her palliative care team had to decide whether to report the case to CPS.

Differences in Advance Care Planning and Circumstances of Death for Pediatric Patients Who Do and Do Not Receive Palliative Care Consults: A Single-Center Retrospective Review of All Pediatric Deaths from 2012 to 2016.

Background: Growing evidence suggests that pediatric palliative care (PPC) teams influence the care received by children and young adults with chronic, life-limiting illnesses. Little is known about how PPC involvement affects advance care planning (ACP) and circumstances of death in pediatric populations with a wide range of diagnoses. Objective: To determine the relationship between PPC involvement, ACP, and circumstances of death for pediatric patients. Design: A retrospective chart review of 558 pediatric patients who died between January 1, 2012 and December 31, 2016 was conducted. Descriptive statistics were used to characterize the sample. A multivariable logistic regression was used to obtain associations between PPC involvement and ACP. Setting: Large, multidisciplinary tertiary care center in a rural state. Measurements: Data abstracted for each patient included the following: demographic information, diagnosis, location of primary unit, hospice involvement, goals of care (GOC), code status, Physician Orders for Life-Sustaining Treatment (POLST) completion, and location of death. Results: Patients with PPC involvement were more likely to have had ACP addressed before death. After adjusting for covariates in the model, patients with PPC were more likely to have their GOC documented (odds ratio [OR] = 96.93), completion of POLST (OR = 24.06), do-not-resuscitate code status (OR = 7.71), and hospice involvement at the time of death (OR = 11.70) compared with those who did not receive PPC. Conclusions: Pediatric patients are more likely to have ACP addressed if they have PPC involvement. Patients with chronic complex conditions are most likely to receive palliative care.

Home Extubation in a Neonate.

End-of-life care for many infants involves the withdrawal of mechanical ventilation. Usually this takes place in the hospital environment, but sometimes parents request that their infant dies at home. Facilitating this has significant practical and resource implications and raises both logistical and ethical questions. In this article, we report a neonatal case involving home extubation, explaining the processes involved as well as providing an ethical context.

Does more education cause lower BMI, or do lower-BMI individuals become more educated? Evidence from the National Longitudinal Survey of Youth 1979.

More educated adults have lower average body mass index (BMI). This may be due to selection, if adolescents with lower BMI attain higher levels of education, or it may be due to causation, if higher educational attainment reduces BMI gain in adulthood. We test for selection and causation in the National Longitudinal Survey of Youth 1979, which has followed a representative US cohort from age 14-22 in 1979 through age 47-55 in 2012. Using ordinal logistic regression, we test the selection hypothesis that overweight and obese adolescents were less likely to earn high school diplomas and bachelor's degrees. Then, controlling for selection with individual fixed effects, we estimate the causal effect of degree completion on BMI and obesity status. Among 18-year-old women, but not among men, being overweight or obese predicts lower odds of attaining higher levels of education. At age 47-48, higher education is associated with lower BMI, but 70-90% of the association is due to selection. Net of selection, a bachelor's degree predicts less than a 1 kg reduction in body weight, and a high school credential does not reduce BMI.

Do work and family care histories predict health in older women?

Background: Social and policy changes in the last several decades have increased women's options for combining paid work with family care. We explored whether specific combinations of work and family care over the lifecourse are associated with variations in women's later life health. Methods: We used sequence analysis to group women in the English Longitudinal Study of Ageing according to their work histories and fertility. Using logistic regression, we tested for group differences in later life disability, depressive symptomology and mortality, while controlling for childhood health and socioeconomic position and a range of adult socio-economic circumstances and health behaviours. Results: Women who transitioned from family care to either part-time work after a short break from the labour force, or to full-time work, reported lower odds of having a disability compared with the reference group of women with children who were mostly employed full-time throughout. Women who shifted from family care to part-time work after a long career break had lower odds of mortality than the reference group. Depressive symptoms were not associated with women's work and family care histories. Conclusion: Women's work histories are predictive of their later life disability and mortality. This relationship may be useful in targeting interventions aimed at improving later life health. Further research is necessary to explore the mechanisms linking certain work histories to poorer later life health and to design interventions for those affected.

Relationship between employment histories and frailty trajectories in later life: evidence from the English Longitudinal Study of Ageing.

BACKGROUND: Given the acceleration of population ageing and policy changes to extend working lives, evidence is needed on the ability of older adults to work for longer. To understand more about the health impacts of work, this study examined the relationship between employment histories before retirement and trajectories of frailty thereafter. METHODS: The sample comprised 2765 women and 1621 men from the English Longitudinal Study of Ageing. We used gendered typologies of life-time employment and a frailty index (FI). Multilevel growth curve models were used to predict frailty trajectories by employment histories. RESULTS: Women who had a short break for family care, then did part-time work till 59 years had a lower FI after 60 years than those who undertook full-time work until 59 years. Women who were largely family carers or non-employed throughout adulthood, had higher levels of frailty at 60 years but experienced a slower decline with age. Men who worked full-time but early exited at either 49 or 60 years had a higher FI at 65 years than those who worked full-time up to 65 years. Interaction between employment histories and age indicated that men in full-time work who experienced an early exit at 49 tended to report slower declines. CONCLUSIONS: For women, experiencing distinct periods throughout the lifecourse of either work or family care may be advantageous for lessening frailty risk in later life. For men, leaving paid employment before 65 years seems to be beneficial for decelerating increases in frailty thereafter. Continuous full-time work until retirement age conferred no long-term health benefits.

Obesity and the natural environment across US counties.

OBJECTIVES: We estimated the association between obesity and features of the natural environment. We asked whether the association is mediated by diet or by physical activity. METHODS: Using county-level data from the contiguous United States, we regressed adult obesity prevalence on 9 measures of the natural environment. Our regression model accounted for spatial correlation, and controlled for county demographics and the built environment. We included physical activity and diet (proxied by food purchases) as potential mediators. RESULTS: Obesity was more prevalent in counties that are hot in July or cold in January. To a lesser degree, obesity was more prevalent in counties that are dark in January or rainy (but not snowy) year-round. Other aspects of the natural environment-including wind, trees, waterfront, and hills and mountains-had little or no association with obesity. Nearly all of the association between obesity and the natural environment was mediated by physical activity; none was mediated by diet. CONCLUSIONS: Hot summers and cold winters appear to promote obesity by discouraging physical activity. Attempts to encourage physical activity should compensate for the effects of extreme temperatures.

Rapid CD40-mediated rescue from CD95-induced apoptosis requires TNFR-associated factor-6 and PI3K.

The activation molecule CD40 and the death receptor CD95/Fas play important roles in regulating B cells so that effective antimicrobial immunity occurs without autoimmunity. CD40 signaling increases CD95 expression, sensitizing cells to apoptosis, but sustained CD40 signals rescue B cells from CD95 killing. Here we describe a mechanism of early CD40-mediated rescue from CD95-induced apoptosis in B cells. Maximal rescue was achieved when CD40 signals were given within 1-2 h of initiating CD95 apoptosis. CD40 signaling did not block association of Fas-associated death domain-containing protein with CD95, but decreased CD95-induced activation of caspases 3 and 8. Rapid CD40 rescue did not require NF-kappaB activation and was independent of de novo protein synthesis, but was dependent upon active PI3 K. Signaling via a CD40 mutant that does not bind TNFR-associated factor (TRAF)1, TRAF2, and TRAF3 rescued B cells from CD95-induced apoptosis. TRAF1/2/3-independent rescue was confirmed in B cell lines made deficient in these TRAF molecules by gene targeting. In contrast, CD40 rescue was completely abrogated in TRAF6-deficient B cells, which showed reduced activation of Akt in response to CD40 engagement. These results reveal a new rapid mechanism to balance B cell activation and apoptosis.