Coming together as a whole: lessons from connecting across sectors, cultures, and contexts to elevate efforts for planetary health.

BACKGROUND: Addressing complex and interconnected ecological, social, and health issues necessitates upstream, solutions-oriented, and whole-systems thinking. Specifically, exploring what it means to live in reciprocity with the planet and all living systems, now and for generations to come, can have a crucial role in advancing planetary health. METHODS: In this presentation, we show findings from four gatherings that we co-designed and co-hosted to connect communities, lands, waters, climate, and health. We draw lessons from two events in the Cowichan watershed (co-hosted by Cowichan Tribes) and the Stellako and Nechako watersheds (co-hosted by Stellat'en First Nation) that were co-designed with the ECHO Network. These gatherings brought together youth, Indigenous leaders, researchers, and health, community, and environmental decision-makers across British Columbia to learn how to address connected health, environmental, and community concerns. We supplement these findings with insights from two co-hosted conversations, that connected five continents and more than 40 countries, each enabling 24 h of continuous dialogue on the theme of working together for a healthy, just, and sustainable planet. FINDINGS: Gatherings took place between Oct 12, 2022, and Dec 1, 2023. These gatherings each provided lessons about how Indigenous-led, integrative approaches that connect the health of people to lands, waters, and ecosystems can elevate and enhance our work and scholarship to address ecological, social, and health issues. Specifically, initiatives co-designed in this way help overcome challenges that arise when addressing boundary-crossing, intersectional and intersectoral issues at the nexus of climate, public health, and planetary health. Our findings include insights into strengthening research and public health capacity for integrative approaches to complex issues that are relevant to place-based contexts and have implications and applications for planetary health. INTERPRETATION: Our presentation summarises how these gatherings-each of which were fuelled by a sense of love for the planet, each other, and future generations-have progressed intersectoral, intergenerational, boundary-crossing, and transformative approaches to planetary health. These insights help guide future directions for planetary health research, practice, and policy. FUNDING: The Canadian Institute of Health Research Environment (IP4150712), Michael Smith Health Research BC (RA-2022-2872), and Vancouver Foundation (FOI19-1781).

Promoting community health and climate justice co-benefits: insights from a rural and remote island climate planning process.

Climate change is an environmental crisis, a health crisis, a socio-political and an economic crisis that illuminates the ways in which our human-environment relationships are arriving at crucial tipping points. Through these relational axes, social structures, and institutional practices, patterns of inequity are produced, wherein climate change disproportionately impacts several priority populations, including rural and remote communities. To make evidence-based change, it is important that engagements with climate change are informed by data that convey the nuance of various living realities and forms of knowledge; decisions are rooted in the social, structural, and ecological determinants of health; and an intersectional lens informs the research to action cycle. Our team applied theory- and equity-driven conceptualizations of data to our work with the community on Cortes Island-a remote island in the northern end of the Salish Sea in British Columbia, Canada-to aid their climate change adaptation and mitigation planning. This work was completed in five iterative stages which were informed by community-identified needs and preferences, including: An environmental scan, informal scoping interviews, attending a community forum, a scoping review, and co-development of questions for a community survey to guide the development of the Island's climate change adaptation and mitigation plan. Through this community-led collaboration we learned about the importance of ground truthing data inaccuracies and quantitative data gaps through community consultation; shifting planning focus from deficit to strengths- and asset-based engagement; responding to the needs of the community when working collaboratively across academic and community contexts; and, foregrounding the importance of, and relationship to, place when doing community engagement work. This suite of practices illuminates the integrative solution-oriented thinking needed to address complex and intersecting issues of climate change and community health.

Measuring negative emotional responses to climate change among young people in survey research: A systematic review.

BACKGROUND: Climate change is a threat to the mental and emotional wellbeing of all humans, but young people are particularly vulnerable. Emerging evidence has found that young people's awareness of climate change and the danger it poses to the planet can lead to negative emotions. To increase our understanding about this, survey instruments are needed that measure the negative emotions young people experience about climate change. RESEARCH QUESTIONS: (1) What survey instruments are used to measure negative emotional responses to climate change in young people? (2) Do survey instruments measuring young people's negative emotional responses to climate change have evidence of reliability and validity? (3) What factors are associated with young people's negative emotional responses to climate change? METHODS: A systematic review was conducted by searching seven academic databases on November 30, 2021, with an update on March 31, 2022. The search strategy was structured to capture three elements through various keywords and search terms: (1) negative emotions, (2) climate change, and (3) surveys. RESULTS: A total of 43 manuscripts met the study inclusion criteria. Among the 43 manuscripts, 28% focused specifically on young people, while the other studies included young people in the sample but did not focus exclusively on this population. The number of studies using surveys to examine negative emotional responses to climate change among young people has increased substantially since 2020. Survey instruments that examined worry or concern about climate change were the most common. CONCLUSION: Despite growing interest in climate change emotions among young people, there is a lack of research on the validity of measures of such emotions. Further efforts to develop survey instruments geared to operationalize the emotions that young people are experiencing in relation to climate change are needed.

Validation of prediction models for radiation-induced late rectal bleeding: Evidence from a large pooled population of prostate cancer patients.

PURPOSE: To validate published models for the risk estimate of grade ≥ 1 (G1+), grade ≥ 2 (G2+) and grade = 3 (G3) late rectal bleeding (LRB) after radical radiotherapy for prostate cancer in a large pooled population from three prospective trials. MATERIALS AND METHODS: The external validation population included patients from Europe, and Oceanian centres enrolled between 2003 and 2014. Patients received 3DCRT or IMRT at doses between 66-80 Gy. IMRT was administered with conventional or hypofractionated schemes (2.35-2.65 Gy/fr). LRB was prospectively scored using patient-reported questionnaires (LENT/SOMA scale) with a 3-year follow-up. All Normal Tissue Complication Probability (NTCP) models published until 2021 based on the Equivalent Uniform Dose (EUD) from the rectal Dose Volume Histogram (DVH) were considered for validation. Model performance in validation was evaluated through calibration and discrimination. RESULTS: Sixteen NTCP models were tested on data from 1633 patients. G1+ LRB was scored in 465 patients (28.5%), G2+ in 255 patients (15.6%) and G3 in 112 patients (6.8%). The best performances for G2+ and G3 LRB highlighted the importance of the medium-high doses to the rectum (volume parameters n = 0.24 and n = 0.18, respectively). Good performance was seen for models of severe LRB. Moreover, a multivariate model with two clinical factors found the best calibration slope. CONCLUSION: Five published NTCP models developed on non-contemporary cohorts were able to predict a relative increase in the toxicity response in a more recent validation population. Compared to QUANTEC findings, dosimetric results pointed toward mid-high doses of rectal DVH. The external validation cohort confirmed abdominal surgery and cardiovascular diseases as risk factors.

On the possibility of decolonising planetary health: exploring new geographies for collaboration.

Decolonial planetary health aspires to centre the diversity and importance of Indigenous thought and stewardship. In this Viewpoint, we explore research in planetary health across holistic worldviews and western scientific approaches. We base our examination of decolonising interventions in planetary health by exploring how global trajectories play out in British Columbia, Canada. A central part of this analysis is highlighting intercultural thinking to promote an anti-colonial, anti-racist, and reciprocal approach to climate change and global health inequities across geographical space and within planetary health discourse. Our perspective encompasses an asset-based examination, which focuses on the Indigenous scholarship in planetary health that is already underway and considers how rigorous engagement with epistemic and geographical diversity can strengthen and advance planetary health. This is a place-based response to planetary health, as British Columbia experiences climate catastrophes that are impacting whole communities, cutting through major transportation systems, disrupting supply chains, and creating a further burden on public health agencies and authorities that are spread thin by COVID-19 response. We argue for a progressive acknowledgment of decolonising work that is pushing research and practice in planetary health forward.

Measuring negative emotional responses to climate change among young people in survey research: a systematic review protocol.

INTRODUCTION: Many young people report experiencing negative emotional responses to their awareness of climate change and the threats it poses to their future. With that, an increasing number of survey instruments have been developed to examine young people's negative emotional responses to their awareness of climate change. This report describes a protocol for a systematic review that aims to identify, synthesise and critically appraise how negative emotional responses to climate change among young people have been measured in survey research. The research questions addressed in this review are: (1) How has negative emotional responses to climate change been defined and measured among young people? (2) How do survey instruments measuring young people's negative emotional responses to climate change vary in terms of reliability and validity? (3) What factors are associated with negative emotional responses to climate change among young people? METHODS AND ANALYSIS: Seven academic databases (CINAHL, ERIC, MEDLINE, PsycINFO, Web of Science, Scopus, and Environment Complete) will be searched to retrieve studies published between 1 January 2006 and 31 March 2022 and published in English. Studies including survey instruments that measure negative emotional responses among young people (aged 10-24 years) will be eligible for inclusion. Targeted journals will be hand-searched. This review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systematic reviews. The methodological quality, in terms of reliability and validity, of the included studies will be assessed using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist for risk of bias of patient-reported outcome measures. To rate the quality of the instruments, we will use a modified Grading of Recommendations, Assessment, Development and Evaluations technique defined by the COSMIN guidelines. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study. We will disseminate the findings through publication in peer-reviewed journals and presentations. PROSPERO REGISTRATION NUMBER: CRD42022295733.

"Syndemic moral distress": sexual health provider practices in the context of co-occurring, socially produced sexual and mental health epidemics.

BACKGROUND: 'Syndemic' refers to socially produced, intertwined, and co-occurring epidemics. Syndemic theory is increasingly used to understand the population-level relationships between sexual health (including HIV) and mental health (including problematic substance use) epidemics. Syndemic-informed clinical interventions are rare. METHODS: We therefore asked 22 sexual health practitioners from six sexual health clinics in British Columbia, Canada to define the word 'syndemic' and then asked how the theory related to their clinical practice. RESULTS: Responses to syndemic theory ranged widely, with some practitioners providing nuanced and clinically informed definitions, others expressing a vague familiarity with the term, and others still having no prior knowledge of it. Where practitioners acknowledged the relevance of syndemic theory to their practice, they articulated specific ways in which syndemics create moral distress, that is, feeling that the most ethical course of action is different from what they are mandated to do. While some practitioners routinely used open-ended questions to understand the social and economic contexts of patients' sexual health needs, they described an uneasiness at potentially having surfaced concerns that could not be addressed in the sexual health clinic. Many observed persistent social, mental health, and substance use-related needs among their patients, but were unable to find feasible solutions to these issues. CONCLUSIONS: We therefore propose that interventions are needed to support sexual health practitioners in addressing psychosocial health needs that extend beyond their scope of practice, thereby reducing 'syndemic moral distress'.

Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging.

PURPOSE: Hypoxia has been linked to radioresistance. Strategies to safely dose escalate dominant intraprostatic lesions have shown promising results, but further dose escalation to overcome the effects of hypoxia require a novel approach to constrain the dose in normal tissue.to safe levels. In this study, we demonstrate a biologically targeted radiotherapy (BiRT) approach that can utilise multiparametric magnetic resonance imaging (mpMRI) to target hypoxia for favourable treatment outcomes. METHODS: mpMRI-derived tumour biology maps, developed via a radiogenomics study, were used to generate individualised, hypoxia-targeting prostate IMRT plans using an ultra- hypofractionation schedule. The spatial distribution of mpMRI textural features associated with hypoxia-related genetic profiles was used as a surrogate of tumour hypoxia. The effectiveness of the proposed approach was assessed by quantifying the potential benefit of a general focal boost approach on tumour control probability, and also by comparing the dose to organs at risk (OARs) with hypoxia-guided focal dose escalation (DE) plans generated for five patients. RESULTS: Applying an appropriately guided focal boost can greatly mitigate the impact of hypoxia. Statistically significant reductions in rectal and bladder dose were observed for hypoxia-targeting, biologically optimised plans compared to isoeffective focal DE plans. CONCLUSION: Results of this study suggest the use of mpMRI for voxel-level targeting of hypoxia, along with biological optimisation, can provide a mechanism for guiding focal DE that is considerably more efficient than application of a general, dose-based optimisation, focal boost.

The Interplay between Social and Ecological Determinants of Mental Health for Children and Youth in the Climate Crisis.

Children and youth are showing increasing levels of mental health distress due to the climate crisis, characterized by feelings of sadness, guilt, changes in sleep and appetite, difficulty concentrating, solastalgia, and disconnection from land. To gain a deeper understanding of the relationship between climate change and children and youth's mental health, we conducted a rapid review and a thematic analysis of the results in NVivo 12. Our findings show that children and youth experience a plethora of direct and indirect effects from climate change and this impacts their mental wellbeing in diverse and complex ways. Young people also have varied perceptions of climate change based on their social locations and many are dealing with feelings of immense worry and eco-anxiety. The mental health impacts of climate change on children/youth are tied to Social Determinants of Health (SDoH) but also need to be understood in relation to the Ecological Determinants of Health (EDoH). Through an eco-social lens, this paper explores these conceptual issues and uses them to provide a framework for understanding the interplay of social and ecological determinants of mental health for children/youth.

Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials.

Purpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy. Methods and Materials: Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar CT dataset. Voxel- based multiple comparison permutation dose difference testing, Cox regression modeling and LASSO feature selection were used to identify regions where 3D dose-increase was associated with late grade ≥ 2 genitourinary dysuria, incontinence and frequency, and late grade ≥ 1 haematuria. This was externally validated by registering dose distributions from the RT01 (up to n = 388) and CHHiP (up to n = 247) trials onto the same exemplar and repeating the voxel-based tests on each of these data sets. All three datasets were then combined, and the tests repeated. Results: Voxel-based Cox regression and multiple comparison permutation dose difference testing revealed regions where increased dose was correlated with genitourinary toxicity. Increased dose in the vicinity of the membranous and spongy urethra was associated with dysuria for all datasets. Haematuria was similarly correlated with increased dose at the membranous and spongy urethra, for the RADAR, CHHiP, and combined datasets. Some evidence was found for the association between incontinence and increased dose at the internal and external urethral sphincter for RADAR and the internal sphincter alone for the combined dataset. Incontinence was also strongly correlated with dose from posterior oblique beams. Patients with fields extending inferiorly and posteriorly to the CTV, adjacent to the membranous and spongy urethra, were found to experience increased frequency. Conclusions: Anatomically-localized dose-toxicity relationships were determined for late genitourinary symptoms in the urethra and urinary sphincters. Low-intermediate doses to the extraprostatic urethra were associated with risk of late dysuria and haematuria, while dose to the urinary sphincters was associated with incontinence.

Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials.

BACKGROUND AND PURPOSE: This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy. MATERIALS AND METHODS: Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined. RESULTS: Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS). CONCLUSIONS: The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.

Reduced Dose Posterior to Prostate Correlates With Increased PSA Progression in Voxel-Based Analysis of 3 Randomized Phase 3 Trials.

PURPOSE: Reducing margins during treatment planning to decrease dose to healthy organs surrounding the prostate can risk inadequate treatment of subclinical disease. This study aimed to investigate whether lack of dose to subclinical disease is associated with increased disease progression by using high-quality prostate radiation therapy clinical trial data to identify anatomically localized regions where dose variation is associated with prostate-specific antigen progression (PSAP). METHODS AND MATERIALS: Planned dose distributions for 683 patients of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (RADAR) trial were deformably registered onto a single exemplar computed tomography data set. These were divided into high-risk and intermediate-risk subgroups for analysis. Three independent voxel-based statistical tests, using permutation testing, Cox regression modeling, and least absolute shrinkage selection operator feature selection, were applied to identify regions where dose variation was associated with PSAP. Results from the intermediate-risk RADAR subgroup were externally validated by registering dose distributions from the RT01 (n = 388) and Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer Trial (CHHiP) (n = 253) trials onto the same exemplar and repeating the tests on each of these data sets. RESULTS: Voxel-based Cox regression revealed regions where reduced dose was correlated with increased prostate-specific androgen progression. Reduced dose in regions associated with coverage at the posterior prostate, in the immediate periphery of the posterior prostate, and in regions corresponding to the posterior oblique beams or posterior lateral beam boundary, was associated with increased PSAP for RADAR and RT01 patients, but not for CHHiP patients. Reduced dose to the seminal vesicle region was also associated with increased PSAP for RADAR intermediate-risk patients. CONCLUSIONS: Ensuring adequate dose coverage at the posterior prostate and immediately surrounding posterior region (including the seminal vesicles), where aggressive cancer spread may be occurring, may improve tumor control. It is recommended that particular care be taken when defining margins at the prostate posterior, acknowledging the trade-off between quality of life due to rectal dose and the preferences of clinicians and patients.

Rectal and Urethro-Vesical Subregions for Toxicity Prediction After Prostate Cancer Radiation Therapy: Validation of Voxel-Based Models in an Independent Population.

PURPOSE: Recent voxel-based studies have shown that the dose to specific rectal and urethro-vesical subregions is predictive of toxicities after prostate cancer intensity modulated radiation therapy. The objective of this study was to validate the discriminatory power of these subregions with respect to the whole organs in a large independent population. METHODS AND MATERIALS: The validation cohort consisted of 450 patients from the TROG03.04-RADAR trial treated with 3-dimensional conformal radiation therapy at 66 to 74 Gy. Previous voxel-based analyses identified an inferoanterior rectal subregion as predictive of rectal bleeding and 5 subregions in the urethra and the posterior and superior part of the bladder as predictive of urinary incontinence, dysuria, retention, and hematuria. In the validation cohort, these subregions were segmented in each patient's anatomy. Dose-volume histograms (DVHs) of the whole organs and the 6 subregions were compared bin-wise between patients with and without toxicities. The discriminatory power of DVHs for grade ≥2 toxicity endpoints was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Subregion DVHs were significantly different between patients with and without toxicities for late rectal bleeding (V44-V74), acute urinary incontinence (V68-V72), late dysuria (V56-V68), and late retention (V14-V64). The dose to the rectal subregion and the whole rectum were equally predictive of rectal bleeding (V68; AUC = 0.61). The doses to 3 out of the 5 urethro-vesical subregions were found to be more predictive than the dose to the whole bladder: in the urethra for acute incontinence (V71 AUC = 0.69 vs V71 AUC = 0.66), in the posterior part of the bladder for late dysuria (V65 AUC = 0.66 vs V68 AUC = 0.59), and late retention (V39 AUC = 0.74 vs no significant AUC). CONCLUSIONS: Three subregions located in the urethra and the bladder were successfully validated as more predictive of urinary toxicity than the whole bladder for urinary incontinence, retention, and dysuria. Sparing the posterior part of the bladder in particular in treatment planning may reduce the risk of late urinary retention.

Similarity clustering-based atlas selection for pelvic CT image segmentation.

PURPOSE: To demonstrate selection of a small representative subset of images from a pool of images comprising a potential atlas (PA) pelvic CT set to be used for autosegmentation of a separate target image set. The aim is to balance the need for the atlas set to represent anatomical diversity with the need to minimize resources required to create a high quality atlas set (such as multiobserver delineation), while retaining access to additional information available for the PA image set. METHODS: Preprocessing was performed for image standardization, followed by image registration. Clustering was used to select the subset that provided the best coverage of a target dataset as measured by postregistration image intensity similarities. Tests for clustering robustness were performed including repeated clustering runs using different starting seeds and clustering repeatedly using 90% of the target dataset chosen randomly. Comparisons of coverage of a target set (comprising 711 pelvic CT images) were made for atlas sets of five images (chosen from a PA set of 39 pelvic CT and MR images) (a) at random (averaged over 50 random atlas selections), (b) based solely on image similarities within the PA set (representing prospective atlas development), (c) based on similarities within the PA set and between the PA and target dataset (representing retrospective atlas development). Comparisons were also made to coverage provided by the entire PA set of 39 images. RESULTS: Exemplar selection was highly robust with exemplar selection results being unaffected by choice of starting seed with very occasional change to one of the exemplar choices when the target set was reduced. Coverage of the target set, as measured by best normalized cross-correlation similarity of target images to any exemplar image, provided by five well-selected atlas images (mean = 0.6497) was more similar to coverage provided by the entire PA set (mean = 0.6658) than randomly chosen atlas subsets (mean = 0.5977). This was true both of the mean values and the shape of the distributions. Retrospective selection of atlases (mean = 0.6497) provided a very small improvement over prospective atlas selection (mean = 0.6431). All differences were significant (P < 1.0E-10). CONCLUSIONS: Selection of a small representative image set from one dataset can be utilized to develop an atlas set for either retrospective or prospective autosegmentation of a different target dataset. The coverage provided by such a judiciously selected subset has the potential to facilitate propagation of numerous retrospectively defined structures, utilizing additional information available with multimodal imaging in the atlas set, without the need to create large atlas image sets.

Multi-observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest.

INTRODUCTION: This study quantified inter-observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies. METHODS: Five prostate cancer patient datasets (CT and T2-weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri-rectal space (PRS). MR contours included CTV, trigone, membranous urethra, penile bulb, neurovascular bundle and multiple pelvic floor muscles. Contouring variations were assessed using the intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and multiple additional metrics. RESULTS: Clinical target volume (CT and MR), bladder, rectum and PRS contours showed excellent inter-observer agreement (median ICC = 0.97; 0.99; 1.00; 0.95; 0.90, DSC = 0.83 ± 0.05; 0.88 ± 0.05; 0.93 ± 0.03; 0.81 ± 0.07; 0.80 ± 0.06, respectively). Seminal vesicle contours were more variable (ICC = 0.75, DSC = 0.73 ± 0.14), while colon and bowel bag contoured volumes were consistent (ICC = 0.97; 0.97), but displayed poor overlap (DSC = 0.58 ± 0.22; 0.67 ± 0.21). Smaller MR structures showed significant inter-observer variations, with poor overlap for trigone, membranous urethra, penile bulb, and left and right neurovascular bundles (DSC = 0.44 ± 0.22; 0.41 ± 0.21; 0.66 ± 0.21; 0.16 ± 0.17; 0.15 ± 0.15). Pelvic floor muscles recorded moderate to strong inter-observer agreement (ICC = 0.50-0.97), although large outlier variations were observed. CONCLUSIONS: Inter-observer contouring variation was significant for multiple pelvic structures contoured on MR.

Estimation of Hounsfield unit conversion parameters for pelvic CT images.

Linear scaling is used to convert raw computed tomography (CT) pixel values into Hounsfield units corresponding to different tissue values. Analysis of a benchmarking study, presented here, where the same CT scan was imported into and then exported from multiple radiotherapy treatment planning systems, found inconsistencies in HU scaling parameter values exported along with the images, particularly when images were exported using the Radiation Therapy Oncology Group format. Several methods of estimating conversion parameters, based on estimating pixel values corresponding to air and water within the image, for pelvic CT images from a large multi-centre trial were compared against original Digital Imaging and Communications in Medicine export parameters. In general using the mean of a sample region at the centroid of the bladder to estimate the value of water was more accurate than using the minimum or maximum or a single value at the centroid. Accuracy of methods of air estimation tested were dependent in part on features of the CT scanners and treatment planning systems, making it difficult to pick one method as superior that was independent of scanner and treatment planning system type. Based on the above analysis, methods for estimating air and water were selected for use in performing linear scaling of a set of pelvic CT images prior to their use in an interpatient image registration application. The selected methods were validated against a more recent and homogeneous dataset. Estimation error was found to be much lower within the validation set.

Association between treatment planning and delivery factors and disease progression in prostate cancer radiotherapy: Results from the TROG 03.04 RADAR trial.

BACKGROUND AND PURPOSE: To evaluate the impact of treatment planning and delivery factors on treatment outcome as measured by post-treatment disease progression. MATERIALS AND METHODS: Accruing 813 external beam radiotherapy participants during 2003-2007, the RADAR trial collected a comprehensive range of clinical treatment factor data for each participant. Both the Fine and Gray competing risks modelling and the Kaplan-Meier (KM) analysis were undertaken to determine the impact of these factors on local-composite progression (LCP), with 709 participants available for analysis. RESULTS: Participants with treatments involving 7 or more beams experienced significantly higher incidence of LCP, with a sub-hazard ratio (relative to 3-beam participants) of 3.056 (CI: 1.446-6.458, p < 0.0034). Participants treated with a more rigorous dose calculation algorithm also displayed significantly higher incidence of LCP, with a sub-hazard ratio of 1.686 (CI: 1.334-2.132, p < 0.0001). The KM analysis resulted in the same groups showing a higher incidence of LCP, with log-rank test results of p = 0.0005 and p = 0.0008 respectively. CONCLUSIONS: The RADAR dataset has enabled a successful secondary analysis in which the impact of technical modifications has been assessed, challenging several established hypotheses. Increasingly precise treatments should be complemented with increasing accuracy to avoid potential geometric miss.

Association between measures of treatment quality and disease progression in prostate cancer radiotherapy: An exploratory analysis from the TROG 03.04 RADAR trial.

INTRODUCTION: Quality assurance methods are incorporated into multicentre radiotherapy clinical trials for ensuring consistent application of trial protocol and quantifying treatment uncertainties. The study's purpose was to determine whether post-treatment disease progression is associated with measures of the quality of radiotherapy treatment. METHODS: The TROG 03.04 RADAR trial tested the impact of androgen deprivation on prostate cancer patients receiving dose-escalated external beam radiation therapy. The trial incorporated a plan-review process and Level III dosimetric intercomparison at each centre, from which variables suggestive of treatment quality were collected. Kaplan-Meier statistics and Fine and Gray competing risk modelling were employed to test for associations between quality-related variables and the participant outcome local composite progression. RESULTS: Increased 'dose-difference' at the prostatic apex and at the anterior rectal wall, between planned and measured dose, was associated with reduced progression. Participants whose treatment plans included clinical target volume (CTV) to planning target volume (PTV) margins exceeding protocol requirements also experienced reduced progression. Other quality-related variables, including total accrual from participating centres, measures of target coverage and other variations from protocol, were not significantly associated with progression. CONCLUSIONS: This analysis has revealed the association of several treatment quality factors with disease progression. Increased dose and dose margin coverage in the prostate region can reduce disease progression. Extensive and rigorous monitoring has helped to maximise treatment quality, reducing the incidence of quality-indicator outliers, and thus reduce the chance of observing significant associations with progression rates.

Modeling Urinary Dysfunction After External Beam Radiation Therapy of the Prostate Using Bladder Dose-Surface Maps: Evidence of Spatially Variable Response of the Bladder Surface.

PURPOSE: We assessed the association of the spatial distribution of dose to the bladder surface, described using dose-surface maps, with the risk of urinary dysfunction. METHODS AND MATERIALS: The bladder dose-surface maps of 754 participants from the TROG 03.04-RADAR trial were generated from the volumetric data by virtually cutting the bladder at the sagittal slice, intersecting the bladder center-of-mass through to the bladder posterior and projecting the dose information on a 2-dimensional plane. Pixelwise dose comparisons were performed between patients with and without symptoms (dysuria, hematuria, incontinence, and an International Prostate Symptom Score increase of ≥10 [ΔIPSS10]). The results with and without permutation-based multiple-comparison adjustments are reported. The pixelwise multivariate analysis findings (peak-event model for dysuria, hematuria, and ΔIPSS10; event-count model for incontinence), with adjustments for clinical factors, are also reported. RESULTS: The associations of the spatially specific dose measures to urinary dysfunction were dependent on the presence of specific symptoms. The doses received by the anteroinferior and, to lesser extent, posterosuperior surface of the bladder had the strongest relationship with the incidence of dysuria, hematuria, and ΔIPSS10, both with and without adjustment for clinical factors. For the doses to the posteroinferior region corresponding to the area of the trigone, the only symptom with significance was incontinence. CONCLUSIONS: A spatially variable response of the bladder surface to the dose was found for symptoms of urinary dysfunction. Limiting the dose extending anteriorly might help reduce the risk of urinary dysfunction.