The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation.

BACKGROUND AND PURPOSE: Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. MATERIAL AND METHODS: For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. RESULTS: The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p < .001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 GyRBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p < .001), 20.1% (p < .001) and 29.9% (p < .001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans. CONCLUSIONS: We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.

Neuropsychological functioning in childhood cancer survivors following cranial radiotherapy - results from a long-term follow-up clinic.

Treatment of malignant childhood posterior fossa tumors (CPFT) often includes surgical resection and craniospinal radiotherapy (CSI). Nasopharyngeal tumors in childhood (CNPHT) are often treated with surgery and radiotherapy (RT), leading to incidental brain irradiation. RT to the developing brain is associated with risks for cognitive impairments. We studied cognitive functioning, health-related quality of life (HRQOL), fatigue, and psychological distress, in adult survivors of CPFT and CNPHT, representing two groups, which had received high and low radiation dose-exposure to the brain, respectively. Cognitive tests were used to compare CPFT (n = 12) and CNPHT (n = 7) survivors to matched healthy controls (n = 28). HRQOL data was compared to the general population (GP) (n = 1415-1459). Average follow-up was 23 (CPFT) and 19 years (CNPHT). CPFT survivors had significant deficits in all cognitive domains. CNPHT survivors showed results below the control group but differed statistically only on one executive test. HRQOL-ratings indicated that both groups had similar self-reported cognitive problems. CPFT survivors reported more emotional problems and fatigue. Anxiety was seen in both CPFT and CNPHT survivors. This study confirmed long-term cognitive sequelae after RT in adult survivors of CPFT,and possible RT-induced cognitive deficits in adult CNPHT survivors.

Referral of patients with cancer to palliative care: Attitudes, practices and work-related experiences among Swedish physicians.

OBJECTIVE: This study aimed to explore the attitudes, practices and work-related experiences among Swedish physicians regarding the referral process, integration and transition between oncology care and palliative care (PC). METHODS: A cross-sectional online survey was performed with a study-specific questionnaire in 2016-2017 in south-eastern Sweden. Physicians working with cancer patients within surgical specialties, medical specialties and paediatric oncology participated. RESULTS: The vast majority of the 130 participating physicians (99.2%) stated that PC was beneficial for the patient and were positive about early integration of PC (65.5%). Still, only 27.6% of the participants introduced PC at an early stage of non-curable disease. However, paediatric oncologists had a very early introduction of PC in comparison with medical specialties (p = 0.004). Almost 90% of the study population said they wanted to know that the patient had been taken care of by another care facility. CONCLUSIONS: Despite the physicians' positive attitude towards early integration and referral to PC, they often acted late in the disease trajectory. This late approach can reduce the patient's opportunity of improving quality of life during severe circumstances. There is a need for in-depth knowledge of the physicians' challenges in order to bridge the gap between intentions and actions.

An analytical approach to aggregate patient inflows to a simulation model over the radiotherapy process.

BACKGROUND: In meeting input data requirements for a system dynamics (SD) model simulating the radiotherapy (RT) process, the number of patient care pathways (RT workflows) needs to be kept low to simplify the model without affecting the overall performance. A large RT department can have more than 100 workflows, which results in a complex model structure if each is to be handled separately. Here we investigated effects on model performance by reducing the number of workflows for a model of the preparatory steps of the RT process. METHODS: We created a SD model sub-structure capturing the preparatory RT process. Real data for patients treated in 2015-2016 at a modern RT department in Sweden were used. RT workflow similarity was quantified by averaged pairwise utilization rate differences (%) and the size of corresponding correlation coefficients (r). Grouping of RT workflows was determined using two accepted strategies (80/20 Pareto rule; merging all data into one group) and a customized algorithm with r≥0.75:0.05:0.95 as criteria for group inclusion by two strategies (A1 and A2). Number of waiting patients for each grouping strategy were compared to the reference of all workflows handled separately. RESULTS: There were 128 RT workflows for 3209 patients during the studied period. The 80/20 Pareto rule resulted in 14/8/21 groups for curative/palliative/disregarding treatment intent. Correspondingly, A1 and A2 resulted in 7-40/≤4-36/7-82 groups depending on r cutoff. Results for the Pareto rule and A2 at r≥85 were comparable to the reference. CONCLUSIONS: The performance of a simulation model over the RT process will depend on the grouping strategy of patient input data. Either the Pareto rule or the grouping of patients by resource use can be expected to better reflect overall departmental effects to various changes than when merging all data into one group. Our proposed approach to identify groups based on similarity in resource use can potentially be used in any setting with variable incoming flows of objects which go through a multi-step process comparable to RT where the aim is to reduce the complexity of associated model structures without compromising with overall performance.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Evaluation of quality of care in relation to health-related quality of life of patients diagnosed with brain tumor: a novel clinic for proton beam therapy.

PURPOSE: Patients with brain tumors constitute a vulnerable group, and it is important that they receive the highest quality of care (QoC). The study aim was to describe the perceptions of QoC and its association with health-related quality of life in brain tumor patients undergoing proton beam therapy in a newly established clinic. METHOD: Data were collected at the start of treatment and after 3 and 6 weeks. Adult patients (≥ 18 years old) with brain tumors (n = 186) completed two self-administered questionnaires: a modified Quality from the Patients' Perspective, which measures perceived reality and subjective importance of care, and the EORTC QLQ-C30. Data were analyzed using parametric and non-parametric statistical tests. RESULTS: The perceived QoC was highest for treatment information and lowest for dietician and smoking information, whereas interaction with doctors and nurses was rated as the most important aspect of quality of care. Subjective importance ratings were significantly higher than perceived reality ratings for 60% of items. A better global health was moderately correlated with a higher perceived support for fatigue. CONCLUSIONS: A need for quality improvement was identified for several aspects of patient care. Greater symptom distress during the treatment period led to greater perceived importance of symptom support. Ensuring QoC is complex and collaboration with other health care professionals is essential. RELEVANCE TO CLINICAL PRACTICE: The clinic could improve QoC regarding information about possible symptoms, adjust care according to patient perceptions of importance, and involve patients in care decisions.

Evaluating the implementation and use of the regional cancer plan in Western Sweden through concept mapping.

QUALITY PROBLEM OR ISSUE: Within healthcare, policy documents are often used to strategically standardize, streamline or change how general health issues are managed for a specific patient group or treatment. Despite significant effort in developing policy and strategic planning documents, these may not have the intended impact and their value has long been questioned by practitioners. CHOICE OF SOLUTION: To identify barriers and affordances for the implementation and use of a strategic plan for cancer care in the Western Sweden Healthcare Region, we used Concept Mapping; a participatory mixed method approach to inquiry consisting of both qualitative and quantitative tasks intended to elicit and integrate the diverse perspectives of multiple stakeholders. IMPLEMENTATION: The study was carried out between April and October 2017 and consisted of several sequential data collection steps: idea generation, sorting and rating ideas for importance and feasibility. Stakeholders from different levels and professions in cancercare participated, but the number varied in the separate steps of data collection: idea generation (n = 112), sorting (n = 16) and rating (n = 38). EVALUATION: A concept map visualized seven areas that stakeholders throughout the cancer-care process considered necessary to address in order to enable the implementation of the plan. Skills provision was considered the most important cluster but also rated as least feasible. A consistent theme emerged that information, or lack thereof, might be a barrier for the plan being put into action to a greater extent in the cancer-care units. Nine actionable ideas rated highly on both importance and feasibility were presented as a go-zone. LESSONS LEARNED: Our results suggest that efforts might be better spent on ensuring information about and accessibility to strategic documents throughout the organization, rather than frequently updating them or producing new ones. Having sufficient skills provision seems to be the prerequisite for successful implementation.

A novel mouse model of radiation-induced cancer survivorship diseases of the gut.

A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1.5 cm of the colorectum using a linear accelerator. Each mouse received 6 or 8 Gy, two times daily in 12-h intervals in two, three, or four fractions. Acute cell death was examined at 4.5 h postirradiation and histological changes at 6 wk postirradiation. Another group was given four fractions of 8 Gy and followed over time for development of visible symptoms. Irradiation caused immediate cell death, mainly limited to the colorectum. At 6 wk postirradiation, several crypts displayed signs of radiation-induced degeneration. The degenerating crypts were seen alongside crypts that appeared perfectly healthy. Crypt survival was reduced after the fourth fraction regardless of dose, whereas the number of macrophages increased. Angiogenesis was induced, likely as a compensatory mechanism for hypoxia. Four months postirradiation, mice began to show radiation-induced symptoms, and histological examination revealed an extensive crypt loss and fibrosis. Our model is uniquely suitable for studying the long-term trajectory and underlying mechanisms of radiation-induced gastrointestinal injury.NEW & NOTEWORTHY A novel mouse model for studying the long-term trajectory of radiation-induced gut injury. The method allows for the use of high doses and multiple fractions, with minor impact on animal health for at least 3 mo. Crypt loss and a slow progression of fibrosis is observed. Crypt degeneration is a process restricted to isolated crypts. Crypt degeneration is presented as a convenient proxy endpoint for long-term radiation-induced gut injury.

Use of PET/CT instead of CT-only when planning for radiation therapy does not notably increase life years lost in children being treated for cancer.

BACKGROUND: PET/CT may be more helpful than CT alone for radiation therapy planning, but the added risk due to higher doses of ionizing radiation is unknown. OBJECTIVE: To estimate the risk of cancer induction and mortality attributable to the [F-18]2-fluoro-2-deoxyglucose (FDG) PET and CT scans used for radiation therapy planning in children with cancer, and compare to the risks attributable to the cancer treatment. MATERIALS AND METHODS: Organ doses and effective doses were estimated for 40 children (2-18 years old) who had been scanned using PET/CT as part of radiation therapy planning. The risk of inducing secondary cancer was estimated using the models in BEIR VII. The prognosis of an induced cancer was taken into account and the reduction in life expectancy, in terms of life years lost, was estimated for the diagnostics and compared to the life years lost attributable to the therapy. Multivariate linear regression was performed to find predictors for a high contribution to life years lost from the radiation therapy planning diagnostics. RESULTS: The mean contribution from PET to the effective dose from one PET/CT scan was 24% (range: 7-64%). The average proportion of life years lost attributable to the nuclear medicine dose component from one PET/CT scan was 15% (range: 3-41%). The ratio of life years lost from the radiation therapy planning PET/CT scans and that of the cancer treatment was on average 0.02 (range: 0.01-0.09). Female gender was associated with increased life years lost from the scans (P < 0.001). CONCLUSION: Using FDG-PET/CT instead of CT only when defining the target volumes for radiation therapy of children with cancer does not notably increase the number of life years lost attributable to diagnostic examinations.

No clinically relevant effect on cognitive outcomes after low-dose radiation to the infant brain: a population-based cohort study in Sweden.

UNLABELLED: While the detrimental effects of cranial radiotherapy on the developing brain are well known, the effects on cognitive performance of low doses of ionizing radiation is less studied. We performed a population-based cohort study to determine whether low doses of ionizing radiation to the brain in infancy affects cognitive function later in life. Further we hypothesized that the dose to the hippocampus predicts cognitive late side effects better than the anterior or the posterior brain doses. MATERIAL AND METHODS: During 1950-1960 3860 boys were treated with radiation in Sweden for cutaneous hemangiomas before the age of 18 months. Of these, 3030 were analyzed for military test scores at the age of 18 years and 2559 for the highest obtained educational level. RESULTS: Logical, spatial and technical test scores were not affected by increasing irradiation doses. The verbal test scores displayed a significant trend for decreasing scores with increasing doses to the hippocampus (p = 0.005). However, the absolute mean difference between the zero dose and the highest dose category (median 680 mGy) was very small, only 0.64 stanine points, and the significance was dependent on the highest dose category, containing few subjects. The educational level was not affected by brain irradiation. Overall, the hippocampal dose was a better predictor of late cognitive side effects than the doses to the anterior or the posterior brain. In conclusion, there was no decrease in logical, spatial and technical verbal or global test scores after ionizing radiation doses up to 250 mGy, but a subtle decrease in verbal test scores if the highest dose category was included (median 680 mGy). However, the clinical relevance of this decline in the highest dose group is questionable, since we could not find any effect on the highest obtained educational level.

Optimizing the radiation therapy dose prescription for pediatric medulloblastoma: minimizing the life years lost attributable to failure to control the disease and late complication risk.

BACKGROUND: A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. METHODS: Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton therapy; 3) risk-adaptive photon treatment lowering the dose to part of the craniospinal (CS) target volume situated close to critical risk organs. RESULTS: Late toxicity is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th thoracic vertebrae (Th1-Th10), and 36 Gy to the remaining CS volume, estimated a LYL reduction of 0.90 years (95% CI -0.18-2.41 years). Proton therapy with 36 Gy to the whole CS volume was associated with significantly fewer LYL compared to the risk-adapted photon strategies, with a mean LYL difference of 0.50 years (95% CI 0.25-2.60 years). CONCLUSIONS: Optimization of RT prescription strategies considering both late complications and the risk of recurrence, an all-cause mortality dose painting approach, was demonstrated. The risk-adapted techniques compared favorably to the standard, and although in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk-adapted strategies.

Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma.

Background and Purpose: Hippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT. Materials and Methods: HS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation. Results: The median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region. Conclusions: A substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region.

Pituitary disease mortality: is it fiction?

During the last 20 years a tremendous improvement in the care of patients with pituitary tumors and of hypopituitarism has been achieved. If we resolve most of the possible causes of the increased cardiovascular disease and stroke mortality a normal survival is expected in these patients. Recently, a large population based study showed a decline in the risk of non-fatal stroke and of non-fatal cardiac events in GH deficient patients. This improvement was achieved by complete hormone replacement, including long term GH replacement, together with prescription of cardio protective drugs. If we follow the latest achievements in pituitary imaging, surgery techniques, hormone substitutions, cardio protective medications, we would expect a normal longevity in these patients. This review will focus on; (1) pituitary insufficiencies and hormone substitutions, (2) modes of cranial radiotherapy, and (3) new techniques in the surgery of a pituitary adenoma.

Automated data extraction tool (DET) for external applications in radiotherapy.

Oncological Information Systems (OIS) manage information in radiotherapy (RT) departments. Due to database structure limitations, stored information can rarely be directly used except for vendor-specific purposes. Our aim is to enable the use of such data in various external applications by creating a tool for automatic data extraction, cleaning and formatting. METHODS AND MATERIALS: We used OIS data from a nine-linac RT department in Sweden (70 weeks, 2015-16). Extracted data included patients' referrals and appointments with details for RT sub-tasks. The data extraction tool to prepare the data for external use was built in C# programming language. It used excel-automation queries to remove unassigned/duplicated values, substitute missing data and perform application-specific calculations. Descriptive statistics were used to verify the output with the manually prepared dataset from the corresponding time period. RESULTS: From the initial raw data, 2030 (51 %)/907 (23 %) patients had known curative and palliative treatment intent for 84 different cancer diagnoses. After removal of incomplete entries, 373 (10 %) patients had unknown treatment intents which were substituted based on the known curative/palliative ratio. Automatically- and manuallyprepared datasets differed < 1 % for Mould, Treatment planning, Quality assurance and ± 5 % for Fractions and Magnetic resonance imaging with overestimations in 80/140 (57 %) entries by the tool. CONCLUSION: We successfully implemented a software tool to prepare ready-to-use OIS datasets for external applications. Our evaluations showed overall results close to the manually-prepared dataset. The time taken to prepare the dataset using our automated strategy can reduce the time for manual preparation from weeks to seconds.

Life years lost--comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale.

BACKGROUND: The authors developed a framework for estimating and comparing the risks of various long-term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach, and thyroid cancer; heart failure, and myocardial infarction were derived from large published clinical series. Combined with age-specific and sex-specific hazards in the US general population, the dose-response analysis yielded excess hazards of complications for a cancer survivor as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication for 3-dimensional conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction, and stomach cancer. The estimates of breast or thyroid cancer incidence were higher than those for lung and stomach cancer incidence, but LYL were lower because of the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years for IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty, but including prognosis and attained age at an event to obtain the more informative LYL estimate added relatively little to this uncertainty.

Insights Gained From a Re-analysis of Five Improvement Cases in Healthcare Integrating System Dynamics Into Action Research.

BACKGROUND: Healthcare is complex with multi-professional staff and a variety of patient care pathways. Time pressure and minimal margins for errors, as well as tension between hierarchical power and the power of the professions, make it challenging to implement new policies or procedures. This paper explores five improvement cases in healthcare integrating system dynamics (SD) into action research (AR), aiming to identify methodological aspects of how this integration supported multi-professional groups to discover workable solutions to work-related challenges. METHODS: This re-analysis was conducted by a multi-disciplinary research group using an iterative abductive approach applying qualitative analysis to structure and understand the empirical material. Frameworks for consultancy assignments/client projects were used to identify case project stages (workflow steps) and socio-analytical questions were used to bridge between the AR and SD perspectives. RESULTS: All studied cases began with an extensive AR-inspired inventory of problems/objectives and ended with an SD-facilitated experimental phase where mutually agreed solutions were tested in silico. Time was primarily divided between facilitated group discussions during meetings and modelling work between meetings. Work principles ensured that the voice of each participant was heard, inspired engagement, interaction, and exploratory mutual learning activities. There was an overall pattern of two major divergent and convergent phases, as each group moved towards a mutually developed point of reference for their problem/objective and solution, a case-specific multi-professional knowledge repository. CONCLUSION: By integrating SD into AR, more favourable outcomes for the client organization may be achieved than when applying either approach in isolation. We found that SD provided a platform that facilitated experiential learning in the AR process. The identified results were calibrated to local needs and circumstances, and compared to traditional top-down implementation for change processes, improved the likelihood of sustained actualisation.

Designing and Implementing a Population-based Organised Prostate Cancer Testing Programme.

BACKGROUND: European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT). OBJECTIVE: To report the process for designing and implementing OPT programmes. DESIGN, SETTING, AND PARTICIPANTS: Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded. RESULTS AND LIMITATIONS: Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15 ng/ml/cm3 are referred for a prostate biopsy. Test results are registered for quality control and research. By June 2021, a total of 16 515 men were invited, of whom 6309 (38%) participated; 147 had an MRI scan and 39 underwent prostate biopsy. The OPT framework, algorithm, and diagnostic pathways have been working well. CONCLUSIONS: We designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa. PATIENT SUMMARY: We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.

Fatigue in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Prospective Study of Patient-Reported Outcomes and Their Association With Radiation Dose to the Cerebellum.

Purpose: Although fatigue is a known side effect in patients with head and neck cancer (HNC) receiving radiation therapy, knowledge regarding long-term fatigue and dose-response relationships to organs at risk is scarce. The aim of this prospective study was to analyze patient-reported fatigue in patients with HNC receiving radiation therapy and to explore any possible association with organ-at-risk doses. Methods and Materials: Patients with HNC referred for curative radiation therapy were eligible for inclusion in the study. To assess patient-reported fatigue, quality of life questionnaires (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-FA12) were distributed before treatment and 1, 3, 6, 12, 24, and 60 months after the start of treatment. Mean dose (Dmean) and near maximum dose (D2%) of the cerebellum and brain stem were evaluated in relation to baseline-adjusted fatigue scores at 3 months. Results: One hundred twenty-six patients treated with intensity modulated radiation therapy between 2008 and 2010 were available for final analysis. Female sex and age <60 years were associated with higher fatigue at baseline, whereas patients also treated with chemotherapy had reduced physical and emotional fatigue at 6 months. Physical fatigue (QLQ-FA12 scale) increased from baseline up to 3 months (29 vs 59; P < .0001) but showed no difference compared with baseline from 1 to 5 years. Emotional fatigue was significantly lower at 5 years compared with baseline (14 vs 28; P < .0001). Patients with cerebellum Dmean > 3.5 Gy had higher mean physical fatigue scores at 3 months (38 vs 27; P = .036). Conclusions: Although there is a significant increase in fatigue scores for patients with HNC up to 1 year after radiation therapy, this study showed a return to baseline levels at 5 years. A possible association was found between physical fatigue and a higher mean dose to the cerebellum.

Effectiveness of tobacco cessation interventions for different groups of tobacco users in Sweden: a study protocol for a national prospective cohort study.

INTRODUCTION: Tobacco is still one of the single most important risk factors among the lifestyle habits that cause morbidity and mortality in humans. Furthermore, tobacco has a heavy social gradient, as the consequences are even worse among disadvantaged and vulnerable groups. To reduce tobacco-related inequity in health, those most in need should be offered the most effective tobacco cessation intervention. The aim of this study is to facilitate and improve the evaluation of already implemented national tobacco cessation efforts, focusing on 10 disadvantaged and vulnerable groups of tobacco users. METHODS AND ANALYSIS: This is a prospective cohort study. Data will be collected by established tobacco cessation counsellors in Sweden. The study includes adult tobacco or e-cigarette users, including disadvantaged and vulnerable patients, receiving in-person interventions for tobacco or e-cigarette cessation (smoking, snus and/or e-cigarettes). Patient inclusion was initiated in April 2020. For data analyses patients will be sorted into vulnerable groups based on risk factors and compared with tobacco users without the risk factor in question.The primary outcome is continuous successful quitting after 6 months, measured by self-reporting. Secondary outcomes include abstinence at the end of the treatment programme, which could be from minutes over days to weeks, 14-day point prevalence after 6 months, and patient satisfaction with the intervention. Effectiveness of successful quitting will be examined by comparing vulnerable with non-vulnerable patients using a mixed-effect logistic regression model adjusting for potential prognostic factors and known confounders. ETHICS AND DISSEMINATION: The project will follow the guidelines from the Swedish Data Protection Authority and have been approved by the Swedish Ethical Review Authority before patient inclusion (Dnr: 2019-02221). Only patients providing written informed consent will be included. Both positive and negative results will be published in scientific peer-reviewed journals and presented at national and international conferences. Information will be provided through media available to the public, politicians, healthcare providers and planners as these are all important stakeholders. TRIAL REGISTRATION NUMBER: NCT04819152.