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.

Patients' experiences of well-being when being cared for in the intensive care unit-An integrative review.

OBJECTIVE: The aim of this integrative review was to identify facilitators and barriers to patients' well-being when being cared for in an ICU setting, from the perspective of the patients. BACKGROUND: To become critically ill and hospitalised in an ICU is a stressful, chaotic event due to the life-threatening condition itself, as well as therapeutic treatments and the environment. A growing body of evidence has revealed that patients often suffer from physical, psychological and cognitive problems after an ICU stay. Several strategies, such as sedation and pain management, are used to reduce stress and increase well-being during ICU hospitalisation, but the ICU experience nevertheless affects the body and mind. DESIGN; METHODS: Since research exploring patients' sense of well-being in an ICU setting is limited, an integrative review approach was selected. Searches were performed in CINAHL, Medline, Psych Info, Eric and EMBASE. After reviewing 66 studies, 12 studies were included in the integrative review. Thematic analysis was used to analyse the studies. The PRISMA checklist for systematic reviews was used. RESULTS: The results are presented under one main theme, 'Well-being as a multidimensional experience-interwoven in barriers and facilitators' and six sub-themes representing barriers to and facilitators of well-being in an ICU. Barriers identified were physical stressors, emotional stressors, environmental disturbances and insecurity relating to time and space. Facilitators were meeting physical needs and activities that included dimensions of a caring and relational environment. CONCLUSION: Our main findings were that experiences of well-being were multidimensional and included physical, emotional, relational and environmental aspects, and they were more often described through barriers than facilitators of well-being. RELEVANCE FOR CLINICAL PRACTICE: This integrative review has shown that it is necessary to adopt an individual focus on patient well-being in an ICU setting since physical, emotional, relational and environmental stressors might impact each patient differently.

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.

Low Spatial Peak-to-Average Power Ratio Transmission for Improved Energy Efficiency in Massive MIMO Systems.

A significant portion of the operating power of a base station is consumed by power amplifiers (PAs). Much of this power is dissipated in the form of heat, as the overall efficiency of currently deployed PAs is typically very low. This is because the structure of conventional precoding techniques typically results in a relatively high variation in output power at different antennas in the array, and many PAs are operated well below saturation to avoid distortion of the transmitted signals. In this work, we use a realistic model for power consumption in PAs and study the impact of power variation across antennas in the array on the energy efficiency of a massive MIMO downlink system. We introduce a family of linear precoding matrices that allow us to control the spatial peak-to-average power ratio by projecting a fraction of the transmitted power onto the null space of the channel. These precoding matrices preserve the structure of conventional precoders; e.g., they suppress multiuser interference when used together with zeroforcing precoding and bring advantages over these precoders by operating PAs in a more power-efficient region and reducing the total radiated distortion. Our numerical results show that by controlling the power variations between antennas in the array and incorporating the nonlinearity properties of PA into the precoder optimization, significant gains in energy efficiency can be achieved over conventional precoding techniques.

Hermeneutic observational studies: describing a method.

There is a need to develop and use research observations in the clinical field, primarily to gain insight into and assess evidence of what comprises caring in a real-life situation and confirm what is actually taking place. In addition, assessments lead to a new and different understanding of what caring constitutes, thereby enabling the identification of what kind of care is being provided and is required. Such observations also enable the observer to perceive and verbalise caring. There are ongoing discussions, specifically in Nordic countries, on how to use caring science-based observations as a means of collecting and interpreting qualitative data through the application of a hermeneutic approach, which constitutes describing what has been seen and reporting on it by way of ethical obligation. This article contributes to the debate through the provision of additional content and by reflecting on the development and usability of hermeneutical research observations from a method and methodological perspective, thereby refining previous ideas and extending previous assumptions. The primary study objective was to report on the experience of utilising observations as a single data collection method for hermeneutic research with the aim of evaluating the interplay between intensive care unit (ICU) patients and their next of kin. A secondary objective was to highlight the impact of preknowledge and preunderstanding on the interpretation process. An intensive care context was assessed as the most appropriate, as the majority of patients are unable to engage in verbal narratives during ongoing treatment and care. The benefits of employing hermeneutic observation as well as interpretation and preunderstanding from a caring science perspective are considered.

BioMAX - the first macromolecular crystallography beamline at MAX IV Laboratory.

BioMAX is the first macromolecular crystallography beamline at the MAX IV Laboratory 3 GeV storage ring, which is the first operational multi-bend achromat storage ring. Due to the low-emittance storage ring, BioMAX has a parallel, high-intensity X-ray beam, even when focused down to 20 µm × 5 µm using the bendable focusing mirrors. The beam is tunable in the energy range 5-25 keV using the in-vacuum undulator and the horizontally deflecting double-crystal monochromator. BioMAX is equipped with an MD3 diffractometer, an ISARA high-capacity sample changer and an EIGER 16M hybrid pixel detector. Data collection at BioMAX is controlled using the newly developed MXCuBE3 graphical user interface, and sample tracking is handled by ISPyB. The computing infrastructure includes data storage and processing both at MAX IV and the Lund University supercomputing center LUNARC. With state-of-the-art instrumentation, a high degree of automation, a user-friendly control system interface and remote operation, BioMAX provides an excellent facility for most macromolecular crystallography experiments. Serial crystallography using either a high-viscosity extruder injector or the MD3 as a fixed-target scanner is already implemented. The serial crystallography activities at MAX IV Laboratory will be further developed at the microfocus beamline MicroMAX, when it comes into operation in 2022. MicroMAX will have a 1 µm × 1 µm beam focus and a flux up to 1015 photons s-1 with main applications in serial crystallography, room-temperature structure determinations and time-resolved experiments.

Family members' lived experiences when a loved one undergoes an interhospital intensive care unit-to-unit transfer: A phenomenological hermeneutical study.

AIMS AND OBJECTIVES: To reveal meanings of family members' lived experiences when a loved one undergoes an interhospital intensive care unit-to-unit transfer. BACKGROUND: Interhospital intensive care unit-to-unit transfers take place between different hospitals and their respective intensive care units (ICUs). These types of transfers are an increasing phenomenon but are sparsely studied from the family members' perspective. Indeed, the patient's critical illness and care can have a major impact on family members. During the transfer process, there is a demand for the involved intensive care health personnel to make family members feel safe and cared for. DESIGN: A qualitative design based on phenomenological hermeneutics. METHODS: The study was conducted at two Swedish general ICUs. Data were generated through individual in-depth interviews with seven family members and analysed using a phenomenological hermeneutical approach. The Criteria for Reporting Qualitative Research principles were applied in the conduct and reporting of this study. RESULTS: Four themes that reveal meanings of family members' lived experiences were developed: losing your safe haven, dealing with uncertainty, carrying your own and others' burdens and a wish to be close. CONCLUSIONS: The study reveals that an interhospital intensive care unit-to-unit transfer affects the whole family and is characterised by family members experiencing many negative feelings. The findings also illustrate that being a family member when a loved one is transferred means being exposed to the core existential elements of being human, such as loneliness and searching for meaning. RELEVANCE TO CLINICAL PRACTICE: The study highlights the importance of maintaining a family-centred approach during the transfer process. Our findings can provide deeper knowledge for intensive care health personnel, better preparing them for the delicate task of providing family-centred care during the interhospital intensive care unit-to-unit transfer process.

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.

Low-dose CT of postoperative pelvic fractures: a comparison with radiography.

BACKGROUND: Computed tomography (CT) is superior to conventional radiography (CR) for assessing internal fixation of pelvic fractures, but with a higher radiation exposure. Low-dose CT (LDCT) could possibly have a sufficient diagnostic accuracy but with a lower radiation dose. PURPOSE: To compare postoperative diagnostic accuracy of LDCT and CR after open reduction and internal fixation of pelvic fracture. MATERIAL AND METHODS: Twenty-one patients were examined with LDCT and CR 0-9 days after surgery. The examinations were reviewed by two musculoskeletal radiologists. Hardware, degree of fracture reduction, image quality, and reviewing time were assessed, and effective radiation dose was calculated. Inter-reader agreement was calculated. RESULTS: LDCT was significantly better than CR in determining whether hardware positioning was assessable ( P < 0.001). Acetabular congruence was assessable in all fractured patients with LDCT. In 12 of the 32 assessments with CR of patients with an acetabular fracture, joint congruence was not assessable due to overlapping hardware ( P = 0.001). Image quality was significantly higher for LDCT. Median time to review was 240 s for LDCT compared to 180 s for CR. Effective dose was 0.79 mSv for LDCT compared to 0.32 mSv for CR ( P < 0.001). CONCLUSION: LDCT is more reliable than CR in assessing hardware position and fracture reduction. Joint congruency is sometimes not possible to assess with CR, due to overlapping hardware. The image quality is higher, but also the effective dose, with LDCT than with CR.

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.

The Patient's Situation During Interhospital Intensive Care Unit-to-Unit Transfers: A Hermeneutical Observational Study.

Interhospital intensive care unit-to-unit transfers are an increasing phenomenon, earlier mainly studied from a patient safety perspective. Using data from video recordings and participant observations, the aim was to explore and interpret the observed nature of the patient's situation during interhospital intensive care unit-to-unit transfers. Data collection from eight transfers resulted in over 7 hours of video material and field notes. Using a hermeneutical approach, three themes emerged: being visible and invisible; being in a constantly changing space; and being a fettered body in constant motion. The patient's situation can be viewed as an involuntary journey, one where the patient exists in a constantly changing space drifting in and out of the health personnel's attention and where movements from the journey become part of the patient's body. Interhospital transfers of vulnerable patients emerge as a complex task, challenging the health personnel's ability to maintain a caring atmosphere around these patients.

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.

Goniometer-based femtosecond crystallography with X-ray free electron lasers.

The emerging method of femtosecond crystallography (FX) may extend the diffraction resolution accessible from small radiation-sensitive crystals and provides a means to determine catalytically accurate structures of acutely radiation-sensitive metalloenzymes. Automated goniometer-based instrumentation developed for use at the Linac Coherent Light Source enabled efficient and flexible FX experiments to be performed on a variety of sample types. In the case of rod-shaped Cpl hydrogenase crystals, only five crystals and about 30 min of beam time were used to obtain the 125 still diffraction patterns used to produce a 1.6-Å resolution electron density map. For smaller crystals, high-density grids were used to increase sample throughput; 930 myoglobin crystals mounted at random orientation inside 32 grids were exposed, demonstrating the utility of this approach. Screening results from cryocooled crystals of ß2-adrenoreceptor and an RNA polymerase II complex indicate the potential to extend the diffraction resolution obtainable from very radiation-sensitive samples beyond that possible with undulator-based synchrotron sources.

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.