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1.
Radiother Oncol ; 198: 110414, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942120

ABSTRACT

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

2.
Phys Med Biol ; 69(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38774985

ABSTRACT

Objective.This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (LET-) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations.Approach.Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- (LET-f) and dose-averaged LET (LET-d) were determined. For both quantities, two sub-types of averages were calculated, either considering the contributions from primary and secondary protons or from all protons and heavier, charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE).Main results.All types ofLET-could be assessed with the luminescence detectors. The experimental determination ofLET-fis in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand,LET-dcan present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from theLET-dcalculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy betweenLET-fandLET-d. Assessment of RBE through the experimentally determinedLET-dvalues agrees with independently acquired reference values, indicating that the investigated detectors can determineLET-with sufficient accuracy for proton therapy.Significance.OSLDs, TLDs, and FNTDs can be used to determineLET-and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived fromLET-, OSLDs and TLDs can simultaneously ascertain dose,LET-, and RBE. This makes passive detectors appealing for measurements in phantoms to facilitate validation of clinical treatment plans or experiments related to proton therapy.


Subject(s)
Linear Energy Transfer , Monte Carlo Method , Proton Therapy , Proton Therapy/instrumentation , Radiation Dosage , Relative Biological Effectiveness
3.
Nephrol Dial Transplant ; 39(7): 1150-1158, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38168720

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new-onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalization and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression. METHODS: Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017-2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2/year), kidney failure, all-cause hospitalization and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease. RESULTS: Among 133 443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% [95% confidence interval (CI) 14.4-14.8]. The 3-year risks of kidney failure, hospitalization and death were 0.3% (95% CI 0.3-0.4), 53.3% (95% CI 53.0-53.6) and 18.1% (95% CI 17.9-18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46%-47% in males and females with severe albuminuria, diabetes and hypertension/cardiovascular disease. CONCLUSION: This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimized prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression.


Subject(s)
Disease Progression , Renal Insufficiency, Chronic , Humans , Male , Female , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Risk Factors , Middle Aged , Aged , Denmark/epidemiology , Glomerular Filtration Rate , Adult , Cohort Studies , Hospitalization/statistics & numerical data
5.
Acta Oncol ; 62(11): 1455-1460, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37773941

ABSTRACT

BACKGROUND: Inter-fractional anatomical changes challenge robust delivery of whole-pelvic proton therapy for high-risk prostate cancer. Pre-treatment robust evaluation (PRE) takes uncertainties in isocenter shifts and distal beam edge in treatment plans into account. Using weekly control computed tomography scans (cCTs), the aim of this study was to evaluate the PRE strategy by comparing to an off-line during-treatment robust evaluation (DRE) while also assessing plan robustness with respect to protocol planning constraints. MATERIAL AND METHODS: Treatment plans and cCTs from ten patients included in the pilot phase of the PROstate PROTON Trial 1 were analysed. Treatment planning followed protocol guidelines with 78 Gy to the primary clinical target volume (CTVp) and 56 Gy to the elective target (CTVe) in 39 fractions. Recalculations of the treatment plans were performed for a total of 64 cCTs and dose/volume measures corresponding to clinical constraints were evaluated for this DRE against the simulated scenario interval from the PRE. RESULTS: Of the 64 cCTs, 59 showed DRE CTVp measures within the robustness range from the PRE; this was also the case for 39 of the cCTs for the CTVe measures. However, DRE CTVe coverage was still within constraints for 57 of the 64 cCTs. DRE dose/volume measures for CTVp fulfilled target coverage constraints in 59 of 64 cCTs. All DRE measures for the rectum, bladder, and bowel were inside the PRE range in 63, 39, and 31 cCTs, respectively. CONCLUSION: The PRE strategy predicted the DRE scenarios for CTVp and rectum. CTVe, bladder, and bowel showed more complex anatomical variations than simulated by the PRE isocenter shift. Both original and recalculated nominal treatment plans showed robust treatment delivery in terms of target coverage.


Subject(s)
Prostatic Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Male , Humans , Proton Therapy/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Organs at Risk , Radiotherapy Dosage
6.
Pharmacoecon Open ; 7(5): 751-764, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37552432

ABSTRACT

OBJECTIVES: To examine costs of care from a healthcare sector perspective within 1 year before death in patients with non-cancer diseases and patients with cancer. METHODS: This nationwide registry-based study identified all Danish citizens dying from major non-cancer diseases or cancer in 2010-2016. Applying the cost-of-illness method, we included costs of somatic hospitals, including hospital-based specialist palliative care, primary care, prescription medicine and hospice expressed in 2022 euros. Costs of patients with non-cancer diseases and cancer were compared using regression analyses adjusting for sex, age, comorbidity, residential region, marital/cohabitation status and income level. RESULTS: Within 1 year before death, mean total healthcare costs were €27,185 [95% confidence interval (CI) €26,970-27,401] per patient with non-cancer disease (n = 109,723) and €51,348 (95% CI €51,098-51,597) per patient with cancer (n = 108,889). The adjusted relative total healthcare costs, i.e. the ratio of the mean costs, of patients with non-cancer diseases was 0.64 (95% CI 0.63-0.66) at 12 months before death and 0.91 (95% CI 0.90-0.92) within 30 days before death compared with patients with cancer. Mean costs of hospital-based specialist palliative care and hospice in the year leading up to death were €17 (95% CI €13-20) and €90 (95% CI €77-102) per patient with non-cancer disease but €1552 (95% CI €1506-1598) and €3411 (95% CI €3342-3480) per patient with cancer. CONCLUSIONS: Within 1 year before death, total healthcare costs, mainly driven by hospital costs, were substantially lower for patients with non-cancer diseases compared with patients with cancer. Moreover, the costs of hospital-based specialist palliative care and hospice were minimal for patients with non-cancer diseases.

7.
Clin Transl Radiat Oncol ; 41: 100632, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37441541

ABSTRACT

The Danish Prostate Cancer Group is launching the randomized trial, PROstate PROTON Trial 1 (NCT05350475), that compares photons and protons to the prostate and pelvic lymph nodes in treatment of high-risk prostate cancer. The aim of the work described in this paper was, in preparation of this trial, to establish a strategy for conventionally fractionated proton therapy of prostate and elective pelvic lymph nodes that is feasible and robust. Proton treatments are image-guided based on gold fiducial markers and on-board imaging systems in line with current practice. Our established proton beam configuration consists of four coplanar fields; two posterior oblique fields and two lateral oblique fields, chosen to minimize range uncertainties associated with penetrating a varying amount of material from both treatment couch and patient body. Proton plans are robustly optimized to ensure target coverage while keeping normal tissue doses as low as is reasonably achievable throughout the course of treatment. Specific focus is on dose to the bowel as a reduction in gastrointestinal toxicity is the primary endpoint of the trial. Strategies have been established using previously treated patients and will be further investigated and evaluated through the ongoing pilot phase of the trial.

8.
Gynecol Oncol ; 172: 1-8, 2023 05.
Article in English | MEDLINE | ID: mdl-36905767

ABSTRACT

OBJECTIVE: To examine hospital-based specialist palliative care (SPC) utilisation among patients with gynaecological cancer, including temporal trends, predictors and associations with high-intensity end-of-life care. METHODS: We conducted a nationwide registry-based study for all patients dying from gynaecological cancer in Denmark during 2010-2016. We estimated the proportions of patients receiving SPC by year of death and used regression analyses to examine predictors of SPC utilisation. Use of high-intensity end-of-life care according to SPC utilisation was compared by regression analyses adjusting for type of gynaecological cancer, year of death, age, comorbidities, residential region, marital/cohabitation status, income level and migrant status. RESULTS: Among 4502 patients dying from gynaecological cancer, the proportion of patients receiving SPC increased from 24.2% in 2010 to 50.7% in 2016. Young age, three or more comorbidities, residence outside the Capital Region and being immigrant/descendant were associated with increased SPC utilisation, whereas income, cancer type and stage were not. SPC was associated with lower high-intensity end-of-life care utilisation. Particularly, when compared with patients not receiving SPC, patients who accessed SPC >30 days before death had 88% lower risk of intensive care unit admissions within 30 days before death (adjusted relative risk: 0.12 (95% CI: 0.06; 0.24)) and 96% lower risk of surgery within 14 days before death (adjusted relative risk: 0.04 (95% CI: 0.01; 0.31)). CONCLUSIONS: Among patients dying from gynaecological cancer, SPC utilisation increased over time and age, comorbidities, residential region and migrant status were associated with access to SPC. Furthermore, SPC was associated with lower use of high-intensity end-of-life care.


Subject(s)
Genital Neoplasms, Female , Hospice Care , Neoplasms , Terminal Care , Female , Humans , Palliative Care , Genital Neoplasms, Female/therapy , Hospitals
9.
Clin Epidemiol ; 14: 653-664, 2022.
Article in English | MEDLINE | ID: mdl-35548265

ABSTRACT

Purpose: Socioeconomic disparities in end-of-life care have been reported across underlying diseases, but there is a paucity of information on potential time trends. Thus, we aimed to examine time trends in use of health-care services at the end of life according to socioeconomic position in patients dying from cancer and non-cancer diseases. Materials and Methods: We conducted a nationwide registry-based study among adults dying from cancer or non-cancer diseases (diabetes, dementia, heart failure, ischemic heart disease, stroke, chronic liver disease, and chronic obstructive pulmonary disease) in Denmark in 2006-2016. We obtained data on patients' educational level and income level and use of health-care services within three months before death. Use of health-care services according to educational level and income level was plotted by calendar year of death and compared by regression analyses adjusting for age, sex, comorbidity, cohabitation, and municipality. Results: In both cancer (n = 169,694) and non-cancer patients (n = 180,350), we found limited socioeconomic disparities and no clear temporal trends in use of hospital, intensive care, emergency room, general practice, home care nurse, and hospice. In 2006/2007, one percentage point more cancer patients with high income level compared with low income level were affiliated with hospital-based specialist palliative care (adjusted mean difference: 0.01 (95% confidence interval (CI): 0.01; 0.02)), whereas this was 12 percentage points in 2016 (adjusted mean difference: 0.12 (95% CI: 0.09; 0.14)). Conclusion: Socioeconomic disparities in specialist palliative care tended to increase over time among cancer patients but were limited and without clear time trends in use of other health-care services in both cancer and non-cancer patients.

10.
J Bus Ethics ; 176(2): 227-240, 2022.
Article in English | MEDLINE | ID: mdl-33424067

ABSTRACT

Social media platforms have been vested with hope for their potential to enable 'ordinary citizens' to make their judgments public and contribute to pluralized discussions about organizations and their perceived legitimacy (Etter et al. in Bus Soc 57(1):60-97, 2018). This raises questions about how ordinary citizens make judgements and voice them in online spaces. This paper addresses these questions by examining how Western citizens ascribe responsibility and action in relation to corporate misconduct. Empirically, it focuses on modern slavery and analyses online debates in Denmark on child slavery in the cocoa industry. Conceptually, it introduces the notion of cosmopolitanism as a general disposition of care and responsibility towards distant others, conceived as a prerequisite for the critical evaluation of corporate (ir)responsibility in the Global South. The analysis of online debates shows that citizens debate child slavery in terms of individual consumer responsibility rather than corporate responsibility. Corporations are not considered potential agents of change. As a consequence, online citizen debates did not reflect a legitimacy crisis for the cocoa industry, as debates over responsibility were overwhelmingly concerned with the agency of the Western individual, the individual agency of the speakers themselves. Participants in debates understood their agency strictly as consumer agency.

11.
Acta Oncol ; 61(2): 206-214, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34686122

ABSTRACT

BACKGROUND: Clinical data suggest that the relative biological effectiveness (RBE) in proton therapy (PT) varies with linear energy transfer (LET). However, LET calculations are neither standardized nor available in clinical routine. Here, the status of LET calculations among European PT institutions and their comparability are assessed. MATERIALS AND METHODS: Eight European PT institutions used suitable treatment planning systems with their center-specific beam model to create treatment plans in a water phantom covering different field arrangements and fulfilling commonly agreed dose objectives. They employed their locally established LET simulation environments and procedures to determine the corresponding LET distributions. Dose distributions D1.1 and DRBE assuming constant and variable RBE, respectively, and LET were compared among the institutions. Inter-center variability was assessed based on dose- and LET-volume-histogram parameters. RESULTS: Treatment plans from six institutions fulfilled all clinical goals and were eligible for common analysis. D1.1 distributions in the target volume were comparable among PT institutions. However, corresponding LET values varied substantially between institutions for all field arrangements, primarily due to differences in LET averaging technique and considered secondary particle spectra. Consequently, DRBE using non-harmonized LET calculations increased inter-center dose variations substantially compared to D1.1 and significantly in mean dose to the target volume of perpendicular and opposing field arrangements (p < 0.05). Harmonizing LET reporting (dose-averaging, all protons, LET to water or to unit density tissue) reduced the inter-center variability in LET to the order of 10-15% within and outside the target volume for all beam arrangements. Consequentially, inter-institutional variability in DRBE decreased to that observed for D1.1. CONCLUSION: Harmonizing the reported LET among PT centers is feasible and allows for consistent multi-centric analysis and reporting of tumor control and toxicity in view of a variable RBE. It may serve as basis for harmonized variable RBE dose prescription in PT.


Subject(s)
Linear Energy Transfer , Proton Therapy , Humans , Monte Carlo Method , Protons , Radiotherapy Planning, Computer-Assisted , Relative Biological Effectiveness
13.
BMJ Open ; 11(11): e049661, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34819282

ABSTRACT

OBJECTIVES: To investigate illness trajectories as reflected by healthcare utilisation, including hospital and intensive care unit admissions, consultations in general practice and home care provision, before death comparing people dying from chronic obstructive pulmonary disease (COPD), heart failure and cancer. DESIGN: Nationwide register-based cohort study. SETTING: Data on all hospital admissions, including intensive care unit admissions, consultations in general practice and home care provision were obtained from nationwide Danish registries. PARTICIPANTS: All adult decedents in Denmark dying from COPD, heart failure or cancer between 2006 and 2016. OUTCOME MEASURES: For each day within 5 years before death, we computed a daily prevalence proportion (PP) of being admitted to hospital or consulting a general practitioner. For each day within 6 months before death, we computed PPs of being admitted to intensive care or receiving home care. The PPs were plotted and compared by regression analyses adjusting for age, gender, comorbidity level, marital/cohabitation status, municipality and income level. RESULTS: Among 1 74 086 patients dying from COPD (n=22 648), heart failure (n=11 498) or cancer (n=139 940), the PPs of being admitted to hospital or consulting a general practitioner showed similar steady progression and steep increase in the last year of life for all patient populations. The PP of being admitted to intensive care showed modest increase during the last 6 months of life, accelerating in the last month, for all patient populations. For patients with COPD and heart failure, the PP of receiving home care remained stable during the last 6 months of life but increased steadily for patients with cancer. CONCLUSION: We found limited differences in healthcare resource utilisation at the end of life for people with COPD, heart failure or cancer, indicating comparable illness trajectories.This supports the need to reconsider efforts in achieving equal access to palliative care interventions, which is still mainly offered to patients with cancer.


Subject(s)
Heart Failure , Neoplasms , Pulmonary Disease, Chronic Obstructive , Terminal Care , Adult , Cohort Studies , Heart Failure/epidemiology , Heart Failure/therapy , Humans , Neoplasms/therapy , Palliative Care , Patient Acceptance of Health Care , Pulmonary Disease, Chronic Obstructive/therapy
14.
Future Oncol ; 17(25): 3331-3341, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34156281

ABSTRACT

Aim: To estimate current real-world costs of drugs and supportive care for the treatment of multiple myeloma in a tax-based health system. Methods: Forty-one patients were included from a personalized medicine study (2016-2019). Detailed information was collected from patient journals and hospital registries to estimate the total and mean costs using inverse probability weighting of censored data. Results: Total observed (censored) costs for the 41 patients was €8.84 million during 125 treatment years, with antineoplastic drugs as the main cost driver (€5.6 million). Individual costs showed large variations. Mean 3-year cost per patient from first progression was €182,103 (€131,800-232,405). Conclusion: Prediction of real-world costs is hindered by the availability of detailed costing data. Micro-costing analyses are needed for budgeting and real-world evaluation of cost-effectiveness.


Lay abstract In recent years, there has been a dramatic improvement in the treatment of multiple myeloma due to the introduction of new drugs. These drugs have significantly increased survival but have also had an immense impact on healthcare budgets. In this study, we used detailed treatment information for multiple myeloma patients in combination with billing data from the hospital pharmacy at a Danish hospital to calculate individual cost histories for both drugs and supportive care. Using these data, we estimated the mean 3-year cost of a multiple myeloma patient to be €182.103, but we also found large variation between patients, causing an uncertainty of €50.000 in either direction. We believe that detailed costing studies, similar to the present one, are necessary for evaluation of cost-effectiveness of drugs in clinical practice.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/economics , Cost of Illness , Health Care Costs/statistics & numerical data , Multiple Myeloma/economics , Palliative Care/economics , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cost-Benefit Analysis/statistics & numerical data , Denmark/epidemiology , Disease Progression , Female , Follow-Up Studies , Humans , Male , Medical Oncology/economics , Medical Oncology/standards , Medical Oncology/statistics & numerical data , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/therapy , National Health Programs/economics , National Health Programs/standards , National Health Programs/statistics & numerical data , Palliative Care/statistics & numerical data , Practice Guidelines as Topic , Progression-Free Survival , Registries/statistics & numerical data , Time Factors
15.
Z Med Phys ; 31(2): 145-153, 2021 May.
Article in English | MEDLINE | ID: mdl-33712295

ABSTRACT

PURPOSE: An independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe. METHODS: The audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom. RESULTS: For all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was -0.1±1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of -0.5±0.6%. CONCLUSION: The developed dosimetry audit method was successfully applied at five proton centers including various "turn-key" Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy.


Subject(s)
Proton Therapy , Phantoms, Imaging , Protons , Radiometry , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
16.
Acta Oncol ; 59(10): 1151-1156, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33000988

ABSTRACT

BACKGROUND: This paper presents an insight into the critical discussions and the current strategies of the Nordic countries for handling the variable proton relative biological effectiveness (RBE) as presented at The Nordic Collaborative Workshop for Particle Therapy that took place at the Skandion Clinic on 14th and 15th of November 2019. MATERIAL AND METHODS: In the current clinical practice at the two proton centres in operation at the date, Skandion Clinic, and the Danish Centre for Particle Therapy, a constant proton RBE of 1.1 is applied. The potentially increased effectiveness at the end of the particle range is however considered at the stage of treatment planning at both places based on empirical observations and knowledge. More elaborated strategies to evaluate the plans and mitigate the problem are intensely investigated internationally as well at the two centres. They involve the calculation of the dose-averaged linear energy transfer (LETd) values and the assessment of their distributions corroborated with the distribution of the dose and the location of the critical clinical structures. RESULTS: Methods and tools for LETd calculations are under different stages of development as well as models to account for the variation of the RBE with LETd, dose per fraction, and type of tissue. The way they are currently used for evaluation and optimisation of the plans and their robustness are summarised. A critical but not exhaustive discussion of their potential future implementation in the clinical practice is also presented. CONCLUSIONS: The need for collaboration between the clinical proton centres in establishing common platforms and perspectives for treatment planning evaluation and optimisation is highlighted as well as the need of close interaction with the research academic groups that could offer a complementary perspective and actively help developing methods and tools for clinical implementation of the more complex metrics for considering the variable effectiveness of the proton beams.


Subject(s)
Neoplasms/radiotherapy , Proton Therapy , Humans , Internationality , Radiotherapy Planning, Computer-Assisted , Relative Biological Effectiveness , Scandinavian and Nordic Countries
17.
BMJ Open ; 10(6): e033493, 2020 06 28.
Article in English | MEDLINE | ID: mdl-32595146

ABSTRACT

OBJECTIVES: End-of-life hospitalisations may not be associated with improved quality of life. Studies indicate differences in end-of-life care for cancer and non-cancer patients; however, data on hospital utilisation are sparse. This study aimed to compare end-of-life hospitalisation and place of death among patients dying from cancer, heart failure or chronic obstructive pulmonary disease (COPD). DESIGN: A nationwide register-based cohort study. SETTING: Data on all in-hospital admissions obtained from nationwide Danish medical registries. PARTICIPANTS: All decedents dying from cancer, heart failure or COPD disease in Denmark between 2006 and 2015. OUTCOME MEASURES: Data on all in-hospital admissions within 6 months and 30 days before death as well as place of death. Comparisons were made according to cause of death while adjusting for age, sex, comorbidity, partner status and residential region. RESULTS: Among 154 235 decedents, the median total bed days in hospital within 6 months before death was 19 days for cancer patients, 10 days for patients with heart failure and 11 days for patients with COPD. Within 30 days before death, this was 9 days for cancer patients, and 6 days for patients with heart failure and COPD. Compared with cancer patients, the adjusted relative bed day use was 0.65 (95% CI, 0.63 to 0.68) for heart failure patients and 0.68 (95% CI, 0.66 to 0.69) for patients with COPD within 6 months before death. Correspondingly, this was 0.65 (95% CI, 0.63 to 0.68) and 0.70 (95% CI, 0.68 to 0.71) within 30 days before death.Patients had almost the same risk of dying in hospital independently of death cause (46.2% to 56.0%). CONCLUSION: Patients with cancer, heart failure and COPD all spent considerable part of their end of life in hospital. Hospital use was highest among cancer patients; however, absolute differences were small.


Subject(s)
Heart Failure/epidemiology , Hospitalization , Neoplasms/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Terminal Care , Aged , Aged, 80 and over , Denmark/epidemiology , Female , Heart Failure/mortality , Humans , Male , Middle Aged , Neoplasms/mortality , Pulmonary Disease, Chronic Obstructive/mortality , Quality of Life , Registries
18.
Front Cell Neurosci ; 14: 114, 2020.
Article in English | MEDLINE | ID: mdl-32499680

ABSTRACT

A fundamental interest in circuit analysis is to parse out the synaptic inputs underlying a behavioral experience. Toward this aim, we have devised an unbiased strategy that specifically labels the afferent inputs that are activated by a defined stimulus in an activity-dependent manner. We validated this strategy in four brain circuits receiving known sensory inputs. This strategy, as demonstrated here, accurately identifies these inputs.

19.
Phys Med Biol ; 65(21): 215023, 2020 11 06.
Article in English | MEDLINE | ID: mdl-32526719

ABSTRACT

Organic plastic scintillation detectors (PSDs) are known to produce less light per absorbed dose in highly dense radiations in comparison with e.g. 60Co gamma beams. This so-called ionization density quenching can be experimentally determined by comparison of the scintillator output with the absorbed dose established with a reference detector. The hypothesis of this work was that a newly developed small-core graphite calorimeter (core size: ø5mm × 7mm) can be used as reference for such measurements. The potential benefit of a calorimetric reference would be to have a robust and accurate reference with well-understood dosimetry properties even in high-intensity FLASH beams. As a first step, the hypothesis was tested by comparing previously established quenching parameter estimates for the BCF-60 scintillating material with data obtained with the new instrument at different depths along the central axis of a 170 MeV scanned proton beam. After the calorimetric measurements, scintillator measurements were acquired under equivalent conditions by positioning the PSD in a replica graphite core nominally identical to the core used for calorimetry. To experimentally document details of the irradiations, the spot width was mapped along the central beam axis using a new technique based on a PSD and a time-to-distance conversion procedure. Analysing the proton data in the framework of the Birks model, the graphite calorimeter gave a [Formula: see text] quenching parameter for BCF-60 in agreement with literature values. The consistency between the calorimetric results and the other sources of information supports the validity of the new method, and we therefore aim to apply it for characterization of other detectors in more intense beams where ionometry cannot serve as reference.


Subject(s)
Calorimetry/instrumentation , Graphite , Proton Therapy , Radiometry/instrumentation , Scintillation Counting/instrumentation , Monte Carlo Method , Plastics
20.
Alzheimer Dis Assoc Disord ; 34(3): 254-261, 2020.
Article in English | MEDLINE | ID: mdl-32332202

ABSTRACT

INTRODUCTION: Inequalities in life expectancy and mortality by social deprivation in the general population of the United Kingdom are widening. For people with dementia, data on potential gradients in life expectancy and mortality by social deprivation are sparse. This study aimed to explore potential differentials in life expectancy and mortality in people with dementia according to social deprivation. METHODS: Using The Health Improvement Network (THIN) primary care database, we included people with a diagnosis of dementia in the United Kingdom in 2000 to 2016 and obtained data on age at death and mortality. Comparisons were made according to social deprivation quintiles adjusting for age at diagnosis. RESULTS: Among 166,268 people with dementia there were no differences in life expectancy and mortality in the most deprived compared with the least deprived. This pattern has been stable during the study period, as no increasing inequalities in life expectancy and mortality according to social deprivation were found. DISCUSSION: Contrary to the general population, there were limited inequalities in life expectancy and mortality according to social deprivation for people with dementia.


Subject(s)
Dementia , Life Expectancy/trends , Primary Health Care , Socioeconomic Factors , Aged , Aged, 80 and over , Cohort Studies , Databases, Factual , Dementia/epidemiology , Female , Humans , Male , Middle Aged , United Kingdom/epidemiology
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