The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with ...immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies.
This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan-Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis.
A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25).
OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis.
Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate ...cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer.
Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife® with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT.
One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D'Amico classification) at a median age of 69 years (range, 48-90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity ≥ grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p=0.001), however returned to baseline at 3 months (p=0.60). Twenty one percent of patients experienced a late transient urinary symptom flare in the first two years following treatment. Of patients who were sexually potent prior to treatment, 79% maintained potency at 2 years post-treatment.
SBRT for clinically localized prostate cancer was well tolerated, with an early biochemical response similar to other radiation therapy treatments. Benign PSA bounces were common. Late GI and GU toxicity rates were comparable to conventionally fractionated radiation therapy and brachytherapy. Late urinary symptom flares were observed but the majority resolved with conservative management. A high percentage of men who were potent prior to treatment remained potent two years following treatment.
Immune checkpoint inhibitors (ICIs) are used to treat locally-advanced and metastatic lung cancer, which can lead to severe immunogenic-related cardiotoxicities. We assessed the risk of ...cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy.
Retrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed in correlation with the timing of radiotherapy (RT) in relation to ICI, and the mean RT heart dose. The rate of cardiac events in relation to RT timing and heart dose was compared using multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy.
Of 194 ICI-treated patients evaluated, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). 38 patients who received RT concurrently with ICI did not develop any cardiotoxicity whereas 14.1% (n=22/156) of those who did not receive concurrent RT developed cardiotoxicities (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.
ICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy in this retrospective review. Further validation of prospective studies is needed to confirm these results.
Due to its ability to induce heterogenous, patient-specific damage in pulmonary alveoli and capillaries, COVID-19 poses challenges in defining a uniform profile to elucidate infection across all ...patients. Computational models that integrate changes in ventilation and perfusion with heterogeneous damage profiles offer valuable insights into the impact of COVID-19 on pulmonary health. This study aims to develop an in silico hypothesis-testing platform specifically focused on studying microvascular pulmonary perfusion in COVID-19-infected lungs. Through this platform, we explore the effects of various acinar-level pulmonary perfusion abnormalities on global lung function. Our modelling approach simulates changes in pulmonary perfusion and the resulting mismatch of ventilation and perfusion in COVID-19-afflicted lungs. Using this coupled modelling platform, we conducted multiple simulations to assess different scenarios of perfusion abnormalities in COVID-19-infected lungs. The simulation results showed an overall decrease in ventilation-perfusion (V/Q) ratio with inclusion of various types of perfusion abnormalities such as hypoperfusion with and without microangiopathy. This model serves as a foundation for comprehending and comparing the spectrum of findings associated with COVID-19 in the lung, paving the way for patient-specific modelling of microscale lung damage in emerging pulmonary pathologies like COVID-19.
Background
Despite increasing support for stakeholder inclusion in research, there is limited evaluative research to guide safe (i.e., youth‐friendly) and meaningful (i.e., non‐tokenistic) ...partnerships with young people with lived experience of mental ill‐health in research. This paper describes a pilot evaluation and iterative design of a Youth Lived Experience Working Group (LEWG) protocol that was established by the Youth Mental Health and Technology team at The University of Sydney's Brain and Mind Centre, based on the results of two studies.
Methods
Study one consisted of a pilot evaluation of the extent to which youth partners felt empowered to contribute, to qualitatively explore how LEWG processes could be improved. Youth partners completed online surveys, and results were shared over two LEWG meetings in 2021 to empower youth partners to collectively identify actions of positive change regarding LEWG processes. These meetings were audio‐recorded and transcripts were subsequently coded using thematic analysis. Study two assessed whether LEWG processes and proposed improvements were acceptable and feasible from the perspective of academic researchers via an online survey in 2022.
Results
Quantitative and qualitative data collected from nine youth partners and 42 academic researchers uncovered initial learnings regarding facilitators, motivators, and barriers to partnering with young people with lived experience in research. Implementing clear processes for youth partners and academic researchers on effective partnership strategies, providing training opportunities for youth partners to develop research skills, and providing regular updates on how youth partner contributions led to research outcomes were identified as key facilitators.
Conclusions
This pilot study provides insight into a growing international field on how to optimise participatory processes so that researchers and young people with lived experience can be better supported and engaged to make meaningful contributions to mental health research. We argue that more transparency is needed around participatory research processes so that partnerships with young people with lived experience are not merely tokenistic.
Consumer Contributions
Our study has also been approved by and reflects the concepts and priorities of our youth lived experience partners and lived experience researchers, all of whom are authors of this paper.
There is a paucity of information regarding the demographic factors associated with the development of neck fibrosis in head and neck cancer (HNC) patients following radiotherapy. A retrospective ...review of all patients being treated for HNC at a tertiary care center between 2013 and 2017 was performed. Chi-squared and Mann-Whitney U tests were used to identify differences in incidence and grade of fibrosis, respectively, between populations. A total of 90 patients aged 19 to 99 years were included. Factors associated with an increased incidence of fibrosis included smoking during radiotherapy (
p
< 0.001), alcohol use (
p
= 0.026), recurrent disease (
p
= 0.042), and age less than 60 (
p
< 0.001) on univariate analysis. Factors associated with increased grade of fibrosis in HNC patients included recurrent HNC (
p
= 0.033), alcohol use (
p
= 0.013), patient age younger than 60 years (
p
= 0.018), smoking during radiotherapy (
p
< 0.001), and non-Caucasian race (
p =
0.012). Identification and intervention directed at patients that possess risk factors associated with fibrosis prior to treatment has the potential to improve the long-term quality of life for HNC patients.
Abstract Purpose Realizing the benefits of adopting electronic health records (EHRs) in large measure depends heavily on clinicians and providers’ uptake and meaningful use of the technology. This ...study examines EHR adoption among family physicians using 2 different data sources, compares family physicians with other office-based medical specialists, assesses variation in EHR adoption among family physicians across states, and shows the possibility for data sharing among various medical boards and federal agencies in monitoring and guiding EHR adoption. Method We undertook a secondary analysis of American Board of Family Medicine (ABFM) administrative data (2005-2011) and data from the National Ambulatory Medical Care Survey (NAMCS) (2001-2011). Results The EHR adoption rate by family physicians reached 68% nationally in 2011. NAMCS family physician adoption rates and ABFM adoption rates (2005-2011) were similar. Family physicians are adopting EHRs at a higher rate than other office-based physicians as a group; however, significant state-level variation exists, indicating geographical gaps in EHR adoption. Conclusion Two independent data sets yielded convergent results, showing that adoption of EHRs by family physicians has doubled since 2005, exceeds other office-based physicians as a group, and is likely to surpass 80% by 2013. Adoption varies at a state level. Further monitoring of trends in EHR adoption and characterizing their capacities are important to achieve comprehensive data exchange necessary for better, affordable health care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Physics-based multi-scale in silico models offer an excellent opportunity to study the effects of heterogeneous tissue damage on airflow and pressure distributions in COVID-19-afflicted lungs. The ...main objective of this study is to develop a computational modeling workflow, coupling airflow and tissue mechanics as the first step towards a virtual hypothesis-testing platform for studying injury mechanics of COVID-19-afflicted lungs. We developed a CT-based modeling approach to simulate the regional changes in lung dynamics associated with heterogeneous subject-specific COVID-19-induced damage patterns in the parenchyma. Furthermore, we investigated the effect of various levels of inflammation in a meso-scale acinar mechanics model on global lung dynamics. Our simulation results showed that as the severity of damage in the patient's right lower, left lower, and to some extent in the right upper lobe increased, ventilation was redistributed to the least injured right middle and left upper lobes. Furthermore, our multi-scale model reasonably simulated a decrease in overall tidal volume as the level of tissue injury and surfactant loss in the meso-scale acinar mechanics model was increased. This study presents a major step towards multi-scale computational modeling workflows capable of simulating the effect of subject-specific heterogenous COVID-19-induced lung damage on ventilation dynamics.
•Developed CT-based modeling approach to simulate heterogeneous COVID-19 lung damage.•Ventilation was redistributed to less injured lung lobes.•Overall tidal volume decreased as tissue injury and surfactant loss increased.•Implemented a multi-scale subject-specific computational model of COVID-19 lung.
We aimed to explore whether the imaging of antiporter system XC- of immune cells with (4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in ...murine models and patients (NCT03546868). Methods: 18F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer–induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system XC- and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68+xCT+ and CD3+xCT+ cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68+xCT+ cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system XC- in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18F-FSPG PET imaging of system XC- activity may noninvasively assess the IBD activity.
Increasing accumulation and retention of nanomedicines within tumor tissue is a significant challenge, particularly in the case of brain tumors where access to the tumor through the vasculature is ...restricted by the blood–brain barrier (BBB). This makes the application of nanomedicines in neuro-oncology often considered unfeasible, with efficacy limited to regions of significant disease progression and compromised BBB. However, little is understood about how the evolving tumor–brain physiology during disease progression affects the permeability and retention of designer nanomedicines. We report here the development of a modular nanomedicine platform that, when used in conjunction with a unique model of how tumorigenesis affects BBB integrity, allows investigation of how nanomaterial properties affect uptake and retention in brain tissue. By combining different in vivo longitudinal imaging techniques (including positron emission tomography and magnetic resonance imaging), we have evaluated the retention of nanomedicines with predefined physicochemical properties (size and surface functionality) and established a relationship between structure and tissue accumulation as a function of a new parameter that measures BBB leakiness; this offers significant advancements in our ability to relate tumor accumulation of nanomedicines to more physiologically relevant parameters. Our data show that accumulation of nanomedicines in brain tumor tissue is better correlated with the leakiness of the BBB than actual tumor volume. This was evaluated by establishing brain tumors using a spontaneous and endogenously derived glioblastoma model providing a unique opportunity to assess these parameters individually and compare the results across multiple mice. We also quantitatively demonstrate that smaller nanomedicines (20 nm) can indeed cross the BBB and accumulate in tumors at earlier stages of the disease than larger analogues, therefore opening the possibility of developing patient-specific nanoparticle treatment interventions in earlier stages of the disease. Importantly, these results provide a more predictive approach for designing efficacious personalized nanomedicines based on a particular patient’s condition.
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