Dosimetric comparison of protons vs photons in re-irradiation of intracranial meningioma

Objectives: Re-irradiation of recurrent intracranial meningiomas represents a major challenge due to dose limits of critical structures and the necessity of sufficient dose coverage of the recurrent tumor for local control. The aim of this study was to investigate dosimetric differences between pencil beam scanning protons (PBS) and volumetric modulated arc therapy (VMAT) photons for intracranial re-irradiation of meningiomas. Methods: Nine patients who received an initial dose &gt;50 Gy for intracranial meningioma and who were re-irradiated for recurrence were selected for plan comparison. A volumetric modulated arc therapy photon and a pencil beam scanning proton plan were generated (prescription dose: 15 × 3 Gy) based on the targets used in the re-irradiation treatment. Results: In all cases, where the cumulative dose exceeded 100 or 90 Gy, these high dose volumes were larger for the proton plans. The integral doses were significantly higher in all photon plans (reduction with protons: 48.6%, p &lt; 0.01). In two cases (22.2%), organ at risk (OAR) sparing was superior with the proton plan. In one case (11.1%), the photon plan showed a dosimetric advantage. In the remaining six cases (66.7%), we found no clinically relevant differences in dose to the OARs. Conclusions: The dosimetric results of the accumulated dose for a re-irradiation with protons and with photons were very similar. The photon plans had a steeper dose falloff directly outside the target and were superior in minimizing the high dose volumes. The proton plans achieved a lower integral dose. Clinically relevant OAR sparing was extremely case specific. The optimal treatment modality should be assessed individually. Advances in knowledge: Dose sparing in re-irradiation of intracranial meningiomas with protons or photons is highly case specific and the optimal treatment modality needs to be assessed on an individual basis. </jats:sec

Narrowband ultraviolet B treatment for psoriasis is highly economical and causes significant savings in cost for topical treatments

Background: Narrowband ultraviolet B (NB-UVB) treatment for psoriasis is considered expensive. However, existing data are based on estimates and do not consider indirect cost savings. Objectives: To define the actual costs of NB-UVB incurred by the service provider, as well as treatment-associated cost savings. Methods: We performed data linkage of (i) comprehensive treatment records and (ii) prescribing data for all NB-UVB treatment episodes spanning 6 years in a population of 420 000. We minimized data fluctuation by compiling data from four independent treatment sites, and using drug prescriptions unrelated to psoriasis as a negative control. Results: National Health Service Tayside spent an average of £257 per NB-UVB treatment course (mean 257 ± 63, range 150–286, across four independent treatment sites), contrasting sharply with the estimate of £1882 used by the U.K. National Institute for Health and Care Excellence. The cost of topical treatments averaged £128 per patient in the 12 months prior to NB-UVB, accounting for 42% of the overall drug costs incurred by these patients. This was reduced by 40% to £53 per patient over the 12-month period following NB-UVB treatment, while psoriasis-unrelated drug prescription remained unchanged, suggesting disease-specific effects of NB-UVB. The data were not due to site-specific factors, as confirmed by highly similar results observed between treatment sites operated by distinct staff. Finally, we detail all staff hours directly and indirectly involved in treatment, allowing direct translation of cost into other healthcare systems. Conclusions: NB-UVB is a low-cost treatment; cost figures currently used in health technology appraisals are an overestimate based on the data presented here. Creating or extending access to NB-UVB is likely to offer additional savings by delaying or avoiding costly third-line treatments for many patients.PostprintPeer reviewe

Interrelations of vegetation growth and water scarcity in Iran revealed by satellite time series

Iran has experienced a drastic increase in water scarcity in the last decades. The main driver has been the substantial unsustainable water consumption of the agricultural sector. This study quantifies the spatiotemporal dynamics of Iran’s hydrometeorological water availability, land cover, and vegetation growth and evaluates their interrelations with a special focus on agricultural vegetation developments. It analyzes globally available reanalysis climate data and satellite time series data and products, allowing a country-wide investigation of recent 20+ years at detailed spatial and temporal scales. The results reveal a wide-spread agricultural expansion (27,000 km$^2$) and a significant cultivation intensification (48,000 km$^2$). At the same time, we observe a substantial decline in total water storage that is not represented by a decrease of meteorological water input, confirming an unsustainable use of groundwater mainly for agricultural irrigation. As consequence of water scarcity, we identify agricultural areas with a loss or reduction of vegetation growth (10,000 km$^2$), especially in irrigated agricultural areas under (hyper-)arid conditions. In Iran’s natural biomes, the results show declining trends in vegetation growth and land cover degradation from sparse vegetation to barren land in 40,000 km$^2$, mainly along the western plains and foothills of the Zagros Mountains, and at the same time wide-spread greening trends, particularly in regions of higher altitudes. Overall, the findings provide detailed insights in vegetation-related causes and consequences of Iran’s anthropogenic drought and can support sustainable management plans for Iran or other semi-arid regions worldwide, often facing similar conditions

Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo

We have previously shown that peroxisome proliferator activating receptor ß/δ (PPAR β/δ is overexpressed in psoriasis. PPAR β/δ is not present in adult epidermis of mice. Targeted expression of PPAR β/δ and activation by a selective synthetic agonist is sufficient to induce an inflammatory skin disease resembling psoriasis. Several signalling pathways dysregulated in psoriasis are replicated in this model, suggesting that PPAR β/δ activation contributes to psoriasis pathogenesis. Thus, inhibition of PPAR β/δ might harbour therapeutical potential. Since PPAR β/δ has pleiotropic functions in metabolism, skin-targeted inhibition offer the potential of reducing systemic adverse effects. Here, we report that three selective PPAR β/δ antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for topical application to the skin and that their skin concentration can be accurately quantified using ultra-high performance liquid chromatography (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse model in reducing psoriasis-like changes triggered by activation of PPAR β/δ. PPAR β/δ antagonists GSK0660 and compound 3 do not exhibit systemic drug accumulation after prolonged application to the skin, nor do they induce inflammatory or irritant changes. Significantly, the irreversible PPAR β/δ antagonist (GSK3787) retains efficacy when applied topically only three times per week which could be of practical clinical usefulness. Our data suggest that topical inhibition of PPAR β/δ to treat psoriasis may warrant further exploration

Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition

Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. Conclusions: Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.Peer Reviewe

Taking shortcuts: Cognitive conflict during motivated rule-breaking

Deliberate rule violations have typically been addressed from a motivational perspective that asked whether or not agents decide to violate rules based on contextual factors and moral considerations. Here we complement motivational approaches by providing a cognitive perspective on the processes that operate during the act of committing an unsolicited rule violation. Participants were tested in a task that allowed for violating traffic rules by exploiting forbidden shortcuts in a virtual city maze. Results yielded evidence for sustained cognitive conflict that affected performance from right before a violation throughout actually committing the violation. These findings open up a new theoretical perspective on violation behavior that focuses on processes occurring right at the moment a rule violation takes place

Taking shortcuts: Cognitive conflict during motivated rule-breaking

Deliberate rule violations have typically been addressed from a motivational perspective that asked whether or not agents decide to violate rules based on contextual factors and moral considerations. Here we complement motivational approaches by providing a cognitive perspective on the processes that operate during the act of committing an unsolicited rule violation. Participants were tested in a task that allowed for violating traffic rules by exploiting forbidden shortcuts in a virtual city maze. Results yielded evidence for sustained cognitive conflict that affected performance from right before a violation throughout actually committing the violation. These findings open up a new theoretical perspective on violation behavior that focuses on processes occurring right at the moment a rule violation takes place

Additional Primary Tumors Detected Incidentally on FDG PET/CT at Staging in Patients with First Diagnosis of NSCLC: Frequency, Impact on Patient Management and Survival

We aimed to assess the frequency of additional primary malignancies detected incidentally on [18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) at staging in NSCLC patients. Moreover, their impact on patient management and survival was assessed. Consecutive NSCLC patients with available staging FDG-PET/CT between 2020 and 2021 were retrospectively enrolled. We reported whether further investigations of suspicious findings presumably not related to NSCLC were recommended and performed after FDG-PET/CT. Any additional imaging, surgery or multimodal management was considered as an impact on patient management. Patient survival was defined using overall survival OS and progression-free survival PFS. A total of 125 NSCLC patients were included, while 26 findings in 26 different patients were suspicious for an additional malignancy on FDG-PET/CT at staging. The most frequent anatomical site was the colon. A total of 54.2% of all additional suspicious lesions turned out to be malignant. Almost every malignant finding had an impact on patient management. No significant differences were found between NSCLC patients with suspicious findings versus no suspicious findings with regards to their survival. FDG-PET/CT performed for staging might be a valuable tool to identify additional primary tumors in NSCLC patients. Identification of additional primary tumors might have substantial implications for patient management. An early detection together with interdisciplinary patient management could prevent a worsening of survival compared to patients with NSCLC only.Peer Reviewe