A new CT-based method to quantify radiation-induced lung damage in patients

SummaryA new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this method may improve lung toxicity assessment and thereby facilitate development of more accurate predictive models for RILT

ACE inhibition attenuates radiation-induced cardiopulmonary damage

BACKGROUND AND PURPOSE: In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that combined irradiation intensifies cardiopulmonary toxicity. Unfortunately, current clinical practice does not include preventative measures to attenuate radiation-induced lung or cardiac toxicity. Here, we investigate the effects of the ACE inhibitor captopril on radiation-induced cardiopulmonary damage.MATERIAL AND METHODS: After local irradiation of rat heart and/or lungs captopril was administered orally. Cardiopulmonary performance was assessed using biweekly breathing rate measurements. At 8weeks post-irradiation, cardiac hemodynamics were measured, CT scans and histopathology were analyzed.RESULTS: Captopril significantly improved breathing rate and cardiopulmonary density/structure, but only when the heart was included in the radiation field. Consistently, captopril reduced radiation-induced pleural and pericardial effusion and cardiac fibrosis, resulting in an improved left ventricular end-diastolic pressure only in the heart-irradiated groups.CONCLUSION: Captopril improves cardiopulmonary morphology and function by reducing acute cardiac damage, a risk factor in the development of radiation-induced cardiopulmonary toxicity. ACE inhibition should be evaluated as a strategy to reduce cardiopulmonary complications induced by radiotherapy to the thoracic area.</p

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement

Background: Low intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation (tACS or tDCS), applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional magnetic resonance imaging (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. Objective: To develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency, and reproducibility (ContES Checklist). Methods: A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists (EP) through the International Network of the tES-fMRI (INTF) Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC based on a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed using the checklist. Results: Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (1) technological factors, (2) safety and noise tests, and (3) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. Conclusions: Use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies, and increase methodological transparency and reproducibility

Pathophysiology of thoracic irradiation

Radiotherapie speelt een belangrijke rol bij de behandeling van de, in de thorax gelegen tumoren. Ondanks dat moderne bestralingstechnieken ontworpen zijn om de dosis stralingsenergie optimaal in de tumor af te geven, komt er toch een hoeveelheid straling in de omliggend normale weefsels b.v. de longen en/of het hart. Dit kan schade toebrengen aan deze weefsels en aanleiding geven tot levensbedreigende complicaties. Een van de meest voorkomende complicaties na de behandeling met bestraling van thoracale tumoren is respiratoire dysfunctie. 5-20% van de patiënten met thoracale tumoren vooral patiënten met longkanker hebben na deze behandeling last van respiratoire dysfunctie in de vorm van dyspneu. Longkanker is de meest voorkomende oorzaak van kankersterfte in de wereld. Lokaal uitgebreide niet-klein cellig longcarcinoom (NKCLC) is de meest voorkomende vorm van longkanker. Voor patiënten met deze tumoren is behandeling met radiotherapie in combinatie met chemotherapie de enige hoop op genezing. Ondanks deze behandeling sterft de meerderheid van de patiënten binnen twee jaar na de diagnose. Dit komt doordat de optimale dosis om het NKCLC te vernietigen hoger ligt dan tolerantie van het normale weefsels. Momenteel in de radiotherapie van NKCLC, wordt de voorgeschreven bestralingsdosis bepaald door de dosis die de totale kankerpatiënten populatie kan verdragen, dus ook de 5% meest gevoelige. Om een efficiëntere behandeling met radiotherapie te bereiken moet een voor elk individu aangepaste specifieke behandeling de kans op respiratoire dysfunctie verminderen. Dit kan bereikt worden door nauwkeurige voorspelling van het risico, betere preventie en/of behandeling van respiratoire dysfunctie. Bijvoorbeeld in het geval van NKCLC wanneer de risicopopulatie (~ 20% van totale NKCLC patiënten) door nauwkeurige voorspelling van het risico van respiratoire dysfunctie adequaat geïdentificeerd kan worden, de overige 80% van totale NKCLC patiënten de mogelijkheid hebben om met een hogere bestraling dosis te behandeld worden en daardoor een betere tumor controle te krijgen.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the doselimiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the doselimiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment. (C) 2016 Elsevier Inc. All rights reserved