Radiation-induced cardiac side-effects:The lung as target for interacting damage and intervention

Radiotherapy is part of the treatment for many thoracic cancers. During this treatment heart and lung tissue can often receive considerable doses of radiation. Doses to the heart can potentially lead to cardiac effects such as pericarditis and myocardial fibrosis. Common side effects after lung irradiation are pneumonitis and pulmonary fibrosis. It has also been shown that lung irradiation has effects on cardiac function. In a rat model lung irradiation caused remodeling of the pulmonary vasculature increasing resistance of the pulmonary vascular bed, leading to enhanced pulmonary artery pressure, right ventricle hypertrophy and reduced right ventricle performance. Even more pronounced effects are observed when both, lung and heart are irradiated. The effects observed after lung irradiation show striking similarities with symptoms of pulmonary arterial hypertension. In particular, the vascular remodeling in lung tissue seems to have similar underlying features. Here, we discuss the similarities and differences of vascular remodeling observed after thoracic irradiation compared to those in pulmonary arterial hypertension patients and research models. We will also assess how this knowledge of similarities could potentially be translated into interventions which would be beneficial for patients treated for thoracic tumors, where dose to lung tissue is often unavoidable

Regional Responses in Radiation-Induced Normal Tissue Damage

Simple SummarySide effects caused by the concomitant irradiation of normal tissue during radiotherapy for cancer treatment can negatively affect the patient's quality of life and limit the radiation dose that can safely be administered to the tumor. Recently, considerable developments have been achieved in radiotherapy and imaging technologies, allowing the selective sparing of the regions within organs that contribute most to the development of these side effects. This review discusses regional variation in the response to radiation in several organs, including the brain, salivary glands, cardiopulmonary system, pancreas, and bladder. Regional responses are shown to originate from general principles, such as the localization of target cells or function. We conclude that regional responses are a general phenomenon that should be studied in other organs. This will facilitate further optimization of the use of modern radiotherapy technologies.Normal tissue side effects remain a major concern in radiotherapy. The improved precision of radiation dose delivery of recent technological developments in radiotherapy has the potential to reduce the radiation dose to organ regions that contribute the most to the development of side effects. This review discusses the contribution of regional variation in radiation responses in several organs. In the brain, various regions were found to contribute to radiation-induced neurocognitive dysfunction. In the parotid gland, the region containing the major ducts was found to be critical in hyposalivation. The heart and lung were each found to exhibit regional responses while also mutually affecting each other's response to radiation. Sub-structures critical for the development of side effects were identified in the pancreas and bladder. The presence of these regional responses is based on a non-uniform distribution of target cells or sub-structures critical for organ function. These characteristics are common to most organs in the body and we therefore hypothesize that regional responses in radiation-induced normal tissue damage may be a shared occurrence. Further investigations will offer new opportunities to reduce normal tissue side effects of radiotherapy using modern and high-precision technologies.</p

Radiation-induced cardiac side-effects: The lung as target for interacting damage and intervention

Radiotherapy is part of the treatment for many thoracic cancers. During this treatment heart and lung tissue can often receive considerable doses of radiation. Doses to the heart can potentially lead to cardiac effects such as pericarditis and myocardial fibrosis. Common side effects after lung irradiation are pneumonitis and pulmonary fibrosis. It has also been shown that lung irradiation has effects on cardiac function. In a rat model lung irradiation caused remodeling of the pulmonary vasculature increasing resistance of the pulmonary vascular bed, leading to enhanced pulmonary artery pressure, right ventricle hypertrophy and reduced right ventricle performance. Even more pronounced effects are observed when both, lung and heart are irradiated.The effects observed after lung irradiation show striking similarities with symptoms of pulmonary arterial hypertension. In particular, the vascular remodeling in lung tissue seems to have similar underlying features. Here, we discuss the similarities and differences of vascular remodeling observed after thoracic irradiation compared to those in pulmonary arterial hypertension patients and research models. We will also assess how this knowledge of similarities could potentially be translated into interventions which would be beneficial for patients treated for thoracic tumors, where dose to lung tissue is often unavoidable

Academic achievement of children with autistic symptoms compared to typically developing children

Children with autistic symptoms experience challenges in school settings, yet little is known about their academic profiles and the mechanisms underlying the association between autistic symptoms and academic achievement. This study examined the association between autistic symptoms and academic achievement in a population-based sample of children with and without (sub)clinical autism spectrum disorder (ASD). We also investigated potential sex differences and assessed if the association is mediated by vocabulary skills and behavior problems. Information was available for 2038 participants (48.3% boys), and autistic symptoms were assessed using the Social Responsiveness Scale (M = 6.8 years). Diagnosis of ASD was clinically confirmed in 28 children. Academic achievement was determined by a nationwide, standardized test assessed at the end of primary school (M = 11.8 years). Children with more autistic symptoms in early childhood had lower achievement scores in language, mathematics, and world orientation by the end of primary education. There were no sex differences. Furthermore, vocabulary skills and behavior problems partly mediated the association between autistic symptoms and academic achievement. Then, by using propensity matching technique, we compared 140 matched typically developing peers with 28 children diagnosed with ASD. These results indicated no differences in academic achievement between children diagnosed with ASD and their matched typically developing peers. We conclude that autistic symptoms associate with lower academic achievement but by carefully matching on background variables and potential confounders, the academic achievement of children with clinical ASD might not differ from that of their typically developing peers.</p

Prediction of Radiation-Induced Parotid Gland-Related Xerostomia in Patients With Head and Neck Cancer:Regeneration-Weighted Dose

Purpose: Despite improvements to treatment, patients with head and neck cancer (HNC) still experience radiation-induced xerostomia due to salivary gland damage. The stem cells of the parotid gland (PG), concentrated in the gland's main ducts (stem cell rich [SCR] region), play a critical role in the PG's response to radiation. Treatment optimization requires a dose metric that properly accounts for the relative contributions of dose to this SCR region and the PG's remainder (non-SCR region) to the risk of xerostomia in normal tissue complication probability (NTCP) models for xerostomia.Materials and methods: Treatment and toxicity data of 1013 prospectively followed patients with HNC treated with definitive radiation therapy (RT) were used. The regeneration-weighted dose, enabling accounting for the hypothesized different effects of dose to the SCR and non-SCR region on the risk of xerostomia, was defined as Dreg PG = Dmean SCR region + r × Dmean non-SCR region, where Dreg is the regeneration-weighted dose, Dmean is the mean dose, and r is the weighting factor. Considering the different volumes of these regions, r &gt; 3.6 in Dreg PG demonstrates an enhanced effect of the SCR region. The most predictive value of r was estimated in 102 patients of a previously published trial testing stem cell sparing RT. For each endpoint, Dreg PG, dose to other organs, and clinical factors were used to develop NTCP models using multivariable logistic regression analysis in 663 patients. The models were validated in 350 patients.Results: Dose to the contralateral PG was associated with daytime, eating-related, and physician-rated grade ≥2 xerostomia. Consequently, r was estimated and found to be smaller than 3.6 for most PG function-related endpoints. Therefore, the contribution of Dmean SCR region to the risk of xerostomia was larger than predicted by Dmean PG. Other frequently selected predictors were pretreatment xerostomia and Dmean oral cavity. The validation showed good discrimination and calibration.Conclusions: Tools for clinical implementation of stem cell sparing RT were developed: regeneration-weighted dose to the parotid gland that accounted for regional differences in radiosensitivity within the gland and NTCP models that included this new dose metric and other prognostic factors

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