Volume-Dependent Expression of In-Field and Out-of-Field Effects in the Proton-Irradiated Rat Lung

Coppes, Robert P.; Muijs, Christina T.; Faber, Hette; Groß, Sascha; Schippers, Jacobus Maarten; Brandenburg, S.; Langendijk, Johannes A.; Luijk, Peter van

doi:10.1016/j.ijrobp.2011.03.021

Cited by 14 publications

(8 citation statements)

References 42 publications

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“…The occurrence of actual neointimal lesions in this radiation-induced pulmonary hypertension may offer such a novel model. A unique feature of the radiation-induced model is the dependence of irradiated lung volume on the induction of damage52 and consequent changes in PAP (present work), which facilitates well controlled induction to predetermined levels of PAH to study different stages of disease development in a controlled manner.…”

Section: Discussionmentioning

confidence: 99%

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

Ghobadi

Bartelds

Veen

et al. 2011

Thorax

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Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension. Methods Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage. Results Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction. Conclusions The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

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Section: Discussionmentioning

confidence: 99%

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

Ghobadi

Bartelds

Veen

et al. 2011

Thorax

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“…Episomal reprogramming: system that reprograms somatic cells into induced PSCs, which are able to differentiate into almost any type of cell in the body.The risk and severity of lung radiation side effects depend on the dose and volume of the tissue involved [65,[72][73][74]. Therefore, technical advances that enable treatment optimization are currently used to reduce dose and volume of normal tissue receiving radiation.…”

Section: Box 2 Glossarymentioning

confidence: 99%

Prevention and treatment of radiotherapy‐induced side effects

2020

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Radiotherapy remains a mainstay of cancer treatment, being used in roughly 50% of patients. The precision with which the radiation dose can be delivered is rapidly improving. This precision allows the more accurate targeting of radiation dose to the tumor and reduces the amount of surrounding normal tissue exposed. Although this often reduces the unwanted side effects of radiotherapy, we still need to further improve patients' quality of life and to escalate radiation doses to tumors when necessary. Highprecision radiotherapy forces one to choose which organ or functional organ substructures should be spared. To be able to make such choices, we urgently need to better understand the molecular and physiological mechanisms of normal tissue responses to radiotherapy. Currently, oversimplified approaches using constraints on mean doses, and irradiated volumes of normal tissues are used to plan treatments with minimized risk of radiation side effects. In this review, we discuss the responses of three different normal tissues to radiotherapy: the salivary glands, cardiopulmonary system, and brain. We show that although they may share very similar local cellular processes, they respond very differently through organ-specific, nonlocal mechanisms. We also discuss how a better knowledge of these mechanisms can be used to treat or to prevent the effects of radiotherapy on normal tissue and to optimize radiotherapy delivery.

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“…x FOR PEER REVIEW 9 of 2 The effect of lung irradiation is not limited to the irradiated part, but also occurs i surrounding shielded tissue [131,132,135,136]. For instance, micronuclei formation in non irradiated areas has been suggested to relate to the release of cytokines or reactive oxyge species (ROS) formation in irradiated areas [131,132].…”

Section: Alveolar and Microvascular Dense Regions Of The Lungmentioning

confidence: 99%

Regional Responses in Radiation-Induced Normal Tissue Damage

Voshart

Wiedemann

Luijk

et al. 2021

Cancers

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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.

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Volume-Dependent Expression of In-Field and Out-of-Field Effects in the Proton-Irradiated Rat Lung

Cited by 14 publications

References 42 publications

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

Prevention and treatment of radiotherapy‐induced side effects

Regional Responses in Radiation-Induced Normal Tissue Damage

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