Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

Tsoutsou, Pelagia G.; Koukourakis, Michael I.

doi:10.1016/j.ijrobp.2006.08.058

Cited by 288 publications

(225 citation statements)

References 129 publications

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“…Although new radiotherapeutic techniques are applied, such as the Three-Dimensional Conformal Radiation Therapy, which definitely induce decreased radiation toxicity to adjacent healthy tissues, the radiation-induced lung injury remains a recurrent complication of radiation on the pulmonary parenchyma (Tarbell et al, 1990;Tsoutsou and Koukourakis, 2006;Kocak et al, 2007). Clinically, radiation-induced lung injury is divided into two phases: the early phase of RP and the late phase of radiation-induced fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Ever since, the pathophysiology, the clinical and radiological image of the said disease is analysed in many bibliographical references. Albeit developments in radiotherapy techniques, such as the Three-Dimensional Conformal Radiation Therapy (3DCRT) and the IntensityModulated Radiation Therapy (IMRT), which offer greater protection to adjacent healthy tissues and, at the same time, increase the dose absorbed by the tumour target, the frequency of RP has not been eliminated (Bucci et al, 2005;Tsoutsou and Koukourakis, 2006;Guckenberger et al, 2010). Although, some inflammatory mediators such as amifostine (Kouvaris et al, 2007) or Toll-like receptor agonism (Wang et al, 2012) have shown evidence of radioprotection in vitro and in vivo studies, RP clearly remains a radiation dosimetric-related morbidity (Zhang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Suggestion for a New Grading Scale for Radiation Induced Pneumonitis Based on Radiological Findings of Computerized Tomography: Correlation with Clinical and Radiotherapeutic Parameters in Lung Cancer Patients

Kouloulias

Zygogianni²,

Efstathopoulos³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: The objective of this research is the computed axial tomography (CT) imaging grading of radiation induced pneumonitis (RP) and its correlation with clinical and radiotherapeutic parameters. Materials and Methods: The chest CT films of 20 patients with non-small cell lung cancer who have undergone threedimensional conformal radiation therapy were reviewed. The proposed CT grading of RP is supported on solely radiological diagnosis criteria and distinguishes five grades. The manifestation of RP was also correlated with any positive pre-existing chronic obstructive pulmonary disease (COPD) history, smoking history, the FEV1 value, and the dosimetric variable V20. Results: The CT grading of RP was as follows: 3 patients (15%) presented with ground glass opacity (grade 1), 9 patients (45%) were classified as grade 2, 7 patients (35%) presented with focal consolidation, with or without elements of fibrosis (grade 3), and only one patient (5%) presented with opacity with accompanying atelectasis and loss of pulmonary volume (grade 4). Both univariate and multivariate analysis revealed as prognostic factors for the radiological grading of RP the reduction of FEV1 and the V20 (P=0.026 and P=0.003, respectively). There was also a significant (P<0.001) correlation of radiological grading of RP with FEV1 and V20 (spearman rho 0.92 and 0.93, respectively). Conclusions: The high correlation of the proposed radiological grading with the FEV1 and the V20 is giving a satisfactory clinical validity. Although the proposed grading scale seems relevant to clinical practice, further studies are needed for the confirmation of its validity and reliability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Suggestion for a New Grading Scale for Radiation Induced Pneumonitis Based on Radiological Findings of Computerized Tomography: Correlation with Clinical and Radiotherapeutic Parameters in Lung Cancer Patients

Kouloulias

Zygogianni²,

Efstathopoulos³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The histopathological changes to the irradiated lung have been well described (18,20,21). The inflammatory phase is generally characterized by alveolar cell depletion and inflammatory cell accumulation (4,22). This process initiated the activation of specific leukocyte subsets to produce important biological mediators, including cytokines, growth factors and chemokines, which participate in the majority of the aspects of the inflammatory response (4).…”

Section: A B Cmentioning

confidence: 99%

“…Following the treatment of patients by radiation, acute inflammation may be resolved with the recruitment of fibroblasts, resulting in interstitial collagen deposition and alveolar septal thickening during alveolar epithelial regeneration (4). Endothelial dysfunction is mainly caused by vascular damage and endothelial barrier injury, which may activate various pathophysiological cascades (5).…”

Section: Introductionmentioning

confidence: 99%

Radiation-induced pulmonary injury accelerated pulmonary metastasis in a mouse model of breast cancer

Gong

et al. 2015

Oncology Letters

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Abstract. The aim of the present study was to investigate the acceleration of pulmonary metastasis due to pulmonary injury caused by radiation treatment in a mouse model of breast cancer, in addition to determining the associated mechanism. The passive metastatic breast cancer model was used in radiation-treated BALB/c mice. In total, 24 mice were randomly separated into two groups, with 12 mice per group, and the groups were treated with or without pulmonary radiation. The survival time and variation of the weights of the lungs, spleen and liver were recorded. Lung metastasis was also evaluated, and chemokine (C-X-C motif) ligand 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) expression was determined. The results revealed that the group with radiation-induced pulmonary injury exhibited an increased incidence of pulmonary metastasis and shorter survival time compared with the mice without pulmonary radiation. The radiation-treated group possessed an increased number of metastatic nodules in the lungs, but metastasis was not evident in the liver and spleen. The CXCL12/CXCR4 axis was markedly expressed and the expression was significantly increased subsequent to radiation compared with the expression in normal lung tissues. The present study demonstrated that radiation-induced pulmonary injury may accelerate metastatic tumor growth and decrease the overall survival rate of the mice following in situ injection of tumor cells. Tumor localization and growth may have been favored by metastatic conditioning in the lung subsequent to radiotherapy. The CXCL12/CXCR4 axis may affect key elements in the multistep process of metastasis induced by radiation injury.

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“…However, current RT techniques expose both, normal tissues and tumors, to a wide range of dose size and fractionation, with a substantial amount of normal tissue being potentially irradiated (51). Herein, the high intrinsic sensitivity of normal tissues to ionizing radiation (IR) often precludes the application of curative radiation doses (32,76). In particular, thorax irradiation induces tissue inflammation (pneumonitis) and fibrosis within 12 weeks and 6-24 months after RT as dose-limiting side effects (12,22,37).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

Klein

Steens

Wiesemann

et al. 2017

Antioxidants & Redox Signaling

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Aims: Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect to the vascular compartment remain elusive, and no causative radioprotective treatment is available to date. Results: The importance of injury to EC for radiation-induced late toxicity in lungs after whole thorax irradiation (WTI) was investigated using a mouse model of radiation-induced pneumopathy. We show that WTI induces EC loss as long-term complication, which is accompanied by the development of fibrosis. Adoptive transfer of mesenchymal stem cells (MSCs) either derived from bone marrow or aorta (vascular wall-resident MSCs) in the early phase after irradiation limited the radiation-induced EC loss and fibrosis progression. Furthermore, MSC-derived culture supernatants rescued the radiation-induced reduction in viability and longterm survival of cultured lung EC. We further identified the antioxidant enzyme superoxide dismutase 1 (SOD1) as a MSC-secreted factor. Importantly, MSC treatment restored the radiation-induced reduction of SOD1 levels after WTI. A similar protective effect was achieved by using the SOD-mimetic EUK134, suggesting that MSCderived SOD1 is involved in the protective action of MSC, presumably through paracrine signaling. Innovation: In this study, we explored the therapeutic potential of MSC therapy to prevent radiation-induced EC loss (late effect) and identified the protective mechanisms of MSC action. Conclusions: Adoptive transfer of MSCs early after irradiation counteracts radiation-induced vascular damage and EC loss as late adverse effects. The high activity of vascular wall-derived MSCs for radioprotection may be due to their tissue-specific action. Antioxid. Redox Signal. 26, 563-582.

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Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

Cited by 288 publications

References 129 publications

Suggestion for a New Grading Scale for Radiation Induced Pneumonitis Based on Radiological Findings of Computerized Tomography: Correlation with Clinical and Radiotherapeutic Parameters in Lung Cancer Patients

Suggestion for a New Grading Scale for Radiation Induced Pneumonitis Based on Radiological Findings of Computerized Tomography: Correlation with Clinical and Radiotherapeutic Parameters in Lung Cancer Patients

Radiation-induced pulmonary injury accelerated pulmonary metastasis in a mouse model of breast cancer

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

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