Radiation-Induced Lung Injury

Hanania, Alexander N.; Mainwaring, W.I.P.; Ghebre, Yohannes T.; Hanania, Nicola A.; Ludwig, Michelle

doi:10.1016/j.chest.2019.03.033

Cited by 341 publications

(151 citation statements)

References 92 publications

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“…As noted above, TGF-β is probably the most widely studied pro-fibrotic factor that has a clear relationship to RT-induced collagen deposition and lung fibrosis [2,3,53,54]. Indeed, TGF-β plays a critical role in every stage of RT-induced fibrosis, including its initiation, development, and persistence [75].…”

Section: Discussionmentioning

confidence: 99%

“…Although there was considerable variability among the individual animals, the levels of the active form TGF-β1 was clearly decreased by DEX at 7 weeks after five fractions of RT in adipose tissue ( Figure 8A,B). Connective tissue growth factor (CTGF), a downstream effector of TGF-β and another key mediator of the fibrotic cascade [53,54], was also decreased by DEX. DEX treatment at the time of RT decreased the concentration of CXCL2 and increased that of LIF in the adipose tissue after 7 weeks ( Figure 7A).…”

Section: Dexamethasone Attenuates Rt-induced Fibrosis At 7 Weeks In Tmentioning

confidence: 99%

“…We also studied the effect of DEX treatment on the pro-fibrotic cytokine, transforming growth factor β (TGF-β), which has a well-known role in the pathogenesis of RT-induced fibrosis of the lung and other tissues in both rodent models and humans [50][51][52][53][54]. We focused on TGF-β1 since it is the most ubiquitously distributed isoform in mammalian tissues and it contributes largely to the pro-fibrotic effects of TGF-β.…”

Section: Dexamethasone Attenuates Rt-induced Fibrosis At 7 Weeks In Tmentioning

confidence: 99%

“…Although there was considerable variability among the individual animals, the levels of the active form TGF-β1 was clearly decreased by DEX at 7 weeks after five fractions of RT in adipose tissue ( Figure 8A,B). Connective tissue growth factor (CTGF), a downstream effector of TGF-β and another key mediator of the fibrotic cascade [53,54], was also decreased by DEX. We indirectly assessed the effect of DEX on oxidative stress, another recognized mediator of fibrosis [2,53], in our model system by monitoring the level of the antioxidant transcription factor nuclear factor erythroid 2-like factor 2 (Nrf2), which is modulated by ionizing radiation [55].…”

Section: Dexamethasone Attenuates Rt-induced Fibrosis At 7 Weeks In Tmentioning

confidence: 99%

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Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Meng

Wuest

Tang

et al. 2020

Cancers

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We recently showed that radiation-induced DNA damage in breast adipose tissue increases autotaxin secretion, production of lysophosphatidate (LPA) and expression of LPA1/2 receptors. We also established that dexamethasone decreases autotaxin production and LPA signaling in non-irradiated adipose tissue. In the present study, we showed that dexamethasone attenuated the radiation-induced increases in autotaxin activity and the concentrations of inflammatory mediators in cultured human adipose tissue. We also exposed a breast fat pad in mice to three daily 7.5 Gy fractions of X-rays. Dexamethasone attenuated radiation-induced increases in autotaxin activity in plasma and mammary adipose tissue and LPA1 receptor levels in adipose tissue after 48 h. DEX treatment during five daily fractions of 7.5 Gy attenuated fibrosis by ~70% in the mammary fat pad and underlying lungs at 7 weeks after radiotherapy. This was accompanied by decreases in CXCL2, active TGF-β1, CTGF and Nrf2 at 7 weeks in adipose tissue of dexamethasone-treated mice. Autotaxin was located at the sites of fibrosis in breast tissue and in the underlying lungs. Consequently, our work supports the premise that increased autotaxin production and lysophosphatidate signaling contribute to radiotherapy-induced breast fibrosis and that dexamethasone attenuated the development of fibrosis in part by blocking this process.

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Section: Discussionmentioning

confidence: 99%

Section: Dexamethasone Attenuates Rt-induced Fibrosis At 7 Weeks In Tmentioning

confidence: 99%

Section: Dexamethasone Attenuates Rt-induced Fibrosis At 7 Weeks In Tmentioning

confidence: 99%

“…Although there was considerable variability among the individual animals, the levels of the active form TGF-β1 was clearly decreased by DEX at 7 weeks after five fractions of RT in adipose tissue ( Figure 8A,B). Connective tissue growth factor (CTGF), a downstream effector of TGF-β and another key mediator of the fibrotic cascade [53,54], was also decreased by DEX. We indirectly assessed the effect of DEX on oxidative stress, another recognized mediator of fibrosis [2,53], in our model system by monitoring the level of the antioxidant transcription factor nuclear factor erythroid 2-like factor 2 (Nrf2), which is modulated by ionizing radiation [55].…”

Section: Dexamethasone Attenuates Rt-induced Fibrosis At 7 Weeks In Tmentioning

confidence: 99%

See 2 more Smart Citations

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Meng

Wuest

Tang

et al. 2020

Cancers

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“…In addition to the heart, the lungs are also at risk of developing short-and long-term injuries after exposure to ionizing radiation [98][99][100]. In the pathogenesis of radiation-induced lung injury, several Cancers 2020, 12, 415 6 of 22 phases are recognized [100]. An early inflammatory phase is followed by the gradual development of radiation fibrosis and loss of lung function.…”

Section: Cardiopulmonary Tissue Toxicity From Rtmentioning

confidence: 99%

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

Schlaak

SenthilKumar

Boerma

et al. 2020

Cancers

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Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short-and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.

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A pilot study of function‐based radiation therapy planning for lung cancer using hyperpolarized xenon‐129 ventilation MRI

Ding

Yang

Zhou

et al. 2022

J Applied Clin Med Phys

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Purpose Radiation‐induced lung injury (RILI) is a common side effect in patients with non‐small cell lung cancer (NSCLC) treated with radiotherapy. Minimizing irradiation into highly functional areas of the lung may reduce the occurrence of RILI. The aim of this study is to evaluate the feasibility and utility of hyperpolarized xenon‐129 magnetic resonance imaging (MRI), an imaging tool for evaluation of the pulmonary function, to guide radiotherapy planning. Methods Ten locally advanced NSCLC patients were recruited. Each patient underwent a simulation computed tomography (CT) scan and hyperpolarized xenon‐129 MRI, then received 64 Gyin 32 fractions for radiotherapy. Clinical contours were drawn on CT. Lung regions with good ventilation were contoured based on the MRI. Two intensity‐modulated radiation therapy plans were made for each patient: an anatomic plan (Plan‐A) based on CT alone and a function‐based plan (Plan‐F) based on CT and MRI results. Compared to Plan‐A, Plan‐F was generated with two additional steps: (1) beam angles were carefully chosen to minimize direct radiation entering well‐ventilated areas, and (2) additional optimization criteria were applied to well‐ventilated areas to minimize dose exposure. V20Gy, V10Gy, V5Gy, and the mean dose in the lung were compared between the two plans. Results Plan‐A and Plan‐F were both clinically acceptable and met similar target coverage and organ‐at‐risk constraints (p > 0.05) except for the ventilated lungs. Compared with Plan‐A, V5Gy (Plan‐A: 30.7 ± 11.0%, Plan‐F: 27.2 ± 9.3%), V10Gy (Plan‐A: 22.0 ± 8.6%, Plan‐F: 19.3 ± 7.0%), and V20Gy (Plan‐A: 12.5 ± 5.6%, Plan‐F: 11.0 ± 4.1%) for well‐ventilated lung areas were significantly reduced in Plan‐F (p < 0.05). Conclusion In this pilot study, function‐based radiotherapy planning using hyperpolarized xenon‐129 MRI is demonstrated to be feasible in 10 patients with NSCLC with the potential to reduce radiation exposure in well‐ventilated areas of the lung defined by hyperpolarized xenon‐129 MRI.

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Radiation-Induced Lung Injury

Cited by 341 publications

References 92 publications

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Dexamethasone Attenuates X-Ray-Induced Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle in Breast Tissue and Subsequent Breast Fibrosis

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

A pilot study of function‐based radiation therapy planning for lung cancer using hyperpolarized xenon‐129 ventilation MRI

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