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Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic lung disease with an unknown cause. Uncertainties still remain regarding the pathogenesis of IPF, and the prognosis of this disease is poor despite some recent improvements in treatment. Radiation induced lung injury (RILI) is a common complication and a dose-limiting toxicity of thoracic radiotherapy. Importantly, IPF is a crucial risk factor for pulmonary toxicity after thoracic radiotherapy. Although IPF is not universally accepted as a definite contraindication for thoracic radiotherapy at present, it has been shown that IPF can increase the risk of severe and fatal complications after thoracic radiotherapy. Proton beam therapy has shown promising results in reducing the incidence of thoracic radiotherapy related life-threatening complications in IPF patients, but the current evidence is not sufficient to recommend the standard use of it. Many similarities are noticeable between IPF and RILI in terms of pathogenesis and underlying mechanisms. Better understanding of the mechanisms of IPF and RILI may enable clinicians to provide safer and more effective thoracic radiotherapy treatments in cancer patients with IPF. In this review, we summarize the current knowledge of IPF, present the importance of IPF in radiation oncology practice, and highlight the similarities and relationship between IPF and RILI. (C) 2020 Elsevier B.V. All rights reserved.

Normal tissue complication probability (NTCP) models that were formulated in the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) are one of the pillars in support of everyday's clinical radiation oncology. Because of steady therapeutic refinements and the availability of cutting-edge technical solutions, the ceiling of organs-at-risk-sparing has been reached for photon-based intensity modulated radiotherapy (IMRT). The possibility to capture heterogeneity of patients and tissues in the prediction of toxicity is still an unmet need in modern radiation therapy. Potentially, a major step towards a wider therapeutic index could be obtained from refined assessment of radiation-induced morbidity at an individual level. The rising integration of quantitative imaging and machine learning applications into radiation oncology workflow offers an unprecedented opportunity to further explore the biologic interplay underlying the normal tissue response to radiation. Based on these premises, in this review we focused on the current-state-of-the-art on the use of radiomics for the prediction of toxicity in the field of head and neck, lung, breast and prostate radiotherapy.

// Wen-Yan Pan 1, 2 , Chao Bian 3 , Guan-Lian Zou 3 , Cui-Ying Zhang 1, 2 , Ping Hai 1, 2 , Ren Zhao 1, 2 and Yan-Yang Wang 1, 2 1 Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China 2 Cancer Institute, Ningxia Medical University, Yinchuan 750004, Ningxia, China 3 Graduate School, Ningxia Medical University, Yinchuan 750004, Ningxia, China Correspondence to: Yan-Yang Wang, email: fdwyy1981@hotmail.com , wangyy@nxmu.edu.cn Ren Zhao, email: nxzr1964@hotmail.com Keywords: neutrophil to lymphocyte ratio (NLR), V20, mean lung dose, radiation induced lung injury, lung cancer Received: March 06, 2017 Accepted: June 18, 2017 Published: July 06, 2017 ABSTRACT The purpose was to evaluate the predictive value of baseline neutrophil to lymphocyte ratio (NLR) level in the incidence of grade 3 or higher radiation induced lung injury (RILI) for lung cancer patients. A retrospectively analysis with 166 lung cancer patients was performed. All of the enrolled patients received chemoradiotherapy at our hospital between April 2014 and May 2016. The Cox proportional hazard model was used to identify the potential risk factors for RILI. In this cohort, the incidence of grade 3 or higher RILI was 23.8%. Univariate analysis showed that radiation dose, volume at least received 20Gy (V20), mean lung dose and NLR were significantly associated with the incidence of grade 3 or higher RILI ( P = 0.012, 0.008, 0.012, and 0.039, respectively). Multivariate analysis revealed that total dose ≥ 60 Gy, V20 ≥ 20%, mean lung dose ≥ 12 Gy, and NLR ≥ 2.2 were still independent predictive factors for RILI ( P = 0.010, 0.043, 0.028, and 0.015, respectively). A predictive model of RILI based on the identified risk factors was established using receiver operator characteristic curves. The results demonstrated that the combination analysis of V20, mean lung dose and NLR was superior to either of the variables alone. Additionally, we found that the constraint of V20 and mean lung dose were meaningful for patients with higher baseline NLR level. If the value of V20 and mean lung dose lower than the threshold value, the incidence of grade 3 or higher RILI for the high NLR level patients could be decreased from 63.3% to 8.7%. Our study showed that radiation dose, V20, mean lung dose and NLR were independent predictors for RILI. Combination analysis of V20, mean lung dose and NLR may provide a more accurate model for RILI prediction.

Purpose: The standard of care in Locally-Advanced Non-Small Cell Lung Cancer (LA-NSCLC) is chemotherapy and radiation; however, Radiation-Induced Lung Injury (RILI), which may be prevented by the anti-inflammatory and anti-oxidant properties of Flaxseed (FS), impedes its maximum benefit. Materials and Methods: Patients with LA-NSCLC requiring definitive RT were randomized to one FS or control muffin daily from start to 2 weeks after RT. Blood and urine were collected to quantify plasma FS metabolites, Enterodione (ED) and Enterolactone (EL), and urinary oxidative stress biomarkers, 8, 12-iso-iPF2a-VI (isoprostane) and 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxo-dGuo). Tolerability was defined as consuming ≥ 75% of the intended muffins and no ≥ grade 3 gastrointestinal toxicities. Results: Fourteen patients (control,7; FS,7) were enrolled. The tolerability rates were 42.9 versus 71.4% (p=0.59) for FS and control, respectively. Mean percentages of intended number of muffins consumed were 37% versus 73% (p=0.12). ED and EL increased at onset of FS and decreased with discontinuation, confirming bioavailability. Isoprostane and 8-oxo-dGuo were detectable. There was a trend towards decreased rates of pneumonitis in FS. Conclusions: This is the first study to report FS bioavailability and quantify oxidative stress markers in NSCLC patients. FS in the administered muffin formulation did not meet tolerability criteria. Given the promising mechanism of FS as a radioprotectant, further investigations should focus on the optimal method for administration of FS.

Imaging of the lungs using non-ionizing approaches such as hyperpolarized 3He and 129Xe magnetic resonance imaging (MRI) is a useful tool both for research and clinical applications. This work focused on development of 129Xe MRI techniques to investigate inflammation in rat lungs. A rodent model of inflammation, specifically radiation-induced lung injury (RILI) was developed using a collimated 60Co source. A quantitative MRI technique measuring absolute ventilated lung volume (|VLV|) was performed using 129Xe and 3He. Following a comparison between |VLV| values obtained from rats using the previously established 3He method and those obtained with 129Xe, the usefulness of 129Xe for future investigations of |VLV| in rodent models of inflammation was demonstrated. 129Xe dynamic spectroscopy was used to investigate the predicted gas transfer deficiencies represented by xenon gas transfer time constants (TTr) for 129Xe dissolved within tissue (TTr_tissue) and blood (TTr_RBC) in a model of RILI. Increases in TTr_tissue were measured at two weeks post irradiation together with decreases in the partial pressure of arterial oxygen (paO2), consistent with the assumption of gas exchange impairment. Finally, a novel minimally invasive intubation technique was investigated to support longitudinal studies in rodent models of inflammation. This serves to reduce the overall numbers of animals used within a given study as well as reduce uncertainty in measurements due to biological differences in end-point studies. These investigations lay the groundwork for future reliance on 129Xe for hyperpolarized imaging studies of the lung as well as strengthening the methodology for future longitudinal investigations of inflammation.

PURPOSE: Therapeutic radiation doses for thoracic tumors are significantly restricted to decrease the risk of nontumor tissue damage, yet radiation-induced lung injury (RILI) still occurs in over 1/3 of thoracic radiation treatment cases. Although RILI can be clinically monitored using pulmonary function measurements, the regional functional effects of the injury are not well understood. Hyperpolarized 3He magnetic resonance imaging provides measurements of regional lung function and structure with high spatial and temporal resolution; the authors use this tool longitudinally for the first time in seven subjects after clinical diagnosis of RILI in order to better understand regional changes in lung function and structure post-RILI. METHODS: All subjects underwent spirometry, plethysmography, and MRI at 3.0 T 35.1 +/- 12.2 weeks after radiation therapy commenced. Thoracic 1H, static 3He ventilation, and 3He diffusion-weighted images were acquired to generate the 3He apparent diffusion coefficient (ADC) and 3He percent ventilated volume (PVV). Four subjects returned 22.0 +/- 0.8 weeks after baseline imaging for follow-up spirometry and 3He MRI measurements of ADC and PVV. RESULTS: At baseline, PVV was significantly different (p = 0.025) and lower in the ipsilateral diseased lung (55 +/- 29%) compared to the contralateral nondiseased lung (88 +/- 5%). Longitudinally, significant increases were observed for 3He MRI PVV (16% +/- 6%, p = 0.012) and 3He MRI ADC (0.02 +/- 0.01 cm2/s, p = 0.003) in the contralateral lung only, in the four subjects who returned for follow-up, while no changes in the ipsilateral lung were reported. CONCLUSIONS: Hyperpolarized 3He MRI was well tolerated in all subjects with moderate to severe RILI. Functional improvements and microstructural changes were observed in the contralateral lung, while the ipsilateral lung remained stable, suggesting that functional compensatory changes may have occurred in the contralateral lung due to ipsilateral lung radiation-induced injury.