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Abstract Background Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. Results Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. Conclusions Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Background: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. Results: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. Conclusions: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Try to create a dose gradient function (DGF) and test its effectiveness in reducing radiation induced lung injury in breast cancer radiotherapy. MATERIALS AND METHODS: Radiotherapy plans of 30 patients after breast-conserving surgery were included in the study. The dose gradient function was defined as D G H = V D V p 3 , then the area under the DGF curve of each plan was calculated in rectangular coordinate system, and the minimum area was used as the trigger factor, and other plans were triggered to optimize for area reduction. The dosimetric parameters of target area and organs at risk in 30 cases before and after re-optimization were compared. RESULTS: On the premise of ensuring that the target dose met the clinical requirements, the trigger factor obtained based on DGF could further reduce the V5, V10, V20, V30 and mean lung dose (MLD) of the ipsilateral lung in breast cancer radiotherapy, P < 0.01. And the D2cc and mean heart dose (MHD) of the heart were also reduced, P < 0.01. Besides, the NTCPs of the ipsilateral lung and the heart were also reduced, P < 0.01. CONCLUSION: The trigger factor obtained based on DGF is efficient in reducing radiation induced lung injury in breast cancer radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate computed tomography (CT) patterns of post-SBRT lung injury in lung cancer and identify time points of serial CT changes. Materials and methods One hundred eighty-three tumors in 170 patients were evaluated on sequential CTs within 29 months (median). Frequencies of post-SBRT CT patterns and time points of initiation and duration were assessed. Duration of increase of primary lesion or surrounding injury without evidence of local recurrence and time to stabilization or local recurrence were evaluated. Results Post-SBRT CT patterns could overlap in the same patient and were nodule-like pattern (69%), consolidation with ground glass opacity (GGO) (41%), modified conventional pattern (39%), peribronchial/patchy consolidation (42%), patchy GGO (24%), diffuse consolidation (16%), “orbit sign” (21%), mass-like pattern (19%), scar-like pattern (15%) and diffuse GGO (3%). Patchy GGO started at 4 months post-SBRT. Peribronchial/patchy consolidation and consolidation with GGO started at 4 and 5 months respectively. Diffuse consolidation, diffuse GGO and orbit sign started at 5, 6 and 8 months respectively. Mass-like, modified conventional and scar-like pattern started at 8, 12 and 12 months respectively. Primary lesion (n = 11) or surrounding injury (n = 85) increased up to 13 months. Primary lesion (n = 119) or surrounding injury (n = 115) started to decrease at 4 and 9 months respectively. Time to stabilization was 20 months. The most common CT pattern at stabilization was modified conventional pattern (49%), scar-like pattern (23%) and mass-like pattern (12%). Local recurrence (n = 15) occurred at a median time of 18 months. Conclusion Different CT patterns of lung injury post-SBRT appear in predictable time points and have variable but predictable duration. Familiarity with these patterns and timeframes of appearance helps differentiate them from local recurrence.

Abstract The glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism.

Purpose: Radiation-induced lung injury (RILI) is a progressive condition with an early phase (radiation pneumonitis) and a late phase (lung fibrosis). RILI may occur after partial-body ionizing radiation exposures or internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aimed to provide new insights into the pathogenesis and progression of RILI in the nonhuman primate (NHP) rhesus macaque model.Methods and Materials: We used an integrative approach to understand RILI and its evolution at clinical and molecular levels in 17 NHPs exposed to 10 Gy of whole-thorax irradiation in comparison with 3 sham-irradiated control NHPs. Clinically, we monitored respiratory rates, computed tomography (CT) scans, plasma cytokine levels, and bronchoalveolar lavage (BAL) over 8 months and lung samples collected at necropsy for molecular and histopathologic analyses using RNA sequencing and immunohistochemistry.Results: Elevated respiratory rates, greater CT density, and more severe pneumonitis with increased macrophage content were associated with early mortality. Radiation-induced lung fibrosis included polarization of macrophages toward the M2-like phenotype, TGF-β signaling, expression of CDKN1A/p21 in epithelial cells, and expression of α-SMA in lung stroma. RNA sequencing analysis of lung tissue revealed SERPINA3, ATP12A, GJB2, CLDN10, TOX3, and LPA as top dysregulated transcripts in irradiated animals. In addition to transcriptomic data, we observed increased protein expression of SERPINA3, TGF-β1, CCL2, and CCL11 in BAL and plasma samples.Conclusions: Our combined clinical, imaging, histologic, and transcriptomic analysis provides new insights into the early and late phases of RILI and highlights possible biomarkers and potential therapeutic targets of RILI. Activation of TGF-β and macrophage polarization appear to be key mechanisms involved in RILI. [ABSTRACT FROM AUTHOR]

The glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism. [ABSTRACT FROM AUTHOR]

• Idiopathic pulmonary fibrosis (IPF) has a poor prognosis. • IPF and radiation induced lung injury share many similarities in pathogenesis. • IPF increases complication risk in patients receiving thoracic radiotherapy. • Multidisciplinary evaluation is required regarding thoracic radiotherapy for patients with IPF. • Proton beam therapy seems to be a safer thoracic radiotherapy technique for patients with IPF. 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. [ABSTRACT FROM AUTHOR]

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.

It is reported inflammatory cytokine interleukin-8 (IL-8) could predict radiation-induced lung toxicity (RILT). RILT is believed to be a consequence of a cascade of cytokine production. It is considered that vascular endothelial cell and macrophages are the mainly source of cytokines. This study was investigated the production of IL-8 from cancer cells induced by X-rays may involve in the radiation-induced inflammation. We analyzed IL-8 in human lung cancer cell lines after expose to X-rays, and we also detect IL-8 in HUVEC cells and THP1 cells as endothelial cell and macrophage model to identify the change in normal cells after expose. Furthermore, we added the inhibitors to the culture with or without radiation to identify the role of MAPK and NF-κB pathways on the radiation-induced secretion of IL-8. Radiation could induce IL-8 production both in non-lung cancer cells (HUVECs and THP1 cells) and in lung cancer cells (A549 cells, H446 cells, PC-9 cells). Simultaneously, radiation activated p38/MAPK and NF-κB signal pathways in lung cancer cells. Moreover, p38/MAPK inhibitor SB203580 and NF-κB inhibitor BAY11-7082 could block the IL-8 up-regulated by X-rays but JNK inhibitor SP600125, ERK inhibitor U0126, ROS Scavenger NAC could not inhibit this phenomenon. X-rays could induce IL-8 production in lung cancer cells, which may be related to the activation of p38/MAPK and NF-κB signaling pathway, providing a new point for elucidating the mechanism of radiation pneumonitis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Alveolar macrophages are a key component of the lung microenvironment and alter their functionality according to signals they encounter. • Macrophages accumulate in the lung following exposure to ionizing radiation and are implicated in chronic inflammation and pathogenesis of radiation induced pulmonary fibrosis. • A novel uni-lung irradiation approach allows for investigation of the role the pulmonary microenvironment plays in macrophage and T cell dynamics in murine models. • Findings from this study contribute to a better understanding of the mechanisms responsible for immune-regulated radiation toxicities to the lung, both locally and systemically. The lung is sensitive to radiation, increasing normal tissue toxicity risks following radiation therapy. Adverse outcomes include pneumonitis and pulmonary fibrosis, which result from dysregulated intercellular communication within the pulmonary microenvironment. Although macrophages are implicated in these pathogenic outcomes, the impact of their microenvironment is not well understood. C57BL/6J mice received 6Gyx5 irradiation to the right lung. Macrophage and T cell dynamics were investigated in ipsilateral right lungs, contralateral left lungs and non-irradiated control lungs 4-26wk post exposure. Lungs were evaluated by flow cytometry, histology and proteomics. Following uni-lung irradiation, focal regions of macrophage accumulation were noted in both lungs by 8wk, however by 26wk fibrotic lesions were observed only in ipsilateral lungs. Infiltrating and alveolar macrophages populations expanded in both lungs, however transitional CD11b + alveolar macrophages persisted only in ipsilateral lungs and expressed lower CD206. Concurrently, arginase-1 + macrophages accumulated in ipsilateral but not contralateral lungs at 8 and 26wk post exposure, while CD206 + macrophages were absent from these accumulations. While radiation expanded CD8 + T cells in both lungs, T regulatory cells only increased in ipsilateral lungs. Unbiased proteomics analysis of immune cells revealed a substantial number of differentially expressed proteins in ipsilateral lungs when compared to contralateral lungs and both differed from non-irradiated controls. Pulmonary macrophage and T cell dynamics are impacted by the microenvironmental conditions that develop following radiation exposure, both locally and systemically. While macrophages and T cells infiltrate and expand in both lungs, they diverge phenotypically depending on their environment. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of hyperpolarized (HP) 129Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a 60Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (LPT) and relative blood volume (VRBC) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in LPT and VRBC were observed between the irradiated and non-irradiated cohorts. In particular, LPT of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, VRBC of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the MRI measurements for both the non-irradiated (r = 0.79, P < 0.01) and irradiated groups (r = 0.91, P < 0.01). Conclusions: Regional RILI can be detected two weeks post-irradiation using HP 129Xe MRI and analysis of gas exchange curves. This approach correlates well with histology and can potentially be used clinically to assess radiation pneumonitis associated with early RILI to improve radiation therapy outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Ligustrazine Injection on plasma TGF- beta 1 level and preventive effect on radiation-induced lung injury. Methods: 120 patients with thoracic tumor radiotherapy were randomly divided into observation group and control group, 60 cases, 60 cases, all the patients were treated with three-dimensional conformal radiation therapy. The observation group was treated with ligustrazine injection 1 times daily. Results: The plasma levels of TGF- beta 1 were detected before and after radiotherapy. The incidence of radiation induced lung injury was observed in the two groups after radiotherapy 3 months and 6 months. The plasma levels of TGF- 1 in the two groups were increased, and the levels of TGF- in June and March were significantly lower than those in the control group (P<0.05) (19.12 ± 5.23) vs (26.69 ± 5.38) ng/mL, (5.62 ± 3.48) vs (9.64 ± 7.82) ng/mL, (3.28 ± 1.81) vs (7.98 ± 5.16) ng/mL. The incidence of lung injury in the observation group was significantly lower than that in the control group (FVC). The TLC, DLCO and P<0.05 were significantly lower than those in the control group (P<0.05). Conclusion: ligustrazine injection can reduce the content of TGF- beta 1 in patients with lung injury, reduce the incidence of radiation pneumonia and pulmonary fibrosis, improve lung function, no obvious adverse reactions, good safety, can play a good role in preventing radiation-induced lung injury after radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized 129Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points). Methods: In this study, dynamic 129Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (TTr_tissue and TTr_RBC) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a 60Co source. A separate group of six healthy age-matched rats served as a control group. Results: TTr_tissue values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms). TTr_RBC did not show any significant changes between groups. TTr_tissue was strongly correlated with TTr_RBC in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mmHg) compared to those from a representative control group (85.0 ± 10.0 mmHg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post-irradiation, TTr_tissue returned to values (35.6 ± 9.6 ms) that were not significantly different from baseline. Conclusions: Whole-lung tissue transfer time constants for 129Xe (TTr_tissue) can be used to detect the early phase of RILI in a rat model involving 14 Gy thoracic 60Co exposure as early as two weeks post-irradiation. This knowledge combined with more sophisticated models of gas exchange and imaging techniques, may allow functional lung avoidance radiation therapy planning to be achievable, providing more beneficial treatment plans and improved quality of life for recovering lung cancer patients. [ABSTRACT FROM AUTHOR]

To mainly analyze the prescription rules of Chinese herbal drugs for radiation induced lung injury, optimize the prescriptions, and provide a reference for the clinical treatment of radiation induced lung injury. The major Chinese databases CNKI, CBM and Wanfang data were searched to obtain the literature on Chinese herbal drugs for radiation induced lung injury. BICOMS 2 software was used to extract and collect all Chinese herbal drugs information and generate the co-occurrence matrix; NetDraw and Gcluto software were then used to make network map and visualization matrix for analysis. A total of 552 articles (19 types and 304 Chinese herbal drugs) were included. Ophiopogon japonicus had the highest frequency (229 times), followed by Astragalus membranaceus(181 times), Glycyrrhiza uralensis (166 times), and Scutellaria baicalensis (150 times). After the classification of efficacy, deficiency-supplementing medicinal (69 kinds of Chinese herbs), heat-clearing medicine (51 kinds of Chinese herbs) and phlegm cough medicine (42 kinds of Chinese herbs) accounted for 53.29% of all the Chinese herbs, acting in the main position. After the prescription analysis for the top 25 herbal prescriptions, six main structures of common prescriptions were found for the treatment of radiation induced lung injury. There are many kinds of Chinese herbal drugs for the treatment of radiation induced lung injury in clinical application. In the future, researchers can mainly focus on Ophiopogon japonicus etc. as the main drugs, combine with other high-frequency Chinese herbal drugs found in this study, or directly refer to the main structures of commonly used prescriptions found in this analysis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

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., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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.