Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

The evaluation of DLCO changes in patients with relatively higher lung shunt fractions receiving TARE.

OBJECTIVE: Transarterial radioembolization (TARE) with Yttrium-90 (90Y) labeled microspheres is an effective locoregional treatment option for patients with primary and metastatic liver cancer. However, TARE is also associated with radiation-induced lung injury due to hepatopulmonary shunting. If a large proportion of the injected radionuclide microspheres (more than 15%) is shunted, a rare but lethal complication may develop: radiation-induced pneumonitis (RP). Diffusion capacity of the lungs for carbon monoxide (DLCO) is a valuable test to assess lung function and a decrease in DLCO may indicate an impairment in gas exchange caused by the lung injury. Some previous researches have been reported the most consistent changes in pulmonary function tests after external beam radiotherapy are recorded with DLCO. This study aimed to examine the changes in DLCO after TARE with glass microspheres in newly treated and retreated patients with relatively higher lung shunt fractions. METHODS: We prospectively analyzed forty consecutive patients with liver malignancies who underwent lobar or superselective TARE with 90Y glass microspheres. DLCO tests were performed at baseline and on days 15, 30, and 60 after the treatment. All patients were followed up clinically and radiologically for the development of RP. RESULTS: A statistically significant decrease was found in the DLCO after the first treatment (81.4 ± 13.66 vs. 75.25 ± 13.22, p = 0.003). The frequency of the patients with impaired DLCO at baseline was significantly increased after the first treatment (37.5 vs 57.5% p < 0.05). In the retreated group (n = 8), neither the DLCO (71.5 ± 10.82 vs. 67.50 ± 11.24, p = 0.115) nor the frequency of patients with impaired DLCO (25 vs 25%, p = 1) did not significantly change. Also, the change in DLCO values did not significantly correlate with lung shunt fraction, administered radiation dose, and absorbed lung dose after the first and second treatments (p > 0.05 for all). None of the patients developed RP. CONCLUSION: Our study showed that a significant reduction in DLCO after TARE may occur in patients with relatively higher lung shunt fractions. Further studies with larger sample sizes are needed to better investigate the changes in DLCO in patients with high lung shunt fractions.

Analysis of the risk factors of radiation pneumonitis in patients after radiotherapy for esophageal squamous cell carcinoma.

Objective: To predict the risk factors of radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy. Methods: From January 2015 to October 2021, 477 ESCC patients were enrolled and were assessed retrospectively. All these patients received radiotherapy for primary lesions or mediastinal metastatic lymph nodes. Clinical efficacy and adverse events (AEs) were observed. Univariate analysis identified clinical and dosimetric factors associated with the development of RP, and multivariate logistic regression analysis identified independent potential risk factors associated with the development of RP. Nomograms were constructed to predict RP based on the results of multivariate logistic regression analysis. Results: Among the 477 ESCC patients, the incidence of RP was 22.2%, and the incidence of grade 4 or higher RP was 1.5%. Univariate analysis indicated that chronic obstructive pulmonary disease (COPD), pulmonary infection, leucopenia, PTV volume, V5, V20, V30 and MLD affected the occurrence of RP. The multivariate logistic regression analysis indicated that COPD (OR:1.821, 95%CI:1.111-2.985; P=0.017), pulmonary infection (OR:2.528, 95%CI:1.530-4.177; P<0.001), higher V20 (OR: 1.129, 95% CI:1.006-1.266; P=0.029) were significant independent predictors of RP in ESCC patients. COPD, pulmonary infection, V20 have been integrated for the RP nomogram. The rate of RP was significantly reduced in the V20<21.45% group. Further analysis indicated that the old age, diabetes, higher V20, and higher MLD were risk factors for grade 4 or higher RP. The area under the curve (AUC) value for V20 was 0.73 (95% CI, 0.567-0.893, P < 0.05). Conclusion: We have determined the risk factors of RP and grade 4 or higher RP in ESCC patients after radiotherapy. MLD, V20, COPD were independent factors for RP. It was necessary to take measures to reduce or avoid the occurrence of RP for patients with these risk factors at the early stage.

Association of volumetric-modulated arc therapy with radiation pneumonitis in thoracic esophageal cancer.

The lung volume receiving low-dose irradiation has been reported to increase in volumetric-modulated arc radiotherapy (VMAT) compared with three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal cancer, which raises concerns regarding radiation pneumonitis (RP) risk. This single institutional retrospective cohort study aimed to explore whether VMAT for thoracic esophageal cancer was associated with RP. Our study included 161 patients with thoracic esophageal cancer, of whom 142 were definitively treated with 3DCRT and 39 were treated with VMAT between 2008 and 2018. Radiotherapy details, dose-volume metrics, reported RP risk factors and RP incidence were collected. The RP risk factors were assessed via multivariate analysis. Dose-volume analysis showed that VMAT delivered more conformal dose distributions to the target volume (P < 0.001) and reduced V30 Gy of heart (57% vs 41%, P < 0.001) but increased V5 Gy (54% vs 41%, P < 0.001) and V20 Gy (20% vs 17%, P = 0.01) of lungs compared with 3DCRT. However, the 1-year incidence rates of RP did not differ between the two techniques (11.3% in 3DCRT vs 7.7% in VMAT, P = 0.53). The multivariate analysis suggested that the presence of interstitial lung disease (ILD) (P = 0.01) and V20 Gy of lungs ≥20% (P = 0.008) were associated with RP. Conclusively, VMAT increased the lung volume receiving low to middle doses irradiation, although this might not be associated with RP. Further studies are needed to investigate the effect of using VMAT for delivering conformal dose distributions on RP.

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice.

Radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), is a common clinical complication associated with thoracic radiotherapy for malignant tumors. However, the specific contributions of each cell subtype to this process are unknown. Here, we provide the single-cell pathology landscape of the RP in a mouse model by unbiased single-cell RNA-seq (scRNA-seq). We found a decline of type 2 alveolar cells in the RP lung tissue, with an expansion of macrophages, especially the Fabp4low and Spp1high subgroup, while Fabp4high macrophages were almost depleted. We observed an elevated expression of multiple mitochondrial genes in the RP group, indicating a type 2 alveolar cell (AT2) response to oxidative stress. We also calculated the enrichment of a cGAS-STING signaling pathway, which may be involved in regulating inflammatory responses and cancer progression in AT2 cells of PR mice. We delineate markers and transcriptional states, identify a type 2 alveolar cell, and uncover fundamental determinants of lung fibrosis and inflammatory response in RP lung tissue of mice.

Radiation Recall Pneumonitis: A Rare Syndrome That Should Be Recognized.

Radiation recall pneumonitis (RRP) is a rare but severe condition which has been mainly detected in the previously irradiated lung of patients with cancer after administering inciting agents, most commonly antineoplastic regimens including chemotherapy, targeted therapy, or immunotherapy. More recently, coronavirus disease vaccines were found to induce RRP. In addition to typical radiation pneumonitis (RP) or drug-induced interstitial lung disease, the management of RRP requires withholding inciting agents and steroid therapy. Thus, the occurrence of RRP could significantly impact cancer treatment, given that inciting agents are withheld temporarily and even discontinued permanently. In the present review, we discuss the current understanding and evidence on RRP and provide additional insights into this rare but severe disease.

A simple-to-use nomogram for predicting the risk of radiation pneumonitis in patients with thoracic segment esophageal squamous cell carcinoma.

Background: Radiation pneumonitis (RP) is one of the most severe complications of radiotherapy (RT) or concurrent chemoradiotherapy for thoracic segment esophageal squamous cell carcinoma (TSESCC) with delayed diagnose by conventional computed tomography (CT). The study aimed to develop a nomogram to predict the risk of RP early. Methods: Data was collected from 174 patients with clinicopathologically confirmed TSESCC from October 2013 to June 2020. Procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) levels in serum were dynamically monitored during radiotherapy. Lasso analysis was used for feature screening before multivariate logistic regression analysis to reduce the multicollinearity of variables. A nomogram combined with biological factors and clinical signs for individualized risk assessment and precise prediction of RP was developed and assed the performance with respect to its calibration, discrimination. Results: Of the 174 patients, 30 patients developed RP (grade ≥2) while 144 patients did not. After variable screening by Lasso analysis and logistics multivariate regression analysis, the predictor variables that were finally retained in the nomogram prediction model included IL-6, CRP, and radiotherapy techniques. The model displayed good discrimination with an area under the curve (AUC) of 0.898 (95% CI: 0.849-0.947), with the sensitivity and specificity of 0.967 and of 0.736, respectively. This model also shows good calibration and clinical practical value. In addition, the study provided a web-based version of the dynamic nomogram to facilitate clinical application. Conclusions: The study provides a nomogram model containing IL-6, CRP, RT techniques, which could be conveniently used for individualized prediction of RP in patients with TSESCC during radiotherapy or concurrent chemoradiotherapy.

Development and validation of a random forest model for predicting radiation pneumonitis in lung cancer patients receiving moderately hypofractionated radiotherapy: a retrospective cohort study.

Background: Radiation pneumonitis (RP) is a type of toxicity commonly associated with thoracic radiation therapy. We sought to establish a random forest (RF) model and evaluate its ability to predict RP in patients with non-small cell lung cancer (NSCLC) receiving moderately hypofractionated radiotherapy (hypo-RT). Methods: A total of 106 patients with stage II-IVa NSCLC who received moderately hypofractionated helical tomotherapy (2.3-3.0 Gy/fraction) at Zhongshan Hospital were included. All enrolled patients were divided chronologically into the training (67 patients) and validation (39 patients) groups. Higher than or equal to grade 2 RP was defined as the end point. Logistic regression and RF models were established and compared using the receiver operating characteristic (ROC) and a confusion matrix in the training and validation groups. Results: The cumulative incidence of the end point was 25.4% and 17.9% in the training and validation groups, respectively. Logistic regression models were constructed by dosage parameters of total lungs, ipsilateral or contralateral lungs, respectively. ROC analysis revealed that the dosimetric factors of total lungs yielded a superior classification performance than did that of the ipsilateral or contralateral lungs [area under the curve (AUC) =0.920, AUC =0.701, and AUC =0.661, respectively]. Furthermore, the RF model yielded a better prediction capacity than did the traditional logistic model based on the dosimetric factors of the total lungs (accuracy: 88.06%; precision: 84.62%; sensitivity: 64.71%; specificity: 96.00%). Moreover, the RF identified mean lung dose [MLD; mean decrease gini (MDG) =5.74], V20 (MDG =4.62), and V35 (MDG =3.08) of total lungs as the most common primary differentiators of RP. Conclusions: Our RF model established based on the dosimetric parameters of the total lungs could accurately predict the RP risk in patients with NSCLC treated with moderately hypofractionated tomotherapy.

Clinical value of serum Ape1/Ref-1 combined with TGF-ß1 monitoring in predicting the occurrence of radiation pneumonitis (RP) in non-small cell lung cancer patients.

BACKGROUND: The aim of the present study was to explore the predictive value of serum apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) combined with transforming growth factor ß1 (TGF-ß1) levels in the occurrence of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLS). METHODS: Eighty-one patients with NSCLS who were admitted from August 2017 to July 2019 were enrolled in the present study. All patients were treated with concurrent radiotherapy and chemotherapy. Serum Ape1/Ref-1 and TGF-ß1 levels were measured before treatment and 12 weeks after treatment. Patients with radiation-induced lung injury were assessed and divided into the RP group (lung injury ≥2) and non-RP (NRP) group (grade <2). The levels of serum Ape1/Ref-1 and TGF-ß1 before and after treatment between the 2 groups were compared. The relationship between clinical characteristics, serum Ape1/Ref-1, TGF-ß1 levels, and the occurrence of RP were then analyzed, and the relationship between serum Ape1/Ref-1, TGF-ß1 levels, and their predictive value for the occurrence of RP was also assessed. RESULTS: The incidence of RP in 81 patients was 30.86%. After treatment, the serum Ape1/Ref-1 and TGF-ß1 levels of the 2 groups were significantly higher than those before treatment (P<0.05). Furthermore, after treatment, the levels of serum Ape1/Ref-1 and TGF-ß1 in the RP group were significantly higher than those of the NRP group (P<0.05). Multivariate logistic regression analysis showed that V20, Ape1/Ref-1, and TGF-ß1 were associated with the occurrence of RP (P<0.05). The levels of serum Ape1/Ref-1 were positively correlated with TGF-ß1 (r=0.734, P<0.05). Finally, the area under the curve of RP occurrence, which was predicted by the levels of serum Ape1/Ref-1, TGF-ß1, and the combination of both were 0.779, 0.69, and 0.842, respectively. CONCLUSIONS: The occurrence of RP in NSCLS patients is closely related to the levels of serum Ape1/Ref-1 and TGF-ß1, and the combination of both has important predictive values for the occurrence of RP.

Intermediate Dose-Volume Parameters, Not Low-Dose Bath, Is Superior to Predict Radiation Pneumonitis for Lung Cancer Treated With Intensity-Modulated Radiotherapy.

PURPOSE: Although intensity-modulated radiotherapy (IMRT) is now a preferred option for conventionally fractionated RT in lung cancer, the commonly used cutoff values of the dosimetric constraints are still mainly derived from the data using three-dimensional conformal radiotherapy (3D-CRT). We aimed to compare the prediction performance among different dosimetric parameters for acute radiation pneumonitis (RP) in patients with lung cancer received IMRT. METHODS: A total of 236 patients treated with IMRT were retrospectively reviewed in two independent groups of lung cancer from January 2014 to August 2018. The primary endpoint was grade 2 or higher acute RP (RP2). Dose metrics were generated from the bilateral lung volume outside GTV (VdoseG) and PTV (VdoseP). The associations of RP2 with clinical variables, dose-volume parameters and mean lung dose (MLD) were analyzed by univariate and multivariate logistic regression. The power of discrimination among each predictor was assessed by employing the bootstrapped area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULTS: Thirty-four (14.4%) out of 236 patients developed acute RP2 after the end of IMRT. The clinical parameters were identified as less important predictors for RP2 based on univariate and multivariate analysis. In both studied groups, the significance of association was more convincing in V20P, V30P, and MLDP (smaller Ps) than V5G and V5P. The largest bootstrapped AUC was identified for the V30P. We found a trend of better discriminating performance for the V20P and V30P, and MLDP than the V5G and V5P according to the higher values in AUC, IDI, and NRI analysis. To limit RP2 incidence less than 20%, the V30P cutoff was 14.5%. CONCLUSIONS: This study identified the intermediate dose-volume parameters V20P and V30P with better prediction performance for acute RP2 than low-dose metrics V5G and V5P. Among all studied predictors, the V30P had the best discriminating power, and should be considered as a supplement to the traditional dose constraints in lung cancer treated with IMRT.

Robust Optimization of SBRT Planning for Patients With Early Stage Non-Small Cell Lung Cancer.

PURPOSE: Setup uncertainty is a known challenge for stereotactic body radiotherapy planning. Using the internal target volume-based robust optimization was proposed as a more accurate way than the conventional planning target volume-based optimization when considering the robustness criteria. In this study, we aim to investigate the feasibility of internal target volume-based robust optimization in stereotactic body radiotherapy planning using 4-dimensional computed tomography and develop a novel dose-volume histogram band width metric to quantitatively evaluate robustness. METHOD AND MATERIALS: A total of 50 patients with early stage non-small cell lung cancer, who underwent stereotactic body radiotherapy, were retrospectively selected. Each of the 50 patients had 2 stereotactic body radiotherapy plans: one with the conventional planning target volume-based optimization and the other with patient-specific robustly optimized internal target volume and with a uniform 5 mm setup error. These were compared with the planning target volume-based optimization method based on both plan quality and robustness. The quality was evaluated using dosimetric parameters and radiobiology parameters, such as high-dose spillage (V90%RX, conformity index), intermediate-dose spillage (dose falloff products), low-dose spillage (normal tissue: V50%RX), and lung tissue complication probability. The robustness was evaluated under a uniform 3 to 5 mm setup errors with a novel proposed metric: dose-volume histogram band width. RESULTS: When compared with planning target volume-based optimization plans, the internal target volume-based robust optimization plans have better conformity of internal target volume coverage (conformity index: 1.17 vs 1.27, P < .001), intermediate-dose spillage (dose falloff product: 129 vs 167, P < .001), low-dose spillage in normal tissue (V50%RX: 0.8% vs 1.5%, P < .05), and lower risk of radiation pneumonitis (lung tissue complication probability: 4.2% vs 5.5%, P < .001). For the robustness, dose-volume histogram band width analysis shows that the average values in internal target volume, D95%, D98%, and D99%, of internal target volume-based robust optimization are smaller than that of planning target volume-based optimization (unit cGy) under 3-, 4-, and 5-mm setup uncertainties (3-mm setup uncertainty: 42 vs 73 cGy; 4-mm setup uncertainty: 88 vs 176 cGy; 5-mm setup uncertainty: 229 vs 490 cGy), which might indicate that internal target volume-based robust optimization harbored a greater robustness regardless of the setup errors. CONCLUSIONS: Internal target volume-based robust optimization may have clinical potential in offering better plan quality in both target and organs at risk and lower risk of radiation pneumonitis. In addition, the proposed internal target volume-based robust optimization may demonstrate robustness regardless of different setup uncertainties in the stereotactic body radiotherapy planning. REGISTRATION: Retrospective study with local ethics committee approval.

Excluding PTV from lung volume may better predict radiation pneumonitis for intensity modulated radiation therapy in lung cancer patients.

BACKGROUND: Lung dose-volume histogram (DVH) in radiotherapy could be calculated from multiple normal lung definitions. The lung dosimetric parameters generated from various approaches are significantly different. However, limited evidence shows which definition should be used to more accurately predict radiation pneumonitis (RP). We aimed to compare the RP prediction accuracy of dosimetric parameters from three lung volume methods in lung cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT). METHODS: We retrospectively reviewed 183 consecutive lung cancer patients treated with IMRT from January 2014 to October 2017. The normal lungs were defined by total bilateral lung volume (Total Lung), excluding PTV (Lung-PTV) or PGTV (Lung-PGTV). V5, V20, and mean lung dose (MLD) have been extracted from three definitions. The primary endpoint was acute grade 2 or higher RP (RP2). Correlation between RP2 and dose parameters were analyzed by logistic regression. We evaluated prediction performance using area under the receiver operating characteristic curve (AUC) and normal tissue complication probability (NTCP) model. RESULTS: Twenty-six patients (14.2%) developed acute RP2 after IMRT treatment. Significant dosimetric differences were found between any 2-paired lung volumes (Ps < 0.001). To limit RP2 incidence less than 20%, the cutoff MLDs were 12.5 Gy, 14.2 Gy, and 15.0 Gy, respectively, for Lung-PTV, Lung-PGTV, and Total Lung methods. There were 54% (13% vs. 20%) and 45% (20% vs. 29%) RP2 probability variances detected at each MLD cutoff points from Lung-PTV and Lung-PGTV definitions. The best RP prediction performance was found in MLD from Lung-PTV method (AUC = 0.647), which is significantly better (P = 0.006) than the MLD from Lung-PGTV method (AUC = 0.609). CONCLUSION: There are significant differences in acute RP2 rate prediction using dosimetric parameters from various normal lung definitions. Excluding PTV from total lung volume may be more accurate and promising to predict acute symptomatic radiation pneumonitis in IMRT treated lung cancer patients.

The Influence of Radiotherapy on AIM2 Inflammasome in Radiation Pneumonitis.

This study aims to investigate the influence of radiotherapy on absent in melanoma 2 (AIM2) inflammasome in radiation pneumonitis (RP). A rat model of RP was established. H&E staining was used to test radiation-induced lung tissue injury. Immunohistochemistry (IHC) was used to detect the expression of AIM2 and IL-1ß in rat lung tissues. Milliplex assay was used to test cytokine levels in rat serum. Comet assay was adopted to examine DNA breaks in THP1 cells. RT-PCR was used to detect the messenger RNA (mRNA) expression of AIM2, caspase-1, and IL-1ß in THP1 cells. As a result, the rat model indicated that irradiation induced obvious lung injury. A large amount of inflammatory cells infiltrated to the irradiated lung tissues. The structure of lung tissues collapsed. IHC revealed that AIM2 and IL-1ß expressions were significantly higher in irradiated lung tissues than in the control. IL-1ß level in rat serum significantly elevated on the 7th day post-irradiation, gradually decreased on the 15th day, and became minimal on the 30th day. Irradiation induced dsDNA break in a dose-dependent manner at 24 h after irradiation. Radiotherapy increased the mRNA expression level of AIM2 and IL-1ß in a time-dependent manner. In conclusion, radiotherapy triggered some critical components of AIM2 inflammasome in RP. The activation of AIM2 inflammasome by radiotherapy may contribute to the pathogenesis of RP.

A lot to a little or a little to a lot-which dose-volume relationship ensures the best clinical outcome in the high dose radiation therapy of thoracic tumors? A prospective approach.

BACKGROUND: The purpose of this prospective randomized trial is to determine which constellation of dose and corresponding volume of the lung tissue-either a lot to a little or a little to a lot-should be preferred to ensure the best possible outcome for patients with thoracic carcinomas. METHODS: From Apr 2012 to Oct 2015, 81 patients with NSCLC, SCLC or esophageal carcinoma were randomized and treated with either a 4-field-IMRT or a VMAT technique with or without additional chemotherapy. Data regarding clinical outcome, pulmonary function tests (PFT) and quality of life (QoL) was collected before RT, 6 weeks, 12 weeks and 6 months after treatment, QoL data additionally 1 year post RT. Follow up CTs were done 12 weeks and 6 months after RT. RESULTS: There is no significant difference regarding the local (P=0.954) and distant (P=0.206) outcome, side effects (all P>0.05) or survival (P=0.633) at any follow-up appointment. The comparison of the PFT shows a statistically significant difference for the DLCO 6 weeks post RT (P=0.028). All other parameters do not differ significantly at any follow up appointment. Regarding the QoL there is no statistically significant difference at any follow up appointment (P>0.1). There is a statistically significant difference between the mean density of the lung parenchyma at 12 weeks (P<0.0005) and 6 months post RT (P<0.0005). CONCLUSIONS: Since there is no significant and relevant difference between both treatment arms regarding PFT, clinical outcome and QoL it does not seem to relevant how the DVH is shaped exactly as long as established dose constraints for the organs at risk are respected. As to whether the difference between the CT density changes is clinically relevant further analysis is needed.

Serum KL-6 predicts the risk of pneumonitis induction after radiotherapy of human lung cancer / 中华放射医学与防护杂志

Objective To explore the irradiation-increased krebs yon den lungen-6 (KL-6) in predicting radiation pneumonitis (RP) after lung cancer radiotherapy.Methods A total of 87 hospitalized patients with Ⅰ-Ⅲ stages of lung cancer from June 2015 to December 2015 were followed up,and their clinicopathological data and serum KL-6,transforming growth factor-beta 1 (TGF-β1)and lactate dehydrogenase (LDH)before and 3 months after radiotherapy were analyzed to determine their role in predicting RP induction in lung cancer.Results Among the 87 lung cancer patients based on clinical symptoms and chest CT,13 patients were diagnosed with ≥2 grape RP.Before radiotherapy,the average levels of serum KL-6 were (247 ± 105.44) U/ml in 13 patients with ≥ 2 grape RP and (209 ± 71.09) U/ml in 74 cases 0/1 grape RP,respectively.Within 3 months after radiotherapy,the highest level of KL-6 approached to (456 ± 202.84) and (222 ± 80.42) U/ml with increase ratios of 2.01 ± 1.04 and 1.13 ± 0.60 in the ≥2 grape RP and 0/1 grape RP,respectively.The difference of KL-6 levels between these two groups was significant (t =2.901,P ＜ 0.005).While the levels of TGF-β1 and LDH did not change.ROC analysis showed that the sensitivity of the ratio of serum KL-6 increased after radiotherapy was 0.923％ and the specificity was 0.851％ at 1.435 as the critical value.Furthermore,the multi-variate logistic regression analysis showed that the ratio of KL-6 increased as an independent risk factor of ≥ 2 grade RP in lung cancer (OR =12.886,95％ CI =3.372-49.247,P =0.002).Conclusions The increased ratio (≥ 1.435) of KL-6 is closely correlated with the ≥2 grape RP in lung cancer,which could be used as a predictor of ≥2 grape RP in lung cancer.