Incidence Of Radiation Pneumonitis Research Articles

143 Using ProKnow to explore the incidence of radiation pneumonitis in relation to GTV size in Stage III Non-Small Cell Lung Cancer (NSCLC) concurrent Chemoradiotherapy (cCRT) patients and its impact on survival. A Pilot Study

143 Using ProKnow to explore the incidence of radiation pneumonitis in relation to GTV size in Stage III Non-Small Cell Lung Cancer (NSCLC) concurrent Chemoradiotherapy (cCRT) patients and its impact on survival. A Pilot Study

Effects of intensity-modulated radiotherapy combined with chemotherapy and prognostic factors in patients with locally advanced oesophageal cancer

PurposeWe explored the efficacy and influencing factors of chemoradiotherapy and radiotherapy alone in patients with locally advanced oesophageal squamous cell carcinoma. MethodsWe retrospectively analysed 226 locally advanced oesophageal squamous cell carcinoma patients who underwent chemoradiotherapy and radiotherapy alone. Univariate and multivariate Cox regression analyses were used to analyse the impact of relevant factors. The endpoint was overall survival and progression-free survival. ResultsCompared with the radiotherapy group, the chemoradiotherapy group had a significant difference in the overall survival rate and the progression-free survival rate between 3 and 5 years (both p ​< ​0.05). The incidences of radiation pneumonitis and radiation oesophagitis were analysed, and the differences were not significant (all p ​> ​0.05). The incidence of haematological toxicity in the chemoradiotherapy group was significantly higher than that in the radiotherapy group (p ​= ​0.001). There was a significant difference in the incidence of haematological toxicity between the ≤65 and the >65 age groups (p ​< ​0.05). Tumour location, T stage, tumour length, tumour target volume, and short-term curative effect were the main factors affecting the prognosis (all p ​< ​0.05). T stage, gross tumour volume, and short-term curative effect were all independent factors affecting the prognosis (all p ​< ​0.05). ConclusionsPatients with locally advanced oesophageal cancer who received intensity-modulated radiotherapy (IMRT) combined with chemotherapy had significant survival benefits compared with radiotherapy alone. Haematological toxicity was the main adverse reaction. T-stage, gross tumour volume and short-term curative effect were independent factors influencing the prognosis.

Radiation pneumonitis after concurrent aumolertinib and thoracic radiotherapy in EGFR-mutant non-small cell lung cancer patients

BackgroundThe superior efficacy of concurrent thoracic radiotherapy (TRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been proven in locally advanced and advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, the high incidence of radiation pneumonitis (RP) reduced by concurrent TRT and TKIs has attracted widespread attention. Thus, this study was designed to investigate the rate and risk factors for RP in EGFR-positive NSCLC patients simultaneously treated with aumolertinib and TRT. MethodsWe retrospectively evaluated stage IIIA-IVB NSCLC patients treated with concurrent aumolertinib and TRT between May 2020 and December 2022 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed by two senior radiologists and then graded from 1 to 5 according to the Common Terminology Criteria for Adverse Events v5.0. All risk factors were evaluated by univariate and multivariate logistic regression analyses.ResultsA total of 49 patients were included, the incidence of grade ≥ 2 RP was 42.9%. Grade 2 and 3 RP were observed in 28.6% and 14.3% of patients, respectively. Grade 4 to 5 RP were not observed. the gross total volume (GTV) ≥ 21 ml and ipsilateral lung V20 ≥ 25% were risk factors for RP. The median progression-free survival (PFS) in the first-line therapy group and second-line therapy group were 23.5 months and 17.2 months, respectively (p = 0.10).ConclusionsBetter local control is achieved with concurrent TRT and aumolertinib, and special attention should be given to controlling ipsilateral lung V20 and GTV to reduce the risk of RP.

Predicting radiation pneumonitis in lung cancer: a EUD-based machine learning approach for volumetric modulated arc therapy patients.

This study aims to develop an optimal machine learning model that uses lung equivalent uniform dose (lung EUD to predict radiation pneumonitis (RP) occurrence in lung cancer patients treated with volumetric modulated arc therapy (VMAT). We analyzed a cohort of 77 patients diagnosed with locally advanced squamous cell lung cancer (LASCLC) receiving concurrent chemoradiotherapy with VMAT. Patients were categorized based on the onset of grade II or higher radiation pneumonitis (RP 2+). Dose volume histogram data, extracted from the treatment planning system, were used to compute the lung EUD values for both groups using a specialized numerical analysis code. We identified the parameter α, representing the most significant relative difference in lung EUD between the two groups. The predictive potential of variables for RP2+, including physical dose metrics, lung EUD, normal tissue complication probability (NTCP) from the Lyman-Kutcher-Burman (LKB) model, and lung EUD-calibrated NTCP for affected and whole lung, underwent both univariate and multivariate analyses. Relevant variables were then employed as inputs for machine learning models: multiple logistic regression (MLR), support vector machine (SVM), decision tree (DT), and K-nearest neighbor (KNN). Each model's performance was gauged using the area under the curve (AUC), determining the best-performing model. The optimal α-value for lung EUD was 0.3, maximizing the relative lung EUD difference between the RP 2+ and non-RP 2+ groups. A strong correlation coefficient of 0.929 (P< 0.01) was observed between lung EUD (α = 0.3) and physical dose metrics. When examining predictive capabilities, lung EUD-based NTCP for the affected lung (AUC: 0.862) and whole lung (AUC: 0.815) surpassed LKB-based NTCP for the respective lungs. The decision tree (DT) model using lung EUD-based predictors emerged as the superior model, achieving an AUC of 0.98 in both training and validation datasets. The likelihood of developing RP 2+ has shown a significant correlation with the advancements in RT technology. From traditional 3-D conformal RT, lung cancer treatment methodologies have transitioned to sophisticated techniques like static IMRT. Accurately deriving such a dose-effect relationship through NTCP modeling of RP incidence is statistically challenging due to the increased number of degrees-of-freedom. To the best of our knowledge, many studies have not clarified the rationale behind setting the α-value to 0.99 or 1, despite the closely aligned calculated lung EUD and lung mean dose MLD. Perfect independence among variables is rarely achievable in real-world scenarios. Four prominent machine learning algorithms were used to devise our prediction models. The inclusion of lung EUD-based factors substantially enhanced their predictive performance for RP 2+. Our results advocate for the decision tree model with lung EUD-based predictors as the optimal prediction tool for VMAT-treated lung cancer patients. Which could replace conventional dosimetric parameters, potentially simplifying complex neural network structures in prediction models.

Novel model integrating computed tomography-based image markers with genetic markers for discriminating radiation pneumonitis in patients with unresectable stage III non-small cell lung cancer receiving radiotherapy: a retrospective multi-center radiogenomics study

BackgroundChemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC.MethodsIn this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively.ResultsThe Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram.ConclusionHistology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.

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

To predict the risk factors of radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy. 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. 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). 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.

Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease

BackgroundWe aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy.MethodsWe retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03).ResultsThe median follow-up duration was 15 months (range: 3–47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09–347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group.ConclusionsThis study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy.

The relationship of body mass index to setup errors, dosimetric parameters and incidence of radiation pneumonitis in non-small cell lung cancer patients undergoing intensity-modulated radiation therapy: a single-center observational study

Background The relationship among body mass index (BMI), setup error and radiation pneumonitis is not clearly illustrated. Objective The present study aimed to investigate the role of BMI in non-small cell lung cancer (NSCLC) patients’ radiation treatment, focusing on its relationship with setup error of patient positioning, the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and the incidence of radiation pneumonitis. Methods This prospective observational study included 523 cases of NSCLC patients during 2020–2022. Patients were divided into different groups by different BMI. The setup error was obtained by cone beam CT (CBCT) at three positions, lateral (LAT), longitudinal (LNG) and vertical (VRT). IMRT dosimetric parameters of V 5, V 20, and mean dose were collected. Results Patients with BMI ≥28 kg/m2 showed significantly higher absolute values of LAT, LNG and VRT, higher V 5, V 20, mean dose, as well as higher total incidence of radiation pneumonitis and grade III radiation pneumonitis compared with patients with BMI <24 kg/m2 or 24–28 kg/m2. Spearman’s analysis demonstrated that the absolute values of LAT, LNG and VRT were positively correlated with BMI, and positive correlation existed among BMI, dosimetric parameters and setup errors. ROC curves showed that LAT in setup errors and V 5 in dosimetric parameters had the best diagnostic value for prediction of radiation pneumonitis. Only BMI, LAT, V 5 and V 20 were the independent risk factors for radiation pneumonitis. Conclusions Setup error caused by higher BMI might be associated with the dosimetric parameters, as well as the incidence of radiation pneumonitis in NSCLC patients.

Analysis of the risk factors of radiation pneumonitis and the predictive ability of dosiomics in non-small-cell lung cancer.

Purpose: This prospective study investigated the incidence of radiation pneumonitis (RP) after immunotherapy followed by radiotherapy in non-small-cell lung cancer, analyzed the risk factors for RP, and explored the predictive performance of dosimetry and dosiomics. Methods & materials: Risk factors for grade ≥2 RP were calculated by using a logistic regression model. Predictive performance was compared on the basis of area under thecurvevalues. Results: Grade ≥2 RP occurred in 16 cases (26.7%). The AUC values of V5Gy, gray-level dependence matrix-small dependence high gray-level emphasis (GLDM-SDHGLE)and combined features were 0.685, 0.724and 0.734, respectively. Conclusion: Smoking history, bilateral lung V5Gyand GLDM-SDHGLE were independent risk factors for RP. Dosiomics can effectively predict RP.

Multi-Criteria Optimization and RapidPlan for Improved Organs at Risk Sparing in Treatment Planning of Malignant Pleural Mesothelioma

Treatment planning for malignant pleural mesothelioma is complex and time-consuming owing to the large volume of the target as well as its overlap and proximity to critical organs. Knowledge-based planning (KBP) model using RapidPlan (RP) was previously developed and clinically tested at our institution for treatment planning of these cases that had undergone pleurectomy-decortication, and therefore had two intact-lungs. The aim of this work is to investigate if multi-criteria optimization (MCO) can further improve the RP model with respect to organ at risk (OAR) sparing without compromising target coverage. The RP model was trained with clinically accepted plans of 57 patients that used Volumetric Modulated Arc Therapy (VMAT) with 2 partial arcs and 6 MV photons. The dose volume histogram (DVH) estimation model was trained to estimate doses to the heart, ipsilateral lung, total lung, contralateral lung, stomach, esophagus, kidneys and liver. Clinical treatment plans for 12 patients were re-planned using RP as well as a combination of RP and MCO. Application of MCO was after RP and used tradeoff exploration to navigate to the improved dose distribution on a Pareto surface. Selection of a plan that further improved OAR sparing while maintaining coverage constraints of PTV D95 and V95 ≥ 94% was made. Dosimetric parameters for clinical plans (CP), plans using RP as well as plans generated with RP and MCO were all compared for 12 new validation cases. Wilcoxon sign-rank test was used for statistical significance testing. The mean heart dose was reduced from 20.9 Gy ± 3.2 Gy for CP to 17.1 Gy ± 4.2 Gy with RP and further to 13.8 Gy ± 3.3 Gy with RP and MCO. The heart V30 Gy was reduced from 23.7% ± 8% to 18.2% ± 9.4% with RP and further to 13.6% ± 5.7% with RP and MCO. The corresponding results for contralateral lung V5 Gy were 68.6% ± 14.1% with CP, 50% ± 26.3% with RP and 45.3% ± 22.8% with RP and MCO, while the mean esophagus dose was reduced from 26.5 Gy ± 3.1 Gy to 21.5 Gy ± 4.7 Gy with RP and further to 19.1 Gy ± 4.2 Gy with RP and MCO. All these dosimetric improvements were statistically significant (p<0.001). However, improvements with RP and MCO for the total lung mean and V20 Gy, liver mean, stomach mean and kidney V18 Gy were marginal over the RP. Sparing of ipsilateral lung V20 Gy was maintained at ≥ 50 cc on average for all plans. PTV D95 and V95 were both normalized at 94%. Combination of RP and MCO significantly improved sparing of the OARs, especially the heart, contralateral lung and esophagus without compromising coverage or doses to other structures. Since doses to the heart, and contralateral lung are known to correlate with incidence of radiation pneumonitis, it would be prudent to consider planning with both RP and MCO to help determine the optimal treatment plan for the individual patient's anatomy.

Noninvasive Radiation Markers Based on Lung Cancer CT Images and Dosimetry Features to Predict the Immune Response to Radiotherapy in Tumor Microenvironment

For lung cancer patients with complex conditions, doctors need to determine treatment plan in combination with changes of immune response during radiotherapy. It was urgent to find a strategy to predict immune response to intervene the treatment at an early stage. The radiotherapy process and tumor microenvironment status of 105 lung cancer patients were tracked and recorded in our hospital from 2019 to 2022, public database TCGA-LUAD/LUSC queue of TCIA image data was downloaded as external verification set. Data was analyzed according to the following methods: First, the 3D slicer software was used to process the CT imageomics data, and the doseomics information was calculated by DVHmetrics package from R software. Then Python was brought in to develop a non-invasive radiation scoring system through machine learning methods (T-test, LASSO, random forest and Xgboost). Finally, combined with the clinical information related to the patient's immune response, a nomogram was made to study the correlation between the score markers and the ratio of CD4 cells/CD8 cells in the tumor microenvironment, the prognosis of lung cancer, as well as the incidence of radiation pneumonia. The radiation markers score formula was obtained with CT imageomics and DVH dosimics features, which achieved an AUC of 0.67-0.75 in predicting CD4/CD8 condition in tumor microenvironment after radiotherapy. It was worth noticing that in predicting the prognosis of lung cancer, it was difficult to distinguish between the radiation score and the patient's survival status (P>0.05). However, we found that the radiation pneumonitis of lung cancer patients in the low score group (42.6%) was significantly higher than that in the high score group (13.4%). Radiation markers score was a non-invasive method to evaluate the immune response of patients with lung cancer, which can be used to predict the incidence of radiation pneumonitis.

Daily Adaptive vs. Non-Adaptive External Beam Radiation Therapy with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC): A Prospective Randomized Trial of an Individualized Approach for Toxicity Reduction (ARTIA-Lung)

Radiotherapy (RT) with concurrent chemotherapy is a standard treatment for Stage III NSCLC. However, radiation pneumonitis incidence increases rapidly with volume of lung irradiated, and esophagitis increases with dose to the esophagus. Both conditions can have adverse impacts on patients' quality of life. Daily online adaptive RT (ART) may allow for reduced normal tissue doses due to smaller margins around the target, as well as target size reduction with tumor response. This prospective, randomized controlled trial tests the hypothesis that the proportion of study participants who experience score ≥3 PRO-CTCAE cough, dyspnea, or dysphagia will be at least 20% lower with daily ART than with non-adapted RT. Enrollment goals are 244 subjects at up to 10 cancer centers worldwide. Eligibility criteria include stage IIIA-IIIC (AJCC v8) NSCLC; baseline grade 0-2 dyspnea, cough, and dysphagia; and no contralateral hilar or supraclavicular/cervical lymph node involvement. Subjects will be randomized (1:1) to CBCT-based daily ART or non-adapted RT using IMRT or VMAT delivering 60-66 Gy in 30-33 fractions with concurrent platinum doublet chemotherapy. Adjuvant immunotherapy with durvalumab is permitted. Follow-up for study participants will be for 1-year post-completion of chemoRT. Study endpoints include: frequency of PRO-CTCAE score ≥3 cough, dyspnea, or dysphagia from randomization to 30 days post-chemoRT; patient-reported quality of life (FACT-L and EQ-5D-5L questionnaires); percentage of lung receiving ≥20 Gy; mean doses to lung, heart, and esophagus; primary tumor response on CT or PET-CT (RECIST v1.1); local disease progression; and incidence of grade ≥2 pneumonitis within 1 year. Stratification factors are the treating institution and the presence of contralateral mediastinal lymph node metastases (associated with increased volume of irradiated lung). Interim analyses for futility and superiority will be performed when the primary endpoint data have been collected for 50% of evaluable participants. This study opened to enrollment on 20 October 2022 and is expected to be completed in approximately 3 years. This prospective, randomized clinical trial rigorously evaluates the impacts of daily online ART on radiation pneumonitis, esophagitis, and quality of life in patients with advanced NSCLC. It will collect standard tumor response and disease progression metrics to assure that reduced margins do not have an adverse impact on outcomes. Online ART is emerging as an innovative approach enabling increased sparing of normal tissues. The results of this clinical study will support evidence-based clinical decisions around ART technologies.

External validation of NTCP-models for radiation pneumonitis in lung cancer patients treated with chemoradiotherapy

PurposeNormal tissue complication probability (NTCP) models can be used to estimate the risk of radiation pneumonitis (RP). The aim of this study was to externally validate the most frequently used prediction models for RP, i.e., the QUANTEC and APPELT models, in a large cohort of lung cancer patients treated with IMRT or VMAT. [1–2] Methods and materialsThis prospective cohort study, included lung cancer patients treated between 2013 and 2018. A closed testing procedure was performed to test the need for model updating. To improve model performance, modification or removal of variables was considered. Performance measures included tests for goodness of fit, discrimination, and calibration. ResultsIn this cohort of 612 patients, the incidence of RP ≥ grade 2 was 14.5%. For the QUANTEC-model, recalibration was recommended which resulted in a revised intercept and adjusted regression coefficient (from 0.126 to 0.224) of the mean lung dose (MLD),. The APPELT-model needed revision including model updating with modification and elimination of variables. After revision, the New RP-model included the following predictors (and regression coefficients): MLD (B = 0.250), age (B = 0.049, and smoking status (B = 0.902). The discrimination of the updated APPELT-model was higher compared to the recalibrated QUANTEC-model (AUC: 0.79 vs. 0.73). ConclusionsThis study demonstrated that both the QUANTEC- and APPELT-model needed revision. Next to changes of the intercept and regression coefficients, the APPELT model improved further by model updating and performed better than the recalibrated QUANTEC model. This New RP-model is widely applicable containing non-tumour site specific variables, which can easily be collected.

Renin-angiotensin system inhibitors mitigate radiation pneumonitis by activating ACE2-angiotensin-(1–7) axis via NF-κB/MAPK pathway

Radiation pneumonitis (RP) affects both patients and physicians during radiation therapy for lung cancer. To date, there are no effective drugs for improving the clinical outcomes of RP. The activation of angiotensin-converting enzyme 2 (ACE2) improves experimental acute lung injury caused by severe acute respiratory syndrome coronavirus, acid inhalation, and sepsis. However, the effects and underlying mechanisms of ACE2 in RP remain unclear. Therefore, this study aimed to investigate the effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on RP and ACE2/angiotensin-(1–7)/Mas receptor pathway activation. We found that radiotherapy decreased the expression of ACE2 and that overexpression of ACE2 alleviated lung injury in an RP mouse model. Moreover, captopril and valsartan restored ACE2 activation; attenuated P38, ERK, and p65 phosphorylation; and effectively mitigated RP in the mouse model. Further systematic retrospective analysis illustrated that the incidence of RP in patients using renin-angiotensin system inhibitors (RASis) was lower than that in patients not using RASis (18.2% vs. 35.8% at 3 months, p = 0.0497). In conclusion, the current findings demonstrate that ACE2 plays a critical role in RP and suggest that RASis may be useful potential therapeutic drugs for RP.

Subpleural fibrotic interstitial lung abnormalities are implicated in non-small cell lung cancer radiotherapy outcomes.

The relationship between interstitial lung abnormalities (ILAs) and the outcomes of lung cancer radiotherapy is unclear. This study investigated whether specific ILA subtypes are risk factors for radiation pneumonitis (RP). This retrospective study analysed patients with non-small cell lung cancer treated with radical-intent or salvage radiotherapy. Patients were categorised into normal (no abnormalities), ILA, and interstitial lung disease (ILD) groups. The ILA group was further subclassified into non-subpleural (NS), subpleural non-fibrotic (SNF), and subpleural fibrotic (SF) types. The Kaplan-Meier and Cox regression methods were used to determine RP and survival rates and compare these outcomes between groups, respectively. Overall, 175 patients (normal, n = 105; ILA-NS, n = 5; ILA-SNF, n = 28; ILA-SF, n = 31; ILD, n = 6) were enrolled. Grade ≥2 RP was observed in 71 (41%) patients. ILAs (hazard ratio [HR]: 2.33, p = 0.008), intensity-modulated radiotherapy (HR: 0.38, p = 0.03), and lung volume receiving 20 Gy (HR: 54.8, p = 0.03) contributed to the cumulative incidence of RP. Eight patients with grade 5 RP were in the ILA group, seven of whom had ILA-SF. Among radically treated patients, the ILA group had worse 2-year overall survival (OS) than the normal group (35.3% vs 54.6%, p = 0.005). Multivariate analysis revealed that the ILA-SF group contributed to poor OS (HR: 3.07, p =0.02). ILAs, particularly ILA-SF, may be important risk factors for RP, which can worsen prognosis. These findings may aid in making decisions regarding radiotherapy.

Comparison of the Incidence Rate of Radiation Pneumonitis Observed in Patients with Advanced Lung Adenocarcinoma Treated with Simultaneous Thoracic Radiotherapy and 1G/2G/3G EGFR-TKIs.

The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT). Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015-2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups. A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p<0.001) and imaging grade of 46% vs 10% (p<0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades. Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.

Preliminary results of randomized phase II study of etoposide plus lobaplatin or etoposide plus cisplatin with concurrent thoracic radiotherapy in the treatment of limited-stage small cell lung cancer.

The purpose is to compare the clinical efficacy and toxicity of etoposide plus lobaplatin (EL) or etoposide plus cisplatin (EP) with concurrent thoracic radiotherapy during the treatment of limited-stage small cell lung cancer (LS-SCLC). Forty-two patients with LS-SCLC were randomly divided into EL ( n = 19) or EP ( n = 23) regimens combined with thoracic intensity-modulated radiotherapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The 1-, 2-, and 3-year PFS rates in the EL and EP cohorts were 50.8, 38.1, and 12.7%; and 56.5, 43.5, and 29.0%, respectively ( P = 0.527), whereas the 1-, 2-, and 3-year overall survival (OS) rates were 72.2, 52.5, and 43.8%; and 73.9, 48.4, and 48.4%, respectively ( P = 0.923). The hematological toxicities were similar in two cohorts. However, gastrointestinal reactions were more severe in the EP group. The incidence of nausea and vomiting in EL and EP cohorts were 31.6% vs. 73.9% ( P = 0.006) and 20.1% vs. 60.9% ( P = 0.009), respectively. The two cohorts did not show ≥grade 4 radiation esophagitis and ≥grade 3 radiation pneumonitis. The incidence of acute radiation esophagitis in EL group was lower ( P = 0.038), both groups showed a similar incidence of radiation pneumonitis ( P = 1.000). EL or EP chemotherapy with concurrent thoracic radiotherapy showed similar PFS and OS. The EL group showed milder gastrointestinal toxicity and radiation esophagitis. Radiation pneumonitis and hematological toxicity were similar in the two regimens, which can be tolerated by patients.

Radiation pneumonitis following Yttrium-90 radioembolization: A Korean multicenter study.

To report the incidence of radiation pneumonitis after radioembolization. In this retrospective study, from May 2009 to July 2021, 782 consecutive patients underwent radioembolization in two institutes. Medical internal radiation dose dosimetry and partition dosimetry were used for glass and resin Yttrium-90-labeled microspheres (90Y-microspheres), respectively. Medical records and radiological findings were retrospectively evaluated with emphasis on the symptomatic radiation pneumonitis. Of the 732 patients with lung shunt study and follow-up, 13 (1.8%) had symptomatic radiation pneumonitis and six patients died due to radiation pneumonitis. Of the 721 patients whose lung doses were calculated, 10 patients who were treated with glass (n = 5) and resin (n = 5) 90Y-microspheres had radiation pneumonitis. No significant statistical difference between glass and resin 90Y-microspheres (p = 0.304) was noted in terms of radiation pneumonitis incidence. Among the patients with radiation pneumonitis, all five patients treated with glass 90Y-microspheres had estimated lung doses > 29 Gy, whereas five patients treated with resin 90Y-microspheres had relatively wide range of lung dose reaching much lower value (13.21Gy). The present study suggests that radiation pneumonitis after radioembolization may occur even though the manufacturer's instructions are followed.

Incidence and Treatment Outcome of Radiation Pneumonitis in Patients With Limited-stage Small Cell Lung Cancer Treated With Concurrent Accelerated Hyperfractionated Radiation Therapy and Chemotherapy

PurposeThis study aimed to clarify the characteristics of and evaluate the risk factors for radiation pneumonitis (RP) induced by chemoradiation therapy (CRT) using accelerated hyperfractionated (AHF) radiation therapy (RT) in patients with limited-stage small cell lung cancer (LS-SCLC). Methods and MaterialsBetween September 2002 and February 2018, 125 patients with LS-SCLC were treated with early concurrent CRT using AHF-RT. Chemotherapy was comprised of carboplatin/cisplatin with etoposide. RT was administered twice daily (45 Gy/30 fractions). We collected data regarding onset and treatment outcomes for RP, and analyzed the relationship between RP and total lung dose–volume histogram findings. Uni- and multivariate analyses were performed to assess patient- and treatment-related factors for grade ≥2 RP. ResultsThe median age of patients was 65 years, and 73.6% of participants were men. In addition, 20% and 80.0% of participants presented with disease stage II and III, respectively. The median follow-up time was 73.1 months. Grades 1, 2, and 3 RP were observed in 69, 17, and 12 patients, respectively. Grades 4 to 5 RP were not observed. RP was treated with corticosteroids in patients with grade ≥2 RP, without recurrence. The median time from initiation of RT to onset of RP was 147 days. Three patients developed RP within 59 days, 6 within 60 to 89 days, 16 within 90 to 119 days, 29 within 120 to 149 days, 24 within 150 to 179 days, and 20 within ≥180 days. Among the dose–volume histogram parameters, the percentage of lung volume receiving >30 Gy (V30) was most strongly related to the incidence of grade ≥2 RP, and the optimal threshold to predict RP incidence was V30 ≥20%. On multivariate analysis, V30 ≥20% was an independent risk factor for grade ≥2 RP. ConclusionsThe incidence of grade ≥2 RP correlated strongly with a V30 of ≥20%. Contrarily, the onset of RP induced by concurrent CRT using AHF-RT may occur later. RP is manageable in patients with LS-SCLC.

Risk analysis of grade ≥ 2 radiation pneumonitis based on radiotherapy timeline in stage III/IV non-small cell lung cancer treated with volumetric modulated arc therapy: a retrospective study

BackgroundRadiotherapy is an important treatment for patients with stage III/IV non-small cell lung cancer (NSCLC), and due to its high incidence of radiation pneumonitis, it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥ 2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model.MethodsThis study retrospectively collected data from 91 stage III/IV NSCLC cases treated with Volumetric modulated arc therapy (VMAT). Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. Receiver operating characteristic (ROC), decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination.ResultsSmoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (area under curve [AUC]: 0.67,95% confidence interval [CI]: 0.52–0.81), (AUC: 0.82,95%CI: 0.70–0.94), (AUC: 0.90,95%CI: 0.80–1.00), and (AUC:0.90,95%CI: 0.80–1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(ratio:3.6%; 0 < score < 135), intermediate-(ratio:30.7%, 135 < score < 160) and high-risk group (ratio:80.0%, score > 160).ConclusionsIn our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonitis at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient’s risk level after completion of radiation therapy.