Radiation Pneumonitis In Patients Research Articles

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

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. 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. 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. 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.

Predictive role of circulatory levels of high-mobility group box 1 for radiation pneumonitis in patients with non-small cell lung cancer treated with definitive thoracic radiotherapy.

High-mobility group box 1 (HMGB1) is a pro-inflammatory protein associated with the pathophysiology of lung injury and lung tumorigenesis. Here, we investigated the predictive potential of serum HMGB1 levels for radiation pneumonitis in patients with lung cancer. This was a retrospective biomarker study of 73 patients with non-small cell lung cancer treated with definitive thoracic radiotherapy between August 2007 and January 2021. We measured HMGB1 levels in serum stored before treatment, and analyzed its association with the development of grade ≥ 2 or grade ≥ 3 radiation pneumonitis. Additionally, baseline characteristics affecting HMGB1 levels were identified. Of the 73 patients, 21 (28.8%) and 6 (8.2%) patients experienced grade 2 and ≥ 3 radiation pneumonitis, respectively. Univariate and multivariate logistic regression analyses revealed that higher baseline levels of serum HMGB1 were significantly associated with a higher risk of grade ≥ 3, but not grade ≥ 2, radiation pneumonitis. The incidence of grade ≥ 3 radiation pneumonitis was higher in patients with HMGB1 levels ≥ 6.2ng/mL than in those with levels < 6.2ng/mL (25.0% vs. 3.5%, p = 0.019). Baseline serum levels of HMGB1 were independently and positively associated with gross tumor volume. Higher serum HMGB1 levels were significantly associated with the risk of grade ≥ 3 radiation pneumonitis in patients with lung cancer, and therefore, HMGB1 could be a potential blood biomarker for predicting severe radiation pneumonitis.

EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting

Durvalumab is the new standard of care for unresectable locally advanced NSCLC, with PD-L1 ≥1% and who did not have progression after CRT treatment in the European Union. Our study compares the effectiveness and the frequency of radiation pneumonitis in patients treated with concurrent CRT with or without durvalumab consolidation during the same period in real clinical practice.

Using deep learning to predict radiation pneumonitis in patients treated with stereotactic body radiotherapy (SBRT) for pulmonary nodules: preliminary results

Using deep learning to predict radiation pneumonitis in patients treated with stereotactic body radiotherapy (SBRT) for pulmonary nodules: preliminary results

Research Progress on Radiotherapy Combined with Immunotherapy for Associated Pneumonitis During Treatment of Non-Small Cell Lung Cancer.

Radiation pneumonitis is a common and serious complication of radiotherapy for thoracic tumours. Although radiotherapy technology is constantly improving, the incidence of radiation pneumonitis is still not low, and severe cases can be life-threatening. Once radiation pneumonitis develops into radiation fibrosis (RF), it will have irreversible consequences, so it is particularly important to prevent the occurrence and development of radiation pneumonitis. Immune checkpoint inhibitors (ICIs) have rapidly altered the treatment landscape for multiple tumour types, providing unprecedented survival in some patients, especially for the treatment of non-small cell lung cancer (NSCLC). However, in addition to its remarkable curative effect, ICls may cause immune-related adverse events. The incidence of checkpoint inhibitor pneumonitis (CIP) is 3% to 5%, and its mortality rate is 10% to 17%. In addition, the incidence of CIP in NSCLC is higher than in other tumour types, reaching 7%–13%. With the increasing use of immune checkpoint inhibitors (ICls) and thoracic radiotherapy in the treatment of patients with NSCLC, ICIs may induce delayed radiation pneumonitis in patients previously treated with radiation therapy, or radiation activation of the systemic immune system increases the toxicity of adverse reactions, which may lead to increased pulmonary toxicity and the incidence of pneumonitis. In this paper, the data about the occurrence of radiation pneumonitis, immune pneumonitis, and combined treatment and the latest related research results will be reviewed.

VMAT-Based Planning Allows Sparing of a Spatial Dose Pattern Associated with Radiation Pneumonitis in Patients Treated with Radiotherapy for a Locally Advanced Lung Cancer.

Simple SummaryA sub-region localized in the posterior right lung was significantly associated with the risk of grade ≥ 2 acute pulmonary toxicity in patients with locally advanced lung cancer treated with radiotherapy. Avoiding this sub-region with volumetric-arctherapy-based planification leads to a significant reduction of the predicted APT risk by reclassifying 43.2% (19/44) of the patients.Introduction: In patients treated with radiotherapy for locally advanced lung cancer, respect for dose constraints to organs at risk (OAR) insufficiently protects patients from acute pulmonary toxicity (APT), such toxicities being associated with a potential impact on the treatment’s completion and the patient’s quality of life. Dosimetric planning does not take into account regional lung functionality. An APT prediction model combining usual dosimetry features with the mean dose (DMeanPmap) received by a voxel-based volume (Pmap) localized in the posterior right lung has been previously developed. A DMeanPmap of ≥30.3 Gy or a predicted APT probability (ProbAPT) of ≥8% were associated with a higher risk of APT. In the present study, the authors aim to demonstrate the possibility of decreasing the DMeanPmap via a volumetric arctherapy (VMAT)-based adapted planning and evaluate the impact on the risk of APT. Methods: Among the 207 patients included in the initial study, only patients who presented with APT of ≥grade 2 and with a probability of APT ≥ 8% based on the prediction model were included. Dosimetry planning was optimized with a new constraint (DMeanPmap < 30.3 Gy) added to the usual constraints. The initial and optimized treatment plans were compared using the t-test for the independent variables and the non-parametric Mann–Whitney U test otherwise, regarding both doses to the OARs and PTV (Planning Target Volume) coverage. Conformity and heterogeneity indexes were also compared. The risk of APT was recalculated using the new dosimetric features and the APT prediction model. Results: Dosimetric optimization was considered successful for 27 out of the 44 included patients (61.4%), meaning the dosimetric constraint on the Pmap region was achieved without compromising the PTV coverage (p = 0.61). The optimization significantly decreased the median DMeanPmap from 28.8 Gy (CI95% 24.2–33.4) to 22.1 Gy (CI95% 18.3–26.0). When recomputing the risk of APT using the new dosimetric features, the optimization significantly reduced the risk of APT (p < 0.0001) by reclassifying 43.2% (19/44) of the patients. Conclusion: Our approach appears to be both easily implementable on a daily basis and efficient at reducing the risk of APT. Regional radiosensitivity should be considered in usual lung dose constraints, opening the possibility of new treatment strategies, such as dose escalation or innovative treatment associations.

Association of T Cell Senescence with Radiation Pneumonitis in Patients with Non-small Cell Lung Cancer

Associations between immunosenescence and radiation pneumonitis (RP) are largely unknown. We aimed to identify a peripheral blood T cell senescence biomarker to predict RP in patients with non-small cell lung cancer (NSCLC). Patients with locally advanced NSCLC who received definitive concurrent chemoradiotherapy (dCRT) were prospectively registered (cohort 1, n=23; cohort 2, n=31). Peripheral blood was collected at baseline, during dCRT, and at 1 month post-dCRT. Patients were dichotomized to grade ≥2 (G2+) RP and grade 0-1 (G0-1) RP. Flow cytometry was performed to assess phenotypes and functional properties of T cell subsets. RP incidence was estimated via competing risk analysis. Five and six patients exhibited G2+ RP following dCRT in cohorts 1 and 2, respectively. Patients with G2+ RP exhibited a more aged T cell pool and higher frequencies of senescent CD57+CD28-CD8+ T cells than patients with G0-1 RP at baseline, during dCRT, and at 1 month post-dCRT. These senescent cells exhibited increased granzyme B, IFN-γ, and TNF-α production. Higher baseline frequency of CD57+CD28-CD8+ T cells was an independent predictor of G2+ RP (hazard ratio, 8.42; 95% confidence interval, 2.58-27.45; P<0.001). Recursive partitioning analysis revealed three distinct risk groups stratified by baseline CD57+CD28-CD8+ T cell frequency and lung V20 Gy, with 1-year cumulative G2+ RP incidences of 50.0%, 16.7%, and 0% for high-, intermediate-, and low-risk groups, respectively (P=0.002). Higher baseline frequencies of CD57+CD28-CD8+ T cells correlated with increased G2+ RP risks. Our results suggest the need for further investigation of the role of T cell senescence on radiation-induced organ damage.

Efficacy of Thymosin α1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043)

To evaluate the efficacy of thymosin α1 in management of radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemoradiotherapy (CCRT). This phase 2, single-arm trial enrolled patients with unresectable LANSCLC of 18 to 75 years' old and an Eastern Cooperative Oncology Group performance status of 0 to 1. Eligible patients received definitive CCRT and weekly thymosin α1 from the start of CCRT until 2 months after CCRT. Patients were administered 51 Gy in 17 daily fractions or 40 Gy in 10 daily fractions in the first course followed by a re-evaluation and those patients without disease progression had an adaptive plan of 15 Gy in 5 daily fractions or 24 Gy in 6 daily fractions as a boost. Concurrent chemotherapy consisted of weekly docetaxel (25 mg/m2) and nedaplatin (25 mg/m2) during radiation therapy. The primary endpoint was the incidence of Grade (G) ≥2 RP. Secondary endpoints included the incidence of late pulmonary fibrosis, total lymphocyte count (TLC), serum C-reactive protein (CRP) levels, and the composition of gut microbiota. TLC and CRP data were collected at baseline, 2 to 3 weeks during CCRT, the end of CCRT, 2 and 6 months after CCRT. Fecal samples were collected at baseline and the end of CCRT. Patients treated with CCRT but without thymosin α1 intervention during the same period were selected as the control group by the propensity score matching method. Sixty-nine patients were enrolled in the study, and another 69 patients were selected as the control group. The incidence of G≥2 RP was lower in the study group compared with control cases (36.2% vs 53.6%, P=.040). G1 late pulmonary fibrosis occurred in 2 (3.7%) patients of the control group compared with no event in the study group (P=.243). Compared with the control group, the incidence of G3 to G4 lymphopenia (19.1% vs 62.1%, P < .001) was lower, and the median TLC nadir (0.51 k/µL vs 0.30 k/µL, P < .001) was higher in the study group. The proportion of patients with maximum CRP ≥100 mg/L was lower in the study group (13.8% vs 29.7% P=.029). The diversity and community composition of the gut microbiota were not significantly different between the 2 groups. Administration of thymosin α1 during and after CCRT was associated with significant reductions in G≥2 RP and G3 to G4 lymphopenia in patients with LANSCLC compared with historic controls.

Development and Validation of a Radiomics Nomogram Using Computed Tomography for Differentiating Immune Checkpoint Inhibitor-Related Pneumonitis From Radiation Pneumonitis for Patients With Non-Small Cell Lung Cancer.

BackgroundThe combination of immunotherapy and chemoradiotherapy has become the standard therapeutic strategy for patients with unresected locally advance-stage non-small cell lung cancer (NSCLC) and induced treatment-related adverse effects, particularly immune checkpoint inhibitor-related pneumonitis (CIP) and radiation pneumonitis (RP). The aim of this study is to differentiate between CIP and RP by pretreatment CT radiomics and clinical or radiological parameters.MethodsA total of 126 advance-stage NSCLC patients with pneumonitis were enrolled in this retrospective study and divided into the training dataset (n =88) and the validation dataset (n = 38). A total of 837 radiomics features were extracted from regions of interest based on the lung parenchyma window of CT images. A radiomics signature was constructed on the basis of the predictive features by the least absolute shrinkage and selection operator. A logistic regression was applied to develop a radiomics nomogram. Receiver operating characteristics curve and area under the curve (AUC) were applied to evaluate the performance of pneumonitis etiology identification.ResultsThere was no significant difference between the training and the validation datasets for any clinicopathological parameters in this study. The radiomics signature, named Rad-score, consisting of 11 selected radiomics features, has potential ability to differentiate between CIP and RP with the empirical and α-binormal-based AUCs of 0.891 and 0.896. These results were verified in the validation dataset with AUC = 0.901 and 0.874, respectively. The clinical and radiological parameters of bilateral changes (p < 0.001) and sharp border (p = 0.001) were associated with the identification of CIP and RP. The nomogram model showed good performance on discrimination in the training dataset (AUC = 0.953 and 0.950) and in the validation dataset (AUC = 0.947 and 0.936).ConclusionsCT-based radiomics features have potential values for differentiating between patients with CIP and patients with RP. The addition of bilateral changes and sharp border produced superior model performance on classifying, which could be a useful method to improve related clinical decision-making.

Dosimetric Risk Factors for Acute Radiation Pneumonitis in Patients With Prior Receipt of Immune Checkpoint Inhibitors.

PurposeDosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far.Methods and MaterialsAll included patients underwent thoracic intensity-modulated radiotherapy, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis.ResultsMedian follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Neither the number of prior ICI cycles nor the delivery of concurrent systemic therapy significantly associated with aRP risk. Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD (continuous variables).ConclusionsThis is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. However, these data should not be extrapolated to patients without pre-radiotherapy receipt of prior ICIs, or to evaluate the risk of chronic pulmonary effects. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.

Radiation pneumonitis in patients with non-small-cell lung cancer receiving chemoradiotherapy and an immune checkpoint inhibitor: a retrospective study

BackgroundImmunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients.MethodsWe evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated.ResultsAfter CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0–28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed.ConclusionsPatients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.

Immune-Related Radiation Pneumonitis in Patients Undergoing Durvalumab Treatment After Concurrent Chemo-Proton Therapy

Although the PACIFIC trial did not suggest that the administration of durvalumab increased the risk of radiation pneumonitis (RP) compared to placebo, the timing of durvalumab administration following concurrent chemo-radiotherapy was various and the method used to evaluate RP including interstitial pneumonia was unclear. Thus, further studies are needed to better understand the development of immune-related adverse event (irAE), in particular RP. In the present study, we performed a preliminary analysis to investigate RP after concurrent chemo-proton therapy (CCPT) followed by durvalumab.Between October 2018 and March 2020, 17 patients were administered durvalumab (mg/kg, q2w) within 14 days after CCPT (70 GyRBE/35 fractions and cisplatin (60 mg/m2) on day 1 and S-1 (w40 mg/m2 twice daily) on days 1 to 14, q4w, for up to 2 cycles). As a control, 47 patients who underwent CCPT in our previous phase II trial conducted between August 2013 and December 2017 were analyzed. These 47 patients were administered adjuvant chemotherapy (same regimen for up to 2 cycles) after CCPT. In patients suspected to have developed RP as a result of irAE, their treatment plans were compared with CT images obtained at the time of RP onset to examine the association between the dose distribution and RP.In our previous study, acute grade 2 RP within 3 months after the end of irradiation was observed in 4 patients (8.5%), and no patients developed grade 3 or higher RP. However, all occurred after completion of adjuvant chemotherapy, that is, within 2-3 months after the end of irradiation. On the other hand, 6 patients developed symptomatic grade 2 RP within 1 month of treatment among 17 patients who were administered durvalumab. Unlike CT findings of RP in the control patients, RP in 6 patients who received durvalumab was identified in the areas that received low-to-medium doses of proton irradiation and/or outside of the irradiation field, whereas the areas that received a high dose of proton irradiation exhibited little to no inflammatory response. In 3 patients who were subsequently administered steroids, CT revealed a rapid decrease in the lung volume and inflammatory response that progressed every week, in addition to traction ectasia and rapid progression of fibrosis. For the remaining 3 patients, the symptoms were mild without fever and improved only by stopping durvalmab without using steroids, and the course of CT images were similar.Administration of durvalumab soon after CCPT resulted in the unexpected or unusual course of development of RP, which was likely an irAE. Further studies are needed to better understand the cause of immune-related RP.

Computed Tomography-Based Delta-Radiomics Analysis for Discriminating Radiation Pneumonitis in Patients With Esophageal Cancer After Radiation Therapy.

Our purpose was to construct a computed tomography (CT)-based delta-radiomics nomogram and corresponding risk classification system for individualized and accurate estimation of severe acute radiation pneumonitis (SARP) in patients with esophageal cancer (EC) after radiation therapy. Four hundred patients with EC were enrolled from 2 independent institutions and were divided into the training (n=200) and validation (n=200) cohorts. Eight hundred fifty radiomics features of lung were extracted from treatment planning images, including the positioning CT before radiation therapy (CT1) and the resetting CT after receiving 40 to 45 Gy (CT2). The longitudinal net changes in radiomics features from CT1 to CT2 were calculated and defined as delta-radiomics features. Least absolute shrinkage and selection operator algorithm was performed to features selection and delta-radiomics signature building. Integrating the signature with multidimensional clinicopathologic, dosimetric, and hematological predictors of SARP, a novel CT-based delta-radiomics nomogram was established according to multivariate analysis. The clinical application values of nomogram were both evaluated in the training and validation cohorts by concordance index, calibration curves, and decision curve analysis. Recursive partitioning analysis was used to generate a risk classification system. The delta-radiomics signature consisting of 24 features was significantly associated with SARP status (P < .001). Incorporating it with other high-risk factors, Subjective Global Assessment score, pulmonary fibrosis score, mean lung dose, and systemic immune inflammation index, the developed delta-radiomics nomogram showed increased improvement in SARP discrimination accuracy with concordance index of 0.975 and 0.921 in the training and validation cohorts, respectively. Calibration curves and decision curve analysis confirmed the satisfactory clinical feasibility and utility of nomogram. The risk classification system displayed excellent performance on identifying SARP occurrence (P < .001). The delta-radiomics nomogram and risk classification system as low-cost and noninvasive means exhibited superior predictive accuracy and provided individualized probability of SARP stratification for patients with EC.

Assessment of chemotherapy regimens on radiation pneumonitis in patients with unresectable stage III non-small-cell lung cancer after definitive chemoradiotherapy.

BackgroundConsolidation therapy with durvalumab after concurrent chemoradiotherapy has been reported to significantly prolong progression‐free survival and overall survival in patients with stage III unresectable non‐small cell lung cancer (NSCLC). However, which chemotherapy regimen should be selected for consolidation therapy with durvalumab is currently unknown.MethodsWe retrospectively reviewed consecutive patients with unresectable stage III NSCLC who received concurrent definitive chemoradiotherapy with platinum‐based chemotherapy. We reviewed the timing and severity of radiation pneumonitis by assessing chemotherapy regimens and histology.ResultsA total of 103 patients were identified. Fourteen patients (13.6%) developed grade 2 or greater radiation pneumonitis within 42 days after chemoradiotherapy. No adenocarcinoma patients treated with a regimen of cisplatin plus pemetrexed developed grade 2 or greater radiation pneumonitis within 42 days; however, 20% of patients who were treated with carboplatin plus paclitaxel developed grade 2 or greater radiation pneumonitis. Furthermore, the objective response rates and disease control rates of cisplatin plus pemetrexed were equal to or greater than those of carboplatin plus paclitaxel in adenocarcinoma patients.ConclusionCisplatin plus pemetrexed regimen may be a preferable option to consider for subsequent consolidation therapy with durvalumab in patients with unresectable stage III adenocarcinoma.

Chemoradiotherapy for limited-stage small-cell lung cancer and interstitial lung abnormalities

BackgroundPatients with lung cancer and interstitial lung disease treated with radiotherapy are at risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILAs) and radiation pneumonitis in patients with limited-stage small-cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is uncertain for patients with SCLC and ILAs treated with chemoradiotherapy. We investigated the impact of ILAs on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILAs treated with chemoradiotherapy.MethodsWe retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016.ResultsIn the univariate analysis, the patients with ILAs showed a higher incidence rate of radiation pneumonitis compared with those without ILAs (64% vs. 10%, P < 0.001). Multivariate analysis confirmed that ILAs were significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILAs showed poorer overall survival than those without ILAs (median, 18.9 vs. 67.9 months, P = 0.0338). Multivariate analysis showed that ILAs were a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILAs treated with chemoradiotherapy were 36% and 26%, respectively, and 8% and 0%, respectively, for those treated with chemotherapy alone.ConclusionsILAs were found to be a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. Patients with LS-SCLC and ILAs who were treated with chemoradiotherapy had both the possibility of long-term survival and risk of radiation pneumonitis.

Establishment and Verification of a Prediction Model for Symptomatic Radiation Pneumonitis in Patients with Esophageal Cancer Receiving Radiotherapy

BackgroundThis study aimed to determine the value of the significant index in predicting symptomatic radiation pneumonitis (RP) in esophageal cancer patients, establish a nomogram prediction model, and verify the model.Material/MethodsThe patients enrolled were divided into 2 groups: a model group and a validation group. According to the logistic regression analysis, the independent predictors for symptomatic RP were obtained, and the nomogram prediction model was established according to these independent predictors. The consistency index (C-index) and calibration curve were used to evaluate the accuracy of the model, and the prediction ability of the model was verified in the validation group. Recursive partitioning analysis (RPA) was used for the risk stratification analysis.ResultsThe ratio of change regarding the pre-albumin at the end of treatment (P=0.001), platelet-to-lymphocyte ratio during treatment (P=0.027), and neutrophil-to-lymphocyte ratio at the end of treatment (P=0.001) were the independent predictors for symptomatic RP. The C-index of the nomogram model was 0.811. According to the risk stratification of RPA, the whole group was divided into 3 groups: a low-risk group, a medium-risk group, and a high-risk group. The incidence of symptomatic RP was 0%, 16.9%, and 57.6%, respectively. The receiver operating characteristic curve also revealed that the nomogram model has good accuracy in the validation group.ConclusionsThe developed nomogram and corresponding risk classification system have superior prediction ability for symptomatic RP and can predict the occurrence of RP in the early stage.

The Plasma Levels and Polymorphisms of Vitronectin Predict Radiation Pneumonitis in Patients With Lung Cancer Receiving Thoracic Radiation Therapy

Our previous findings have identified vitronectin (VTN) as a potential biomarker for radiation pneumonitis (RP) through proteomics and molecular mechanism studies. In a recent study, we further explored associations of plasma level and single nucleotide polymorphisms of VTN with the risk of RP in patients with lung cancer receiving radiation therapy. A total of 165 patients with lung cancer were prospectively enrolled with detection of VTN concentration before radiation therapy. VTN reference single nucleotide polymorphisms, rs704 and rs2227721, were genotyped by Taqman probe method. Cox proportional hazard models were performed to identify clinical variables and genotypes associated with the risk of RP on univariate and multivariate analyses, and t tests and analysis of variance were conducted to evaluate the expression level of VTN. The baseline secretion level of VTN in patients with grade ≥3 RP was significantly higher than that in grade <3 RP patients (P < .0001), and elevated levels were observed in patients having the AA genotype compared with GA/GG genotypes of rs704. The VTN rs704 GA/GG and rs2227721 AA/AC genotypes had a significantly lower risk of RP (hazard ratio [HR], 0.448, P = .005; HR, 0.419, P = .008, respectively). In addition, combining cut-off values of mean lung dose (MLD) and VTN plasma level, grade ≥3 RP risk groupings were as follows: high risk: MLD ≥12 Gy and VTN level ≥132 μg/mL (RP rate, 10 of 16 patients, 62.5%); intermediate risk: MLD ≥12 Gy and VTN level <132 μg/mL or MLD <12 Gy and VTN level ≥132 μg/mL (8 of 70 patients, 11.4%); and low risk: MLD <12 Gy and VTN level <132 μg/mL (1 of 79 patients, 1.3%) (P < .0001). Among patients receiving radiation therapy, relatively high plasma levels of VTN before radiation therapy were associated with the higher incidence of RP, and VTN rs704 and rs2227721 each had a significant effect on predicting RP risk. Combining VTN concentration with MLD appeared to facilitate stratification of patients with lung cancer who received radiation therapy into low-, intermediate-, and high-risk RP groups. This study indicated that VTN may serve as a blood biomarker for susceptibility to RP in patients with lung cancer.

Factors Associated With Radiation Pneumonitis in Patients Receiving Electron Boost Radiation for Breast-Conserving Therapy: A Retrospective Review

PurposeThis study aimed to investigate risk factors for radiation pneumonitis (RP) caused by electron beam (EB) boost irradiation during breast-conserving therapy. Methods and MaterialsThis single-institution retrospective study included patients with breast cancer treated with breast-conserving therapy from 2013 to 2019. Radiation therapy comprised whole-breast irradiation with a dose of 50 Gy and 10 Gy EB boost dose to the tumor bed. EB energies were 4, 6, 9, 12, and 15 MeV. The lung volume receiving ≥1.25 Gy (V1.25) was calculated and considered because the EB energies have a short range. All patients underwent computed tomography and positron emission tomography/computed tomography within 1 year of irradiation. Imaging evaluation was based on the Common Terminology Criteria for Adverse Events, version 5.0. ResultsOverall, 105 patients (median age, 62 years; range, 33-85) were included for analysis with a median follow-up period of 5 months. Average area of EB boost irradiation was 72 cm2 (range, 36-196). Grade 1 RP developed in the EB irradiation field in 22 (20.6%) patients; grade 2 RP developed in 1 (0.93%) patient. Even in patients with central lung distance (CLD) ≥1.8 cm, a positive correlation was found between RP and both energy (r = 0.36; P = .005) and V1.25 (r = 0.26; P = .04). No correlation was found between RP and irradiation field size (P = .47). The EB energy and V1.25 cutoff values were 12 MeV and 24 cm3, respectively. ConclusionsCLD of ≥1.8 cm, EB energy of ≥12 MeV, and V1.25 of ≥24 cm3 were risk factors associated with RP. Although the frequency of severe RP was not high, patients receiving high-energy electron treatment and those with a large CLD should be closely monitored.

Amiodarone Use and Radiation Pneumonitis in Patients Undergoing Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

Stereotactic body radiation therapy (SBRT) has become a standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. Amiodarone is a well-known cause of pneumonitis and an increasing number of patients treated with SBRT are also on amiodarone. Given this potential risk of pulmonary toxicity, it is of interest to examine whether amiodarone may potentiate the risk of RP. We sought to examine the impact of amiodarone use on RP in patients treated with SBRT. Patients with early-stage NSCLC who were taking amiodarone and underwent SBRT from January 2005 to January 2019 were identified from an IRB-approved institutional database. Amiodarone was required to be taken within 3 months before or after SBRT for inclusion. RP status was confirmed using CTCAE guidelines. Follow-up was defined as the time from the end of SBRT treatment until the most recent follow-up or date of death. Thirty-three patients met the inclusion criteria. Median follow up was 14 months (range, 1 to 55 months). The median dose of radiation was 54 Gy (range, 45 to 60) delivered in 3 to 12 fractions. Three patients (9%) developed radiation pneumonitis; all cases of pneumonitis were grade 2. One patient (3%) had a diagnosis of interstitial lung disease (ILD) and no presence of pneumonitis. In this single-institution series, the use of amiodarone in concert with lung SBRT was not associated with numerically increased rates of RP compared with the established literature. These results will need to be validated in larger cohorts with proper control of established metrics (lung V20, ILD), as well as other patient populations such as those undergoing cardiac radio-ablation, where the risks and mechanisms of injury may be different.

Factors Associated with Radiation Pneumonitis in Patients Receiving Electron Boost Radiation for Breast-Conserving Surgery: A Retrospective Review

Factors Associated with Radiation Pneumonitis in Patients Receiving Electron Boost Radiation for Breast-Conserving Surgery: A Retrospective Review