Multiple regression analysis of risk factors related to radiation pneumonitis

BACKGROUND Radiation pneumonitis(RP)is a severe complication of thoracic radiotherapy that may lead to dyspnea and lung fibrosis,and negatively affects patients’quality of life.AIM To carry out multiple regression analysis on the influencing factors of radiation pneumonitis.METHODS Records of 234 patients receiving chest radiotherapy in Huzhou Central Hospital(Huzhou,Zhejiang Province,China)from January 2018 to February 2021,and the patients were divided into either a study group or a control group based on the presence of radiation pneumonitis or not.Among them,93 patients with radiation pneumonitis were included in the study group and 141 without radiation pneumonitis were included in the control group.General characteristics,and radiation and imaging examination data of the two groups were collected and compared.Due to the statistical significance observed,multiple regression analysis was performed on age,tumor type,chemotherapy history,forced vital capacity(FVC),forced expiratory volume in the first second(FEV1),carbon monoxide diffusion volume(DLCO),FEV1/FVC ratio,planned target area(PTV),mean lung dose(MLD),total number of radiation fields,percentage of lung tissue in total lung volume(vdose),probability of normal tissue complications(NTCP),and other factors.RESULTS The proportions of patients aged≥60 years and those with the diagnosis of lung cancer and a history of chemotherapy in the study group were higher than those in the control group(P<0.05);FEV1,DLCO,and FEV1/FVC ratio in the study group were lower than those in the control group(P<0.05),while PTV,MLD,total field number,vdose,and NTCP were higher than in the control group(P<0.05).Logistic regression analysis showed that age,lung cancer diagnosis,chemotherapy history,FEV1,FEV1/FVC ratio,PTV,MLD,total number of radiation fields,vdose,and NTCP were risk factors for radiation pneumonitis.CONCLUSION We have identified patient age,type of lung cancer,history of chemotherapy,lung function,and radiotherapy parameters as risk factors for radiation pneumonitis.Comprehensive evaluation and examination should be carried out before radiotherapy to effectively prevent radiation pneumonitis.

Study of the impact of CT/CT image fusion radiotherapy on V_(20) and radiation pneumonitis of non-small cell lung cancer

Objective:The aim of our study was to investigate the value of CT/CT image fusion radiation treatment planning in non-small cell lung cancer(NSCLC) and the impact on V20 and radiation pneumonitis(RP).Methods:Patients who were pathologically or cytologically diagnosed of stage IIIA and IIIB NSCLC were treated with three-dimensional conformal radiation therapy(4000 cGy).Forty patients got at least 25% tumor reduction were randomly divided into two groups:group A of regular shrink field radiotherapy(20 cases) and group B of CT/CT image fused shrink field radiotherapy(20 cases).Dosage reached 6600 cGy.Clinical data,V20 and RP were observed within 3 months after radiotherapy.Statistical analysis was conducted for the NSCLC patients.Results:22.5%(9/40) patients got RP during follow-up.Group A accounted for 6 cases(30%),and group B had 3 cases(15%).There was no marked difference between the two groups(P = 0.256),univariate analysis revealed that the IV20 of A and B groups,and IV20 and CV20 of all patients were statistically related to the incidence of RP(P < 0.05).With Wilcoxon method assay,the ipsilateral lung V20 and contralateral lung V20 had statistical significance between the two groups(P < 0.05).Conclusion:The CT/CT image infusion treatment planning could increase the radical dosage with better tumor control probability but won't increase adverse reaction.

Symptomatic Radiation Pneumonitis in NSCLC Patients Receiving EGFR-TKIs and Concurrent Oncedaily Thoracic Radiotherapy:Predicting the Value of Clinical and Dose-volume Histogram Parameters

Background and objectives:The incidence of symptomatic radiation pneumonitis(RP)and its relationship with dose-volume histogram(DVH)parameters in non-small cell lung cancer(NSCLC)patients receiving epidermal growth factor receptortyrosine kinase inhibitors(EGFR-TKIs)and concurrent once-daily thoracic radiotherapy(TRT)remain unclear.We aim to analyze the values of clinical factors and dose-volume histogram(DVH)parameters to predict the risk for symptomatic RP in these patients.Methods:Between 2011 and 2019,we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and oncedaily TRT simultaneously(EGFR-TKIs group)and 129 patients who had received concurrent chemoradiotherapy(CCRT group).The symptomatic RP was recorded according to the Common Terminology Criteria for Adverse Event(CTCAE)criteria(grade 2 or above).Statistical analyses were performed using SPSS 26.0.Results:In total,the incidences of symptomatic(grade≥2)and severe RP(grade≥3)were 43.5%(37/85)and 16.5%(14/85)in EGFR-TKIs group vs 27.1%(35/129)and 10.1%(13/129)in CCRT group respectively.After 1:1 ratio between EGFR-TKIs group and CCRT group was matched by propensity score matching,chi-square test suggested that the incidence of symptomatic RP in the MATCHED EGFR-TKIs group was higher than that in the matched CCRT group(χ^(2)=4.469,P=0.035).In EGFRTKIs group,univariate and multivariate analyses indicated that the percentage of ipsilateral lung volume receiving≥30 Gy(ilV_(30))[odds ratio(OR):1.163,95%CI:1.036-1.306,P=0.011]and the percentage of total lung volume receiving≥20 Gy(tlV_(20))(OR:1.171,95%CI:1.031-1.330,P=0.015),with chronic obstructive pulmonary disease(COPD)or not(OR:0.158,95%CI:0.041-0.600,P=0.007),were independent predictors of symptomatic RP.Compared to patients with lower iIV_(30)/tlV_(20)values(ilV_(30)and tlV_(20)<cut-off point values)and without COPD,patients with higher ilV_(30)/tlV_(20)values(ilV_(30)and tlV_(20)>cut-off point values)and COPD had a significantly higher risk for developing symptomatic RP,with a hazard ratio(HR)of 1.350(95%CI:1.190-1.531,P<0.001).Conclusion:Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy.The ilV_(30),tlV_(20),and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.

A missense variant of MASP2 is associated with increased risk of radiation pneumonitis in lung cancer patients treated with radiation therapy

Objective In this study,mannan-binding lectin-associated serine protease 2(MASP2)gene variant was evaluated to assess the risk of radiation pneumonitis(RP)in patients with pulmonary malignancies.Methods A total of 169 lung cancer patients with radiotherapy were included in our prospective study(NCT02490319)and genotyped using the Sanger sequencing method.Multivariate Cox hazards analysis and multiple testing were applied to estimate the hazard ratio(HR)and 95%confidence intervals(CIs)of all factors possibly associated with RP risk.Results Patients with mean lung disease≥15 Gy and V20≥24%had higher risk of RP≥grade 2 compared with their counterparts(HR=1.888,95%CI:1.186-3.004,P=0.007;HR=2.126,95%CI:1.338-3.378,P=0.001,respectively).Importantly,CC+CA genotype of MASP2:rs12711521 was strongly associated with an increased occurrence of RP≥grade 2(HR=1.949,95%CI:1.278-2.971,P=0.002).Conclusion MASP2:rs12711521 was found to be significantly associated with RP≥grade 2 in our cohort and may thus be one of the important predictors of severe RP before radiotherapy,if further validated in larger population.

Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis

Radiation therapy is an effective method to kill cancer cells and shrink tumors using highenergy X-ray or γ-ray. Radiation pneumonitis(RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here,we prepared curcumin-loaded mesoporous polydopamine nanoparticles(CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles(MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π-π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2 B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of15 Gy^(60)Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

[^18F]2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography in predicting radiation pneumonitis

Background Prevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [^18F]2-fluoro-2-deoxyglucose （FDG） uptake changes in the lung after radiotherapy could be used as a new predictor for acute radiation pneumonitis （RP）. Methods Forty-one patients with lung cancer underwent FDG positron emission tomography/computed tomography （FDG-PET/CT） imaging before and after radiotherapy. The mean standardized uptake value （SUV） was measured for the isodose regions of 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy. The mean SUV of these regions after radiotherapy was compared with baseline. The mean SUV in patients who developed RP was also compared with that in those who did not. The statistical difference was determined by matched pair t test. The Radiation Therapy Oncology Group （RTOG） criteria were used for diagnosis and grading of RP. Results With a median follow-up of 12 months, 11 （26.8%） of the 41 patients developed grade 2 and above acute RP. The mean SUV of regions （10-19 Gy, 20-29 Gy, 30-39 Gy, 40-49 Gy） increased after radiation therapy in all 41 patients. The mean SUVs after radiation therapy were 0.54, 0.68, 1.31, 1.74 and 2.27 for 0-9 Gy, 10-19 Gy, 20-29 Gy, 30-39 Gy and 40-49 Gy, respectively. Before the radiation therapy, the mean SUV in each region was 0.53, 0.52, 0.52, 0.53 and 0.54, respectively. These patients had significantly higher FDG activities in regions receiving 10 Gy or more （P 〈0.001）. Compared with their counterparts, the elevation of SUV was significantly greater in those patients who developed acute RP subsequently. Conclusion The mean SUV of the lung tissue may be a useful predictor for the acute RP. FDG-PET/CT may play a new role in the study of the radiation damage of the lung.

The Study of Early Application with Dixiong Decoction for Non-small Cell Lung Cancer to Decrease the Incidence and Severity of Radiation Pneumonitis: A Prospective, Randomized Clinical Trial

Objective： To evaluate the efficacy of compound Dixiong Decoction （地芎汤, a Chinese herbal decoction） on early prevention of radiation pneumonitis. Methods： Forty-six patients with non-small cell lung cancer who were planning to receive radiotherapy were randomly assigned to the treatment group treated with the compound Dixiong Decoction and the control group treated with a commonly used herbal decoction which has the effects of supplementing qi and nourishing yin, clearing heat and detoxifying at the time of radiotherapy. Primary measure was the incidence of radiation pneumonitis after radiotherapy. Secondary outcomes included Watters clinical radiographic physiologic （CRP） dyspnea score, the Radiation Therapy Oncology Group （RTOG） grading score, Karnofsky Performance Status （KPS） score, and the application of corticosteroids. Results： The incidence of radiation pneumonitis in the treatment group was 10.0%, while that in the control group was 26.3% （P=0.0032）. The Watters CRP dyspnea score and RTOG grading score in the treatment group were significantly lower than those in the control group （P0.05）. The KPS score in the treatment group was significantly higher than that in the control group （P0.01）. The dosage of corticosteroids was smaller with a shorter duration of therapy in the treatment group than that in the control group. Conclusion： The early application of the Chinese herbal decoction compound Dixiong Decoction can decrease the incidence of radiation pneumonitis, reduce the injury of the lung, and improve the life quality of the patients.

Treatment of Interstitial Peumopathy by Fei Tong Oral Liquid in the Malignant Tumor Patients after Radio-and/or Chemotherapy

Fei Tong Kou Fu Ye (肺通口服液 Fei Tong Oral Liquid) was used to treat 30 cases of interstitial pneumopathy after radio- and/or chemotherapy.In comparison with the control group (15 cases) treated with hormones,the therapeutic effects in improving dyspnea,cough,respiratory rate,cyanosis,findings in X-films and CT examination,partial pressure of oxygen in artery,FVC and VC were found significantly better (P<0.05).The total effective rate obtained was 83.33%.

Results of flexible 3D-conformal radiotherapy for patients with diffuse malignant pleural mesothelioma and comparative study of this technique with conventional radiotherapy

Objective： To observe the effects of the new technique of flexible 3D-conformal radiotherapy with combination of photon and electron （3DCRT） in the treatment of the patients with diffuse malignant pleural mesothelioma （MPM）, and carry out the comparative study between flexible 3DCRT and hemithoracic conventional radiotherapy （CRT）. Methods： From January 2004 to October 2007, 8 patients with MPM were treated with flexible 3DCRT. 5 patients had received cycles of chemotherapy before radiation. New technique of flexible 3DCRT with combination of photon and electron was used in our study, and DT 32.2-64 Gy with conventional split were delivered. CRT technique was mimicked to compare with 3DCRT technique to predict the possibility of lung damage in two methods. Results： One patient reached CR and other 7 patients got PR after radiation. Two patients died during the follow-up. The median survival time （MST） was 15.4 months and it was 18.8 months for sequential chemotherapy and radiotherapy group and 9.7 months for radiotherapy alone group. The V20, V30, and ipsilateral and contralateral median lung dosage （MLD） were 20.5%, 15.6%, 18.8 Gy and 2.2 Gy respectively when the flexible 3DCRT technique was used, whereas they were 36.8%, 27.9%, 31.1 Gy and 1.2 Gy respectively when the CRT technique was used. They were statistically different for the lung V20, V30 and ipsilateral MLD between the two techniques （P 〈 0.01）, whereas there was no different for the contralateral MLD （P = 0.08）. All patients received radiation were found to have lung fibrosis and classified as grades 1-2 radiation pneumonitis. The quality of life was increased from score 2.83 to 3.76 and it was significantly different （P 〈 0.01）. Conclusion： MPM is moderately sensitive to radiation. The flexible 3DCRT technique is feasible in the treatment of MPM and lung damage is reduced apparently comparing with the CRT technique. The quality of life of patients with MPM is improved after irradiation.

Inhaled amifostine for the prevention of radiation-induced lung injury

Objective:To alleviate radiation-induced lung injury and prevent the related pneumonitis and pulmonary fibrosis by inhaled amifostine(AMI).Methods:15 Gy 60Coγ-ray irradiation was performed on the thoracic area of rats once to establish the radiation injury model.AMI was intraperitoneally(i.p.)injected or intratracheally(i.t.)administered to the rats 30 min preirradiation.The protective effects of the two AMI administration manners were compared in the aspects of hematopoietic system,lung edema,and histopathological examination,and the mechanisms were explored.Results:Compared to i.p.AMI,i.t.AMI remarkably alleviated radiation-induced lung injury and prevented consequent pneumonitis or pulmonary fibrosis.Specifically,i.t.AMI notably protected white blood cells and platelets,reduced the lung wet/dry weight ratio,and decreased collagen volume fractions compared to the model group(P<0.05),while i.p.AMI showed no significant difference with the model group(P>0.05).The high therapeutic efficiency of i.t.AMI was related to its high antioxidation and anti-inflammation effects with downregulation of pro-inflammatory cytokines,the enhanced superoxide dismutase activity,the low levels of malondialdehyde and total proteins.Conclusion:Inhaled AMI is a promising medicine for preventing radiation-induced lung injury,including pneumonitis and pulmonary fibrosis.