Gut Microbiota Characteristics Are Associated With Severity of Acute Radiation-Induced Esophagitis.

Background: Acute radiation-induced esophagitis (ARIE) is one of the most debilitating complications in patients who receive thoracic radiotherapy, especially those with esophageal cancer (EC). There is little known about the impact of the characteristics of gut microbiota on the initiation and severity of ARIE. Materials and Methods: Gut microbiota samples of EC patients undergoing radiotherapy (n = 7) or concurrent chemoradiotherapy (n = 42) were collected at the start, middle, and end of the radiotherapy regimen. Assessment of patient-reported ARIE was also performed. Based on 16S rRNA gene sequencing, changes of the gut microbial community during the treatment regimen and correlations of the gut microbiota characteristics with the severity of ARIE were investigated. Results: There were significant associations of several properties of the gut microbiota with the severity of ARIE. The relative abundance of several genera in the phylum Proteobacteria increased significantly as mucositis severity increased. The predominant genera had characteristic changes during the treatment regimen, such as an increase of opportunistic pathogenic bacteria including Streptococcus. Patients with severe ARIE had significantly lower alpha diversity and a higher abundance of Fusobacterium before radiotherapy, but patients with mild ARIE were enriched in Klebsiella, Roseburia, Veillonella, Prevotella_9, Megasphaera, and Ruminococcus_2. A model combining these genera had the best performance in prediction of severe ARIE (area under the curve: 0.907). Conclusion: The characteristics of gut microbiota before radiotherapy were associated with subsequent ARIE severity. Microbiota-based strategies have potential use for the early prediction of subsequent ARIE and for the selection of interventions that may prevent severe ARIE.

Radiation-Induced Esophagitis in Non-Small-Cell Lung Cancer Patients: Voxel-Based Analysis and NTCP Modeling.

The aim of our study is to characterize the risk of radiation-induced esophagitis (RE) in a cohort of Non-Small-Cell Lung Cancer (NSCLC) patients treated with concurrent chemotherapy and photon/proton therapy. For each patient, the RE was graded according to the CTCAE v.3. The esophageal dose-volume histograms (DVHs) were extracted. Voxel-based analyses (VBAs) were performed to assess the spatial patterns of the dose differences between patients with and without RE of grade ≥ 2. Two hierarchical NTCP models were developed by multivariable stepwise logistic regression based on non-dosimetric factors and on the DVH metrics for the whole esophagus and its anatomical subsites identified by the VBA. In the 173 analyzed patients, 76 (44%) developed RE of grade ≥ 2 at a median follow-up time of 31 days. The VBA identified regions of significant association between dose and RE in a region encompassing the thoracic esophagus. We developed two NTCP models, including the RT modality and a dosimetric factor: V55Gy for the model related to the whole esophagus, and the mean dose for the model designed on the thoracic esophagus. The cross-validated performance showed good predictions for both models (ROC-AUC of 0.70 and 0.73, respectively). The only slight improvement provided by the analysis of the thoracic esophageal subsites might be due to the relevant sparing of cervical and lower thoracic esophagus in the analyzed cohort. Further studies on larger cohorts and a more heterogeneous set of dose distributions are needed to validate these preliminary findings and shed further light on the spatial patterns of RE development.

Establishment of acute radiation-induced esophagitis model of Wistar rats based on a small animal precision radiotherapy platform / 中华放射医学与防护杂志

Objective:To establish an in vivo model of acute radiation esophagitis in Wistar rats based on a small animal precision radiotherapy platform (SARRP). Methods:Thirty-six Wistar rats were randomly divided into control group, 40, 60 and 75 Gy groups. Based on MRI images, the esophageal target area of rats was outlined and the radiotherapy plan was formulated. The rats were respectively irradiated with 0, 8, 12 and 15 Gy per day for 5 consecutive days. The changes of body weight, food intake, esophageal pathology and magnetic resonance imaging were observed.Results:The body weight of rats in 75 Gy group decreased significantly on the 6th day after irradiation (IR) ( P<0.05). The esophageal tissue of rats in each IR group was thicker than that in control ( F = 14.20, P < 0.05). HE staining showed that the formation rate of radiation-induced esophagitis in 40 Gy and 60 Gy groups were 4/5 and 5/5, respectively, mainly mild. In 75 Gy group, the incidence of radiation-induced esophagitis approached to 5/5, of which 3/5 was severe at 9 d post-IR. The pathological injury scores [ M( Q1, Q3)] of rats in each group were 0, 1.0 (0.5, 2.5), 1.0 (1.0, 2.5) and 4.0 (1.5, 6.0) on the 9th day after IR. There was significant difference between the 75 Gy group and the control group ( H=12.69, P<0.05). After dynamic monitoring of neck MRI images, it was found that the esophageal signal of rats in each IR group increased and widened at 9 d post-irradiation. Conclusions:The animal model of acute radiation-induced esophagitis in rats was successfully established based on a small animal precision radiotherapy platform combined with MRI. 75 Gy was the best irradiation dose and the 9th day was the best observation time point.

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study.

BACKGROUND: Previous analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival. METHODS: All patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints. RESULTS: A total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001). CONCLUSION: The study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.

A novel nomogram containing acute radiation esophagitis predicting radiation pneumonitis in thoracic cancer receiving radiotherapy.

BACKGROUND: Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP. METHODS: Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0. RESULTS: A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP. CONCLUSIONS: As an early index that can reflect the tissue's radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future's clinical work.

Therapeutic effects of Co-Venenum Bufonis Oral Liquid on radiation-induced esophagitis in rats.

To investigate the effects of Co-Venenum Bufonis Oral Liquid (cVBOL) on radiation-induced esophagitis in rats. Irradiation (30 Gy) with X-RAD 225 x-ray was applied to induce esophagitis in 64 Wistar rats and treated by different methods. The body weight of rats either in RT group, cVBOL+RT, or EM+RT group was significantly decreased when compared with that in normal group (P<0.0001). After irradiation, histopathological studies, immunohistochemistry, and MRI scanning on esophagus were performed. Serum TNF-α,IL-6 and IL-10 were also determined by ELISA at 7, 14, 21 and 28 days after radiation treatment. The results demonstrated that radiation caused esophageal injury and thickening of esophageal tissue layers. The esophageal tissues after radiation treatment showed typical pathological changes of esophagitis. Radiation also caused esophagus edema. Treatment of cVBOL reduced the severity of histological esophageal lesion, decreased the expression of bFGF and TGF-ß1, and lowered serum levels of inflammatory cytokines including TNF-α, IL-6 and IL-10 over 28 days after radiation treatment. In conclusion, cVBOL treatment is effective to prevent radiation induced esophagitis and reduces radiation induced esophagitis may be mediated through its ant-inflammatory effects.

Lyman-Kutcher-Burman normal tissue complication probability modeling for radiation-induced esophagitis in non-small cell lung cancer patients receiving proton radiotherapy.

PURPOSE: To develop and test an Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model to predict radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving passive-scattering proton therapy (PSPT). MATERIAL AND METHODS: We retrospectively reviewed 328 NSCLC patients receiving PSPT at our institution. Esophagitis severity was graded by physicians according to the Common Toxicity Criteria for Adverse Events version 3.0, and the primary endpoint was grade ≥2 RE within 6 months from the first treatment. LKB model parameters (n, m, and TD50) were determined using maximum likelihood estimation. Overall performance of the model was quantified by Nagelkerke's R2 and the scaled Brier score. Discriminative ability was evaluated using the area under the receiver operating curve (AUC), and calibration was assessed with the Hosmer-Lemeshow goodness-of-fit test. Bootstrap internal validation was performed to assess the model uncertainty and generalizability. RESULTS: Grade 2-3 RE was observed in 136 (41.5%) patients, and no grade 4-5 RE was reported. The optimal LKB parameters were: n = 0.24, m = 0.51, and TD50 = 44.83 Gy (relative biological effectiveness). The optimism-corrected AUC was 0.783, and the Hosmer-Lemeshow test showed significant agreement between predicted and observed morbidity. Bootstrap validation verified that the model was robust to similar future populations. CONCLUSION: Our LKB NTCP model to predict grade ≥2 RE in NSCLC patients who received PSPT showed good predictive performance and robustness to similar future populations, and a smaller volume effect than the previously observed in photon-treated populations. External validation of the model is warranted.

Phase II Trial of Epigallocatechin-3-Gallate in Acute Radiation-Induced Esophagitis for Esophagus Cancer.

Acute radiation-induced esophagitis (ARIE) is among the most serious form of toxicities associated with definitive radiotherapy or chemoradiotherapy used for treatment of patients with esophageal cancer. Our preliminary phase I and II trials of lung cancer patients who received radiotherapy indicated epigallocatechin-3-gallate (EGCG) as a promising therapeutic option against ARIE. Therefore, we conducted a prospective phase II study to validate the efficacy and safety of EGCG in the treatment of ARIE. The patients who received chemoradiotherapy or definitive radiotherapy for treatment of esophageal cancer in the Shandong Cancer Hospital and Institute in China were enrolled for the present study. EGCG (440 µM) was administered with first onset of ARIE and then at weeks after final radiotherapy. The patients were monitored every week for dysphagia, Radiation Therapy Oncology Group (RTOG) score, and esophagitis-related pain. Moreover, tumor response and the effect on survival following the treatment were also evaluated. Comparison of the RTOG score in the first, second, third, fourth, fifth, and even sixth week after EGCG prescription and the first and second week after radiotherapy with baseline indicates a significant reduction. The tumor response rate was 86.3%. The overall survival rate in 1, 2, and 3 years was found to be 74.5%, 58%, and 40.5%. Oral administration of EGCG solution seems to be feasible for treating ARIE in patients with esophageal cancer who receive radiation therapy. EGCG might be an ARIE-reliever without compromising the efficacy of radiation therapy. A randomized study with a control group is needed for further evaluation.

A prospective, three-arm, randomized trial of EGCG for preventing radiation-induced esophagitis in lung cancer patients receiving radiotherapy.

BACKGROUND AND PURPOSE: This trial investigated whether epigallocatechin-3-gallate (EGCG), a radioprotector, could be effective in the prevention and treatment of acute radiation-induced esophagitis (ARIE). METHODS AND MATERIALS: This is a phase II study of EGCG combined with chemoradiation in unresectable stage III non-small-cell lung cancer or limited stage small cell lung cancer. Patients were randomized into a prophylactic EGCG group (arm A), a therapeutic EGCG group after the occurrence of esophagitis (arm B) or conventional therapy group (arm C). Esophagitis grades, pain and dysphagia scores were recorded weekly. Adjusted esophagitis index (AEI), pain index (API) and dysphagia index (ADI) were calculated to reflect changes in esophagitis grade, pain score and dysphagia score throughout treatment. RESULTS: A total of 83 patients were eligible for toxicity analysis (arm A vs arm B vs arm C: N = 28:27:28). There was no significant difference in the baseline characteristics among three arms of the patients. The difference in the maximum esophagitis grade among three groups was statistically significant (P = 0.004). The maximum ARIE for patients with EGCG was significantly lower than for those with conventional therapy. The mean AEI of arm A was lower than that of arm B, while the mean AEI of arm C was the highest (arm A vs arm B, P = 0.028; arm B vs arm C, P = 0.002). Furthermore, API and ADI were significantly lower in patients receiving EGCG than in conventionally treated patients. CONCLUSION: The application of EGCG could effectively alleviate acute radiation esophagitis in advanced lung cancer without obvious side effects. Prophylactic application of EGCG had a slight advantage over therapeutic use in treatment of acute esophagitis.

The effects of oral glutamine on clinical and survival outcomes of non-small cell lung cancer patients treated with chemoradiotherapy.

PURPOSE: To assess the efficacy of oral glutamine (Gln) supplementation on clinical and survival outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS/METHODS: Between 2010 and 2014, 122 stage III NSCLC patients were retrospectively analyzed. All patients received curative intent chemoradiotherapy (CRT). Prophylactic oral Gln powder was applied at a dose of 10 g tid. Effect of oral Gln supplementation in the prevention of severe (≥grade 2-3) acute radiation-induced esophagitis (ARE) and weight loss, and their relation with overall survival (OS) and disease-free survival (DFS) was measured. RESULTS: Median follow-up was 13.14 months (range; 1.97-55.36). Fifty-six (46%) patients had received oral Gln. Severe ARE was significantly lower in Gln-supplemented group (30% vs 70%; p = 0.002). Gln-free patients demonstrated a higher weight loss (p = 0.0001). In multivariate analysis hemoglobin (hb) level (<12 g/dL; p = 0.01) and nodal stage (N3; p = 0.01) were poor prognostic factors that affect OS; Weight loss (p = 0.06) and Gln-free (p = 0.05) reached nearly significant levels that poorly affect OS. Similarly, nodal stage (N3, p = 0.014) and Gln-free (p = 0.035) were poor prognostic factors that affect DFS. Weight loss (≥2%, p = 0.06) and hb level (<12 g/dL, p = 0.07) reached borderline significance that poorly affect DFS. Nodal stage (N3) was the only poor prognostic factor that affect OS and DFS in univariate analysis (p = 0.01, p = 0.009; respectively). CONCLUSION: Oral Gln supplementation significantly reduces grade 2-3 esophagitis and weight loss and also no negative impact on tumor control and survival outcomes in patients with LA-NSCLC.

Effect of compound Zhuye Shigao Granule ( ) on acute radiation-induced esophagitis in cancer patients: A randomized controlled trial.

OBJECTIVE: To observe the efficacy and safety of the Chinese medicine (CM) Compound Zhuye Shigao Granule (, CZSG) on acute radiation-induced esophagitis (ARIE) in cancer patients. METHODS: In a blinded, randomized, Kangfuxin Solution (, KFX)-controlled, single-centre clinical trial, 120 patients with lung, esophagus or mediastinal cancer were prospectively enrolled and assigned to the treatment group (60 cases) and control group (60 cases) by the random number table method. All patients received concurrent or sequential radiotherapy (2 Gy per day, 5 times per week, for 4 weeks) and were treated for 4 weeks since the radiation therapy. Patients in the treatment group were given 12 mg CZSG orally, thrice daily, while patients in the control group were given 10 mL KFX orally, thrice daily. The major indicators were observed, including the incidence and grade of esophagitis, time of occurrence and duration. Minor indicators were changes of CM symptoms, weight and Karnofsky Performance Status (KPS) Scale during 4 weeks from the beginning, recorded once a week. Blood routine examination and hepatorenal function were detected at the 2nd and 4th weeks. RESULTS: The incidence and grade of ARIE were significantly decreased in the treatment group compared with the control group (P<0.05). CZSG appeared to significantly delay the time of ARIE occurrence and reduce the duration compared with KFX (P<0.05). The scores of CM symptoms, KPS and weight were improved significantly in the treatment group compared with the control group (P<0.05). There were no blood routine and hepatorenal function abnormal or obvious side-effects in both groups. Hemoglobin was improved and neutrophil and interleukin 6 were decreased in both groups after 4-week treatment compared with before treatment (P<0.05), and there was no significant difference between the two groups (P>0.05). CONCLUSIONS: CZSG can decrease the incidence and grade of ARIE, delay the time of occurrence, reduce duration and alleviate the damage of ARIE. It is safe and effective in the prevention and cure of ARIE.

Effect of compound Zhuye Shigao Granule ( ) on acute radiation-induced esophagitis in cancer patients: A randomized controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the efficacy and safety of the Chinese medicine (CM) Compound Zhuye Shigao Granule (, CZSG) on acute radiation-induced esophagitis (ARIE) in cancer patients.</p><p><b>METHODS</b>In a blinded, randomized, Kangfuxin Solution (, KFX)-controlled, single-centre clinical trial, 120 patients with lung, esophagus or mediastinal cancer were prospectively enrolled and assigned to the treatment group (60 cases) and control group (60 cases) by the random number table method. All patients received concurrent or sequential radiotherapy (2 Gy per day, 5 times per week, for 4 weeks) and were treated for 4 weeks since the radiation therapy. Patients in the treatment group were given 12 mg CZSG orally, thrice daily, while patients in the control group were given 10 mL KFX orally, thrice daily. The major indicators were observed, including the incidence and grade of esophagitis, time of occurrence and duration. Minor indicators were changes of CM symptoms, weight and Karnofsky Performance Status (KPS) Scale during 4 weeks from the beginning, recorded once a week. Blood routine examination and hepatorenal function were detected at the 2nd and 4th weeks.</p><p><b>RESULTS</b>The incidence and grade of ARIE were significantly decreased in the treatment group compared with the control group (P<0.05). CZSG appeared to significantly delay the time of ARIE occurrence and reduce the duration compared with KFX (P<0.05). The scores of CM symptoms, KPS and weight were improved significantly in the treatment group compared with the control group (P<0.05). There were no blood routine and hepatorenal function abnormal or obvious side-effects in both groups. Hemoglobin was improved and neutrophil and interleukin 6 were decreased in both groups after 4-week treatment compared with before treatment (P<0.05), and there was no significant difference between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>CZSG can decrease the incidence and grade of ARIE, delay the time of occurrence, reduce duration and alleviate the damage of ARIE. It is safe and effective in the prevention and cure of ARIE.</p>

Impact of dose volume parameters and clinical factors on severe acute radiation-induced esophagitis for NSCLC patients treated with tomotherapy / 实用医学杂志

Objective To identify clinical and dosimetric parameters from dose-volume histogram(DVH) relating with incidence of severe acute radiation-induced esophagitis(RE)in patients with non-small cell lung can-cer(NSCLC)underwent tomotherapy with concurrent or sequential chemotherapy. Methods Records about clini-cal information and treatment plan parameters from DVH of 62 NSCLC patients treated with tomotherapy were pro-spectively collected to assess the correlation to severe acute RE from January 2012 to December 2016. Results There were 24.2％patients developed grade 3 RE,grade 4 or 5 in 0％patients. Multivariate analysis indicated that concurrent chemotherapy,esophagus median dose and esophagus V25 and V55 were the influencing factors of RE. The incidence of low frequencies RE was correlated with sequential chemotherapy ,esophagus median dose < 49 Gy,esophagus V25 < 64％ ,V55 < 33％ and V60 < 15％. Conclusions For NSCLC patients treated with tomo-therapy and chemotherapy,the occurrence of acute RE was similar to that of other techniques. It is recommended to balance such parameters for optimizing treatment planning.

Impact of dose volume parameters and clinical factors on severe acute radiation-induced esophagitis for NSCLC patients treated with tomotherapy / 实用医学杂志

Objective To identify clinical and dosimetric parameters from dose-volume histogram(DVH) relating with incidence of severe acute radiation-induced esophagitis(RE)in patients with non-small cell lung can-cer(NSCLC)underwent tomotherapy with concurrent or sequential chemotherapy. Methods Records about clini-cal information and treatment plan parameters from DVH of 62 NSCLC patients treated with tomotherapy were pro-spectively collected to assess the correlation to severe acute RE from January 2012 to December 2016. Results There were 24.2％patients developed grade 3 RE,grade 4 or 5 in 0％patients. Multivariate analysis indicated that concurrent chemotherapy,esophagus median dose and esophagus V25 and V55 were the influencing factors of RE. The incidence of low frequencies RE was correlated with sequential chemotherapy ,esophagus median dose < 49 Gy,esophagus V25 < 64％ ,V55 < 33％ and V60 < 15％. Conclusions For NSCLC patients treated with tomo-therapy and chemotherapy,the occurrence of acute RE was similar to that of other techniques. It is recommended to balance such parameters for optimizing treatment planning.

A prospective phase II trial of EGCG in treatment of acute radiation-induced esophagitis for stage III lung cancer.

BACKGROUND: Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients' quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. MATERIALS AND METHODS: We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440µmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. RESULTS: Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly (P=0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline (P=0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). CONCLUSION: This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment.

Radiation-induced esophagitis in local advanced non-small cell lung cancer after three-dimensional conformal radiotherapy / 中华放射医学与防护杂志

Objective To explore radiation-induced esophagitis and its related factors in the patients with local advanced non-small cell lung cancer ( NSCLC ) which were treated with three-dimensional conformal radiation therapy (3D-CRT). Methods From January 2001 to December 2008, 203 patients who suffered from stageⅢNSCLC were achieved, including 163 males and 40 females, with a median age of 63 years old, while 79 cases were in stageⅢa and 124 in stageⅢb . The equivalent median dose of tumor was 62 Gy( range of 50-78 Gy) . Among them, 74 cases were administered with radiotherapy alone, 45 with sequential radiotherapy and chemotherapy, 87 cases with concurrent radiochemotherapy. Radiation esophagitis was evaluated with RTOG standard. The dosimetric parameters was estimated from dose volume histogrma ( DVH ) . The clinical and dosimetric parameters of radiation esophagitis were evaluated by spearman correlatived univariate and Logistic multivariable analysis. Results After radiotherapy, out of 203 patients, 87 had acute radiation esophagitis(RE), 47 in grade 1, 37 in grade 2, and 3 in grade 3 RE. According to spearman correlatived analysis, the correlatived factors included ages, chemotherapy, GTV, PTV, the mean doses of PTV and lung, the max and mean dose of esophagus, V40 , V45 ,V50 ,V55 ,V60 , length of esophagus( total circumference) treated with 45 Gy ( LETT45 ) , and LETT50 ( r=-0. 162-0. 235,P0. 05). There were 21 factors, such as gender, age, smoking, clinical stage, site of tumor, chemotherapy, GTV, PTV, mean dose of PTV and lung, max and mean dose of esophagus, V40 -V60 of esophagus, LETT45-60 , incorporated into multivariable analysis, only chemotherapy and V45 of esophagus were independent predicted factors(Wald=4. 626, 9?882, P<0. 05). Conclusions In local advanced NSCLC after 3D-CRT, chemotherapy ( especially concurrent radiochemotherapy) could increase radiation-induced esophagitis. The parameter of DVH could also be used to predict radiation-induced esophagitis, V45 of esophagus may be the most valuable predictor.

Immunostimulatory effect of a composition isolated from white peony root oral liquid in the treatment of radiation-induced esophagitis.

The aim of this study was to explore the immune repairing effect of a composition isolated from white peony root oral liquid (cWPROL), a traditional Chinese herbal composition, in the treatment of experimental radiation-induced esophagitis in rats. A total of 128 Wistar rats were randomly divided into eight groups, irradiated with 43 Gy 60Co γ-rays to induce esophagitis and treated by different methods. Flow cytometry, hematological analysis and immune nephelometry were used to detect the absolute numbers and percentages of CD3+, CD4+ and CD8+ T lymphocytes, numbers and classification of leukocytes, and the levels of IgG and complement C3 in the peripheral blood of the rats at each experimental time point. Following irradiation, the total number of leukocytes, absolute numbers and percentages of CD3+, CD4+ and CD8+ T lymphocytes, and levels of IgG and complement C3 in the peripheral blood of the rats were decreased. Furthermore, the total numbers of leukocytes, absolute numbers and percentages of CD3+, CD4+ and CD8+ T lymphocytes, and levels of IgG and complement C3 in the peripheral blood were higher in the administered with cWPROL by intra-esophageal perfusion compared with those in the untreated irradiated groups, but lower in the groups treated with a mixture of lidocaine hydrochloride, dexamethasone sodium phosphate and gentamicin sulfate. This study suggested that cWPROL is able to repair the impaired cellular and humoral immunity of rats with radiation-induced esophagitis.

Therapeutic effect of compound of White Peony Root Oral Liquids on radiation-induced esophageal toxicity via the expression of EGF and TGF-ß1.

The predominant pathological processes of radiation-induced esophageal toxicity include inflammatory reactions in the early stage and the fibrotic process in the late stage. An increased expression of the epidermal growth factor (EGF) and transforming growth factor ß1 (TGF-ß1) is capable of reducing inflammatory reactions and TGF-ß1 is considered responsible for the initiation, development and persistence of fibrosis. In the present study, we investigated in vivo the therapeutic effect of the compound of white peony root oral liquids (cWPROL) on reducing the toxicity via modulating the expression levels of EGF and TGF-ß1. Adult male Wistar rats were treated and tissue sections were obtained. The tissue sections were stained using histological, Masson and immunohistochemical staining. The results revealed that cWPROL had a higher rate of repairing damaged structures compared with the control group. In addition, immunohistochemistry showed that although cWPROL and the mixture of lidocaine, dexamethasone and gentamycin (mLDG) induced levels of EGF and TGF-ß1 expression, there were differences between the two types of intervention. These results are significant for understanding that the mechanism of therapeutic effect of cWPROL varied to some extent from that of mLDG.

Dosimetry analysis on radiation-induced acute esophagitis after three-dimensional conformal radiotherapy for non-small cell lung cancer / 中华放射医学与防护杂志

Objective To analyze the related factors with radiation-induced esophagitis after threedimensional conformal radiotherapy for non-small cell lung cancer (NSCLC) ,in order to explore the predictors for optimizing the treatment planning of NSCLC.Methods From Aug 2000 to Dec 2004,104 NSCLC patients received radiotherapy and were eligible for this study,45 cases squamous cell carcinoma,20 cases adenocarcinoma,33 cases carrying with cancer cells by test and 6 case with no definitive pathologic feature.46 patients were treated with three dimensional conformal radiotherapy(3DCRT) ,the other 58 patients conventional radiotherapy (CRT) before later-course 3DCRT.All the patients received the prescribed dose between 60-78 Gy and the median dose 66 Gy.The correlation of the variables were evaluated by Spearman relationship analysis.The morbidity of radiation-induced esophagitis was analyzed by X~2 test.The multivariate effect on radiation-induced esophagitis was statistically processed by Logistic regression model.Results In 104 patients,the morbidity of radiation- induced esophagitis was 46.2% ,including 32 cases at grade 1,15 cases at grade 2,1 case at grade 3.Univariate analysis showed the maximal and mean dose of esophagus,the volume of esophagus irradiated,the values of V_(40) ,V_(45),V_(50) ,V_(55),V_(60) ,LETT_(45),LETT_(50) ,LETT_(55),LETT_(60) for the esophagus were correlated with radiation-induced esophagitis.Logistic regression model showed that the maximum dose received by the esophagus was the independent factor of ≥2 grade radiation-induced esophagitis.Conclusions The maxmal dose of esophagus received might be the important factor of radiation-induced esophagitis.

Acute esophageal toxicities in patients with stage Ⅲ non-small cell lung cancer treated by three-dimensional conformal radiotherapy combined with concurrent chemotherapy / 中华放射肿瘤学杂志

Objective To investigate the radiation-induced esophageal toxicities in Ⅲ stage non-small cell lung cancer (NSCLC) treated by three-dimensional conformal radiotherapy (3DCRT) combined with concurrent chemotherapy, and to find the relevant predictive factors. Methods From September 2006 to October 2007, 37 patients with stage Ⅲ NSCLC were treated by 3 DCRT (60 Gy in 30-34 fractions) con-currently with navelbine and cisplatin (NP). Chemotherapy was given in the first and fifth week. Univariate and multivariate analyses and receiver operating characteristic curves (ROC) were used to assess the associ-ation of radiation-induced esophagitis and correlated factors. Results Of all the patients, 91.89% (34/37) developed radiation-induced esophagitis, including grade 1 in 11 patients, grade 2 in 9, grade 3 in 14 and grade 4 in none. According to Spearman correlative analysis, the correlative factors included mean esophagus dose (MED), the LETT_(40)、LETT_(45)、LETT_(50)、LETT_(55)、LETT_60)of esophagus.All the 11 factors had good correlation with esophagitis in univariate analysis, while only V_55 was independ-ently associated with esophagitis in multivariate analysis. The ROC analysis indicated that the cut-off point of the curve was 30% with the area under ROC curve of 0.906, (P=0.000). Grade 2 or 3 radiation esophagi-tis occurred in all the patients with esophageal V_55 > 30%, while only in 36% ( 8/22 ) of those with V_55<30%. Conclusions 3DCRT combined with concurrent chemotherapy in patients with stage Ⅲ NSCLC could develop severe esophagitis. Dosimetric parameters (MED, LETT_(40),LETT_(45),LETT_(50),LETT_(55),LETT_(60),V_(40),V_(45),V_50,V_55,V_(60))are related with esophagitis,V_55 with V_55 > 30% being the most valuable predictor.