1.Efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma
Yaowen ZHANG ; Yunsong LIU ; Zhouguang HUI ; Xinyu CHENG ; Ying GUO ; Runchuan REN ; Linzhi JIN ; Heming ZHANG ; Chenyu WANG
Chinese Journal of Radiation Oncology 2024;33(9):810-817
Objective:To evaluate the efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC).Methods:A retrospective analysis was conducted on the data of 75 patients with R/M ESCC treated with sintilimab at Anyang Tumor Hospital from January 2020 to October 2021. The patients were divided into the radiotherapy (RT) group ( n=37) and non-radiotherapy (NRT) group ( n=38) based on whether they received radiotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse effects were compared between two groups. Count data were expressed as composition ratios and analyzed using Chi-square test or Fisher's exact test. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:There was no statistically significant difference in ORR and DCR between the RT and NRT groups (70% vs. 61%, P=0.375; 95% vs. 89%, P=0.414). However, the complete response (CR) rate in the RT group was higher compared to that in the NRT group (19% vs. 3%, P=0.022). The median follow-up duration was 25.4 months. There was no statistically significant difference in the median PFS and OS between the RT and NRT groups (13.8 months vs. 9.9 months, P=0.221; 20.2 months vs. 18.9 months, P=0.214). Subgroup analysis demonstrated that among patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes, there was no statistically significant difference in the median PFS between the RT and NRT groups (15.1 months vs. 8.4 months, P=0.115), but the median OS in the RT group was better than that in the NRT group (not reached vs. 12.3 months, P=0.036). Compared to the NRT group, besides an increase in grade 1-2 pneumonitis (41% vs. 18%, P=0.035), no significant increase in treatment-related toxicity was observed in the RT group. Conclusion:Immunotherapy combined with radiotherapy is safe in patients with R/M ESCC, and shows survival benefit in patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes.
2.Identification of key genes in response to radiotherapy and chemotherapy in esophageal squamous cell carcinoma based on multiple datasets
Yaowen ZHANG ; Yunsong LIU ; Zhouguang HUI ; Shasha CAO ; Chenyu WANG ; Xinyu CHENG ; Linzhi JIN ; Runchuan REN
Chinese Journal of Radiation Oncology 2024;33(10):950-957
Objective:To explore the biomarkers of radiochemotherapy sensitivity and potential mechanisms in esophageal squamous cell carcinoma (ESCC), and validate the screened biomarkers at human tissue, animal and cellular levels.Methods:Based on bioinformatics system, clinical and transcriptome data of ESCC were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. HUB genes related to chemoradiotherapy sensitivity were identified by weighted correlation network analysis (WGCNA) and cytoscape software and survival differences were analyzed. CellMiner database was used to predict and screen drugs with strong correlation with HUB genes. The expression levels of HUB genes in clinical tissues was detected by real-time reverse transcription PCR (qRT-PCR). Then, oe-AKR1C1 mouse model, cisplatin-resistant cells and radiation-resistant cells were constructed, and the effects of HUB genes on tumor size and mass, and cell proliferation ability were analyzed.Results:A total of 5 HUB genes were identified, among which NAD(P)H quinone dehydrogenase 1 (NQO1), AKR1C1 and NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) were significantly correlated with ESCC survival (all P<0.05). Dacarbazine, alectinib and obatoclax were the anti-tumor drugs predicted to have a strong correlation with HUB genes in this study. Human tissue test results showed that the expression levels of NQO1, AKR1C1 and NDUFS2 were up-regulated in patients with chemoradiotherapy resistance, and AKR1C1 and NDUFS2 had statistical significance (both P<0.05). The results of mouse tumor bearing experiment showed that the tumor volume and mass of oe-AKR1C1 mice after radiotherapy and chemotherapy were significantly higher than those in the control group (both P<0.05). The cell experiment results showed that the expression levels of AKR1C1 and NDUFS2 in radiation-resistant cells and cisplatin-resistant cells were significantly higher than those in control cells ( P<0.05), while there was no statistically significant difference in the relative expression level of NQO1. Conclusion:NQO1, AKR1C1 and NDUFS2 are HUB genes significantly related to the survival of ESCC, which can be used as important therapeutic tumor targets for ESCC.
3.Image-based artificial intelligence predicts the efficacy of neoadjuvant chemoradiotherapy for esophageal cancer
Yunsong LIU ; Zeliang MA ; Yu MEN ; Zhouguang HUI
Chinese Journal of Radiation Oncology 2024;33(11):1070-1076
Neoadjuvant chemoradiotherapy combined with surgery is the standard treatment for patients with locally advanced esophageal cancer. However, there is significant variability in how patients respond to neoadjuvant chemoradiotherapy. The value of existing conventional diagnostic methods in predicting the effectiveness of neoadjuvant chemoradiotherapy is limited. Image-based artificial intelligence (AI), particularly radiomics and deep learning technologies, have shown great potential in predicting the efficacy of neoadjuvant chemoradiotherapy by automatically quantifying and analyzing a vast amount of information in medical images. This review summarizes AI research based on CT, positron emission computed tomography (PET-CT), and other imaging modalities, highlighting the current limitations and future directions of the research.
4.Research progress in minimal residual disease in locally advanced non-small cell lung cancer
Wanting ZHANG ; Xu YANG ; Zhouguang HUI
Chinese Journal of Radiation Oncology 2023;32(10):939-944
For locally advanced unresectable non-small cell lung cancer (NSCLC), the standard regimen is concurrent chemoradiotherapy (CCRT) followed by consolidation immunotherapy. Nevertheless, the majority of patients will experience recurrence. Traditional imaging examination has its limitations of passively identifying recurrence, unable to forecast the risk in advance. Minimal residual disease (MRD) based on circulating tumor DNA (ctDNA) has become a novel tumor biomarker. Existing studies have demonstrated that the levels of ctDNA initially increase and then decrease during CCRT for NSCLC. Monitoring ctDNA-MRD can not only robustly predict recurrence, but also guide the consolidation immunotherapy, evaluate the efficacy and predict clinical prognosis. Furthermore, ctDNA-MRD can be a reliable biomarker to explore other effective treatments. However, few ctDNA-MRD clinical studies related to guiding consolidation therapy have been performed, with small sample size and low-level evidence. The value of ctDNA-MRD still needs to be confirmed by prospective randomized studies.
5.Postoperative radiotherapy for non-small cell lung cancer treated with neoadjuvant chemotherapy followed by surgery
Chinese Journal of Radiation Oncology 2022;31(1):90-96
Neoadjuvant chemotherapy followed by surgery (NCS) is a common therapy pattern of non-small cell lung cancer (NSCLC). However, patients treated with NCS still suffer from relatively high locoregional recurrence. Postoperative radiotherapy (PORT) plays an important role in improving locoregional control, whereas its effect on survival remains controversial. Some studies propose that PORT yields no survival benefits for stage Ⅱ-Ⅲ A(N 2) patients treated with NCS, whereas other researches indicate that PORT can bring survival benefits for high-risk patients. The indications of PORT include R 1/R 2 resection and ypN 2. PORT is recommended with three-dimensional conformal therapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) within the dose range of 50-54 Gy (R 0 resection). The target volume is inconclusive and the irradiation range of mediastinum involving with the metastatic lymph node regions is recommended in many studies. The adverse effects of PORT are acceptable in most studies.Nevertheless, the evidence level of relevant studies is relatively low. These results remain to be clarified by prospective randomized clinical trials.
6.Comparison of setup errors in supraclavicular regions of lung and esophageal cancer treated with radiotherapy
Bao WAN ; Xu YANG ; Fukui HUAN ; Yanxin ZHANG ; Xin FENG ; Yu ZHAO ; Yingwei WU ; Songsong GENG ; Kuo MEN ; Zhouguang HUI
Chinese Journal of Radiation Oncology 2022;31(3):272-276
Objective:To compare the setup errors in the supraclavicular regions of two different postures (arms placed on each side of the body, namely the body side group; arms crossed and elbows placed above forehead, namely the uplifted group) using the chest and abdomen flat frame fixation device in lung and esophageal cancer.Methods:Clinical data of patients with stage Ⅰ to Ⅳ lung or esophageal cancer who received three-dimensional radiotherapy with chest and abdomen flat frame fixation device in our institution from November 2020 to April 2021 were retrospectively analyzed. The setup errors of two postures were compared.Results:A total of 56 patients were included, including 31 patients (55%) in the body side group and 25 patients (45%) in the uplifted group. A total of 424 CBCTs were performed in the whole group. The overall setup errors in the X, Y and Z directions were similar in both groups ( P>0.05). The setup errors of sternoclavicular joint in the X and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.163±0.120) cm vs. (0.209 ±0.152) cm, P=0.033; 0.715°±0.628° vs. 0.910°±0.753°, P=0.011]. The setup errors of acromioclavicular joint in the Y, Z and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.233±0.135) cm vs. (0.284±0.193) cm, P=0.033; (0.202±0.140) cm vs. (0.252±0.173) cm, P=0.005; 0.671°±0.639° vs. 0.885°±0.822°, P=0.023]. The margins of target volume for setup errors were smaller in the X (0.45 cm vs. 0.54 cm) and Y (0.54 cm vs. 0.65 cm) directions of the sternoclavicular joint, as well as in the Y (0.59 cm vs. 0.78 cm) and Z directions (0.53 cm vs. 0.72 cm) of the acromioclavicular joint in the body side group. Conclusions:For lung and esophageal cancer patients requiring supraclavicular irradiation, the body side group yields smaller setup errors and corresponding margins of target volume than the uplifted group. In clinical practice, it is necessary to take comprehensive consideration of the accuracy of radiotherapy and additional radiation of the limbs to select appropriate posture.
7.Simultaneous integrated boost vs. routine IMRT in limited-stage small-cell lung cancer: an open-label, non-inferiority, randomized, phase 3 trial
Tianyou ZHAN ; Tao ZHANG ; Zongmei ZHOU ; Wenbin YAN ; Yirui ZHAI ; Lei DENG ; Wenqing WANG ; Nan BI ; Jianyang WANG ; Xin WANG ; Wenyang LIU ; Zefen XIAO ; Qinfu FENG ; Dongfu CHEN ; Jima LYU ; Zhouguang HUI ; Jun LIANG ; Lyuhua WANG
Chinese Journal of Radiation Oncology 2022;31(5):425-430
Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.
8.Research Progress on Risk Factors of Brain Metastasis in Non-small Cell Lung Cancer.
Shuang SUN ; Yu MEN ; Zhouguang HUI
Chinese Journal of Lung Cancer 2022;25(3):193-200
Brain metastasis of non-small cell lung cancer (NSCLC) is a common treatment failure mode, and the median survival time of NSCLC patients with brain metastasis is only 1 mon-2 mon. Prophylactic cranial irradiation (PCI) can delay the occurrence of brain metastasis, but the survival benefits of NSCLC patients are still controversial. It is particularly important to identify the patients who are most likely to benefit from PCI. This article reviews the high risk factors of brain metastasis in NSCLC.
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Brain Neoplasms/secondary*
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Carcinoma, Non-Small-Cell Lung/pathology*
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Cranial Irradiation
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Humans
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Lung Neoplasms/pathology*
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Risk Factors
9.Active surveillance and response evaluation strategy after neoadjuvant therapy for esophageal cancer
Yunsong LIU ; Yu MEN ; Zhouguang HUI
Chinese Journal of Radiation Oncology 2022;31(9):848-853
A considerable proportion of esophageal carcinoma patients could achieve pathological complete response (pCR) after neoadjuvant therapy, for whom accurate response evaluation and active surveillance rather than surgery-aiming to avoid the complications, mortality and reduced quality of life after surgery-has become a research hotspot. To detect residual disease and predict pCR accurately by appropriate method(s) is the key of active surveillance strategy. In this article, we elaborated the active surveillance strategy of esophageal cancer and characteristics of different evaluation methods in terms of radiology, pathology and combined detection.
10.Establishment and identification of C57BL/6 mouse model with radiation-induced pulmonary fibrosis
Meng YUAN ; Yu MEN ; Xin SUN ; Maoyuan ZHAO ; Dan BAO ; Xu YANG ; Shuang SUN ; Yongxing BAO ; Zeliang MA ; Yunsong LIU ; Zhouguang HUI
Chinese Journal of Radiation Oncology 2022;31(10):928-932
Objective:To establish the mouse model with radiation-induced pulmonary fibrosis, and to identify and analyze it from the aspects of function, imaging and pathology.Methods:Thirty C57BL/6 mice were randomly divided into the control group, 16 Gy irradiation group and 20Gy irradiation group. The mice in the irradiation groups received a single 16 Gy or 20 Gy chest X-ray irradiation, and underwent functional examination, imaging examination and pathological examination at 3 and 6 months after irradiation.Results:At 6 months after irradiation, hair on the chest and back of the mice turned white and fell off, and the airway resistance was increased significantly. CT images showed extensive patch shadows and consolidation in the lung. Three dimensional reconstruction suggested that the lung of mice was distorted and deformed, and the volume was decreased significantly. Pathological examination confirmed that there was extensive pulmonary fibrosis.Conclusions:Significant pulmonary fibrosis occurs after 6 months of chest irradiation in mice. The animal model of radiation-induced pulmonary fibrosis in C57BL/6 mice was successfully established.

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