Consolidation with immunotherapy following concurrent chemoradiotherapy is current standard for treating unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, in clinical practice, many patients are ineligible for chemotherapy. Additionally, with the development of precision medicine, there is growing interest in chemotherapy-free regimen in order to enhance efficacy while reducing toxicity. In this article, current progress, challenges, and future directions of clinical research on the combination of chemotherapy-free radiotherapy and immunotherapy for LA-NSCLC were illustrated.

Consolidation with immunotherapy following concurrent chemoradiotherapy is current standard for treating unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, in clinical practice, many patients are ineligible for chemotherapy. Additionally, with the development of precision medicine, there is growing interest in chemotherapy-free regimen in order to enhance efficacy while reducing toxicity. In this article, current progress, challenges, and future directions of clinical research on the combination of chemotherapy-free radiotherapy and immunotherapy for LA-NSCLC were illustrated.

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.

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.

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.

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.

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.

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.

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* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Cranial Irradiation ; Humans ; Lung Neoplasms/pathology* ; Risk Factors

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.