Influencing factors of pneumonitis in the period of thoracic radiotherapy combined with immunotherapy / 国际肿瘤学杂志

The combination of thoracic radiotherapy and immunotherapy is increasingly widely used in clinical practice, which not only brings survival benefits but also increases the incidence of pneumonitis. The occurrence of pneumonitis affects the subsequent immunotherapy and can be life-threatening in severe cases. The occurrence and severity of pneumonitis after combination therapy depends on a variety of factors, including patient's age, physical strength, pulmonary function, race, combination therapy mode, radiotherapy dose parameters, type of immune checkpoint inhibitor, history of checkpoint inhibitor-related pneumonitis or radiation pneumonitis, serum indexes and so on. At present, further research is needed to find out the influencing factors of the occurrence and severity of pneumonitis attributed to combined therapy, so as to better avoid, predict, identify and treat related pneumonitis in clinical practice.

Diagnostic and Therapeutic Strategy Updates of Rare Oncogenic Mutations in Chinese Society of Clinical Oncology Guidelines on Diagnosis and Treatment of Non-small Cell Lung Cancer (2023 Edition) / 肿瘤防治研究

The Chinese Society of Clinical Oncology (CSCO) issued the new version of the guidelines on diagnosis and treatment of NSCLC in April 2023.The new version updated the diagnostic and therapeutic strategy of rare oncogenic mutations, including ROS1 fusion, BRAF V600E mutation, NTRK fusion, MET exon 14 skipping mutation, RET fusion, and EGFR exon 20 insertion mutation, in NSCLC.This review will interpret the most important updates in the guidelines 2023 regarding the diagnosis as well as first-line and post-line therapies of these rare oncogenic mutations.

Progress of relationship between cytokines and treatment-related adverse events of immune checkpoint inhibitors in tumors and the clinical values / 肿瘤研究与临床

The use of immune checkpoint inhibitor (ICI) has significantly improved the efficacy of different types of malignancies, but the immune-related adverse event (irAE) callsed by ICI involves multiple organs and systems, affects the treatment, threatens the health of patients and even endangers their life. Therefore, it is necessary to select biomarkers to predict and monitor the occurrence of irAE, assist in the early diagnosis of high-risk patients, and guide individualized treatment. Recent studies have shown that some certain cytokines may be involved in the genesis and development of irAE. The article provides a review of studies related to cytokines and irAE to provide a reference for clinical prediction and monitoring of irAE.

Predictive value of tissue TSR for the efficacy of immunotherapy in non-small lung cancer / 国际肿瘤学杂志

Objective:To explore the value of tumor stroma ratio (TSR) in non-small lung cancer (NSCLC) tissue in predicting the efficacy of tumor immunotherapy.Methods:The clinical and histopathological data of patients with stage ⅢB-Ⅳ NSCLC treated with immune checkpoint inhibitors in the Renmin Hospital of Wuhan University from January 2017 to December 2020 were collected. Taking 50% as the TSR boundary value, the patients were divided into low TSR group (≤50%) and high TSR group (>50%) . The histopathological features, 4-cycle objective response rate (ORR) and disease control rate (DCR) , 6-cycle ORR and DCR, and progression-free survival (PFS) were compared between the two groups. Univariate and multivariate Cox regression models were used to analyze the prognostic factors related to PFS.Results:A total of 50 patients were included, including 27 with low TSR and 23 with high TSR. There were no significant differences between the two groups in age ( χ2=0.59, P=0.441) , gender ( P=0.578) , smoking history ( χ2=0.12, P=0.730) , histopathological type ( χ2=2.33, P=0.313) , TNM stage ( χ2=0.22, P=0.636) , 4-cycle ORR ( χ2=0.48, P=0.487) and DCR ( P=0.593) , 6-cycle ORR ( χ2=0.05, P=0.818) and DCR ( P=0.641) . The incidence of brain metastasis was higher in the high TSR group than that in the low TSR group [34.8% (8/23) vs. 7.4% (2/27) , χ2=4.23, P=0.040]. Kaplan-Meier survival analysis showed that the PFS in the low TSR group was significantly longer than that in the high TSR group (15.6 months vs. 10.2 months, χ2=13.84, P<0.001) . Univariate analysis showed that TSR value ( HR=0.29, 95% CI: 0.14-0.58, P<0.001) and brain metastasis ( HR=2.38, 95% CI: 1.12-5.05, P=0.024) were correlated with the worse prognosis of NSCLC patients. Multivariate Cox regression analysis showed that TSR value was an independent prognostic factor for NSCLC immunotherapy ( HR=0.32, 95% CI: 0.14-0.70, P=0.004) . Conclusion:TSR is an independent predictor of immunotherapy for NSCLC, but whether it can predict the short-term efficacy of immunotherapy for advanced NSCLC still needs further research.

Analysis on the incidence and risk factors of pneumonia in patients with lung cancer receiving thoracic radiotherapy and immunotherapy / 国际肿瘤学杂志

Objective:To analyze the incidence, risk factors and occurrence time of radiation pneumonia (RP) and immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer and lung metastatic cancer who received both thoracic radiotherapy and immunotherapy.Methods:The clinicopathological data of 137 patients with lung cancer and lung metastatic cancer receiving thoracic radiotherapy and at least one cycle of immunotherapy from January 2019 to January 2022 in Renmin Hospital of Wuhan University were retrospectively analyzed. The occurrence of RP and CIP was determined according to the clinical symptoms and thin-slice chest CT. The risk factors of symptomatic RP were evaluated by univariate and multivariate analyses of clinical data and treatment plan. The relationship between the occurrence time of symptomatic RP and the sequence of thoracic radiotherapy and immunotherapy was compared.Results:In the 137 patients with lung cancer and lung metastatic cancer who received both thoracic radiotherapy and immunotherapy, symptomatic RP was observed in 42 patients (30.7%) , including grade 2 RP in 33 patients (24.1%) , grade 3 RP in 6 patients (4.4%) , grade 4 RP in 1 patient (0.7%) , and grade 5 RP in 2 patients (1.5%) . The incidence of symptomatic RP was 40.0% (28/70) in patients who received thoracic radiation concurrent with immunotherapy and 20.9% (14/67) in non-synchronous patients, and the incidence of severe RP was 10.0% (7/70) and 3.0% (2/67) respectively. CIP was observed in 11 (8.0%) of 137 patients, including grade 2 CIP in 4 patients (2.9%) , grade 3 CIP in 6 patients (4.4%) , grade 5 CIP in 1 patient (0.7%) . There were 54.5% (6/11) of CIP patients with prior or concurrent symptomatic RP. Univariate analysis showed that smoking history ( χ2=9.85, P=0.002) , chronic obstructive pulmonary disease (COPD) history ( χ2=31.34, P<0.001) , thoracic radiotherapy concurrent with immunotherapy ( χ2=5.88, P=0.015) , total radiotherapy dose ( χ2=8.57, P=0.003) were associated with symptomatic RP. Multivariate logistic regression analysis showed that COPD history ( OR=9.96, 95% CI: 3.40-29.14, P<0.001) , thoracic radiotherapy concurrent with immunotherapy ( OR=2.84, 95% CI: 1.15-7.00, P=0.024) , and total radiotherapy dose ≥60 Gy ( OR=4.76, 95% CI: 1.68-13.50, P=0.003) were independent risk factors for symptomatic RP. RP occurred earlier in patients who received immunotherapy before thoracic radiotherapy [68.5 d (47.0 d, 101.8 d) ] than in patients who received immunotherapy after thoracic radiotherapy [117.5 d (79.0 d, 166.3 d) ], with a statistically significant difference ( Z=2.54, P=0.010) . Conclusion:The incidence of symptomatic RP is high in patients who receive both thoracic radiotherapy and immunotherapy. The history of COPD, thoracic radiotherapy concurrent with immunotherapy, and the total radiotherapy dose ≥60 Gy are independent influencing factors of symptomatic RP in patients with thoracic radiotherapy combined with immunotherapy. Symptomatic RP occurs earlier in patients who receive immunotherapy before thoracic radiotherapy than in patients who receive immunotherapy after thoracic radiotherapy.

CRISPR/Cas9 genome editing technology and its applications in tumor therapy / 国际肿瘤学杂志

Gene editing technology CRISPR/Cas9 and its derivative editing technologies including base editor and prime editor can precisely edit the target genome sequences, having been widely used in tumor therapy and achieved remarkable clinical results in tumor immunotherapy, human papilloma virus infection treatment and oncolytic virotherapy, providing a new means for tumor therapy.

Effect of tumor cells on tumor microenvironment / 国际肿瘤学杂志

Tumor cells and tumor microenvironment (TME) are closely related. It is known that many factors will change the TME, then affect tumor development, however the change of TME is also inseparable from tumor cells. More and more studies have confirmed that the regulation of TME is the key to anti-tumor therapy. Therefore, it is critical to understand the effect of tumor cells on TME.

Practice and exploration of general education curriculum of oncology in comprehensive university / 中华医学教育探索杂志

General education curriculum in Wuhan University has entered "3.0 era", in which general education curriculum of oncology has opened several cycles and been loved by the majority of students, meanwhile some problems have come up. In this article, the background of setting up general education curriculum of oncology in Wuhan University is reviewed. By sorting out teaching concepts and curriculum objectives, teaching content and organizational processes, teaching methods and evaluation methods and preliminary teaching effects, we emphatically discuss the role of clarifying teaching goals, optimizing curriculum designs, compiling basic teaching materials, improving teaching methods and reforming the evaluation system in promoting the setting and development of general education curriculum of oncology in comprehensive universities.

Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2019 version) / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Progression of Anti-oxygen Therapy in Radiation-Induced Lung Injury / 中国肺癌杂志

Radiation induced lung injury (RILI) is a serious complication in patients received thoracic radiotherapy. The main clinical symptom of RILI includes short of breath, low fever and cough, seriously affect the survival of patients. How to better prevent and treat RILI is an urgent problem. Target theory, cytokine theory, free radical theory, and vascular endothelial cell damage theory are the main mechanisms of RILI. Among them, reactive oxygen species (ROS) produced during radiotherapy can induce tissue damage throughout the course of RILI, and have a direct effect on both radiation pneumonitis and radiation-induced lung fibrosis. Anti-oxygen therapy including thiol compounds, antioxidant enzymes, and plant antioxidants have been applied in the prevention and treatment of RILI. This article reviews the research and application of antioxidant therapy in RILI.
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Construction of a prognostic nomogram model for patients with rhabdomyosarcoma / 中国肿瘤临床

Objective: To construct a nomogram for predicting the 1-year, 3-year, and 5-year survival of patients with rhabdomyosarco-ma. Methods: We retrieved data of patients diagnosed with rhabdomyosarcoma from The National Cancer Institute's Surveillance, Epi-demiology, and End Results (SEER) database between 1975 and 2016. After screening, 861 eligible patients were selected. The univari-ate Kaplan-Meier method and multivariate Cox model were used to determine independent prognostic factors, which were then uti-lized to construct a nomogram to predict 1-year, 3-year, and 5-year survival of patients with rhabdomyosarcoma. The resulting nomo-gram was internally verified using the consistency index (C-index) to measure its predictive accuracy. Results: Patient age, tumor histol-ogy, tumor grade, stage of the disease, surgery, radiotherapy, and chemotherapy were independent prognostic factors for patients with rhabdomyosarcoma (P<0.05). Based on these factors, the nomogram was successfully constructed. The C-index value for internal validation of the nomogram was 0.776, and the calibration curves of the model were consistent. Conclusions: The proposed nomo-gram is a reliable tool for accurate prognostic prediction in patients with rhabdomyosarcoma. It could be helpful for clinicians to indi-vidualize diagnosis, assess prognosis, and guide treatment plans for rhabdomyosarcoma patients.

Survival benefit of radiotherapy for metastatic nasopharyngeal carcinoma: a retrospective analysis based on SEER database / 中华放射肿瘤学杂志

Objective To analyze survival benefits of radiotherapy in patients with nasopharyngeal carcinoma (NPC) with distant metastases and analyze relevant prognostic factors.Methods Medical records of 329 patients newly diagnosed with metastatic NPC screened from the Surveillance,Epidemiology and End Results (SEER) database (199 of 329 patients received radiotherapy) between 2010 and 2015 were retrospectively analyzed.Overall survival (OS) and disease-specific survival (DSS) were calculated by Kaplan-Meier curve.The effect of different clinicopathological factors on the clinical prognosis of metastatic NPC patients was evaluated by logrank test and Cox regression analysis.Results The median follow-up time was 12 months.The 3-and 5-year OS rates were 27.4％ and 19.7％.The median OS was 17.9 months.Univariate analysis demonstrated that patients aged＜ 50 years,male,undifferentiated type,stage T3 or T4,positive regional lymph node,brain and liver metastases and 1-2 metastatic sites obtained OS and DSS benefits at 3 years after radiotherapy.Univariate and multivariate Cox analyses after propensity score matching showed that radiotherapy was an independent prognostic factor for metastatic NPC (OS,P=0.004;DSS,P=0.014).Besides,patients aged 60-69 years (OS,P=0.033;DSS,P=0.045),keratinizing squamous cell carcinoma (OS,P＜ 0.05;DSS,P＜ 0.05),stage T4 (OS,P =0.002;DSS,P =0.024),1-2 metastatic sites (OS,P =0.039;DSS,P =0.058),3-4 metastatic sites (OS,P =0.003;DSS,P =0.005) and no chemotherapy (OS,P=0.000;DSS,P=0.000) had poor OS and DSS,whereas sex,race and degree of differentiation exerted no effect on OS and DSS.Conclusions Radiotherapy can significantly improve the OS and DSS of patients with metastatic NPC.Prospective and randomized controlled studies are required to further explore the role of radiotherapy in the management of metastatic NPC.

Mechanism of microRNA-138 in inhibiting invasion and migration of breast cancer by regulating epithelial mesenchymal transformation / 中国医师进修杂志

Objective To investigate the molecule mechanism of microRNA (miR)-138 in inhibiting invasion and migration of breast cancer by regulating epithelial mesenchymal transformation (EMT). Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect expression of miR-138 after transfecting miR negative control simulacrum (miR-NC) and miR-138 simulacrum in human normal mammary epithelial cell (MCF-10A) and breast cancer cells (MCF-7 and MDA-MB-231) from July 2017 to June 2018. MTT method was used to detect the breast cancer cell activity. Cell scratch test and Transwell test were used to detect the breast cancer cell migration distance and invasion rate. RT-PCR was used to detect the expression of the EMT key molecules Vimentin, N-cadherin and E-cadherin after transfecting miR-138 simulacrum. Results The expression level of miR-138 in MCF-10A was significantly higher than that in MCF-7 and MDA-MB-231 (1.006 ± 0.009 vs. 0.324 ± 0.027 and 0.512 ± 0.068), and there was statistical difference (P<0.05);there was no statistical difference in the expression level of miR-138 between MCF-7 and MDA-MB-231 (P>0.05). The breast cancer cell viabilities of MCF-7 and MDA-MB-231 at third and fourth day after transfecting miR-138 simulacrum were significantly lower than those of transfecting miR-NC (MCF-7: 0.514 ± 0.052 vs. 0.593 ± 0.061 and 0.643 ± 0.074 vs. 0.784 ± 0.081;MDA-MB-231:0.552 ± 0.043 vs. 0.614 ± 0.063 and 0.673 ± 0.074 vs. 0.792 ± 0.077), and there were statistical differences (P<0.05). The breast cancer cell migration distances and invasion rates of MCF-7 and MDA-MB-231 after transfecting miR-138 simulacrum were significantly lower than those of transfecting miR-NC (MCF-7: 0.572 ± 0.051 vs. 1.003 ± 0.012 and 0.624 ± 0.043 vs. 1.002 ± 0.007, MDA-MB-231:0.472 ± 0.051 vs. 1.003 ± 0.095 and 0.573 ± 0.044 vs. 1.004 ± 0.091), and there were statistical differences (P<0.05). The expressions of Vimentin and N-cadherin mRNA in MCF-7 and MDA-MB-231 after transfecting miR-138 simulacrum were significantly lower than those of transfecting miR-NC, but the expression of E-cadherin mRNA was significantly increased, and there were statistical differences (P<0.05). Conclusions The expressions of miR-138 in both breast cancer cells decreased. Overexpression of miR-138 in breast cancer cell can inhibit proliferation, migration and invasion via regulating EMT.

New strategies for the treatment of clear cell renal cell carcinoma:target the metabolic reprogramming / 国际肿瘤学杂志

For the last decade,the incidence of kidney neoplasms has shown an obvious rising trend in the world. The most common histopathological type of kidney neoplasms is clear cell renal cell carcinoma (ccRCC),which has a poor prognosis. ccRCC is generally accompanied by reprogramming of glucose,fatty acid,glutamine,tryptophan and arginine metabolic networks and pathways. Reprogramming of metabolic net-works and pathways enables tumor cells to proliferate rapidly,survive in conditions of nutrient depletion and hy-poxia,and escape surveillance by epidemic systems. New strategies have been developed to the treatment of ccRCC by targeting key proteins or enzymes involved in metabolic reprogramming pathways.

Expression of DLL3 in small cell lung cancer and its application in targeted therapy / 国际肿瘤学杂志

Small cell lung cancer (SCLC) has a poor biological behavior,high probability of recurrence and metastasis,and limited treatment.The Notch signaling pathway is an evolutionarily conserved pathway that regulates the growth of many cell types through local cell-cell interactions.It controls the differentiation,proliferation and survival of cells.As a ligand for the Notch pathway,delta-like protein 3 (DLL3) is highly expressed on the membrane of SCLC cells.DLL3 plays an important role in cancer initiation and epithelial mesenchymal transition,invasion and metastasis of SCLC.Rovalpituzumab tesirine is a conjugate of directed against DLL3,which shows great potential for SCLC therapy.

Advances of bifunctional anti-PD-L1/TGF-β fusion protein M7824 / 国际肿瘤学杂志

With the development of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors,the second generation of combined immunosuppressive agents emerge as the times require.As a bifunctional anti-PD-L1/transforming growth factor-β (TGF-β) fusion protein,M7824 can antagonize PD-L1 pathway and trap TGF-β at the same time,which can effectively enhance the immune response and reduce the occurrence of immune escape and drug resistance.The drug has achieved remarkable results in many preclinical studies,however,the indications,safety and efficacy still need to be confirmed by large-scale clinical research data.

Mechanism of EGFR Over-expression and Mutations Leading to Biological Characteristics Changes of Human Lung Adenocarcinoma Cells through CXCR4/CXCL12 Signaling Pathway / 中国肺癌杂志

BACKGROUND@#The epidermal growth factor receptor (EFGR) mutation was closely related to the invasion and metastasis of lung adenocarcinoma and the biological axis of CXCR4/CXCL12 (chemokine receptor 4/chemokine ligand 12) played an important role in the organ-specific metastasis of the tumor. It was a question surrounding whether there is interaction between them in the process of lung adenocarcinoma metastasis. To investigate the potential molecular mechanisms of EGFR over-expression and EFGR-mutations effects on cell proliferation, migration and invasion, we constructed EGFR over-expression and three EFGR-mutant human lung adenocarcinoma H1299 cell sublines.@*METHODS@#EGFR over-expression and three EFGR-mutant (EGFR-E746-A750del, EGFR-T790M and EGFR-L858R) plasmid were designed and transfected H1299 cells with Lipofectamine 2000. H1299 cells transfected with empty vector were negative control (NC), and H1299 cells without transfection were set as blank control (BC). The effects of EGFR over-expression and mutations on the proliferation, migration and invasion of H1299 cells were detected by cell cloning assay, wound healing assay and Transwell assay. The mRNA and protein expression levels of MMP-2, MMP-9, CXCR4 and CXCL12 were detected by RT-PCR and Western blot.@*RESULTS@#Compared with negative control group and blank control group, EGFR over-expression and EGFR-E746-A750 deletion have significantly higher colony formation (28±2, 28.33±4.16; respectively) (P<0.05) and the cell migration and invasion ability were significantly increased (P<0.05). RT-PCR and Western blot assay showed that the mRNA and protein expression of MMP-2, MMP-9, CXCR4 and CXCL12 in EGFR over-expression and EGFR-E746-A750 deletion group were remarkably higher than that in negative control and blank control group (P<0.05).@*CONCLUSIONS@#EGFR over-expression and 19 exon deletion can promote the expression of MMP-2 and MMP-9 by up-regulating CXCR4/CXCL12 signaling pathway, leading to the change of tumor biological characteristics such as higher proliferation, migration and invasion ability.

Progress of circulating tumor cells in clinical application / 国际肿瘤学杂志

Circulating tumor cells (CTCs)are cancerous cells that shed from the primary tumor or metastases into the bloodstream. The currently clinical applicability of CTCs approved by the US Food and Drug Administration (FDA)is that CTCs can be prognostic biomarker for patients with metastatic breast cancer, prostate cancer and colorectal cancer. CTCs also have great potential in the prognosis assessment of other meta-static or localized tumors,as well as early screening of tumors,analysis of molecular profiling,guiding treat-ment decisions,and monitoring of treatment response. Currently,various studies are being carried out to further explore the clinical application of CTCs,and provide new strategies and new prospects for individualized and precise treatment of cancer patients.

Roles of platelets in tumor progression / 国际肿瘤学杂志

Platelets play important roles in tumor progression.Increased platelets count is associated with poor overall survival and prognosis.Tumor cell-induced platelet activation and platelet-induced tumor growth form a malignant amplification loop which plays a crucial role in tumor cell proliferation,metastasis and angiogenesis.Antiplatelet therapy may break the platelet-tumor amplification loop and play a key role in reducing tumor metastasis.