
Unresectable stage III non-small cell lung cancer (NSCLC) exhibits substantial heterogeneity and complexity. The landmark LAURA and POLESTAR studies have established a standard therapeutic model involving targeted consolidation therapy with osimertinib or aumolertinib after definitive chemoradiotherapy for NSCLC patients harboring EGFR-sensitive mutations. However, treatment strategies for patients with other driver gene mutations (e.g., ALK fusions, ROS1 rearrangement) still lack robust support from high-level evidence-based medical study. To enhance the standardization of diagnosis and treatment for unresectable stage III driver-positive NSCLC patients, the Radiotherapy Committee of the Chinese Society of Clinical Oncology convened an expert working group. This group identified common clinical practice issues and conducted an in-depth, problem-oriented analysis of domestic and international guidelines alongside evidence-based medical data. Through multiple rounds of comprehensive discussion and expert voting, this consensus was jointly developed. It provides evidence-based recommendations addressing frequently encountered clinical questions regarding unresectable stage III driver-positive NSCLC, aiming to serve as a key reference for clinical practice.
Objective: To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022. Methods: The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years. Results: From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95%CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95%CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion: The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.
Purpose/Objective(s) The abscopal effect—the regression of malignancies outside the irradiation zone—can be increased by combining radiotherapy (RT) with immunotherapy. In this study, we aimed to investigate whether the gut microbiota affected the abscopal effect following immunoradiotherapy (iRT) in rectal cancer. Materials/Methods Bilateral MC38 subcutaneous tumors (primary and abscopal tumor) were established in C57/B6 mice with or without oral antibiotic treatment (preadministration of vancomycin, streptomycin, and ampicillin 14 days before therapy). Mice with or without antibiotic therapy were then randomized into eight groups to receive one of four treatments: (1) RT to the primary tumor + anti-PD-1 therapy (iRT), (2) RT to the primary tumor (RT), (3) anti-PD-1 therapy (anti-PD-1), and (4) no treatment. Flow cytometry was used to determine the composition and function of immune cells in the primary and abscopal tumors as well as in the spleen. 16S rRNA sequencing was used to assess the gut microbiome alteration following antibiotic intervention. Multiple bioinformatics were then explored to investigate the impact of specific flora that related to abscopal antitumor effect. Results We found that radiation on primary tumors exhibited cytotoxic effect in nonirradiated (abscopal) tumors (p=0.0057, RT vs. untreated group; p=0.0037, iRT vs. anti-PD-1 group). In contrast, abscopal tumors were resistant to the anticancer effects of RT when antibiotics were given (p=0.5374, RT + antibiotics vs. untreated group + antibiotics; p=0.42, iRT + antibiotics vs. anti-PD-1 + antibiotics group). Comparing the RT+antibiotics group to the RT group, we discovered that the number of CD8+CD44+ T cells decreased significantly in both abscopal tumors (p<0.001) and spleens (p=0.0061). In anti-PD-1-treated groups, antibiotics significantly reduced the number of CD8+GranzymeB+ T cells in primary tumors (p=0.0061) and CD4+CD25+ T cells in spleens (p<0.001). In iRT-treated groups, the antibiotic reduced the fraction of CD4+INF-γ+ cells in abscopal tumors (p=0.0134), and increased the number of CD4+PD-1+ T cells in spleens (p<0.001). Moreover, we found that both α- and β-diversity decreased significantly in the gut microbiota after antibiotic treatment (p=0.0079 and p<0.001, respectively). The abundance of g_Alistipes, g_Lactobacillus, g_Lachnospiraceae and g__Lactobacillus fell dramatically in the presence of antibiotics. In addition, functional analyses of Picrust2 and KEGG revealed that antibiotic therapy had the most profound impact on the D-Alanine metabolism pathway (p<0.001). Conclusion We found that the alteration of the gut microbiome by antibiotics significantly affects the local and systemic antitumoral effect of iRT, our results may provide new insight on how gut modification converts the local anticancer effects of RT into a systemic response that targets metastatic tumors.
IntroductionWe aim to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) in breast cancer patients by constructing a Nomogram based on radiomics models, clinicopathological features, and ultrasound features.MethodsUltrasound images of 464 breast cancer patients undergoing NAC were retrospectively analyzed. The patients were further divided into the training cohort and the validation cohort. The radiomics signatures (RS) before NAC treatment (RS1), after 2 cycles of NAC (RS2), and the different signatures between RS2 and RS1 (Delta-RS/RS1) were obtained. LASSO regression and random forest analysis were used for feature screening and model development, respectively. The independent predictors of pCR were screened from clinicopathological features, ultrasound features, and radiomics models by using univariate and multivariate analysis. The Nomogram model was constructed based on the optimal radiomics model and clinicopathological and ultrasound features. The predictive performance was evaluated with the receiver operating characteristic (ROC) curve.ResultsWe found that RS2 had better predictive performance for pCR. In the validation cohort, the area under the ROC curve was 0.817 (95%CI: 0.734-0.900), which was higher than RS1 and Delta-RS/RS1. The Nomogram based on clinicopathological features, ultrasound features, and RS2 could accurately predict the pCR value, and had the area under the ROC curve of 0.897 (95%CI: 0.866-0.929) in the validation cohort. The decision curve analysis showed that the Nomogram model had certain clinical practical value.DiscussionThe Nomogram based on radiomics signatures after two cycles of NAC, and clinicopathological and ultrasound features have good performance in predicting the NAC efficacy of breast cancer.
光动力治疗具有毒副作用小、适用瘤种广和可反复治疗等优势,在临床上已用于食管癌、中央型肺癌、脑胶质瘤等的根治、辅助或姑息治疗.光动力治疗除了通过产生活性氧,直接杀伤肿瘤细胞外,还可产生肿瘤原位疫苗,引起肿瘤的免疫原性细胞死亡,促进树突状细胞的成熟和细胞毒性T细胞的浸润,具有一定免疫治疗的属性.但光动力治疗存在氧气依赖和光敏剂的肿瘤选择性不足等缺陷,且单独光动力治疗诱导的弱免疫不足以触发全身抗肿瘤免疫反应.本文重点介绍光动力免疫治疗的机制,并针对上述不足阐述提高光动力免疫治疗疗效的策略.
Objective To explore the safety and feasibility of Billroth Ⅰ reconstruction by double staplers after totally lapa-roscopic distal gastrectomy.Methods We reviewed the clinical data of 105 patients with gastric cancer who underwent Billroth Ⅰ reconstruction by double staplers after totally laparoscopic distal gastrectomy(the double staplers group)in the Affiliated Hospital of Nantong University from January 2014 to December 2020.Meanwhile,66 patients with gastric cancer who were performed laparoscopy-assisted Billroth Ⅰ reconstruction during the same period by the same surgical team were divided a control(the laparoscopy-assisted group).Intraoperative and postoperative outcomes,postoperative complications were observed.T-test analysis was used to compare intraoperative and postoperative outcomes between the two groups,such as the mean time of reconstruction,proximal resection margin,intraoperative blood loss,out-of-bed mo-bilization,first flatus after the operation,first liquid after the operation,postoperative hospital stay,the length of the in-cision.Chi-square analysis was performed on postoperative complications between the two groups.Results The mean time of reconstruction in the double staplers group was(21.60±4.15)min,which was significantly less than that in the laparos-copy-assisted group[(24.84±3.56)min],t=2.963,P=0.005.The length of the incision in the double staplers group was(3.39±0.68)cm,which was significantly shorter than that in the laparoscopy-assisted group[(6.15±1.27)cm](t=8.553,P<0.001).In the double stapler group and the laparoscopy-assisted group,there was no significant differ-ence for the following factors(P>0.05),including proximal resection margin[(5.63±1.53)cm vs(5.01±1.21)cm],intraoperative blood loss[(53.23±13.53)ml vs(51.71±9.14)ml],out-of-bed mobilization[(1.50±0.51)days vs(1.87±0.69)days],first flatus after the operation[(3.02±0.83)days vs(3.66±1.31)days],first liquid after the op-eration[(3.80±0.99)days vs(4.36±1.03)days],postoperative hospital stay[(7.20±1.62)days vs(7.90±1.06)days],P>0.05.Two complications in the double stapler group were observed,including a case of anastomotic stenosis and a case of anastomotic bleeding.There were three complications in the laparoscopy-assisted group,including a case of anastomotic stenosis,a case of wound fat liquefaction,and a case of wound pain(VAS=4).There was no significant difference in the frequency of postoperative complications between the two groups(P>0.05).Conclusion It is safe and feasible for Billroth Ⅰ reconstruction by double staplers after the totally laparoscopic distal gastrectomy.
Objective To review the clinical applications and research progress of fibroblast growth factor receptor inhibi-tors(FGFRIs),including drug resistance mechanisms and potential solutions,as well as combined immunotherapy re-search progress.Methods With"FGFR,drug resistance,immune microenvironment"as the keywords,the relevant lit-erature of PubMed and CNKI were retrieved from December 2000 to December 2022.Inclusion criteria were as follows:(1)relevant clinical trials;(2)the mechanism of FGFR in tumor occurrence,progression and drug resistance;(3)studies on the relationship between FGFR and the immune microenvironment.Exclusion criteria were:(1)articles with similar or repeated content;(2)articles with ambiguous and controversial research mechanisms.A total of 50 literature was included(2 in Chinese and 48 in English).Results FGFRIs have been incorporated into the treatment guidelines for cholangiocar-cinoma and urothelial malignant tumors,and multiple ongoing clinical trials are exploring their use in the treatment of sol-id malignant tumors.FGFRIs resistance may be related to gatekeeper gene mutations,lysosomal sequestration mecha-nisms,and abnormal activation of signaling pathways.Current research indicates that FGFRIs may improve the inhibitory immune microenvironment and synergistically enhance the effectiveness of immunotherapy.Conclusion With the ongoing development of clinical trials and further research into the resistance mechanisms of FGFRIs and their combination with immunotherapy,FGFRIs are poised to have a greater role in the clinical treatment of malignant tumors.
Objective To explore the relationship with demoralization syndrome and social support or resourcefulness in cancer patients,and to analyze the mediating effect of resourcefulness level on demoralization syndrome and social sup-port.Methods This study was a cross-sectional survey.A total of 500 cancer inpatients who were treated in Shandong Cancer Hospital from September 1,2022 to March 31,2023 were investigated and scored with general data questionnaire,Chinese version of failure scale Ⅱ,intelligence scale and social support scale.Pearson correlation was used to analyze the correlation among social support level,resourcefulness level and demoralization syndrome level.AMOS 25.0 was used to analyze the intermediary effect of resourcefulness level on demoralization syndrome and social support level,and a struc-tural equation model was constructed.In this study,a total of 500 questionnaires were sent out,and 489 valid question-naires were recovered,with an effective rate of 97.80%(489/500).Results The median total score of demoralization syndrome,resourcefulness and social support of cancer patients were 11.0(7.0,15.0),47.94±2.57 and 29.06±12.89,respectively.The total score of demoralization syndrome was negatively correlated with the total scores of mental re-sourcefulness(r=-0.576,P=0.003)and social support(r=-0.689,P=0.005),while the total score of social sup-port was positively correlated with the total score of resourcefulness(r=0.492,P=0.009).Resourcefulness played a partial mediating effect between social support and demoralization syndrome,accounting for 36.33%of the total effect.Conclusions Social support can directly predict the demoralization syndrome of cancer patients,and resourcefulness plays an intermediary role on social support and demoralization syndrome of cancer patients.Taking effective measures to improve the level of social support and resourcefulness of cancer patients is one of the effective ways to reduce the demoralization syndrome of cancer patients.
Objective To explore the current research status and advance of contrast-enhanced ultrasound in tracing sentinal lymph nodes(SLN)and providing a reference for the clinical application.Methods In this literature review,relevant study from January 1st,2001 to April 1st,2023 were retrieved in Chinese National Knowledge Infrastructure databases and PubMed with the key words"breast neoplasms,sentinel lymph node,internal mammary lymph nodes,contrast-en-hanced ultrasound and lymph node biopsy".The inclusion criteria were as follows:(1)Axillary SLN tracing of breast cancer;(2)Axillary lymph node puncture biopsy;(3)Tracing of lymph nodes in the inner breast region.Exclusion crite-ria were:Literature with statistical mistakes and similar or repetitive content.Totally 7 Chinese literatures and 42 English literatures were collected.Results Contrast-enhanced ultrasound can reveal the network structure of lymphatic drainage and SLN,the first lymph node traced conforms to the definition of SLN,proving that this is SLN in the true sense.Cur-rently,diagnosing SLN properties solely based on image classification has strong subjectivity,while combining biopsy results can improve diagnostic accuracy and contribute to preoperative diagnosis of SLN properties.Adopting appropriate preoperative methods for SLN tracing is beneficial for rapid intraoperative search and shortened surgical time.CEUS trac-ing does not require special radiological diagnosis and treatment qualifications,which is conducive to popularization and can provide a basis for clinical staging,formulation of treatment plans,and postoperative prediction.Conclusion The combination of CEUS tracing and puncture biopsy is a reliable preoperative assessment method of SLN,which is more fit for the future development trend of precise and minimally invasive surgical procedures compared to mainstream SLN trac-ing methods.
Objective To investigate the effect of gender,position fixation method,age,and body mass index(BMI)on the precision of positioning in patients with esophageal cancer based on CBCT image guidance and to provide a reference for clinical decision-making.Methods The clinical data of 353 patients with esophageal cancer undergoing radiotherapy from 2021-08-12 to 2022-07-19 were retrospectively analyzed and 3 855 CBCT scans were performed in 353 patients.Ac-cording to the height,weight,age,sex and fixation mode before the first treatment and the position error data after each CBCT scan,the univariate analysis method was used to analyze the relationship between the position error and BMI value in the left right(LR),superior inferior(SI)and anterior posterior(AP)direction.The Pearson correlation analysis was applied to analyze the relationship between patient positioning error in LR,SI and AP directions with age and sex.For fe-male patients,according to whether there were male therapists involved,they were divided into no female therapist in-volved or a female therapist involved,and the relationship with positioning error in the two groups was analyzed by univa-riate analysis.Results A total of 3 855 CBCT scans were performed in 353 patients and in the LR,SI and AP directions.The three-dimensional placement errors were(3.32±1.80),(2.03±1.13)and(2.20±1.18)mm for male patients and(3.84±1.91),(2.01±0.88)and(2.93±1.70)mm for female patients with F values of 4.213,0.014 and 16.254 and P values of 0.41,0.904 and<0.001.Positioning errors in the LR,SI and AP directions in the group without the partici-pation of female therapists were(4.43±3.24),(2.00±1.64)and(3.33±2.91)mm and those in the group with the participation of female therapists were(4.15±3.42),(2.00±1.44)and(2.74±2.30)mm with F values of 1.353,0.001 and 9.030 and P values of 0.245,0.979 and<0.001.The differences in the positioning errors of the three posi-tional immobilization devices of vacuum bags[(3.81±1.96)and(2.59±1.41)mm],styrofoam[(3.09±1.58)and(2.12±1.18)mm]and styrofoam combined with thermoplastic masks[(2.49±1.80)and(1.64±1.00)mm]were sta-tistically significant in the LR and AP directions,with F-values of 8.841 and 7.775,all P<0.001.In the SI direction[(2.02±1.10),(2.03±1.11)and(1.94±0.79)mm]the difference was not statistically significant,F=0.047,P=0.954.The results showed that BMI was mildly positively correlated with positioning error in the LR direction(r=0.134,P=0.012),and there was no correlation between age and positioning error in any of them.Conclusions Positio-ning errors are greater in female patients than in male patients and can be reduced when a female therapist is involved in positioning.The use of styrofoam and styrofoam combined with a thermoplastic mask is better than vacuum bags for posi-tional devices and the patient's BMI and age have no effect on the precision of positional fixation.
Objective To explore the surgical treatment of pediatric testicular leukemia(TL),in order to provide novel ref-erences for the clinical diagnosis and treatment of TL.Methods The clinical data of 12 children with TL from January 1st,2018 to July 31st,2022,In the First Affiliated Hospital of Shandong First Medical University,were retrospective analyzed,and the clinical treatment and prognosis were investigated.Meanwhile,literature about TL treatment in chil-dren,published from April 15th,1995 to September 1st,2023,was retrieved from Pubmed and Wanfang databases,in or-der to analyze the progress in the diagnosis and treatment of TL.Results Totally 12 male children were enrolled in this study,and all cases were long-term(>2 years)recurrence after chemotherapy.Their age ranged from 3.7 to 13.8 years(median age 6.5 years).Their ultrasound location was classified:left testis(9 cases),right testis(2 cases),and both testes(1 case).The onset of time ranged from 2.0 to 5.5 years(median time 3.0 years).Among them,11 cases were diagnosed as B cell-acute lymphoblastic leukemia(B-ALL)and 1 case was acute myeloid leukemia(AML).Once admis-sion,the children underwent systemic intensive chemotherapy regimens for acute leukemia.After induction chemothera-py,testicular swelling disappeared in 4 cases(clinical TL).There were 8 children with swelling testes,which were con-firmed by testicular biopsy with the consent of their parents(pathological TL).Among the children with positive testicu-lar biopsy,6 cases underwent orchiectomy on the affected side and 2 cases underwent bilateral testicular radiotherapy.Following the principle of tumor-free during testicular surgery,the spermatic cord should be ligated as high as possible,and inguinal lymph node biopsy could not be performed routinely.Except for 2 children who died after giving up treat-ment,the remaining 10 patients were alive up to March 1st,2023.Conclusions Primary treatment regimen of pediatric TL is systemic chemotherapy combined with testicular radiotherapy or orchiectomy.Surgical treatment(including testicu-lar biopsy and orchiectomy)plays an indispensable role in the diagnosis and treatment of recurrent TL in children.
Objective To explore the effects of circCLK3/miR-216a-5p molecular axis on the proliferative,apoptotic,mi-gratory and invasive abilities of breast cancer MDA-MB-453 cells and their possible mechanisms.Methods We collected the cancerous and paracancerous tissues of 63 patients diagnosed as breast cancer by pathology in the Tianjin Medical Uni-versity Cancer Institute and Hospital from February 1,2020 to May 31,2022.The expressions of circCLK3 and miR-216a-5p were detected by qRT-PCR;human breast cancer cells MDA-MB-453 were cultured in vitro,and si-NC,si-circCLK3,miR-NC,miR-216a-5p were transfected into MDA-MB-453 cells,respectively.Meanwhile,si-circCLK3 and anti-miR-NC,si-circCLK3 and anti-miR-216a-5p were co-transfected into MDA-MB-453 cells,respectively.The dual lu-ciferase reporter experiment was used to detect the targeting relationship between circCLK3 and miR-216a-5p.MTT,col-ony formation,flow cytometry,and transwell assays were applied to examine cell proliferative,apoptotic,migratory,and invasive abilities.Western blot assay was used to detect Bax and Bcl-2 protein expression.Results Compared with para-cancerous tissues(0.96±0.13),the expression of circCLK3 was elevated in breast cancer tissues(2.37±0.38),t=27.866,P<0.001,and the expression of miR-216a-5p was decreased(1.03±0.14 vs 0.43±0.08),t=29.535,P<0.001;Transfection with si-circCLK3 up-regulated miR-216a-5p expression compared with si-NC group(t=29.684,P<0.001),inhibited the clone number of cells(t=20.743,P<0.001),invasion(t=22.395,P<0.001),and migration a-bility(t=27.915,P<0.001),and increased apoptosis(t=37.221,P<0.001);compared with the miR-NC group,transfection with miR-216a-5p resulted in inhibition of cell clone number(t=21.266,P<0.001),invasion(t=28.590,P<0.001),migration ability(t=27.756,P<0.001)and increased apoptosis(t=36.884,P<0.001).Compared with the si-circCLK3+anti-miR-NC group,the clonogenesis,migration and invasion of cells in the si-circCLK3+anti-miR-216a-5p co-transfection group were enhancedthe t-values were 10.447,20.211 and 18.429,respectively,both P<0.001.Conclu-sion circCLK3 knockdown inhibited breast cancer cell growth,migration,and invasion through upregulation of miR-216a-5p expression.
Objective To analyze the clinical features,treatment and prognosis of patients with large granular lymphocytic leukemia(LGLL).Method The clinical characteristics,treatment regimens and prognosis of 37 patients with LGLL in the First Affiliated Hospital of Zhengzhou University from October 5,2019 to July 22,2022 were analyzed retrospective-ly.Kaplan-Meier method was used for survival analysis.Result The median age was 64 years old.The common initial symptoms included fatigue and chest tightness after activity(19 cases,61.3%),repeated infection(21 cases,67.7%)and fever(4 cases,12.9%).Nineteen patients(61.3%)had comorbidities of autoimmunity diseases,and the most com-mon type was pure red cell aplastic anemia,followed by rheumatoid arthritis;Blood routine test of LGLL patients usually manifested as anemia(29 cases,93.5%),granulocytopenia(14 cases,45.2%),and increased proportion of lymphocytes(19 cases,61.3%).Flow cytometry showed that 27 of the 28 patients had T-LGLL and 1 had NK-LGLL(immunophe-notype was CD3-CD94+CD56-CD4-CD16-).According to phenotype,27 T-LGLL patients were divided into CD4-CD8+(24 cases)and CD4-CD8-(3 cases).The clinical manifestations of the two groups were similar,with no statistical significance,both P>0.05.T cell antigen receptor(TCR)gene rearrangement was performed in 16 patients,of which 15 patients(93.8%)were positive for TCR gene rearrangement.Of the 16 patients,12 had TCR αβ+rearrangement and 4 had TCRγδ+rearrangement.Twenty-six patients were treated with immunosuppressants as first-line therapy,with an overall response rate of 53.8%.As of 2022-11-30,the median follow-up time of enrolled patients was 15 months,and 26 patients survived.The 1 and 5-year OS rates were 89.2%and 84.2%,respectively.Conclusions The initial symptoms of LGLL are diverse,which are mainly hematological and immunologic functional abnormalities,with no clear difference in clinical features across immunophenotypes.The prognosis of LGLL is relatively good,and the survival time is longer.Immunosuppression remains the most effective treatment at present,but long-term maintenance therapy is needed.
Objective To explore the changes of lymphocytes and dendritic cells(DC)subsets in peripheral blood of patients with locally advanced nasopharyngeal carcinoma before and after induction chemotherapy and concurrent radiotherapy and chemotherapy,as well as their relationship with clinical prognosis.Methods Clinical data of patients with 134 patients with local advanced nasopharyngeal cancer at the Guizhou Medical University Affiliated Cancer Hospital of from 2016-12-05 to 2018-05-31 were retrospectively analyzed.All patients accept 2 to 3 cycles of Doxisca+Cisplatin+Fluoropromoline(TPF scheme)induced chemotherapy+platinum scheme combined with radiation chemotherapy.Before and after induc-tion chemotherapy and 1 week within concurrent radiation and chemotherapy,flow cytometry was used to detect lympho-cytes and DC subgroups in peripheral blood.The follow-up was once in every 3 months within 2 years after the treat-ment;once in every 6 months in 3 to 5 years.The survival was observed.The Friedman M test was used to compare lym-phocytes and DC subgroups in peripheral blood before treatment,after induction chemotherapy,and after concurrent che-moradiotherapy.ROC curves were used to determine the critical values of corresponding indicators.The Kaplan-Meier method and the COX regression model were used for survival analysis.Results The levels of CD3+[60.29(51.76,67.49)vs 63.85(58.63,70.10)],CD4+[32.31(25.97,38.26)vs 34.10(28.28,40.90)],CD8+[20.64(16.26,27.48)vs 23.32(18.37,29.10)],activated CD4+[1.36(0.90,2.61)vs 2.02(1.14,2.82)],activated CD8+[0.77(0.38,2.11)vs 1.90(0.78,4.00)],CD8+CD28+[12.08(9.16,15.01)vs 13.86(10.34,16.63)]and the myeloid dendritic cells[MDC;5.04(2.73,7.07)vs 6.06(4.26,9.28)]in peripheral blood increased after TPF induction chemotherapy(P<0.05).Af-ter concurrent radiotherapy and chemotherapy,the levels of CD3+[60.29(51.76,67.49)vs 57.60(47.39,66.50)],CD4+[32.31(25.97,38.26)vs 26.06(20.06,32.29)],CD8+CD28+[12.08(9.16,15.01)vs 10.09(6.74,13.15)],CD4+/CD8+[1.58(1.07,1.97)vs 1.22(0.82,1.71)]and CD4+CD25+[4.10(2.79,5.60)vs 3.15(1.49,5.37)]reduced(P<0.05).Kaplan Meier univariate analysis showed that the proportions of CD3+,CD4+,activated CD4+,CD8+CD28+,CD4+/CD8+,CD3-CD16+,plasmacytoid dendritic cells(pDC)and MDC in peripheral blood before treatment were correlated with patient survival prognosis(P<0.05).The prognostic analysis of the COX model found that high-lev-el CD4+(HR=0.39,95%CI:0.18-0.89,P=0.021)and PDC(HR=0.37,95%CI:0.15-0.90,P=0.030)were in-dependent influencing factors of overall survival for locally advanced nasopharyngeal cancer.Conclusions TPF-based in-duction chemotherapy may kill tumor cells,release tumor-related antigens,relieve the immunosuppressive state of locally advanced nasopharyngeal carcinoma,improve the tumor microenvironment and restore the body's immune function.After concurrent radiotherapy and chemotherapy,the body's immune function declines.CD4+and pDC in peripheral blood be-fore treatment may be independent influencing factors of OS in locally advanced nasopharyngeal carcinoma.
目的 探讨自然杀伤(NK)细胞中自然杀伤2组成员D(NKG2D)受体-配体信号轴发挥抗肿瘤作用及肿瘤对此信号轴的逃逸机制,通过多种方法利用该途径提高肿瘤清除率,为临床肿瘤免疫治疗提供新思路.方法 应用PubMed及中国知网数据库检索系统,以"natural killer(NK)、natural killer group 2 member D(NKG2D)、nkg2d ligands、tumor、tumor escape"为英文关键词,以"自然杀伤细胞、NKG2D受体、NKG2D配体、肿瘤、肿瘤逃逸"为中文关键词,交叉检索1999年1月—2023年4月的相关文献.纳入标准:NKG2D受体及配体的结构和作用;肿瘤逃逸NK细胞NKG2D受体-配体信号轴的机制;利用NK细胞NKG2D受体-配体信号轴治疗肿瘤的方法.排除标准:与肿瘤治疗相关性较低的文章.最终纳入文献65篇.结果 肿瘤通过调节NKG2D受体和配体的表达,或通过阻断该信号轴作用逃避NK细胞的清除.通过提高NKG2D受体或配体表达提高其识别特异性,明显提高肿瘤治疗效果.结论 通过抗体清除可溶性NKG2D配体,解除NKG2D受体-配体轴的阻断;通过小分子化合物提高NKG2D受体或配体表达;通过过继抗原嵌合受体NK细胞提高NK细胞对肿瘤细胞的治疗效果.
目的 分析二甲双胍对卵巢癌患者生存率的影响,为降低癌症风险、提高患者生存率提供参考.方法 搜索PubMed、Embase和Web of Science数据库自建库至2022-10-25的相关文献.搜索医学主题词和文本词包括metform-in、biguanides、diabetic medications、ovarian、ovary、cancer、neoplasms、tumor、carcinoma、survival、mortality、prognosis、death,提取每项研究的数据和特征,并计算95%CI和HR值以评估二甲双胍对糖尿病卵巢癌患者总生存期(OS)和无进展生存期(PFS)的影响,最终纳入10篇文献.结果 二甲双胍对卵巢癌患者生存率有显著益处,HR=0.59,95%CI:0.49~0.72.亚组分析显示二甲双胍可以改善糖尿病卵巢癌患者OS,HR=0.65,95%CI:0.53~0.81.但二甲双胍与糖尿病卵巢癌患者的PFS无关联,HR=0.48,95%CI:0.22~1.05.与无糖尿病卵巢癌患者相比,二甲双胍与糖尿病卵巢癌患者OS和PFS有关联,合并HR值分别为0.39(95%CI:0.20~0.76)和0.39(95%CI:0.26~0.57).二甲双胍使用时间>720 d可以改善糖尿病卵巢癌患者的OS,HR=0.31,95%CI:0.16~0.57.二甲双胍与糖尿病卵巢癌患者的疾病特异性生存率无关,HR=0.59,95%CI:0.31~1.12.结论 目前的研究初步证实二甲双胍可能与卵巢癌患者的生存获益相关,但需要更多的研究来证实.
目的 总结能量代谢参与黑色素瘤靶向治疗耐药的相关研究,分析代谢表型转换调控黑色素瘤耐药的机制,探讨靶向代谢重编程对黑色素瘤药物敏感性的影响,为干预和延缓黑色素瘤耐药提供新思路.方法 以"黑色素瘤、耐药、靶向治疗、代谢、MAPK通路、BRAFV600E、BRAFV600K、谷氨酰胺、线粒体、肿瘤微环境"为中文关键词,以"melanoma、resist-ance、targeted therapy、metabolism、MAPK pathway、BRAFV600E、BRAFV600K Aglutamine、mitochondria、tumor microenviron-ment"为英文关键词,检索PubMed和中国知网数据库,共检索到中文文献23篇,英文文献548篇.纳入标准:(1)黑色素瘤流行病学、生物学和预后;(2)糖酵解参与黑色素瘤靶向耐药的机制;(3)代谢转换对黑色素瘤靶向耐药的影响.排除标准:(1)研究对象为黑色素瘤靶向治疗外的其他治疗方法;(2)会议论文、报告和信函等.根据标准共纳入文献61篇,中文2篇,英文59篇.结果 临床使用靶向药物治疗黑色素瘤高效快速,毒副作用较小.但耐药性的发展限制了靶向药物的疗效,导致预后不良.在靶向治疗过程中,黑色素瘤主动调节代谢和供能方式,包括增强糖酵解和线粒体活性,增加谷氨酰胺分解,促进氧化磷酸化等方式,以维持细胞增殖,同时释放乳酸和CO2等副产物,促进肿瘤微环境酸化,以进一步促进耐药发生.结论 异常的能量代谢方式及伴随的肿瘤微环境酸化,是耐药黑色素瘤细胞赖以生存的重要因素,针对这些异常靶点进行干预,有望延缓黑色素瘤耐药发生.
目的 总结国内外与鳞状细胞癌(简称鳞癌)发病相关的基因组学研究,为寻找不同解剖部位鳞癌共同遗传变异,进而识别鳞癌高危人群并降低疾病负担提供思路和参考.方法 以鳞癌、遗传变异、危险因素为中文关键词,以squa-mous cell carcinoma、genetic variations、risk factors 为英文关键词,检索 PubMed、Web of Science 和中国知网(CNKI)数据库中2016-2022年发表的与鳞癌相关的基因组学研究.纳入标准:(1)可获取全文,语种限中文和英文;(2)所研究肿瘤的组织类型包括鳞癌;(3)研究遗传变异对鳞癌的影响.排除标准:(1)综述、摘要、个案;(2)效应指标仅包含药物疗效.共纳入70篇文献,其中中文文献9篇,英文文献61篇.结果 单核苷酸多态性(SNPs)、染色体畸变(CAs)和甲基化修饰等遗传变异均可促进鳞癌的发生发展,随着测序技术的发展,驱动基因突变和基因环境交互作用也是探索鳞状细胞癌变过程中关键基因的研究热点.结论 不同解剖部位鳞癌存在相同的遗传危险因素,但研究证据不完全一致,因此,需要更多的研究来探讨其在发病机制上的共性,进而应用于鳞癌的预防治疗.
目的 比较脑寡转移瘤分次立体定向放射治疗中容积旋转调强放射治疗(VMAT)与动态适形弧放射治疗(DCAT)计划的剂量学特点,为临床治疗方式的选择提供参考.方法 纳入2020-07-08-2022-05-27中国科学院合肥肿瘤医院收治的20例脑寡转移瘤患者,采用相同计划参数分别优化VMAT与DCAT计划,当靶区剂量覆盖率相同时,采用Wilcoxon符号秩检验比较靶区与危及器官剂量、机器跳数(MU)、控制点数(CP)及计划复杂度(MU/CP)等指标差异,采用Spearman相关性分析评估靶区球形度与2种计划剂量参数的相关性.结果 VMAT计划靶区适形度指数(0.87±0.07)高于DCAT计划(0.65±0.08),梯度指数(4.97±1.00)低于DCAT计划(6.78±1.26),剂量均匀性指数(1.08±0.01)亦低于 DCAT 计划(1.15±0.04),Z 值均为-3.920,均 P<0.001.VMAT 计划健康脑组织的 V12Gy、V19.6 Gy和V23.1Gy分别为(87.72±23.62)、(36.01±9.45)和(24.66±7.39)cm3,均低于 DCAT 计划,Z 值均为-3.920,均 P<0.001.DCAT 计划的 MU 为 763.17±40.12,CP 为 65.95±15.78,低于 VMAT 的 1 153.75±241.72 和 162.55± 11.48,Z值分别为-3.920 和-3.922,均 P<0.001;MU/CP 为 12.45±4.15,高于 VMAT 的 2.61+0.68,Z=-3.920,P<0.001.DCAT计划的靶区球形度与梯度指数呈中等正相关,rs=0.465,P=0.039.结论 VMAT和DCAT均能满足临床剂量限制要求,但VMAT具有更优靶区适形度、剂量梯度和剂量均匀性,对健康脑组织的保护更佳,而DCAT执行效率更高.对于需高度适形和正常组织保护的患者,优先推荐VMAT,而对于长时间放疗耐受性差的患者,可考虑选用DCAT.
目的 探讨锝-99m(99mTc)-硫胶体(SC)SPECT/CT淋巴显像术前评估前哨淋巴结(SLN)转移风险的价值,并结合3D融合模式定位SLN,探寻SLN的分布规律.方法 选取2020-01-01-2022-12-31内蒙古医科大学附属医院收治的拟行前哨淋巴结活检术(SLNB)且术前行99mTc-SC SPECT/CT淋巴显像的女性乳腺癌患者288例.采用单因素及多因素logistic回归分析方法分析与SLN转移有关的淋巴显像及临床病理因素.淋巴显像阳性的患者使用3D融合重建技术重建皮肤和骨骼,再应用腋窝体表标线及肋间隙对SLN进行定位.结果 共有59例(20.49%)患者SLN发生转移.单因素分析结果显示,年龄(x2=4.318,P=0.038)、月经状态(x2=8.090,P=0.004)和SPECT/CT显像个数(x2=5.631,P=0.018)与SLN转移有关联.多因素分析结果显示,SPECT/CT显像个数(OR=2.387,95%CI:1.137~5.013,P=0.022)对SLN转移有诊断价值.当SPECT/CT淋巴显像个数≤1枚时,SLN转移率为24.14%(49/203);当SPECT/CT淋巴显像个数>1枚时,SLN转移率为11.76%(10/85).SPECT/CT淋巴显像法诊断SLN转移的灵敏度为83.05%(49/59),特异度为32.75%(75/229).淋巴显像阳性的204例患者中,"最热"SLN分布于腋中线附近最多,其次为腋前线和腋后线附近;"最热"SLN分布于第2肋间隙最多,其次为第1、3、4和5肋间隙.结论 99mTc-SC SPECT/CT淋巴显像在术前评估SLN转移风险方面具有一定价值,其诊断SLN转移的灵敏度较高.99mTc-SC SPECT/CT淋巴显像结合3D融合模式可用于SLN定位,绝大多数SLN分布于腋前线、腋中线与第1~3肋间隙围成的四边形区域内.