Neoadjuvant immunotherapy improves outcomes for resectable gastroesophageal junction cancer: A systematic review and meta-analysis.

BACKGROUND: In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. METHODS: A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta-analyses were performed using Stata BE17 software. RESULTS: For these meta-analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36-0.54; pCR: ES = 0.26; 95% CI: 0.21-0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48-0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR < 30%; pCR: ES = 3%-17%; nodal downstage to ypN0 rate: ES = 21%-29%). Safety was assessed using the treatment-related adverse events (trAEs) incidence rate, surgical delay rate, surgical complications incidence rate, and surgical resection rate. In conclusion, the incidence of trAEs, incidence of surgical complications, and surgical delay rate had ES values of 0.66, 0.48, and 0.09, respectively. These rates were comparable to those from nCT or nCRT (95% CI: 0.60-0.70; 0.15-0.51; and 0, respectively). The reported resection rates of 85%-95% with nCT or nCRT were comparable to the mean surgical resection rate of 90%. CONCLUSION: NAIT is an effective treatment for resectable GEJC; additionally, the level of NAIT toxicity is acceptable. The long-term effects of NAIT require further study.

Efficacy and safety of neoadjuvant therapy in gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness and safety of neoadjuvant therapy in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and provide evidence-based suggestions for clinical treatment. METHODS: The Cochrane Library, Embase, PubMed, and Web of Science were searched for articles published that analyzed the effectiveness and safety of GEP-NEN-targeted neoadjuvant therapy before March 2023. A confidence interval (CI) of 95%, a subgroup analysis, heterogeneity, and effect size (ES) were analyzed, and a meta-analysis of the literature was performed using the Stata BE17 software. RESULTS: A total of 417 patients from 13 studies were included in this meta-analysis. The primary variables comprised the objective response rate (ORR), disease control rate (DCR), surgical resection rate, and R0 resection rate with ES values of 0.42 (95% CI: 0.25-0.60), 0.96 (95% CI: 0.93-0.99), 0.67 (95% CI: 0.50-0.84), and 0.60 (95% CI: 0.54-0.67), respectively. The secondary variables were the incidence rates of treatment-related adverse events (TRAEs), Grade 3 or higher TRAEs, and surgical complications with ES values of 0.29 (95% CI: -0.03-0.21), 0.13 (95% CI: -0.07-0.33), and 0.35 (95% CI: 0.27-0.44), respectively. CONCLUSION: Neoadjuvant therapy is an effective and safe treatment method for GEP-NENs. However, further studies are required to determine the optimal regimen for this therapy in these tumors.

Targeting complement C5a to improve radiotherapy sensitivity in non-small cell lung cancer.

Background: Tumor local and distant relapse recurrence after radiotherapy (RT) is one of the critical factors leading to poor prognosis. The effective antitumor effects of RT are dependent upon the participation of innate and adaptive components of the immune system. C5a/C5aR1 signaling can regulate antitumor immune effect in the tumor microenvironment (TME). Thus, exploring the changes and mechanism in the TME induced by RT-mediated complement activation may provide a novel perspective for reversing radioresistance. Methods: First, fractionated radiation of 8 Gy ×3 fractions were targeted at Lewis lung carcinoma (LLC) tumor-bearing female mice to measure the infiltration of CD8+ T cell and analyze the RNA sequencing (RNA-seq) in RT-recruited CD8+ T cells. Second, tumor growth was measured in LLC tumor-bearing mice treated with RT either with or without C5aR1 inhibitor to clarify the antitumor effect of RT combined with C5aR1 inhibitor. Third, we detected the expression of C5a/C5aR1 and their signaling pathways on radiated tumor tissues. Furthermore, we investigated the expression of C5a in tumor cells at different time points after different doses of RT. Results: In our system, RT induced the increased infiltration of CD8+ T cells and local activation of complement C5a/C5aR. Concurrent administration of RT and blocking of C5aR improved radiosensitivity and tumor-specific immune response, which was reflected by high C5aR expression in CD8+ T cells. The AKT/NF-κB pathway was found to be an important signaling pathway in C5a/C5aR axis mediation by RT. Conclusions: RT promotes the release of C5a from tumor cells and leads to up-regulation of C5aR1 expression via the AKT/NF-κB pathway. Inhibition of the combination of complement C5a and C5aR could improve RT sensitivity. Our work provides evidence that the combination of RT and C5aR blockade opens a new window of opportunity to promote anti-tumor therapeutic effects in lung cancer.

Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review.

Background: Ectopic adrenocortical tissues and neoplasms are rare and usually found in the genitourinary system and abdominal cavity. The thorax is an extremely rare ectopic site. Here, we report the first case of nonfunctional ectopic adrenocortical carcinoma (ACC) in the lung. Case presentation: A 71-year-old Chinese man presented with vague left-sided chest pain and irritable cough for 1 month. Thoracic computed tomography revealed a heterogeneously enhancing 5.3 × 5.8 × 6.0-cm solitary mass in the left lung. Radiological findings suggested a benign tumor. The tumor was surgically excised upon detection. Histopathological examination using hematoxylin and eosin staining showed that the cytoplasm of the tumor cells was rich and eosinophilic. Immunohistochemical profiles (inhibin-a+, melan-A+, Syn+) indicated that the tumor had an adrenocortical origin. The patient showed no symptoms of hormonal hypersecretion. The final pathological diagnosis was non-functional ectopic ACC. The patient was disease-free for 22 months and is still under follow-up. Conclusions: Nonfunctional ectopic ACC in the lung is an extremely rare neoplasm that can be easily misdiagnosed as primary lung cancer or lung metastasis, both preoperatively and on postoperative pathological examination. This report may provide clues to clinicians and pathologists regarding the diagnosis and treatment of nonfunctional ectopic ACC.

Effect of intensity modulated radiotherapy on lymphocytes in patients with esophageal squamous cell carcinoma and its clinical significance.

Background: Radiotherapy usually leads to a decrease in the total number of lymphocytes in patients with esophageal cancer. The factors that causing lymphopenia and the clinical significance of lymphopenia are studied in this article. Patients and methods: 110 patients with esophageal squamous cell carcinoma who had undergo intensity-modulated radiation therapy were enrolled. Statistical methods were used to analyze the correlation between lymphopenia and total survival in patients with esophageal cancer during radiotherapy, and analyze the correlations between nutritional factors and lymphopenia. Results: There were 11 patients with the lowest lymphocyte value with level 1-2 during radiotherapy, accounting for 10% of all the patients, and 110 patients with level 3-4, accounting for 90% of all the patient. In all the enrolled patients, the incidence of lymphocyte nadir G1, G2, G3 and G4 MinALC during radiotherapy accounted for 0.91%, 9.09%, 62.73% and 27.27%, respectively.KM survival analysis showed that the overall survival of patients in the group (MinALC ≤ 0.41×109/L) was significantly lower than that of the patients in the other group (MinALC>0.43×109/L). Nutritional indicators were positively correlated with the decline degree of lymphocytes. The minimal value of lymphocyte can predict the occurrence of grade 3-4 radiation pneumonitis. Conclusion: Lymphopenia induced by radiotherapy can predict survival and radiation pneumonitis. Nutritional factors such as hemoglobin and albumin were positively correlated with total lymphocytes numbers induced by radiotherapy.

Effectiveness and safety of electroacupuncture combined with conventional drugs in the treatment of stable angina pectoris in coronary artery disease: A systematic evaluation and meta-analysis.

BACKGROUND: The objective of this study is to systematically evaluate the clinical effectiveness and safety of electroacupuncture combined with conventional drugs in the treatment of stable angina pectoris. METHODS: Computer searches of 3 Chinese literature databases (CNKI, VIP, WangFang) and 4 English literature databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science), all searched from the time of database construction to October 2022. Two researchers were selected to independently perform literature screening, data extraction, and risk of bias evaluation, and meta-analysis of the included studies was performed using RevMan 5.3 software. RESULTS: A total of 7 publications with a total of 1042 patients were included, and electroacupuncture combined with conventional drug therapy compared with drug therapy alone was effective in improving clinical symptoms of angina pectoris (relative risk [RR] = 1.19, 95% CI = [1.09, 1.31], P = .0002), clinical treatment efficiency of electrocardiography (RR = 1.34, 95% CI = [1.19, 1.50], P = .00001), visual analog score (VAS) (mean deviation = 0.07, 95% CI = [-0.11, 0.25], P = .44), and Seattle Angina Scale (mean deviation = 4.91, 95% CI = [2.91, 6.91], P < .00001) were better than conventional drug therapy, while the number of adverse events in the intervention group was lower than that in the control group. One of the outcome indicators with greater heterogeneity was tested by sensitivity analysis, and each outcome indicator was found to be more robust. The risk of bias evaluation of each outcome indicator using funnel plots suggested the possibility of publication bias. CONCLUSION: The current study results found that electroacupuncture combined with conventional drugs can significantly improve the clinical symptoms of patients with stable angina pectoris compared with conventional drug therapy, with a low incidence of adverse reactions, but the number of high-quality literature with rigorous study design protocols is currently low, which may cause bias in the results of this study, so the above conclusions need to be further verified through clinical trials.

The Role of Myeloid-Derived Suppressor Cells in the Treatment of Pancreatic Cancer.

Pancreatic cancer has the highest mortality rate of all major cancers, with a 5-year survival rate of about 10%. Early warning signs and symptoms of pancreatic cancer are vague or nonexistent, and most patients are diagnosed in Stage IV, when surgery is not an option for about 80%-85% of patients. For patients with inoperable pancreatic cancer, current conventional treatment modalities such as chemotherapy and radiotherapy (RT) have suboptimal efficacy. Tumor progression is closely associated with the tumor microenvironment, which includes peripheral blood vessels, bone marrow-derived inflammatory cells, fibroblasts, immune cells, signaling molecules, and extracellular matrix. Tumor cells affect the microenvironment by releasing extracellular signaling molecules, inducing peripheral immune tolerance, and promoting tumor angiogenesis. In turn, the immune cells of the tumor affect the survival and proliferation of cancer cells. Myeloid-derived suppressor cells are key cellular components in the tumor microenvironment and exert immunosuppressive functions by producing cytokines, recognizing other immune cells, and promoting tumor growth and metastasis. Myeloid-derived suppressor cells are the main regulator of the tumor immune response and a key target for tumor treatments. Since the combination of RT and immunotherapy is the main strategy for the treatment of pancreatic cancer, it is very important to understand the immune mechanisms which lead to MDSCs generation and the failure of current therapies in order to develop new target-based therapies. This review summarizes the research advances on the role of Myeloid-derived suppressor cells in the progression of pancreatic cancer and its treatment application in recent years.

Neoadjuvant Immunotherapy Improves Treatment for Early Resectable Non-Small-Cell Lung Cancer: A Systematic Review and Meta-analysis.

Objective: Immunotherapy has shown better efficacy and less toxicity than chemotherapy in the treatment of non-small-cell lung cancer (NSCLC) at advanced stage. This study evaluates the safety and efficacy of neoadjuvant immunotherapy for resectable NSCLC. Methods: Literature examination was performed by searching the PubMed, the Cochrane Library, and Embase for articles evaluating the efficacy and safety of neoadjuvant immunotherapy for resectable NSCLC. The 95% confidence interval (CI) and effect sizes (ES) were evaluated. Heterogeneity and subgroup analysis were performed. Meta-analysis was carried out using Stata BE17 software. Results: In total, 678 patients from eighteen studies were recruited in this meta-analysis. The pathological complete response (pCR) and major pathological response (MPR) were used to evaluate the efficacy of neoadjuvant immunotherapy. Significantly higher MPR values were observed in neoadjuvant immunotherapy (MPR : ES = 0.44; 95% CI: 0.33-0.55; pCR : ES = 0.22; 95% CI: 0.15-0.30) compared with neoadjuvant chemotherapy (MPR < 25% and PCR : ES = 2%-15%). Treatment-related adverse events (TRAE), surgical resection rate, surgical delay rate, and incidence of surgical complications were used to evaluate the safety. In summary, ES values for the incidence of TRAE, incidence of surgical complications, and surgical delay rate were 0.4, 0.24, and 0.04, respectively, that were significantly lower than those for neoadjuvant chemotherapy (95% CI: 0.04-0.90; 0.22-0.75; and 0.01-0.10, respectively). The mean surgical resection rate of 89% was similar to the reported 75%-90% resection rate with neoadjuvant chemotherapy (OR = 7.61, 95% CI: 4.90-11.81). Conclusion: Neoadjuvant immunotherapy is safe and effective for resectable NSCLC.

The Relationship Among Intestinal Bacteria, Vitamin K and Response of Vitamin K Antagonist: A Review of Evidence and Potential Mechanism.

The vitamin K antagonist is a commonly prescribed effective oral anticoagulant with a narrow therapeutic range, and the dose requirements for different patients varied greatly. In recent years, studies on human intestinal microbiome have provided many valuable insights into disease development and drug reactions. A lot of studies indicated the potential relationship between microbiome and the vitamin K antagonist. Vitamin K is absorbed by the gut, and the intestinal bacteria are a major source of vitamin K in human body. A combined use of the vitamin K antagonist and antibiotics may result in an increase in INR, thus elevating the risk of bleeding, while vitamin K supplementation can improve stability of anticoagulation for oral vitamin K antagonist treatment. Recently, how intestinal bacteria affect the response of the vitamin K antagonist remains unclear. In this review, we reviewed the research, focusing on the physiology of vitamin K in the anticoagulation treatment, and investigated the potential pathways of intestinal bacteria affecting the reaction of the vitamin K antagonist.

Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer.

Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74-4.14, P < 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P < 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8+ T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P < 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer.

TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation.

TEA domain family members (TEADs) play important roles in tumor progression. Till now, the genomic status of TEADs in patients with glioma has not been well investigated. To confirm whether the genomic status of TEADs could affect the prognosis of patients with glioma, the copy number variation (CNV), mutation and expression data of glioma cohorts in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas were comprehensively analyzed. Results showed that TEAD CNV frequency in lower grade gliomas (LGGs) was higher than in glioblastoma multiforme (GBM). Multivariate cox regression analysis showed that TEAD4 CNV increase was significantly associated with overall survival (OS) and disease-free survival (DFS) in LGGs (OS p = 0.022, HR = 1.444, 95% CI: 1.054-1.978; DFS p = 0.005, HR = 1.485, 95% CI: 1.124-1.962), while not in GBM. Patients with TEAD4 CNV increase showed higher expression level of TEAD4 gene. In LGG patients with IDH mutation, those with higher TEAD4 expression levels had shorter OS and DFS. Integrating TEAD4 CNV increase, IDH mutations, TP53 mutation, ATRX mutation and 1p19q co-deletion would separate patients with LGG into four groups with significant differences in prognosis. These study results suggested that TEAD4 variations were independent predictive biomarkers for the prognosis in patients with LGG with IDH mutation.

Doses of intensity-modulated radiotherapy and its association with cardiac disease in esophageal cancer patients.

BACKGROUND: No clear guidelines or available studies exist regarding the effects of intensity-modulated radiotherapy (IMRT) of esophageal cancer (EC) on the cardiovascular system. We therefore analyzed a wide range of cardiac vascular dosimetric parameters and clinical characteristics to assess the prognostic factors for EC patients treated with IMRT. METHODS: A total of 112 patients receiving IMRT at the Qianfoshan Hospital between July 2012 and May 2017 were retrospectively reviewed. The dose per fraction was 1.8-2.0 Gy, and the total dose range was 54-66 Gy. Kaplan-Meier analysis was used to estimate death due to heart disease. Univariate and multivariate logistic regression models were calculated to test for associations between patient characteristics and dose-volume histogram (DVH) parameters. A t-test and chi-squared or Fisher's exact test was used to analyze the comparisons. RESULTS: The maximum and mean doses received by the heart were 57.34±13.51 and 24.83±11.40 Gy, respectively. Among the parameters examined, which included the maximum dose received by the heart, the mean dose received by the right and left ventricle (RV and LV), and the maximum dose received by the right atrium (RA), the mean dose received by the RV predicted survival and was included in our multivariate analysis. The results indicated that patients with basic heart disease who were undergoing concurrent radiochemotherapy were more likely to have cardiac disease. CONCLUSIONS: This is first study to examine the prognosis of cardiovascular vessels exposed to various radiation doses during the treatment of EC, the findings of which suggest that limiting radiation exposure may be an important measure in IMRT application. These findings of this study may provide theoretical support for prediction of radiation-induced heart disease (RIHD). Furthermore, to curb the risk of RIHD, the modality of chemotherapy also needs to be attentively monitored and managed.

Impact of radiotherapy on circulating lymphocyte subsets in patients with esophageal cancer.

Radiotherapy (RT) can affect the immune function of patients with cancer. The purpose of this study was to investigate the effect of RT on lymphocyte and its subsets in patients with esophageal cancer (EC).All patients received RT with a mean dose of 5369 cGy (gray). Blood parameters were measured in 31 patients on 3 occasions (before, at the end of radiotherapy, and at 3 months follow-up). The whole blood count and lymphocyte subsets were measured and correlated with short time efficiency and radiation dose parameters.White blood count (WBC) and lymphocyte count (ALC) were greatly decreased at the end of radiotherapy, and the percentages of CD3+, CD3+CD8+ T cells were significantly increased, on the other hand, a decrease in the CD4/CD8 ratio was observed. The percentages of CD3-CD16/56+NK cells and CD19+ B cell were decreased at the end of RT compared with prior RT. The percentages of CD3+ T cells before RT and the WBC and ALC count after RT can be used as prognostic indicators for survival. The PTV dose can cause significant changes in lymphocytes count after RT. CD3+T cells after RT were significantly correlated with mean heart dose and heart V50.Our study identified that RT causes changes in lymphocyte subsets, and these changes may indicate differences in immune function between individuals. Radiotherapy plan should be designed to minimize normal tissue dose to reduce the impact on WBC and lymphocytes.

Prognostic value of combined preoperative prognostic nutritional index and neutrophil to lymphocyte ratio in esophageal squamous cell carcinoma.

BACKGROUND: Preoperative nutritional status and some inflammatory indexes are associated with survival in various malignancies. Prognostic nutritional index (PNI) or neutrophil to lymphocyte ratio (NLR) was demonstrated associated with survival in patients with esophageal squamous cell carcinoma (ESCC). The purpose of the present study was to investigate whether the combination index of PNI and NLR (PNI-NLR) is superior to either alone in survival prognosis of patients with ESCC. METHODS: In total, 271 patients with ESCC who underwent radical esophagectomy from Qianfoshan Hospital from May 2009 to July 2014 were enrolled. Preoperative PNI and other clinical data were collected and analyzed. Using the 5-year survival rate as an end point, a receiver operating characteristic (ROC) analysis was used to find the best cutoff value for PNI and NLR was 49.1 and 3.14, respectively. And all the enrolled patients were classified into three groups: group 1 (score 0, NLR ≤3.14 and PNI >49.1), group 2 (score 1, NLR >3.14 or PNI ≤49.1) and group 3 (score 2, NLR >3.14 and PNI ≤49.1). RESULTS: The combined index of PNI-NLR was a sensitive index in survival prognosis, and patients in the group 1, 2 and 3 had median survival times of 64, 47 and 36 months, respectively. Patients in group1 had significantly longer survival time than those of group 2 and group 3. In multivariate analyses, TNM stage, lymph stage, PNI and PNI-NLR affected the overall survival (OS). PNI was significantly correlated with TNM stage. CONCLUSIONS: Preoperative PNI-NLR was an independent predictor of survival of patients with ESCC. The index of PNI-NLR can improve the accuracy of prognoses for patients with ESCC than the index of NLR.

Odds ratio of programmed cell death-1 or ligand 1 inhibitor-related endocrine dysfunction in patients with lung cancer: A systematic review and meta-analysis.

PURPOSE: We designed the study to investigate the incidence risk of Programmed Cell Death-1 (PD-1) or Ligand 1 (PD-L1) inhibitor-related endocrine dysfunction in patients with lung cancer. METHOD: All the data were collected by 1 primary reviewer and then independently reviewed by 2 secondary reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines. Incidence risk of all-grade and grade 3-5 PD-1/PD-L1 inhibitors related endocrine dysfunction in patients with lung cancer were taken into account. RESULTS: Overall, 12 clinical trials comprising 6108 patients were identified in this systematic review and meta-analysis. The incidence risk of hypothyroidism, hyperthyroidism and adrenal insufficiency was higher in NSCLC patients receiving combination treatments. The incidence rate of all-grade of hypothyroidism was lower in PD-1/PD-L1 inhibitor subgroup compared to chemotherapy (OR = 22.62, 95%CI:9.79-52.25), while the similar result was seen in another treatment regimen (PD-1 + platinum-based chemotherapy vs platinum-based chemotherapy) (OR = 2.93, 95%CI: [2.08, 4.11). The different result can be seen in the group related to the other treatment regimen (1PD-1/PD-L1 inhibitor vs 2 PD-1/PD-L1 inhibitors) (OR = 0.40, 95%CI:0.21-0.76). All the results of the above analysis were considered to be statistical significant. Similar result could also be seen in meta-analysis related to hyperthyroidism and adrenal insufficiency. CONCLUSION: The incidence risk of endocrine dysfunctions, including hypothyroidism, hyperthyroidism and adrenal insufficiency, were higher for PD-1/PD-L1 inhibitors group.

Intensity-modulated radiotherapy, coplanar volumetric-modulated arc, therapy, and noncoplanar volumetric-modulated arc therapy in, glioblastoma: A dosimetric comparison.

OBJECTIVE: Advanced techniques such as volumetric-modulated arc therapy (VMAT) may reduce radiation damage and improve the quality of life for patients.We performed a study comparing dose distributions to the planning target volumes(PTVs) and other organs at risk (OARs) of intensity-modulated radiotherapy (IMRT),coplanar VMAT (coVMAT), and non-coplanar VMAT (ncVMAT). PATIENTS AND METHODS: 13 patients with GBM who had undergone postoperative radiotherapy were enrolled. Three plans for each patient were created, namely, IMRT, coVMAT, and ncVMAT. Prescription doses and normal-tissue constraints were identical for these three plans. The dosimetric differences of target dose distribution, conformity index (CI), homogeneity index (HI), the gradient index (GI), dose of OARs, monitor units (MUs) and beam-on times among these three plans were investigated. RESULTS: These three techniques resulted in comparable maximum, minimum, and mean PTV doses. Small but insignificant differences were observed in GI,CI, and HI. Compared with IMRT, VMAT plans showed statistically significant reductions in the mean doses to the optic chiasm (P < 0.05). Compared with IMRT, VMAT techniques significantly reduced the number of MUs and less beam-on time than IMRT techniques (P ＜ 0.05). However, calculation times were significantly longer for ncVMAT and coVMAT plans at 12 and 12.3 min, versus 2.6 min for IMRT. Our study showed that IMRT or VMAT planning is feasible and efficient for patients with GBM.Compared to IMRT plans, ncVMAT or coVMAT plans showed similar PTV coverage and comparable OARs sparing. VMAT plans significantly reduces the mean doses to the optic chiasm than IMRT plans. CONCLUSION: There was no obvious superiority of ncVMAT over coVMAT in target coverage and sparing of OARs.Compared with IMRT, VMAT techniques significantly reduced the number of MUs and beam-on time but extended the calculation times.

Reversible posterior leukoencephalopathy syndrome following apatinib for gastric cancer in an adult: A case report and a review of the literature.

RATIONALE: Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by rapidly progressive hypertension, headache, and disturbance of consciousness. Moreover, RPLS is rarely reported after apatinib treatment. PATIENT CONCERNS: We present a case of RPLS induced by apatinib in this report. The patient had dizziness and bilateral lower limb weakness after apatinib use for 12 days. DIAGNOSIS AND INTERVENTIONS: Cranial T2-weighted magnetic resonance imaging (MRI) revealed symmetrical increased signal intensity in bilateral areas of the basal ganglia, radiation crown, frontal lobe, parietal lobe, and occipital lobe, which was suggestive of RPLS. The patient discontinued apatinib use and was administered dexamethasone, mannitol, and antihypertensive drugs. OUTCOMES: The patient's blood pressure returned to normal and neurological symptoms improved after 3 days of discontinuation of apatinib use. Moreover, brain MRI showed complete resolution of previous changes after 44 days of discontinuation of apatinib use. LESSONS: Increased blood pressure may damage the normal blood-brain barrier, resulting in the extravasation of the fluid into the brain parenchyma. Hypertension is a significant cause of RPLS. It is important to strictly monitor blood pressure during apatinib treatment.

The Association Between the Incidence Risk of Peripheral Neuropathy and PD-1/PD-L1 Inhibitors in the Treatment for Solid Tumor Patients: A Systematic Review and Meta-Analysis.

Purpose: We conducted this study to determine the relationship between PD-1/PD-L1 inhibitors and the incidence risk of peripheral neuropathy in patients with solid tumors. Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Incidence of all-grade and grade 3-5 treatment-related peripheral neuropathy in patients with solid tumors were taken into account. Results: After screening and eligibility assessment, a total of 17 clinical trials involving 10,500 patients were selected for the final meta-analysis. The incidence risk of peripheral neuropathy for all grade was significantly lower in the PD-1/PD-L1 inhibitor group than that of the control group, either monotherapy (OR = 0.08, 95%CI:[0.03, 0.19]) or chemotherapy (OR = 0.05, 95%CI:[0.03, 0.11]). Similar incidence trend could also be seen for the incidence risk of grade 3-5 peripheral neuropathy. When PD-1/PD-L1 inhibitors were used in combination with chemotherapy, the incidence risk of peripheral neuropathy was higher than in the control chemotherapy group, whether it was all-grade (OR = 1.22, 95%CI:[1.00, 1.49]) or grade 3-5 degree (OR = 1.74, 95%CI:[1.03, 2.92]). Conclusion: Compared with chemotherapy, incidence risk of peripheral neuropathy related to PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while PD-1/PD-L1 inhibitor increased the incidence risk of peripheral neuropathy when it was combined with chemotherapy.

Targeted therapy with anlotinib for patient with recurrent glioblastoma: A case report and literature review.

RATIONALE: Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. The first choice for GBM is surgery, and followed by a combination of radiotherapy and chemotherapy. There are limited treatments for patients with recurrent GBM. Relapsed patients usually have a worse prognosis, and with a median survival time of <6 months. Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor that can inhibit tumor angiogenesis and inhibit tumor cell growth. This drug has been used to treat advanced lung cancer. PATIENT CONCERNS: We present a case of recurrent GBM was treated with anlotinib in this report. The patient was diagnosed with GBM in August 2016 and treated with surgery and temozolomide (TMZ) chemotherapy. She was diagnosed with recurrence in February 2017 following which she was treated with gamma knife and TMZ chemotherapy. In November 2017, the patient presented with decreased vision in left eye. She was given radiation and her left eye vision returned to normal after radiation. On May23, 2018, the patient reported a decrease in left visual acuity again. DIAGNOSES: Brain magnetic resonance imaging (MRI) showed progression of the disease, and the tumor invaded the left optic nerve. INTERVENTIONS: This patient was administer anlotinib 12 mg po qd (d1-14, 21days as a cycle). Three cycles anlotinib were given to this patient. OUTCOMES: The patient reported her left visual acuity increased over 10 days after first cycle of anlotinib treatment. MRI scan revealed tumor volume shrinks, especially the part that invades the left optic nerve shrinks significantly at 26 days after anlotinib treatment on August 11, 2018. However, the tumor progressed in 2 months after using of anlotinib. From the beginning of the application of anlotinib to death, her survival time was 110 days. LESSONS: Anlotinib treatment with mild side effects may be a new option for the patients with recurrent glioblastoma.

Methotrexate, doxorubicin, and cisplatinum regimen is still the preferred option for osteosarcoma chemotherapy: A meta-analysis and clinical observation.

BACKGROUND: We designed the study to investigate whether methotrexate, doxorubicin, and cisplatinum (MAP) chemotherapy strategy was still the preferred option for the survival of osteosarcoma patients. METHOD: We collected some trials of osteosarcoma to make a meta-analysis first. Then, we retrospectively collected data from 115 patients with osteosarcoma and performed further analysis to verify the impact of MAP regimen on the survival of patients. RESULTS: Seven studies including 3433 participants met the preliminary inclusion criteria. Meta-analysis of the 3-year disease-free survival (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 0.88-1.28; P = .52) and overall survival (OR = 1.21, 95% CI: 0.70-2.11; P = .54), 5-year disease-free survival (OR = 1.07, 95% CI: 0.87-1.30; P = .54) and overall survival (OR = 0.86, 95% CI: 0.65-1.12; P = .26), and mortality rate (OR = 0.90, 95% CI: 0.70-1.17; P = .44), showed no statistically significant differences. The most common grade 3/4 adverse events were neutropenia (498 [85.9%] patients in MAP vs 533 [93.3%] in MAP plus ifosfamide and etoposide, or other adjuvant therapy drugs [MAP]). MAP was associated with less frequent toxicities than MAP group with statistical significance in thrombocytopenia, febrile neutropenia, anemia, and hypophosphatemia. The same phenomenon could also be seen in the analysis of clinical data. CONCLUSION: MAP regimen remains the preferred option for osteosarcoma chemotherapy.