Publications by authors named "Jinming Yu"

492 Publications

Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging.

Radiat Oncol 2021 Jun 7;16(1):97. Epub 2021 Jun 7.

Department of Radiation Oncology, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao Road 6699, Jinan, 250117, Shandong, People's Republic of China.

Introduction: In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy.

Materials And Methods: The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model.

Results: Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: Y = 0.672 + 0.513X + 0.380X + 0.439X + 0.320X + 0.333X. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001).

Conclusion: ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-021-01819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186169PMC
June 2021

Prognostic Significance of SUVmax Combined With Lactate Dehydrogenase in Advanced Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Retrospective Study.

Front Oncol 2021 18;11:652312. Epub 2021 May 18.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Purpose: This research aims to investigate the predictive capacity of PET/CT quantitative parameters combined with haematological parameters in advanced lung cancer patients treated with immune checkpoint inhibitor (ICI) plus chemotherapy.

Methods: A total of 120 patients who underwent F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) were enrolled before therapy. The following parameters were calculated: the maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); total tumour volume (MTV) and total lesion glycolysis (TLG); and whole-body metabolic values (MTVwb, TLGwb, SUVmeanwb, and SUVmaxwb). Lactate dehydrogenase (LDH) levels, absolute neutrophil count, absolute platelet count, albumin levels and derived neutrophil to lymphocyte ratio (dNLR) were also computed. The associations between the variables and therapy outcome (evaluated by iRECIST) were analyzed.

Results: Based on iRECIST, 32 of 120 patients showed iPD, 43 iSD, 36 iPR and 9 iCR. Multivariate analysis found that SUVmax, MTVwb, LDH and absolute platelet count were associated with treatment response (P =0.015, P =0.005, P <0.001 and P =0.015, respectively). Kaplan-Meier survival analyses showed that SUVmax ≥11.42 and LDH ≥245 U/L were associated with shorter OS (P = 0.001 and P = 0.004, respectively). Multivariate Cox regression revealed that SUVmax and LDH alone were not correlated with survival prognosis (p>0.05), but the combination of SUVmax and LDH was independently associated with OS (P=0.015, P=0.001, respectively). The median survival time (MST) for the low (LDH<245 and SUVmax<11.42), intermediate(LDH<245 or SUVmax<11.42), and high(SUVmax≥11.42 and LDH≥245) groups was 24.10 months (95% CI: 19.43 to 28.77), 17.41 months (95% CI: 15.83 to 18.99), and 13.76 months (95% CI: 12.51 to 15.02), respectively.

Conclusion: This study identified that SUVmax plus LDH correlated with the survival outcome in patients with advanced lung cancer receiving PD-1/PD-L1 blockade plus chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.652312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171668PMC
May 2021

Downregulation of lncRNA XR_429159.1 Linked to Brain Metastasis in Patients With Limited-Stage Small-Cell Lung Cancer.

Front Oncol 2021 17;11:603271. Epub 2021 May 17.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

The purpose of this study was to identify aberrant long non-coding RNAs (lncRNAs) and explore the predictive value of lncRNA expression patterns on the risk of brain metastases (BMs) in patients with limited-stage small-cell lung cancer (SCLC). We executed an array of lncRNA and mRNA chip assays to examine the expression in peripheral blood mononuclear cells obtained from SCLC patients with BMs and compared the expression patterns against those from patients without BMs to identify lncRNAs associated with BMs. Validation was performed against clinical data to further confirm the relationship between lncRNAs and BM. Kaplan-Meier analysis was applied to estimate the cumulative incidence of BMs, and differences between the groups were analyzed using the log-rank test. The expression of 67 lncRNAs (27 upregulated and 40 downregulated) and 47 mRNAs (20 upregulated and 27 downregulated) was significantly different between the BM and non-BM groups (fold change ≥ 2.0, -value ≤ 0.05), based on the lncRNA and mRNA chip assays. Four lncRNAs were verified by quantitative real-time polymerase chain reaction (qRT-PCR) to confirm the accuracy of the microarray data, and the results of 11 patient pairs (11 patients with BM and 11 patients without BM) revealed that low LncRNA XR_429159.1 expression was a high-risk factor for BM. Further clinical data showed that the incidence of BM among 25 patients with low-level LncRNA XR_429159.1 expression was 31% at 1 year, compared with 14.3% among the 18 patients with high-level LncRNA XR_429159.1 expression ( = 0.035). Our present study identified the low-level expression of lncRNA XR_429159.1 as a high-risk factor among BM in patients with limited-stage SCLC. LncRNA XR_429159.1 is a critical molecule that regulates SCLC metastasis, involved in the neuroepithelial transforming gene 1 (NET1) pathway, and serum levels of this lncRNA are significantly associated with the risk of BM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.603271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166247PMC
May 2021

Induction of Humoral and Cellular Immunity by Intradermal Delivery of SARS-CoV-2 Nucleocapsid Protein Using Dissolvable Microneedles.

J Immunol Res 2021 17;2021:5531220. Epub 2021 May 17.

Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.

The nucleocapsid protein (NP) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains immunogenic epitopes that can induce cytotoxic T lymphocyte (CTL) against viral infection. This makes the nucleocapsid protein a suitable candidate for developing a vaccine against SARS-CoV-2 infection. This article reports the intradermal delivery of NP antigen using dissolvable microneedle skin patches that could induce both significant B cell and T cell responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5531220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130907PMC
June 2021

The landscape of bispecific T cell engager in cancer treatment.

Biomark Res 2021 May 26;9(1):38. Epub 2021 May 26.

Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

T cell-based immunotherapies have revolutionized treatment paradigms in various cancers, however, limited response rates secondary to lack of significant T-cell infiltration in the tumor site remain a major problem. To address this limitation, strategies for redirecting T cells to treat cancer are being intensively investigated, while the bispecific T cell engager (BiTE) therapy constitutes one of the most promising therapeutic approaches. BiTE is a bispecific antibody construct with a unique function, simultaneously binding an antigen on tumor cells and a surface molecule on T cells to induce tumor lysis. BiTE therapy represented by blinatumomab has achieved impressive efficacy in the treatment of B cell malignancies. However, major mechanisms of resistance to BiTE therapy are associated with antigen loss and immunosuppressive factors such as the upregulation of immune checkpoints. Thus, modification of antibody constructs and searching for combination strategies designed to further enhance treatment efficacy as well as reduce toxicity has become an urgent issue, especially for solid tumors in which response to BiTE therapy is always poor. In particular, immunotherapies focusing on innate immunity have attracted increasing interest and have shown promising anti-tumor activity by engaging innate cells or innate-like cells, which can be used alone or complement current therapies. In this review, we depict the landscape of BiTE therapy, including clinical advances with potential response predictors, challenges of treatment toxicity and resistance, and developments of novel immune cell-based engager therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40364-021-00294-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157659PMC
May 2021

A novel nomogram containing acute radiation esophagitis predicting radiation pneumonitis in thoracic cancer receiving radiotherapy.

BMC Cancer 2021 May 22;21(1):585. Epub 2021 May 22.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, 250117, Shandong, China.

Background: Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP.

Methods: Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0.

Results: A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP.

Conclusions: As an early index that can reflect the tissue's radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future's clinical work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08264-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140476PMC
May 2021

Computed Tomography-Based Delta-Radiomics Analysis for Discriminating Radiation Pneumonitis in Patients With Esophageal Cancer After Radiation Therapy.

Int J Radiat Oncol Biol Phys 2021 May 8. Epub 2021 May 8.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. Electronic address:

Purpose: Our purpose was to construct a computed tomography (CT)-based delta-radiomics nomogram and corresponding risk classification system for individualized and accurate estimation of severe acute radiation pneumonitis (SARP) in patients with esophageal cancer (EC) after radiation therapy.

Methods And Materials: Four hundred patients with EC were enrolled from 2 independent institutions and were divided into the training (n = 200) and validation (n = 200) cohorts. Eight hundred fifty radiomics features of lung were extracted from treatment planning images, including the positioning CT before radiation therapy (CT) and the resetting CT after receiving 40 to 45 Gy (CT). The longitudinal net changes in radiomics features from CT to CT were calculated and defined as delta-radiomics features. Least absolute shrinkage and selection operator algorithm was performed to features selection and delta-radiomics signature building. Integrating the signature with multidimensional clinicopathologic, dosimetric, and hematological predictors of SARP, a novel CT-based delta-radiomics nomogram was established according to multivariate analysis. The clinical application values of nomogram were both evaluated in the training and validation cohorts by concordance index, calibration curves, and decision curve analysis. Recursive partitioning analysis was used to generate a risk classification system.

Results: The delta-radiomics signature consisting of 24 features was significantly associated with SARP status (P < .001). Incorporating it with other high-risk factors, Subjective Global Assessment score, pulmonary fibrosis score, mean lung dose, and systemic immune inflammation index, the developed delta-radiomics nomogram showed increased improvement in SARP discrimination accuracy with concordance index of 0.975 and 0.921 in the training and validation cohorts, respectively. Calibration curves and decision curve analysis confirmed the satisfactory clinical feasibility and utility of nomogram. The risk classification system displayed excellent performance on identifying SARP occurrence (P < .001).

Conclusions: The delta-radiomics nomogram and risk classification system as low-cost and noninvasive means exhibited superior predictive accuracy and provided individualized probability of SARP stratification for patients with EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2021.04.047DOI Listing
May 2021

A preclinical study: correlation between PD-L1 PET imaging and the prediction of therapy efficacy of MC38 tumor with Ga-labeled PD-L1 targeted nanobody.

Aging (Albany NY) 2021 04 27;13(9):13006-13022. Epub 2021 Apr 27.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250017, P.R. China.

Although immunotherapy has achieved great clinical success in clinical outcomes, especially the anti-PD-1 or anti-PD-L1 antibodies, not all patients respond to anti-PD-1 immunotherapy. It is urgently required for a clinical diagnosis to develop non-invasive imaging meditated strategy for assessing the expression level of PD-L1 in tumors. In this work, a Ga-labeled single-domain antibody tracer, Ga-NOTA-Nb109, was designed for specific and noninvasive imaging of PD-L1 expression in an MC38 tumor-bearing mouse model. Comprehensive studies including Positron Emission Tomography (PET), biodistribution, blocking studies, immunohistochemistry, and immunotherapy, have been performed in differences PD-L1 expression tumor-bearing models. These results revealed that Ga-NOTA-Nb109 specifically accumulated in the MC38-hPD-L1 tumor. The content of this nanobody in MC38 hPD-L1 tumor and MC38 Mixed tumor was 8.2 ± 1.3, 7.3 ± 1.2, 3.7 ± 1.5, 2.3 ± 1.2%ID/g and 7.5 ± 1.4, 3.6 ± 1.7, 1.7 ± 0.6, 1.2 ± 0.5%ID/g at 0.5, 1, 1.5, 2 hours post-injection, respectively. Ga-NOTA-Nb109 has the potential to further noninvasive PET imaging and therapy effectiveness assessments based on the PD-L1 status in tumors. To explore the possible synergistic effects of immunotherapy combined with chemotherapy, MC38 xenografts with different sensitivity to PD-L1 blockade were established. In addition, we found that PD-1 blockade also had efficacy on the PD-L1 knockout tumors. RT-PCR and immunofluorescence analysis were used to detect the expression of PD-L1. It was observed that both mouse and human PD-L1 expressed among three types of MC38 tumors. These results suggest that PD-L1 on tumor cells affect the efficacy, but it on host myeloid cells might be essential for checkpoint blockade. Moreover, anti-PD-1 treatment activates tumor-reactive CD103 CD39 CD8+T cells (TILs) in tumor microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148448PMC
April 2021

Feasibility of semiquantitative 18F-fluorodeoxyglucose PET/computed tomography in patients with advanced lung cancer for interim treatment evaluation of combining immunotherapy and chemotherapy.

Nucl Med Commun 2021 Apr 21. Epub 2021 Apr 21.

Department of Clinical Medicine, Weifang Medical University, Weifang Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences Department of Radiation Oncology, School of Medicine, Shandong University, Jinan, Shandong, China.

Objective: This study aimed to investigate the prognosis value of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in advanced lung cancer patients with immunotherapy combined with chemotherapy.

Methods: Fifty-one advanced lung cancer patients were included in this retrospective study, who underwent 18F-FDG PET/CT imaging before four cycles of immunotherapy combined with chemotherapy at our institution between January 2018 and January 2020. The following PET/CT parameters were calculated: standardized uptake value SUVmax, SUVmean, SUVpeak, SUVsd, metabolic tumor volume (MTV), total lesion glycolysis (TLG), MTV25%, MTV42%, MTV50%, MTV75%, global lung glycolysis (GLG), target-to-background ratio (TBR), SUVpeakwb, MTVwb, TLGwb, SUVmeanwb, SUVmaxwb. Logistics regression analyses were used for assessing the association between baseline metabolic parameters and response to treatment. Kaplan-Meier estimator curves and the log-rank test were constructed for survival analyses.

Results: According to RECIST, nine patients (18%) showed partial response, 25 (49%) had SD, and 17 (33%) had progressive disease. The mean ± SD of SUVmax, SUVpeak, MTV were lower in clinical benefit (CB) group than no-clinical benefit (no-CB) group (all P < 0.05). Median PFS was 3.7 months in no-CB group and 9.9 months in CB group (P < 0.001). Multivariate logistic analysis indicated that SUVmax and histology were independent factors significantly related to the evaluation of therapeutic efficiency. Furthermore, SUVmax is an independent predictor of efficacy in non-small cell lung cancer.

Conclusion: SUVmax can be used to predict interim treatment response of immunotherapy combination with chemotherapy for advanced lung cancer. Moreover, the combination of SUVmax and histology may predict treatment response with acceptable reliability. However, a large prospective multicenter trial is still needed to examine the above finding for lacking limited evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNM.0000000000001428DOI Listing
April 2021

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review.

Front Immunol 2021 30;12:627197. Epub 2021 Mar 30.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.

Background: The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.

Methods: An electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.

Results: Eleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.

Conclusion: Most AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.627197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042254PMC
March 2021

Associations between glucocorticoids, antiphospholipid antibodies and femur head necrosis in patients with SLE: a directed acyclic graph-based multicentre study.

Ther Adv Musculoskelet Dis 2021 29;13:1759720X211002677. Epub 2021 Mar 29.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, NO 600, Yishan Road, Xuhui district, Shanghai 200233, China.

Background: Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE.

Methods: We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis.

Results: Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0-1.1; GC therapy duration (3-5 years: aOR 3.3, 95% CI 1.4-7.8; >5 years: aOR 8.0, 95% CI 3.3-19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9-10.1); positive aPLs (aOR 2.8, 95% CI 1.4-5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4-19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82-0.94).

Conclusion: Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1759720X211002677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010842PMC
March 2021

Corrigendum: Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect?

Front Immunol 2021 23;12:649620. Epub 2021 Mar 23.

Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China.

[This corrects the article DOI: 10.3389/fimmu.2018.02916.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.649620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023273PMC
March 2021

Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study.

Front Oncol 2021 15;11:628124. Epub 2021 Mar 15.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Pre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC.

Methods: Sixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1-14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival.

Results: With a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3-4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.

Conclusion: Anti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.628124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005709PMC
March 2021

The role of exosomes in tumour immunity under radiotherapy: eliciting abscopal effects?

Biomark Res 2021 Mar 31;9(1):22. Epub 2021 Mar 31.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.

As a curative treatment of localized tumours or as palliative control, radiotherapy (RT) has long been known to kill tumour cells and trigger the release of proinflammatory factors and immune cells to elicit an immunological response to cancer. As a crucial part of the tumour microenvironment (TME), exosomes, which are double-layered nanometre-sized vesicles, can convey molecules, present antigens, and mediate cell signalling to regulate tumour immunity via their contents. Different contents result in different effects of exosomes. The abscopal effect is a systemic antitumour effect that occurs outside of the irradiated field and is associated with tumour regression. This effect is mediated through the immune system, mainly via cell-mediated immunity, and results from a combination of inflammatory cytokine cascades and immune effector cell activation. Although the abscopal effect has been observed in various malignancies for many years, it is still a rarely identified clinical event. Researchers have indicated that exosomes can potentiate abscopal effects to enhance the effects of radiation, but the specific mechanisms are still unclear. In addition, radiation can affect exosome release and composition, and irradiated cells release exosomes with specific contents that change the cellular immune status. Hence, fully understanding how radiation affects tumour immunity and the interaction between specific exosomal contents and radiation may be a potential strategy to maximize the efficacy of cancer therapy. The optimal application of exosomes as novel immune stimulators is under active investigation and is described in this review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40364-021-00277-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011088PMC
March 2021

Immunotherapy for recurrent glioblastoma: practical insights and challenging prospects.

Cell Death Dis 2021 Mar 19;12(4):299. Epub 2021 Mar 19.

Departmenlt of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.

Glioblastoma (GB) is the most common high-grade intracranial malignant tumor with highly malignant biological behavior and a high recurrence rate. Although anti-PD-1/PD-L1 antibodies have achieved significant survival benefits in several kinds of solid tumors, the phase III clinical trial Checkmate 143 demonstrated that nivolumab, which targets PD-1, did not achieve survival benefits compared with bevacizumab in recurrent glioblastoma (rGB) patients. Nevertheless, neoadjuvant anti-PD-1 therapy followed by surgery and adjuvant anti-PD-1 therapy could effectively activate local and systemic immune responses and significantly improve the OS of rGB patients. Furthermore, several studies have also confirmed the progress made in applying tumor-specific peptide vaccination or chimeric antigen receptor-T (CAR-T) cell therapy to treat rGB patients, and successes with antibodies targeting other inhibitory checkpoints or costimulatory molecules have also been reported. These successes inspired us to explore candidate combination treatments based on anti-PD-1/PD-L1 antibodies. However, effective predictive biomarkers for clinical efficacy are urgently needed to avoid economic waste and treatment delay. Attempts to prolong the CAR-T cell lifespan and increase T cell infiltration through engineering techniques are addressing the challenge of strengthening T cell function. In this review, we describe the immunosuppressive molecular characteristics of rGB; clinical trials exploring anti-PD-1/PD-L1 therapy, tumor-specific peptide vaccination, and CAR-T cell therapy; candidate combination strategies; and issues related to strengthening T cell function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03568-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979733PMC
March 2021

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer.

J Immunother Cancer 2021 Mar;9(3)

Department of Oncology, Chelsea and Westminster Hospital, London, UK.

Background: Atezolizumab treatment improves survival, with manageable safety, in patients with previously treated advanced/metastatic non-small cell lung cancer. The global phase III/IV study TAIL (NCT03285763) was conducted to evaluate the safety and efficacy of atezolizumab monotherapy in a clinically diverse population of patients with previously treated non-small cell lung cancer, including those not eligible for pivotal trials.

Methods: Patients with stage IIIB/IV non-small cell lung cancer whose disease progressed after 1-2 lines of chemotherapy were eligible for this open-label, single-arm, multicenter study, including those with severe renal impairment, an Eastern Cooperative Oncology Group performance status of 2, prior anti-programmed death 1 (PD-1) therapy, and autoimmune disease. Atezolizumab was administered intravenously (1200 mg every 3 weeks). Coprimary endpoints were treatment-related serious adverse events and immune-related adverse events.

Results: 619 patients enrolled and 615 received atezolizumab. At data cutoff, the median follow-up was 12.6 months (95% CI 11.9 to 13.1). Treatment-related serious adverse events occurred in 7.8% and immune-related adverse events in 8.3% of all patients and as follows, respectively, in these subgroups: renal impairment (n=78), 11.5% and 12.8%; Eastern Cooperative Oncology Group performance status of 2 (n=61), 14.8% and 8.2%; prior anti-PD-1 therapy (n=39), 5.1% and 7.7%; and autoimmune disease (n=30), 6.7% and 10.0%. No new safety signals were reported. In the overall population, the median overall survival was 11.1 months (95% CI 8.9 to 12.9), the median progression-free survival was 2.7 months (95% CI 2.1 to 2.8) and the objective response rate was 11%.

Conclusions: This study confirmed the benefit-risk profile of atezolizumab monotherapy in a clinically diverse population of patients with previously treated non-small cell lung cancer. These safety and efficacy outcomes may inform treatment decisions for patients generally excluded from checkpoint inhibitor trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-001865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978274PMC
March 2021

A nomogram for the predicting of survival in patients with esophageal squamous cell carcinoma undergoing definitive chemoradiotherapy.

Ann Transl Med 2021 Feb;9(3):233

Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Definitive chemoradiotherapy (dCRT) is widely accepted for esophageal squamous cell carcinoma (ESCC), although the outcomes can vary. Therefore, we aimed to develop a nomogram for the pre-treatment prediction of survival after dCRT for ESCC.

Methods: This retrospective study evaluated 204 patients (169 patients in a primary cohort and 35 patients in a validation cohort) who received dCRT for ESCC between July 2013 and June 2017.

Results: Pre-treatment parameters that predicted long-term survival in this setting were body mass index (BMI), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), wall thickness, concurrent chemoradiotherapy, radiotherapy modality, and American Joint Committee on Cancer (AJCC) stage. The nomogram incorporated these factors and provided C-index values of 0.691 [95% confidence interval (CI): 0.641-0.740] in the primary cohort and 0.816 (95% CI: 0.700-0.932) in the validation cohort. The calibration curve analysis revealed that the nomogram had good ability to predict 2-year progression-free survival (PFS). The nomogram also performed better than the AJCC staging system by the C-index values (0.691 . 0.560) and the area under the curve values (0.702 . 0.576). Decision curve analysis (DCA) also indicated that the nomogram had better clinical utility.

Conclusions: These results suggest that pre-treatment parameters may help predict the efficacy of dCRT for ESCC. Furthermore, as the nomogram provided better prognostic accuracy than the AJCC staging system, the nomogram may be useful in clinical practice for prognostication among patients who are going to receive dCRT for ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-1460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940874PMC
February 2021

Estimating Survival in Patients with Non-Small-Cell Lung Cancer and Brain Metastases: A Verification of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA).

Onco Targets Ther 2021 2;14:1623-1631. Epub 2021 Mar 2.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.

Purpose: A new tool based on clinical characteristics and molecular factors (Lung-molGPA) was developed to predict the survival of patients with non-small-cell lung cancer but was has not been validated. This study aims to validate the feasibility of the Lung-molGPA in NSCLC.

Patients And Methods: Patients diagnosed NSCLC between Feb 2012 and July 2018 were retrospectively reviewed and scored using the Lung-molGPA tool to compare clinical outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox regression analyses.

Results: A total of 618 patients (524 adenocarcinoma [ADC], 94 non-adenocarcinoma [non-ADC]) were collected. For all patients, the median survival time (MST) was 33.0 months (33.6 and 28 months in the ADC and non-ADC groups, respectively; = 0.21). In the ADC group, the MST for patients with a Lung-molGPA score of 3.5 to 4 was more than 4 years, while the MST was only 25 months in patients scoring 0-1, 30.0 months in patients scoring 1.5-2, and 35.0 months for scores of 2.5-3 ( = 0.048). For the non-ADC group, the MST for scores 0-1, 1.5-2, 2.5-3, and 3.5-4 were 12.0, 20.2, 29.0, and 33.0 months, respectively ( = 0.017).

Conclusion: Our findings provided evidence validating the Lung-molGPA score as a useful tool to determine treatment strategies and to predict prognosis. The model is still exploratory and needs to be evaluated further in combination with additional prognostic markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S288928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936709PMC
March 2021

Case Report: Transformation From Cold to Hot Tumor in a Case of NSCLC Neoadjuvant Immunochemotherapy Pseudoprogression.

Front Immunol 2021 17;12:633534. Epub 2021 Feb 17.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute Affiliated to Shandong University, Jinan, China.

A 56-year-old male was diagnosed with right lung upper lobe squamous cancer with right hilar and mediastinum lymph node metastasis. After four cycles of neoadjuvant immunochemotherapy, reexamination by computed tomography showed progressive disease of the primary lesion. Then, the patient underwent a right lung upper lobectomy, and hilar and mediastinum lymph node dissection. Surgical pathology showed a partial response to immunochemotherapy. Single-cell RNA sequencing was used to characterize the infiltrating immune cell atlas after neoadjuvant immunochemotherapy; the most common infiltrating immune cell types were cytotoxic CD8+ T cells, monocyte-derived dendritic cells, and macrophages. Imaging mass cytometry revealed a transformation from cold to hot tumor after neoadjuvant immunochemotherapy. In this case study, we are the first to report a case of neoadjuvant immunochemotherapy pseudoprogression, proved by surgical pathology, single-cell RNA sequencing, and imaging mass cytometry. Both single-cell RNA sequencing and imaging mass cytometry revealed an activated immune microenvironment after neoadjuvant immunochemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.633534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925896PMC
February 2021

The Predictive Value of Tumor Volume and Its Change on Short-Term Outcome for Esophageal Squamous Cell Carcinoma Treated With Radiotherapy or Chemoradiotherapy.

Front Oncol 2020 1;10:586145. Epub 2021 Feb 1.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Objectives: To investigate the tumor volume and its change on short-term outcome in esophageal squamous cell carcinoma (ESCC) patients who underwent definitive radiotherapy or chemoradiotherapy.

Methods And Materials: All data were retrospectively collected from 418 ESCC patients who received radiotherapy or chemoradiotherapy at our institution between 2015 and 2019. Short-term outcome using the treatment response evaluation was assessed according to the RECIST 1.1. The tumor volume change rate (TVCR) was defined as follows: TVCR {1 [gross tumor volume (GTV) at shrinking irradiation field planning)]/(GTV at the initial treatment planning)} ×100%. Chi square test was used to compare the clinic characteristics in different TVCR groups, and the difference between initial GTV (GTVi) and shrinking GTV (GTVs) was compared using Wilcoxon's sign rank test. Logistic regression analysis and Spearman correlation was performed.

Results: There was a significant decrease in GTVi compared to GTVs ( < 0.001). In univariate analysis, age, cT-stage, TNM stage, treatment modality, GTVi, and TVCR were associated with short-term outcome (all 0.05). In multivariate analysis, gender and TVCR were statistically significant ( = 0.010, <0.001) with short-term outcome, and the combined predictive value of gender and TVCR exceeded that of TVCR (AUC, 0.876 0.855).

Conclusions: TVCR could serve to forecast short-term outcome of radiotherapy or chemoradiotherapy in ESCC. It was of great significance to guide the individualized treatment of ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.586145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901880PMC
February 2021

Overlap time is an independent risk factor of radiation pneumonitis for patients treated with simultaneous EGFR-TKI and thoracic radiotherapy.

Radiat Oncol 2021 Feb 23;16(1):41. Epub 2021 Feb 23.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute Affiliated to Shandong University, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, Shandong Province, China.

Background: The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT.

Patients And Methods: We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses.

Results: Of the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07-13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP.

Conclusions: Grade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-021-01765-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903606PMC
February 2021

Sleep Status and the Associated Factors: A Large Cross-Sectional Study in Shaanxi Province, China.

Int J Environ Res Public Health 2021 01 30;18(3). Epub 2021 Jan 30.

School of Public Health, Fudan University, Shanghai 200032, China.

This study aimed at investigating the sleep status and its associated factors in Shaanxi province, China. We conducted a cross-sectional study among 11,399 subjects in Shaanxi Province, China. Data were collected via spot field questionnaire surveys. The contents included demographic characteristics, sleep status, lifestyles, disease history and other associated factors. Logistic regression analysis was used to estimate the effect of associated factors on sleep quality. A total of 11,036 subjects were included in the final analysis. In total, 12.8% of the participants had bad or very bad sleep. In the last month, 8.4% of the participants had difficulty in initiating sleep, 7.6% of the participants had difficulty in maintaining sleep, 8.8% of the participants suffered from awakening earlier and 10.3% of the participants had the problem of feeling sleepy during the day ≥3 times per week. Poorer sleep quality was associated with being female, being unmarried or without cohabiting with a boyfriend/girlfriend, being divorced or widowed, heart diseases, musculoskeletal diseases, concerns about their own health, drinking alcohol, taking hypnotics, and a longer daily screen time. Better sleep quality was associated with medium education level, high family monthly income, good self-reported health status, and having breakfast regularly. In conclusion, more than one in ten people did not sleep well and suffered from different sleep problems in Shaanxi, China. Sleep quality was associated with sex, marital status, educational level, family monthly income, heart disease, musculoskeletal diseases, degree of concerning about their own health, self-reported health status, drinking alcohol, having breakfast, taking hypnotics and daily screen time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18031250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908339PMC
January 2021

Use of Chemoradiotherapy as a Treatment Option for Patients with Limited-Stage Primary Small Cell Carcinoma of the Esophagus.

Cancer Manag Res 2021 25;13:613-623. Epub 2021 Jan 25.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China.

Purpose: Currently, there are no standard treatments for primary small cell carcinoma of the esophagus (PSCCE), particularly in cases of limited-stage disease. This retrospective study aimed to assess the treatment strategies and the relevant prognostic factors of limited-stage PSCCE (LS-PSCCE).

Patients And Methods: We retrospectively evaluated 129 patients with LS-PSCCE between June 2009 and December 2018. The χ2 test was performed to examine the frequencies between different groups. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS).

Results: Through a median follow-up of 23 months, the median OS of all patients was 25.0 months and the median recurrence-free survival (RFS) was 15.0 months. Univariate and multivariate analyses showed that alcohol abuse (=0.046) and TNM stage (<0.001) were independent prognostic factors. There was no significant difference in OS and RFS rates between the patients treated with chemoradiotherapy (CRT) and those treated with surgery and chemotherapy with or without radiotherapy (S+CT±RT) (>0.05). Patients who received concurrent CRT had better OS and RFS than those who received sequential CRT (<0.05). Postoperative adjuvant RT for high-risk patients can further improve the local control rate but has no significant effect on OS.

Conclusion: LS-PSCCE patients treated with CRT had similar OS and RFS compared to those treated with S+CT±RT. This study shows that concurrent CRT confers a survival advantage for patients with LS-PSCCE compared to those with sequential CRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S278914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846826PMC
January 2021

CD155 Overexpression Correlates With Poor Prognosis in Primary Small Cell Carcinoma of the Esophagus.

Front Mol Biosci 2020 7;7:608404. Epub 2021 Jan 7.

Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.

CD155/TIGIT overexpression has been detected in various human malignancies; however, its expression status in primary small cell carcinoma of the esophagus (PSCCE) and its prognostic significance remain unclear. In this study, we aimed to explore the expression and prognostic value of CD155 and TIGIT in PSCCE. We detected CD155 and TIGIT expression in 114 cases of PSCCE using immunohistochemistry (IHC) and evaluated their relationship with the clinicopathological characteristics and survival of the patients. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. Nomogram performance was assessed via the concordance index (C-index) and calibration plots. Decision curve analysis (DCA) was performed to evaluate the net benefit of the nomogram. We found that CD155 and TIGIT were overexpressed in PSCCE tissues, CD155 expression correlated positively with TIGIT ( < 0.001) and was significantly associated with tumor size, T stage, distant metastasis, TNM stage, and Ki-67 score. TIGIT expression was also significantly associated with T stage, distant metastasis, and TNM stage. Patients with high CD155 and TIGIT expression had a significantly shorter overall survival (OS) and progression-free survival (PFS), while the multivariate model showed that CD155 expression and the therapeutic strategy are independent prognostic factors for PSCCE. In the validation step, OS was shown to be well-calibrated (C-index = 0.724), and a satisfactory clinical utility was proven by DCA. In conclusion, our findings revealed that CD155 and TIGIT are highly expressed in patients with PSCCE and are associated with shorter OS and PFS, supporting their role as prognostic biomarker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2020.608404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817973PMC
January 2021

Pre-radiotherapy lymphocyte count and platelet-to-lymphocyte ratio may improve survival prediction beyond clinical factors in limited stage small cell lung cancer: model development and validation.

Transl Lung Cancer Res 2020 Dec;9(6):2315-2327

Department of Radiation Oncology, Seidman Cancer Center, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

Background: Few small sample size studies have reported lymphocyte count was prognostic for survival in small-cell lung cancer (SCLC). This study aimed to validate this finding, to build prediction model for overall survival (OS) and to study whether novel models that combine lymphocyte-related variables can predict OS more accurately than a conventional model using clinical factors alone in a large cohort of limited-stage SCLC patients.

Methods: This study enrolled 544 limited-stage SCLC patients receiving definitive chemo-radiation with pre-radiotherapy lymphocyte-related variables including absolute lymphocyte count (ALC), platelet-to-lymphocyte ratio (P/L ratio), neutrophil-to-lymphocyte ratio (N/L ratio), and lymphocyte-to-monocyte ratio (L/M ratio). The primary endpoint was OS. These patients were randomly divided into a training dataset (n=274) and a validation dataset (n=270). Multivariate survival models were built in the training dataset, and the performance of these models were further tested in the validation dataset using the concordance index (C-index).

Results: The median follow-up time was 36 months for all patients. In the training dataset, univariate analysis showed that ALC (P=0.020) and P/L ratio (P=0.023) were significantly correlated with OS, while L/M ratio (P=0.091) and N/L ratio (P=0.436) were not. Multivariate modeling demonstrated the significance of ALC (P=0.063) and P/L ratio (P=0.003), and the improvement for OS prediction in combined models with the addition of ALC (C-index =0.693) or P/L ratio (C-index =0.688) over the conventional model (C-index =0.679). The validation dataset analysis confirmed a modest improvement of C-index with the addition of ALC or P/L ratio. All these models showed reasonable discriminations and calibrations.

Conclusions: This study validated the significant value of pre-radiotherapy ALC and P/L ratio on OS in limited-stage SCLC. The combined model with ALC or P/L ratio showed additional OS prediction values than the conventional model with clinical factors alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr-20-666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815357PMC
December 2020

Intrinsic dialogues between the two hemispheres in middle-aged male alcoholics: a resting-state functional MRI study.

Neuroreport 2021 02;32(3):206-213

Departments of Radiology.

Background: The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics.

Methods: Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis.

Results: We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems.

Conclusions: Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNR.0000000000001579DOI Listing
February 2021

Anti-PD-(L)1 immunotherapy for brain metastases in non-small cell lung cancer: Mechanisms, advances, and challenges.

Cancer Lett 2021 Apr 13;502:166-179. Epub 2021 Jan 13.

Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address:

The brain is one of the most common metastatic sites in non-small cell lung cancer (NSCLC), which is associated with an extremely poor prognosis. Despite the availability of several therapeutic options, the treatment efficacy remains unsatisfactory for NSCLC brain metastases. Anti-programmed cell death-1 (PD-1) and its ligand (PD-L1) monoclonal antibodies have reshaped therapeutic strategies in advanced NSCLC. Preliminary evidence has shown that anti-PD-(L)1 monotherapy is also effective in NSCLC patients with brain metastases. However, the traditional view asserted that these therapeutic antibodies were incapable of crossing the blood-brain barrier (BBB) with large molecular size, thus most patients with brain metastases were excluded from most studies on anti-PD-(L)1 immunotherapy. Therefore, the efficacy and its mechanisms of action of anti-PD-(L)1 immunotherapy against brain metastases in NSCLC have not been clarified. In this review, we will survey the underlying mechanisms and current clinical advances of anti-PD-(L)1 immunotherapy in the treatment of brain metastases in NSCLC. The trafficking of activated cytotoxic T cells that are mainly derived from the primary tumor and deep cervical lymph nodes is critical for the intracranial response to anti-PD-(L)1 immunotherapy, which is driven by interferon-γ (IFN-γ). Additionally, promising combined strategies with the rationale in the treatment of brain metastases will be presented to provide future directions for clinical study design. Several significant challenges in the preclinical and clinical studies of brain metastases, as well as potential solutions, will also be discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2020.12.043DOI Listing
April 2021

Carbon-based nanomaterials for viral infection management.

Biomicrofluidics 2021 Jan 4;15(1):011501. Epub 2021 Jan 4.

Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.

Carbon-based nanomaterials such as graphene and nanodiamonds have demonstrated impressive physical and chemical properties, such as remarkable strength, corrosion resistance, and excellent electrical and thermal conductivity, and stability. Because of these unique characteristics, carbon nanomaterials are explored in a wide range of fields, including the diagnosis and treatment of viruses. As there are emerging concerns about the control of virus including Middle East respiratory syndrome virus (MERS), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this review highlights the recent development of carbon based-nanomaterials for the management of viral infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0032427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785324PMC
January 2021

Development of EGFR TKIs and Options to Manage Resistance of Third-Generation EGFR TKI Osimertinib: Conventional Ways and Immune Checkpoint Inhibitors.

Front Oncol 2020 18;10:602762. Epub 2020 Dec 18.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have been first-line therapy in the treatment of non-small cell lung cancer (NSCLC) harboring sensitive mutations. Progression inevitably happens after 10-14 months of first- or second-generation EGFR TKIs treatment for acquired resistance. Owing to the successful identification of T790M, third-generation EGFR TKIs such as osimertinib were developed to target such resistance mutation. Nowadays, osimertinib has shown its efficacy both in first-line and second-line after resistance to previous generations of TKI treatment of -mutant NSCLC. However, drug resistance also emerges on third-generation EGFR TKIs. Multiple mechanisms of acquired resistance have been identified, and some novel strategies were reported to overcome third-generation TKI resistance. Immune checkpoint inhibitors (ICIs) have dramatically changed the prognosis of selected patients. For patients with -addicted metastatic NSCLC, ICIs have also revealed a potential role. In this review, we will take stock of mechanisms of acquired resistance to third-generation TKIs and discuss current challenges and future perspectives in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.602762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775519PMC
December 2020

GINS2 attenuates the development of lung cancer by inhibiting the STAT signaling pathway.

J Cancer 2021 1;12(1):99-110. Epub 2021 Jan 1.

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 272173, China.

GINS complex subunit 2 (GINS2) controls DNA replication. GINS2 expression is upregulated in several kinds of aggressive tumors. However, the effect of GINS2 in lung cancer remains unclear. We performed TCGA database analysis to confirm the clinical significance of GINS2 in lung cancer. After silencing GINS2 in A549 cells, we performed MTT assays, flow cytometry assays, colony formation assays, cell cycle analyses and RNA sequence analysis to elucidate the effect of GINS2 on lung cancer. Moreover, we assessed tumor growth and analyzed body fluorescence in mice as a measure of tumor burden. The TCGA database analysis demonstrated that GINS2 mRNA and protein was highly expressed in three kinds of lung cancer tissues. Subsequently, knockdown of GINS2 inhibited cell proliferation, colony formation, cell cycle arrest and apoptosis in A549 cells. On the other hand, we also investigated the effect of GINS2 on tumor formation in vivo. The analysis of nude mouse tumors showed that the tumor volume and weight of shGINS2 mice were significantly smaller than those of the control mice. To reveal the mechanism of GINS2 in lung cancer, we collected A549 cells with GINS2 knockdown to examine the downstream gene expression changes. The results showed that STAT1 and STAT2 mRNA and protein expression were significantly upregulated after GINS2 knockdown in A549 cells. Our results suggest that GINS2 inhibits the proliferation of lung cancer cells by inhibiting the STAT signaling pathway, which may be a potential biomarker for the diagnosis or prognosis of lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.46744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738824PMC
January 2021