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Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.
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Objective:To investigate the effects of temozolomide combined with γ-fractional stereotactic radiotherapy on the expression of S100B and exosomal microRNA-330(miR-330) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases.Methods:A total of 82 patients with NSCLC brain metastases from February 2018 to October 2020 were selected prospectively, and they were divided into the control group and the observation group by the random number table method, each with 41 patients. The control group received γ-fractional stereotactic radiotherapy, and the observation group received temozolomide on the basis of the control group. The therapeutic efficacy and prognosis of the two groups were compared, and the levels of serum myelin basic protein (MBP), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) levels, liver and kidney function indexes, serum S100B, carcinoembryonic antigen (CEA), exosomal miR-330 were compared between the two groups before and after the treatment. The neurologic function of the patients were evaluated by Mini Mental State Examination (MMSE) and National Institutes Health Stroke Scale (NIHSS).Results:The total remission rate in the observation group was higher than that in the control group: 65.85%(27/41) vs. 34.15%(14/41), there was statistical differences ( χ2 = 8.24, P<0.05), but the disease control rate between the two groups had no significant difference ( P>0.05). After the treatment, the levels of serum MBP, GFAP and NSE in the observation group were lower than those in the control group: (10.13 ± 2.07) μg/L vs. (14.39 ± 2.58) μg/L, (0.57 ± 0.12) μg/L vs. (0.75 ± 0.16) μg/L, (5.09 ± 1.16) μg/L vs. (7.17 ± 1.35) μg/L, there were statistical differences ( P<0.05). The levels alanine aminotransferase, blood urea nitrogen and serum creatinine after treatment between the two groups had no significant differences ( P>0.05). After the treatment, the NIHSS scores in the observation group was lower than that in the control group, MMSE scores was higher than that in the control group: (4.16 ± 0.52) scores vs. (4.73 ± 0.44) scores, (22.07 ± 2.51) scores vs. (20.68 ± 2.19) scores, there were statistical differences ( P<0.05). After treatment, the serum levels of S100B and CEA in the observation group were lower than those in the control group, and the expression of exosomal miR-330 was higher than that in the control group: (62.37 ± 10.54) mg/L vs. (68.05 ± 9.39) mg/L, (12.61 ± 2.05) μg/L vs.(14.08 ± 1.97) μg/L, 0.49 ± 0.12 vs. 0.42 ± 0.05, there were statistical differences ( P<0.05). The median survival time in the observation group was 14.6 months, while that in the control group was 11.50 months. There were no significant differences in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Treatment with temozolomide combined with γ-fractional stereotactic radiotherapy for NSCLC patients with brain metastases can improve the therapeutic efficacy, neurological function, inhibit the expression of serum S100B, CEA and exosomal miR-330, and prolong the survival time of patients.
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Purpose To explore the value of three-dimensions densely connected convolutional networks(3D-DenseNet)in the differential diagnosis of high-grade gliomas(HGGs)and single brain metastases(BMs)via MRI,and to compare the diagnostic performance of models built with different sequences.Materials and Methods T2WI and T1WI contra-enhanced(T1C)imaging data of 230 cases of HGGs and 111 cases of BMs confirmed by surgical pathology in Lanzhou University Second Hospital from June 2016 to June 2021 were retrospectively collected,and the volume of interest under the 3D model was delineated in advance as the input data.All data were randomly divided into a training set(n=254)and a validation set(n=87)in a ratio of 7∶3.Based on the 3D-DenseNet,T2WI,T1C and two sequence fusion prediction models(T2-net,T1C-net and TS-net)were constructed respectively.The predictive efficiency of each model was evaluated and compared by the receiver operating characteristic curve,and the predictive performance of models built with different sequences were compared.Results The area under curve(AUC)of T1C-net,T2-net and TS-net in the training and validation sets were 0.852,0.853,0.802,0.721,0.856 and 0.745,respectively.The AUC and accuracy of the validation set of T1C-net were significantly higher than those of T2-net and TS-net,respectively,and the AUC and accuracy of the validation set of TS-net were significantly higher than those of T2-net.There was a significant difference between T1C-net and T2-net models(P<0.05),while there were no statistical differences between the models of TS-net and T2-net,T1C-net and TS-net(P>0.05).The T1C-net model based on 3D-DenseNet had the best performance,the accuracy of the validation set was 80.5%,the sensitivity was 90.9%,the specificity was 62.5%.Conclusion The 3D-DenseNet model based on MRI conventional sequence has better diagnostic performance,and the model built by T1C-net sequence has better performance in differentiating HGGs and BMs.Deep learning models can be a potential tool to identify HGGs and BMs and to guide the clinical formulation of precise treatment plans.
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Objective:To evaluate the accuracy of the optical surface imaging system (OSI) using stereotactic radiosurgery (SRS) algorithm in single-center non-coplanar treatment of multiple brain metastases.Methods:Data of phantom and 15 patients with multiple brain metastases who underwent single-center non-coplanar radiotherapy in West China Hospital of Sichuan University from February to April 2022 were retrospectively analyzed. kV/MV and OSI imaging were used for imaging of the patients and phantoms under the same non-coplanar couch angle, respectively. The accuracy of OSI imaging of the phantoms and patients was evaluated using kV/MV imaging as reference image. The difference between the OSI and kV/MV systems is defined as accuracy, and the percentage of the absolute difference ≤1.00 mm in the translational direction or ≤0.50° in the rotational direction is defined as the threshold pass rate. Origin software was used to draw radar maps and Bland-Altman plots for statistical analysis.Results:When OSI images were used for the phantom imaging, the average differences in six-dimensional directions of lateral, long, vertical, rotational, roll and pitch were 0.03 mm, -0.09 mm, -0.27 mm, 0.04°, 0.17° and -0.19°, respectively. The maximum values were -2.20 mm, -2.30 mm, -1.20 mm, 0.60°, -1.00°, and -1.00°, respectively. When OSI system was utilized for the imaging of 15 patients, the average differences in six-dimensional directions were 0.44 mm, 0.16 mm, -0.20 mm, -0.11°, 0.10°, and -0.12°, respectively. The maximum values were -1.80 mm, 2.00 mm, 0.90 mm, -0.90°, -0.70°, and 0.80°, respectively. The translational errors mainly occurred in the lateral and long directions. The qualified rates of the threshold values of the phantoms and patients were 77% and 75% in the lateral direction, 82% and 89% in the long direction, respectively. In addition, 57% and 56% of patients met the threshold conditions of ±1.00 mm and ±0.50° in the six-dimensional directions, respectively.Conclusions:The OSI system using new SRS algorithm cannot meet the high accuracy requirements of single-center non-coplanar radiotherapy for multiple brain metastasis, especially in the lateral and long directions. It is not recommended for non-coplanar image guidance.
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Lung cancer is the second most common cancer worldwide, and 40% of patients with non-small cell lung cancer may develop brain metastases. Radiotherapy is a classic treatment for brain metastases, and immunotherapy has emerged for advanced non-small cell lung cancer. This article discusses the theoretical bases, clinical efficacy and safety, and the optimum timing of radiotherapy combined with immunotherapy for brain metastases from non-small cell lung cancer to provide reference for clinical practice and scientific research.
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Objective:To investigate the efficacy and safety of fractionated stereotactic radiotherapy (FSRT) based on linear accelerator for small volume brain metastases.Methods:A total of 21 patients with small volume brain metastases who received FSRT from August 2020 to June 2022 were enrolled as subjects, including 45 lesions. Small-volume brain metastases were defined as ≤3 cm in diameter and ≤6 cm 3 in volume, and the dose/fractionation scheme was 27-30 Gy/3 F or 30-40 Gy/5 F. Three months after radiotherpy, the efficacy of FSRT in small brain metastases and the incidence of radiation brain injury were evaluated, and the incidence of radiation brain injury in subgroup analysis was performed according to the diameter, volume, dose/fractionation scheme, biological effective dose (BED) 10, and location of lesions. Results:Twenty-four lesions (53.33%, 24/45) were evaluated as complete response, another 13 lesions (28.89%, 13/45) were evaluated as partial response, and in the remaining 8 lesions (17.78%, 8/45) were evaluated as stable disease. The local control rate was 100% (45/45), the objective remission rate was 82.22% (37/45), and the intracranial distant progression rate was 23.81% (5/21). During the treatment and follow-up, there were 7 lesions (15.56%, 7/45) of radiation-induced brain injury, and the incidence of symptomatic radiation-induced brain injury was 11.11% (5/45). Subgroup analysis showed that the incidence of radiation brain injury in the group with a lesion diameter of 2-3 cm was higher than that with a lesion diameter of <2 cm group, with a statistically significant difference [80.00% (4/5) vs. 7.50% (3/40), χ2=12.69, P<0.001]; the incidence rate of radiation brain injury in the group with lesion volume of 4-6 cm 3 was higher than that with lesion volume of <4 cm 3 group, with a statistically significant difference [57.14% (4/7) vs. 7.89% (3/38), χ2=7.49, P=0.006]. There was no significant difference in the incidence of radiation brain injury between the dose/fractionation scheme of lesions 27-30 Gy/3 F and 30-40 Gy/5 F [9.52% (2/21) vs. 20.83% (5/24), χ2=0.40, P=0.527]. There was no significant difference in the incidence of radiation brain injury between the BED 10<60 Gy and ≥60 Gy [28.57% (2/7) vs. 13.16% (5/38), χ2=0.22, P=0.641]. There was no significant difference in the incidence of radiation brain injury between the lesions in the same lobe and the single or multiple lesions in different lobes [28.57% (4/14) vs. 9.68% (3/31), χ2=1.38, P=0.240) . Conclusion:FSRT based on linear accelerator is effective for small volume brain metastases. Brain metastases with the diameter <2 cm or volume <4 cm 3 are associated with a lower incidence of radiation brain injury than that of lesions with the diameter of 2-3 cm or volume of 4-6 cm 3.
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Objective:To investigate the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) by meta-analysis.Methods:Studies published from January 1, 1980 to August 30, 2021 were searched systematically in PubMed, Embase, Cochrane Systematic Review database and China National Knowledge Infrastructure Database. The searching keywords included "non-small cell lung cancer", "randomized controlled trial", "prophylactic cranial irradiation" and "clinical trial". The data extracted from the above studies were analyzed using Review Manager 5.3 and Stata 12.0 software. Outcomes included the development of brain metastases (BM), overall survival (OS), disease-free survival (DFS), toxicity, and quality of life (QoL).Results:Ten trials, including 2005 NSCLC patients, met the inclusion criteria. Patients who underwent PCI had a significantly lower risk of BM than those who did not ( OR=0.29, 95% CI: 0.22-0.40, P<0.001). Compared with non-PCI group, DFS in PCI group was significantly increased ( HR=0.75, 95% CI: 0.63-0.89, P=0.001). However, there was no significant difference in OS ( OR=0.90, 95% CI: 0.69-1.18, P=0.45). In addition, the incidence of fatigue was significantly increased in the PCI group ( OR=2.64, 95% CI: 1.58-4.40, P<0.001). There was no significant difference in cognitive impairment between the PCI and non-PCI groups ( OR=3.60, 95% CI: 0.97-13.32, P=0.06). Conclusions:PCI is the standard treatment for NSCLC. Compared with non-PCI, PCI significantly reduces the incidence of BM and prolongs the DFS of NSCLC patients. The effect of PCI-related toxicity on the QoL and long-term OS needs further study.
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Objective:To analyze the prognosis and risk factors for brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete resection, aiming to identify those most likely to benefit from prophylactic cranial irradiation (PCI).Methods:Clinical data of 94 patients with LS-SCLC treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2005 to December 2018 who underwent complete resection were retrospectively analyzed, including 31 cases treated with PCI and 63 without PCI. Prognostic factors and risk factors of BM were analyzed by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. Independent risk factors of overall survival (OS) and BM were assessed by multivariate Cox regression model.Results:The 2-year and 5-year OS rates were 80.6% and 61.3% in the PCI group, and 61.9% and 46.0% in the non-PCI group, respectively ( P=0.001). The 2-year and 5-year brain metastasis-free survival (BMFS) rates were 80.6% and 54.8% in the PCI group, and 57.1% and 42.9% in the non-PCI group, respectively ( P=0.045). The 2-year and 5-year progression-free survival (PFS) rates were 71.0% and 48.4% in the PCI group, and 49.2% and 34.9% in the non-PCI group, respectively ( P=0.016). PCI could improve OS in patients with pII/III stage LS-SCLC ( P=0.039, P=0.013), but the OS benefit in patients with pI stage LS-SCLC was not significant ( P=0.167). BM occurred in 3 patients (9.7%) in the PCI group, which was significantly lower than that in the non-PCI group ( n=17, 27.0%; P=0.044); there was no significant difference in the BM rate of patients with pI and pII stage LS-SCLC between PCI and non-PCI groups ( P=0.285, P=0.468); and the BM rate of patients with pIII stage LS-SCLC in the PCI group was significantly lower than that in the non-PCI group ( P=0.041). Multivariate analysis showed age ≥60 ( HR=2.803, P=0.001), BM ( HR=2.239, P=0.022), no PCI ( HR=0.341, P=0.004) and pathological stage pII/III ( HR=4.963, P=0.002) were the independent high-risk factors affecting OS; and pathological stage pII/III ( HR=11.665, P=0.007) was an independent high-risk factor affecting BM. Conclusions:LS-SCLC patients with pII-III stage have a higher risk of developing BM and poor prognosis after complete resection, and should receive PCI treatment. However, LS-SCLC patients with pI stage may not benefit significantly.
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Objective:To evaluate the accuracy and stability of stereotactic radiosurgery (SRS) algorithm in optical surface imaging (OSI) system in non-coplanar radiotherapy.Methods:Three OSI imaging systems were used to measure the phantom repeatedly at different couch rotation angles to analyze the accuracy and stability of OSI system. Seven patients with multiple brain metastases who underwent single-center non-coplanar radiotherapy were randomly selected, and the accuracy and stability of OSI for patient imaging were analyzed. Stability is defined as the difference between the two OSI measurements when the couch is turned from 0° to a non 0° angle, and then back to 0°, using the 0° cone beam CT (CBCT) as the "gold standard". Accuracy is defined as the difference between OSI and CBCT (at 0° couch angle) measurement data. The measurement data with normal distribution were described as Mean ± SD. The data with non-normal distribution were expressed as M (Q). The difference of the former data was compared by one-way ANOVA, and the difference of the latter data was assessed by Kruskal-Wallis H nonparametric test. Results:For non-coplanarity, the translation accuracy of the phantom and the patient was ≤ 1.30 mm and ≤ 1.00 mm, and the rotation accuracy was ≤ 0.50° and ≤ 0.60°, respectively. The translation errors mainly occurred in the left-right and head-foot directions. In terms of stability, the maximum standard deviation of phantom coplanar translation and rotation was 0.06 mm and 0.06°. The maximum standard deviation of patient translation and rotation was 0.17 mm and 0.19°.Conclusions:Although the new SRS algorithm improves the non-coplanar accuracy, it still cannot meet the precise requirements of non-coplanar single isocenter radiotherapy for multiple brain metastases, especially in the left-right and head-foot directions. When the couch rotation angle is large, OSI is not recommended for image-guided radiotherapy. However, its high stability can be used to monitor the intrafractional motion of patients.
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Purpose To investigate the expression of PD-1,PD-L1,CD3 and CD8 in the immune microenvironment of non-small cell lung cancer(NSCLC)and their clinical signifi-cance.Methods The clinical data of 39 patients with NSCLC brain metastasis(BM)were collected.The expression of PD-1,PD-L1,CD3 and CD8 in the tumor and stroma of BM was detec-ted using an immunofluorescence-based tissue microenvironment analysis panel.Targeted sequencing was carried out to catalog cancer-related genes.The clinical pathological features were an-alyzed with review of relevant literature.Results Thity-nine patients with NSCLC presented with tumor-infiltrating lympho-cytes(TIL)in different degree.CD3+TIL(P=0.000 7)and CD8+TIL(P=0.0006)were more prominent in the tumor stroma,and the positive PD-L1 expression was significantly higher in the interstitial tissues of tumor(P=0.025 8).Com-pared with the whole wild-type driver gene cohort,the expres-sion of PD-L1 in the stroma of BM was significantly increased in the EGFR mutation cohort(P=0.039).Patients with high in-filtration of stroma CD8+TIL had longer median overall survival than those with low infiltration(16 months vs 6 months,P=0.032);PD-L1-positive patients(36 months)were longer sur-vival time than PD-L1-negative patients(5.5 months,P=0.056).Compared with lung primary lesions,the variant allele frequencies(VAFs)in BM generally increased,and samples with higher VAFs corresponded to higher expression of PD-1,PD-L1,CD3 and CD8.Conclusion The TIL infiltration is most prominent in the stroma of NSCLC BM.The EGFR muta-tion of a tumor might affect the immune microenvironment of me-tastases;PD-L1 expression and TIL infiltration were correlated with overall survival.
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Objective To explore the dosimetric effects of a self-developed planning mode of boundary range scattering dose(BRSD)on Cyberknife treatment of lung cancer brain metastases.Methods The positioning images of 15 patients with lung cancer brain metastases treated in the radiotherapy department of some institution from January 1,2021 to December 31,2021 were selected and introduced into Cyberknife Multiplan 4.0.3 treatment planning system.A fractionated stereotactic radiotherapy(FSRT)plan(as the FSRT planning group)and a BRSD plan(as the BRSD planning group)were developed for each patient.The FSRT planning group developed a plan for the planning target volume(PTV)in the conventional way,so that V100 covered more than 95％of the PTV;the BRSD planning group prepared a plan for the gross tumor volume(GTV)with the same parameter conditions as the FSRT planning group and the prescription dose was normalized to the PTV so that V100 covered more than 95％of the PTV.The dosimetric parameters of the target area and normal tissue of the 2 groups were compared by dose-volume histograms and isodose curves.Statistical analysis was performed using SPSS 24.0 software.Results The D98,Dmax and Dmean in the target area of the BRSD planning group were significantly higher than those of the FSRT planning group,and the differences were statistically significant(P<0.05);the differences in the conformity index,dose gradient index,and Dmean,V30,V24 and D3cc in normal tissue of the 2 groups were not statistically significant(P>0.05);the BRSD planning group gained a denser dose distribution when compared with the FSRT planning group.Conclusion The BRSD planning mode gains significant dosimetric advantage by enhancing the absorbed dose to the target area without increasing or decreasing the dose to normal tissue.
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Abstract Objective To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design A retrospective single-institution cohort study. Patients The perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors' institution between November 2012 and June 2019 were retrospectively analyzed. Methods The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations The number of enrolled patients was relatively small and patients' treatment options varied. Conclusions A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target.
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Introduction: Brain metastasis (BM) is significantly seen in lung adenocarcinoma and adversely affects survival. We aimed to evaluatethe factors affecting the prognosis in patients with BM diagnosed with lung adenocarcinoma. Materials and Methods: Patients with BM between 2012 and 2022 were reviewed retrospectively. Demographic characteristics of the patients, primary tumor characteristics,presence of mutation, BM number, localization, size, development time, and treatment characteristics were evaluated. Inflammatoryindices at the time of BM were examined. The overall survival time was calculated. Results: About 92.9% of 113 patients were male, the median age was 62 years (54.5–68.5), and follow‑up was 8 months (3–18). BM was detected at the time of diagnosis in 62 (54.9%)of the patients, whereas BM developed later in 51 (45.1%) patients. Systemic treatment was applied to 72.5% of the patients. Survivalwas lower in patients with BM at diagnosis (4 vs. 14 months, P < 0.001). Primary tumor maximum standardized uptake value level was higher on fluorodeoxyglucose‑positron emission tomography‑computed tomography at diagnosis in patients with late BM (P = 0.004). The development time of BM was 9 months (4–16), and the median survival was 8 months (6.2–9.8). There was no difference betweentumor localization or inflammatory indices and the development of BM and prognosis. The presence of BM at diagnosis and lack of systemic treatment were found to be factors that independently reduced survival (P < 0.001, P = 0.007). Conclusion: The presence of BM at diagnosis significantly reduces survival. It has been observed that systemic treatments applied in addition to local treatments have a positive effect on the prognosis.
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Abstract Objective To analyze the Prolyl 4-Hydroxylase subunit Alpha-2 (P4HA2) expression in Lung Adenocarcinoma (LAUD). Methods The authors assessed P4HA2 expression in the LUAD tumor ecosystem using single-cell analysis. The authors analyzed the relationship between P4HA2 expression and clinical features in LUAD and Brain Metastasis (BM) cases. The authors assessed the biological functions of P4HA2 using The Cancer Genome Atlas-LUAD dataset. Results P4HA2 was more highly expressed in fibroblasts than in epithelial cells in normal lung and lung adenocarcinoma tissues (p < 0.001). P4HA2 was more highly expressed in malignant epithelial cells than in fibroblasts in the BM tissue (p = 0.002). P4HA2 expression was significantly higher in female cases than in male cases (p = 0.049) and was related to lymph node metastasis (p = 0.019) and a higher TNM stage (p = 0.020). High P4HA2 expression indicated a poor prognosis and served as an independent prognostic risk factor in lung cancer. P4HA2 was mainly enriched in the extracellular matrix organization, NADH regeneration, and canonical glycolysis. P4HA2 expression was negatively correlated with naive B cells, T-cells, CD8, and activated natural killer cells, but positively correlated with CD4 memory-activated T cells, regulatory T-cells, resting dendritic cells, and dendritic cell activation. P4HA2 messenger RNA expression was correlated with programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4. Conclusion P4HA2 is highly expressed in LUAD tumor cells, especially for the BM subtype, and is a valuable prognostic indicator of LUAD. It may be involved in a biological activity of distant metastasis of LUAD tumor cells and serve as a potential treatment target.
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Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.
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With the increasing understanding of the unique tumor microenvironment in the brain, immunotherapy have emerged as a new and promising treatment for brain metastases. Radiotherapy and immunotherapy have a synergistic effect, and it is of great value to understand its mechanism in the treatment of breast cancer brain metastases. At present, the study of immune checkpoint inhibitors combined with radiotherapy in breast cancer brain metastases is being actively carried out, bringing new hope to patients with breast cancer brain metastases.
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Objective To evaluate the clinical efficacy and safety of simultaneous enhanced accelerated radiation therapy for brain metastases (SMART-Brain) combined with functional area protection. Methods SMART-Brain was planned for 60 patients with multiple brain metastases. Using the whole brain intensity modulation technique, important functional areas such as hippocampus were protected against irradiation by delivering a dose of 30 Gy in 10 fractions. Meanwhile, a high dose of 40 Gy was delivered to brain metastases in 10 fractions. All patients were followed up to evaluate the efficacy, incidence of adverse reactions, median overall survival (OS), and intracranial progression-free survival (IPFS). Results The effective rate was 73.33% (44 cases), the disease control rate was 91.67% (55 cases), median OS was 15.2 months, and IPFS was 12 months. The 1 and 2-year OS was 66.7% and 26.4%, and the 1-year IPFS was 46.7%. The MMSE scores at 1, 3, and 6 months after SMART showed no significant differences compared with baseline scores (P > 0.05). Grade 2 and above inner ear damage such as otitis media, hearing loss, and dizziness was absent. Conclusion Smart-Brain can significantly reduce the treatment time and better protect the organs at risk, and serves as an economical, safe, and effective radiotherapy regimen in areas with limited technical conditions.
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Abstract Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyse retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes, are factors that significantly influence patient survival.
Resumen Antecedentes: La radioterapia holocraneal (WBRT) y la radiocirugía estereotáctica (SRS) son dos modalidades de tratamiento comúnmente empleados para el tratamiento de las metástasis cerebrales (BMs). Objetivo: El propósito de este estudio es analizar de forma retrospectiva el control local y la supervivencia de los pacientes con BMs de cáncer de mama (BC) tratados mediante radiocirugía empleando arcoterapia volumétrica modulada (VMAT-RS). Métodos: Se analizaron 18 pacientes con 41 BMs de BC tratados mediante VMAT-RS. Se clasificaron según el subtipo molecular de BC y el GPA (Graded Prognostic Assessment) modificado de cáncer de mama. Los pacientes presentaron de 1-4 BMs, las cuales fueron tratadas con 5 arcos VMAT no coplanares. Se analizó la distribución espacial de las BMs, la influencia del status del receptor en la localización de las lesiones y la supervivencia evaluada mediante el modelo de Kaplan-Meier. Resultados: La mediana del tiempo de supervivencia (MST) fue de 19.7 meses. Se hallaron diferencias estadísticamente significativas en el MST según el índice de Karnofsky (p= 0.02) y el status de HER2 (p= 0.004), siendo más prolongado en las pacientes HER2+. Por último, nuestros resultados mostraron que el cerebelo es el lugar predominante de las BMs de cáncer de mama, y también sugirieron que las BMs HER2+ presentaban una predilección por algunas estructuras de la circulación posterior, como el cerebelo, el tronco cerebral y los lóbulos occipitales (p= 0.048). Conclusiones: VMAT-RS es una técnica con una supervivencia global comparable a otras técnicas de radiocirugía. La situación basal en el momento del tratamiento, el GPA modificado de cáncer de mama así como los subtipos moleculares de cáncer de mama, son factores que influyen de forma significativa en la supervivencia de los pacientes.
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Objective: To investigate the effect of alectinib in the treatment of brain metastases from anaplastic lymphoma kinase(ALK)positive non-small cell lung cancer (NSCLC). Methods: Thirty-four cases of ALK-positive NSCLC in Tianjin Medical University Cancer Institute and Hospital, between August 2016 to October 2019, were retrospectively analyzed. Thirteen cases received first-line single drug therapy (600 mg PO bid) of Alectinib. 7 cases (53.8%) were male, 6 cases were female (46.2%), the median age was 51 (35-72). The Kaplan-Meier method was used to examine progression-free survival (PFS). Results: The median progression-free survival (mPFS) of the alectinib group was 24.5 months, and the adverse drug reactions were mild. Conclusions: The use of alectinibas first-line treatment after the local treatment of measurable intracranial lesions significantly increased the PFS of patients with brain metastases from ALK-positive NSCLC.
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With the advancement of imaging diagnosis and the development of modern radiotherapy, the survival of cancer patients has been prolonged and the incidence rate of brain metastases (BM) has been significantly increased. The quality of life of patients and potential radiotherapy-induced neurocognitive impairment have gradually captivated widespread attention. Whole brain radiotherapy (WBRT) is one of the common local therapies for BM patients. However, the application of WBRT is controversial because it may lead to neurocognitive impairment. The incidence of metastatic tumors in hippocampus and radiation-induced neurocognitive impairment can accelerate the implementation of hippocampal-avoidance WBRT (HA-WBRT). In this article, the feasibility of HA-WBRT was discussed and research progress in recent years was reviewed.