Objective:To explore the effects of multimodal imaging on the performance of automatic segmentation of glioblastoma targets for radiotherapy based on a deep learning approach.Methods:The computed tomography (CT) images and the contrast-enhanced T1 weighted (T1C) sequence and the T2 fluid attenuated inversion recovery (T2- FLAIR) sequence of magnetic resonance imaging (MRI) of 30 patients with glioblastoma were collected. The gross tumor volumes (GTV) and their corresponding clinical target volumes CTV1 and CTV2 of the 30 patients were manually delineated according to the criteria of the Radiation Therapy Oncology Group (RTOG). Moreover, four different datasets were designed, namely a unimodal CT dataset (only containing the CT sequences of 30 cases), a multimodal CT-T1C dataset (containing the CT and T1C sequences of 30 cases), a multimodal CT-T2-FLAIR dataset (containing the CT and T2- FLAIR sequences of the 30 cases), and a trimodal CT-MRI dataset (containing the CT, T1C, and T2- FLAIR sequences of 30 cases). For each dataset, the data of 25 cases were used for training the modified 3D U-Net model, while the data of the rest five cases were used for testing. Furthermore, this study evaluated the segmentation performance of the GTV, CTV1, and CTV2 of the testing cases obtained using the 3D U-Net model according to the indices including Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and relative volume error (RVE).Results:The best automatic segmentation result of GTV were achieved using the CT-MRI dataset. Compared with the segmentation result using the CT dataset (DSC: 0.94 vs. 0.79, HD95: 2.09 mm vs. 12.33 mm, and RVE: 1.16% vs. 20.14%), there were statistically significant differences in DSC ( t=3.78, P<0.05) and HD95 ( t=4.07, P<0.05) obtained using the CT-MRI dataset. Highly consistent automatic segmentation result of CTV1 and CTV2 were also achieved using the CT-MRI dataset (DSC: 0.90 vs. 0.91, HD95: 3.78 mm vs. 2.41 mm, RVE: 3.61% vs. 5.35%). However, compared to the CT dataset, there were no statistically significant differences in DSC and HD95 of CTV1 and CTV2 ( P>0.05). Additionally, the 3D U-Net model yielded some errors in predicting the upper and lower bounds of GTV and the adjacent organs (e.g., the brainstem and eyeball) of CTV2. Conclusions:The modified 3D U-Net model based on the multimodal CT-MRI dataset can achieve better segmentation result of glioblastoma targets and its application potentially benefits clinical practice.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease. MicroRNA has been shown to play an important role in RA. MicroRNA-124a (miR-124a) has anti-proliferative and anti-inflammatory effects in RA fibroblast synovial cells. This study aims to explore the effects of miR-124a overexpression on arthritis in collagen-induced arthritis (CIA) mice and the underlying mechanisms. METHODS: Bovine type II collagen and complete Ferris adjuvant were used to induce CIA model from DBA/1 mice. Twenty-eight days after initial immunization (D28), CIA mice were randomly divided into a model group, a miR-124a treatment group, and a negative control (NC) group. Physiological saline, miR-124a agomir, and miR-124a agomir NC were injected into the skin at the tail root of mice every 3 days for 4 times, respectively. The degree of joint swelling and arthritis index of mice were recorded accordingly. Sixty-three days after initial immunization (D63), the mice were sacrificed to obtain the synovial tissue of ankle joint. HE staining was used to observe the proliferation of synovial cell, infiltration of inflammatory cell, pannus, and bone erosion of synovial tissues; TUNEL staining was used to detect cell apoptosis; qRT-PCR was used to detect the mRNA expression of miR-124a, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) and its downstream genes Bcl-2 and Bax. Immunohistochemistry was used to detect the protein expression of PIK3CA, Bcl-2, and Bax protein in synovial tissues of each group. RESULTS: Different degrees of swelling presented in the paws of DBA/1 mice at D28, which indicated the CIA model was constructed successfully. Forty-eight days after initial immunization (D48), the paws of mice in the miR-124a treatment group were only slightly red and swollen, while the paws of mice in the model group and the NC group were obviously red and swollen. The arthritis index of mice in the miR-124a treatment group were decreased significantly compared to the NC group at D51, D53, D59, and D62 (51, 53, 59, 62 days after initial immunization) (all P<0.05). Sixty-three days after initial immunization (D63), HE staining indicated that the scores of synovial cell proliferation, inflammatory cell infiltration, synovial pannus, and bone erosion were significantly reduced in the miR-124a treatment group (P<0.05 or P<0.01), while cell apoptosis was increased in the miR-124a treatment group compared with the model group and NC group (P<0.01 or P<0.001). Besides, the expression of miR-124a and Bax in the synovial tissue in miR-124a treatment group was significantly higher than those in the model group and NC group (P<0.01 or P<0.001), while the expressions of PIK3CA and Bcl-2 were decreased (P<0.05 or P<0.01 or P<0.001), and the ratio of Bcl-2 to Bax was significantly decreased (P<0.01 or P<0.001). CONCLUSIONS Overexpression of miR-124a can reduce arthritis in CIA mice bacause it could promote synovial cell apoptosis and inhibit synovial cell proliferation via targeting PIK3CA and regulating its downstream pathways.
Animals ; Arthritis, Experimental/metabolism* ; Arthritis, Rheumatoid/genetics* ; Cattle ; Cell Proliferation ; Class I Phosphatidylinositol 3-Kinases/metabolism* ; Mice ; Mice, Inbred DBA ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Synovial Membrane ; bcl-2-Associated X Protein/metabolism*

Objective To compare curative effect between lenvatinib combined with locoregional therapy and locoregional therapy on PD-L1-positive hepatocellular carcinoma patients with type Ⅰ-Ⅲ portal vein tumor thrombus according to Cheng's classification. Methods The patients in lenvatinib combined with locoregional therapy group received orally-administered lenvatinib at a dose of 12 mg qd for patients≥60 kg or 8 mg qd for patients < 60 kg. The locoregional therapy group only received locoregional therapy. We retrospectively analyzed the clinical data and prognosis of two groups. Results The CR+PR were 78.1% and 53.6% in the combination group and locoregional therapy group, respectively (P < 0.05). The response rate, disease control rate and overall survival of the combination group were higher than those in the locoregional therapy group (P < 0.05). Conclusion The curative effect and overall survival of lenvatinib combined with locoregional therapy is better than locoregional therapy on PD-L1-positive hepatocellular carcinoma patients with type Ⅰ-Ⅲ portal vein tumor thrombus according to Cheng's classification.

Objective To evaluate the prognosis-related factors of colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Methods We reviewed retrospectively the clinical data of 68 colorectal cancer patients with positive PD-L1 expression in liver metastases receiving personalized comprehensive treatment which was mainly consisted of surgical resection. We observed the results and prognosis after surgical resection and analyzed related factors. Results Univariate analysis showed that no radiotherapy, N stage, RAS mutation status, T stage, dMMR, Duck stage, disease free interval from primary to metastases≤12 months and largest hepatic tumor diameter > 5 cm had obvious significance (all P < 0.05). Multivariate logistic analysis regression revealed that without dMMR (P=0.012), Duck A stage (P=0.000), disease free interval from primary to metastases > 12 months (P=0.020) and largest hepatic tumor diameter < 5 cm (P=0.006) were independent protective factors for the prognosis of colorectal cancer patients with positive PD-L1 expression in liver metastases after surgical resection. Conclusion Personalized comprehensive treatment which is mainly consisted of surgical resection still has a good effect on colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Without dMMR, Duck A stage, disease free interval from primary to metastases > 12 months and largest hepatic tumor diameter ≤5cm are independent protective factors for patients' prognosis.

Objective:To develope a deep-learning-based auto-segmentation model to segment organs at risk (OARs) in head and neck (H&N) region and compare with atlas-based auto-segmentation software (Smart segmentation).Methods:The auto-segmentation model consisted of classification model and segmentation model based on deep learning neural network. The classification model was utilized to classify CT slices into six categories in the cranio-caudal direction, and then the CT slices corresponding to the categories for different OARs were pushed to the segmentation model respectively. The CT image data of 150 patients were used for auto-segmentation model training and building atlas library in Smart segmentation software. Another 20 patients were used as testing dataset for both auto-segmentation model and Smart segmentation software. Dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to evaluate the accuracy of two method, and auto-segmentation time cost was recorded. Paired Student′s t-test or non-parametric Wilcoxon signed-rank test was performed depending on result of normality test. Results:The DSC and HD of auto-segmentation model for brainstem, left eye, right eye, left optic nerve, right optic nerve, left temporal lobe, right temporal lobe, mandible, left parotid and right parotid were 0.88 and 4.41 mm, 0.89 and 2.00 mm, 0.89 and 2.12 mm, 0.70 and 3.00 mm, 0.80 and 2.24 mm, 0.81 and 7.98 mm, 0.84 and 8.82 mm, 0.89 and 5.57 mm, 0.70 and 11.92 mm, 0.77 and 11.27 mm respectively. The results of auto-segmentation model were better than those of Smart segmentation ( t=3.115-7.915, Z=-1.352 to -3.921, P<0.05) except left and right parotids. In addition, the speed of auto-segmentation model was 51.28% faster than that of Smart segmentation. Conclusions:In this study, the deep-learning-based auto-segmentation model demonstrated superior performance in accuracy and efficiency on segmenting OARs in H&N CT images, which was better than Smart segmentation software.

Objective:To investigate the effect of Halo-Vest on the dose distribution of different radiotherapy techniques for primary cervical spine malignant tumors.Methods:Ten patients with primary cervical spine malignancies who underwent radiotherapy after Halo-Vest surgery were retrospectively studied. The IMRT and VMAT plans were designed on the contoured CT images including Halo-Vest delineations using Monaco planning system. The IMRT and VMAT plans with the same field parameters were duplicated to the CT images without the Halo-Vest delineations, and the dose distribution was recalculated. The dose distribution of the target, organs at risk and normal tissues was analyzed and compared for the plans with and without the Halo-Vest delineation.Results:For most dosimetric parameters of VMAT plans, the mean deviations induced by the Halo-Vest were less than 1%, except for PGTV 107%. Without Halo-Vest delineation, the mean maximum dose of spinal cord and spinal cord-PRV increased by 0.38 Gy and 0.42 Gy ( Z=-2.803, -2.803, P<0.05), respectively. The mean Dmean of spinal cord and spinal cord PRV increased by 0.35 Gy and 0.37 Gy, respectively ( Z=-2.703, -2.701, P<0.05). The maximum deviation observed in the mean V5, V30, and Dmean of mucosa, thyroid, parotid gland, mandible, mandibular joint, and normal tissues was 0.74%. For IMRT plans, larger dosimetric deviations than VMAT plans were observed in PTV and PGTV, most of which were more than 1.0% and the maximum deviation was 4.55%. The absence of Halo-Vest delineation increased the mean maximum dose of spinal cord and spinal cord-PRV by 0.48 Gy and 0.59 Gy ( P>0.05), respectively. The mean Dmean of spinal cord and spinal cord PRV increased by 0.57 Gy and 0.59 Gy, respectively ( Z=-2.293, -2.293, P<0.05). The maximum deviation of other organs at risk was 1.98%. Conclusions:There are no clinically significant dose differences for VMAT planning with or without Halo-Vest delineation on the CT images. But the dosimetric impact of absent or partial Halo-Vest delineation on IMRT planning is relatively large and should be considered.

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

Objective To evaluate the outcomes and prognostic factors of image-guided 125I seed implantation for locally recurrent soft tissue sarcoma(RSTS).Methods A total of 60 patients with RSTS who received image-guided 125I seed implantation in Peking University Third Hospital,from September 2002 to December 2015,were retrospectively analyzed.The enrollment criteria: KPS ＞60 points,refused or could not tolerate surgery or radiotherapy,the expecting survival time ＞3 months,relapsed after multiple treatment of soft tissue sarcoma,and underwent CT or ultrasound guided 125 I seed implantation treatment.In all,the median activity of seeds was 25.9×106Bq(range,11.1×106-29.6×106Bq),median number of implanted seeds was 58(range,3-133),and the median D90was 120 Gy(range,36.50-460.97 Gy).The local progression-free survival(LPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.The log-rank test and Cox regression model were used for the univariate and multivariate analyses.Results The median follow-up was 18.75 months(range,1-146).The median OS was 18.5 months(95％CI 13.1-23.9).The 1-,3-and 5-year OS rate were 63.3％,33.0％and 29.5％,respectively.The 1-,3-and 5-year LPFS rate were 72.5％,63.7％and 59.7％,respectively.The general rate of pain relieving was 100％(6/6).8.3％(5/60)presented grade Ⅳskin toxicity.No fatal complications ocurred.The univariate analysis suggested that tumor size,tumor volume,KPS score,D90were prognostic factors of OS and LPFS.The multivariate analysis demonstrated that previous chemotherapy history and distant metastases were independent prognostic factors of survival.Conclusions Image-guided 125I seed implantation for recurrent soft tissue sarcoma is a safe treatment option with high efficacy and low morbidity.Tumor size and D90were the prognostic factors of OS and LPFS.

Objective To evaluate the efficacy and adverse effects of 125I seeds implantation for pelvic recurrence of cervical cancer (PRCC) after radiotherapy.Methods From July 2005 to October 2015,36 PRCC patients (median 44 years) after radiotherapy in Peking University Third Hospital were enrolled in this retrospective study.All patients underwent 125I seeds implantation under ultrasound or CT guidance.Treatment planning was performed before implantation to estimate the number and activity of 125I seeds.The seed numbers ranged from 10-140 (median:62.5),and the activity ranged from 18.5-29.6 (median:25.9) MBq.Postoperatively,the median dose delivered to 90％ gross tumor volume (D90) was 127.3 Gy.Kaplan-Meier method was used to calculate local progress free survival (LPFS) rate and overall survival (OS) rate,and log rank test and Cox regression were used for univariate and multivariate analyses.Results The median follow-up time was 11.5 months.The local control rate was 88.89％(32/36).The 1-year LPFS rate was 34.9％ and the 1-year OS rate was 52.0％.Thirty-one patients died,of which 22 (70.97％,22/31) died from cancer.Univariate analysis showed that the location of recurrence (x2=5.195),volume of lesion (hazard ratio (HR)=1.012) and D90(HR=0.988) were significantly correlated with LPFS (all P＜0.05).Multivariate analysis showed that the location of the recurrence was significantly related with LPFS (HR =0.215,P＜0.05).The 1-year LPFS rates of pelvic wall recurrence and central recurrence were 41.6％ and 26.7％ (x2 =5.195,P＜0.05),and 1-year OS rates were 54.7％ and 49.5％ (x2 =2.535,P＞0.05),respectively.Vaginal fistula,which may be caused by the treatment,occurred in 1 case.No other sever adverse effects were observed.Conclusions 125I seeds implantation is a safe and effective treatment for PRCC after radiotherapy.With the treatment of 125I seeds implantation,patients with pelvic wall recurrence may achieve better therapeutic effects than those with central recurrence.

To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.
Antibodies, Monoclonal ; blood ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Humans ; Infliximab ; blood ; therapeutic use ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood