Application of deep learning-based multimodal imaging to the automatic segmentation of glioblastoma targets for radiotherapy / 中华放射医学与防护杂志

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.

Curative Effect of Lenvatinib Combined with Locoregional Therapy on PD-L1-positive Hepatocellular Carcinoma Patients with Type Ⅰ-Ⅲ Portal Vein Tumor Thrombus According to Cheng's Classification / 肿瘤防治研究

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.

Prognosis-related Factors of Colorectal Cancer Patients with Positive PD-L1 Expression in Liver Metastases After Hepatectomy / 肿瘤防治研究

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.

Effect of Halo-Vest on dose distribution of radiotherapy for primary cervical spine malignant tumors / 中华放射医学与防护杂志

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.

Comparative study of two different methods for automatic segmentation of organs at risk in head and neck region / 中华放射医学与防护杂志

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.

Efficacy and dosimetry analysis of image-guided radioactive ¹²⁵I seed implantation as salvage treatment for pelvic recurrent cervical cancer after external beam radiotherapy / 부인종양

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.

Efficacy and clinical prognostic factors of image-guided 125I seed implantation for locally recurrent soft tissue sarcoma / 中华放射医学与防护杂志

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.

Efficacy of 125I seeds implantation for pelvic recurrence of cervical cancer after radiotherapy / 中华核医学与分子影像杂志

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.

Phase Ⅰ study of weekly PTX+DDP, and postoperative radiotherapy for early cervical cancer in Chinese women / 中华放射肿瘤学杂志

Objective To determine the maximum tolerated dose ( MTD) and dose?limiting toxicity ( DLT) of weekly PTX and DDP concurrent postoperative radiotherapy in Chinese women with high?and intermediate?risk early cervical cancer. Methods Women with high risks postoperative cervical carcinoma, ECOG≤2 were eligible. Pelvis RT (6/10 MV X?ray,3DCRT 40 Gy/20f,para?metrial boost 10?20 Gy/5?10f) was followed by 2?4f brachytherapy applications ( 192 Ir,5 Gy/f) . Concurrent weekly chemotherapy was started at DDP 20 mg/m2 and PTX 10 mg/m2 weekly,and escalated in three?patient cohorts according to 3+3 methods. Results 25 patients were enrolled and treated over seven doses levels until dose?limiting toxicity (DLT) was reached. Median age was 48 years (range,34?66).All of patients finished RT in 7 weeks. Grade 3,4 non?hematologic toxicities were diarrhea and observed in two patients (4 cycles,DLT) at level 7.Grade 3,4 hematologic,principally leukopenia and neutropenia,and occurs late cycles. One grade 4 leukopenia and neutropenia was observed at dose level 6 but not seen in three additional patients. No one was delayed treatment time by concurrent chemotherapy.22 patients finished 6 cycles. Median follow?up is 59. 5 months. Three patients have died of cancer metastasis and recurrence. One patient has died of respiratory failure. Conclusions Combination PTX and DDP administered concurrently with pelvic EBRT can be safely administered at the MTD of DDP 35 mg/m2 and PTX 30 mg/m2 weekly for six cycles in Chinese women with postoperative cervical cancer.

Efficacy and dosimetry of computed tomography image-guided 125 I radioactive seed implantation for locally recurrent rectal cancer / 中华放射肿瘤学杂志

Objective To evaluate the efficacy of computed tomography ( CT ) image?guided 125 I radioactive seed implantation for locally recurrent rectal cancer ( LRRC ) , and to analyze the relationship between the dosimetry and prognosis. Methods A retrospective analysis was performed on the clinical data of 36 patients with LRRC who received CT image?guided 125 I seed implantation in our hospital from 2003 to 2011. Dosimetric verification was performed using CT scan immediately after 125 I seed implantation. The D90 , D100 , V100 , and V150 values were evaluated. In all the patients, the median activity of seeds was 0?7 mCi (0?4?0?8 mCi) and the median number of implanted seeds was 74(33?137). The local control (LC) and overall survival ( OS ) rates were calculated using the Kaplan?Meier method. The log?rank test and Cox regression model were used for the univariate and multivariate analyses, respectively. Results The median OS time was 16?2 months ( 95% CI= 13?5?18?9 months ) . The median LC time was 10?0 months (95% CI=6?2?13?8 months). The D90 and V100 values were (118.6±25?1) Gy and (90.0±0?3)%, respectively. The univariate analysis suggested that D90 was correlated with the LC time ( P=0?048) and V100 was correlated with the OS time ( P=0?035) . The multivariate analysis showed that a V100 value higher than 90% was a prognostic factor of OS (P=0?044). Conclusions In the treatment of LRRC using CT image?guided 125 I radioactive seed implantation, a D90 value larger than 140 Gy and a V100 value higher than 90% in the postoperative verification plan help improve the LC and OS rates. The D90 and V100 values in the postoperative verification plan may predict treatment outcomes in patients.

CT-guided 125I radioactive seed implantation for locally recurrent rectal cancer / 中华放射医学与防护杂志

Objective To evaluate the efficacy and adverse reactions of CT-guided 125I radioactive seed implantation in treatment of locally recurrent rectal cancer (LRRC).Methods Thirty patients with LRRC who refused operation or were unable to endure pelvic radiotherapy received 125I seed implantation under CT guidance.Three-dimensional treatment planning system was used to calculate the number,activity,and dose of the seeds needed.The activity of seeds ranged from 14.8 to 29.6 MBq with a median of 25.9 MBq,the seed numbers ranged from 33 to 137 with a median of 74.5,the prescription doses ranged from120-160 Gy,and the actual verification dose D90 ranged from 75.91 to 159.32 Gy with a median of 119.77 Gy.Dosimetric verification by CT scanning was conducted immediately after the treatment.Follow-up was conducted for 15.2 months(4.2-35.0 months).Results The follow-up rate was 93.3％.The pain relief rate was 95.2％.The overall response rate was 50.0％,including a complete response rate of 13.3％ and a partial response rate of 36.7％.The 1-and 2-year local control rates were 30.0％ and 8.0％ respectively.The median local control survival time was 7.8 month.The 1-and 2-year survival rates were 66.5％ and 32.9％ respectively.The median overall survival time was 21.5 months.Complications,mainly adverse effects of skin and urinary system (frequent urination,urgent urination,and dysuria) occurred in 6 patients with a rate of 20.0％.Conclusions Minimally invasive and with satisfying efficacy and tolerable complications,CT-guided 125I radioactive seed implantation is a favorable option for treatment of LRRC,especially for the patients who have undergone previous pelvic radiation.

Clinical effect observation of 125I seed implantation combined with endocrinal therapy for prostate cancer / 中华放射医学与防护杂志

Objective To retrospectively study the efficacy and side-effect of 125I seed implantation combined with endocrinal therapy in stage T3N0M0 prostate cancer.Methods The study included 22 patients with clinical stage T3 N0 M0 prostate cancer who were treated with transperineal 125I seed implantation guided by transrectal ultrasound,real time TPS and endocrinal therapy.The minimum peripheral doses (MPD) were 140-160 Gy.The median number of seeds was 74(26-90).The activity of each seed was 1.55 × 107 (1.30 × 107-1.85 × 107) Bq.11 patients were treated with orchidectomy,and 11 patients were treated with androgen deprivation therapy.Results All 22 patients completed the seed implantation successfully.The 5-year biochemical progression-free survival was 70.6％,and 5-year overall survival was 81.8％.2 patients were found biochemical failure in 12 months after seed implantation,and another 1 patient failed in 90 months.Endocrinal therapy was followed thereafter.After the seed implantation,the urinary complications of grade 1 and 2 were 54.5％ and 9.1％ respectively,and the rectum side-effect of grade 1 and 2 were 22.7％ and 9.1％.1 patient suffered rectal complication of grade 4.Conclusions Good effect and tolerance are observed in prostate cancer patients of stage T3N0M0 receiving 125I seed implantation plus endocrinal therapy.The treatment can be considered for those who refuse to receive external beam radiotherapy.

Radiosensitization of cetuximab on human tongue cancer cell line Tca8113 / 中华放射医学与防护杂志

Objective To investigate the mechanism of radiosensitization by cetuximab (C225) on human tongue cancer Tca8113 cell line in vitro.Methods Tca8113 cell line with and without C225 treatment received 6 MV X-ray irradiation of different doses (0, 2,4,6, 8 and 10 Gy). Cell proliferation,cell-cycle distribution and clonogenic survival were analyzed through cell counting,MTT,colony formation assay,and flow cytometry,respectively.Results After irradiation of different doses,the growth inhibition rates in C225 group were higher than control (t =- 15.6 - -3.0,P＜0.05),the radiobiological parameters (D0,Dq,N,and SF2 ) in C225 group were lower than control so that SER of C225 group was 1.353,and the proportions of G0/G1 cells in C225 group were higher than control ( t =-7.64,-7.89,-4.78,P ＜0.05 ) at 4,6,8 Gy.When the irradiation doses increased,the early phase apoptosis in both groups increased at first and then decreased with the maximum difference at 4 Gy [(7.96±0.36)％ in C225 group and (4.13 ±0.29)％ in control group,t =-12.75,P＜0.01 ].Conclusions C225 has radiosensitization effect on Tca8113 cell line,possible through Go/G1 arrest and induction of apoptosia.

A dosimetric research on permanent radioactive ~(125)I seed plane implantation / 中国微创外科杂志

Objective To establish the isodose curves and dose calculation models of()~(125)I seed plane implantation using the three-dimensional treatment planning system(3D-TPS). Methods The isodose cures of 1 000 cGy,3 000 cGy,6 000 cGy,9 000 cGy,12 000 cGy,15 000 cGy,and 20 000 cGy and dose calculation models of triangular,quadrilateral,hexagon,and dodecagon patterns of()~(125)I seed plane implantation were created using the 3D-TPS.The isocenter dose pattern of 0,0.5,1.0,1.5,2.0,2.5,3.0,and 4.0 cm from the plane center was calculated with 3D-CRT. Results The study showed that if doses were less than 10 Gy at 2.0 cm,2.5 cm,3.0 cm and 4.0 cm apart from the center of triangular,quadrilateral,hexagon,and dodecagon patterns and the distance was beyond 1 cm between seeds,there was a low dose region in the centeral point. Conclusions The study showed that the isodose distribution curves and dose calculation models in plane implantation were primarily established using the seed implantation 3D-TPS.