Objective To analyze the efficacy and safety of hypofractionated stereotactic radiotherapy ( FSRT ) combined with temozolomide ( TMZ ) for large brain metastases ( BMs ) in a prospective phaseⅡclinical trial.Methods From 2010 to 2015, a total of 33 patients were enrolled as subjects.The median Karnofsky Performance Status scores before and after treatment were 70 and 80, respectively.The major primary tumor was non-small cell lung cancer (57.6%).The brain metastasis had a diameter of≥3 cm or a volume of ≥6 cm3 .The radiation dose was 52 Gy in 13 fractions or 52.2 Gy in 15 fractions.Patients received TMZ at a dose of 75 mg/m2 per day concurrently.The radiotherapy was followed by 6 cycles of adjuvant treatment with TMZ (150 mg/m2, days 1-5, 28 days per cycle).Patients were reexamined by magnetic resonance imaging ( MRI) during the treatment.The radiation field would be shrunk if the gross target volume ( GTV) was reduced by≥20%.The treatment outcomes were evaluated by MRI at 2-3 months after treatment.Results The total numbers of tumors and GTVs were 95 and 38, respectively. Twenty-four (63%) out of the 38 GTVs had a volume larger than 10 cm3 and the median GTV was 15.3 cm3 (5.7-142.8 cm3).Twenty-two (67%) out of the 33 patients achieved field shrinking during the treatment, and the median reduction rate of GTV was 44%( 21%-88%) .The median total dose was 59.5 Gy, and 100%and 21.2%of patients completed the concurrent and adjuvant treatment with TMZ, respectively.In all patients, the overall response rate was 97.0%;the 1-year local control, intracranial progression-free
survival, and overall survival rates were 97%, 70%, and 62%, respectively;the median survival time was 15.3 months.The main adverse reactions were grade 1-2 nausea and vomiting.One patient got grade 3 liver function impairment.Conclusions FSRT combined with TMZ is a safe and effective approach for treating large BMs.More than 50%of patients can achieve field shrinking to shorten treatment duration and reduce toxicity.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT02654106.

Objective:To analyze the expression of tubulin-tyrosine ligase-like 12 (TTLL12) in hilar cholangiocarcinoma and its adjacent tissues, and to explore the relationship between TTLL12 and clinicopathological features and prognosis of patients with hilar cholangiocarcinoma.Methods:The carcinoma tissues and paracancerous tissues of 45 patients with hilar cholangiocarcinoma who had been operated in Qingdao Municipal Hospital from January 2016 to December 2020 were collected to prepare paraffin sections, including 27 males and 18 females, aged (58.8±8.5) years. The expression of TTLL12 and Ki-67 was detected by immunohistochemical staining. According to TTLL12 expression in cancer tissues, 45 patients were divided into negative group ( n=15) and positive group ( n=30). The relationship between TTLL12 positive expression and clinicopathological features such as lymph node metastasis and tumor differentiation was analyzed. The correlation between TTLL12 and Ki-67 expression in cancer tissues was analyze by Spearman correlation analysis. Kaplan-Meier method was used for survival analysis, and log-rank test was used to compare the survival rate. Results:Immunohistochemical staining showed that the expression of TTLL12 and Ki-67 in 45 patients with hilar cholangiocarcinoma was significantly higher than that in paracancerous tissues. The expression of TTLL12 in hilar cholangiocarcinoma was positively correlated with that of Ki-67 (correlation coefficient was 0.601, P<0.001). The positive expression rates of TTLL12 and Ki-67 in 45 cases of hilar cholangiocarcinoma were 66.7% (30/45) and 77.8% (35/45), respectively, which were higher than those in adjacent tissues 11.1% (5/45) and 15.6% (7/45), and the differences were statistically significant ( χ2=11.25, 29.01, both P<0.001). The positive expression of TTLL12 and Ki-67 in hilar cholangiocarcinoma was correlated with lymph node metastasis and tumor differentiation (all P<0.05). The median overall survival time was 44 months in TTLL12 negative group and 21 months in TTLL12 positive group. The 5-year survival rate of TTLL12 carcinoma tissue negative expression group was 33.1%, which was better than that of TTLL12 carcinoma tissue expression positive group (18.3%), and the difference was statistically significant ( χ2=6.12, P=0.013). Conclusions:The expression of TTLL12 in hilar cholangiocarcinoma was higher than that in paracancerous tissues, and there was a positive correlation between TTLL12 and Ki-67 in carcinoma tissues. The positive expression of TTLL12 is closely related to tumor differentiation, lymph node metastasis and poor prognosis of patients. TTLL12 may be a marker for predicting the prognosis of patients with hilar cholangiocarcinoma.

Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases.Methods Between 2009 and 2017,84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT,n=42) and RT group (FSRT alone,n=42).The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions.Patients were reexamined by magnetic resonance imaging (MRI) during treatment.The radiation field would be shrunk if the gross target volume (GTV) was reduced.The clinical efficacy was evaluated at postoperative 2 to 3 months.The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),brain metastasis-specific survival (BMSS) and adverse events.The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis.Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75％ of the lesions in the CRT group were reduced compared with 34％ in the RT group (P=0.000).The local control (LC) rate in the CRT and RT groups was 100％ and 98％.The median follow-up time was 16.1 months (range,2.1-105.7 months).In the CRT group,the LRFS (P=0.040),IPFS (P=0.022),PFS (P=0.045),OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group,respectively.In the CRT group,the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33％,significantly higher compared with 26％ in the RT group (P=0.006).No grade Ⅳ-Ⅴ adverse events occurred in both groups.Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.

Objective To retrospectively analyze the dosimetry and efficacy of whole-brain irradiation (WBRT) with simultaneous integrated boost (SIB) by helical tomotherapy (HT) in the treatment of multiple brain metastases (BMs),and to evaluate the feasibility,efficacy,and safety of HT.Methods From 2014 to 2017,a total of 43 patients with multiple BMs (no less than 3 lesions) were enrolled as subjects.A dose of 40 Gy was delivered to the whole brain in 20 fractions,while a dose of 60 Gy was delivered to the gross target volume (GTV) in 20 fractions.Patients were reexamined by magnetic resonance imaging during treatment.The radiation field would be shrunk if GTV was reduced.Target coverage (TC),conformity index (CI),prescription isodose/target volume (PITV) ratio,and homogeneity index (HI) were assessed.Clinical indices included local recurrence-free survival (LRFS),intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),and toxicities.Results The median lesion number was 6(3-36) and the median total volume of GTV was 8.74 cm3.The TC,CI,PITV,and HI for GTV were 0.96±0.028,0.51±0.164,2.09±1.245,and 0.12±0.066,respectively,while the TC and HI for the whole brain were 0.95±0.033 and 0.43±0.161,respectively.In all the patients,26％ had replarming during treatment.The two-stage treatment reduced the radiation dose to organs at risk.The 1-year LRFS,IPFS,PFS,and OS rates were 96％,80％,39％,and 86％,respectively.No grade ≥3 toxicities were observed.Conclusions WBRT with SIB by HT achieves satisfactory conformity,homogeneity,efficacy,and safety,which is a recommended treatment plan for multiple BMs.Replanning during treatment can better protect normal tissue.

Objectives To evaluate the clinical efficacy and safety of hypofractionated radiotherapy for cancer patients with hepatic metastases. Methods From May 2007 to November 2016,45 patients ( male:female=20:25) with inoperable hepatic metastases were enrolled in this investigation. The median age was 58 years old ( range:25-83).The median Karnofsky performance score ( KPS) was 80.Primary colorectal cancer was detected in 14 patients,primary breast cancer in 9 and primary lung cancer in 6 cases. Twenty-one patients had extrahepatic metastases. A total of 52 lesions were treated. Thirty-four cases received radiotherapy for one single lesion. The fractional dose was 45 Gy/3 fractions and 60 Gy/10-15 fractions. The median gross tumor volume (GTV) was 10. 1 cm3(0. 3-175. 2 cm3) and 29. 8 cm3(5. 0-209. 6 cm3) for planning target volume ( PTV).Seventeen CT images were fused with MRI and IMRT was adopted in 43 cases. The median dose of PTV was 60 Gy (40-60 Gy) and 90 Gy (60-132 Gy) for bioequivalent dose (BED). Results The median follow-up time was 23. 5 months and the median survival time was 26. 0 months (95%CI:21.4-30.6 months).The 1-year local control (LC),disease-free survival (DFS) and overall survival ( OS ) were 94%, 27% and 91%, respectively. Six cases died of liver metastases and abnormal liver function. Conclusion Hypofractionated radiotherapy is an efficacious and safe local treatment for inoperable hepatic metastases.

Object the current radiological health situation of different ranks medical institutions of interventional radiology in a city of Pearl Delta. Methods all the medical institutions in the city, which had carried out interventional radiology before December 31, 2019 as the research objects by survey. By using the method of field epidemiological investigation, the basic situation of general messages, the status of protective facilities, environmental radiation does, personal protective equipment, occupational health monitoring were investigated. Results There were 12 interventional radiology equipment and 180 employees in 7 medical institutions in the city, before December 31, 2019. There was no statistical significance in the composition of employees of different ranks medical institutions (P > 0.05). There was no statistical significance in the composition of protective facilities for interventional treatment in different ranks hospitals (P > 0.05). The environmental radiation dose in interventional radiology devices room of grade A class 3 hospital was higher than that of grade A class 2 hospital (P < 0.05). There was no statistical significance in the composition of individual protective equipment for interventional therapy in different ranks medical institutions (P > 0.05). The proportion of occupational health examination before work and during work in grade A class 2 hospital was higher than A class 3 hospital (P < 0.01). Conclusion The current situation of radiological health of different ranks medical institutions of interventional radiology in a city of Pearl Delta was good momentum. It may be helpful to improve the radiological health protection level of interventional therapy in this city by strengthening the radiological protection management of applying for interventional therapy, actively carrying out the evaluation of radiological protection against occupational disease hazards in construction projects, and urging the employee to carry out the occupational health monitoring inspection as required.