Objective To present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Objective:To evaluate the clinical application value of the adaptive aperture by comparing intensity-modulated proton radiotherapy(IMPT) plans using and not using the aperture for brain tumors.Methods:A total of twenty patients treated with postoperative radiotherapy for brain tumors were enrolled in this study. IMPT plans were developed for each patient using and not using the adaptive aperture under the same optimization conditions. The target conformal index (CI) value, target homogeneity index (HI) value, and the dose to normal tissues of the two sets of plans were compared.Results:The IMPT plans designed using the adaptive aperture significantly increased the mean CI value from 0.58 to 0.66, while decreasing the mean 50% prescription dose volume from 797.70 cm 3 to 638.15 cm 3. These plans also reduced the irradiation doses to the cochlea, brainstem, optic chiasm, optic nerve, and lens ( t = 2.06, 3.02, 2.11, 2.58, 2.67, P < 0.05). Additionally, there was no significant difference in the HI value of the target volumes and the machine jumps (MU) between the two sets of plans ( P > 0.05). Conclusions:The adaptive aperture can significantly reduce the irradiation dose to normal tissues outside the target volumes, positively impacting the protection of organs at risk (OARs) around the target values. This demonstrates its great potential for clinical application.

Objective To analyze the daily quality assurance(QA)measurement results of IBA Sphinx Compact device on the Mevion compact pencil beam scanning proton therapy system for evaluating its clinical application value in proton therapy.Methods The daily QA measurement of Mevion S250i proton therapy system was carried out with Sphinx Compact device for 30 consecutive days,and the measurement results were analyzed.Results The average deviation between the positioning laser and the image center was(0.42±0.27)mm in 30 days.All of the proximal and distal depth errors of the high-and low-energy pencil beams were within 0.50 mm.The position deviation of all the spots measured did not exceed 1.00 mm,and the size deviation was less than 7.5%.The deviation between the image center and the beam center was not more than 0.75 mm.The relative deviation of the flatness of the rectangular field was about 0.5%.The deviation of the output dose of the square field was within 1.0%.Conclusion The proton system daily QA measurement items recommended by AAPM TG-224 report can be accurately and rapidly measured with Sphinx Compact device.The device is a practical and efficient daily QA tool with high practical value in clinic.

Objective:To discuss the acceptance test of beam performance and mechanical precision of the first Mevion type S250i proton therapy system in China,and verify the stability and reliability of that in clinical treatment.Methods:According to the requirements of acceptance report of manufacturer,the output and range of machine unit(MU),the accuracy and stability of size and position of beam spot,the penumbra and position accuracy of adaptive aperture(AA)of Mevion type S250i proton therapy system,as well as the tests of mechanical properties and functions of the requirement of clinical use,were checked and tested for acceptance.Results:The maximum deviation of MU output was 1.3%,and the maximum deviation of the range was 0.037 g/cm2,and the maximum distal fall-off was 0.465 cm,and the minimum range of energy modulation was 0.21 g/cm2.The maximum deviations of the size of beam spot and the maximum deviation of the position were respectively 0.07 cm and 0.05 cm.The maximum AA penumbra was 0.007 cm,and the AA position accuracy was less than 0.1 cm.Conclusion:The acceptance test of the Mevion type S250i proton therapy system indicates that the parameters of the beam performance and mechanical precision can meet the requirements of the acceptance contract and AAPM-TG224 report of manufacturer,which has verified the machine has better favorable stability and reliability.

Objective:To measure and assess relevant radiation doses at the radiotherapy site of the first domestic single-vault proton therapy system.Methods:The radiation levels of the therapy system during and after beam irradiation were measured, and annual effective doses were assessed for personnel at the site.Results:During beam irradiation, the highest radiation dose was detected at the shielded door of the equipment floor, with a gamma radiation level of 2.140 μSv/h and a neutron radiation level of 0.850 μSv/h. Neutron radiation disappeared immediately once the beams stopped. In contrast, the radiation activated originated mostly from gamma rays. A longer time after beams stopped was associated with lower induced radiation intensity at the same location. Furthermore, a farther distance from the irradiated object corresponded to lower induced radiation intensity at the same time. The assessment result reveal that the annual effective doses to the personnel were at the safe level, with physicists exposed to the highest dose of 2.138 mSv.Conclusions:The radiation level at the studied proton therapy site meets the safety requirement, and the treatment can be performed safely at this site.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective To investigate the expression of Nodal and its receptors in different tissues and organs of different development stages of mice.Methods Ten pairs(male and female each for a pair) of mice were divided into the four groups:3 pairs served as adult mice group,the rest 7 pairs were allowed to mate,among them 3 pregnant mice served as the fetal group,and 3 pregnant mice served as the neonatal group and 1 pregnant mouse served as filial group.The multiple tissues and organs such as brain,liver,kidney,heart,lung were selected from fetal,neonatal,filial and adult mice for preparing the protein samples.Western blot was performed to detect the expression of Nodal and its type Ⅰ receptors of ALK7 and ALK4 as well as auxiliary receptor Cripto-1.Results Only cerebrum,cerebellum,liver and kidney had Nodal express in the four different mouse ontogenetic stages,in which only liver and kidney simultaneously expressed Nodal and its receptor protein in the whole four ontogenetic stages.Besides,most tissues and organs of adult mice expressed Nodal and its receptor protein,which was significantly different from the fetal,neonatal and filial mice.Conclusion Nodal signaling might have a certain effect on the growth and development of mouse liver and kidney during the late development stage.

Objective To obsevre the clinical efficacy of acupuncture at bilateral sphenopalatine ganglions in treating allergic rhinitis. Methods Patients with allergic rhinitis were selected, and then were randomly divided into bilateral group, unilateral group, and control group, with 35 cases in each group. By the end of the study, 5 cases of bilateral group, 3 cases of unilateral group, and 2 cases of control group were removed. The bilateral sphenopalatine ganglions were acupunctured simultaneously in bilateral group, and the unilateral sphenopalatine ganglion was treated by acupuncture in unilateral group, once a week, for 4 weeks. The control group received routine acupuncture on Yingxiang (LI20), Bitong (EX-HN8), Yintang (EX-HN3), and Hegu (LI4), twice a week, for 4 weeks. Rhinitis symptom scale and life quality of nasal conjunctival scale score before and after treatment in the three groups were observed. The clinical efficacy was evaluated and the adverse reactions were recorded. Results The total effective rates of bilateral group, unilateral group and control group were 93.33% (28/30), 90.63% (29/32) and 72.73% (24/33), respectively, and the bilateral group and unilateral group were better than the control group (χ2=19.507, P=0.001), without statistical significance between bilateral group and unilateral group (P>0.05). Rhinitis symptoms and life quality were improved in the three groups (P<0.05), and the bilateral group and unilateral group were better than the control group (P<0.05), without statistical significance between bilateral group and unilateral group (P>0.05). Only 1 case of subcutaneous hematoma showed in unilateral group. Conclusion Acupuncture at sphenopalatine ganglions has confirmed efficacy, and there is no difference in the efficacy between acupuncture on bilateral sphenopalatine ganglions and unilateral sphenopalatine ganglion.

Objective To investigate the design and manufacture of 3D printed compensator in electron radiation therapy for Merkel cell carcinoma,and to verify the feasibility of this technique in electron radiation therapy.Methods Computed tomography was used to collect images of a human head phantom.The delineation of target volume of Merkel cell carcinoma was simulated in the planning system and a radiotherapy plan was formulated after adding the compensator.The compensator was printed out by a 3D printer and fixed on the head phantom.A second CT scan was performed to make a new treatment plan.For the two plans,several planes parallel to the beam were selected to calculate gamma passing rates.The actual dose distribution was measured using disposable films.The gamma passing rate was compared between the film system and the planning system.The conformity index (CI) and the heterogeneity index (HI) of target volume were compared between the plans using the printed compensator and the conventional compensator of the same thickness.Comparison between the two plans was made by paired t test.Results Using the dose distribution of the plan with simulated compensator,the gamma passing rate was 94.7±2.3％ in the plan with 3D printed compensator.Using the dose distribution measured by the film,the gamma passing rate was 96.6％ in the plan with 3D printed compensator.Compared with the conventional compensator,the 3D printed compensator achieved a significantly elevated CI (0.85 vs.0.69,P=0.004) and a slightly improved HI (1.30 vs.1.26,P=0.001).Conclusions The conformal dose distribution provided by 3D printed compensator for tumors at different depths meets the clinical need.