1.Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.
Yanze SUN ; Xinmiao YU ; Xiao WANG ; Kai YUAN ; Gefei WANG ; Lingrong HU ; Guoyu ZHANG ; Wenli PEI ; Liping WANG ; Chengliang SUN ; Peng YANG
Acta Pharmaceutica Sinica B 2023;13(9):3583-3597
In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.
2.Actual measurement verification of dose calculation accuracy based on cone-beam CT images
Li CHEN ; Gang ZHOU ; Yanze SUN ; Qiliang PENG ; Jieguan HAN ; Ye TIAN
Chinese Journal of Radiation Oncology 2023;32(6):539-545
Objective:To evaluate the dose calculation accuracy of cone-beam CT (CBCT) image by actual measurement method.Methods:CBCT images of 60 patients in the Second Affiliated Hospital of Soochow University from September, 2021 to May, 2022 were retrospectively analyzed. CBCT images of full-fan and half-fan scanning of the head, half-fan scanning of the chest and pelvis were obtained by the Varian OBI system. Hounsfield unit - electron density (HU-ED) curves corresponding to the scanning conditions were established with CIRS electron density phantom. The radiotherapy plans were designed on the CBCT images, and the dose calculation results of the detection point were compared with the ionization chamber measurement results to analyze the dose error. Then, three-dimensional dose verification system was adopted to detect the accuracy of the CBCT image radiotherapy plans implementation process in 60 patients, and the accuracy of dose calculation was verified according to the D 99%, D mean, D 1% of target volume, D mean and D 1% of organs at risk (OAR), and the γ pass rate. Results:In point dose detection in phantom, the dose calculation errors of CBCT images in the above four scanning patterns were -1.06%±0.87%、-1.67%±0.86%, 0.91%±0.73%, -1.54%±0.90%, respectively. In dosimetric verification based on patients' CBCT image treatment plan, the mean difference of D mean, D 99%, and D 1% of planning target volume (PTV) in all scanning modes were not higher than 2%, and the D mean and D 1% differences of other OAR were not higher than 3%, except for the lens of patients in the head. The average γ values of target volume and OAR were less than 0.5 under the criteria of 3%/2 mm. Conclusions:Under the condition of correctly establishing HU-ED curves, intensity-modulated radiation therapy (IMRT) / volumetric-modulated arc therapy (VMAT) planning based on CBCT images can be employed to estimate and monitor the actual dose to target volume and OAR in adaptive radiotherapy. Full-fan scanning patterns can further improve the accuracy of dose calculation for the head of patients.
3.Convolutional neural network-based three-dimensional dose reconstruction using volumetric scintillation light
Shuncheng DONG ; Yanze SUN ; Yue YANG ; Yonghuan DU ; Peiyi ZHANG ; Wensheng ANG ; Wanxin WEN
Chinese Journal of Radiological Medicine and Protection 2023;43(12):1034-1040
Objective:To reconstruct the three-dimensional (3D) dose distribution in radiotherapy based on the convolutional neural networks (CNN) through multi-perspective scintillation light processing.Methods:First, fluorescence images were captured from three orthogonal perspectives using a complementary metal-oxide-semiconductor (CMOS) imaging sensor. Then, the images were converted into 3D images, which were input to the trained CNN for dose reconstruction. Finally, the reconstructed doses in different fields were evaluated in terms of gamma pass rate, mean-square error (MSE), percentage depth dose (PDD), and cross beam profile (CBP). Additionally, as the CNN model, 3D-Unet was pre-trained on a virtual dataset.Results:With the 50% maximum dose of as the threshold and 3%/3 mm as the standard, the central-plane and stereo-mean gamma pass rates of all field reconstruction distributions were over 90%, with MSEs remained below 1%. Besides, the PDD and CBP curves showed MSEs below 1‰ and below 1%, respectively.Conclusions:The deep learning-based method for 3D dose reconstruction using scintillation light contributes to enhanced verification of instantaneous 3D relative dose based on plastic scintillation detectors.
4.Current situation investigation on the standardization of physical dose description in radiobiology researches in China
Yanze SUN ; Jianjun QIAN ; Ye TIAN
Chinese Journal of Radiological Medicine and Protection 2022;42(10):812-816
Objective:To understand the normative status of physical dose description in domestic radiobiology studies through literature study.Methods:According to the scoring system recommended by the National Cancer Institute (NCI) and Desrosiers et al, evaluate (full Score: 10 points) the normalization of physical dosimetry description in the radiobiology-related articles published in two important journals, Chinese Journal of Radiation Oncology and Chinese Journal of Radiological Medicine and Protection, in past 5 years.Results:A total of 222 relevant articles from these two journals were included, and a median score of 5.0 was evaluated. Among them, 72.1% of the literatures scored 4.0-7.0 points, 68.0% of the literatures scored ≤5.5 points, and 18.5% scored ≤3.0 points. 90.1% and 97.7% of the literatures described " the type of ray" and " absorbed dose" , with the highest average score (0.90 and 0.98 points) respectively. The lowest average score of " dosimetry calibration" was 0 point.Conclusions:Although the most of literatures described " the type of ray" and " absorbed dose" , most other details of dosimetric parameters were not reported. Therefore, there is a deficiency in the standardized description of physical dosimetry in domestic radiobiology literatures, which may affect the reproducibility and interpretability of research result.
5.Study of improving IMRT dose accuracy in patients with metal implants by density filling and artifact reduction
Peifeng ZHAO ; Gang ZHOU ; Yanze SUN ; Yongqiang YANG ; Pengfei XING
Chinese Journal of Radiation Oncology 2020;29(5):378-382
Objective:To explore the method of improving the accuracy of dose calculation of treatment plan in radiotherapy for patients with metal implants.Methods:A CT simulator with metal artifact reduction technique (MAR) was utilized to scan the CIRS intensity-modulated phantom with metal rods and 8 patients with steel nails implanted in the centrum for radiotherapy. Radiotherapy plans were designed using conventional CT images, MAR images and density-filled images. The dose calculation errors between single field and intensity-modulated radiotherapy (IMRT) plan were compared. The effect of mental implants and their artifacts on the irradiation dose of IMRT plan was evaluated.Results:In the conventional CT images of the phantom, when the incident path of the field failed to pass through the metal region, the dose calculation error for a single field was 3.85%, and the range of dose error for the field was 4.46%-74.11% when passing through the metal region. IMRT planning errors might exceed the clinically acceptable range when the incident path of the field passed through the metal region, and the errors tended to increase with the increase of dose weight of this field. After processing the images with density filling and artifact reduction techniques, the errors of the single field were 1.23% and 0.89%-4.73%, respectively, and the dose error of IMRT was 1.84%. The error of IMRT plan was 1.88% if density filling technique alone was employed to process the metal region. Due to the influence of metal implants and their artifacts, the minimum dose, average dose and prescription dose coverage actually received in the tumor target area were lower than IMRT plan results based on conventional CT images. The dosimetric difference of organs at risk was not statistically significant.Conclusions:In the radiotherapy plan based on conventional CT images, there may be a large dose calculation error when the incident path of field passes through the metal region. If the metal material is known, density filling of the metal region in the planning system can effectively improve the accuracy of dose calculation. Metal artifact reduction technique can significantly improve the image quality and further reduce dose calculation error, which should be a routine technique for CT machines equipped with this function to perform simulated localization of patients with metal implants.
6. Evaluation and prediction of pelvic dose in postoperative IMRT for cervical cancer
Yanze SUN ; Yongqiang YANG ; Jianjun QIAN ; Ye TIAN
Chinese Journal of Radiation Oncology 2020;29(2):136-140
Objective:
To evaluate and predict the pelvic dose by analyzing two pelvic contour definitions and identify the influencing factors of the pelvic dose in postoperative IMRT for cervical cancer, aiming to provide reference for postoperative pelvis-sparing IMRT for cervical cancer.
Methods:
Sixty cervical cancer patients receiving postoperative IMRT with unrestricted pelvic dose were selected. Two sets of pelvic contours (pelvic anatomy and pelvic Mell) were delineated as per the anatomical and Mell methods. The dose relationship between two methods was analyzed after redesigning the treatment plan by limiting dose of pelvic anatomy. The correlation analysis was performed by
7.Multileaf collimator shielding technique to reduce cardiac dose in hybrid intensity modulated radiotherapy after breast conserving surgery for left-sided breast cancer
Peifeng ZHAO ; Gang ZHOU ; Yanze SUN ; Li ZOU ; Ye TIAN
Chinese Journal of Radiological Medicine and Protection 2019;39(2):107-112
Objective To reduce the risk of radiation-induced cardiac injury in patients with left breast cancer after breast-conserving surgery by multileaf collimator (MLC) shielding technique.Methods A total of 18 patients with left breast cancer after breast conserving surgery were selected to obtain 3DCT and 4DCT images at free breathing state.The target area was identified on the 3DCT image by registration with 4DCT images and to develop a hybrid intensity-modulated treatment plan (H_IMRT) and a heart sparing hybrid intensity-modulated treatment plan (HSH_IMRT) to introduce MLC shielding technology to reduce the cardiac exposure dose,and to perform dosimetry verification of the treatment plan by using the Compass verification system.The prescription dose was 50 Gy in 25 fractions.The dosimetry parameters of the target area and the organs at risk were compared between the two treatment plans and the dose verification result.Results The result of the treatment plan showed that compared with H_IMRT,the dose uniformity of the target area of HSH_IMRT was better,and the difference of conformability was not statistically significant (P>0.05).The mean dose of the whole heart decreased by 23.67% (t =13.693,P<0.05) compared with the former.Dmax and D of other substructures of the heart were lower than the former.The result of dose verification showed that there was no statistically significant difference in uniformity and conformity between the two planned target doses (P> 0.05).The mean dose of the whole heart of HSH_IMRT was 24.88% (t =13.782,P<0.05) lower than that of H_IMRT,and except for the left ventricle and right ventricle,the Dmax of other heart substructures and D of all heart substructures decreased.Both the planned and the dose verification result showed that the V20 and the D of the affected lung were lower in HSH_IMRT.Conclusions Reasonable introduction of MLC shielding technology in H_IMRT can reduce the exposure dose of cardiac and further reduce the risk of radiation damage in heart.
8.Dose protection of testis with low melting point lead during postoperative radiotherapy for stage Ⅰ-Ⅱ B testicular seminoma
Liming YAN ; Gang ZHOU ; Liesong CHEN ; Li ZOU ; Yanze SUN ; Ye TIAN
Chinese Journal of Radiological Medicine and Protection 2018;38(2):110-114
Objective To assess the protective effect of low melting point lead and field margin on the opposite testicular in testicular seminoma patients during postoperative radiation.Methods A patient with stage Ⅰ seminoma was selected and his phantom measurement was carried out.The PTW 0.6 cm3 type ionization chamber was used to measure the absorbed dose under the conditions of no lead and low melting point lead with thickness of 3,5,7,10 and 15 mm at different distances from the field edge,respectively.Results Under different lead thickness conditions,the measurement result and the distance between the measured points and the boundary of the field were exponentially attenuated.The relative target dose dropped from 8.41% at 1 cm to 0.61% at 25 cm without lead blocking,and dropped from 4.55%,3.98% and 3.47% at 1 cm to0.27%,0.21% and0.17% at 25 cm with 3,5,7 cmlead,respectively.With 10 mm lead,it dropped from 2.55% at 1.5 cm to0.15% at25 cm,and 1.86% at2 cm to0.13% at 25 cm with 15 mm lead.The lead shield of 3,7 and 15 mm thickness can be used to reduce the scatter dose of testis to below 0.5 Gy during radiotherapy for seminoma.Conclusions An appropriate thickness of low melting point lead might reduce the dose of testis conveniently and effectively,which would be beneficial to protect the fertility of the patients with testicular seminoma.
9.Impact of actual gantry angle on accuracy of intensity-modulated radiotherapy for nasopharyngeal carcinoma
Yanze SUN ; Gang ZHOU ; Liesong CHEN ; Jianjun QIAN ; Yaqun ZHU ; Ye TIAN
Chinese Journal of Radiation Oncology 2017;26(10):1182-1186
Objective To investigate the impact of actual gantry angle on the accuracy of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods A total of 27 patients with NPC were enrolled in this study. IMRT plans were designed with Pinnacle treatment planning system (TPS),and 8 beams with an interval of 30°(within 0°-360°) were selected for each plan. These plans were divided into plan A and plan B according to the beam parameters. In plan A,the minimum sub-field area was 5 cm2 ,the minimum number of sub-field monitor unit ( MU) was 5,and the maximum sub-field number was 80;in plan B,the minimum sub-field area was 8 cm2 ,the minimum number of sub-field MUs was 8,and the maximum sub-field number was 60.The gamma passing rate using the criteria of 3%/3 mm and 2%/2 mm at actual and zero degree gantry angles were calculated using Mapcheck 2 device for dose verification,and were compared with the paired t-test. The relationship between the above differences (Δ value) and the beam angle or the beam parameters was also analyzed. Results In plan A with the criteria of 3%/3 mm, the beams were significantly different (P=0000-0007) except for at angles of 270°,300°,and 300°,and the mean Δ value was 090%;under the criteria of 2%/2 mm,all beams were significantly different ( P=0000-0019) except for at an angle of 300°,and the meanΔvalue was 272%.In plan B with the criteria of 3%/3 mm,the beams showed no significant difference ( P=0052-0639) except for at an angle of 300 ° ,and the mean Δ value was 040%;under the criteria of 2%/2 mm,all beams showed no significant difference ( P>005) except for at angles of 210°,240°,270°,and 300°,and the meanΔvalue was 152%.When the plan B parameters were used, the Δ value was reduced;the results of two verification methods were more consistent,so the accuracy was also improved. Conclusions Compared with the validation method at zero degree gantry angle,the validation method at an actual gantry angle is associated with reduced gamma passing rate because of some factors such as gravity,which is not significantly related to the beam angle,but the beam parameters. In the design of IMRT plans for NPC,the total number of sub-fields should be decreased as far as possible,and the minimum sub-field area and the minimum number of MU should be increased, so as to improve the accuracy of treatment plans.
10.Uncertainty of small bowel dose?volume and normal tissue complication probability assessment due to small bowel motility during intensity?modulated radiotherapy for rectal cancer
Jianjun QIAN ; Yanze SUN ; Yongqiang YANG ; Liesong CHEN ; Ye TIAN
Chinese Journal of Radiation Oncology 2017;26(3):310-315
Objective To evaluate the uncertainty of the small bowel dose?volume and the normal tissue complication probability (NTCP) during intensity?modulated radiotherapy (IMRT) for rectal cancer, and to provide a reference for the dose limit and protection of the small bowel during IMRT for rectal cancer. Methods A total of 20 patients with rectal cancer who received postoperative adjuvant radiotherapy from March 2014 to August 2015 were enrolled in this study, including 10 patients receiving CT scan in the supine position and 10 patients in the prone position. All patients received computed tomography ( CT) scan before the treatment and at weeks 1, 2, 3, and 4 of treatment, and they were defined as Plan, 1W, 2W, 3W, and 4W CT groups, respectively. The small bowel loop ( BL ) and peritoneal space ( PS ) were delineated on the images. The IMRT plan based on the Plan CT was copied to the 1W, 2W, 3W, and 4W CT groups, and then the small bowel dose?volume and NTCP were assessed for all CT groups. The paired t?test was used for comparison between groups. The Pearson method was used to analyze the correlation between NTCPC(chronic NTCP) and dose?volume. Results A total of 89 CT images of 20 patients were obtained. In all the patients, the volumes of BL and PS were 25121 cm3 and 132416 cm3 , respectively, and the shift% was 2315% and 1134%, respectively. The V15 of BL and PS was 18486 cm3 and 79245 cm3 , respectively, and the shift% was 3169% and 370%, respectively. The V30 of BL and PS was 8801 cm3 and 64573 cm3 , respectively, and the shift% was 3766% and 1049%, respectively. The V15 of BL in 35% of patients and V15 of PS in 20% of patients, the Dmax of BL in 50% of patients, and the NTCP of 15% of patients in the course of treatment exceeded the safety limits. The 1?4W CT groups had a significantly higher NTCPC than the Plan CT group (402% vs. 320%, P=0104), and their SD% was 4168%. There was a significant correlation between NTCPC and V30?V50 of BL (R>0400, P=0000). The NTCPA ( acute NTCP ) and NTCP C in the supine position were significantly higher than those in the prone position ( 6230% vs. 5674%, P=0061;488% vs. 322%, P=0145 ) . Conclusions Small bowel motility leads to an uncertainty of the adverse event assessment during IMRT for rectal cancer. The change in BL is significantly larger than that in PS and the change in BL and PS in the supine position is significantly larger than that in the prone position. Using the prone position and minimizing V15 and V30 when designing the treatment plan can reduce the NTCP A and NTCP C in the small bowel.

Result Analysis
Print
Save
E-mail