Background and purpose:Deep learning methods can be used for automatic segmentation and detection of lymphocytes on pathological images.This study aimed to assess the performance of using variational autoencoding pre-training method for lymphocyte infiltration detection on pathological images,as well as the impact of removing tumor necrosis regions on model performance.Methods:Using variational autoencoding(VAE)pre-training method,pre-training was performed on a large number of unlabeled pathological images from the Cancer Genome Atlas(TCGA)database(TCGA-COAD and TCGA-READ)to obtain an auto-encoding pre-training model,and then a classifier model of lymphocyte infiltration was trained on the public data samples.To avoid confusion with necrotic regions,a Unet segmentation model for tumor necrotic regions was trained to remove the influence of tumor necrotic regions on lymphocyte identification.Results:The lymphocyte infiltration detection model pre-trained with the VAE model had an area under curve(AUC)of 0.979(95%CI:0.978-0.980),an accuracy of 92.5%(95%CI:92.3%-92.6%),a kappa value of 0.849,sensitivity of 0.908,specificity of 0.941,precision of 0.939,recall of 0.908,and F1 of 0.923 under the receiver operating characteristic(ROC)curve on the training set.The AUC for the validation set was 0.968(95%CI:0.964-0.972),the accuracy was 91.3%(95%CI:90.6%-92.0%),kappa value was 0.826,sensitivity was 0.898,specificity was 0.928,precision was 0.925,recall was 0.898,and F1 was 0.912.The results of Resnet18 model on the labeled dataset were as follows:accuracy of the validation set was 83.2%(95%CI:82.2%-84.1%),kappa value was 0.664,sensitivity was 0.823,specificity was 0.840,precision was 0.838,recall was 0.823 and F1 was 0.830.The Unet model that segmented the necrotic regions of the tumors had a final DICE of 0.78 for the training set,and 0.76 for the validation.After removing the necrotic region,the predictive performance of the pre-trained lymphocyte infiltration detection model using the VAE proposed in this article was improved to some extent,with the AUC on the validation set increasing from 0.968(95%CI:0.964-0.972)to 0.971(95%CI:0.968-0.975).The accuracy was 92.4%(95%CI:91.7%-93.0%),kappa value was 0.849,sensitivity was 0.928,specificity was 0.921,precision was 0.921,recall was 0.928,and F1 was 0.925.Conclusion:Using the variational autoencoding model pre-training method to classify the pathological pictures of lymphocyte infiltration can obtain better model performance compared with direct training,and removing the influence of tumor necrosis areas through Unet can further improve the performance of the model.

Objective:To develop and validate a structure for broadening the Bragg peak to improve the efficiency and conformality of particle radiotherapy.Methods:Techniques of random stacking and regular stacking were employed to fabricate the mesh-stacked porous structure (MPS). In each layer of the grid, the thickness, line width and spacing were set at 0.1 mm, 0.1 mm and 0.5 mm, respectively, resulting in a total size of 10 cm ×10 cm. Monte Carlo code FLUKA was performed to simulate the transportation of 196 MeV/u carbon ion beam and a 105 MeV proton beam through the MPS. Dose distribution, fluence homogeneity, and modulation stability of the modulated beams were evaluated. Moreover, the modulation effect of MPS in clinical radiotherapy plans for nasopharyngeal carcinoma (63 Gy in 21 fractions), lung cancer (77 Gy in 22 fractions) and prostate cancer (70.4 Gy in 16 fractions) was also evaluated, respectively.Results:The MPS was capable of broadening the Bragg peak width by 1.73 mm for proton beams and 2.95 mm for carbon ion beams. For different entrance positions, regular stacking of more than 10 layers could reduce the modulation power difference of MPS to within 5%. For MPS with 30 layers of regular stacking, the modulated fluence homogeneity could achieve a value of less than 3% by transporting 18 cm distance in air. When comparing to the clinically used ripple filters, MPS reduced the isocenter spot size of proton beams by 0.91 mm. In the comparison study of the treatment plan for nasopharyngeal carcinoma, the use of MPS could shorten the treatment time by 213 s (37%) and reduce the maximum dose to the brainstem by 3.28 Gy (7.5%).Conclusions:MPS effectively broadens the Bragg peak of particle beams and improves the efficiency of clinical radiotherapy. Regularly stacked MPS demonstrates robust modulation stability, and the modulated beam achieves relatively well fluence homogeneity, making it a promising clinical application for closer to the patients and reducing lateral scattering.

Background and purpose:In recent years,domestic radiotherapy equipment and related software have made great progress,and testing the functionality and stability of the equipment and software is an essential step.This paper focused on comparing the differences in intensity-modulated radiation therapy(IMRT)plans dosimetry and organ at risk(OAR)volume calculations for common cancers between uRT-treatment planning system(TPS)and Monaco-TPS,and to evaluate the feasibility of dose calculation for Infinity linac(linear accelerator,Elekta,Sweden)using uRT-TPS.Methods:Twenty cases of rectal cancer,lung cancer,breast cancer and nasopharyngeal carcinoma were selected.The IMRT plans were completed in uRT-TPS and Monaco-TPS.The dose uniformity and conformity,mean dose,maximum dose of planning target volume(PTV)and OAR between two plans under the same prescribed dose of PTV were compared.And the pass rates of two TPS plans validated at the same linear accelerator were compared.Meanwhile,monitor units(MU),source skin distance(SSD)and the volume of OAR in uRT-TPS and Monaco-TPS were compared.Results:Wonderful plans that met the clinical requirements were obtained in uRT-TPS and Monaco-TPS.Comparable uniformity and conformability was received in PTV,and the maximum dose of PTV was reduced by 1.1 Gy for uRT-TPS(P = 0.006).For breast cancer and lung cancer,the dose in lung was lower for Monaco-TPS(P＜0.05).For nasopharyngeal carcinoma,the dose indicators that oral cavity and throat in the uRT-TPS was reduced by 9.2%and 5.1%,respectively.The verification results of absolute point dose(＜3%)and three-dimensional surface dose(＞95%)for both plans met the clinical requirements.The region of interest in uRT-TPS was smaller compared with Monaco-TPS(P＜0.05).Conclusion:A comparable IMRT plan was obtained for common tumors in uRT-TPS and Monaco-TPS.It is feasible to calculate the dose of Infinity linac using uRT-TPS.

Background and purpose:BRCA1/2 plays an important role in maintaining the genome stability.Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy,thereby inducing secondary primary cancer after radiotherapy is unclear.This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer(TNBC)patients with BRCA1/2 germline mutation.Methods:This research was based on a previously reported retrospective cohort,i.e.,the Fudan University Shanghai Cancer Center TNBC cohort.Between January 1,2007 and December 31,2014,a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled.We performed logistic regression analysis in patients without BRCA1/2 germline mutation(n=261)and BRCA1/2 germline mutation patients(n=31),respectively,to assess the risk factors affecting the incidence of second primary cancer.We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy.P<0.05 indicates a statistically significant difference.The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee(050432-4-2108),and each patient provided written informed consent.Results:Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy[odds ratio(OR)=2.475,95%confidence interval(CI):1.933-3.167,P<0.001].In patients without BRCA1/2 germline mutation,the effect of radiotherapy on the incidence of second primary tumor was not significant.There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer(OR=9.710,95%CI:0.320-295.250,P=0.193).Conclusion:Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy,there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor.Therefore,patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

The purpose of this study is to establish and apply a correction method for titanium alloy implant in spinal IMRT plan, a corrected CT-density table was revised from normal CT-density table to include the density of titanium alloy implant. Dose distribution after and before correction were calculated and compared to evaluate the dose deviation. Plans were also copied to a spinal cancer simulation phantom. A titanium alloy fixation system for spine was implanted in this phantom. Plans were recalculated and compared with the measurement result. The result of this study shows that the max dose of spinal cord showed significant difference after correction, and the deviation between calculation results and measurement results was reduced after correction. The method for expanding the range CT-density table, which means that the density of titanium alloy was included, can reduce the error in calculation.
Radiotherapy, Intensity-Modulated/methods* ; Titanium ; Radiotherapy Dosage ; Alloys ; Radiometry/methods* ; Radiotherapy Planning, Computer-Assisted/methods*

Objective:To comprehensively evaluate the effects of different bolus usages in postmastectomy intensity-modulated radiotherapy (PM-IMRT) on doses.Methods:Fifty patients receiving PM-IMRT at Fudan University Shanghai Cancer Center from April to October 2021 were retrospectively studied. The planning target volume (PTV) was divided into four parts, namely chest wall (CW), internal mammary node, retained axillary lymph node, and supraclavicular node. The prescription dose was 50 Gy/25 fractions. Three PM-IMRT plans applying boluses with different thicknesses (3, 5 and 10 mm) were designed for each patient. The effects of different thicknesses and usage frequencies of boluses on PTV coverage, high dose volume of the CW skin, and dose to surrounding normal tissues were comprehensively evaluated.Results:When boluses were applied throughout the PM-IMRT, the PTV V95% of plans applying 10 mm-thick boluses was lower than that of plans applying 3 and 5 mm-thick boluses ( F=3.340, P < 0.05), the CI of plans applying 3 mm-thick boluses was higher than that of plans applying 5 and 10 mm-thick boluses ( F = 50.05, P < 0.05), and there was no statistically significant differences in the skin V105% and V110% of three plans( P > 0.05). Both PTV V95% and skin V105% were reduced with a decrease in the usage frequency of boluses. At a frequency of 20, PTV V95% decreased slightly (< 1%), while skin V105% decreased sharply to nearly half of the original values. At a frequency of 15, the PTV V95%, CI, and HI in the three plans showed no statistically significant dosimetric differences ( P > 0.05). The PTV Dmax of plans applying 3 mm-thick boluses was lower than that of plans applying 5 and 10 mm-thick boluses ( F = 9.21, P < 0.05). As for the dose to surrounding normal tissues, different bolus thicknesses and frequencies had negligible effects on doses to heart and lung, causing little different biological effects. Conclusions:For PM-IMRT, different bolus thicknesses have similar effects on doses to the PTV, skin, heart, and lung. Bolus usage frequency, rather than thickness, was the major factor determining the PTV coverage and the dose to CW skin.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

OBJECTIVE: To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR. METHODS: The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed. RESULTS: The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR. CONCLUSION Tissue engineering technology can provide a new treatment method for ATR.
Humans ; Tissue Engineering/methods* ; Tissue Scaffolds ; Rhinitis, Atrophic ; Printing, Three-Dimensional ; Cytokines

Objective:To investigate and understand current status of radiotherapy resources in the Association of Southeast Asian Nations (ASEAN) and analyze the radiotherapy needs of ASEAN countries, aiming to provide suggestions for China's radiotherapy technology international assistance work.Methods:We created a database of 10 ASEAN countries using open-source data, including data on population size, per capita gross national income, new cancer cases, and radiotherapy equipment (megavolt units). We also estimated the number of cases requiring radiotherapy and the demand for radiotherapy equipment. Descriptive statistics were used to present aggregate data and national data.Results:In 2020, the number of new cancer cases in ASEAN countries was 1.0992 million, and the estimated total number of cancer patients requiring radiotherapy was 700 300. The number of radiotherapy equipment required was 1 406. At present, the actual number of radiotherapy equipment in ASEAN countries is 564, and there is a certain gap between the existing radiotherapy resources in some ASEAN countries and the actual needs of cancer patients in their own countries. In 2040, the estimated number of new cancer cases in ASEAN countries will be 1.803 million, and the estimated total number of cancer patients who need radiotherapy in ASEAN countries will be 1.141 2 million. The number of required radiotherapy equipment will be 2 287. By 2040, the growth rate of radiation therapy equipment demand in ASEAN countries will be 305%, and all ASEAN countries need to allocate more radiotherapy resources to cope with the increase in the number of cancer patients and radiotherapy demand.Conclusions:ASEAN countries have a huge demand for radiotherapy in the next two decades, while there are significant differences among different countries. China's precision radiotherapy science and technology have huge potential for ASEAN countries. Radiotherapy science and technology international assistance work based on the needs of ASEAN countries will help China's radiotherapy continue to exert influence and promote the health and well-being of people in ASEAN countries.

Powered by big data and artificial intelligence, the research and clinical application of treatment planning automation for radiation therapy are rapidly growing. The application and supervision of planning automation systems necessitate careful consideration of different levels of automation, as well as the context for use. For autonomous vehicles, the levels of automation have been defined at home and abroad. Nevertheless, no such definitions exist for radiotherapy planning automation. To promote and standardize the development of radiotherapy planning automation and initiate discussion within the community, we developed this recommendation with reference to the taxonomy of driving automation for vehicles and divided the radiotherapy planning automation into six levels (level 1 to 6).