Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

Objective To investigate the safety and efficacy of camrelizumab added to second-line therapy after drug- eluting bead transarterial chemoembolization (DTACE) combined with apatinib for unresectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 89 HCC patients with camrelizumab added to second-line therapy who attended The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) after the application of camrelizumab, and the secondary endpoints were objective remission rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). The Kaplan-Meier method was used to plot survival curves, the Log-rank test was used for stratified analysis of subgroups based on baseline characteristics, and the influencing factors for prognosis were analyzed. Results A total of 89 patients were screened and followed up in this study. The patients were followed up to December 2021, with a median follow-up time of 16 months, a median OS time of 17.0 (95% confidence interval [ CI ]: 15.3-18.7) months, and a median PFS time of 7.0 (95% CI : 6.2-7.8) months. There were significant differences in OS and PFS between the patients with different ECOG-PS scores, liver function Child-Pugh classes, portal vein invasion, patterns of progression, times of DTACE treatment, durations of oral administration of apatinib, and durations of application of camrelizumab (all P < 0.05). At 3 and 6 months after the application of camrelizumab, ORR was 39.3% and 22.4%, respectively, and DCR was 80.9% and 54.1%, respectively. The univariate analysis using the Log-rank test showed that compared with the patients receiving 0 time of DTACE treatment, the patients receiving 3-4 or 1-2 times of DTACE treatment had significant improvements in median OS [22.0 (95% CI : 21.1-22.9) months and 17.0 (95% CI : 15.8-18.2) months vs 10.0 (95% CI : 7.0-13.0) months, χ 2 =31.423, P < 0.001] and PFS [10.0 (95% CI : 7.0-13.0) months and 7.0 (95% CI : 6.2-7.8) months vs 3.0 (95% CI : 1.9-4.1) months, χ 2 =20.741, P < 0.001]; compared with the patients using apatinib for ≤4 months, the patients using apatinib for > 4 months had significant improvements in median OS [21.0 (95% CI : 19.1-22.9) months vs 14.0 (95% CI : 10.4-17.6) months, χ 2 =19.399, P < 0.001] and PFS [9.0 (95% CI : 7.3-10.7) months vs 5.0 (95% CI : 4.0-6.0) months, χ 2 =27.733, P < 0.001]; compared with the patients using camrelizumab for ≤5 months, the patients using camrelizumab for > 5 months had significant improvements in median OS [22.0 (95% CI : 20.2-23.8) months vs 13.0 (95% CI : 9.3-16.7) months, χ 2 =22.336, P < 0.001] and PFS [9.0 (95% CI : 7.0-11.0) months vs 5.0 (95% CI : 4.1-5.9) months, χ 2 =26.141, P < 0.001]. Post-embolization syndrome was the adverse event after DTACE and resolved after symptomatic treatment. Adverse reactions related to targeted drugs and immunotherapy all resolved after symptomatic supportive treatment, with no grade ≥4 adverse reactions, and no patients withdrew from target-free therapy due to TRAEs. Conclusion As for DTACE combined with apatinib in the treatment of unresectable HCC, camrelizumab added after progression has a marked therapeutic efficacy with safe and controllable TRAEs.

Objective To study the effects of cleavage of Bcl-2 by two DNAzymes on apoptosis of human hepatoma cell line (HepZ1).Methods Two “10-23” DNAzymes(DzT and DzTi) targeting Bcl-2 mRNA and their analogues(DzT' and DzTi') were synthesized and used to cleave Bcl-2 mRNA in vitro and in BEL-7402 cells.The RT-PCR was performed to assess the cleaving efficiency.Expression of Bcl-2 protein was determined by immunofluorescent method.Cell apoptosis was detected by flow cytometry.Results The unmodified Enzymes DzT,and its modified form DzTi,which had an added 3'-inverted thymidine,could effectively cleave Bcl-2 mRNA in vitro.After transfected into BEL-7402 cells,DzTi exhibited more powerful cleaving ability than DzT,significantly down-regulated the level of Bcl-2 protein(P ＜0.01) and inhibited the cell growth(P ＜0.05).The results of flow cytometry suggested that the apoptosis rate of DzT and DzTi significantly increased,appeared apoptotic peak.Cell cycle was delayed in DzT and DzTi group,proportion of cells in G0/G1 increased,S phase cells decreased.Conclusion The synthesized DNAzymes could effectively cleave Bcl-2 mRNA,decrease the level of Bcl-2 protein and induce hepatoma cells apoptosis.