Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

目的 探讨将放疗流程的中期评估作为临床质量保证(QA)和质量控制(QC)环节的必要性.方法111例同期放化疗Ⅲ期局部晚期非小细胞肺癌患者,放射治疗36～40Gy时进行中期评估,根据评估结果分为修改靶区组(78例,重新定位、融合图像)和未修改靶区组(33例,执行原放疗计划);采用同期放化疗,化疗以铂类为基础的两药联合方案,放疗为调强放疗技术,初始和中期评估均采用相同的增强CT定位扫描、靶区勾画、计划设计和评估原则;观察2组剂量体积参数[双肺平均肺剂量(MLD)、全肺接收5Gy或以上辐射剂量的体积百分比(V5)、平均心脏剂量(MHD)]、放射性肺炎(RP)及放射性食管炎(RE);随访两组局部复发(LR)及局部无进展生存(LRPFS)情况.结果放疗疗程中期评估时,修改靶区组较未修改靶区组,在剂量体积参数中正常组织MLD、V5和MHD有降低,差异有统计学意义(P<0.05),表明在放疗流程中进行中期评估并及时调整放疗计划,可以降低正常肺、心脏受照射的剂量体积,从而保护正常组织器官;2组病例RE、RP发生率、局部复发、局部无进展生存比较,差异无统计学意义(P>0.05),结果表明放射治疗流程中重新调整放疗计划的中期评估,对放射性肺炎、放射性食管炎及局部控制率无影响,修改靶区安全可行.结论放疗流程中期进行中期评估并对肿瘤缩小明显患者调整放疗计划不影响疗效,可作为放射治疗临床QA/QC质控环节.

Objective:To study the effects of gantry acceleration limitations of a linear accelerator (linac) on the dosimetry of volumetric modulated arc therapy (VMAT) plans, machine efficiency, and dose verification result of VMAT plans and to explore the optimal selection of gantry motion models in the Pinnacle treatment planning system.Methods:Ten cases of nasopharyngeal carcinoma, non-small cell lung cancer, sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, and invasive ductal carcinoma of the breast were each selected for this study. Then two models were set up in the Pinnacle v9.10 treatment planning system, namely the one allowing gantry acceleration and the one limiting gantry acceleration. The same field arrangement, optimized target parameters, and optimized weights of VMAT plans were adopted in the two models, in order to analyze the dosimetric variations in targets and organs at risk (OARs) and compare the differences in treatment time and gamma passing rates.Results:The treatment time of the enrolled patients under the model allowing gantry acceleration was significantly lower than that of the patients under the model limiting gantry acceleration was adopted ( t=-6.751, -0.209, -19.523, -28.999; P< 0.05) and decreased by 15.27%, 18.07%, 19.71%, and 28.75%, respectively. Meanwhile, the conformity and uniformity of target areas were affected, while there was no statistical significance in the gamma passing rates in the validation of VMAT plans ( P>0.05). For the cases of nasopharyngeal carcinoma (NPC), the maximum dose to brainstem PRV increased by 1.25%. For the cases of lung cancer, the maximum dose to the spinal cord and lung V20 increased by 1.19% and 1.21%, respectively, while lung V5 decreased by 1.21%. For the cases of sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, the mean doses to bilateral kidneys, livers, small intestine, and colon all increased. For the cases of breast cancer, lung V10 on the opposite side of cancer increased by 1.66% and the mean dose to the lungs on the same side of cancer decreased by 7.45%. Conclusions:The model allowing gantry acceleration allows the treatment time to be significantly shortened and the treatment efficiency improved. Although this model had the shortcomings such as affecting the conformity and uniformity of target areas to a certain extent and increasing the doses to some OARs, clinical requirements for dosimetry were still met. Therefore, it is recommended to use the model allowing gantry acceleration in the Pinnacle planning system.

Abstract Purpose Maximum leaf speed is a configurable parameter of MLC in a treatment‐planning system. This study investigated the influence of MLC on the quality of VMAT plans. Methods Seven MLCs with different maximum leaf speeds (1.0, 1.5, 2.25, 3.5, 5.0, 7.5, and 10 cm/s) were configured for an accelerator in treatment‐planning system. Correspondingly, seven treatment plans, with the identical initial optimization parameter, were designed with the mdaccAutoPlan system. Six nasopharyngeal carcinoma (NPC) patients and nine rectal cancer patients were selected, representing complex and simple clinical circumstances. VMAT plan quality was evaluated with PlanIQTM software. The results were statistically analyzed with a one‐way analysis of variance (ANOVA) and pairwise comparison tests. Results The relative changes of plan scores achieved by the seven configured accelerators, with specific maximum MLC leaf speed (MMLS) for each patient, were studied. Two apparent trends of MMLS influence on VMAT plan scores were observed: Plan scores increased with MMLS; Plan scores increased rapidly when MMLS increased from 1 to 3.5, thus the relative change of plan score decreased in this MMLS range. The stationary point of maximum MLC speed (MMSSP) is defined, for the specific MMLS when the relative changes of plan scores is first <5%, as MMLS increases from 1.0 to 10. For rectal plans, MMSSPs were 2.25 for six patients and 3.5 for the other three patients. For NPC plans, MMSSPs were 3.5 for five patients and 2.25 for one patient. Conclusion This work indicates that MMLS directly influences VMAT plan quality in NPC cases and rectal cancer cases. VMAT plan quality improved conspicuously as MMLS increased from 1 to 3.5, VMAT plan quality with marginal improvement when MMLS is above 3.5.