ABSTRACT
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.
ABSTRACT
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.