OBJECTIVE: To study effective methods for reducing lung V₅, V₁₀, and mean lung dose (MLD) in the design of volumetric modulated arc therapy for central lung cancer by using different arc configurations and dose-limiting blocks designs. METHODS: Five groups of plans were designed for the enrolled patients. Group A used a full-arc field. Group B used a partial-arc field. Groups C, D, and E used full-arc fields with vertical-length, semi-ring, and triangular dose-limiting blocks added respectively. The dosimetric similarities of target areas and the dosimetric differences in lung V₅, V₁₀, V₂₀, and MLD among the groups were compared. RESULTS: Compared with group A, groups B, C, D, and E had decreased homogeneity and conformity of the target area, but significantly lower V₅ and V₁₀ of the whole lung. The MLD of groups C, D, and E was lower than that of group A. CONCLUSION Using a full-arc field combined with dose-limiting blocks can effectively reduce lung V₅, V₁₀, MLD, and monitor units (MU).
Lung Neoplasms/radiotherapy* ; Humans ; Radiotherapy, Intensity-Modulated/methods* ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Lung/radiation effects*

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective:To explore the radiological damage to cells induced by the delayed particles of 9C-ions for heavy ion therapy, as well as the microdosimetric distribution and biological effects of these particles on a single model of V79 Chinese hamster lung cells. Methods:The Monte Carlo program was employed to simulate the endonuclear absorbed doses of α particles with various energies (3-10 MeV) transported in cells (cell radius RC = 10 μm, nucleus radius RN = 5 μm). Then, the result were compared with the S values ( SN←N, SN←Cy, and SN←CS) derived using the medical internal radiation dose (MIRD) method to demonstrate the feasibility of Monte Carlo simulations. Finally, the energy deposition of the delayed particles of 9C-ions generated at three sites (i.e., on the surface and in the cytoplasm and nucleus of the V79 cell model) during their transport in targets was simulated, and the result ing cell surviving fraction was analyzed. Results:Monte Carlo and MIRD method yielded differences in S values of 1.91%-4.95% for SN←N (nucleus to nucleus), 1.48%-5.11% for SN←Cy (cytoplasm to nucleus), and -1.99% to 0.80% for SN←CS(surface to nucleus), indicating highly consistent S values derived using both method(differences < 6%). When a 9C-ion decayed on the surface of the V79 cell model and the produced secondary particles entered the cell, the average endonuclear absorbed dose was 10 -2 Gy orders of magnitude, with a cell surviving fraction of about 88%. In the case where decay occurred in the cytoplasm, the cell surviving fraction was about 80%. However, when the 9C ion decayed in the nucleus, α particles had short ranges and deposited most of their energy in the cell (mean endonuclear absorbed dose: 0.1 Gy). In this case, severe cell damage was induced, with the cell surviving fraction reducing to about 53%. Conclusions:9C-ions emit secondary charged particles due to decay, among which α particles cause great damage to cells when entering the nucleus and trigger evident biological effects.

Objective:To investigate the correlations of urinary adverse reactions with dose to the bladder and urethra during external pelvic irradiation for locally advanced cervical cancer.Methods:This study retrospectively collected relevant dosimetric parameters and urinary symptoms, such as frequent, urgent, and painful urination, from locally advanced cervical cancer patients treated with external pelvic irradiation in the Department of Oncology, Affiliated Hospital of Guizhou Medical University. The dosimetric parameters examined in this study included the maximum, minimum, and mean doses to bladder and urethra (i.e., Dmax, Dmin and Dmean), mean doses received in an area of 0.1, 1, and 2 cm 3 around the planning target volume, D0.1 cm 3, D1 cm 3, D2 cm 3, and percentages of irradiated volumes in the whole organ volume under doses of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 Gy, V5 Gy, V10 Gy, V15 Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy, V50 Gy. Then the correlations between urinary symptoms and these dosimetric parameters were analyzed using the independent-sample t-test and the Logistic regression model. Results:The median volumes of bladder and urethra were 294.8 and 4.71 cm 3, respectively. Patients were divided into two groups based on the median division. The univariate analysis showed that urethral Dmax, Dmin, Dmean, V5 Gy, V10 Gy, V15Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy and V50 Gy correlated with urinary complications ( t = 14.30, 21.65, 32.19, 33.36, 16.62, 17.91, 21.52, 20.11, 12.27, 37.25, 30.18, 36.24 and 21.98, P<0.05). The multivariate analysis further indicates that urethral D2 cm 3, V20 Gy, V40 Gy and Bladder V40 Gy, D1 cm 3, D2 cm 3 were independent predictors of grade 2 urinary adverse reactions ( P<0.05). Conclusions:This study reported the correlations of relevant dosimetric parameters of urethra with urinary toxicity during external pelvic irradiation. It holds that urethral D2 cm 3, V20 Gy and V40 Gy should be restricted to minimize the risks of grade 2 urinary complications.

Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

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.

Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.