Purpose: To evaluate the sensitivity to set up the uncertainty of VMAT plans in Nasopharyngeal carcinoma (NPC) treatment by proposing a plan robustness evaluation method. Methods: 10 patients were selected for this study. A 2-arc volumetric-modulated arc therapy (VMAT) plan was generated for each patient using Varian Eclipse (13.6 Version) treatment planning system (TPS). 5 uncertainty plans (U-plans) were recalculated based on the first 5 times set-up errors acquired from cone-beam computer tomography (CBCT). The dose differences of the original plan and perturbed plan corresponded to the plan robustness for the structure. Tumor control probability (TCP) and normal tissues complication probability (NTCP) were calculated for biological evaluation. Results: The mean dose differences of D_98% and D_95% (ΔD_98% and ΔD_95%) of PTVp were respectively 3.30 Gy and 2.02 Gy. The ΔD_98% and ΔD_95% of CTVp were 1.12 Gy and 0.58 Gy. The ΔD_98% and ΔD_95% of CTVn were 1.39 Gy and 1.03 Gy, distinctively lower than those in PTVn (2.8 Gy and 2.0 Gy). The CTV-to-PTV margin increased the robustness of CTVs. The ΔD_98% and ΔD_95% of GTVp were 0.56 Gy and 0.33 Gy. GTVn exhibited strong robustness with little variation of D_98% (0.64 Gy) and D_95% (0.39 Gy). No marked mean dose variations of D_mean were seen. The mean reduction of TCP (ΔTCP) in GTVp and CTVp were respectively 0.4% and 0.3%. The mean ΔTCPs of GTVn and CTVn were 0.92% and 1.3% respectively. The CTV exhibited the largest ΔTCP (2.2%). In OARs, the brain stem exhibited weak robustness due to their locations in the vicinity of PTV. Bilateral parotid glands were sensitive to set-up uncertainty with a mean reduction of NTCP (ΔNTCP) of 6.17% (left) and 7.70% (right). The D_max of optical nerves and lens varied slightly. Conclusion: VMAT plans had a strong sensitivity to set-up uncertainty in NPC radiotherapy, with increasing risk of underdose of tumor and overdose of vicinal OARs. We proposed an effective method to evaluate the plan robustness of VMAT plans. Plan robustness and complexity should be taken into account in photon radiotherapy.

Purpose: We aim to evaluate the robustness of multi-field IMRT and VMAT plans to target motion for left-sided BC radiotherapy. Methods: The 7-field hybrid IMRT (7F-H-IMRT) and 2-arc VMAT (2A-VMAT) plans were generated for ten left-sided BC patients. Shifts of 3 mm, 5 mm, and 10 mm in six directions were introduced and the perturbed dose distributions were recalculated. The dose differences (∆D) of the original plan and perturbed plan corresponded to the plan robustness for the structure. Results: Higher ∆D_98%, ∆D_95%, and ∆D_mean of CTV were observed in 2A-VMAT plans, which induced higher tumor control probability reductions. A higher ∆Dmean of CTV Boost was found in 7F-H-IMRT plans despite lower ∆D_98% and ∆D_95%. Shifts in the S-I direction exerted the largest effect on CTV and CTV Boost. Regarding OARs, shifts in R, P, and I directions contributed to increasing the received dose. The 2A-VMAT plans performed better dose sparing, but had a higher robustness in a high-dose volume of the left lung and heart. The 2A-VMAT plans decreased the max dose of LAD but exhibited lower robustness. Conclusion: The 2A-VMAT plans showed higher sensitivity to position deviation. Shifts in the S-I direction exerted the largest effect for CTV and CTV Boost.

Purpose: To identify the dosimetric predictors of lymphocytopenia and retrospectively analyze the changing trend of peripheral lymphocyte counts and lymphocyte-related inflammatory indicators in patients with simple pelvic radiotherapy. Methods and Materials: We retrospectively reviewed the clinical data of 188 patients with pelvic malignancies undergoing pelvic radiotherapy. The absolute count of neutrophils, lymphocytes, monocytes, and platelets at each time point was collected, and lymphocyte-related inflammation indicators were obtained, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII). The total pelvic bone (TPB) and the body within the 5 Gy coverage were retrospectively delineated for each patient. Dose-volume histograms corresponding to the delivered volumetric arc therapy plan were used to assess the dose volumes received by the TPB and body. A paired-samples t-test or Wilcoxon signed-rank test for matched pairs was applied for pairwise comparisons. We also established a stepwise multiple linear regression model for the peripheral lymphocyte count (PLC) value at the end of radiotherapy. Results: The PLC and lymphocyte-related inflammatory indicators changed significantly after the start of radiotherapy and persisted for 3-6 months after radiotherapy. The nadirs of PLC occurred at RT-End, and the PLC was still significantly lower than the baseline value at RT-3 months and RT-6 months. NLR, PLR, and SII at RT-End are about 3.5 times the value at RT-Baseline, while LMR is one-fourth of the basal value. In a further multiple stepwise linear regression analysis, the basal PLC (β = 0.156, p ≤ .001), gender (β = 0.096, p = .005), and TPB-V5 (β = −0.016, p ≤ .001) turned out to be the predictor of the absolute value of lymphocytes at the end of radiotherapy. Conclusions: The impact of pelvic radiotherapy on PLC and lymphocyte-related inflammatory indicators is considerable and long-lasting. Minimizing pelvic bone radiation exposure dose (5 Gy) may help to avoid severe cases of lymphocytopenia.

Purpose: To explore clinical and dosimetric predictors of acute hematologic toxicity (HT) in cervical cancer patients treated with concurrent chemotherapy and volumetric-modulated arc therapy (VMAT). Methods and materials: We retrospectively reviewed the clinical data of 184 cervical cancer patients who had concurrent chemotherapy and VMAT. Hematological parameters were collected during the treatment period. The total pelvic bone (TPB) was delineated retrospectively for dose-volume calculations. To compare the differences between two groups, the normality test findings were used to run a paired-samples t-test or Wilcoxon signed-rank test. Pearson's correlation analysis or Spearman's correlation was used to testing the correlation between the two variables. Binary logistic regression analysis was used to analyze associations between HT and possible risk factors. The receiver operating characteristic curve(ROC) was used to evaluate the best cut-off point for dosimetric planning constraints. Results: The nadir of absolute monocyte count (AMC) was found to be positively correlated with the nadir of absolute white blood cells (WBC) count (r = 0.5378, 95% CI 0.4227–0.6357, P < 0.0001) and the nadir of absolute neutrophil count(ANC) (r = 0.5000, 95% CI 0.3794–0.6039, P < 0.0001). The AMC decreased and increased before the ANC and WBC. In multivariate logistic regression analysis, the chemotherapy regimens and the TPB_V20 were independent risk factors for developing grade ≥ 3 HT. The optimal TPB_V20 cut-off value identified by ROC curves and the Youden test was 71% (AUC = 0.788; 95% CI 0.722–0.845; P value < 0.001). Conclusions: The changing trend of AMC can be used as an effective predictor for the timing and severity of the ANC/WBC nadirs and prophylactic G-CSF administration. Maintain TPB_V20 < 71% and selecting single-agent cisplatin or carboplatin could significantly reduce grade ≥ 3 HT in cervical cancer patients undergoing concurrent chemoradiotherapy.

Objective: We aimed to compare the dosimetric characteristics of 6‐MV flattening filter mode (FF) and flattening filter‐free mode (FFF) volumetric‐modulated arc therapy (VMAT) plans in preoperative radiotherapy for rectal cancer using an Edge linear accelerator.Methods: Two‐arc FF‐VMAT and FFF‐VMAT plans were generated for 15 patients with rectal cancer using the Philips Pinnacle treatment planning system (version 9.10). The homogeneity index, conformity index, planning target volume covered by 105% isodose lines, organ‐at‐risk dosimetry characteristics, and monitor units (MUs) were compared between the plans. The results were analyzed using paired t‐tests.Results: The conformity index of the FF‐VMAT plan and FFF‐VMAT plan were (0.93 ± 0.01) and (0.92 ± 0.02), and the homogeneity index of the two groups were (0.07 ± 0.03) and (0.08 ± 0.01), the differences were not statistically significant (both P > 0.05). The volume covered by 105% isodose lines of the FFF‐VMAT plan was significantly higher than that of the FF‐VMAT plan. The FFF‐VMAT plan required a higher monitor unit (t = 11.49, P = 0.002) and shorter beam‐on time (t = 5.78, P = 0.001) compared with the FF‐VMAT plan. There were no significant differences in the absolute volume receiving 30 Gy and 40 Gy of the bladder between the plans. The absolute volume receiving 30 Gy and absolute volume receiving 40 Gy of the intestine and colon in the FFF‐VMAT plan increased by 5.5% and 2.1% compared with those in the FF‐VMAT plans that increased by 7.2% and 2.2%, respectively (both P > 0.05). The absolute volume receiving 20 Gy of the left and right femoral head in the FFF‐VMAT plan decreased by 3.7% and 4.9% compared with those in the FF‐VMAT plans (P > 0.05).Conclusion: Both FF‐VMAT and FFF‐VMAT plans met the clinical requirements.

Purpose: We aimed to investigate RF-EMR-induced cell malignant transformation. Methods: We divided Balb/c-3T3 cells into sham and expo groups. The expo groups were exposed to a 1800 MHz RF continuous wave for 40 and 60 days, for 4 h per day. The sham group was sham-exposed. Cells were harvested for a cell transformation assay, transplantation in severe combined immune deficient (SCID) mice, soft agar clone formation detection, and a transwell assay. The mRNA microarray assay was used to declare key genes and pathways. Results: The exposed Balb/c-3T3 cells showed a strong increase in cell proliferation and migration. Malignant transformation was observed in expo Balb/c-3T3 cells exposed for 40 days and 60 days, which was symbolized with visible foci and clone formation. Expo Balb/c-3T3 cells that were exposed for 40 days and 60 days produced visible tumors in the SCID mice. Lipid metabolism was the key biological process and pathway involved. The mevalonate (MVA) pathway was the key metabolic pathway. The interacted miRNAs could be further research targets to examine the molecular mechanism of the carcinogenic effects of long-term exposure. Conclusion: Exposure for 40 and 60 days to 1800 MHz RF-EMR induced malignant transformation in Balb/c-3T3 cells at the SAR of 8.0 W/kg. We declared that lipid metabolism was the pivotal biological process and pathway. The MVA pathway was the key metabolic pathway.