To further explore relative biological effectiveness (RBE) variability, the RBE of different intracerebral cells at various irradiation (IR) dosages and time were determined in this study. A total of 120 rabbits were randomly divided into proton groups (0, 10, 20, 30, 40 Gy, RBE) (n = 3) and photon groups (0, 10, 20, 30, 40 Gy) (n = 3). The rabbits were sacrificed at 2, 4, 6, 8 weeks after brain IR. Neuronal survival, identified via Hematoxylin and Eosin (H&E) staining, and immunohistochemical detection of neurofilament (NF), Olig2, and CD68 in the hippocampus and thalamus, were analyzed. Dose- and time-dependent RBE curves were fitted using the LQ model. Proton IR showed higher neuronal survival at 4-, 6-, and 8-weeks post 10 Gy, 20 Gy, 30 Gy IR (p < 0.05) compared to photon IR. Oligodendrocyte populations in photon group at 4-, 6-, and 8-weeks post 10 Gy IR and 6-, 8-weeks post 20 Gy were consistently higher than proton subgroups (p < 0.05). While proton IR showed higher microglial activation which was observed only at 4-weeks post 30y IR. Proton RBE for neurons and oligodendrocytes remained below 1.1 but exceeded 1.1 for microglial activation. These findings demonstrate the dose- and time- dependent nature of proton RBE and suggest brain tissue tolerates higher proton IR doses compared to photon IR, which fully confirmed the biological advantages of proton IR. These will help clinicians more precisely set the organ limit at risk and tailor radiotherapy plans.

The purpose of the study was to evaluate the dosimetric characteristics of volumetric modulated arc therapy (VMAT), helical tomotherapy (HT), and intensity-modulated proton therapy (IMPT) and to compare the dosimetric differences between the two IMPT plans with coplanar and non-coplanar beams in prophylactic cranial irradiation (PCI) with hippocampal-sparing for small cell lung cancer (SCLC). Twenty-five patients diagnosed with limited-stage SCLC and received PCI were enrolled in the study. Four treatment plans were designed: VMAT, HT, and two IMPT plans with coplanar and non-coplanar beams (referred to as IMPT-cop and IMPT-noncop, respectively). The prescription dose was 25 Gy in 2.5 Gy(RBE) fractions. The PTV was optimized in both the VMAT and HT plans. In IMPT plans, multifield optimization and CTV robust optimization with a 3-mm setup uncertainty and 3.5

BackgroundThe purpose of the study was to evaluate the dosimetry of the Halcyon in prophylactic cranial irradiation (PCI) with volumetric modulated arc therapy (VMAT) and hippocampal-sparing for small cell lung cancer (SCLC).MethodsFive VMAT plans were designed on CT images of 15 patients diagnosed with SCLC and received PCI. Three plans with two full arcs were generated on the Trilogy and the TrueBeam accelerators, and flattening filter (FF) and flattening filter free (FFF) modes were used on TrueBeam. Two Halcyon plans with two and three full arcs were generated, referred to as H-2A and H-3A, respectively. The prescription dose was 25 Gy in 2.5-Gy fractions. The dose limit for hippocampus were D100 ≤ 9Gy and Dmax ≤ 16Gy. The Wilcoxon matched-paired signed-rank test was used to evaluate the significance of the observed differences between the five plans.ResultsH-2A plans significantly increased the D2 of PTV, and H-3A plans showed comparable or even better target dosimetry (better conformity) compared to the three plans on C-arm accelerators. Compared to T and TB plans, the two Halcyon plans significantly reduced the D100 and mean doses of bilateral hippocampus, the mean doses of eyeballs, and the maximum doses of lenses. D100 of hippocampus was reduced in TrueBeam plans comparing to Trilogy plans. The FFF plans on TrueBeam also represented advantages in Dmean and D100 of hippocampas, Dmean and Dmax of eyeballs, and the Dmax of lenses compared to FF plans. Halcyon plans and TrueBeam plans with FFF mode increased the MUs compared to FF plans. Comparing to H-2A, the H-3A plans exhibited additional dosimetric advantages, including D2, CI and HI of PTV, as well as the maximum and mean doses of hippocampus and eyeballs, and the maximum doses of optic nerves and brainstem. The two Halcyon plans significantly reduced the delivery time and showed the higher gamma passing rate than the three plans of C-arm accelerators.ConclusionsCompared with the C-arm accelerators, the dose of hippocampus and the delivery times on Halcyon are relatively significantly reduced for hippocampal-sparing PCI. Three arcs are recommended for VMAT plans with the Halcyon in hippocampal-sparing PCI.

Background:Traditional intensity-modulated radiation therapy (IMRT) planning for cervical cancer is time-consuming and require iterative repeated optimization. In this study, we focused on leveraging multi-criteria optimization (MCO) to reduce the impact of small bowel high-dose indices on other optimization targets, thereby providing a rapid approach to individualized IMRT for cervical cancer patients.Methods:Our research involved a cohort of 25 cervical cancer patients who underwent IMRT radiotherapy. The patient inclusion criteria were as follows: (I) histopathological confirmation of cervical cancer, (II) underwent IMRT radiation therapy, and (III) a prescribed dose of 180 cGy/28 fractions for the patient. All plans were replanned by an experienced dosimetrist without the MCO (W-IMRT). On the basis of the W-IMRT plan, the individualized IMRT (I-IMRT) plan was generated under the priority trade-off of reducing the D2cc (D2cc is the minimal dose to the 2 cm3 of the small bowel receiving the maximal dose) index of the small bowel using the MCO method, maintaining target coverage and protecting other organs at risk (OARs) as much as possible. Statistical analysis was performed using the Wilcoxon signature rank test.Results:When the MCO method was applied to the IMRT plan, the high dose index decreased in the overlapping area between the small bowel and the planning treatment volume (PTV) (P<0.001, respectively). The D2cc index of the small bowel decreased to below 5,200 cGy in all I-IMRT plans. On the other hand, in PTV, the I-IMRT plan achieved a better homogeneity index (HI) compared to the W-IMRT plan. Significant dose reductions were also observed in the bladder (Dmean 144.8 cGy and V40 1.45%) (P<0.001, respectively), rectum (Dmean 43.9 cGy and V40 2.7%) (P<0.001, respectively) and bilateral femur heads (Dmean 150 cGy) (P<0.001, respectively).Conclusions:Dosimetric differences suggest that the I-IMRT plan using the MCO method provides better protection of other OARs and equivalently in PTV coverage, while lowering the high-dose index in the small bowel as much as possible for patients with cervical cancer, thus providing a rapid approach to achieving individualized IMRT for cervical cancer patients.

Context: Previous studies show that dose escalation for gross tumor volume (GTV) improves local control of esophageal cancer (EC). However, optimal boosting remains uncertain. Recently, functional imaging guidance to achieve dose escalation in high-risk areas of tumors has been proposed. Aims: This study evaluated the feasibility of dose escalation in tumor regions with high fluorodeoxyglucose (FDG) uptake using intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT). Settings and Design: GTVPET was defined as a high FDG uptake region with 50% SUVmax threshold for dose escalation. IMRT and IMPT plans were generated for three boosting modes: plan 50.4 (50.4 Gy in clinical target volume, CTV), plan 63 (50.4 Gy in CTV, 63 Gy in GTV), plan 70 (50.4 Gy in CTV, 63 Gy in GTV, and 70 Gy in GTVPET). Methods and Material: Eleven patients with squamous cell carcinoma were evaluated. Dose parameters for heart, lung, and spinal cord were compared based on the dose-volume histogram (DVH). Statistical Analysis Used: Paired t-test was performed on the doses to organs-at-risk (OARs) among plan 50.4, plan 63, and plan 70 for IMRT and IMPT. Results: Dosimetric parameters for IMRT for heart, lung, and spinal cord increased significantly for plan 63 and some parameters even exceeded dose limits for OARs. Further dose escalation in GTV-PET did not increase dosimetric parameters significantly. Most dosimetric parameters of OARs in IMPT exhibited no statistical change compared with plan 50.4, and doses to OARs were far less than dose constraints. Conclusions: Dose escalation by IMRT may lead to increased risk of radiation-related injury. Further dose escalation in high FDG uptake regions did not increase doses to OARs. This dose escalation is ideal for achieving better outcomes for EC treatment.

Abstract Background and purpose The study evaluated the differences in leaf positioning deviations by the log files of three advanced accelerators with two delivery techniques, and established specific assessment parameters of leaf positioning deviations for different types of accelerators. Methods A total of 420 treatment plans with 5 consecutive treatment log files were collected from the Trilogy, TrueBeam and Halcyon accelerators. Millennium MLC was equipped on the Trilogy and TrueBeam accelerators. A jawless design and dual-layer MLC were adopted on the Halcyon accelerator. 70 IMRT and 70 VMAT plans were selected randomly on each accelerator. The treatment sites of all plans included head and neck, chest, breast, pelvis and other sites. The parsing tasks for 2100 log files were proceeded by SunCheck software from Sun Nuclear Corporation. The maximum leaf root mean square (RMS) errors, 95th percentile errors and percentages of different leaf positioning errors were statistically analyzed. The correlations between these evaluation parameters and accelerator performance parameters (maximum leaf speed, mean leaf speed, gantry and arc angle) were analyzed. Results The average maximum leaf RMS errors of the Trilogy in the IMRT and VMAT plans were 0.44 ± 0.09 mm and 0.79 ± 0.07 mm, respectively, which were higher than the TrueBeam's 0.03 ± 0.01 mm, 0.03 ± 0.01 mm and the Halcyon's 0.05 ± 0.01 mm, 0.07 ± 0.01 mm. Similar data results were shown in the 95th percentile error. The maximum leaf RMS errors were strongly correlated with the 95th percentile errors (Pearson index > 0.5). The leaf positioning deviations in VMAT were higher than those in IMRT for all accelerators. In TrueBeam and Halcyon, leaf position errors above 1 mm were not found in IMRT and VMAT plans. The main influencing factor of leaf positioning deviation was the leaf speed, which has no strong correlation with gantry and arc angles. Conclusions Compared with the quality assurance guidelines, the MLC positioning deviations tolerances of the three accelerators should be tightened. For both IMRT and VMAT techniques, the 95th percentile error and the maximum RMS error are suggested to be tightened to 1.5 and 1 mm respectively for the Trilogy accelerator. In TrueBeam and Halcyon accelerators, the 95th percentile error and maximum RMS error of 1 and 0.5 mm, respectively, are considered appropriate.

Objective Whole lung irradiation (WLI) plays a crucial role in local control in pediatric patients with lung metastases and improves patient survival. The intention of this research was to explore the advantage of cardiac sparing between photons and protons during WLI. We also propose a new solution for cardiac sparing with proton techniques. Methods Eleven patients with pediatric tumors and pulmonary metastasis treated with 12 Gy WLI (all received volumetric-modulated arc therapy (VMAT)) in our institute between 2010 and 2019 were retrospectively selected. Each patient was replanned with intensity-modulated radiation therapy (IMRT), helical tomotherapy (HT), and two intensity-modulated proton radiotherapy (IMPT) plans (IMPT-1 and IMPT-2). IMPT-1 considered the whole lung as the planning target volume (PTV), utilizing the anteroposterior technique (0/180°). IMPT-2 was a new proton solution that we proposed in this research. This approach considered the unilateral lung as the PTV, and 3 ipsilateral fields were designed for each lung. Then, IMPT-2 was generated by summing two unilateral lung plans. The primary objective was to obtain adequate coverage (95% of the prescription dose to the PTV) while maximally sparing the dose to the heart. The PTV coverage, conformity index (CI), homogeneity index (HI), and dose–volume statistics of the heart and substructures were assessed by means of the averages of each comparison parameter. Results All treatment techniques achieved the target volume coverage required by clinical practice. HT yielded the best coverage and homogeneity for the target structure compared with other techniques. The CI from IMRT was excellent. For photon radiation therapy, the HT plan afforded superior dose sparing for the V5, V6, V7, V8, and Dmean of the heart and Dmean of the right ventricle (RV). IMRT displayed the most notable dose reductions in the V9, V10, V11, and V12 of the heart and Dmean of the right atrium (RA). The VMAT plan was the least effective on the heart and substructures. However, compared with photon radiation therapy, IMPT-1 did not show an advantage for heart protection. Interestingly, IMPT-2 provided significant superiority in cardiac sparing, including maximum dose sparing for the V5, V6, V7, V8, V9 and Dmean of the heart and Dmean of the RA, RV, left atrium (LA) and left ventricle (LV) compared to all other techniques. Conclusions Considering the complex anatomical relation between target volumes and organs at risk (OARs), IMPT can provide a dose advantage for organs located outside of the target area rather than within or surrounding the area. It is hoped that advances in proton therapy (PT) plan design will lead to further improvements in radiotherapy approaches and provide the best treatment choice for individual patients.

This study explored the dosimetric difference between hypofractionated whole-breast irradiation (HFWBI) with sequential boost (SEB) and simultaneous integrated boost (SIB) based on supine and prone positions to identify the superior boost mode and superior position. Thirty breast cancer patients eligible for HFWBI after breast-conserving surgery were enrolled. All patients underwent 3DCT simulation scanning in both supine and prone positions. For the SEB-HFWBI plan, the dose prescribed for the planning target volume (PTV) of whole breast (WB) was 2.67 Gy per fraction with a total of 15 fractions, followed by a sequential boost of 3.2 Gy per fraction to the PTV of tumor bed (TB) in 3 fractions. For the SIB-HFWBI plan, the dose prescribed for the PTV of WB was 2.67 Gy per fraction with a total of 15 fractions, with a simultaneously integrated boost of 3.2 Gy per fraction to the PTV of TB with a total of 15 fractions. Regardless of the position, for the PTV of TB, the conformal index (CI) in the SIB-HFWBI plans was greater than those in the SEB-HFWBI plans ( T = − 8.114, − 8.114; both P < 0.05). The CI for the PTV of WB increased significantly in the prone position relative to the supine position in both two plans( Z = − 3.340, − 3.501; all P < 0.05). The study suggested that prone SIB-HFWBI might be more suitable for postoperative radiotherapy after breast-conserving surgery for early-stage breast cancer patients.

Objective: To investigate the effect of anatomic and technical parameters on the incidental internal mammary lymph node (IMN) irradiation (IIMNI) dose among postmastectomy patients. Methods: We retrospectively delineated the IMN on planning CT images from 138 patients who had undergone postmastectomy radiotherapy (PMRT). We analyzed the IIMNI dose coverage and its relationship with anatomic and technical parameters. Results: The IIMNI mean dose was 32.85 ± 9.49 Gy, and 10 of 138 patients (7.25%) treated with PMRT received ≥45 Gy. In univariate analysis, the body weight, body mass index, body surface area, thoracic transverse diameter (DT), ratio of DT to the thoracic anteroposterior diameter (DAP)(RT/AP), planning target volume of IMN (PTVIMN) included in PTV (IMNin) and the ratio of IMNin to PTVIMN (RIMNin) and PTV posterior border were the parameters affecting IIMNI dose. In multivariate analysis, body weight, RT/AP, and RIMNin were correlative factors that affected IIMNI dose. Conclusions: For patients who underwent PMRT without IMN irradiation (IMNI), there was a wide variety in IIMNI doses. A minority of patients had adequate IIMNI dose coverage, and the higher IIMNI doses were associated with the less body weights and more RIMNin.

To investigate the differences in target volumes and dosimetric parameters between the supine and prone positions for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS) for Chinese breast cancer patients, thirty breast cancer patients who underwent three-dimensional conformal radiation therapy (3DCRT) EB-PBI after BCS were enrolled. Supine and prone scan sets were acquired during free breathing for all patients. Target volumes and organs at risk (OARs) including the heart, ipsilateral lung and bilateral breast were contoured by the same radiation oncologist. For each patient, supine and prone EB-PBI plans were generated based on the same planning criteria. The clinical target volume (CTV) and planning target volume (PTV) in the prone position were significantly greater than those in the supine position (P = 0.003, 0.004, respectively). A 0.95 Gy reduction in the mean dose (D-mean) to the heart (P= 0.000) was apparent in the supine position compared to the prone position. The D(mean )to the ipsilateral lung was significantly lower in the prone position than in the supine position (1.59 Gy vs. 1.72 Gy, P= 0.029). Therefore, for Chinese breast cancer patients, carrying out 3DCRT EB-PBI in the prone position during free breathing is feasible.

To validate a gradient-based segmentation method for gross tumor volume(GTV) delineation on 8F-fluorothymidine (FLT)positron emission tomography (PET)/ computer tomography (CT) in esophageal squamous cell cancer through pathologic specimen, in comparison with standardized uptake values (SUV) threshold-based methods and CT. The corresponding impact of this GTV delineation method on treatment planning was evaluated.

We investigated the dosimetric differences among volumetric-modulated arc radiotherapy (RapidArc, RA) plans designed for various target volumes in hepatocellular carcinoma (HCC). Ten HCC patients underwent 3D-CT scanning at free breathing (FB), 3D-CT at end inspiration hold (EIH) assisted by an Active Breathing Coordinator (ABC), and 4D-CT scanning. Gross tumor volumes (GTVs) were manually contoured on CT images. The individualized internal gross target volume (IGTV1) was obtained from 10 GTVs from 4D-CT images. Tumor individual margins were measured from GTVFB to IGTV1. The IGTV2 was obtained from GTVFB by applying individual margins. Four planning target volumes (PTV1-4) were obtained from IGTV1, IGTV2, GTVFB, and GTVEIH, respectively. An RA plan was designed for each of the PTVs (RA1–4). One 358° arc was used for PTVs1–3, while three 135° arcs were used for PTV4. It was found that PTV2 and PTV3 were larger than PTV1 and PTV4. The mean values of PTV3/PTV1 and PTV3/PTV4 were 2.5 and 1.9, respectively. The individual margins in the X, Y and Z axial directions varied greatly among these patients. There were no significant differences in the conformal index or homogeneity index among the four RA plans. RA1 and RA4 significantly reduced the radiation dose of normal liver tissue compared with RA2 and RA3 (P < 0.01). There were no significant differences between the radiation doses of the stomach and duodenum. RapidArc combined with 4D-CT or ABC technology is a promising method in radiotherapy of HCC, and accurately targeted the tumor volume while sparing more normal liver tissue.

Intensity-modulated radiotherapy (IMRT) has played an important role in breast cancer radiotherapy after breast-preservation surgery. Our aim was to study the dosimetric and implementation features/feasibility between IMRT and intensity-modulated arc radiotherapy (Varian RapidArc, Varian, Palo Alto, CA). The forward IMRT plan (f-IMRT), the inverse IMRT, and the RapidArc plan (RA) were generated for 10 patients. Afterward, we compared the target dose distribution of the 3 plans, radiation dose on organs at risk, monitor units, and treatment time. All 3 plans met clinical requirements, with RA performing best in target conformity. In target homogeneity, there was no statistical significance between RA and IMRT, but both of homogeneity were less than f-IMRT's. With regard to the V5 and V10 of the left lung, those in RA were higher than in f-IMRT but were lower than in IMRT; for V20 and V30, the lowest was observed in RA; and in the V5 and V10 of the right lung, as well as the mean dose in normal-side breast and right lung, there was no statistically significance difference between RA and IMRT, and the lowest value was observed in f-IMRT. As for the maximum dose in the normal-side breast, the lowest value was observed in RA. Regarding monitor units (MUs), those in RA were higher than in f-IMRT but were lower than in IMRT. Treatment time of RA was 84.6% and 88.23% shorter than f-IMRT and IMRT, respectively, on average. Compared with f-IMRT and IMRT, RA performed better in target conformity and can reduce high-dose volume in the heart and left lung—which are related to complications—significantly shortening treatment time as well. Compared with IMRT, RA can also significantly reduce low-dose volume and MUs of the afflicted lung.

Objective To evaluate the dose distribution of target volume and normal tissues in forward intensity modulated radiotherapy (fIMRT) and inverse intensity modulated radiotherapy (iIMRT) modes for breast cancer after radical mastectomy.Methods Both fIMRT and iIMRT plans were developed for 10 patients with breast cancer after radical mastectomy.On each patient's CT images the supraclavicular area, chest wall, and internal mammary area were delineated.The prescription dose was 50 Gyin 25fractions.In the fIMRT plan X-ray irradiation at the dose of 6 MV was adopted for the supraclavicular and the chest wall areas and electron irradiation at the dose of 9 - 12 MeV was adopted for the internal mammary area, and the doses of cold and hot spots were adjusted according to the fitting doses of these 3 regions.In the iIMRT plan the supraclavicular area, chest wall, and internal mammary area were taken asa whole target, 6 MV X-rays was used, and inverse optimal design was performed.The dose distribution oftarget volume and normal tissues, conformal index (CI) , and heterogeneous index (HI) , and acceleratormonitor unit (MU) were analyzed using dose-volume histogram (DVH)for the two intensity modulated modes.Results The maximum dose of PTV of the iIMRT plan was significantly lower than that of the fIMRT plan(t = -3.23,P ＜0.05), the minimum dose and V95% of PTV of the iIMRT were significantly higher than those of the fIMRT plan(t = 4.08, -2.69, both P ＜0.05).The CI level of the iIMRT plan was significantly higher than that of the fIMRT plan and the HI level of the iIMRT plan was significantly lower than that of the fIMRT plan (t = -3.13, 2.74, both P ＜0.05).There were not significant differences in V10, V20, V25, V30, and Dmean of the ipsilateral lung between these 2 groups.However, the V15 of ipsilateral lung of the iIMRT group was significantly lower by 4.2% than that of the fIMRT group (t= 3.2, P ＜ 0.05).There were not significant differences in the mean dose (Dmean) and V30 of heart, and Dmean of contralateral lung and contralateral breast between these 2 groups.Conclusions Compared with fIMRT, the iIMRT plan results in more PTV coverage, higher conformity index, and more homogeneous dose distribution, with lower dose upon the lung at the affected side, and better protection of the contralateral lung, heart, and breast.

Objective To investigate how much the patient setup accuracy for irradiation of head and neck cancer can be improved by online setup verification and offline setup verification using cone-beam computed tomography(CBCT), and the feasibility of image-guided adaptive correction procedure to reduce the PIN margin.Methods 16 patients of head-and-neck cancer treated with three-dimensional conformal radiotherapy (3D-CRT)or intensity modulated radiotherapy(IMRT)were investigated. The first online kV CBCT scan, rigid image registration, setup correction were performed before radiotherapy. The second kV CBCT scan were acquired immediately after treatment and analysis was performed as above. CBCT scans were acquired at two or three fractions weekly during the entire course of radiotherapy and CBCT online-guided correction data were recorded. The data was used to calculate the population-based CTV-PTV margins under the condition of non-correction, correction every fraction and compensation of the systematic setup error respectively. The number of initial images required to predict systematic setup error was evaluated with the permission of 0.5 mm residue error. Results Total of 320 sets of CBCT images were analyzed for 16 patients. Under the condition of non-correction, the margins required to account for total error are 5.7 mm,5.6 mm,and 7.3 mm in the left-right(X axis),cranio-eaudal(Y axis), and anterior-posterior (Z axis)directions respectively, when the tumor was corrected every fraction, the margins required to account for intrafraetion error are 1.7 mm,1.7 mm,and 2.3 mm in X, Y,and Z axis.To correct the systematic setup error,8 sets of CBCT images are adequate. After compensation for the effect of the systematic setup error, 2.7 mm,2.5 mm, and 3.6 mm PTV margins are necessary in X, Y, and Z axis respectively. Conclusions There exists some extent of setup error in head and neck 3D-CRT or IMRT.The on-line CBCT correction and the approach based on off-line adaptive correction both can be used to reduce the impact of setup error obviously, the required margins for the PTV was reduced accordingly.