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1.
PurposeTo investigate the dosimetric impact between the anisotropic analytical algorithm (AAA) and the Acuros XB (AXB) algorithm in volumetric-modulated arc therapy (VMAT) plans for high-grade glioma (HGG).MethodsWe used a heterogeneous phantom to quantify the agreement between the measured and calculated doses from the AAA and from the AXB. We then analyzed 14 patients with HGG treated by VMAT, using the AAA. We newly created AXB plans for each corresponding AAA plan under the following conditions: (1) re-calculation for the same number of monitor units with an identical beam and leaf setup, and (2) re-optimization under the same conditions of dose constraints. The dose coverage for the planning target volume (PTV) was evaluated by dividing the coverage into the skull, air, and soft-tissue regions.ResultsCompared to the results obtained with the AAA, the AXB results were in good agreement with the measured profiles. The dose differences in the PTV between the AAA and re-calculated AXB plans were large in the skull region contained in the target. The dose difference in the PTV in both types of plan was significantly correlated with the volume of the skull contained in the target (r = 0.71, p = 0.0042). A re-optimized AXB plan's dose difference was lower vs. the re-calculated AXB plan's.ConclusionsWe observed dose differences between the AAA and AXB plans, in particular in the cases in which the skull region of the target was large. Considering the phantom measurement results, the AXB algorithm should be used in VMAT plans for HGG.  相似文献   

2.
BackgroundAcuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations.Materials and methodsA cohort of 30 patients previously cared for cervix carcinoma (stages II–IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern.ResultsThere was no significant (p > 0.05) difference in D95% and D98% to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D50% (0.26%), D2% (0.80%) and V110% (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V50Gy, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D2% of the left femur and right femur, respectively, between AA and AXB dose estimations.ConclusionFor similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V50Gy of the rectum and overestimates the mean dose and D2% for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique.  相似文献   

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PurposeRadiation therapy plans are assessed using dose volume metrics derived from clinical toxicity and outcome data. In this study, plans for patients with locally advanced non-small cell lung cancer (LA-NSCLC) are examined in the context of the implementation of the Acuros XB (AXB) dose calculation algorithm focussing on the impact on common metrics. Methods: Volumetric modulated arc therapy (VMAT) plans were generated for twenty patients, using the Analytical Anisotropic Algorithm (AAA) and recalculated with AXB for both dose to water (Dw) and dose to medium (Dm). Standard dose volume histogram (DVH) metrics for both targets and organs-at-risk (OARs) were extracted, in addition to tumour control probability (TCP) for targets. Results: Mean dose to the planning target volume (PTV) was not clinically different between the algorithms (within ±1.1 Gy) but differences were seen in the minimum dose, D99% and D98% as well as for conformity and homogeneity metrics. A difference in TCP was seen for AXBDm plans versus both AXBDw and AAA plans. No clinically relevant differences were seen in the lung metrics. For point doses to spinal cord and oesophagus, the AXBDm values were lower than AXBDw, by up to 1.0 Gy. Conclusion: Normalisation of plans to the mean/median dose to the target does not need to be adjusted when moving from AAA to AXB. OAR point doses may decrease by up to 1 Gy with AXBDm, which can be accounted for in clinical planning. Other OAR metrics do not need to be adjusted.  相似文献   

5.
AimTo validate the Acuros®XB (AXB) dose calculation algorithm for a 6 MV beam from the Varian TrueBeam treatment units.BackgroundCurrently Anisotropic Analytic Algorithm (AAA) is clinically used on authors’ department but AXB could replace it for VMAT treatments in regions where inhomogeneities and free air are present.Materials and methodsTwo steps are followed in the validation process of a new dose calculation algorithm. The first is to check the accuracy of algorithm for a homogenous phantom and regular fields. Multiple fields of increasing complexity have been acquired using a MapCheck diode array. The accuracy of the algorithm was evaluated using the gamma analysis method. The second is to validate the algorithm in the presence of heterogeneous media. Planar absolute dose was measured with GafChromic®EBT2 film and was compared with the dose calculated by AXB. Gamma analysis was performed between MapCheck measurements and AXB dose calculations, at a range of clinical source-surface distance.ResultsFor SSDs ranging from 80 to 100 cm, the results show a minimum pass rate of 95% between AXB and MapCheck acquisition. For open 6 MV photon beam interacting with a phantom with an air gap, the agreement after the air gap between AXB and GafChromic®EBT2 is less than 1% in the 3 × 3cm2 field and less than 2% in the 10 × 10 cm2 field.ConclusionsAXB has advanced modelling of lateral electron transport that enables a more accurate dose calculation in heterogeneous regions and, compared with AAA, improves accuracy between different density interfaces. This will be of particular benefit for head/neck treatments.  相似文献   

6.
Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.  相似文献   

7.
PurposeTo investigate the changes in quality of the volumetric modulated arc therapy (VMAT) plans with couch-shift between arcs by half of a multi-leaf collimator (MLC) leaf width.MethodsA total of 22 patients with head-and-neck cancer were retrospectively selected. Since the smallest MLC leaf width was 5 mm in this study, the couch was shifted by 2.5 mm in the longitudinal-direction between arcs to increase the resolution of fluence map. A total of three types of VMAT plans were generated for each patient; the three types of plans were a two-full-arc plan without couch-shift (NS plan), a two-half-arc-pair plan with couch-shift (HAS plan), and a two-full-arc pair plan with couch-shift (FAS plan). Changes in the dose-volumetric parameters were investigated.ResultsThe FAS plan showed the best plan quality for the target volumes and organs at risk compared to the NS and HAS plans. However, the magnitudes of differences among the three types of plans were minimal, and every plan was clinically acceptable. The average integral doses of the NS, HAS, and FAS plans were 160,549 ± 37,600 Gy-cc, 147,828 ± 33,343 Gy-cc, and 156,030 ± 36,263 Gy-cc, respectively. The average monitor unit of the NS, HAS, and FAS plans were 717 ± 120 MU, 648 ± 100 MU, and 763 ± 158 MU, respectively.ConclusionsThe HAS plan was better than the others in terms of normal tissue sparing and plan efficiency. By shifting the couch by half of the MLC leaf width in the longitudinal direction between arcs, the VMAT plan quality could be improved.  相似文献   

8.
AimTo evaluate the performance of volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers.BackgroundRapidArc is a novel technique that has recently been made available for clinical use. Planning study was done for volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers.Materials and methodsTen patients with advanced tumors of the nasopharynx, oropharynx, and hypopharynx were selected for the planning comparison study. PTV was delineated for two different dose levels and planning was done by means of simultaneously integrated boost technique. A total dose of 70 Gy was delivered to the boost volume (PTV boost) and 57.7 Gy to the elective PTV (PTV elective) in 35 equal treatment fractions. PTV boost consisted of the gross tumor volume and lymph nodes containing visible macroscopic tumor or biopsy-proven positive lymph nodes, whereas the PTV elective consisted of elective nodal regions. Planning was done for IMRT using 9 fields and RapidArc with single arc, double arc. Beam was equally placed for IMRT plans. Single arc RapidArc plan utilizes full 360° gantry rotation and double arc consists of 2 co-planar arcs of 360° in clockwise and counter clockwise direction. Collimator was rotated from 35 to 45° to cover the entire tumor, which reduced the tongue and groove effect during gantry rotation. All plans were generated with 6 MV X-rays for CLINAC 2100 Linear Accelerator. Calculations were done in the Eclipse treatment planning system (version 8.6) using the AAA algorithm.ResultsDouble arc plans show superior dose homogeneity in PTV compared to a single arc and IMRT 9 field technique. Target coverage was almost similar in all the techniques. The sparing of spinal cord in terms of the maximum dose was better in the double arc technique by 4.5% when compared to the IMRT 9 field and single arc techniques. For healthy tissue, no significant changes were observed between the plans in terms of the mean dose and integral dose. But RapidArc plans showed a reduction in the volume of the healthy tissue irradiated at V15 Gy (5.81% for single arc and 4.69% for double arc) and V20 Gy (7.55% for single arc and 5.89% for double arc) dose levels when compared to the 9-Field IMRT technique. For brain stem, maximum dose was similar in all the techniques. The average MU (±SD) needed to deliver the dose of 200 cGy per fraction was 474 ± 80 MU and 447 ± 45 MU for double arc and single arc as against 948 ± 162 MU for the 9-Field IMRT plan. A considerable reduction in maximum dose to the mandible by 6.05% was observed with double arc plan. Double arc shows a reduction in the parotid mean dose when compared with single arc and IMRT plans.ConclusionRapidArc using double arc provided a significant sparing of OARs and healthy tissue without compromising target coverage compared to IMRT. The main disadvantage with IMRT observed was higher monitor units and longer treatment time.  相似文献   

9.
AimThis study aimed to evaluate the dosimetric impact of uncorrected yaw rotational error on both target coverage and OAR dose metrics in this patient population.BackgroundRotational set up errors can be difficult to correct in lung VMAT SABR treatments, and may lead to a change in planned dose distributions.Materials and methodsWe retrospectively applied systematic yaw rotational errors in 1° degree increments up to −5° and +5° degrees in 16 VMAT SABR plans. The impact on PTV and OARs (oesophagus, spinal canal, heart, airway, chest wall, brachial plexus, lung) was evaluated using a variety of dose metrics. Changes were assessed in relation to percentage deviation from approved planned dose at 0 degrees.ResultsTarget coverage was largely unaffected with the largest mean and maximum percentage difference being 1.4% and 6% respectively to PTV D98% at +5 degrees yaw.Impact on OARs was varied. Minimal impact was observed in oesophagus, spinal canal, chest wall or lung dose metrics. Larger variations were observed in the heart, airway and brachial plexus. The largest mean and maximum percentage differences being 20.77% and 311% respectively at −5 degrees yaw to airway D0.1cc, however, the clinical impact was negligible as these variations were observed in metrics with minimal initial doses.ConclusionsNo clinically unacceptable changes to dose metrics were observed in this patient cohort but large percentage deviations from approved dose metrics in OARs were noted. OARs with associated PRV structures appear more robust to uncorrected rotational error.  相似文献   

10.
Summary The therapeutic effects of intravenous recombinant human erythropoietin (r-hEPO) administration on anemia induced by radiation therapy (3 cases), chemotherapy (18 cases) and combined therapies (5 cases) in patients with head and neck malignancies were examined. The effectiveness was evaluated by the changes in the hemoglobin concentration examined before and after the r-hEPO administration. The r-hEPO administration combined with anticancer therapies improved anemia induced by all three treatments. The therapeutic effectiveness of r-hEPO injection was also noted on anemia induced by all of four different chemotherapeutic regimens that have been ordinarily used for head and neck malignancies. Furthermore, the efficacy of the different dose schedules, 3000 IU (12 cases) or 6000 IU (14 cases), three times a week, was compared. Both of the r-hEPO dose schedules were effective for anemia, but the efficacy of 6000 IU was superior to that of 3000 IU. No significant changes were observed in the number of white blood cells and platelets and the results of biochemical examinations after the r-hEPO injection. There were no objective side-effects related to the r-hEPO administration. These results suggest that anemia induced by chemotherapy and/or radiotherapy could be prevented by r-hEPO administration. The addition of r-hEPO to anticancer therapies would make it possible to pursue the planned therapeutic schedules, prevent the decrease of immunity after allogeneic blood transfusion and bring about an improvement in the prognosis of patients with malignancies.  相似文献   

11.
AimTo investigate the impact of Acuros XB (AXB) algorithm in the deep-inspiration breath-hold (DIBH) technique used for treatment of left sided breast cancer.BackgroundAXB may estimate better lung toxicities and treatment outcome in DIBH.Materials and MethodsTreatment plans were computed using the field-in-field technique for a 6 MV beam in two respiratory phases - free breathing (FB) and DIBH. The AXB-calculations were performed under identical beam setup and the same numbers of monitor units as used for AAA-calculation.ResultsMean Hounsfield units (HU), mass density (g/cc) and relative electron density were -782.1 ± 24.8 and -883.5 ± 24.9; 0.196 ± 0.025 and 0.083 ± 0.032; 0.218 ± 0.025 and 0.117 ± 0.025 for the lung in the FB and DIBH respiratory phase, respectively. For a similar target coverage (p > 0.05) in the DIBH respiratory phase between the AXB and AAA algorithm, there was a slight increase in organ at risk (OAR) dose for AXB in comparison to AAA, except for mean dose to the ipsilateral lung. AAA predicts higher mean dose to the ipsilateral lung and lesser V20Gy for the ipsilateral and common lung in comparison to AXB. The differences in mean dose to the ipsilateral lung were 0.87 ± 2.66 % (p > 0.05) in FB, and 1.01 ± 1.07% (p < 0.05) in DIBH, in V20Gy the differences were 1.76 ± 0.83% and 1.71 ± 0.82% in FB (p < 0.05), 3.34 ± 1.15 % and 3.24 ± 1.17 % in DIBH (p < 0.05), for the ipsilateral and common lung, respectively.ConclusionFor a similar target volume coverage, there were important differences between the AXB and AAA algorithm for low-density inhomogeneity medium present in the DIBH respiratory phase for left sided breast cancer patients. DIBH treatment in conjunction with AXB may result in better estimation of lung toxicities and treatment outcome.  相似文献   

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13.

Background

IMRT provides highly conformal dose distributions creating non uniform spatial intensity using different segments in the beam.

Material & Methods and Results

Different retrospective studies have shown a high capability of IMRT to treat tumours close to the base of skull. Prospective studies have shown a decrease in xerostomia compared with conventional 3D conformal treatment (3DCRT). Modulation of intensity is performed by the movement of the multileaf collimator (MLC) that can deliver the radiation in different ways, such as static field segments, dynamic field segments and rotational delivery (arc therapy and tomotherapy). There are slight differences among the different techniques in terms of homogeneity, dose conformity and treatment delivery time.

Conclusions

The best method to deliver IMRT will depend on multiple factors such as deliverability, practicality, user training and plan quality.  相似文献   

14.
AimWe compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking.BackgroundThere are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed.Materials and methodsAmong 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis.ResultsPatients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p = 0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p = 0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p = 0.05) required prolonged hospitalization to heal mucositis.ConclusionsIn the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.  相似文献   

15.
A xenogeneic human head and neck squamous cell carcinoma (HNSCC) model in immunocompetent mice was evaluated for its requirement of cyclosporine for progressive tumor growth. Tumor growth and T cell functions were assessed in mice receiving cyclosporine treatment for various lengths of time. Tumor cells were injected s.c. on day 1 and cyclosporine was injected i.p. daily on days 1, 1–7, 1–14, 1–21, or for the entire 28 days of tumor growth. All mice developed tumors. These tumors were confirmed to be squamous carcinomas of human origin histologically and by positive staining for human MHC class I antigen expression. Tumors were largest in mice that received cyclosporine for days 1–21 or days 1–28. Increased tumor size was associated with increased serum levels of tumor-reactive antibodies, an increased intratumoral frequency of CD4+ and CD8+ cells, but a diminished production of interleukin-2 (IL-2) by the tumor infiltrate. Also correlating with increasing tumor size was splenomegaly, a decline in the frequency, but not the absolute levels, of splenic CD4+ and CD8+ cells, and a diminished capacity to proliferate in response to concanavalin A and to be stimulated to secrete IL-2. The HNSCC tumors contributed to the immune decline since T cell functions were more depressed in the tumor bearers than in control mice receiving only cyclosporine treatment. These results demonstrate that human HNSCC tumor xenografts can grow in mice even with limited cyclosporine treatment, and that the survival of these xenografts may, in part, be due to a tumor-induced decline in select T cell functions.This study was supported by the Medical Research Service of the Department of Veterans Affairs, by grants CA-45080 and CA-48080 from the National Institutes of Health  相似文献   

16.
ObjectiveTo investigate potential associations between body mass index (BMI) and head and neck cancer (HNC) risk in an East Asian population.MethodsWe conducted a hospital-based multicenter case-control study in East Asia including 921 cases and 806 controls. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CI) for HNC risks by using logistic regression, adjusting on potential confounders.ResultsCompared to normal BMI at interview (18.5–<25 kg/m2), being underweight (BMI < 18.5 kg/m2) was associated with a higher HNC risk (OR = 2.71, 95% CI 1.40–5.26). Additionally, obesity (BMI > 30 kg/m2) was associated with a lower HNC risk (OR = 0.30, 95% CI 0.16–0.57). Being underweight at age 20 was also associated with an increased risk of HNC. However, being underweight at 5 years or 2 years before interview was not associated with a higher risk of HNC.ConclusionWe observed an inverse association between BMI and HNC risk, which is consistent with previous studies in other geographic regions. Being underweight at age 20 was also associated with a higher risk of HNC, suggesting that reverse causality was not the main source of the association.  相似文献   

17.
目的通过对传统培养法和PCR法在假丝酵母菌感染检出率的比较,拟探索一种能够早期、快速、高效检测头颈部放疗患者假丝酵母菌感染的方法。方法收集120名头颈部放疗患者唾液,分别应用假丝酵母菌显色培养基(CHROMagar)进行分离、培养和鉴定;同时提取基因组DNA,通过假丝酵母菌通用引物、特异性引物、改良引物进行PCR扩增,结果与假丝酵母菌表型进行对比。结果与传统培养法相比,PCR法检出率更高(χ2=47.672,P=0.000);改良特异性引物D扩增的检出率为77%,高于通用引物B(χ2=7.702,P=0.006)和特异性引物C(χ2=12.522,P=0.001)。结论本研究证实PCR技术耗时短,阳性检出率高,可用于头颈部肿瘤放疗患者假丝酵母菌感染的快速检测。  相似文献   

18.
PurposeWhen using volumetric modulated arc therapy (VMAT) for head and neck cancer, setup errors regarding the shoulders can create loss of target coverage or increased organ-at-risk doses. This study created variations of realistic shoulder deformations to understand the associated VMAT dosimetric effects and investigated water-equivalent thickness (WET) differences using in-house software.MethodsTen patients with head and neck cancer with lower neck involvement were retrospectively and randomly enrolled. Their retrospective analysis comprised treatment planning using RayStation 5.0 (RaySearch Laboratories, Stockholm, Sweden), shoulder deformation of 5–15 mm in three-dimensional axes using the ImSimQA package (Oncology Systems Limited, Shrewsbury, Shropshire, UK), and evaluation of the clinical impact of the dose distribution after recalculating the dose distribution using computed tomography images of deformed shoulders and deforming the dose distribution. Additionally, our in-house software program was used to measure WET differences for shoulder deformation.ResultsWET differences were greater in the superoinferior (SI) direction than in the other directions (the WET difference was >20 mm for 15-mm SI deformation). D99%, D98%, and D95% for all clinical target volumes were within 3%. Local dose differences of more than ±10% were found for normal tissues at the level of the shoulder for 15-mm movement in the SI direction.ConclusionsShoulder deformation of >6 mm could cause large dose variations delivered to the targeted tissue at the level of the shoulder. Thus, to ensure delivery of appropriate treatment coverage to the targeted tissue, shoulder deformation should be taken into consideration during the planning stage.  相似文献   

19.
Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stem cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1+ cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1+-lineage cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stem-like properties, and blocked the tumorigenic abilities of CD44+CD24ALDH1+ cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1+ could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC.  相似文献   

20.
PurposeAutomated planning techniques aim to reduce manual planning time and inter-operator variability without compromising the plan quality which is particularly challenging for head-and-neck (HN) cancer radiotherapy. The objective of this study was to evaluate the performance of an a priori-multicriteria plan optimization algorithm on a cohort of HN patients.MethodsA total of 14 nasopharyngeal carcinoma (upper-HN) and 14 “middle-lower indications” (lower-HN) previously treated in our institution were enrolled in this study. Automatically generated plans (autoVMAT) were compared to manual VMAT or Helical Tomotherapy planning (manVMAT-HT) by assessing differences in dose delivered to targets and organs at risk (OARs), calculating plan quality indexes (PQIs) and performing blinded comparisons by clinicians. Quality control of the plans and measurements of the delivery times were also performed.ResultsFor the 14 lower-HN patients, with equivalent planning target volume (PTV) dosimetric criteria and dose homogeneity, significant decrease in the mean doses to the oral cavity, esophagus, trachea and larynx were observed for autoVMAT compared to manVMAT-HT. Regarding the 14 upper-HN cases, the PTV coverage was generally significantly superior for autoVMAT which was also confirmed with higher calculated PQIs on PTVs for 13 out of 14 patients, whereas PQIs calculated on OARs were generally equivalent. Number of MUs and total delivery time were significantly higher for autoVMAT compared to manVMAT. All plans were considered clinically acceptable by clinicians.ConclusionsOverall superiority of autoVMAT compared to manVMAT-HT plans was demonstrated for HN cancer. The obtained plans were operator-independent and required no post-optimization or manual intervention.  相似文献   

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