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This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

Heming Lu,1,* Yuying Wu,2,* Xu Liu,1 Huixian Huang,1 Hailan Jiang,1 Chaohua Zhu,1 Yuping Man,3 Pei Liu,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Shan Deng,1 Junzhao Gu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 3Department of Radiology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 4Department of Oncology, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6 Taoyuan Road, Nanning, 530021, People’s Republic of ChinaTel +86-771-218-6806Email luhming3632@163.comPurpose: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting early treatment response.Materials and Methods: Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) were enrolled. Pelvic DCE-MRI scans were performed before RT (pre-RT), in the middle of RT (mid-RT), and at the end of RT (post-RT), separately. Parameters (ie, Ktrans, Kep, and Ve) were measured. Pre-, mid-, and post-RT Ktrans were denoted as Ktrans-preTx, Ktrans-midTx, and Ktrans-postTx, respectively. And the same denoting rule also went for Kep and Ve. Difference for the same parameter such as Ktrans measured between two consecutive time points was calculated as second Ktrans value minus first Ktrans value. The differences in Ktrans between pre-RT and post-RT, between pre-RT and mid-RT, and between mid-RT and post-RT were denoted as ΔKtrans-post-preTx, ΔKtrans-mid-preTx, and ΔKtrans-post-midTx, respectively, and the same denoting rule was also applied to Kep and Ve.Results: A total of 57 patients were enrolled. After the treatment, 31 patients had complete response (CR group). The remaining 26 patients had partial response (NCR group). Significant differences were found in Ktrans-postTx, Kep-postTx, Ve-midTx, ΔKtrans-post-preTx, ΔKtrans-post-midTx, ΔKep-post-preTx, ΔKep-mid-preTx and ΔKep-post-midTx between the two groups. Receiver operating characteristic (ROC) analysis for their performances in predicting treatment response showed an area under curve (AUC) of 0.656– 0.849, sensitivity of 61.3– 93.5%, specificity of 46.1– 73.1%, and maximal Youden Index of 36.5– 66.6. Among those parameters, Kep-postTx was the best, and its AUC, sensitivity, specificity, maximal Youden Index, and cutoff value were 0.849, 87.1%, 73.1%, 60.2, and 0.341, respectively. These combined parameters showed an AUC of 0.952, with sensitivity of 87.1%, specificity of 96.1%, and maximal Youden Index of 83.2.Conclusion: DCE-MRI parameters can predict early treatment outcome. Among those parameters, Kep-postTx is the best predictor. The combination of multi-parameters can increase the predictive potency.Keywords: cervical cancer, locally advanced disease, dynamic contrast-enhanced magnetic resonance imaging, concurrent chemoradiotherapy, prognosis prediction

The demand for leaf area index (LAI) retrieval from spaceborne full-waveform LiDAR increases due to its direct sampling of the three-dimensional forest structure at a near-global scale. However, the nonrandomness (i.e., clumping effect) of canopy composition limits the reliability of LAI derived from two common methods. They either assume a homogeneous scene in the footprint or just correct for the large gaps-induced between-crown clumping. The clumping in the crown is still an unaddressed issue. We proposed a method to compensate occlusion (i.e., lower canopy layers are occluded by the upper canopy in the process of LiDAR measurement), through which the vertical canopy profile can be resolved from the waveform. Further, we developed a method of deriving relative path length distribution that can reflect the heterogeneity of the canopy from the occlusion-corrected waveform. In addition to correcting the between-crown clumping, we corrected the within-crown clumping further using the derived relative path length distribution, based on path length distribution (PATH) theory. We used simulated waveform data with known LAI and GLAS data with corresponding field-measured LAI to test the performance of our and the other two common LAI retrieval methods. Results show that the errors of our approach are the lowest (with an error generally below 10% and the maximum error below 20%, compared with up to 69% and 47% for the other two methods), and it is relatively stable in various scenes. This study demonstrated the potential of improving LAI retrieval through full utilization of full-waveform data.

Defeng Qing,1,* Yuying Wu,2,* Xu Liu,1,* Hailan Jiang,1,* Chaohua Zhu,1,* Pei Liu,3 Junming Dang,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Luxing Peng,1 Shan Deng,1 Junzhao Gu,1 Renfeng Zhao,2 Changyi Chen,2 Heming Lu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 3Department of Radiation Oncology, Youjiang Medical University for Nationalities, Baise 533000, People’s Republic of China; 4Department of Oncology, Guangxi University of Chinese Medicine, Nanning 530001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City 530021, People’s Republic of ChinaTel +86-771-218-6504Email luhming3632@163.comPurpose: We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).Patients and Methods: Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.Results: Between June 2013 and July 2016, 33 patients with FIGO IB2–IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.Conclusion: Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery

Background As the number of Asian and African students studying medicine in China increases, it is imperative to evaluate the educational experiences of these international medical students (IMSs). This study was intended to investigate opinions of China-educated IMSs towards the medical curriculum and the impact of Chinese language capability on their clinical studies. Methods A self-administered questionnaire was circulated to the final-year IMSs during the graduation time from May 2019 to July 2019 in 4 universities in China. The questionnaire asked IMSs to assess the quality of medical education and provide a self-evaluation of their Chinese language capability. One-way Analysis of Variance (ANOVA) was used to determine whether IMSs’ Chinese language capability was associated with their clinical experiences and clinical competence. Results Overall, we received 209 valid responses, of which 76.1% were satisfied with the quality of medical education. Genetics, physics, and mathematics were perceived as the least relevant basic courses for medical practice, and 21.5% of student reported that community-oriented medicine was a neglected subject. Notably, 58.9% of students had positive views about discussions on ethical topics during their clerkships, and 71.3% believed they had acquired sufficient clinical skills to begin a residency program. Chinese speaking skills and communication initiatives were found to be critical factors in influencing students’ clinical experiences and competence. Conclusion This study presents the perceptions of China-educated IMSs towards medical curriculum from various aspects. Results show that language influences the education experiences of IMSs. Collectively, these results indicate that the curriculum for IMSs in China should be more problem-based and community-engaged to improve IMSs’ learning experiences and preparation for community deployment. Furthermore, training curriculum for the oral Chinese should be improved to equip IMSs with sufficient language competence to enable them to efficiently carry out clinical clerkship and rotations. Our findings provide evidence for benchmarking medical curricular codifications tailored for Asian and African students.

Leaf inclination angle distribution plays an important role in indirect leaf area measurement methods. Path length distribution method (PATH) is an indirect leaf area measurement method based on Beer's Law, which has been applied to isolated trees with Terrestrial Laser Scanning (TLS). However, it can only set the leaf projection G to a constant value. In this paper, the PATH method considering leaf inclination models is introduced, which allows the G function to be a variable corresponding to leaf inclination. On the basis of this method, this paper explores the effect of different leaf inclination angle distribution assumptions on the inversion of the leaf area of isolated trees based on TLS. The results show that compared with the measured leaf inclination, the relative errors of the inversion results based on the six typical leaf inclination assumptions are between −14.3 % to +41.2%, which indicates that leaf inclination has a significant effect on the inversion of the leaf area. Further, experiments in this paper show that the mean value of the G function is a relatively accurate representation of it.

Leaf area index (LAI) is a key parameter of vegetation structure in the fields of agriculture, forestry, and ecology. Optical indirect methods based on the Beer-Lambert law are widely adopted in numerous fields given their high efficiency and feasibility for LAI estimation. These methods have undergone considerable progress in the past decades, thereby making them operational in ground-based LAI measurement and even in airborne estimation. However, several challenges remain, given the requirement of increasing accuracy and new applications. Clumping effect correction attained significant progress for continuous canopies with non-randomly disturbed leaves while non-continuous canopies are rarely studied. Convenient and operational measurement of leaf angle distribution and woody components is lacked. Accurate and comprehensive validations are still very difficult due to the limitations of direct measurement. The introduction of active laser scanning technology is a driving force for addressing several challenges, but its three-dimensional information has not been fully explored and utilized. In order to update the general knowledge and identify the possible error source, this study comprehensively reviews the temporal development, theoretical framework, and issues of indirect LAI measurement, followed by current methods, instruments, and platforms. Latest methods and instruments are introduced and compared to traditional ones. Current challenges, recent advances, and future perspectives are discussed to provide recommendations for further research.

Purpose: We aimed to establish a nomogram model based on computed tomography (CT) imaging radiomic signature and clinical factors to predict the risk of local recurrence in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).Methods: This was a retrospective study consisting of 156 NPC patients treated with IMRT. Radiomics features were extracted from the gross tumor volume for nasopharynx (GTVnx) in pretreatment CT images for patients with or without local recurrence. Discriminative radiomics features were selected after t-test and the least absolute shrinkage and selection operator (LASSO) analysis. The most stable model was obtained to generate radiomics signature (Rad_Score) by using machine learning models including Logistic Regression, K-Nearest neighbor, Naive Bayes, Decision Tree, Stochastic Gradient Descent, Gradient Booting Tree and Linear Support Vector Classification. A nomogram for local recurrence was established based on Rad_Score and clinical factors. The predictive performance of nomogram was evaluated by discrimination ability and calibration ability. Decision Curve Analysis (DCA) was used to evaluate the clinical benefits of the multi-factor nomogram in predicting local recurrence after IMRT.Results: Local recurrence occurred in 42 patients. A total of 1,452 radiomics features were initially extracted and seven stable features finally selected after LASSO analysis were used for machine learning algorithm modeling to generate Rad_Score. The nomogram showed that the greater Rad_Score was associated with the higher risk of local recurrence. The concordance index, specificity and sensitivity in the training cohort were 0.931 (95%CI:0.8765–0.9856), 91.2 and 82.8%, respectively; whereas, in the validation cohort, they were 0.799 (95%CI: 0.6458–0.9515), 79.4, and 69.2%, respectively.Conclusion: The nomogram based on radiomics signature and clinical factors can predict the risk of local recurrence after IMRT in patients with NPC and provide evidence for early clinical intervention.

Leaf angle distribution (LAD) is an important attribute of forest canopy architecture and affects the solar radiation regime within the canopy. Terrestrial laser scanning (TLS) has been increasingly used in LAD estimation. The point clouds data suffer from the occlusion effect, which leads to incomplete scanning and depends on measurement strategies such as the number of scans and scanner location. Evaluating these factors is important to understand how to improve LAD, which is still lacking. Here, we introduce an easy way of estimating the LAD using open source software. Importantly, the influence of the occlusion effect on the LAD was evaluated by combining the proposed complete point clouds (CPCs) with the simulated data of 3D tree models of Aspen, Pin Oak and White Oak. We analyzed the effects of the point density, the number of scans and the scanner height on the LAD and G-function. Results show that: (1) the CPC can be used to evaluate the TLS-based normal vector reconstruction accuracy without an occlusion effect; (2) the accuracy is slightly affected by the normal vector reconstruction method and is greatly affected by the point density and the occlusion effect. The higher the point density (with a number of points per unit leaf area of 0.2 cm−2 to 27 cm−2 tested), the better the result is; (3) the performance is more sensitive to the scanner location than the number of scans. Increasing the scanner height improves LAD estimation, which has not been seriously considered in previous studies. It is worth noting that relatively tall trees suffer from a more severe occlusion effect, which deserves further attention in further study.

Both leaf inclination angle distribution (LAD) and leaf area index (LAI) dominate optical remote sensing signals. The G-function, which is a function of LAD and remote sensing geometry, is often set to 0.5 in the LAI retrieval of coniferous canopies even though this assumption is only valid for spherical LAD. Large uncertainties are thus introduced. However, because numerous tiny leaves grow on conifers, it is nearly impossible to quantitatively evaluate such uncertainties in LAI retrieval. In this study, we proposed a method to characterize the possible change of G-function of coniferous canopies as well as its effect on LAI retrieval. Specifically, a Multi-Directional Imager (MDI) was developed to capture stereo images of the branches, and the needles were reconstructed. The accuracy of the inclination angles calculated from the reconstructed needles was high. Moreover, we analyzed whether a spherical distribution is a valid assumption for coniferous canopies by calculating the possible range of the G-function from the measured LADs of branches of Larch and Spruce and the true G-functions of other species from some existing inventory data and three-dimensional (3D) tree models. Results show that the constant G assumption introduces large errors in LAI retrieval, which could be as large as 53% in the zenithal viewing direction used by spaceborne LiDAR. As a result, accurate LAD estimation is recommended. In the absence of such data, our results show that a viewing zenith angle between 45 and 65 degrees is a good choice, at which the errors of LAI retrieval caused by the spherical assumption will be less than 10% for coniferous canopies.

Additional file 1. Graduation Survey for International Medical Students.

Patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy may experience significant anatomic changes throughout the entire treatment course, and adaptive radiation therapy may be necessary to maintain optimal dose delivered both to the targets and to the critical structures. The timing of adaptive radiation therapy, however, is largely unknown. This study was to evaluate the dosimetric benefits of a 3-phase adaptive radiation therapy technique for nasopharyngeal carcinoma. Twenty patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy were recruited prospectively. After fractions 5 and 15, each patient had repeat computed tomography scans, and adaptive replans with recontouring the targets and organs at risk on the new computed tomography images were generated and used for subsequent treatment (replan 1 and replan 2). Two hybrid intensity-modulated radiation therapy plans (plan 1 and plan 2) were generated by superimposing the initial plan (plan 0) to each repeated new computed tomography image, reflecting the actual dose delivered to the targets and organs at risk if no changes were made to the original plan. Dosimetric comparisons were made between the adaptive replans (adaptive radiation therapy plans: plan 0 + replan 1 + replan 2) and their corresponding nonadaptive radiation therapy plans (plan 0 + plan 1 + plan 2). Comparing with the nonadaptive radiation therapy plans, the adaptive radiation therapy plans resulted in a significant improvement in conformity index for planning target volumes for primary disease, involved lymph node, high-risk clinical target volume, and low-risk clinical target volume (PTVnx, PTVnd, PTV1, and PTV2, respectively). Median V95 for PTVnx; D95, D99, V100, V95, and V93 for PTVnd; D99 and V100 for PTV1; and D95, D99, V100, V95, and V93 for PTV2 were increased significantly. There were significant dose-volume reductions, including maximum doses to the brainstem and temporal lobes, mean doses to the glottis, V50 for the supraglottis, Dmean and V30 for the left parotid, median dose to the right optic nerve, and V55 for the skin. The 3-phase adaptive intensity-modulated radiation therapy for patients with nasopharyngeal carcinoma results in improvements in target coverage and conformity index and decreased doses to some organs at risk.

International audience; Urban leaf area measurement is crucial to properly determining the effect of urban trees on micro-climate regulation, heat island effect, building cooling, air quality improvement, and ozone formation. Previous works on the leaf area measurement have mainly focused on the stand level, although the presence of individual trees is more common than forests in urban areas. The only feasible ways for an operational non-destructive leaf area measurement, namely, optical indirect methods, are mostly limited in urban areas because light path is constantly intercepted by surrounding buildings or other objects. A terrestrial laser scanner (TLS), which can extract an individual tree by using its unique distance information, provides a possibility for indirectly measuring the leaf area index (LAI) in urban areas. However, indirect LAI measurement theory, which uses the cosine of an observation zenith angle for path-length correction, is incompatible for an individual tree because the representative projected area of LAI changes while the observation zenith angle changes, thus making the results incomparable and ambiguous. Therefore, we modified a path length distribution model for the leaf area measurement of an individual tree by replacing the traditional cosine path length correction for a continuous canopy with real path length distribution. We reconstructed the tree crown envelope from a TLS point cloud and calculated a real path length distribution through laser pulse-envelope intersections. Consequently, leaf area density was separated from the path length distribution model for leaf area calculation. Comparisons with reference measurement for an individual tree showed that the TLS-derived leaf area using the path length distribution is insensitive to the scanning resolution and agrees well with an allometric measurement with an overestimation from 5 m 2 to 18 m 2 (3-10%, respectively). Results from different stations are globally consistent, and using a weighted mean for different stations by sample numbers further improves the universality and efficiency of the proposed method. Further automation of the proposed method can facilitate a rapid and operational leaf area extraction of an individual tree for urban climate modeling.

Heming Lu,1,2 Yuying Wu,3 Xu Liu,2 Hailan Jiang,2 Qiang Pang,2 Luxing Peng,2 Jinjian Cheng,2 Shan Deng,2 Junzhao Gu,2 Renfeng Zhao,3 Xiaoxia Hu,3 Changyi Chen,3 Jinming Yu1 1Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China; 2Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; 3Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China Background: To investigate the efficacy and safety of neoadjuvant chemoradiotherapy plus anti-epidermal growth factor receptor monoclonal antibody followed by surgery for locally advanced cervical cancer (LACC). Patients and methods: Patients with histologically proven LACC were enrolled into this prospective study. All patients received intensity-modulated radiation therapy with conventional fractionation. Weekly cisplatin or nedaplatin was administered concurrently with intensity-modulated radiation therapy. Nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, was given at a dose of 200 mg per week for 6 cycles. Approximately 1 month after the completion of neoadjuvant treatment, the patients were assessed for clinical tumor response and operability based on MRI and gynecological examination. For those who were considered to be candidates for surgery, radical hysterectomy, and pelvic lymph node dissection were performed 5–6 weeks after the completion of neoadjuvant therapy. Results: Twenty-eight patients were enrolled. Clinical complete response and partial response were found in 8 (28.5%) and 20 (71.5%) patients, respectively. Four patients were not eligible for surgery and 2 patients refused surgery although they were assessed as surgical candidates. They were not included in this analysis. Radical hysterectomy and pelvic lymph node dissection were performed for the remaining 22 patients. Among them, 8 (36.4%) had complete pathology response, 9 (40.9%) presented with persistent atypical cells or cervical intraepithelial neoplasia, and 5 (22.7%) presented with macroscopic and/or microscopic residual disease, according to the pathological evaluation. Median follow-up time was 22 months (range, 5–39 months). The 2-year locoregional control rate, progression-free survival rate, distant metastasis-free survival rate, and overall survival rate were 95.0%, 85.2%, 84.0%, and 90.0%, respectively. Acute toxicities were mild in general and easily manageable. Chronic toxicities were mainly limited to grade 1. No severe late toxicities were observed. Conclusion: Concurrent chemoradiotherapy plus nimotuzumab followed by surgery is highly effective and safe in LACC. Further studies are warranted to confirm the findings. Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery, hysterectomy

This study aimed to evaluate whether placing dose constraints on the brachial plexus (BP) could provide dosimetric benefits in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). Planning CT images for 30 patients with NPC treated with definitive IMRT were retrospectively reviewed. Target volumes, the BP and other critical structures were delineated; two separate IMRT plans were designed for each patient: one set no restrictions for the BP; the other considered the BP as a critical structure for which a maximum dose limit of ≤66 Gy was set. No significant differences between the two plans were observed in the conformity index, homogeneity index, maximum dose to the planning target volumes (PTVs), minimum dose to the PTVs, percentages of the volume of the PTVnx and PTVnd receiving more than 110% of the prescribed dose, or percentages of the volume of the PTVs receiving 95% and > 93% of the prescribed dose. Dose constraints significantly reduced the maximum dose, mean dose, V45, V50, V54, V60, V66 and V70 to the BP. Dose constraints significantly reduced the maximum dose to the BP, V45, V60 and V66 in both N0–1 and N2–3 disease; however, the magnitude of the dosimetric gain for each parameter between N0–1 and N2–3 disease was not significantly different, except for the V60 and V66. In conclusion, placing dose constraints on the BP can significantly decrease the irradiated volume and dose, without compromising adequate dose delivery to the target volume.

How to test the effect of density estimation methods is the key problem in the statistics. This paper presents a new criterion for assessing the effect of density estimation to select the suitable density e stimation method, using the maximum-entropy non-Gaussian measurement. Comparing withχ 2 -test and Dn-test, the method avoids the problem of the data interval division, and it is su itable for any type probability distribution. Simulation results show that the proposed me thod can accurately discriminate the pros and cons of different density estimation methods..

Background To determine appropriate timing of an adaptive radiation therapy (ART) replan by evaluating anatomic and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods Nineteen NPC patients were recruited. Each patient had repeat computed tomography (CT) scans after each five fractions and at treatment completion. Automatic re-contouring the targets and OARs by using deformable registration algorithm was conducted through CT-CT fusion. Anatomic changes were assessed by comparing the initial CT and repeated CT. Hybrid plans with re-contouring were generated and the dose-volume histograms (DVH) of the hybrid plan and the original plan were compared. Results Progressive volume reductions in gross target volume for primary disease (GTVnx), gross target volume for involved lymph nodes (GTVnd), and parotids were observed over time. Comparing with the original plan, each hybrid plan had no significant difference in homogeneity index (HI) for all the targets. Some parameters for planning target volumes for primary disease and high-risk clinical target volume (PTVnx and PTV1, respectively) improved significantly, notably starting from the 10th fraction. These parameters included mean dose (Dmean), dose to 95 % of the volume (D95), percentage of the volume receiving 95 % of the prescription dose (V95), and conformity index (CI) for PTVnx, and Dmean, D95, and CI for PTV1. The dosimetric parameters for PTVnd remained the same in general except for D95 and V95 which had significant improvement at specific time points; whereas for PTV2, similar trend of dosimetric changes was also observed. Dose to some OARs increased significantly at some time points. Conclusions There were significant anatomic and dosimetric changes in the targets and OARs. The target dose coverage in the hybrid plans did not get worse, but overdose occurred in some critical structures. Significant dosimetric changes should be considered as a trigger point at which ART replanning is indicated. D95/V95/CI for PTV2, Dmax for the brain stem, spinal cord, right eyeball and left lens, and Dmean/V30 for the parotids and glottis were taken into account for predicting the need for ART. Two replans at the 5th and 15th fractions were suggested.

e17000 Background: This study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy plus nimotuzumab followed by surgery for advanced cervical cancer. Methods: The inclusion criteria of this study were as follows: age: 18-75 years old; ECOG 0-1; FIGO stages IB2-IIIB; not eligible for surgery. IMRT with a total dose of 50-54 Gy was delivered to the tumor and the whole uterus, and 45-48.6 Gy to the high-risk regions. Weekly cisplatin or nedaplatin was administered concurrently with IMRT. Weekly nimotuzumab was given for 6 cycles. Patients were then assessed for clinical tumor response and operability. For those who were candidates for surgery, radical hysterectomy and pelvic lymph node dissection were performed 5-6 weeks after the completion of neoadjuvant therapy. Results: Twenty-eight patients were enrolled. Stage distributions were as follows: IB2, 3 pts; IIA, 5 pts; IIB, 16 pts; IIIA, 2 pts; IIIB, 2 pts. Twenty six (92.8%) patients completed ≥ 5 cycles of chemotherapy, and all completed ≥5 cycles of nimotuzumab. Complete clinical response and partial response were found in 8 patients (28.5%) and 20 patients (71.5%), respectively. Four patients were not eligible for surgery and 2 candidates refused surgery. They were not included in this analysis. Radical surgery was performed for the remaining 22 patients. Among them, 8 (36.4%) had complete pathology response, 9 (40.9%) presented with persistent atypical cells or cervical intraepithelial neoplasia, and 5 (22.7%) presented with macroscopic and/or microscopic residual disease. Median follow-up was 22 months (range, 5-39 months). The 2-year locoregional control rate, progression-free survival rate, distant metastasis-free survival rate, and overall survival rate were 95.0%, 85.2%, 84.0%, and 90.0%, respectively. Acute toxicity profiles were mainly manifested as marrow suppression, nausea, diarrhea, and loss of appetite. They were mild in general and easily manageable. Chronic toxicities were mainly limited to grade 1. No severe late toxicities were observed Conclusions: This treatment approach is highly effective and safe in advanced cervical cancer. Further studies are warranted to confirm the findings. Clinical trial information: NCT01938105.