With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects.This study aimed to explore its radio-sensitizing effects and the underlying mechanisms.Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis.Bioinformatic molecular docking prediction and following validation by surface plasmon resonance(SPR)technology,cellular thermal shift assay(CETSA),and isothermal titration calorimetry(ITC)were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha(HSP90α).The effects of ginsenoside Rg5 on HSP90-cell division cycle 37(CDC37)interaction,the client protein stability,and the downstream regulations were further explored.Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis.It could bind to HSP90α with a high affinity,but the affinity was drastically decreased by HSP90α Y61A mutation.Co-immunoprecipitation(Co-IP)and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner.It reduced irradiation-induced upre-gulation of the HSP90-CDC37 client proteins,including SRC,CDK4,RAF1,and ULK1 in A549 cell-derived xenograft(CDX)tumors.Ginsenoside Rg5 or MRT67307(an IKKe/TBK1 inhibitor)pretreatment suppressed irradiation-induced elevation of the LC3-Ⅱ/β ratio and restored irradiation-induced downregulation of p62 expression.In A549 CDX tumors,ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage.In conclusion,ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma.It interacts with HSP90α and reduces the binding between HSP90 and CDC37,thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

Radiotherapy is an essential part of comprehensive treatment, as well as a radical treatment for head and neck cancer (HNC). The COVID-19 has continued so far, imposing a great impact on cancer care. Since conventional fractionated radiotherapy (CFRT, 2 Gy/F) requires as long as more than six weeks of treatment time, a huge challenge for epidemic control is created for both hospitals and patients. Hypofractionated radiotherapy (Hypo-RT) may be more suitable than CFRT for patients during pandemic by increasing the fraction size, thus reducing fraction number and treatment duration. Early studies have explored the application of Hypo-RT in HNC in palliative setting, which partially proved its safety and effectiveness. Recently, the efforts have been made in definitive treatment using hypofractionated regimen, as well as its combination with systemic treatment and immunotherapy. Indeed, regarding the pandemic of COVID-19, Hypo-RT has been recommended by several expert consensus in the HNC. In this review, relevant research progress was summarized and clinical implication of Hypo-RT in COVID-19 pandemic era was discussed.

Objective: To report an implementation method and results of an independent brachytherapy dose verification software (DVS). Methods: The DVS was developed based on Visual C+ + and the modular structure design was adopted. The DICOM RT files exported from the treatment planning system (TPS) were automatically loaded into the DVS. The TG-43 formalism was employed for dose calculation. Six cervical cancer patients who underwent brachytherapy were retrospectively selected to test the DVS. Different applicators were utilized for each patient. Dosimetric parameters and γ analysis (0.1cm, 5%) were used to evaluate the dose difference between the DVS and the TPS. Results: Compared with the TPS dose, the γ pass rates of the doses calculated by the DVS were higher than 98%. For CTV, the dosimetric differences were less than 0.29% and 0.53% for D_100% and D_90%. For bladder, rectum and sigmoid, the agreement of D_0.1cm³, D_1cm³ and D_2cm³ within a 0.5% level. Conclusion With minimal human-computer interactions, the DVS can verify the accuracy of dose calculated by TPS for brachytherapy.

Objective:To explore an implementation method and results of an inverse dose optimization algorithm (gradient-based planning optimization, GBPO) in three-dimensional brachytherapy.Methods:A standard quadratic objective function was used in the GBPO. The optimization code of GBPO was performed based on LBFGS (Limited memory Broyden Fletcher Goldberg Shanno). Seven cervical cancer patients using different applicators and 15 cervical cancer patients using the Fletcher applicator (Nucletron part#189.730) were retrospectively analyzed. The plan quality of GBPO was firstly assessed by isodose lines, then dose-volume histogram (DVH) parameters of CTV(D 100%, V 150%) and organs at risk(D 0.1cm 3, D 1.0cm 3, D 2.0cm 3) were used to evaluate the difference among the GBPO, IPSA and Graphic plans. Results:For the 7 patients using different applicators, GBPO could optimize the conformal dose distribution, and the DVH parameters of the target and organs at risk were basically the same among the GBPO, IPSA and Graphic plans. For 15 patients using the Fletcher applicator, the difference in DVH parameters between the GBPO and IPSA plans was not statistically significant. There was no remarkable difference in the DVH parameters between the GBPO and Graphic plans, but the D 100% of the GBPO plan was significantly higher ( P<0.01), and the V 150% was significantly lower ( P<0.01) than that of the Graphic plan. Conclusions:The quality of the GBPO plan is similar to that of the IPSA plan in terms of target coverage and organ protection. The inverse dose optimization algorithm GBPO can be integrated into a three-dimensional brachytherapy treatment planning system.

Objective: To investigate the radiotherapy (RT)-induced changes in the brain structural network in patients with nasopharyngeal carcinoma (NPC). Methods: Three-dimensional structural magnetic resonance data (3D-T1W) was adopted to investigate the structural network in 103 patients with NPC before and after receiving RT. The structural networks were then reconstructed using 3D-T1W. The radiation-induced changes in topology properties of small world network were analyzed by using graph theoretical analysis. Results: Patients showed small world properties before and after RT. Compared with the pre-RT group, the global and local efficiency were lower, the shortest path length was longer and the clustering coefficient was less in the post-RT group. In addition, the hub regions in the post-RT group were significantly different from those in the pre-RT group, mainly located in the left rolandic operculum, right inferior frontal gyrus, right parahippocampal gyrus, right lingual gyrus, bilateral supramarginal gyrus, left superior temporal gyrus and temporal pole of the right middle temporal gyrus. Conclusion It is speculated that RT leads to high efficiency of network topology and information transmission, which provides a novel perspective for exploring the RT-induced brain changes, diagnosis of RT-induced injury and evaluation of RT efficacy.

Objective To compare the neck skin dose between fixed-field dynamic intensity-modulated radiation therapy (dlMRT),volumetric modulated arc therapy (VMAT),and helical tomotherapy (HT) in the treatment of early-stage nasopharyngeal carcinoma.Methods A total of 16 early-stage nasopharyngeal carcinoma patients undergoing radiotherapy were enrolled as subjects.The neck skin was delineated by contraction of the outer edge of neck by 3 mm.Dose planning was made by the traditional method (TP group)and a new method (NP group),in which the neck skin was considered as the organ at risk.Dmean and V5-V70 for the neck skin were recorded.The paired t-test was used to analyze the differences between two plans in each radiotherapy method.An analysis of variance was used to compare the same plan between the three radiotherapy methods.Results The HT group had significantly higher Dmean and V5-V70 for the neck skin than the dIMRT group and the VMAT group (P=0.00,0.00,0.00,0.00,0.00,0.00,0.00,0.02).Using dIMRT,the D and V10-V60 for the neck skin were reduced by 7％,8％,22％,25％,38％,59％,and 85％ in the NP group than in the TP group (P=0.00,0.00,0.00,0.00,0.00,0.00,0.00).Using VMAT,the D and V20-V40 for the neck skin were reduced by 4％,19％,29％,and 34％ in the NP group than in the TP group (P=0.02,0.01,0.02,0.01).Using HT,the V30-V60 for the neck skin were reduced by 20％,29％,50％,and 67％ in the NP group than in the TP group (P=0.00,0.00,0.00,0.00,0.03).Conclusions In the treatment of early-stage nasopharyngeal carcinoma,HT causes a higher radiation dose to the neck skin than dIMRT and VMAT,while dIMRT and VMAT have similar neck skin doses.The neck skin dose can be significantly reduced with the neck skin as the organ at risk.

Objective To compare the automatic and manual plans of intensity-modulated radiation therapy ( IMRT ) for nasopharyngeal carcinoma and investigate whether the automatic plan possesses advantages over the manual plan. Methods Clinical data of 97 nasopharyngeal carcinoma patients were retrospectively analyzed. All patients received IMRT with Eclipse treatment planning system (Version 11. 0) using manual optimization. The same plans were optimized successively in Pinnacle3( version 9. 10 ) treatment planning system using automatic plan software package module (provided by Prof. Zhang XD from MD Anderson Cancer Center).The D95(dose in 95% of planning target volume,PTV),homogeneity index, conformal index and normal organ dose were statistically compared between two plans. Results The PTV coverage and homogeneity did not significantly differ between two plans. Compared with the manual plan,the automatic plan could more effectively protect the normal organs. Two plans significantly differed in a majority of organ at risk (OAR).The mean dose was decreased by 270-1870 cGy. Conclusions For nasopharyngeal carcinoma patients,IMRT via the automatic plan can meet the clinical requirement for target prescription dose and reduce the dose of normal organs.

Objective The purpose of this study is to investigate the method to reduce the radiation dose to the neck skin in the Tomotherapy treatment plans for early-stage nasopharyngeal carcinoma.Methods The 17 patients with early-stage nasopharyngeal carcinoma that have been treated by the Tomotherapy were selected randomly for this skin sparing study.The neck skin sparing region was generated as an internal margin of 3 mm from the out body contour,excluding the intercrossed area with the targets.Candidate patients were planned using TP and NP method respectively:the TP group was planned with the traditional method.The new neck skin region was considered as an organ at risk (OAR) for planning dose constrain in NP group.The dosimetric metrics of targets and OARs,monitor units (MU) and delivery time were compared as the end points of these two groups.Results The two treatment plan groups satisfied the clinical requirement.There were no significant differences for D98,D95 and D2 of the targets (P ＞ 0.05).The Dmax of brainstem,D1cc of spinal cord,D of right parotid were higher in NP group than in theTPgroup (t =2.47,2.34,2.77,P＜0.05).The Dmax of left mandible joint was lower than TP group(t =2.30,P ＜ 0.05).The V30,V40,V50 and V60 of the skin were considerably lower than TP group (t =8.37,6.02,5.82,4.89,P ＜ 0.05).The mean MU and mean delivery time per fraction of NP group were 6.3％ and 8.1％ less than that of TP group respectively.Conclusions The neck skin region should be delineated as an OAR to be spared in the Tomotherapy treatment planning for early-stage nasopharyngeal carcinoma.This method can reduce the skin radiation dose effectively,alleviate the skin reaction,and improve the life quality of patients in radiotherapy.

Objective To compare dosimetric parameters between automatic three-dimensional conformal radiotherapy (a3DCRT),inverse three-dimensional conformal radiotherapy (i3DRT),inverse intensity-modulated radiotherapy (iIMRT).Methods Ten lung cancer patients with a single target and 10 intracranial tumor patients also with a single target,who were treated in our radiotherapy center from 2014 to 2015,were included in the study.Their image data were transferred to RayStation 4.5 via network,and then the treatment plans for a3DCRT,i3DCRT,and iIMRT were designed for the 20 patients.The dosimetric parameters for planning target volume (PTV) and organs at risk (OAR) were compared between the three plans using multiple dependent variables and two dependent variables.Results For lung cancer patients,iIMRT achieved better results in D98％,D50％,D2％,conformity index (CI),and homogeneity index (HI) than i3DCRT and a3DCRT (P=O.007,0.001,0.002,0.000,and 0.000),and the CI of a3DCRT was superior to that of i3DCRT (P=O.000);there were no significant differences in heart D33,spinal cord Dmax and D1 cm3,and both lungs between the three plans (P=O.702,0.237,0.163,0.739,0.908,0.832,0.886,0.722,0.429,0.840,and 0.702).For intracranial tumor patients,there were no significant differences in dosimetric parameters between the three plans,except that the CI of iIMRT and a3DCRT was superior to that of i3DCRT (P=O.648,0.783,0.256,0.931,0.002,and 0.034);there were no significant differences in whole brain irradiation dose between the three plans (P=0.446,0.755,0.772,0.0266,0.440,0.290,and 0.939).Conclusions For the single target in patients with lung cancer and intracranial tumors,a3DCRT can improve the CI of PTV compared with i3DCRT,and shows no significant dosimetric disadvantage for OARs compared with iIMRT.Considering the simplicity and low cost of 3DCRT,a3DCRT holds promise as a novel radiotherapy technique.