The occurrence and severity of radiotherapy-induced adverse events cannot be accounted for or predicted by therapeutic and clinical factors alone.Evidence suggests that genetic variants are associated with adverse effects following radiotherapy.Radiation genomics is the study of genetic variants associated with radiotherapy toxicity.Radiation genomics aims to develop a risk prediction model and uncover the biological mechanisms responsible for radiotherapy toxicity.With the advances in genomics and bioinformatics in the past two decades,radiation genomics has evolved from candidate gene studies to genome-wide association studies,with a series of progress.In this review,we will discuss the study background,design,approaches,challenges,and future directions for radiation genomics.

Objective To compare the effect of set-up errors to two different body positions that are putting arms on the side of the body (A group) or placing arms folded across the elbow on forehead (B group) in esophageal cancer' fraction radiotherapy.Methods By using case-control study,all supine patients were divided into the A group and the B group.After patients were fixed by thermoplastic membrane,they were located by spiral CT and treated by using IGRT.During treatmwnt,there were three cone-beam CT scans in the first week and then at least one scan weekly.We obtained the linear set-up errors data by using bone registration with manual proofreading in 3 directions that were left and right (x),head and feet (y),abdomen and back (z) by using CBCT.Means were compared by using independent sample t-test,and ratios were compared by chi-square test.Results Every group had 11 cases that the A group had 92 people times and the B group had 87 people times.Absolute set-up errors of two different positions:only x-axis,the mean of the A group was (2.46 ± 1.79) mm.But the mean of the B group was (1.91 ± 1.71)mm,which was significantly less than the A group (P =0.036).Relative set-up errors of two groups:only y-axis,the mean of the B group was (1.91 ± 4.12) mm.The A group was (0.09 ± 3.90) mm,which was significantly less than the B group (P =0.003).There was no significant difference of three-dimensional set-up errors (P=0.751).And there was no significant difference in absolute weekly set-up errors or weekly three-dimensional set-up errors in radiotherapy (P ＞ 0.05).Conclusions The each of two body positions in esophageal cancer' fraction radiotherapy has advantage and disadvantage for set-up errors,but they were in control and didn't affect the radiotherapy planning.We can choose appropriate treatment position according to clinical practice.

Objective To conduct the 7th investigation by Chinese Society of Radiation Oncology,Chinese Medical Association,and to further investigate the current situation of radiotherapy in mainland China,reasonably allocate personnel and equipment resources,and promote the development of radiotherapy in China.Methods From October 8,2015 to December 2015,the office for investigation of radiotherapy information was established,the list and contact information of radiotherapy units were provided by each province,and a special data submission system was used for a complete,rapid,and efficient investigation through the Internet.Results As of January 20,2016,there were 1 413 radiotherapy units in the mainland China with 52,496 employees in total,among which there were 15 839 radiotherapy physicians (4824 with senior professional titles),8 452 technical therapists (260 with senior professional titles),3 292 physicists (562 with senior professional titles),and 938 maintenance engineers (120 with senior professional titles).In the aspect of radiotherapy equipment,there were 1930 linear accelerators,96 Co-60 teletherapy units,173 X-knife units,212 γ-knife units,382 Ir-192 brachytherapy units,436 Co-60 brachytherapy units,1 051 X-ray simulators,1 353 CT simulators,642 MRI simulators,978 sets of multileaf collimators,1922 sets of treatment planning systems,and 974 sets of radiotherapy network systems.As for quality control devices,there were 1 792 dosimeters,2 143 ionization chambers,935 two-dimensional array dosimeters,540 threedimensional dosimetric verification systems,596 three-dimensional water tanks,844 anthropomorphic phantoms,and 1 168 water equivalent phantoms.In the aspect of therapeutic situation,there were 102,170 beds (including beds in departments of oncology in general hospitals),76612 episodes per day,and 919339 episodes per year.Conclusions The results of this investigation show significant increases in radiotherapy units,personnel,and equipment in recent years in mainland China.The distribution of radiotherapy units and equipment and the structure of radiotherapy personnel are becoming more reasonable,but there are still some problems.In some regions,current radiotherapy equipment cannot meet the medical needs,and there is a lack of professional technical personnel.

Objective:To examine the status of personnel and facilities of radiotherapy in county hospital of Chinese mainland and to evaluate the equity of allocation.Methods:All the county level radiotherapy units were chosen for study, and the data were extracted from the 9 th national survey on radiation oncology departments conducted by Chinese Society of Radiation Oncology of Chinese Medical Association from April 10, 2019 to September 20, 2019. Descriptive statistics and statistical analysis were performed. For the further analysis on the equity, the Gini coefficient, Theil index and agglomeration degree were calculated. Results:The number of county level radiotherapy units was 191 in the eastern region, 172 in the central region and only 59 in the western region, and there was no radiotherapy unit in the county area of some provinces in the western region. For the counties with larger population (population over 500 thousand) in Chinese mainland, 23.4% of the counties in the western region had radiotherapy units, lower compared to the eastern region (48.9%) and central region (41.8%). The Gini coefficients of all kinds of radiotherapy health resources according to population allocation were in alert states, and in highly unfair states according to geographical allocation. The intra-regional gap in radiotherapy resource allocation was larger than the inter-regional gap, and the intra-regional gap mainly came from the western region. HRADi,HRADi/ PADi in the eastern and central regions were all greater than 1, while those in the western region were all less than 1. Conclusions:The overall configuration of county level radiotherapy units in Chinese mainland is insufficient, and there is a regional difference. The fairness of geographical allocation of radiotherapy resources is generally poor. Radiotherapy resources should be scientifically configured to improve the fairness of radiotherapy resource distribution.

Objective To investigate the value of DWI using 3.0 T MRI to predict response to radiotherapy(RT) and concurrent chemoradiotherapy(CCRT) in patients with advanced non-small cell lung cancer (NSCLC).Methods From January 2014 to May 2015, 40 patients with stageⅢ(Ⅲa orⅢb) NSCLC underwent DWI using 3.0 T MRI before RT/CCRT were enrolled. The imaging quality of diffusion-weighted images were evaluated on 3-level grades as good, moderate and non-diagnostic.The patients with good or moderate image quality were underwent DWI at 2 weeks after starting therapy(total dose of 20 Gy), and at the end of therapy (total dose of 60 Gy). Apparent diffusion coefficient(ADC) of lung cancer with good and moderate image quality were calculated by Funtool. The following quantitative parameters were recorded and calculated: the mean pretreatment ADC value(ADCpre), the mean mid-treatment ADC value (ADCmid), the mean post-treatment ADC value(ADCpost), the rate of changes inmean ADC value at 2 weeks post therapy (ΔADCmid) and the rate of changes inmean ADC value at the end of therapy(ΔADCpost). The patients were classified into response group and non-response group according to the tumor response, which was assessed with revised response evaluation criteria in solid tumors (RECIST1.1) after CCRT. The Mann-Whitney U test was used to compare parameters between the two groups.The relationship between these obtained parameters and tumor response was evaluated by Spearman correlation analysis. The value of parameters on predicting tumor response was calculated by receiver operating characteristic curve.Results 96.4%(80/83) DW images were graded as good or moderate image quality. The responders had lower median ADCpre[1.32 (0.77—1.96) × 10- 3 mm2/s] than non-responders[1.60(1.12—2.33) × 10- 3 mm2/s], which had statistically significant difference (Z=-2.934,P=0.003).Tumor regression rate after treatment had negative correlation with ADCpre(r=-0.386, P=0.018).The responders had increased ADC [ΔADCmid: 38.9%(12.8%—139.0%),ΔADCpost: 48.3% (25.6%—148.1%)] than non-responders [ΔADCmid: -2.5% (-15%—29.4%), ΔADCpost:14.2% (- 28.1% —71.3% )], which had statistically significant difference (Z=- 2.847, - 2.221, respectively;P<0.05). Tumor regression rate after treatment had positive correlation with ΔADCmid(r=0.637, P=0.001) and ΔADCpost(r=0.631, P=0.005).From ROC analysis,when setting threshold on pretreatment ADCpre=1.38 × 10-3 mm2/s, ΔADCmid=21.6%, ΔADCpost=38.8%, the area under curve was 0.782, 0.838 and 0.813.Conclusion The mean ADC value before RT/CCRT and its changes during treatment is likely to be a valuabletool for predicting the response after RT/CCRT in advanced NSCLC, which may be helpful to clinical decision on individualized therapy.

Objective To evaluate the efficacy of rescue treatment for recurrent esophageal cancer after radical esophagectomy, and to provide insights into the development of comprehensive treatment for esophageal cancer.Methods The clinical data of 218 patients who were confirmed with recurrent metastatic esophageal cancer after R0 resection and received rescue treatment in our hospital from 2004 to 2014 were retrospectively reviewed.The survival rate was determined by the Kaplan-Meier method.Univariate and multivariate prognostic analyses were performed using the log-rank test and Cox proportional hazards model, respectively.Results The median post-recurrence follow-up time was 53 months.The 1-and 3-year overall survival (OS) rates after recurrence were 57.2% and 24.4%, respectively.Among the 163 patients with local recurrence, the 1-and 3-year OS rates were 70% and 42% for patients treated with chemoradiotherapy (n=40), 55% and 24% for those with radiotherapy alone (n=106), and 23% and 8% for those with supportive therapy (n=13)(chemoradiotherapy vs.radiotherapy alone P=0.045, radiotherapy alone vs.supportive therapy P=0.004;none of the patients who were treated with chemotherapy alone survived for one year or more).Univariate analysis showed that N staging, TNM staging, and post-recurrence rescue treatment regimen were independent prognostic factors for esophageal cancer (all P=0.001).On the other hand, multivariate analysis indicated that only rescue treatment regimen was the independent prognostic factor for esophageal cancer (P=0.013).Conclusions Rescue chemoradiotherapy or radiotherapy alone can bring significant survival benefits for patients with recurrent and metastatic, especially locally recurrent, esophageal cancer following radical esophagectomy.

FLASH radiotherapy (FLASH-RT) is a treatment modality that delivers ultra-high dose rate and ultra-fast radiation for cancer treatment. Compared to conventional dose rate radiotherapy, FLASH-RT can yield similar efficacy for tumors and achieve normal tissue protection, translating to an increased therapeutic window. Due to this unique feature, FLASH-RT is attracting increasing attention from the radiotherapy community, both academia and industry. Due to its unique Bragg peak as well as intrinsic high dose rate, application of FLASH has more value and profound significance in proton therapy while achieving highly conformal dose deposition simultaneously. This article reviews research progress on FLASH-RT, relevant cell and animal studies, experimental conditions and results. Moreover, this article also investigates the potential biological mechanisms, technical challenges for implementation and potential clinical applications of FLASH-RT.

Objective:To evaluate the 5-year survival outcome of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) treated with Endostar in combination with platinum-based concurrent chemoradiotherapy.Methods:From March 2009 to June 2015, 115 patients with the unresectable locally advanced NSCLC from two prospective studies[Clinical trials 2009-2012(ClinicalTrials.gov NCT01894) and 2012-2015(ClinicalTrials.gov, NCT01733589)] were treated with Endostar in combination with platinum-based concurrent chemoradiotherapy. A total dose of 60-66 Gy was delivered in 30-33 fractions. Endostar was given 1 week prior to the beginning of radiotherapy, and repeated fortnightly during the concurrent chemoradiotherapy. After long-term follow up, survival outcome was evaluated in 104 patients treated with radiation dose of ≥60 Gy. Kaplan-Meier method was used for survival analysis. Univariate survival analysis was performed using the log-rank test.Results:Of 104 eligible patients, 60.6% of them had squamous carcinoma and 65.4% were classified in stage Ⅲ B. All the patients received ≥2 cycles of Endostar and 93.3% of them received 4 cycles of Endostar. The median follow-up time was 68.3 months. The median overall survival (OS) and median progression-free survival (PFS) were 31.3 and 13.9 months, respectively. The 3-year and 5-year OS were 45.6% and 35.7%, respectively. The 3-year and 5-year PFS were 27.1% and 24.9%, respectively. Univariate analysis indicated that sex, ECOG, pathological type, clinical stage, radiotherapy technique, chemotherapy regimen, chemotherapy cycle and cycle of Endostar use were not associated with OS. Late radiation injury occurred in 14.4% of patients, and no grade 4-5 late injury was observed. Conclusion:Patients with unresectable locally advanced NSCLC treated with Endostar fortnightly in combination with platinum-based concurrent chemoradiotherapy achieve better OS than historical data with tolerable toxicities.

Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.

Objective To explore the incidence and related predictive factors for acute symptomatic esophagitis in patients with locally advanced non?small cell lung cancer ( NSCLC ) treated with intensity?modulated radiation therapy ( IMRT) . Methods Data were collected retrospectively from 256 patients with inoperable or unresectable stage Ⅲ NSCLC treated in our hospital between January 2007 and December 2011. The radiotherapy target volume included primary lung cancer and lymphatic drainage area involved,with a median dose of 60 Gy in 30 fractions (50-70 Gy).Of all the patients,109 patients (42.6%) received concurrent chemotherapy. Grade ≥2 acute esophagitis ( AE ) ( symptomatic esophagitis ) which occurred during radiotherapy and within 3 months after completion of radiotherapy served as the outcome event. National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0( NCI?CTCAE3.0) was used to evaluate the grade of AE. The logistic regression model was used to analyze the predictive factors. Results A total of 174 patients ( 68%) had treatment?related grade ≥2 AE;154 patients ( 60. 2%) had grade 2 AE and 20 patients (7.8%) had grade 3 AE.The median dose when grade≥2 AE occurred was 30 Gy (11?68 Gy).For grade≥2 AE,multivariate analysis showed that esophageal V5?V60,mean dose,and age were independent predictive factors (P=0.021,0,0.010).For grade ≥3 AE,multivariate analysis showed that esophageal V50?V60 ,concurrent chemotherapy,and body mass index ( BMI) were independent predictive factors ( P= 0.010,0.003,0.019 ) . Old age and higher BMI were the protective factors for grade≥2 and ≥3 AE, respectively. Conclusions For patients with locally advanced NSCLC treated with IMRT, esophageal V50—V60 and concurrent chemotherapy are predictive factors for grade ≥3 AE,and esophageal V50 has a high predictive value for both grade ≥2 and ≥3 AE.