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Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.
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Objective:To investigate the current status of radiotherapy personnel and equipment in China, and to provide data basis for scientific allocation and effective use of radiotherapy equipment during the 14 th Five-year Plan period. Methods:From October to December 2020, a group of experts from China Association of Medical Equipment carried out an online questionnaire investigating the basic situation of radiotherapy in China, and the contents of the survey include radiotherapy centers, professional personnel, equipment, technology, equipment utilization rate, forecast of personnel and equipment in the next five years, etc. The data were reviewed by provincial medical societies/associations.Results:There were 1538 radiotherapy centers and 32978 radiotherapy professionals in Mainland China, including 18966 radiotherapy physicians, 4475 physicists and 9537 technicians. There were 2139 linear accelerators, 57 cobalt 60 accelerators, 457 afterloaders, 6 proton/heavy ion machines, 1034 conventional 2D simulators, 1208 CT simulators, and 89 MR simulators. 1459 centers can provide 3D conformal radiotherapy, 1256 centers can deliver intensity-modulated radiotherapy, 514 centers can offer volumetric modulated arc therapy, 422 centers can provide brachytherapy. According to the estimated data reported by the participating centers, in the next five years, the demand of professionals and machines will be increased by 4868 radiotherapy physicians, 2078 physicists and 3796 technicians, and 994 linacs, 896 CT simulators, 313 MR simulators and 54 proton heavy ions.Conclusions:The radiotherapy industry in China grows fast. During the 14 th Five-Year Plan period, the radiotherapy industry still has strong market demand as well as increase demand of personnel and equipment. Strengthening the market competitiveness of domestic radiotherapy enterprises, improving the equipment utilization rate in primary hospitals, providing comprehensive and systematic training and promoting standardized clinical application can resolve the issues of the lack and unbalanced distribution of radiotherapy resources, and maintain the fast and sustainable development of radiotherapy in China.
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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.
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Indoleamine 2, 3-dioxygenase (IDO) is one of the rate-limiting enzymes that degrade tryptophan (Trp) into kynurenine (Kyn). Inflammatory factor IFN-γ mediates tumor′s immune escape by activating the IDO signaling pathway, upregulating theKyn/Trp (K/T ratio) and suppressing the activity of both CD 8+T and regulatory T cells. Radiotherapy plays a major role in treating non-small cell lung cancer. It not only bi-directionally regulates immune response of the host, but also collaborates with immunosuppressive agents to kill tumors. Meanwhile, immune status of the host can affect the therapeutic effect of radiotherapy. In recent years, studies have shown that IDO activity levels change before and after radiotherapy and is related to clinical prognosis. Nevertheless, relevant mechanism remains unclear. This article aims to elucidate the application of IDO signaling pathway in radiotherapy for non-small cell lung cancer.
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Lung cancer is the malignant tumor with the highest mortality in the world, of which non-small cell lung cancer (NSCLC) accounts for about 80%. The orderly combination of surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy is currently the main treatment modality for NSCLC. Liquid biopsy has been increasingly used in clinical practice in recent years due to its advantages of being non-invasive and overcoming tumor heterogeneity, of which circulating tumor DNA (ctDNA) is one of the most commonly used analytical indicators, and ctDNA detection may play a role in the treatment of NSCLC. This article reviews new developments in the use of ctDNA for prognostic assessment, recurrence monitoring and efficacy prediction in NSCLC patients.
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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.
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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.
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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.
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Objective To compare target dosimetric distribution and normal tissue radiation between different static intensity-modulated radiation therapy (IMRT)plans and volumetric modulated arc therapy (VMAT),and to identify the best IMRT plan for lymphoma patients needed mediastinal radiation. Methods A total of 11 patients with lymphoma who received first course radiotherapy in the mediastinal region after che-motherapy in Cancer Hospital & Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from March 2017 to January 2019 were included in the study. There were 8 males and 3 fe-males,2 patients were in Ann Arbor stage Ⅰ-Ⅱ,and 9 cases in Ⅲ-Ⅳ stage. There were 6 patients with Hodgkin lymphoma (HL)and 5 patients with non-Hodgkin lymphoma (NHL). Patients with HL and NHL were given prescript doses of 36 Gy and 50 Gy,respectively. Three plans were designed for each patient:static 5F-IMRT,7F-IMRT and VMAT plan. The target dosimetric distribution,normal tissue radiation dose,and effi-ciency of each plan were evaluated. Results The mean conformity index (CI)and homogeneity index (HI) values of plan target volume (PTV)in 5F-IMRT,7F-IMRT,VMAT plan were 0. 64 ± 0. 06,0. 67 ± 0. 05, 0. 76 ± 0. 04 (F = 17. 045,P < 0. 001)and 1. 07 ± 0. 01,1. 07 ± 0. 01,1. 09 ± 0. 01 (F = 9. 258,P =0. 001),respectively. VMAT showed significantly better CI than two static IMRT plans (both P < 0. 001),but worse HI (both P < 0. 001). The lungs low dose irradiation volume (V (V 5 )and high dose irradiation volume 30 )in 5F-IMRT,7F-IMRT,VMAT plan were (43. 98 ± 7. 77)％,(42. 71 ± 4. 98)％,(55. 92 ± 8. 16)％(F = 8. 281,P = 0. 001)and (8. 19 ± 2. 97)％,(8. 25 ± 2. 87)％,(7. 53 ± 3. 16)％ (F = 0. 140,P =0. 870),respectively. The volume of low dose irradiation in lungs of VMAT plan was significantly higher than 5F-IMRT and 7F-IMRT plans (both P < 0. 001),while high dose volume was no significant difference. The left and right breast low dose irradiation volume (V 4 )in 5F-IMRT,7F-IMRT and VMAT plan were (24. 29 ± 8. 14)％,(23. 87 ± 7. 70)％,(80. 17 ± 22. 92)％ (F = 14. 505,P = 0. 005)and (22. 12 ± 13. 28)％, (21. 13 ± 13. 01)％,(81. 77 ± 20. 76)％ (F = 13. 938,P = 0. 006),respectively. VMAT showed signifi-cantly higher breast low dose irradiation volume than static IMRT plan (both P < 0. 05). The number of monitor units and treatment time in 5F-IMRT,7F-IMRT,VMAT plan were (1622 ± 281)MU,(1729 ± 286)MU, (411 ± 75)MU (F = 105. 277,P < 0. 001)and (6. 79 ± 0. 93)min,(7. 42 ± 0. 95)min,(4. 98 ± 0. 00)min (F = 29. 545,P < 0. 001),respectively. VMAT showed significantly less monitor units than static IMRT (both P < 0. 001)and shorter treatment time (both P < 0. 001). Conclusion For lymphoma patients who have the indication of mediastinal radiotherapy,VMAT is highly efficient and has no definite dose advan-tage,the static 5F-IMRT or 7F-IMRT plan has good conformal and uniform target area,and some organs at risk exposure is even lower.
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Objective@#To evaluate the short-term clinical efficacy and adverse events of volumetric modulated arc therapy (VMAT) in the treatment of locally advanced non-small cell lung cancer (NSCLC).@*Methods@#From January to December 2016, 58 patients (47 male and 11 female) with unresectable locally advanced NSCLC received concurrent or sequential chemoradiotherapy. The radiation dose was ranged from 38 Gy to 66 Gy. The radiation dose was equal or higher than 56 Gy in 53 patients (92%). The median radiotherapy fraction was 30, 1.8 Gy to 3.0 Gy for each fraction. Twenty-eight patients (48%) received concurrent chemoradiotherapy.@*Results@#The median follow-up time was 9 months. The 1-year overall survival (OS) rate was 84% and the 1-year progression-free survival (PFS) rate was 48%.Eleven patients (19%) suffered from symptomatic radiation pneumonitis and one of them died of radiation pneumonitis. Within 6 months after radiotherapy, 31 patients (53%) developed asymptomatic local pulmonary fibrosis on CT images. Seventeen patients (29%) suffered from grade Ⅱ esophagitis. Ten cases (17%) had ≥ grade Ⅲ adverse events and 9 of them presented with leucopenia.@*Conclusions@#VMAT yields high short-term clinical efficacy and tolerable adverse events in the treatment of locally advanced NSCLC, which does not increase the risk of pneumonitis.
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Objective To investigate the clinical efficacy and prognosis of intensity-modulated radiotherapy(IMRT)combined with chemotherapy for limited-stage small cell lung cancer(LS-SCLC). Methods A retrospective analysis was performed on the clinical data of 484 LS-SCLC patients treated with chemoradiotherapy in our center from 2006 to 2014. The patients with partial or complete response to IMRT received prophylactic cranial irradiation(PCI). The Kaplan?Meier method was used to calculate survival rates, and the log-rank test and Cox regression were used for univariate and multivariate analyses, respectively. Results In all the patients, the follow-up rate was 93%;the median overall survival(OS) time was 23.8 months;the 2-,3-,and 5-year OS rates were 48.7%,39.8%,and 28.6%,respectively;the median progression-free survival(PFS)time was 14.1 months;the 2-, 3-, and 5-year PFS rates were 34.4%,30.5%, and 28.3%, respectively. The incidence rates of grade ≥3 bone marrow suppression, grade ≥2 radiation esophagitis, and grade ≥2 radiation pneumonitis were 26.9%, 24.8%, and 18.4%, respectively, in SCLC patients after IMRT. The objective response rate was 84.5%. The univariate analysis showed that age, smoking history, TNM stage, PCI, and the number of chemotherapy cycles before radiotherapy were prognostic factors for OS(P= 0.006, 0.001, 0.047, 0.000, and 0.046). The multivariate analysis showed that smoking history and PCI were independent prognostic factors(P=0.001 and 0.000).Conclusions IMRT combined with chemotherapy achieves satisfactory clinical outcomes in the treatment of LS-SCLC. Smoking history and PCI are independent prognostic factors for OS of LS-SCLC patients.
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Objective To examine the incidence of radiation-induced lung injury(RILI)after involved-field intensity-modulated radiation therapy(IMRT)in patients with locally advanced non-small cell lung cancer(NSCLC),and to evaluate the predictability of different models.Methods The clinical data of 242 inoperable or unresectable stage Ⅲ NSCLC patients treated in our hospital from 2007 to 2011 were reviewed. Grade 2 and grade 3 RILI that occurred within 6 months after IMRT were selected as outcome events in this study. The principal component analysis(PCA)model,Lyman-Kutcher-Burman(LKB)model,and mean lung dose(MLD)model were each used to establish a predictive model of normal tissue complication probability (NTCP)for evaluating the dosimetric parameters of IMRT. Results Four principal components were used in the PCA model. The areas under the receiver operating characteristic curve(AUCs)of grade 2 and grade 3 RILI were 0.652 and 0.611,respectively. For the LKB model, the fitted parameters were m=0.46, n=1.35, and D50=23.59 Gy for grade 2 RILI,and m=0.36,n=0.27,and D50=72.67 Gy for grade 3 RILI. The AUCs of grade 2 and grade 3 RILI in the LKB model were 0.607 and 0.585, respectively. For the MLD model, the estimated parameters were γ50=1.073 and D50=24.66 Gy for grade 2 RILI,and γ50=0.97 and D50=48.45 Gy for grade 3 RILI.The AUCs of grade 2 and grade 3 RILI in the MLD model were 0.604 and 0.569,respectively. Conclusions The use of large data set from a single patient population with the same mode of treatment is very important for improving model predictability and stability. Both the LKB model and PCA model can predict the probability of RILI,whereas the MLD model is less effective in predicting grade 3 RILI.
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Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.
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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.
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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.
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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.
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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.
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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.
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Objective To investigate the incidence of radiation?induced lung injury ( RILI ) in patients with locally advanced non?small cell lung cancer ( LA?NSCLC ) after involved?field intensity?modulated radiotherapy ( IMRT) and concurrent chemotherapy, and to figure out the predictive factors for RILI. Methods Two hundred and fifty?six patients with stage Ⅲ NSCLC who were treated without surgery in our hospital from January 2007 to December 2011 were enrolled as subjects. All patients received involved?field IMRT with a median dose of 60 Gy ( 50?70 Gy) in 30 fractions. In all patients, 109 patients (42.6%) received concurrent chemotherapy. The National Cancer Institute Common Terminology Criteria for Adverse Events Version 3. 0 was used to evaluate the RILI grade. The incidence of grade ≥2 RILI ( symptomatic RILI, SRILI ) within 6 months after radiotherapy served as the end point. The predictive factors for RILI were analyzed using logistic regression model. Results In all patients, 215 ( 84%) were male, and 41(16%) were female. The mean age at diagnosis was 59.2 years. Forty?three (16.7%) patients had grade ≥2 RILI. The mean duration between the incidence of RILI and the beginning of radiotherapy was 64 days ( 20?169 days) . Univariate analysis showed that smoking, peripheral or central tumor location, mean lung dose ( MLD) for both lungs, and V5?V20 for both lungs were suspected to be associated with the development of SRILI (P=0.108,0.106,0.030,0.049). Multivariate analysis showed the MLD and V5?V20 for both lungs were independent predictive factors for SRILI P=(0.048). Conclusions For patients with LA?NSCLC treated with involved?field IMRT, the MLD and the volume of low?dose region in dose volume histogram for both lungs are significantly correlated with the incidence of SRILI.
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<p><b>BACKGROUND</b>The prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer (NSCLC) remains unclear. This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.</p><p><b>METHODS</b>The data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed. There were 41 patients in the surgery group (S), 21 in the postoperative radiotherapy (PORT) group (S+R), 30 in the postoperative chemotherapy (POCT) group (S+C), and 32 in the PORT plus POCT group (S+R+C). The constitute proportion in different groups was tested using the χ(2) method, univariate analysis was performed using the Kaplan-Meier and log-rank method, and multivariate analysis was done using the Cox hazard regression with entry factors including age, sex, pathological type and stage, classification of the residual disease, and treatment procedure. The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.</p><p><b>RESULTS</b>In univariate analysis, survival was more favorable for patients with squamous cell carcinoma, early pathological T or N stage, and chemotherapy or radiotherapy. There was no significant difference in the survival for patients with different types of the residual disease, except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa (P = 0.030). The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone (P = 0.016). In multivariate analysis, the pathological type (HR 2.51, 95% CI 1.59 to 3.96, P = 0.000), pathological T (HR 1.29, 95% CI 1.04 to 1.60, P = 0.021) or N stage (HR 2.04, 95% CI 1.40 to 2.98, P = 0.000), and chemotherapy (HR 0.24, 95% CI 0.13 to 0.43, P = 0.000) were independent prognostic factors.</p><p><b>CONCLUSION</b>Patients with squamous cell carcinoma, early pathological T or N stage, or receiving chemotherapy had a more favorable prognosis.</p>