Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Objective:To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference.Results:1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients ( P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS ( P<0.05). Conclusions:EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Objective:To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference.Results:1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients ( P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS ( P<0.05). Conclusions:EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

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.

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.

Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation ( HS-PCI ) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV,25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment,and the dose distribution in the hippocampal gyrus,survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7. 23 Gy and 8. 46 Gy in the reduction region,which was reduced by 71. 88% and 66. 16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10. 66 Gy and 15. 43 Gy in the reduction region. Among 49 patients,8 died,the 1-year survival rate was 85. 1% and the 2-year survival rate was 70. 3%.Nine patients (18. 3%) had brain metastases,and one of them with extensive multiple brain metastases (n＝13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema,whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased,and declined by 6. 78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment ( P＞0. 05 ). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement,effectively protects the cognitive function and yields slight adverse reactions.

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

[ Abstract] Objective To investigate the clinical efficacy of preoperative three-dimensional radiotherapy (3DRT) with or without concurrent chemotherapy for esophageal carcinoma.Methods We retrospectively analyzed 103 esophageal carcinoma patients who received preoperative 3DRT with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital CAMS.The median radiation dose was 40 Gy, and the TP or PF regimen was adopted for concurrent chemotherapy if needed.The overall survival (OS) and disease-free survival ( DFS) were calculated by the Kaplan-Meier method, and the survival difference and univariate prognostic analyses were performed by the log-rank test.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The number of patients followed at 3-years was 54.The 3-year OS and DFS rates were 61.1% and 54.9%, respectively, for all patients.There were no significant differences between the 3DRT and concurrent chemoradiotherapy (CCRT) groups as to OS (P=0.876) and DFS (P=0.521).The rates of complete, partial, and minimal pathologic responses of the primary tumor were 48.0%, 40.2%, and 11.8%, respectively.There were significant differences in OS and DFS between the complete, partial, and minimal pathologic response groups (P=0.037 and 0.003). No significant difference in pathologic response rate was found between the 3DRT and CCRT groups (P=0.953).The lymph node metastasis rate was 26.5%, and this rate for the complete, partial, and minimal pathologic response groups was 14%, 30%, and 67%, respectively, with a significant difference between the three groups (P=0.001).The OS and DFS were significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (P=0.034 and 0.020).The surgery-related mortality was 7.8% in all patients.Compared with the 3DRT group, the CCRT group had significantly higher incidence rates of leukopenia (P=0.002), neutropenia (P=0.023), radiation esophagitis (P=0.008), and radiation esophagitis ( P=0.023).Pathologic response of the primary tumor and weight loss before treatment were independent prognostic factors for OS and DFS (P=0.030,0.024 and P=0.003,0.042). Conclusions Preoperative 3DRT alone or with concurrent chemotherapy can result in a relatively high complete pathologic response rate, hence increasing the survival rate.Further randomized clinical trials are needed to confirm whether preoperative CCRT is better than 3DRT in improving survival without increasing the incidence of adverse reactions.

Objective To analyze the clinical value of postoperative radiotherapy for node-positive middle thoracic esophageal squamous cell carcinoma ( TESCC ) and to modify the target volume .Methods A total of 286 patients with node-positive middle TESCC underwent radical surgery in Cancer Hospital, Chinese Academy of Medical Sciences, from 2004 to 2009.In addition, 90 of these patients received postoperative intensity-modulated radiotherapy.The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis.The Cox model was used for multivariate prognostic analysis.The chi-square test was used for comparing the recurrence between patients receiving different treatment modalities.Results The 5-year overall survival ( OS) rates of the surgery alone ( S) group and surgery plus postoperative radiotherapy ( S+R) group were 22.9%and 37.8%, respectively, and the median OS times were 23.2 and 34.7 months, respectively ( P=0.003) .For patients with 1 or 2 lymph
node metastases (LNMs), the 5-year OS rates of the S group and S+R group were 27.3%and 44.8%, respectively ( P=0.017);for patients with more than 2 LNMs, the 5-year OS rates of the S group and S+R group were 16.7%and 25.0%, respectively (P=0.043).The peritoneal lymph node metastasis rates of N1 , N2 , and N3 patients in the S group were 2.9%, 10.9%, and 20.0%, respectively ( P=0.024) .The S+R group had a significantly lower mediastinal lymph node metastasis rate than the S group ( for patients with 1 or 2 LMNs:8.0%vs.35.3%, P=0.003;for patients with more than 2 LNMs, 10.0%vs.42.3%, P=0.001) , and had a prolonged recurrence time compared with the S group ( 25.1 vs.10.7 months, P=0.000) .However, for patients with more than 2 LNMs, the S+R group had a significantly higher hematogenous metastasis rate than the S group (46.7%vs.26.1%, P=0.039).Conclusions Patients with node-positive middle TESCC could benefit from postoperative radiotherapy.The target volume can be reduced for patients with 1 or 2 LNMs.Prospective studies are needed to examine whether it is more appropriate to reduce the radiotherapy dose than to reduce the target volume for patients with more than 2 LNMs.A high hematogenous metastasis rate warrants chemotherapy as an additional regimen.