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Background: To evaluate locoregional failure and its impact on survival by comparing involved field irradiation (IFI) with elective lymph node irradiation (ENI) for patients with esophageal squamous cell cancer who underwent post-operative radiotherapy. Methods and Materials: The enrolled patients were randomized allocated to IFI or ENI group. CTV of IFI was generated according to pre-operative primary tumor location and post-operative pathological characters and positive LNs regions. CTV of ENI was generated according to pre-operative tumor position to administer selective lymph node irradiation. Radiotherapy planning was delivered using either 3D-CRT or IMRT. Results: A total of 57 patients were enrolled, 28 patients in ENI group and 29 patients in IFI group. There were not statistical differences between two groups in baseline (p>0.05). The initial locoregional failure rate was 17.9 % in ENI arm and 20.7% in IFI arm respectively (p=0.085). The 1-, 3-, and 5-year Progression-free Survival (PFS) were 63.2, 43.5, and 21.8 % in ENI arm versus 78.2, 60.1, and 55.1% in IFI arm (p =0.038). The 1-, 3-, and 5-year overall survival (OS) were 78.6, 46.9, and 23.5 % in ENI arm versus 72.9, 59.7, and 54.3 % in IFI arm (p=0.06). Acute radiation pneumonitis (p=0.005) and hematological toxicities (p =0.029) also showed statistical differences between groups, ENI arm was more than IFI arm. Conclusions: The results indicated that IFI tended to improve survival and reduce toxicities for patients with operative ESCC and did not increase locoregional failure compared to ENI. It is thus suggested that IFI for ESCC PORT is worthy of clinical recommendation and further study.

Background: The accelerated reproliferation of esophageal squamous cell carcinoma (ESCC) after radiation contributes to conventional fraction radiotherapy (CFRT) failure. Late course accelerated hyperfractionated radiotherapy (LCAHFRT) can improve the long-term survival of esophageal cancer patients in China but is associated with a high rate of side effects due to the large exposure field of two-dimensional treatment and drug toxicity. Intensity-modulated radiotherapy (IMRT) can increase the tumor dose while decreasing the normal tissue dose. Therefore, we compared the outcomes and side effects of LCAHFIMRT plus concurrent chemotherapy (CT) and CFIMRT plus CT for ESCC. Methods and Materials: Between 2013 and 2016, 114 eligible patients with ESCC were recruited and randomly assigned to receive LCAHFIMRT+CT (58 patients) or CFIMRT+CT (56 patients) by a linear accelerator (6-MV X-ray) under image guidance. Two cycles of CT with cisplatin and docetaxel were also administered. Results: The complete response (CR) rates were 79.3% and 61.8% in the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.041). The median duration of local control times was 31.0±1.9 months for the LCAHFIMRT+CT group and 24.0±3.3 months for the CFIMRT+CT groups,and the 1-, 2-, and 3-year local control rates were 86.2%, 63.8%, and 41.4% and 85.7%, 51.8%, and 32.1% for the LCAHFIMRT+CT and CFIMRT+CT groups (P=0.240), respectively. The median survival times were 34.0±1.1 months for the LCAHFIMRT+CT group and 28.0.0±3.7 months for the CFIMRT groups,and the 1-, 2-, and 3-year survival rates were 87.9%, 74.1%, and 44.8% and 87.5%, 60.7%, and 39.3% for the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.405). The incidence of side effects was not significantly different between the two groups. Local recurrence and uncontrolled disease resulted in more deaths in the CFIMRT+CT group than in the LCAHFIMRT+CT group (58.9% vs. 39.7%) (P=0.040). Conclusion: For ESCC patients, LCAHFRT delivered by image-guided intensity-modulated techniques Plus Concurrent Chemotherapy with cisplatin and docetaxel keeps safety and high CR rate, as well as local control and long-term survival rates.

Purpose: To investigate the effectiveness and safety of the combination of Kanglaite injection (KLTi) and gemcitabine and cisplatin (GP) chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods: PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wan-Fang, CBM, and CQVIP were comprehensively searched from January 2010 till November 2020. Randomized controlled trials (RCTs) of KLTi plus GP in the treatment of NSCLC were selected and assessed for inclusion. Review Manager 5.3 software was used for meta-analysis.Results: Twenty-five RCTs on advanced NSCLC examined the inclusion criteria. The meta-analysis showed that compared with GP chemotherapy alone, KLTi plus GP chemotherapy significantly improved objective response rate (ORR) (RR = 1.36, 95% CI 1.23-1.51, p < 0.00001), disease control rate (DCR) (RR = 1.17, 95% CI 1.11 - 1.23, p < 0.00001), and reduced adverse drug reactions(ADRs) such as hair loss (RR = 0.60, 95% CI 0.47 - 0.76, p < 0.0001), gastrointestinal reaction (RR = 0.68, 95% CI 0.62 - 0.75, p < 0.00001), impairment of liver and kidney function (RR = 0.65, 95% CI 0.53 - 0.80, p < 0.001), nervous system damage (RR = 0.42, 95% CI 0.26 - 0.69, p = 0.0005), myelosuppression (I-II phase) (RR = 0.79, 95 % CI 0.66 - 0.95, p = 0.01), myelosuppression (III-IV phase) (RR = 0.44, 95 % CI0.27 - 0.72, p = 0.001), anemia (RR = 0.74, 95 % CI 0.60 - 0.91, p = 0.006), leukopenia (RR = 0.78, 95% CI 0.69, 0.87, p < 0.0001), thrombocytopenia (RR = 0.59, 95 % CI 0.49, 0.72, p < 0.00001), hypochromia (RR = 0.74, 95% CI 0.59, 0.92, p = 0.008).Conclusion: KLTi adjuvant GP chemotherapy reduces adverse effects in patients with advanced NSCLC. Thus, KLTi might be an effective and safe intervention for NSCLC

Objective Postoperative radiotherapy for breast cancer is an effective way to control tumor recurrence; however, there are advantages and disadvantages to different radiotherapy techniques. This study compared dosimetry differences between intensity‐modulated radiation therapy (IMRT) and three‐dimensional conformal radiation therapy (3D‐CRT) plans after radical surgery for left‐sided breast cancer to provide guidance for clinicians to select a radiotherapy technique. Methods A total of 50 women who received radiation therapy for left‐sided breast cancer after radical surgery in Gansu Provincial Cancer Hospital between 9 January 2017 and 30 November 2017 were included. The prescription dose was 50 Gy/25f. IMRT and 3D‐CRT treatment plans were designed for each patient on an Oncentra 4.1 planning system. Statistical analysis of the target dose distribution – conformal index, uniformity index, and irradiation doses to the ipsilateral lung, heart, left ventricle, humeral head, and thyroid – was carried out for the two groups and the differences were compared. Results When comparing the two plans, the target V95% (z = –5.739, P

We focus on the estimation error of a type of filtering algorithm in the scalar case, which is applicable to both linear and nonlinear systems. Under some regularity conditions, we construct a surrogate process that has a moment dominance property with respect to the true filtering error process. Then, moment-based probability inequalities can be used to compute probabilistic bounds for the filtering error. The sharpness of the bounds is tested on a simulated epidemic model with both Gaussian and non-Gaussian noise.

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).Lay abstract The ESO-Shanghai 13 trial is a prospective, multicenter, randomized, Phase II trial to assess the impact of combined local treatment (such as radiotherapy, surgery and thermal ablation) and chemical drugs for patients with esophageal squamous cell carcinoma. Patients with four or less metastases and controlled esophageal lesion will be enrolled. The authors will recruit a total of 102 patients over 3 years from approximately five centers. All patients will be randomized and receive either chemical drugs alone or chemical drugs plus local treatment with the same probability. Patients will then be observed after treatment until disease progression or death or the end of the trial. Patients will need to report their symptoms and physical status and fill out quality of life scales during the treatment and follow-up period.

2526 Background: This phase III study compared clinical efficacy, safety of the first biosimilar QL1206 with denosumab in solid tumor patients with bone metastases. Methods: Patients aged 18-80 years, with bone metastatic solid tumors and ECOG performance status of 0-2 were randomly assigned 1:1 to receive subcutaneous QL1206 or denosumab (120 mg Q4W, both) based on stratification factors (tumor types, previous skeletal-related event [SRE], and current systemic anti-tumor therapy). The primary efficacy endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide/creatinine ratio (uNTX/uCr); Clinical equivalence would be confirmed if the two-sided 90% confidence intervals (CI) of the least-squares mean (LSM) difference of natural log-transformed ratio of week 13 uNTX/uCr to baseline calculated by analysis of covariance were within the margins of ±0.135. The secondary endpoints included the percentage changes from baseline to week 25 and 53 in uNTX/uCr, the percentage changes from baseline to week 13, 25 and 53 in serum bone-specific alkaline phosphatase (s-BALP) and the time to on-study SRE. Adverse events (AE), immunogenicity (IG) and pharmacokinetics (PK) were also assessed. Population PK was analyzed using nonlinear mixed effects model. Results: 717 patients were randomized to the QL1206 (n = 357) and denosumab (n = 360) groups, respectively. The median percentage changes at week 13 in uNTX/uCr were -75.2% for QL1206 and -75.8% for denosumab. LSM of natural log-transformed ratio of week 13 uNTX/uCr to baseline were -1.429 (standard error 0.130) and -1.441 (0.130) in the two groups. The LSM difference between the two groups was 0.012 (90% CI -0.078 to 0.103; P = 0.8208), within the equivalence margins. Analyses for subgroups of sex, age, and randomization strata showed almost no significant differences. The secondary endpoints were also similar between the two groups (median percentage changes in s-BALP from baseline to week 13: -38.0% vs -37.1%; hazard ratio of time to SRE: 1.264 [95% CI 0.670 to 2.383]; both P > 0.05). In the safety set, treatment-emergent AE occurred in 332 of 356 patients (93.3%) in the QL1206 group and 348 of 361 (96.4%) in the denosumab group. The proportions of positive anti-drug antibody (14/345 [4.1%] vs 16/352 [4.5%]), neutralizing antibody (three [0.9%], each), and PK characteristics were similar between the two groups. Conclusions: The results suggest that QL1206, the first biosimilar denosumab, is similar to denosumab with respect to clinical efficacy, acceptable safety, IG, and PK characteristics. The totality of evidence supports clinical equivalence of QL1206 and denosumab. Clinical trial information: NCT04550949.

In the online social network, the spreading process of rumor contains complex dynamics. The traditional research of the rumor propagation mainly studies the spreading process of rumor from the perspectives of rumor and participating user. The symbiosis and confrontation of rumor and anti-rumor information and the dynamic changes of the influence of anti-rumor information are not emphasized. At the same time, people’s profitability and herd psychology are also ignored. In view of the above problems, we fully consider the anti-rumor information and user’s psychological factors, construct a rumor propagation dynamics model based on evolutionary game and anti-rumor information, and provide a theoretical basis for studying the inherent laws in the spreading process of rumor. First of all, we analyze the interaction pattern and characteristic of rumor in social network. In allusion to the symbiosis of rumor and anti-rumor information and the dynamic changes of the influence of anti-rumor information, we constructed the SKIR rumor propagation model based on the SIR model. Secondly, due to rivalry between rumor and anti-rumor information, as well as the user’s profitability and herd psychology, we use evolutionary game theory to construct the driving force mechanism of information and explore the causes of user behavior in the spreading process of rumor. At the same time, we combine the behavior factors and external factors of the user to build the influence of information by multivariate linear regression method, which provides the theoretical basis for the driving force of information. Finally, combining the SKIR model proposed in this paper, we get a rumor propagation dynamics model based on evolutionary game and anti-rumor information. We have proved by experiments that the model can effectively describe the propagating situation of rumor and the dynamic change rule of the influence of anti-rumor information. On the other hand, it can also reflect the influence of people’s psychology on rumor propagation.

Objective: To analyse the impact of survival with three-dimensional radiotherapy for stage IV squamous non-small cell lung cancer (NSCLC). Methods: Data for 629 eligible patients who received three-dimensional radiotherapy between 2002 and 2016 were retrospectively analyzed.161 of 183 cases were included pre-protocol. Patients received platinum-doublet chemotherapy with concurrent irradiation of the primary tumour. Primary endpoints were overall survival (OS) and progress-free survival (PFS). Results: Of 161 patients, the 1-, 2-, 3- and 5-year OS rates and median survival time (MST) were 45.7%, 14.1%, 11.2%, 2.2% and 11months, respectively. Using contrastive analysis PTV dose ≥63 Gy and

The particle filter is a popular Bayesian filtering algorithm for use in cases where the state-space model is nonlinear and/or the random terms (initial state or noises) are non-Gaussian distributed. We study the behavior of the error in the particle filter algorithm as the number of particles gets large. After a decomposition of the error into two terms, we show that the difference between the estimator and the conditional mean is asymptotically normal when the resampling is done at every step in the filtering process. Two nonlinear/non-Gaussian examples are tested to verify this conclusion.

4564 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC). Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) 20 were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. Median follow-up of patients who survived was 36.3 months (IQR 27.9–45.2). The 3-yr OS was 58.2% in TF group and 59.5% in both TP and TC group. (TF vs. TP, HR 0.935, 95% CI 0.627-1.417; TF vs. TC, HR 0.881, 95% CI 0.578-1.342; P = 0.839). No significant differences were found in 3-yr PFS between TF, TP and TC groups [48.3% vs. 45.5%(TP) or 48.3% (TC). P = 0.820]. TP group had a significant higher incidence of acute Grade 3/4 neutropenia [60.7% vs. 16.8%(TF) or 32.7%(TC)], thrombocytopenia [13.1% vs. 2.8%(TF) or 4.7%(TC)], anemia [5.6% vs. 1.9%(TF) or 3.7% (TC)], fatigue [10.3% vs. 1.9%(TF) or 0.9%(TC)] and vomiting [5.6% vs. 0%(TF) or 0.9%(TC))]than other two groups ( P< 0.05). TF group had a significant higher incidence of Grade 3/4/5 esophagitis [11.2% vs. 0.9%(TP) or 4.7%(TC))]and pneumonitis [4.6% vs. 0%(TP) or 1.9% (TC)]than other two groups ( P< 0.05). Conclusions: No statistical differences were found in OS and PFS among TF, TP and TC groups. TC might be an option used in CCR in ESCC patients with mild of side effects compared with other two groups, although it did not significantly prolong OS. Clinical trial information: NCT02459457 .

4055 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC) . Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. TP group had a significant higher incidence of acute grade 3/4 neutropenia (59.7% vs. 16.8%(TF) or 32.4%(TC)), thrombocytopenia (12.7% vs. 3.5%(TF) or 6.2%(TC)), anemia (6.4% vs. 4.4%(TF) or 4.4%(TC)), fatigue (10.0% vs. 0.9%(TF) or 0.9%(TC)) and vomiting (5.5% vs. 0%(TF) or 0.9%(TC)) than other two groups ( P < 0.05). TF group had a significant higher incidence of grade 3/4/5 esophagitis (13.1% vs. 1.8%(TP) or 5.3%(TC)) and pneumonitis (4.4% vs. 0%(TP) or 1.8%(TC)) than other two groups ( P < 0.05). One patient in TF group died of acute pneumonitis. One patient in TF group and one in TC group died of acute esophagitis. Conclusions: TP and TF regimen showed different severe AEs in CCR in ESCC patients and TC showed mild AEs. Clinical trial information: NCT02459457.

Background: Preclinical in vitro experiments demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer (NSCLC), but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations. This study aimed to determine if added TKIs to Thoracic radiotherapy (TRT) improve primary disease response rate (RR) and survival outcomes in advanced or metastatic NSCLC. Methods: We searched MEDLINE, EMBASE, and Cochrane Library from January 2000 to December 2017 for eligible studies where patients received concurrent EGFR TKIs and TRT or CRT. Concerned outcomes were primary tumor RR, overall survival (OS), and adverse events (AEs). The meta-analysis was performed using Stata software (version 12.0). Random effects models were used to pool outcomes across studies. Sensitivity analysis was performed to determine if the results would be different. Results: We found 16 prospective clinical trials with mature results for meta-analyses. Twelve studies including 446 patients reported the RR and survival outcomes of TRT combined TKIs. The CR, PR, SD, and PD, respectively, were 0.06 (95% CI 0.03–0.09, I2 = 0%), 0.44 (95% CI 0.38–0.49, I2 = 64.9%), 0.29 (95% CI 0.24–0.34, I2 = 78.4%), and 0.15 (95% CI 0.11–0.19, I2 = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44–0.60, I2 = 38.8%) and 0.26 (95% CI 0.18–0.33, I2 = 0%). Four studies including 182 patients reported the RR and survival outcomes of CRT combined TKIs. The pooled CR, PR, SD, and PD, respectively, were 0.12 (95% CI 0.02–0.22, I2 = 69.1%), 0.41 (95% CI 0.27–0.55, I2 = 71.6%), 0.31 (95% CI 0.16–0.46, I2 = 79%), and 0.14 (95% CI −0.01–0.30, I2 = 87.8%). Only 1 study reported the survival event rate, 1- and 2-year OS, respectively, were 0.83 (95% CI 0.71–0.94) and 0.67 (95% CI 0.54–0.81). There were not severe adverse events (SAEs) reported either TRT combined TKIs or CRT combined TKIs. Conclusion: There is evidence, albeit of low quality, that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone, TRT alone or CRT.

IntroductionConcurrent chemoradiation is the standard therapy for patients with local advanced oesophageal carcinoma unsuitable for surgery. Paclitaxel is an active agent against oesophageal cancer and it has been proved as a potent radiation sensitiser. There have been multiple studies evaluating paclitaxel-based chemoradiation in oesophageal cancer, of which the results are inspiring. However, which regimen, among cisplatin (TP), carboplatin (TC) or fluorouracil (TF) in combination with paclitaxel concurrent with radiotherapy, provides best prognosis with minimum adverse events is still unknown and very few studies focus on this field. The purpose of this study is to confirm the priority of TF to TP or TF to TC concurrent with radiotherapy in terms of overall survival and propose a feasible and effective plan for patients with local advanced oesophageal cancer.Methods and analysisESO-Shanghai 2 is a three-arm, multicenter, open-labelled, randomised phase III clinical trial. The study was initiated in July 2015 and the duration of inclusion is expected to be 4 years. The study compares two pairs of regimen: TF versus TP and TF versus TC concurrent with definitive radiotherapy for patients with oesophageal squamous cell carcinoma (OSCC). Patients with histologically confirmed OSCC (clinical stage II, III or IVa based on the sixth Union for International Cancer Control-tumour, node, metastasis classification) and without any prior treatment of chemotherapy, radiotherapy or surgery against oesophageal cancer will be eligible. A total of 321 patients will be randomised and allocated in a 1:1:1 ratio to the three treatment groups. Patients are stratified by lymph node status (N0, N1, M1a). The primary endpoint is overall survival and the secondary endpoint is progression-free survival and adverse events.Ethics and disseminationThis trial has been approved by the Fudan University Shanghai Cancer Centre Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations.Trial statusThe trial was initiated in July 2015 and is currently recruiting patients in all of the participating institutions above.Trial registration numberNCT02459457.