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Purpose This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments.Material and methods Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including Ktrans, Kep, Ve, and Vp were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis.Results 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The Ktrans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-Ktrans group (n=67, Ktrans＞164.3×10−3/min) and low-Ktrans group (n=44, Ktrans≤164.3×10−3/min) based on the ROC analysis. The high-Ktrans group had a significantly higher objective response rate than the low-Ktrans group (85.1% (57/67) vs 22.7% (10/44), p

Introduction: Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage. Objectives: To overcome the obstacle and improve therapeutic efficiency, a surface passivation of nanoFe was designed using sodium sulfide. Methods: We prepared iron sulfide nanoclusters and constructed CLP mouse models. Then the effect of sulfide-modified nanoscale zero-valent iron (S-nanoFe) on the survival rate, blood routine parameters, blood biochemical parameters, cardiac function, and pathological indicators of myocardium was observed. RNA-seq was used to further explore the comprehensive protective mechanisms of S-nanoFe. Finally, the stability of S-nanoFe-1d and S-nanoFe-30 d, together with the therapeutic efficacy of sepsis between S-nanoFe and nanoFe was compared. Results: The results revealed that S-nanoFe significantly inhibited the growth of bacteria and exerted a protective role against septic myocardial injury. S-nanoFe treatment activated AMPK signaling and ameliorated several CLP-induced pathological processes including myocardial inflammation, oxidative stress, mitochondrial dysfunction. RNA-seq analysis further clarified the comprehensive myocardial protective mechanisms of S-nanoFe against septic injury. Importantly, S-nanoFe had a good stability and a comparable protective efficacy to nanoFe. Conclusions: The surface vulcanization strategy for nanoFe has a significant protective role against sepsis and septic myocardial injury. This study provides an alternative strategy for overcoming sepsis and septic myocardial injury and opens up possibilities for the development of nanoparticle in infectious diseases.

Introduction: The relationships between body mass index (BMI) and survival rates are complex, and have not been thoroughly investigated in breast cancer patients who received adjuvant chemotherapy. Methods: We collected data on 2394 patients from two randomized, phase III clinical trials that investigated adjuvant chemotherapy in breast cancer identified in Project Data Sphere. The objective was to examine the effect of baseline BMI, BMI after adjuvant chemotherapy, and BMI change from baseline to post-adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS). Restricted cubic splines were used to examine potential non-linear associations between continuous BMI value and survival. Stratified analyses involved chemotherapy regimens. Results: Severe obesity (BMI≥40.0 kg/m2) at baseline was independently associated with worse DFS (hazard ration [HR] = 1.48, 95% confidence interval [CI] 1.02–2.16, P = 0.04) and OS (HR = 1.79, 95%CI 1.17–2.74, P = 0.007) compared with underweight/normal weight (BMI≤24.9 kg/m2). A BMI loss >10% was also an independent prognostic factor for adverse OS (HR = 2.14, 95%CI 1.17–3.93, P = 0.014). Stratified analyses revealed that severe obesity adversely affected DFS (HR = 2.38, 95%CI 1.26–4.34, P = 0.007) and OS (HR = 2.90, 95%CI 1.46–5.76, P = 0.002) in the docetaxel-based group, but not in the non-docetaxel-based group. Restricted cubic splines revealed a “J-shaped” association of baseline BMI with risk of recurrence or all-cause death, and this relationship was more pronounced in the docetaxel-based group. Conclusions: In early breast cancer patients treated with adjuvant chemotherapy, baseline severe obesity was significantly linked to worse DFS and OS, and a BMI loss over 10% from baseline to post-adjuvant chemotherapy also negatively affected OS. Moreover, the prognostic role of BMI might differ between docetaxel-based and non-docetaxel-based groups.

Abstract Background We launched a single‐arm phase II study to determine the efficacy and cost‐effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). Methods Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco‐regional objective response rate (ORR), loco‐regional progression‐free survival (LRFS), overall survival (OS), and toxicities. A 3‐state Markov model was applied for cost‐effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). Results Sixty‐three eligible patients received pretreatment PEG‐based CCRT. The mean change of weight during CCRT was −1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco‐regional ORR and 1‐year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco‐regional ORR (p = 0.036) and longer 1‐year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost‐effectiveness ratio of $3457.65 per quality‐adjusted life‐years (QALY) compared with the ONS group with a probability of cost‐effectiveness of 77.7% at the $10,000 per QALY willingness‐to‐pay threshold. Conclusion Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost‐effective because of its significant clinical benefits.

Anti-sliding stability safety is a critical issue that must be given sufficient and widespread attention during the entire lifecycle of gravity dams. The calculated anti-sliding stability safety factor (ASS-SF) is usually compared with the allowable value required by the standards in the traditional method, which ignores the influence of material parameter uncertainties and leads to unreasonable safety evaluation results. Therefore, the nonlinear functional relationship between the stability safety factor (SF) and the random variable parameters is constructed based on the response surface equations, and the distribution types of SF sequences calculated by the Monte Carlo sampling are determined, then a probabilistic stability evaluation method for concrete gravity dams is proposed. Engineering application shows that the calculated SF obeys the normal distribution; the minimum guaranteed rate of different sliding paths in a gravity dam is 86.66%, and the guaranteed rate for the overload safety factor (OSF) is 36.00%. The results imply that a guaranteed rate for the allowable value of the ASS-SF should be provided when making the stability safety evaluation of the dams, especially the OSF. The outcome of this research will advance the understanding of stability evaluation of concrete dams, and reduce the potential risk of sliding instability of concrete dams.

Background: This study aimed to comprehensively explore the clinical significance of PIK3CA mutation in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with anti-HER2 therapy. Methods: We systematically searched PubMed, Embase, and the Cochrane databases for eligible studies assessing the association between PIK3CA mutation and outcomes in patients with HER2-positive breast cancer receiving anti-HER2 therapy. The main outcomes included: (1) pathological complete response (pCR) or disease-free survival (DFS) for the neoadjuvant setting; (2) DFS or invasive DFS for the adjuvant setting; (3) objective response rate (ORR), progression-free survival (PFS), time-to-progression (TTP), or overall survival (OS) for the metastatic setting. The mutational landscape of HER2-positive breast cancer according to PIK3CA mutation status was examined based on TCGA breast cancer dataset. Results: Totally, 43 eligible studies, covering 11,099 patients with available data on PIK3CA mutation status, were identified. In the neoadjuvant setting, PIK3CA mutation was significantly associated with a lower pCR rate (OR=0.23, 95% CI 0.19–0.27, p

Abstract Background Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. Results NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. Conclusions The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury. Graphical Abstract

Background: Systematic inflammation is believed to play a crucial role in tumorigenesis and metastasis. This study aims at evaluating the prognostic value of time-series behavior of systematic inflammation-immune status before and after definitive chemoradiotherapy (dCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Methods: The relationship between systematic inflammation-immune score (SIS, defined as pretreatment peripheral platelet count × neutrophil count/lymphocyte count) and the prognosis was tested in a retrospective study of 386 consecutive LA-NSCLC patients (Group A) with pretreatment SIS and 161 patients (Group B) with SIS before and one month after the dCRT. Results: SIS of 1400 × 109 was found to be an optimal cutoff point to stratify the patients into high (>1400 × 109) and low (≤1400 × 109) SIS groups. Univariate and multivariate analyses revealed that the SIS, whether before or after dCRT, was an independent predictor for overall survival (OS), progress-free survival (PFS), and distant metastasis-free survival (DMFS). High SIS (>1400 × 109) was shown to predict poor 3-year OS (P=0.006, hazard ratio [HR]=2.427), PFS (P=0.001, HR=2.442) and DMFS (P=0.015, HR=2.119). However, SIS was not related to local regional recurrence-free survival in either Group A (P=0.346) or Group B (P=0.486). Further, the area under the receiver operating characteristic curve of the SIS for OS was higher than the neutrophil count/lymphocyte count ratio, platelet count/lymphocyte count ratio, and other conventional clinic-pathological indices. Conclusions: The SIS is a stable and more sensitive survival predictor than other inflammation-based factors and conventional clinical indices, which may aid in more accurately stratifying patients for risk assessment and treatment decisions.

Purpose: To assess the feasibility and potential benefits of online adaptive MR-guided fractionated stereotatic radiotherapy (FSRT) in patients with brain metastases (BMs). Methods and materials: Twenty-eight consecutive patients with BMs were treated with FSRT of 30 Gy in 5 fractions on the 1.5 T MR-Linac. The FSRT fractions employed daily MR scans and the contours were utilized to create each adapted plan. The brain lesions and perilesional edema were delineated on MR images of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3, Fx4 and Fx5) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume, Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. Planning target volume (PTV) coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. Results: A total of 28 patients with 88 lesions were evaluated, and 23 patients (23/28, 82.1%) had primary lung adenocarcinoma. Significant tumor volume reduction had been found during FSRT compared to Fx0 for all 88 lesions (median −0.75%, −5.33%, −9.32%, −17.96% and −27.73% at Fx1, Fx2, Fx3, Fx4 and Fx5, p

PurposeWe launched this prospective phase II single-arm trial on the combination of moderately hypo-fractionated radiotherapy and S-1, to explore the safety and efficacy of the new potent regimen in inoperable locally advanced esophageal squamous carcinoma (LA-ESCC) patients.MethodsPatients with unresectable stage II-IVB LA-ESCC (UICC 2002, IVB only with metastatic celiac or supraclavicular lymph nodes) were included. Moderately hypofractionated radiotherapy (60Gy in 24 fractions) concurrent with S-1 was delivered. Meanwhile, gastrostomy tube placement by percutaneous endoscopic gastrostomy (PEG) was performed to provide nutritional support. Nutritional supplements were prescribed to meet requirements. The study outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), failure pattern, toxicities, nutritional status and treatment compliance. Endoscopy was routinely performed during post-treatment follow-up.ResultsFifty-eight patients were included with a median follow-up of 24.4 months. The median age was 63 years (range 49-83 years) and 42 patients (72.4%) had stage III or IV diseases. The ORR was 91.3% and the CR rate was 60.3%. The estimated 2-year PFS rate and 2-year OS rate was 44.2% (95% confidence interval (CI), 31.3-57.1%) and 71.4% (95% CI, 59.4-83.4%), respectively. Radiation-induced esophagitis was the most common non-hematologic toxicity and 5 patients (8.6%) developed grade≥3 esophagitis. While, with PEG nutrition support, the nutrition-related indicators presented a clear trend toward a gradual improvement. Treatment-related death was not observed.ConclusionsThe moderately hypo-fractionated radiotherapy combined with S-1 showed promising loco-regional disease control and survival benefit in inoperable LA-ESCC patients. Meanwhile, favorable nutritional status and low incidence of severe radiation-induced esophagitis were observed with PEG nutritional support. Moreover, endoscopy examination contributed to the early detection of recurrent esophageal lesions and timely salvage treatment. The efficacy and toxicity of the combined regimen deserved further evaluation.Trial registrationClinicaltrials.gov, identifier NCT03660449.

ObjectiveThe study aimed to compare the characteristics and prognosis between patients with second primary lung cancer following Hodgkin's lymphoma and those with primary lung cancer.Materials and methodsUsing the SEER 18 database, the characteristics and prognosis were compared between the second primary non-small cell lung cancer following Hodgkin's lymphoma (HL-NSCLC) (n = 466) and the first primary non-small cell lung cancer (n = 469,851)(NSCLC-1), as well as between the second primary small cell lung cancer following Hodgkin's lymphoma (n = 93) (HL-SCLC) and the first primary small cell lung cancer (n = 94,168) (SCLC-1). Comparisons of categorical variables were performed using Chi-square or Fisher's test. Continuous variables were compared using the Mann-Whitney U test. Overall survival (OS) was estimated using the Kaplan-Meier method, and the difference between groups was analyzed by log-rank test.ResultsHL-NSCLC group had more males than NSCLC-1 group, and the median age of HL-NSCLC group was younger than that of NSCLC-1 group. Patients with HL-NSCLC showed inferior OS than those with NSCLC-1 (median: 10 months vs. 11 months, P = 0.006). Both HL-SCLC and SCLC-1 groups had poor prognosis, with median OS of 7 months (P = 0.4). The 3-year cumulative risks of death from any cause for patients with the latencies from HL to NSCLC of 0 to 5 years, >5 to 10 years, >10 to 15 years, >15 to 20 years, and>20 years were 71.8%, 82.6%, 86.8%, 85.7% and 78.5%, respectively(P = 0.020).ConclusionHL-NSCLC patients had worse prognosis than NSCLC-1 patients, while HL-SCLC patients shared similar characteristics and survival with SCLC-1 patients.

The wetting deformation of the upstream dam shell material during the impoundment of the core wall rockfill dam seriously affects the safety of the dam. Based on the proposed Ew−νw wetting model, this paper proposes its corresponding two methods to simulate the collapse settlement of the rockfill dam: the initial strain method and the initial stress method. By simulating the collapse settlement of the Guanyinyan core wall rockfill dam, it is found that the simulated result using the initial stress method is in good agreement with the field monitoring data, while the displacement simulated using the initial strain method is larger. The distribution of displacement contours simulated using the initial strain method is obviously inconsistent in the area where the wetting deformation occurs, and the simulation results of the initial stress method are more reasonable. With the rise in the water level, the wetting deformation of the upstream dam shell material causes the tensile stress zone at the top of the dam. Therefore, the wetting deformation is the direct cause of the crack at the top of the dam, and the initial stress method should be preferred in the simulation of the wetting deformation of rockfill materials.

BackgroundTo evaluate longitudinal changes of concurrent chemoradiotherapy (CCRT) related lymphopenia and its association with survival in locally advanced non-small cell lung cancer (LA-NSCLC) patients.MethodsTotal lymphocyte count (TLC) at baseline, weekly intervals during CCRT and monthly intervals up to 12 months after CCRT were documented. The Common Terminology Criteria for Adverse Events version 5.0 was used to grade the severity of lymphopenia. Cox regression analysis was performed to evaluate the association between overall survival (OS) and CCRT related lymphopenia at different timepoints. Logistic regression model was used to determine the clinical factors associated with TLC level.Results381 LA-NSCLC patients treated with definitive CCRT without consolidation therapy (NCT02573506/NCT02577341) between 2011 to 2020 were analyzed. With a median follow-up of 45.8 months, the median OS was 41.0 months for all patients. Univariable analysis demonstrated that the 3 weeks during CCRT Grade (G) 4 lymphopenia (P=0.018), 2 months after CCRT G1-4 lymphopenia (P=0.004), 6 months after CCRT (6m-post-CCRT) G1-4 lymphopenia (P=0.001), and TLC nadir (P=0.020) were significantly associated with poorer OS. Multivariable analysis suggested that 6m-post-CCRT G1-4 lymphopenia (HR 2.614; P=0.041) were one of the independent predictors of OS. Further analysis inferred that radiation dose (OR: 1.328; P=0.005), GTV volume (OR: 1.004; P=0.036), and baseline TLC (OR: 0.288; P=0.001) were associated with 6m-post-CCRT lymphopenia.ConclusionThe persistent lymphopenia at 6 months after CCRT was an independent prognostic factor of OS in LA-NSCLC patients. Higher radiation dose, larger gross tumor volume and lower baseline TLC were significantly related to 6m-post-CCRT lymphopenia.

BackgroundWe aimed to evaluate the efficacy and feasibility of concurrent weekly docetaxel-nedaplatin and hypo-fractionated radiotherapy (hypo-RT) in atypical histologic subtypes of primary and metastatic mediastinal malignancies.MethodsFifty-four patients diagnosed with atypical primary or metastatic mediastinal malignancies were retrospectively reviewed. 30 patients received concurrent weekly docetaxel and nedaplatin and hypo-RT (CChRT group) and 24 patients had hypo-RT alone (hRT group). Overall response rate (ORR), in-field locoregional progression-free survival (LPFS) and toxicities were analyzed. The radiobiological effect was evaluated by the LQRGC/TCP model, incorporating four “R”s of radiobiology, Gompertzian tumor growth and radio-sensitizing effect of chemotherapeutic agent. The biologically effective doses (BEDs) were calculated.ResultsThe median follow-up time was 29.2 months for all patients. The ORR was 86.7% in CChRT group, compared with 62.5% in hRT group (p=0.033). The 2-year in-field LPFS of CChRT and hRT group was 73.4% and 47.3%, respectively (p=0.003). There was no significant difference of any >=Grade 3 toxicities between the two groups (p=0.754). The mean total dose and mean BED by the LQRGC/TCP model in CChRT group were 58.2Gy and 72.34Gy, versus 52.6Gy and 67.25Gy in hRT group.ConclusionsConcurrent weekly docetaxel-nedaplatin and hypo-RT achieved promising in-field LPFS and tolerable toxicities compared with hypo-RT alone in different histologic subtypes of primary and metastatic mediastinal malignancies.

ObjectiveHigh activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T-cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes.Materials and methodsSystemic IDO1 activity was calculated by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. The dynamic change of IDO1 activity was followed in 24 patients by measuring the Kyn : Trp ratio before, during, and after RT administration.ResultsIn 24 patients with dynamic tracking of plasma IDO1 activity, there were no significant alterations observed among the three time points (Friedman test, p = 0.13). The changing pattern of the Kyn : Trp ratio was divided into four groups: decreased consistently during RT, first increased, then decreased, increased consistently, first decreased then increased. Patients whose Kyn : Trp ratio kept decreasing or first increased then decreased were defined as the good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p = 0.04; p = 0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than the bad-change group (p = 0.01, HR = 0.22). In 113 stage III NSCLC patients with pre-radiation Kyn : Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p = 0.079).ConclusionFavorable change in IDO1 activity during RT was associated with superior OS, PFS, and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients.

PurposeTo evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis.MethodsMetagenome-wide association studies on baseline fecal samples from 18 LA-NSCLC patients before CCRT and 13 controls from healthy first-degree relatives were performed. Among the 18 LA-NSCLC patients, six patients were defined as the long progression-free survival (long-PFS) group (PFS≥11 months) while another 12 were in the short-PFS group (PFS

Abstract Background Consistent results are lacking as regards the comparative effectiveness of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus conventional intensity-modulated radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Therefore, we conducted a retrospective analysis to demonstrate the role of SIB-IMRT for patients. Methods Patients who had histologically confirmed NSCLC, stage III disease and received thoracic IMRT between 2014 and 2016 were retrospectively reviewed. The survival, toxicities and dose to organs at risk (OAR) were compared among patients irradiated with different techniques. The SIB-IMRT plans were designed to deliver 45–59.4Gy (median: 50.4Gy) to PTV while simultaneously delivering 50-70Gy (median: 59.92Gy) to PGTV. As for conventional IMRT plans, a total dose of 50-70Gy (median: 60Gy) was delivered to PTV. Results 426 patients with stage III NSCLC were eligible for analysis, including 128 with SIB-IMRT and 298 with conventional IMRT. The SIB-IMRT group had more stage IIIB disease (69.5% vs. 53%, P = 0.002), larger planning treatment volumes (median: 504 ml vs. 402 ml, P

Background and objective The group of small cell lung cancer (SCLC) are usually highly sensitive to chemotherapy, and less than 15% of them are resistant to drugs. We respectively evaluate the correlation of the sequence and timing of radiotherapy with progression-free survival (PFS) and overall survival (OS) in patients with limited-stage SCLC (LS-SCLC), and to figure out whether concurrent chemoradiotherapy is superior to sequent chemoradiotherapy. Methods Sixty-seven patients diagnosed with LS-SCLC from January 2009 to June 2014 failed to respond to induction chemotherapy. According to the sequence of therapy, they were divided into concurrent chemoradiotherapy group (n=32) and sequent chemoradiotherapy group (n=35). Ninety-four percent of the patients were diagnosed with stage III, and six percent were stage Ib-IIb. Twenty-five patients were treated with prophylactic cranial irradiation (PCI). The Kaplan-Meier method was used to calculate survival time and Log-rank test was used for between-group comparisons. Between-group comparison of categorical data was made by χ2 test. Results In all patients, the 2-year OS, PFS and LC rates were 53.7%, 20.9% and 58.2%. The 2-year OS and PFS rates of concurrent chemoradiotherapy group and sequent chemoradiotherapy were 37.5% vs 54.3% (P=0.048) and 12.5% vs 28.6% (P=0.149). Hematologic toxicities were more common in concurrent group than sequent one (P=0.031), and no statistical difference was observed between the two groups in terms of grade 3 radiation esophagitis, pneumonitis and gastrointestinal reactions (9.4% vs 0, P=0.176; 12.5% vs 2.9%, P=0.318; 12.5% vs 2.9%, P=0.109). Patients treated with PCI have superior OS and PFS comparing with those not (56.0% vs 38.1%, P=0.029; 24% vs 19%, P=0.012). Conclusion Concurrent chemoradiotherapy with original chemotherapy regimens may not be suitable for patients who failed to respond to induction chemotherapy in LS-SCLC, and second-line regimens or radiotherapy alone can be used for them, but prospective trils with large sample are still needed to confirm that.

Comparing with traditional support vector machine，hyperplane support vector machine （HPSVM）and hyperplane support vector machine for regression（HPSVMR）not only reduce the number of support vectors and calculation time but also have comparable accuracy.However，they have different simplification effect on different problems.The reasons for this phenomenon were analyzed，the conclusion that the lower the percentage of non-bound support vectors is，the more obvious the effect of simplification was pointed out.