Induction immunochemotherapy followed by definitive chemoradiotherapy for unresectable locally advanced non-small cell lung cancer: a multi-institutional retrospective cohort study.

This study aimed to evaluate the efficacy and safety of induction immunochemotherapy followed by definitive chemoradiotherapy (CRT) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). We identified unresectable stage III NSCLC patients who received induction immunochemotherapy. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. From February 2019 to August 2022, 158 patients were enrolled. Following the completion of induction immunochemotherapy, the objective response rate (ORR) and disease control rate (DCR) were 52.5% and 83.5%, respectively. The ORR of CRT was 73.5%, representing 68.4% of the total cohort. The median PFS was 17.8 months, and the median OS was 41.9 months, significantly higher than in patients who received CRT alone (p < 0.001). Patients with concurrent CRT demonstrated markedly improved PFS (p = 0.012) and OS (p = 0.017) than those undergoing sequential CRT. Additionally, those with a programmed-death ligand 1 (PD-L1) expression of 50% or higher showed significantly elevated ORRs (72.2% vs. 47.2%, p = 0.011) and superior OS (median 44.8 vs. 28.6 months, p = 0.004) compared to patients with PD-L1 expression below 50%. Hematologic toxicities were the primary severe adverse events (grade ≥ 3) encountered, with no unforeseen treatment-related toxicities. Thus, induction immunochemotherapy followed by definitive CRT demonstrated encouraging efficacy and tolerable toxicities for unresectable LA-NSCLC.

Favorable cervical extension capacity preventing loss of cervical lordosis after laminoplasty due to spontaneous restoration of initial lordosis.

BACKGROUND CONTEXT: Cervical laminoplasty is a common approach for the treatment of multilevel cervical spondylotic myelopathy (CSM). Postoperative loss of cervical lordosis (LCL) was associated with lower extension motion of the cervical spine before laminoplasty. PURPOSE: To analyze the possible causes of preoperative cervical extension capacity affecting LCL after laminoplasty by evaluating the changes in cervical lordosis (CL) at different stages. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: Seventy-two patients undergoing laminoplasty due to multilevel CSM. OUTCOME MEASURES: Radiographic parameters included CL, extension CL (eCL), flexion CL (fCL), range of motion (ROM), extension ROM (eROM), flexion ROM (fROM) and LCL. Clinical outcomes were assessed using the Japanese Orthopedic Association (JOA) and neck disability index (NDI) score. METHODS: The data were recorded before surgery and at 3- and 24-month follow-up. All patients completed a cervical extension test preoperatively. A receiver operating characteristic (ROC) curve of eROM was constructed to discriminate the patients with and without postoperative kyphotic deformity. RESULTS: According to the optimal cut-off value of eROM, the patients were divided into two groups: extension group (eROM≥9.3°) and control group (eROM<9.3°). The radiographic outcomes demonstrated no significant differences in CL, eCL, fCL and ROM between the two groups. Both eROM and fROM were significantly different in the two groups. There was a significant change in CL in the extension group at 3-month follow-up and in the control group at 24-month follow-up. The extension group exhibited significantly lower LCL compared with the control group at follow-up. No significant difference between the two groups was noted in the JOA recovery rate, while the NDI score was significantly different at 24-month follow-up. The positivity ratio of the extension test was significantly greater in the extension group than that in the control group. CONCLUSIONS: eROM in patients with favorable preoperative cervical extension capacity (eROM≥9.3°) consisted of the actual extension capacity and compensatory flexion. The cervical alignment would be spontaneously restored to its initial lordosis in the short term after laminoplasty. These patients had no substantial LCL at 24-month follow-up and would be good candidates for laminoplasty.

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study.

Background: Stereotactic body radiotherapy (SBRT) has proven to provide high rates of tumor control for patients with early-stage non-small cell lung cancer (NSCLC). We are reporting a multicenter experience of long-term clinical outcomes and adverse effect profiles of patients with medically inoperable early-stage NSCLC treated with SBRT. Methods: A total of 145 early-stage NSCLC patients underwent SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Shandong Cancer Hospital and Institute, and Shanghai Pulmonary Hospital between October 2012 and March 2019. Four-dimensional computed tomography (4D-CT) simulation was used for all patients. All received a biologically effective dose (BED; α/ß=10) of 96-120 Gy with the prescribed isodose line covering >95% of the planning target volume (PTV). Survival was analyzed by the Kaplan-Meier method. Survival was estimated using the Kaplan-Meier method. Results: The median tumor diameter was 2.2 (range, 0.5-5.2) cm. The median follow-up was of 65.6 months. Thirty-five patients (24.1%) developed disease recurrence. The rates of local, regional, and distant disease recurrence were, respectively, 5.1%, 7.4%, and 13.2% at 3 years; and 9.6%, 9.8%, and 15.8% at 5 years. Progression-free survival (PFS) rates at 3 and 5 years were 69.2% and 60.5% respectively; the overall survival (OS) rates were 78.1% and 70.1%, respectively. Five patients (3.4%) experienced grade 3 treatment-related adverse events (AEs). No patient experienced grade 4 or 5 toxicity. Conclusions: From our retrospective analysis with long-term follow-up in Chinese population, SBRT achieved high rate of local control (LC) and low toxicity in patients with early-stage NSCLC. This study offered robust long-term outcome data of SBRT in the Chinese population, which was very rarely reported in China before.

Using clinical and radiomic feature-based machine learning models to predict pathological complete response in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation.

OBJECTIVE: This study aimed to build radiomic feature-based machine learning models to predict pathological clinical response (pCR) of neoadjuvant chemoradiation therapy (nCRT) for esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 112 ESCC patients who underwent nCRT followed by surgical treatment from January 2008 to December 2018 were recruited. According to pCR status (no visible cancer cells in primary cancer lesion), patients were categorized into primary cancer lesion pCR (ppCR) group (N = 65) and non-ppCR group (N = 47). Patients were also categorized into total pCR (tpCR) group (N = 48) and non-tpCR group (N = 64) according to tpCR status (no visible cancer cells in primary cancer lesion or lymph nodes). Radiomic features of pretreatment CT images were extracted, feature selection was performed, machine learning models were trained to predict ppCR and tpCR, respectively. RESULTS: A total of 620 radiomic features were extracted. For ppCR prediction models, radiomic model had an area under the curve (AUC) of 0.817 (95% CI: 0.732-0.896) in the testing set; and the combination model that included rad-score and clinical features had a great predicting performance, with an AUC of 0.891 (95% CI: 0.823-0.950) in the testing set. For tpCR prediction models, radiomic model had an AUC of 0.713 (95% CI: 0.613-0.808) in the testing set; and the combination model also had a great predicting performance, with an AUC of 0.814 (95% CI: 0.728-0.881) in the testing set. CONCLUSION: This study built machine learning models for predicting ppCR and tpCR of ESCC patients with favorable predicting performance respectively, which aided treatment plan optimization. CLINICAL RELEVANCE STATEMENT: This study significantly improved the predictive value of machine learning models based on radiomic features to accurately predict response to therapy of esophageal squamous cell carcinoma patients after neoadjuvant chemoradiation therapy, providing guidance for further treatment. KEY POINTS: • Combination model that included rad-score and clinical features had a great predicting performance. • Primary tumor pCR predicting models exhibit better predicting performance compared to corresponding total pCR predicting models.

Recurrence patterns are significantly associated with the 18F­FDG PET/CT radiomic features of patients with locally advanced non­small cell lung cancer treated with chemoradiotherapy.

A model for predicting the recurrence pattern of patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy is of great importance for precision treatment. The present study analyzed whether the comprehensive quantitative values (CVs) of the fluorine-18(18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) radiomic features and metastasis tumor volume (MTV) combined with clinical characteristics could predict the recurrence pattern of patients with LA-NSCLC treated with chemoradiotherapy. Patients with LA-NSCLC treated with chemoradiotherapy were divided into training and validation sets. The recurrence profile of each patient, including locoregional recurrence (LR), distant metastasis (DM) and both LR/DM were recorded. In the training set of patients, the primary tumor prior radiotherapy with 18F-FDG PET/CT and both primary tumors and lymph node metastasis were considered as the regions of interest (ROIs). The CVs of ROIs were calculated using principal component analysis. Additionally, MTVs were obtained from ROIs. The CVs, MTVs and the clinical characteristics of patients were subjected to aforementioned analysis. Furthermore, for the validation set of patients, the CVs and clinical characteristics of patients with LA-NSCLC were also subjected to logistic regression analysis and the area under the curve (AUC) values calculated. A total of 86 patients with LA-NSCLC were included in the analysis, including 59 and 27 patients in the training and validation sets of patients, respectively. The analysis revealed 22 and 12 cases with LR, 24 and 6 cases with DM and 13 and 9 cases with LR/DM in the training and validation sets of patients, respectively. Histological subtype, CV2-5 and CV3-4 were identified as independent variables in the logistic regression analysis (P<0.05). In addition, the AUC values for diagnosing LR, DM and LR/DM were 0.873, 0.711 and 0.826, and 0.675, 0.772 and 0.708 in the training and validation sets of patients, respectively. Overall, the results demonstrated that the spatial and metabolic heterogeneity quantitative values from the primary tumor combined with the histological subtype could predict the recurrence pattern of patients with LA-NSCLC treated with chemoradiotherapy.

A combined predictive model based on radiomics features and clinical factors for disease progression in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

Purpose: To accurately assess disease progression after Stereotactic Ablative Radiotherapy (SABR) of early-stage Non-Small Cell Lung Cancer (NSCLC), a combined predictive model based on pre-treatment CT radiomics features and clinical factors was established. Methods: This study retrospectively analyzed the data of 96 patients with early-stage NSCLC treated with SABR. Clinical factors included general information (e.g. gender, age, KPS, Charlson score, lung function, smoking status), pre-treatment lesion status (e.g. diameter, location, pathological type, T stage), radiation parameters (biological effective dose, BED), the type of peritumoral radiation-induced lung injury (RILI). Independent risk factors were screened by logistic regression analysis. Radiomics features were extracted from pre-treatment CT. The minimum Redundancy Maximum Relevance (mRMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for the dimensionality reduction and feature selection. According to the weight coefficient of the features, the Radscore was calculated, and the radiomics model was constructed. Multiple logistic regression analysis was applied to establish the combined model based on radiomics features and clinical factors. Receiver Operating Characteristic (ROC) curve, DeLong test, Hosmer-Lemeshow test, and Decision Curve Analysis (DCA) were used to evaluate the model's diagnostic efficiency and clinical practicability. Results: With the median follow-up of 59.1 months, 29 patients developed progression and 67 remained good controlled within two years. Among the clinical factors, the type of peritumoral RILI was the only independent risk factor for progression (P< 0.05). Eleven features were selected from 1781 features to construct a radiomics model. For predicting disease progression after SABR, the Area Under the Curve (AUC) of training and validation cohorts in the radiomics model was 0.88 (95%CI 0.80-0.96) and 0.80 (95%CI 0.62-0.98), and AUC of training and validation cohorts in the combined model were 0.88 (95%CI 0.81-0.96) and 0.81 (95%CI 0.62-0.99). Both the radiomics and the combined models have good prediction efficiency in the training and validation cohorts. Still, DeLong test shows that there is no difference between them. Conclusions: Compared with the clinical model, the radiomics model and the combined model can better predict the disease progression of early-stage NSCLC after SABR, which might contribute to individualized follow-up plans and treatment strategies.

Unilateral versus bilateral pedicle screw fixation with transforaminal lumbar interbody fusion for treatment of lumbar foraminal stenosis.

BACKGROUND CONTEXT: Transforaminal lumbar interbody fusion (TLIF) with bilateral pedicle screw fixation (BPSF) is an effective treatment for lumbar foraminal stenosis (LFS). However, the effects of TLIF with unilateral pedicle screw fixation (UPSF) on LFS treatment have not been clearly elucidated. PURPOSE: We conducted this study to compare clinical outcomes and radiographic results of TLIF with UPSF and BPSF 2 years after the surgical treatment. DESIGN: Prospective randomized study. PATIENT SAMPLE: This study included 23 patients undergoing TLIF with UPSF and 25 patients undergoing TLIF with BPSF. OUTCOME MEASURES: Clinical outcomes were evaluated by visual analog scale (VAS) for low back pain and leg pain and Oswestry Disability Index (ODI) score. Radiographic outcomes included foraminal height, disc space height, segmental lordosis, and final fusion rates. METHODS: The clinical and radiographic outcomes were compared between the UPSF and BPSF group. The postoperative improvements were evaluated in either group. Intraoperative data such as duration of operation and estimated blood loss were collected. This study was registered at clinicaltrials.gov. RESULTS: Analysis of the VAS and ODI scores showed significant improvements in clinical outcomes within each group. No significant differences between the 2 groups were noted in the improvements of the VAS and ODI scores. The mean operative duration and blood loss were significantly greater in the BPSF group than in the UPSF group. There were significant improvements in the height of the foramen and intervertebral space and segmental lordosis in both groups, while there was no significant difference between the groups in amount of the improvements. No significant difference was found in the final fusion rates. CONCLUSIONS: TLIF is an appropriate procedure for LFS treatment. With balanced intervertebral support using a cage, UPSF could achieve similar and satisfactory effects on lumbar segmental stability and fusion compared to BPSF. The unilateral approach appears to be associated with slightly shorter operative time and less blood loss.

Outcomes of SBRT for lung oligo-recurrence of non-small cell lung cancer: a retrospective analysis.

The benefit of local ablative therapy (LAT) for oligo-recurrence has been investigated and integrated into the treatment framework. In recent decades, stereotactic body radiation therapy (SBRT) has been increasingly used to eliminate metastasis owing to its high rate of local control and low toxicity. This study aimed to investigate the outcomes of SBRT for patients with lung oligo-recurrence of non-small cell lung cancer (NSCLC) from our therapeutic center. Patients with lung oligo-recurrence of NSCLC treated with SBRT between December 2011 and October 2018 at Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) were reviewed. The characteristics, treatment-related outcomes, and toxicities of the patients were analyzed. Univariable and multivariable Cox regression were performed to identify the factors associated with survival. A total of 50 patients with lung oligo-recurrence of NSCLC were enrolled. The median follow-up period was 23.6 months. The 3-year local progression-free survival (LPFS), progression-free survival (PFS) and overall survival (OS) after SBRT were 80.2%, 21.9% and 45.3%, respectively. Patients in the subgroup with LAT to all residual diseases showed significantly improved OS and PFS. No treatment-related death occurred after SBRT. SBRT is a feasible option to treat patients with lung oligo-recurrence of NSCLC, with high rates of local control and low toxicity. LAT to all residual diseases was associated with better survival outcomes. Future prospective randomized clinical trials should evaluate SBRT strategies for such patients.

A Propensity-Matched Analysis of Survival of Clinically Diagnosed Early-Stage Lung Cancer and Biopsy-Proven Early-Stage Non-Small Cell Lung Cancer Following Stereotactic Ablative Radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) has been increasingly regarded as a reasonable option for early-stage lung cancer patients without pretreatment pathologic results, but the efficacy and safety in a Chinese population remains unclear. The aim of this study was to compare survival outcomes and toxicities between patients with clinically diagnosed early-stage lung cancer or biopsy-proven early-stage non-small cell lung cancer and to demonstrate the rationality of this treatment. MATERIAL AND METHODS: From May 2012 to December 2018, 56 patients with clinically diagnosed early-stage lung cancer and 60 patients with early-stage biopsy-proven were selected into non-pathological group and pathological group, respectively. Propensity score matching (PSM) was performed to reduce patient selection bias. Survival analysis with log-rank test was used to assess the differences of treatment outcomes, which included local control (LC), progression-free survival (PFS), and overall survival (OS). RESULTS: The median age was 76 (range 47-93) years, and the median follow-up time was 58.3 (range 4.3-95.1) months in the cohort without pathologic results. The median age was 74 (range 57-88) years, and the median follow-up time was 56.3 (range 2.6-94) months in the cohort with pathologic results. 45 matched-pair were analyzed. The 5-year LC, PFS, and OS rates in matched-pair patients with or without pathologic biopsy were 85.5% and 89.8%, 40.6% and 70.9%, and 63.2% and 76.1%, respectively. On Kaplan-Meier survival analysis after PSM analysis, there was no significant difference between patients with pathologic results versus patients with no pathologic results in terms of LC (P= 0.498) and OS (P=0.141). Of the matched-pair patients treated with SBRT, only 1 patient experienced grade 3 or above radiation pneumonitis. CONCLUSION: For early-stage lung cancer patients with medically inoperable or not suitable for invasive diagnosis, SBRT may be a good local treatment.

The association between the ERCC1/2 polymorphisms and radiotherapy efficacy in 87 patients with non-small cell lung cancer.

BACKGROUND: This study sought to investigate the association between the ERCC1/2 single-nucleotide polymorphisms (SNPs) and the efficacy of radiotherapy and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: We examined 6 SNPs in the ERCC1 and ERCC2 genes in 87 consecutive patients with NSCLC who were treated with definitive radiotherapy. The objective remission rates (ORR), overall survival (OS), and progressive-free survival (PFS) were assessed. A Cox regression analysis was conducted to analyze the independent factors related to death and recurrence. RESULT: Patients with the G allele had better OS than patients with the A allele, and there was a statistical difference between the two groups (30.9 vs. 16.2 months; P=0.003). Patients with the AA genotype had significantly worse OS than patients with the AG or GG genotypes (6.8 vs. 19.8 vs. 30.9 months, respectively; P=0.000). The median PFS of the G allele was 18.9 months, which was significantly better than that of the A allele (P=0.040). The median PFS of patients with the GG genotype, the AG genotype, and the AA genotype was 18.9, 11.3, and 5.1 months, respectively; the difference among the three groups was statistically significant (P=0.019). Patients with the G allele also had better PFS than those with the A allele (18.9 vs. 11.3 months, P=0.040). The multivariate cox proportional hazard analysis showed that the ERCC1 gene rs11615 was an independent survival indicator [HR: 1.623, 95% confidence interval (CI): 1.018-2.591, P=0.042] but not an independent recurrence indicator (HR: 1.497, 95% CI: 0.932-2.404, P=0.095). CONCLUSIONS: The ERCC1 rs11615 SNP may be a potential biomarker for predicting survival prognosis in Chinese NSCLC patients who have undergone definitive radiotherapy. Patients with the G allele had better OS than those with the A allele.

A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy: the results in a Chinese population.

BACKGROUND: To investigate the comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) considered to be high-risk lobectomy patients. METHODS: From January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection bias in SBRT and SLR patients. RESULTS: Data from 86 SBRT and 79 SLR patients was collected. Median follow-up periods of the SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significantly higher age, higher likelihood of being male, larger tumor diameter, lower forced expiratory volume in 1 second (FEV1), and poorer performance status compared with SLR patients. There were no significant differences between SBRT and SLR patients for 3-year overall survival (OS) (80.3% and 82.3%, P=0.405), cause-specific survival (CSS) (81.3% and 83.4%, P=0.383), and local control (LC) (89.7% and 86.0%, P=0.501). Forty-nine patients were identified from each group after performing PSM. After patients were matched for age, gender, performance status, tumor characteristics and pulmonary function, no significant differences were observed in 3-year OS (85.4% and 73.3%, P=0.649), CSS (87.2% and 74.9%, P=0.637) and LC (95.6% and 82.1%, P=0.055). Prevalence of significant adverse events (grade 3 or worse) was 0% and 10.2% in the matched SBRT and SLR groups (P=0.056), respectively. CONCLUSIONS: Disease control and survival in the SBRT patients was equivalent to that seen in SLR patients with stage I NSCLC considered high-risk lobectomy candidates. SBRT could therefore be an alternative option to SLR in treating patients with a high operative risk.

Radiosensitizing effect of c-Met kinase inhibitor BPI-9016M in esophageal squamous cell carcinoma cells in vitro and in vivo.

BACKGROUND: c-Met is the receptor of hepatocyte growth factor (HGF) which plays a key role in inhibiting apoptosis. BPI-9016M is a small-molecule c-Met inhibitor that can promote apoptosis and enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizing potential of BPI-9016M in Eca109 human esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Clonogenic survival assay and a murine tumor xenograft in male nude mice were used to evaluate the radiosensitizing effect of BPI-9016M. Apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry experiment. Apoptosis-related proteins were detected by western blot. By evaluating the activation of the ATR-Chk1/ATM-Chk2 pathway to detect radiation-induced DNA double-strand break and homologous recombination repair. BPI-9016M induced a radiosensitizing effect in Eca109 cells and reduced the survival rate of clone formation in vitro. RESULTS: The combination of BPI-9016M with irradiation (IR) significantly delayed the growth of ESCC tumor xenografts than treatment alone (P<0.05). The radiosensitizing effects of BPI-9016M were due to increased apoptosis, such as the up-regulation of cleaved-caspase 3 and 9, down-regulation of mutant P53 and Bcl-2, the decreased of phosphorylation of ATR and ATM, and the inhibition of γ-H2AX accumulation in vitro and in vivo. CONCLUSIONS: These findings indicated that BPI-9016M exerts a radiosensitizing effect and enhances apoptosis by inhibiting homologous recombination DNA repair in irradiated ESCC cells.

A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC).

BACKGROUND: Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. METHODS: Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3' untranslated region (3'UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues. RESULTS: Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. CONCLUSIONS: Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

Pretreatment systemic inflammation response index (SIRI) is an independent predictor of survival in unresectable stage III non-small cell lung cancer treated with chemoradiotherapy: a two-center retrospective study.

BACKGROUND: Circulating immune cells influence the efficacy of cancer therapy. This study aimed to investigate the prognostic values of different peripheral blood leukocyte (PBL) biomarkers in non-small lung cancer (NSCLC) patients treated with chemoradiotherapy. METHODS: An independent cohort of 176 stage III NSCLC patients who were diagnosed at Shanghai Pulmonary Hospital and Zhejiang Cancer Hospital between April, 2010, and September, 2018, and had available pretreatment peripheral blood tests was enrolled. The patients were all treated with concurrent or sequential chemoradiotherapy according to international clinical guidelines, with conventional fractionated radical radiotherapy. The receiver operating characteristic curve and the Youden index were used to determine the optional cutoff values of PBL biomarkers for distinguishing prognosis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the factors significantly correlated with overall survival. RESULTS: The cohort had a median follow-up time of 21.7 (3.1-121) months. The 3- and 5-year OS rates of all patients were 34.7% and 27.5%, respectively. Univariate analysis showed that gender (P=0.011), smoking (P=0.011), tumor-node-metastasis (TNM) stage (P=0.002), pretreatment peripheral blood neutrophil-to-leukocyte ratio (P=0.013), and systemic inflammation response index (SIRI, P<0.001) were all correlated with OS in NSCLC patients. Moreover, multivariate analysis revealed that TNM stage (HR =1.541, 95% CI: 1.166-2.036, P=0.010) and SIRI (HR =1.868, 95% CI: 1.016-3.436, P=0.018) were significantly and independently associated with OS. However, the median OS of stage IIIB NSCLC patients with low SIRI (≤2.0) was longer than that of stage IIIA NSCLC patients with high SIRI (>2.0) (33.9±4.1 vs. 19.6±2.5 months). CONCLUSIONS: Pretreatment peripheral blood SIRI was found to be a simple independent predictor of OS in stage III NSCLC patients who underwent chemoradiotherapy. As a novel prognostic marker, the prognostic value of the SIRI is superior to that of the NLR. Low SIRI could be a better prognostic stratification factor for NSCLC patients with different TNM stages.

Four-year follow-up outcomes after stereotactic body radiation therapy for central early-stage non-small cell lung cancer.

BACKGROUND: Previous research has shown that stereotactic body radiation therapy (SBRT) can achieve a high level of tumor control in patients with early-stage non-small cell lung cancer (NSCLC). However, to date, such studies have mainly focused on peripheral early-stage patients. This study aimed to assess the clinical outcomes and toxicity of patients with central lung cancer treated with SBRT in our institution. METHODS: A total of 31 consecutive central early-stage NSCLC patients who were treated with SBRT using the biologically effective dose (BED; α/ß =10) 100-119 Gy in 4-10 fractions between April, 2013, and August, 2016, were reviewed. The RTOG 0813 trial standard was used to define whether the NSCLC was centrally located. All patients received four-dimensional computed tomography (4D CT) simulation. Intensity modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D CRT) techniques were used in treatment planning. The dose to the planning target volume (PTV) was prescribed to the 95% isodose line. Mainly dosimetric parameters, clinical outcomes, and toxicity were analyzed. RESULTS: The 31 patients enrolled in the study had a median follow-up time of 47.7 months, and the median tumor diameter was 2.2 cm (range, 1.3-5.0 cm). A total of 15 patients (48.4%) developed disease recurrence. The incidences of local, regional, and distant disease recurrence at 3 years were 11.7%, 9.7%, and 30.7%, respectively; at 5 years, they were 21.5%, 15.0%, and 35.0%, respectively. The 3- and 5-year progression-free survival (PFS) rates were 55.1% and 40.5%, respectively; the corresponding overall survival (OS) rates were 85.3% and 68.4%, respectively. Toxicities of grade 3 or higher were observed in 6.5% of the patients. None of the patients experienced grade 4 or 5 acute adverse events; however, 2 patients possibly died of treatment-related late toxicity. CONCLUSIONS: SBRT with a BED 100 Gy in 4-10 fractions is effective and acceptable for treating patients with central early-stage NSCLC. Further studies are warranted.

The CT appearance pattern of radiation-induced lung injury and tumor recurrence after stereotactic body radiation therapy in early stage non-small cell lung cancer.

BACKGROUND: Radiographic changes after stereotactic body radiation therapy (SBRT) have not been well studied. The purpose of this study was to investigate the computed tomography (CT) appearance pattern of radiation-induced lung injury (RILI) and recurrence after SBRT in patients with early stage non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed clinical data of inoperable early stage NSCLC patients undergoing SBRT treatment from February 2012 to June 2018. All patients had undergone serial CT scanning before SBRT and after completion of SBRT. An experienced radiation oncologist and radiologist reviewed all CT images, and identified the RILI and CT high-risk features (HRFs). RESULTS: A total of 60 patients were enrolled in this study; 55 patients had RILI (91.67%) and 7 patients had local failure. In the early CT findings of observers 1 and 2, there were diffuse ground glass opacities (GGOs) in 3 and 4 patients, diffuse consolidation in 10 and 12 patients, patchy consolidation in 22 and 15 patients, patchy GGOs in 19 and 24 patients, and no changes in 5 and 4 patients, respectively (kappa =0.706). In the late CT findings of observer 1 and 2, there were modified conventional patterns in 37 and 37 patients, mass-like patterns in 10 and 9 patients, scar-like patterns in 7 and 8 patients, and no changes in 5 and 5 patients, respectively (kappa =0.726). In the results of the CT-based HRFs of disease local failure, there were ≥1 HRFs in 7 patients, ≥2 HRFs in 7 patients, ≥3 HRFs in 6 patients, ≥4 HRFs in 5 patients, and ≥5 HRFs in 3 patients, respectively. Patients with only 1 HRF showed high sensitivity (100%) and low specificity (52.80%), with the specificity increasing and the sensitivity decreasing as the number of HRFs increased. CONCLUSIONS: The agreement of the CT appearance on RILI between 2 observers was good. Regular follow-up and attention to HRFs are vital for better identifying RILI and local disease failure.

Glucocorticoids Enhanced Osteoclast Autophagy Through the PI3K/Akt/mTOR Signaling Pathway.

Autophagy is an evolutionarily conserved dynamic process and present in variety of cells at basal levels to maintain homeostasis and to promote cell survival in response to stresses. The early bone loss with excessive glucocorticoids (GCs) was reported to be related with the extension of the life span of osteoclasts. However, the connection between GCs induced bone loss and osteoclast autophagy remains to be elucidated. Autophagy was detected in a Dexamethasone (Dex) induced osteoporotic mice model and primary osteoclast cultures by autophagosome detection kit, and autophagy-related proteins were assayed by Western blotting and Immunostaining. The bone morphology was examined by micro-CT and TRAP staining. The trabecular bone micro-architecture was deteriorated, and the osteoclast number and spread area were increased in the Dex-treated mice compared with the control group (P < 0.01). Meanwhile, autophagy in pre-osteoclasts was increased in mice under Dex administration evidenced by the increased number of autophagosome and up-regulation of autophagy-related protein levels. Further, the enhanced autophagy under Dex treatment was verified in primary cultured osteoclasts, as shown by the increased levels of Beclin 1 and LC3-II/LC3-I and the autophagy complex formation members including Atg1, Atg13, and Atg7. However, the expressions of PI3K, p-Akt and p-mTOR in primary cultured osteoclasts were inhibited under Dex induced autophagy. Using the selective PTEN inhibitor SF1670 to activate the PI3K/Akt/mTOR pathway reversed this osteoclast autophagy under Dex treatment. Our study suggests that osteoclast autophagy was enhanced in glucocorticoids induced bone loss, and the PI3K/Akt/mTOR signaling pathway mediated the increased autophagy in primary cultured osteoclasts under glucocorticoids treatment.

Stereotactic body radiotherapy for early stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

BACKGROUND: For lung cancer patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD), there is a lack of relatively safe and effective treatment. Stereotactic body radiation therapy (SBRT) can achieve a high level of tumor control with low toxicity in early-stage non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and toxicity of early stage NSCLC patients with subclinical ILD receiving SBRT. METHODS: A total of 109 early stage NSCLC patients receiving SBRT treatment between December 2011 and August 2016 were reviewed in our institutions; patients with clinical ILD were excluded. The median dose of SBRT was 50 Gy in 5 fractions. The median biologically effective dose (BED; α/ß=10) was 100 Gy (range, 72-119 Gy). An experienced radiation oncologist and an experienced radiologist reviewed the presence of subclinical ILD in the CT findings before SBRT. The relationships among the efficacy, radiation-induced lung injury (RILI) and subclinical ILD were explored. RESULTS: In all, 38 (34.9%) of 109 patients were recognized with subclinical ILD before SBRT, 48 (44.0%) of 109 patients were recognized with grade 2-5 RILI after SBRT, and 18 (47.4%) of 38 patients with subclinical ILD were observed with grade 2-5 RILI. Subclinical ILD was not a significant factor of grade 2-5 RILI (P=0.608); however, 3 patients had extensive RILI, and they all suffered from subclinical ILD. Dosimetric factor of the lungs, such as mean lung dose (MLD) was significantly related with Grade 2-5 RILI in patients with subclinical ILD (P=0.042). The progression-free survival (PFS) rates at 3 years in the subclinical ILD patients and those without ILD were 61.6% and 66.8%, respectively (P=0.266). CONCLUSIONS: Subclinical ILD was not a significant factor for RILI or PFS in early stage NSCLC patients receiving SBRT; however, patients with subclinical ILD receiving SBRT may experience uncommon extensive RILI.

Outcomes of stereotactic body radiotherapy versus lobectomy for stage I non-small cell lung cancer: a propensity score matching analysis.

BACKGROUND: Lobectomy is the standard treatment for patients with stage I non-small cell lung cancer (NSCLC). Recent studies have shown promising results of stereotactic body radiation therapy (SBRT) in these patients. We retrospectively compared the outcomes of lobectomy and SBRT in these patients from our therapeutic center. METHODS: Patients who underwent lobectomy or SBRT for clinical T1-2a (T size≤5 cm), N0 M0, NSCLC between December 2011 and August 2016 were reviewed. Patient characteristics, treatment-related outcomes and toxicities were analyzed. Propensity score matching (PSM) was performed to improve comparability between the two groups. RESULTS: Median follow-up period in the lobectomy (n = 246) and SBRT (n = 70) group was 31.4 months and 24.9 months, respectively. Three-year local recurrence-free survival (LRFS) was comparable in the two groups (97% vs. 91.7%, respectively; P = 0.768). Recurrence-free survival (RFS) at 3-year in the lobectomy and SBRT groups was 85.4 and 69.5%, respectively (P = 0.014). Three-year overall survival (OS) after lobectomy and SBRT was 88.2 and 79.7%, respectively (P = 0.027), while 3-year cancer-specific survival (CSS) was 91.3 and 82.5% (P = 0.022). After PSM (45 matched patients in each group), there was no significant between-group difference with respect to 3-year LRFS (89.6% vs. 87.5%, P = 0.635), RFS (77.6% vs. 67.3%, P = 0.446), OS (78.5% vs. 79.5%, P = 0.915) or CSS (86.4 and 79.5%, P = 0.551). In matched subgroup, 30-day mortality after lobectomy was 2.2%, and no treatment-related death occurred after SBRT. CONCLUSIONS: Treatment-related outcomes of SBRT and lobectomy were comparable. SBRT was well tolerated and had a very low toxicity profile in our study. SBRT is a promising alternative treatment option for stage I NSCLC patients. This study indicates that matching these disparate cohorts of patients is challenging. Clinical trials are essential to define the indications and relative efficacy of lobectomy and SBRT in a selected population.

Negative Pressure Wound Therapy Versus Closed Suction Irrigation System in the Treatment of Deep Surgical Site Infection After Lumbar Surgery.

OBJECTIVE: We compared the efficacy of a closed suction irrigation system (CSIS) and negative pressure wound therapy (NPWT) for deep surgical site infection (SSI) after lumbar surgery with instrumentation. METHODS: We included 31 patients (NPWT group, n =16; CSIS group, n = 15) with deep SSIs after lumbar surgery with instrumentation from 2007 to 2017. The medical records were reviewed and patient characteristics, laboratory results, infection details, and treatment interventions were recorded. The Japanese Orthopaedic Association score and Oswestry disability index were used to assess pain and functional outcomes preoperatively and 3 and 12 months postoperatively. The cost of SSIs were compared between the NPWT and CSIS groups. RESULTS: No significant differences were found in the baseline characteristic data between the NPWT and CSIS groups. Implants were retained in all patients in the CSIS group, but required removal from 2 patients with late infections in the NPWT group. The average hospital stay was 36.8 ± 10.5 days and 33.4 ± 18.9 days in the NPWT and CSIS groups, respectively. The cost was greater in the NPWT group than in the CSIS group. Both NPWT and CSIS significantly reduced the Oswestry disability index and improved the Japanese Orthopaedic Association scores, but no significant difference was found between the 2 groups. CONCLUSIONS: Our results have shown that both NPWT and CSIS are efficient techniques for the management of deep SSI after lumbar surgery with instrumentation. CSIS was more economical and the NPWT system was portable and easier for postoperative nursing care.