Preoperative CT-based radiomic prognostic index to predict the benefit of postoperative radiotherapy in patients with non-small cell lung cancer: a multicenter study.

BACKGROUND: The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. METHODS: Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. RESULTS: In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1-6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18-4.52), cohort 2 (HR = 1.64, 95% CI: 1.26-2.14), cohort 3 (HR = 2.53, 95% CI: 1.45-4.3), cohort 4 (HR = 1.24, 95% CI: 1.01-1.52), cohort 5 (HR = 2.56, 95% CI: 0.73-9.02), cohort 6 (HR = 2.30, 95% CI: 0.53-10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60-0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50-0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46-0.70), and RPI (C-index: 0.65, 95% CI: 0.54-0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40-0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. CONCLUSIONS: We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.

MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a multicenter study.

BACKGROUND: More than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT. METHODS: In this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance. RESULTS: A total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933-0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set. CONCLUSION: A machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.

Enhanced prediction of postoperative radiotherapy-induced esophagitis in non-small cell lung cancer: Dosiomic model development in a real-world cohort and validation in the PORT-C randomized controlled trial.

BACKGROUND: Radiotherapy-induced esophagitis (RE) diminishes the quality of life and interrupts treatment in patients with non-small cell lung cancer (NSCLC) undergoing postoperative radiotherapy. Dosimetric models showed limited capability in predicting RE. We aimed to develop dosiomic models to predict RE. METHODS: Models were trained with a real-world cohort and validated with PORT-C randomized controlled trial cohort. Patients with NSCLC undergoing resection followed by postoperative radiotherapy between 2004 and 2015 were enrolled. The endpoint was grade ≥2 RE. Esophageal three-dimensional dose distribution features were extracted using handcrafted and convolutional neural network (CNN) methods, screened using an entropy-based method, and selected using minimum redundancy and maximum relevance. Prediction models were built using logistic regression. The areas under the receiver operating characteristic curve (AUC) and precision-recall curve were used to evaluate prediction model performance. A dosimetric model was built for comparison. RESULTS: A total of 190 and 103 patients were enrolled in the training and validation sets, respectively. Using handcrafted and CNN methods, 107 and 4096 features were derived, respectively. Three handcrafted, four CNN-extracted and three dosimetric features were selected. AUCs of training and validation sets were 0.737 and 0.655 for the dosimetric features, 0.730 and 0.724 for handcrafted features, and 0.812 and 0.785 for CNN-extracted features, respectively. Precision-recall curves revealed that CNN-extracted features outperformed dosimetric and handcrafted features. CONCLUSIONS: Prediction models may identify patients at high risk of developing RE. Dosiomic models outperformed the dosimetric-feature model in predicting RE. CNN-extracted features were more predictive but less interpretable than handcrafted features.

Higher Lung and Heart Doses Decrease Early and Long-Term Survival, Respectively, in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation.

Purpose: Cardiopulmonary toxic effects may reduce the efficacy of postoperative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). However, few studies have examined whether the heart and lung doses affect overall survival (OS). We investigated the correlation of heart and lung doses with OS in patients with NSCLC undergoing PORT. Methods and Materials: This retrospective analysis included 307 patients with NSCLC undergoing PORT. The total dose was 50 Gy. Landmark analyses were performed at 36 months, with hazard ratios (HRs) calculated separately for events occurring up to 36 months (early survival) and after 36 months (long-term survival). Stabilized inverse probability of treatment weighting (sIPTW) was performed to balance the characteristics of the high- and low-dose groups. We performed sensitivity analyses at 24 and 48 months. Results: The median follow-up period was 67.42 months. Heart doses were significantly correlated with long-term survival (HR, 1.14; P = .015) but not with early survival (HR, 0.97; P = .41) or whole survival (HR, 1.02; P = .58). Lung doses were marginally significantly correlated with early survival (HR, 1.03; P = .07) but not with long-term survival (HR, 1.00; P = .85) or whole survival (HR, 1.02; P = .12). Higher heart and lung doses were associated with decreased long-term and early survival, respectively, before and after sIPTW. Landmark analyses at 24 and 48 months showed consistent results. Conclusions: For patients with NSCLC undergoing PORT, a higher heart dose was associated with decreased long-term survival, whereas a higher lung dose was associated with decreased early survival.

Radiotherapy Improves Survival of Patients With Lymphovascular Invasion in pT1b Esophageal Squamous Cell Cancer After Endoscopic Submucosal Dissection.

INTRODUCTION: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This study aimed to evaluate the efficacy of adjuvant radiotherapy after ESD for pT1b ESCC. METHODS: This was a multicenter, cross-sectional study involving 11 hospitals in China. Between January 2010 and December 2019, patients with T1bN0M0 ESCC treated with or without adjuvant radiotherapy after ESD were included. Survival between groups was compared. RESULTS: Overall, 774 patients were screened, and 161 patients were included. Forty-seven patients (29.2%) received adjuvant radiotherapy after ESD (RT group) and 114 (70.8%) underwent ESD alone (non-RT group). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between the RT and non-RT groups. Lymphovascular invasion (LVI) was the only prognostic factor. In the LVI+ group, adjuvant radiotherapy significantly improved survival (5-year OS: 91.7% vs 59.5%, P = 0.050; 5-year DFS: 92.9% vs 42.6%, P = 0.010). In the LVI- group, adjuvant radiotherapy did not improve survival (5-year OS: 83.5% vs 93.9%, P = 0.148; 5-year DFS: 84.2% vs 84.7%, P = 0.907). The standardized mortality ratios were 1.52 (95% confidence interval 0.04-8.45) in the LVI+ group with radiotherapy and 0.55 (95% confidence interval 0.15-1.42) in the LVI- group without radiotherapy. DISCUSSION: Adjuvant radiotherapy could improve survival in pT1b ESCC with LVI+ other than LVI- after ESD. Selective adjuvant radiotherapy based on LVI status achieved survival rates similar to those of the general population.

Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis.

Background: Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy. Methods: A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed. Results: A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups. Conclusions: Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.

Famitinib enhances the antitumor effect of radioimmunotherapy in murine lung cancer.

BACKGROUND: Combining antiangiogenic therapy with radioimmunotherapy is believed to further improve antitumor efficacy, but there is still a lack of evidence to support this. This study aimed to investigate the role of the tumor vascular-targeted agent famitinib with a combination of radiotherapy and an immune checkpoint inhibitor in murine lung cancer. METHODS: The effect of VEGFA and HIF1A on clinical prognosis and the tumor immune microenvironment was analyzed using public databases. Enrichment analyses of post-irradiation gene expression and mRNAs related to immunotherapy efficacy were carried out based on GEO datasets. A C57BL/6 mouse subcutaneous tumor model was used to evaluate the antitumor effects of different treatment schemes. The tumor immunophenotyping was identified by flow cytometry. RESULTS: We demonstrated that high level of VEGFA and HIF1A expression in lung cancer was related to poor prognosis and immunosuppressive tumor microenvironment. In a mouse model, the triple therapy of famitinib, radiotherapy and immunotherapy had the most dramatic antitumor activity. It significantly increased tumor infiltrating lymphocytes and reversed the immunosuppressive state of the tumor microenvironment in mice. Compared with radioimmunotherapy, the addition of famitinib further promoted the infiltration of CD8+ T cells and M1 type tumor associated macrophages, and reduced the number of myeloid suppressor cells. Therefore, triple therapy converted the immunosuppressive tumor microenvironment into an immunostimulatory one. CONCLUSION: Famitinib can synergize with radioimmunotherapy by regulating the tumor immune microenvironment in murine lung cancer.

Comparison of different neoadjuvant treatments for resectable locoregional esophageal cancer: A systematic review and network meta-analysis.

PURPOSE: The best pattern of neoadjuvant therapy for resectable locoregional esophageal cancer has not been determined. Our study evaluated the efficacy and postoperative events of different treatments using the Bayesian network meta-analysis. METHODS: We systematically tracked randomized clinical trials from the Medline, EMBASE, and Cochrane Library databases. The following treatments were included: neoadjuvant chemoradiation followed by surgery (NCRT + S), neoadjuvant chemotherapy followed by surgery (NCT + S), neoadjuvant radiotherapy followed by surgery (NRT + S), and surgery alone (S). The Revised Cochrane risk-of-bias tools were used to assess the quality of included trials. Overall survival (OS) and progression-free survival or disease-free survival (PFS/DFS) were assessed through hazard ratios (HR). Locoregional recurrence, distant metastasis, postoperative mortality, and postoperative morbidity were assessed through odds ratios (OR). These outcomes were compared between different treatments through Bayesian network meta-analysis. RESULTS: Twenty trials with 4384 patients were included. Compared with S, only NCRT + S could significantly improve OS for patients with esophageal cancer (HR = 0.78, 95% confidence interval [CI] 0.68-0.88). NCRT + S and NCT + S significantly improved PFS/DFS compared with S (NCRT + S vs. S, HR = 0.72, 95% CI 0.63-0.81; NCT + S vs. S, HR = 0.81, 95% CI 0.69-0.97). NCRT + S significantly reduced both locoregional recurrence (OR = 0.67, 95% CI 0.51-0.88) and distant metastasis (OR = 0.63, 95% CI 0.45-0.90) compared with S. There were no differences in postoperative morbidity between the four treatments. However, NCRT + S also increased postoperative mortality compared with S (OR = 1.77, 95% CI 1.09-2.82) and NCT + S (OR = 1.96, 95% CI 1.11-3.51). CONCLUSION: NCRT + S is the most efficient neoadjuvant treatment for resectable locoregional esophageal cancer. However, NCRT + S increases the risk of postoperative mortality but not morbidity.

Anlotinib Enhances the Antitumor Activity of High-Dose Irradiation Combined with Anti-PD-L1 by Potentiating the Tumor Immune Microenvironment in Murine Lung Cancer.

BACKGROUND: Radioimmunotherapy has become one of the most promising strategies for cancer treatment. Preclinical and clinical studies have demonstrated that antiangiogenic therapy can improve the efficacy of immunotherapy and sensitize radiotherapy through a variety of mechanisms. However, it is undefined whether angiogenesis inhibitors can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of anlotinib (AL3818) on the combination of radiotherapy and immune checkpoint inhibitors in Lewis lung carcinoma mouse. METHODS: C57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control. Immune response and immunophenotyping including the quantification and activation were determined by flow cytometry, multiplex immunofluorescence, and multiplex immunoassay. RESULTS: Triple therapy (radiotherapy combined with anti-PD-L1 and anlotinib) increased tumor-infiltrating lymphocytes and reversed the immunosuppressive effect of radiation on the tumor microenvironment in mouse model. Compared with radioimmunotherapy, the addition of anlotinib also boosted the infiltration of CD8+ T cells and M1 cells and caused a decrease in the number of MDSCs and M2 cells in mice. The levels of IFN-gamma and IL-18 were the highest in the triple therapy group, while the levels of IL-23, IL-13, IL-1 beta, IL-2, IL-6, IL-10, and Arg-1 were significantly reduced. NF-κB, MAPK, and AKT pathways were downregulated in triple therapy compared with radioimmunotherapy. Thus, the tumor immune microenvironment was significantly improved. As a consequence, triple therapy displayed greater benefit in antitumor efficacy. CONCLUSION: Our findings indicate that anlotinib might be a potential synergistic treatment for radioimmunotherapy to achieve better antitumor efficacy in NSCLC patients by potentiating the tumor immune microenvironment.

Postoperative radiotherapy improves survival of patients with ypN2 non-small cell lung cancer after neoadjuvant chemotherapy followed by surgery - A propensity score matching study of the Surveillance, Epidemiology, and End Results database.

BACKGROUND: For patients with ypN2 non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgery (NCS), the role of postoperative radiotherapy (PORT) is unclear. The aim of our study was to evaluate the effect of PORT on survival of ypN2 NSCLC patients after NCS. METHODS: Between 2004 and 2015, patients with ypN2 NSCLC after NCS were filtrated from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance the baseline characteristics of the PORT and non-PORT groups. Kaplan-Meier method and Cox proportional hazards models were adopted to estimate overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 257 patients who met the criteria were included in the study. After PSM, 115 patients remained in each group. The survival of patients in the PORT group was significantly better than those in the non-PORT group. Median OS was 36 months vs. 26 months, and 5-year OS rate was 40.5% vs. 21.0% (p = 0.002). The median CSS was 38 months vs. 27 months, and the 5-year CSS rate was 43.7% vs. 22.1% (p < 0.001). Multivariable analysis showed that PORT was an independent prognostic factor for OS (HR = 0.59, 95% CI: 0.43-0.82, p = 0.001) and CSS (HR = 0.56, 95% CI: 0.41-0.78, p = 0.001). Subgroup analysis showed that patients in the following subgroups could benefit from PORT: age ≤ 70, diagnosed in the later period (2010-2015), white race, squamous cell carcinoma, grade III-IV, lobectomy, stage T3-4, or with positive regional nodes ≤3 or > 3. CONCLUSIONS: For patients with ypN2 NSCLC after NCS, PORT significantly improves OS and CSS. These results need to be confirmed by further randomized studies.

Survival of Neoadjuvant and Adjuvant Therapy Compared With Surgery Alone for Resectable Esophageal Squamous Cell Carcinoma: A Systemic Review and Network Meta-Analysis.

OBJECTIVE: The optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. Surgery is the primary treatment but with poor results. Attempts to improve patient survival have been made by introducing chemotherapy, radiotherapy, or both. However, randomized comparisons for all these strategies are not always available. This network meta-analysis compared the overall survival of neoadjuvant and adjuvant therapy with surgery alone to identify the most effective approach. METHODS: We systematically searched electronic databases (PubMed, Embase, and Cochrane Library) for relevant studies published before April 2021. Only phase II and III randomized controlled trials comparing the following treatments were included: surgery alone, neoadjuvant chemotherapy (NCT), radiotherapy (NRT) or chemoradiotherapy (NCRT), adjuvant chemotherapy (ACT), radiotherapy (ART), or chemoradiotherapy (ACRT). The hazard ratios (HR) and 95% confidence intervals (CIs) of overall survival (OS) was identified as the measurement of effectiveness. A network meta-analysis was conducted to synthesize the evidence under the Bayesian framework, and the relative effects of all possible comparisons were made. The ranking analysis was performed to support the decision in clinical practice. RESULTS: A total of 19 relevant trials with 3,749 patients were identified. Compared with surgery alone, NCRT (HR 0.76, 95% CI 0.65-0.89) and NCT (HR 0.81, 95% CI 0.70-0.94) significantly improved OS, while other treatments, including NRT (HR 0.86, 95% CI 0.66-1.08), ACRT (HR 0.73, 95% CI 0.49-1.08), ACT (HR 0.96, 95% CI 0.75-1.21), and ART (HR 0.86, 95% CI 0.66-1.14), provided no significant survival advantage. None of the neoadjuvant and adjuvant treatments showed a statistically significant difference in OS to each other when compared in pairs. CONCLUSION: For resectable esophageal squamous cell carcinoma, this network meta-analysis showed that NCRT may be the optimal strategy, NCT may be the second choice, while other multimodality treatments could not improve OS compared with surgery alone. It remains unclear whether ESCC will benefit from adding radiotherapy into the neoadjuvant treatment. SYSTEMATIC REVIEW REGISTRATION: We registered this meta-analysis protocol at the prospective register of systematic reviews, PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=172745 (Identification code: CRD42020172745).

Additional Radiotherapy With or Without Chemotherapy Following Endoscopic Resection for Stage I Esophageal Carcinoma: A Pilot Study.

Objective: To evaluate the safety and efficacy of additional radiotherapy after endoscopic resection (ER) for stage I esophageal carcinoma (EC) with high-risk factors. Materials and methods: Patients with stage cT1N0M0 EC who underwent ER and additional radiotherapy between January 2010 and August 2019 at our institution were retrospectively included. Overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), local control rate, regional control rate, common acute toxicities, esophageal stricture, and dysphagia were analyzed. Results: Thirty-one consecutive patients were included in the study. The median age was 62 years (range, 49-78). Thirty patients (96.8%) had squamous cell carcinoma, and one patient (3.2%) had adenosquamous cell carcinoma. Twenty-six patients (83.9%) had submucosal invasion, 15 patients (48.4%) had lymphovascular invasion, and one patient (3.2%) had a venous invasion. The 1-, 3-, and 5-year OS rates were 100.0%, 86.9%, and 68.5%, respectively. The corresponding DFS rates were 100.0%, 85.2%, and 75.8%, respectively. The corresponding CSS rates were 100.0%, 89.8%, and 78.6%, respectively. The local and regional control rates were 100.0% and 93.5%, respectively. No grade 4-5 acute toxicities were observed. Fifteen patients (48.4%) were endoscopically diagnosed with esophageal strictures after ER. At the last follow-up, 28 patients (90.5%) were able to eat a regular diet, one patient (3.2%) could eat a soft diet, one needed a semifluid diet, and only one (3.2%) had to eat a fluid diet. Conclusions: For patients with stage I EC, additional radiotherapy following ER is safe and effective, with the swallowing function well-preserved. Nevertheless, prospective studies are needed to verify these results.

Endostar (rh-endostatin) improves efficacy of concurrent chemoradiotherapy for locally advanced non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: We aimed to clarify the benefits of the addition of rh-endostatin into concurrent chemoradiotherapy (CCRT) versus CCRT alone for locally advanced non-small cell lung cancer (NSCLC) by a meta-analysis. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically screened from inception to November 2020 using the prespecified terms. Prospective trials (evaluating or) comparing the efficacy of endostar combined with CCRT and CCRT for locally advanced NSCLC were included. The primary endpoints were risk ratios (RRs) for objective response rate (ORR) and disease control rate (DCR). The secondary endpoints were RRs for overall survival (OS) and adverse events (AEs). RESULTS: Ten studies with 716 patients were included in this meta-analysis. Endostar combined with CCRT significantly improved ORR and DCR compared with CCRT. The RRs of ORR and DCR for endostar combined with CCRT versus CCRT were 1.263 (95% CI: 1.137-1.403, p < 0.001) and 1.274 (95% CI: 1.124-1.444, p < 0.001), respectively. Endostar combined with CCRT significantly improved one-year survival rate compared with CCRT with pooled RR = 1.113 (95% CI: 1.006-1.231, p = 0.038). Endostar combination treatments had similar incidences of main adverse events compared with CCRT (p > 0.05). CONCLUSION: Endostar combined with CCRT is associated with significantly higher ORR, DCR and survival rate than CCRT with similar incidences of main adverse events in NSCLC.

The Optimal Treatment for Resectable Esophageal Cancer: A Network Meta-Analysis of 6168 Patients.

The optimal treatment for resectable esophageal cancer remains unclear. This network meta-analysis compares the efficacy of different treatments. PubMed, Embase, and the Cochrane library were systematically screened. Randomized controlled trials comparing the efficacy of different treatments for resectable esophageal cancer were included. Hazard ratios (HR) for overall survival (OS), progression-free survival, or disease-free survival, and odds ratios for locoregional recurrence and distant metastasis rates were identified as the measurements of efficacy. A Bayesian network meta-analysis was performed. In this study, 26 studies were included. Patients received either surgery alone; neoadjuvant chemotherapy (CT), neoadjuvant radiotherapy (RT), or neoadjuvant chemoradiotherapy (CRT) followed by surgery; or surgery followed by adjuvant CT, adjuvant RT, or adjuvant CRT. Neoadjuvant CRT followed by surgery (pooled HR = 0.76, 95% credible interval: 0.67-0.85) and neoadjuvant CT followed by surgery compared with surgery alone were the only two showing statistically confident improvement on OS. Ranking analysis showed that neoadjuvant CRT with surgery was likely to be the best option in terms of efficacy. Therefore, for patients with resectable esophageal cancer, neoadjuvant CRT with surgery is the optimal treatment. Future studies should focus on the optimization of neoadjuvant CRT regimens.

Risk of cardiac-related mortality in stage IIIA-N2 non-small cell lung cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

BACKGROUND: In this study, we aimed to investigate the association between postoperative radiotherapy (PORT) and cardiac-related mortality in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The United States (US) population based on the SEER database was searched for cardiac-related mortality among patients with stage IIIA-N2 NSCLC. Cardiac-related mortality was compared between the PORT and Non-PORT groups. Accounting for mortality from other causes, Fine and Gray's test compared cumulative incidences of cardiac-related mortality between both groups. Univariate and multivariate analysis were performed using the competing risk model. RESULTS: From 1988 to 2016, 7290 patients met the inclusion criteria: 3386 patients were treated with PORT and 3904 patients with Non-PORT. The five-year overall incidence of cardiac-related mortality was 3.01% in the PORT group and 3.26% in the Non-PORT group. Older age, male sex, squamous cell lung cancer, earlier year of diagnosis and earlier T stage were independent adverse factors for cardiac-related mortality. However, PORT use was not associated with an increase in the hazard for cardiac-related mortality (subdistribution hazard ratio [SHR] = 0.99, 95% confidence interval [CI]: 0.78-1.24, p = 0.91). When evaluating cardiac-related mortality in each time period, the overall incidence of cardiac-related mortality was decreased over time. There were no statistically significant differences based on PORT use in all time periods. CONCLUSIONS: With a median follow-up of 25 months, no significant differences were found in cardiac-related mortality between the PORT and Non-PORT groups in stage IIIA-N2 NSCLC patients.

Postoperative radiotherapy for pathological stage IIIA-N2 non-small cell lung cancer with positive surgical margins.

BACKGROUND: The aim of this study was to evaluate the efficacy of postoperative radiotherapy (PORT) in stage pIIIA-N2 non-small cell lung cancer (NSCLC) patients with positive surgical margins. METHODS: Between January 2003 and December 2015, patients who had undergone lobectomy or pneumonectomy plus mediastinal lymph node dissection or systematic sampling in our single institution were retrospectively reviewed. Those with pIIIA-N2 NSCLC and positive surgical margins were enrolled into the study. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used to analyze differences between the groups. Univariate and multivariate analyses using Cox proportional hazards regression models were performed to evaluate potential prognostic factors for OS. Statistically significant difference was set as P < 0.05. RESULTS: Of all the 1547 patients with pIIIA-N2 NSCLC reviewed, 113 patients had positive surgical margins, including 76 patients with R1 resection and 37 with R2 resection. The median overall survival (OS) was 28.3 months in the PORT group and 22.6 months in the non-PORT group (P = 0.568). Subset analysis showed that for patients with R1 resection, the median OS was 52.4 months in the PORT group which was nonsignificantly longer than that of 22.6 months in the non-PORT group (P = 0.127), whereas PORT combined with chemotherapy could significantly improve OS, with a median OS of 52.4 months versus 17.2 months (P = 0.027). For patients with R2 resection, PORT made no significant difference in OS (17.6 vs. 63.8 months, P = 0.529). CONCLUSIONS: For pIIIA-N2 NSCLC patients with positive surgical margins, PORT did not improve OS, but OS was improved in those patients who underwent R1 resection combined with chemotherapy. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Significant findings of the study: Postoperative radiotherapy (PORT) has been recommended to treat patients with positive surgical margins. However, the existing evidence is controversial and high-level evidence is lacking. WHAT THIS STUDY ADDS: What this study adds: The PORT group had markedly, but not statistically significant, longer median OS compared with the non-PORT group in patients with R1 resection. OS was significantly longer in the patients with R1 resection receiving adjuvant CRT than the surgery alone group.

Multivariate gene expression-based survival predictor model in esophageal adenocarcinoma.

BACKGROUND: Despite the recent development of molecular-targeted treatment and immunotherapy, survival of patients with esophageal adenocarcinoma (EAC) with poor prognosis is still poor due to lack of an effective biomarker. In this study, we aimed to explore the ceRNA and construct a multivariate gene expression predictor model using data from The Cancer Genome Atlas (TCGA) to predict the prognosis of EAC patients. METHODS: We conducted differential expression analysis using mRNA, miRNA and lncRNA transciptome data from EAC and normal patients as well as corresponding clinical information from TCGA database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of those unique differentially expressed mRNAs using the Integrate Discovery Database (DAVID) database. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network of EAC and used Cox proportional hazard analysis to generate a multivariate gene expression predictor model. We finally performed survival analysis to determine the effect of differentially expressed mRNA on patients' overall survival and discover the hub gene. RESULTS: We identified a total of 488 lncRNAs, 33 miRNAs, and 1207 mRNAs with differentially expressed profiles. Cox proportional hazard analysis and survival analysis using the ceRNA network revealed four genes (IL-11, PDGFD, NPTX1, ITPR1) as potential biomarkers of EAC prognosis in our predictor model, and IL-11 was identified as an independent prognostic factor. CONCLUSIONS: In conclusion, we identified differences in the ceRNA regulatory networks and constructed a four-gene expression-based survival predictor model, which could be referential for future clinical research.

A unique variation with five branches of the aortic arch.

Here, we present a unique case with 5 branches of the aortic arch (AA), namely the right common carotid artery, left common carotid artery, left thyrocervical trunk, left subclavian artery and right subclavian artery (RSA), from right to left. We found that the left thyrocervical trunk originated directly from the AA rather than the left subclavian artery. In addition, the RSA arose dorsally as the last branch of the AA and passed posteriorly to the oesophagus to supply the right upper limb. In addition, the right vertebral artery originated from the right common carotid artery instead of the RSA. Despite numerous studies on AA variations, to our knowledge, this is the first case of the left thyrocervical trunk originating directly from the AA and the RSA arising dorsally as the last branch of a 5-branch AA. Our case provides useful information to anatomists, radiologists and neck and thoracic surgeons.