BackgroundTo compare the efficiency and toxicity of bevacizumab by intrapleural or intravenous infusion in the management of malignant pleural effusion in patients with non‐small‐cell lung cancer (NSCLC).MethodsSensitizing mutation negative NSCLC patients with malignant pleural effusion were randomized into two groups in 1:1 ratio. The pleural effusion was completely drained in 24 hours; one group received intrapleural infusion and the second group received intravenous infusion of bevacizumab at a dose of 7.5 mg per kg bodyweight. The serum vascular endothelial growth factor (VEGF) was tested before and 72 hours after injection of bevacizumab. Computerized tomography (CT) scan to evaluate pleural effusions was carried out at four weeks for each patient and their survival followed‐up.ResultsA total of 67 patients were screened and 43 enrolled into the study. The response rate was 80% (16 of 20) in the intrapleural group and 66.7% (14 of 21) in the intravenous group. The median duration of response (DoR) of pleural effusion was 4.50 months and 3.70 months, respectively. The median serum VEGF level at 72 hours decreased 67.25% in the intrapleural group and 57.19% in the intravenous group compared to baseline level (P = 0.276). The median serum VEGF level at 72 hours decreased 52.02% compared to baseline level in patients’ DoR less than three months and 68.33% in patients' DoR longer than three months, respectively (P = 0.014). The main side effects noted were mild to moderate hypertension, proteinuria and epistaxis.ConclusionsBevacizumab intrapleural infusion had higher efficiency and higher safety than intravenous infusion in the management of malignant pleural effusion caused by NSCLC. The decreased level of serum VEGF at 72 hours after bevacizumab treatment was closely related to the response rate and duration of the response of pleural effusion.

<b><i>Background:</i></b> Distant metastasis of esophageal cancer (EC) is prone to be neglected, so it is necessary to screen out the high-risk population for more sensitive and rigorous pretreatment imaging evaluations. <b><i>Objective:</i></b> The aim of this study was to evaluate the risk factors for distant metastasis in patients with EC and to construct a clinical nomogram. <b><i>Methods:</i></b> Eligible patients diagnosed from 2010 to 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. Multivariable logistic regression analysis was applied to establish a prediction nomogram. Discrimination, calibration, clinical usefulness, and reproducibility were assessed by C-index, receiver-operating characteristic curve/the area under the curve (AUC), calibration plot, decision curve analysis (DCA), and bootstrapping validation. DCA was also used to compare the novel model with the conventional predictive methods. <b><i>Results:</i></b> A total of 9,026 patients were included for analysis. The nomogram incorporated the predictors: age, sex, race, grade, T stage, N stage, histology, tumor location, and pathological grading. The prediction model presented good discrimination with an AUC of 0.738 and a concordance index of 0.747 (95% confidence interval: 0.734–0.760), which was confirmed to be 0.745 through bootstrapping validation. Calibration plot and DCA showed satisfactory calibration and good net benefit, respectively. Comparing with the conventional prediction methods, the nomogram yielded superior net benefit. <b><i>Conclusions:</i></b> We constructed and validated a novel nomogram to help clinicians access the risk of distant metastasis in patients with EC.

<b><i>Objective:</i></b> Esophageal fistula is a critical and fatal complication of esophageal cancer. The aim of this meta-analysis was to explore the risk factors for esophageal perforation in esophageal cancer patients treated with radiotherapy. <b><i>Methods:</i></b> Data from the PubMed and Embase databases were retrieved for clinical research published between 1990 and 2018. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. A meta-analysis was performed using the RevMan 5.3 software provided by the Cochrane Collaboration Network. <b><i>Results:</i></b> Seventeen articles were eligible for the meta-analysis. In these articles, over 35 risk factors for esophageal fistula formation were described and 17 risk factors were analyzed. Significant differences in the odds of developing an esophageal perforation were found with regard to age (OR 2.34, 95% CI 1.08–5.03, <i>p</i> = 0.001), ulcerative type (OR 2.72, 95% CI 1.43–5.16, <i>p</i> = 0.002), histology (OR 4.16, 95% CI 1.14–15.12, <i>p</i> = 0.03), T stage (OR 2.66, 95% CI 1.44–4.91, <i>p</i> = 0.002), short-term response (OR 2.21, 95% CI 1.06–4.62, <i>p</i> = 0.03), chemotherapy regimen (OR 2.80, 95% CI 1.38–5.68, <i>p</i> = 0.005), and stenosis (OR 2.00, 95% CI 1.03–3.89, <i>p</i> = 0.04). <b><i>Conclusions:</i></b> An age of &#x3c;60–65 years, ulcerative type, squamous cell cancer, T4 stage, incomplete response, fluorouracil-based regimen, and stenosis were associated with an increased risk of esophageal fistula during or after radiotherapy. However, further, large-scale prospective studies are needed to establish the validity of this associ­ation.

Objective: To study the efficacy and toxicity of irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma. Patients and methods: Previously untreated patients with cytologically or histologically confirmed metastatic pancreatic adenocarcinoma underwent a treatment regimen consisting of an intravenous infusion of irinotecan 165 mg/m2 and oxaliplatin 85 mg/m2 on day 1, and oral S-1 40 mg/m2 twice daily on days 1–14, repeating the regimen every 21 days until one of the following occurred: disease progression, intolerable toxicity, or patient death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate, toxicity, and quality of life. This ongoing study had been registered on ClinicalTrials.gov, NCT03726021. Results: A total of 41 patients were enrolled in this study, 18 men and 23 women. The median PFS was 4.33 months [95% confidence interval (CI): 2.83–5.88] and the median OS was 11.00 months (95% CI: 9.16–12.84). There were no instances of a complete response; the partial response, stable disease, and disease progression rates were 39.02% (16/41), 29.27% (12/41), and 31.71% (13/41), respectively. The most common adverse side effects were mild to moderate nausea, vomiting, neutropenia, and thrombocytopenia. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 29.27% (12/41) and 12.20% (5/41) of the patients, respectively. No treatment-related death was observed. Conclusion: Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. A larger study population is needed for further evaluation.

Small-cell lung cancer (SCLC) is a recalcitrant cancer for its dismal prognosis although extensive research had been done. Four to 6 cycles platinum-based chemotherapy is the mainstay treatment for the extensive-stage disease; but the role of maintenance treatment is not fully understood. This is a phase 2, open-label study. Patients with extensive-stage SCLC reaching an objective response or stable disease (SD) after induction chemotherapy were randomly assigned (1:1) with a minimization procedure. One group received oral S-1 and the other group received placebo as maintenance treatment until disease progression or unacceptable toxicities. The primary end point of this study was progression-free survival (PFS), and the secondary end points were overall survival (OS), response rates, and toxicities. This study was based on earlier work, the preliminary results was reported on 2019 ASCO annual meeting. A total of 89 patients were enrolled, of whom 45 received S-1 maintenance therapy and 44 received placebo. The median PFS and OS were 6.35 months and 10.82 months in the S-1 group, as compared to 5.98 months and 10.09 months in the placebo group. The PFS was 7.2 months and 5.3 months, and OS was 12.9 months and 10.9 months in patients with an objective response compared to in patients with SD after induction chemotherapy, respectively. S-1 maintenance therapy did not prolong PFS or OS in patients with extensive-stage SCLC; tumor regression rate was the prognostic factor of PFS or OS. Further research with novel agents in the maintenance setting is warranted.