ObjectiveThis study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and methodsA total of 50 newly diagnosed patients with LA-NPC treated at the Affiliated Hospital of Jiangnan University between November 2011 and January 2017 were retrospectively analyzed. All patients received the combined treatment modality of nimotuzumab plus IMRT. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Neoadjuvant, concurrent or adjuvant chemotherapy with the doublet regimen of taxanes (docetaxel or paclitaxel) plus platinum (cisplatin or nedaplatin) were administered. Among the 50 patients, 43 (86.0%) received ≥6 cycles of nimotuzumab (median 7 cycles, range 2–14 cycles) and 29 (58.0%) received two cycles of CCT with docetaxel plus nedaplatin.ResultsWith a median follow-up of 28.0 months, the 2-year progression-free survival (PFS) and overall survival were 83.29% (95% confidence interval [CI]: 67.93%–91.72%) and 97.67% (95% CI: 84.62%–99.67%), respectively. Both univariate and multivariate analyses revealed that cycles of nimotuzumab were significantly associated with PFS. Patients who received ≥6 cycles of nimotuzumab showed a better PFS than those receiving <6 cycles (P=0.006), whereas the addition of CCT failed to improve PFS. Oral mucositis was the most common adverse event, which was recorded as grade 3–4 in 18 (36.0%) patients. Besides, two (4.0%) patients experienced nimotuzumab-related anaphylaxis, and no skin rash was found in any patient. Subgroup analysis revealed that the patients who received CCT had more grade 3–4 adverse events as compared to those who did not receive CCT (62.1% vs 33.3%, P=0.045).ConclusionThe regime of nimotuzumab plus IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC. Further clinical trials are needed to confirm these findings.

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Background Lung cancer has some of the highest morbidity and mortality worldwide among cancers, with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer diagnoses. Severe pulmonary hemorrhage (PH) is a serious potential adverse event in the treatment of lung cancer with bevacizumab. Significant clinical differences have been observed between patients with lung adenocarcinoma (LUAD) and those with lung squamous cell carcinoma (LUSC) after bevacizumab treatment; however, the underlying causes is unclear and requires further study. Methods First, tumor tissues from LUAD and LUSC patients were stained with antibodies targeting CD31 and CD34 to assess the difference in microvessel density (MVD). Tube formation assays were performed using HMEC-1 cells cocultured with lung cancer cells. Single-cell sequencing data obtained from lung cancer tissues were then downloaded and analyzed to identify differentially expressed genes related to angiogenesis in LUAD and LUSC tumors. Real-time polymerase chain reaction, immunofluorescence analysis, small interfering RNA analysis, and enzyme-linked immunosorbent assay were performed to clarify the underlying causes. Results The MVD of LUAD tissues was higher than that of LUSC tissues. Additionally, endothelial cells cocultured with LUAD cells had a higher MVD than did those cocultured with LUSC cells. Although bevacizumab mainly targets vascular endothelial growth factor ( VEGF ), the expression of VEGF in LUSC and LUAD cells was not significantly different (P>0.05). Further experiments showed that interferon regulatory factor 7 (IRF7 ) and interferoninduced protein with tetratricopeptide repeats 2 ( IFIT2 ) were differentially expressed between LUSC and LUAD tumors. Higher IRF7 levels and lower IFIT2 levels in LUAD tumors were associated with higher MVD in LUAD tissues, which may be responsible for the different hemorrhage outcomes after bevacizumab treatment. Conclusions Our data indicated that IRF7 and IFIT2 may account for the differential hemorrhage outcomes in patients with NSCLC after bevacizumab treatment, revealing a new mechanism underlying bevacizumab-induced pulmonary hemoptysis.