Radiotherapy is the preferred treatment for NPC. Radiation not only kills tumor cells, but also damages normal tissues and cells around the tumor. In NPC patients, the main cause of nasopharyngeal hemorrhage after radiotherapy is damage to adjacent blood vessels. Previous studies have shown that radiation may lead to vascular endothelial damage, resulting in elastic fiber rupture and increased vascular wall fragility . In addition, tissue necrosis in areas surrounding the tumor may impair the delivery of nutrition to the vascular wall, which may exacerbate any pre-existing damage and increase risk for vascular wall rupture and massive bleeding in the presence of infection.
In a case-control study, Chen et.al found that secondary-course radiotherapy and radiation-induced skull base osteonecrosis were key factors predicting carotid artery rupture syndrome after radiotherapy . Results from the univariate analysis in our study showed that T-stage, secondary-course radiotherapy, radioactive skull base osteonecrosis, results of nasopharyngeal bacterial culture, and nasopharyngeal tumor recurrence were significantly correlated with nasopharyngeal hemorrhage. These results were similar to those reported by Chen et al. We found that T-stage was closely related to nasopharyngeal hemorrhage after radiotherapy. One reason for this observation may be tumor invasion of bone tissue and even arteries afterT3 stage. In such cases, a high radiation dose during radiotherapy may cause bone necrosis, impairment of the nutrition supplied to bone, or direct radiation damage to blood vessels.
Secondary-course radiotherapy is performed to treat recurrent head and neck tumors after radiotherapy. It has been reported that this therapy achieves a good rate of local control. However, after application of this therapy,32.5% of patients die of carotid artery rupture syndrome or carotid hemorrhage . We also found that the incidence of nasopharyngeal hemorrhage increased significantly after the second course of radiotherapy. We speculate that an increase in radiation dose aggravates damage to the bone, mucosa, and blood vessels.
Wu et.al found that nasopharyngeal necrosis was closely related to infection after radiotherapy, and that lesions could erode the internal carotid artery and cause massive hemorrhage . Our study found that patients with positive results on nasopharyngeal bacterial culture were more likely to experience nasopharyngeal hemorrhage. The toxins and enzymes released by bacteria may damage the arterial wall, especially in areas where necrosis affects the bone and mucosa, which aggravates tissue damage and causes bleeding.
The results of our univariate analysis indicated that the recurrence of nasopharyngeal tumor was closely related to nasopharyngeal hemorrhage. One possible reason is that recurrent nasopharyngeal tumor is more likely to invade damaged bone, and even directly destroy the vulnerable artery wall, after radiotherapy, resulting in massive hemorrhage.
Further logistic multivariate analysis showed that only radioactive skull base osteonecrosis was related to nasopharyngeal hemorrhage after radiotherapy, which indicated that destruction or necrosis of the skull base may be the decisive factor leading to nasopharyngeal hemorrhage after radiotherapy. The other four factors investigated appeared to act only as synergistic or influencing factors.
Previous studies have shown that platinum-based concurrent chemotherapy may improve the survival rate of NPC patients [15, 16] and may also cause damage to coagulation function and blood vessels .However, our study did not find a clear correlation between treatment with chemotherapy drugs and nasopharyngeal bleeding. The presence of diabetes, hypertension, or other systemic diseases were reported to lead to peripheral vascular lesions, which may increase the risk of bleeding in tissue with radiation-related damage. However, the results from our study indicated no significant correlation between such complications and nasopharyngeal bleeding after radiotherapy.
In NPC patients who have undergone radiotherapy, nasopharyngeal hemorrhage mostly involves the internal carotid artery or external carotid artery branch and a high mortality rate. Most patients die of hemorrhagic shock or asphyxia caused by the aspiration of blood fluid. The present study included 64 cases with massive hemorrhage, including 55 sent immediately to the hospital, and 46 rescued successfully. The successful rescue was 83.6%. After successful rescue, DSA should be performed to identify the vessel that caused the bleed. In the case of bleeding from the external carotid artery branch, vascular interventional embolization can be performed for hemostasis; tissue ischemia and necrosis can be avoided because collateral circulation is abundant. However, in the case of internal carotid artery hemorrhage, vascular interventional embolization or a covered stent may be used, depending on the pattern of intracranial artery vascularization. Jung et al. found that the average survival time in such patients could be increased by 9 months through the use of interventional therapy .
Mak et al.  analyzed 15 patients with massive hemorrhage caused by rupture of an internal carotid artery pseudoaneurysm after radiotherapy for NPC. Four patients underwent arterial embolization, 11 patients were implanted with covered stents, and bleeding was stopped in all cases. However, during the follow-up period, pseudoaneurysm occurred again in 2 cases, with cerebral infarction in 2 cases and brain abscess in 1 case. During an average follow-up of 13 months, the stent patency rate was 67%. There were no clinical symptoms in 3 cases with stent occlusion. Therefore, it is considered that good results are achieved with embolization and use of a covered stent. Tsang et al.  reached a similar conclusion. In our study, the rate of survival after external carotid artery branch bleeding was significantly higher than the rate of survival after internal carotid artery bleeding. Embolization of the external carotid artery branch therefore appears to be the more effective treatment strategy, because the embolization of internal carotid artery hemorrhage is associated with complications such as hemiplegia and cerebral infarction. Therefore, we elected to use the covered stent to achieve an immediate hemostatic effect. However, the covered stent is short, and the portion of the vessel wall that remains uncovered may be fragile due to radiotherapy, sometimes leading to a second massive hemorrhage and a low survival rate. In this study, 19 patients died of rebleeding after receiving a covered stent.