Discussion
A lthough NPC is radiosensitive, recurrence of the tumor after radiotherapy is a common cause of treatment failure. It is generally recommend to perform actively salvage treatment for local recurrence of NPC, owing to high success rate of the procedure 8 The OS of patients receiving salvage treatment was significantly higher than patients who did not receive the treatment.9Re-irradiation is often accompanied by serious complications, such as radiation necrosis of bone, multiple cranial nerve dysfunction and brain necrosis, which damages the quality of life of patients and even leads to death.10 In addition, Yu et al. reported that re-irradiation could only improve the survival rate of patients with tumor stages rT1 and rT2, while patients with rT3 and rT4 showed no significant change.2 Wang et al. also concluded that NPCs with advanced recurrence (rT3, rT4, and bulky rT2) have poor re-irradiation effect, low control rate, and high incidence of complications.11
I n our study, the overall 3-year survival rates of salvage endoscopic nasopharyngectomy were 59.5%. However, Kong et al. demonstrated 46.0% 3-year survival rate after re-irradiation in 184 patients with recurrent NPC.12 In addition, the five-year OS of patients with rT3 and rT4 tumors were 44.1% and 32.5% respectively in our institution, which were higher than that of salvage re-irradiation treatment reported in the literature (the 5-year OS for patients with rT3 and rT4 tumors was only 35.5–36 and 19–30.2 %, respectively).11,13Chua et al. also reported that patients who underwent salvage surgeries had higher survival rates compared to re-irradiation for rT1 and rT2 tumors.14 Therefore, we hypothesize that salvage surgery may be associated with better survival prognosis than re-irradiation alone; however, more clinical case studies and prospective studies are needed to confirm this perspective.
P atients with tumor stages rT3 and rT4 have significantly worse prognosis for OS in univariate and multivariate analyses. This is because salvage surgery for recurrent rT3 and rT4 NPC is challenging, which could damage various neurovascular structures, base of the skull, dura, and possibly cause intracranial destruction. Chan et al. revealed that the probability of achieving clear resection margins during salvage nasopharyngectomy is significantly lower for late (rT3 and rT4) compared to early (rT1 and rT2) tumors.15 Meanwhile, Bian et al. also supported the observations that tumors with high recurrence (rT3 and rT4) are associated with unfavorable survival after nasopharyngectomy.8 In the present study, we chose another prognostic factor, metastatic lymph nodes, in univariate and multivariate analyses, because most patients with NPC have cervical lymph node metastasis at the time of initial diagnosis. New evidence suggests that lymph node metastasis increases the risk of distant organ metastasis and is associated with poor prognosis.16,17Consistent with previous reports, our study further supports the relationship between metastatic lymph nodes and poor clinical outcomes.
S ome studies have found that the pretreatment NLR independently affects the survival rate of patients with NPC undergoing radiotherapy.18-20 In this study, we found for the first time that the serum NLR marker could be a potential prognostic indicator of recurrent NPC. NLR reflects the number of neutrophils and lymphocytes, which can be easily measured clinically by peripheral blood test. A previous study conducted on more than 12000 patients also supported the relationship between high NLR and poor OS in different types of cancer.21 One possible reason is that neutrophils can inhibit the immunosuppression induced by activated T cells and NK cells, while lymphocytes can inhibit tumor cell proliferation and metastasis through anti-tumor reactions involving cytokine production and cytotoxic cell death.22
M ultivariate analyses in our previous study on 91 patients with residual and recurrent NPC who underwent endoscopic nasopharyngectomy showed that tumor necrosis was an independent risk factor for OS.4 In this study, ROC analysis also revealed that tumor necrosis was the best predictor for OS. The cause of necrosis in recurrent NPCs and the mechanism associated with adverse clinical outcomes remains unclear. The general assumption of development of tumor necrosis is the rapid growth of malignant cells, especially in more aggressive cancer types, increase in blood supply with subsequent creation of a hypoxic environment leading to necrosis of tissue. Immune factors, such as innate and adaptive immune systems, also play a role in necrosis; however, further studies are needed to elucidate their potential effects.23,24Atanasov et al. reported that assessment of tumor necrosis was a valuable additional prognostic tool for hilar cholangiocarcinoma, which may have implications for monitoring and planning more personalized multimodal treatment strategies.25 Postoperative pathological examination done in other studies also reported that tumor necrosis was related to the decrease in survival rate of patients with different tumor entities.26-28