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