Retrospective Study Of Chemoradiotherapy Combined With Anti-epidermal Growth Factor Monoclonal Antibody In The Treatment Of ?-?b Nasopharyngeal Carcinoma

BackgroundNasopharyngeal carcinoma is prone to metastasize in the early stage,and over 80%of patients are at a local advanced stage by initial diagnosis.For patients with locally advanced stage NPC,concurrent cisplatin-based chemoradiotherapy may enable longer survival than pure radiotherapy.Even so,5%-15%of NPC patients develop recurrence,and 15%-30%of patients develop distant metastasis.Therefore,it is urgent to explore new therapeutic regimens to prolong survival time.Chemoradiotherapy combined with anti-EGFR monoclonal antibodies are increasingly used in the treatment of nasopharyngeal carcinoma.The benefits ofadding anti-EGFR therapy to conventional chemoradiotherapy(CRT)for nasopharyngeal carcinoma(NPC)remain uncertain,Over 89%of nasopharyngeal carcinoma patients have high expression of EGFR,but there is no significant correlation between the expression of EGFR and the prognosis of patients receiving anti-EGFR therapy.Currently,combined anti-EGFR therapy for nasopharyngeal carcinoma lacks a marker to predict the efficacy.To address this issue,we compared the efficacy of CRT plus cetuximab(CTX)or nimotuzumab(NTZ)to CRT alone for stage ?-?b NPC and explored the prognostic indicators associated with combined anti-EGFR therapy.MethodThis retrospective study enrolled 1,812 patients at initial NPC diagnosis at Nanfang Hospital Affiliated to Southern Medical University between January 2005 and December 2015.Potential prognostic factors such as age,sex,KPS,total clinical disease stages,T stage,N stage,induction chemotherapy,concurrent chemotherapy,adjuvant chemotherapy condition and total number of chemotherapy cycles were adjusted by propensity score.The cetuximab or nimotuzumab plus CRT group(CRT+NTZ/CTX)and the conventional chemoradiotherapy group(CRT)were matched by propensity scoring at 1:5,yielding 282 patients at clinical stage ?-?b with 47 in the CRT+NTZ/CTX group and 235 in the CRT group.Survival result are described by Kaplan-Meier curve analysis and compared between groups by the log-rank test.Multivariate analysis was conducted using the Cox proportional hazard model with prognostic factors.The expression of EGFR,VEGF,Ki67,MMP2 and MMP9 in nasopharyngeal neoplasms of 31 patients in CRT+NTZ/CTX group before therapy was detected by immunohistochemistry.The relationship between these indicators expression levels were analyzed by the Spearman rank correlation test,and the relationships between expression and prognostic parameters were assessed by Kaplan-Meier curve analysis and log-rank test comparisons,The prognostic differences of immunohistochemical expression at different intensities were evaluated.ResultsThere were no significant differences in 3-year LRFS(82.2%vs 84%,P=0.761)?3-yearDMFS(81.7%vs 83.6%,P?0.802)?3-yearOS(90.5%vs91.1%,P=0.541),Conventional radiochemotherapy combined with cetuximab or nimotuzumab did not increase the blood system and gastrointestinal toxicity of the patients,and there was no significant difference in oral mucositis and radiotherapy-associated dermatitis between the two groups.Multivariate analysis of all 1,338 patients verified that CRT+NTZ/CTX and CRT groups did not differ in loco-regional relapse,distant metastasis,and death rates during follow-up.COX regression analysis revealed that higher N stage and male are independent risk factor for shorter LRFS,DMFS,and OS;while concurrent chemotherapy reduced the risk of distant metastasis.There was a positive correlation between EGFR and VEGF expression levels(P=0.001 R=0.548).Among CRT+NTZ/CTX patients,those with high EGFR and VEGF expression levels exhibited better DMFS(HR 0.097,95%Cl 0.010-0.912,P=0.041).ConclusionsThis study demonstrates that nimotuzumab or cetuximab in combination with chemoradiotherapy did not improve LRFS,DMFS,and OS in patients with nasopharyngeal carcinoma.In addition,nimotuzumab or cetuximab combined with chemoradiotherapy did not increase the patient's toxicity.Addition of anti-EGFR to cisplatin-based CRT appears to benefit only a subset of stage ?-?b NPC patients,those with elevated EGFR and VEGF expression levels.