Neoadjuvant Chemotherapy Combined With Low-dose Ultra-fractionated Radiotherapy Followed With Concurrent Chemoradiotherapy For Locally Advanced Nasopharyngeal Carcinoma:A Prospective Results Of Phase Ⅱ Trial

Objective:The main failure model of locally advanced nasopharyngeal carcinoma（LA-NPC）is local failure and distant metastasis.N stage is a prognostic factor for distant metastasis of NPC.Some characteristics of lymph nodes based on MRI,such as the size,number,laterality,extra-nodal neoplastic spread and central necrosis,were the high-risk factors for treatment failure.Nowadays,neoadjuvant chemotherapy followed with concurrent chemo radiotherapy was recommended for LA-NPC patients according to NCCN and CSCO,especially for some high-risk patients.Low-dose radiotherapy（LDRT）,which is<100cGy,induces enhanced cell killing in vitro and in vivo by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy.Therefore,we aimed to investigate the efficacy and toxicity of LDRT combined with neoadjuvant chemotherapy for high-risk LA-NPC.Methods:Squamous Ⅲ-ⅣA NPC patients（UICC/AJCC 8th）with high-risk factors of lymph nodes were prospectively enrolled in the study.The high-risk factors should include one of these followings:lymph node with central necrosis,extranodal neoplastic spread and the shortest diameter of lymph nodes≥3cm.3 cycles of neoadjuvant chemotherapy were given,the regimen was docetaxel（75mg/m₂ D1）and cisplatin（75mg/m₂ D1）.LDRT was delivered as 50cGy per fraction twice a day for gross nodal disease on D1 and D2 of neoadjuvant chemotherapy.Propensity score matching was used to select the patients as control group.RECIST 1.1 criteria was used to evaluate the ORR.CTCAE 5.0 was used to evaluate the toxicity.Results:From Jun 2020 to Jan 2021,54 patients were enrolled,including 27 patients in LDRT group,and 27 patients in control group.The median age were 43 years（23-57）for the whole patients.Ⅲ and IVA Clinical stages were 25.9%,74.1%and 29.6%,70.4%respectively for LDRT and control group（P=0.761）.The overall ORR of primary tumor and lymph nodes was higher in LDRT group（77.1%vs 50.3%,P=0.224）.As for the lymph nodes,the ORR of LDRT group was significantly higher than control group（100%vs 85.2%,P=0.038）.The average regression rate for the volume of lymph nodes was 89.4%in LDRT group,CR and PR was 7.4%and 92.6%.However,the average regression rate of it was only 56.24%in control group.There was no CR,PR and SD were 88.9%and 11.1%.For the primary tumor ORR,there was no significant difference.But we found the improved tendency for it.The ORR of it was higher in LDRT group（96.3%vs 81.5%,P=0.083）.The most common related grade 3-5 adverse events were leukopenia and neutropenia,the two groups had no difference（14.8%vs 7.4%,P=0.386;22.2%vs 18.5%,P=0.735）.Conclusions:LDRT combined with neoadjuvant chemotherapy followed with Concurrent Chemoradiotherapy could improve the ORR for high-risk LA-NPC patients,in which the ORR of lymph nodes had been significantly improved.This new comprehensive treatment model could be a promising strategy to increase the efficacy of chemotherapy and improve the prognosis.