The Efficacy Of Resistance To Anti-PD-1 Combined With Palliative Radiotherapy For Recurrent Or Metastatic Nasopharyngeal Carcinoma

ObjectiveThis study aims to investigate the efficacy of anti-PD-1 resistance combined with palliative radiotherapy for recurrent or metastatic nasopharyngeal carcinoma(R/M-NPC).Meanwhile,To observe that on palliative radiotherapy basis whether the resistance to anti-PD-1 can be reversed and whether have the phenomenon of "abscopal effect".Materials and MethodThis retrospective study included 12 Patients with R/M NPC who were asse ssed as tumor progression by Response Evaluation Criteria in Solid Tumors(REC ISTv1.1)after anti-PD-1 therapy.All cases were given local palliative radiotherapy with 18 Gy to 36Gy——one fractionated dose of 3Gy-6Gy.Furthermore,they rec eiving systemic therapy with anti-PD-1(pembrolizumab 2mg/kg Q3 w or nivolum ab 3mg/kg Q2w).We analyze the curative effect of the combined regimen after a nti-PD-1 resistance,according to the Clinical Characteristics and follow-up results of 12 patients.Primary end point was DCR and PFS of the lesions in the field.Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors(RECIST;version 1.1).Evaluation standard of acute radioactive reaction refer to Radiation Therapy Oncology Group(RTOG).ResultMedian follow-up time 23 months.On the 12 cases,83.3% had received three or more therapies.The DCR and PFS inside of the radiation field were 100%(3 cases of CR,7 cases of PR and 2 cases of SD),but no regression of tumors outside of the radiation field(no CR+no PR).CR,PR and SD were observed in three,two and five patients,respectively,for an whole ORR of 66.6% and an whole DCR was 83.3%,of which 7 cases achieved long-term disease control(no disease progression ≥ 6months).The results of survival analysis revealed the median OS had not yet arrived,the OS and outfield PFS of 6 months and 12 months were 87.5%、50% and 63.5%、39.3%,respectively.Up to the last follow-up,8 cases(66.7%)disease progress was observed in outfield.Grade 4 radiotherapy-related adverse events occurred in only one patient with local recurrence.ConclusionOn the basis of anti-PD-1 resistance,combined with palliative radiotherapy can effectively improve the objective response rate,and the disease control rate of inside of the radiation field is extremely high,which is expected to prolong progression-free survival and overall survival,with low toxicity and good tolerance.However,there were no remission in out of the irradiated field lesions,suggesting that different fractionated doses of palliative radiotherapy negative to observe reverse the resistance to anti-PD-1and no find out the phenomenon of "abscopal effect".As the sample size is small of this study,it still needs to be further verified.