Clinical Practice And Exploration Of Precision Medicine In Head And Neck Cancer

Background:Palliative chemotherapy has been the mainstay treatment for recurrent or metastatic nasopharyngeal carcinoma(R/M-NPC).However,the efficacy of chemotherapy drugs in advanced patients is still unsatisfactory,and new drug is still needed to improve survival.Nimotuzumab(NTZ)is a monoclonal antibody drug targeting epidermal growth factor receptor.Now,little is known about the efficacy of NTZ plus chemotherapy(CT)versus CT alone for these R/M-NPC patients.Methods:The case information platform at Cancer Hospital of Chinese Academy of Medical Sciences was queried for patients diagnosed with NPC who received CT with or without NTZ between 2004 and 2018.Treatment compliance,survival outcomes,and adverse effects were compared among these groups.Results:Records of 70 patients with R/M-NPC were reviewed:21(30%)received NTZ plus CT(NTZ+CT)and 49(70%)received CT.CT regimens included gemcitabine plus platinum,taxane plus platinum(TP),and fluorouracil plus platinum.Comparing the CT group with NTZ+CT group,the median follow up was 62 months(range=3-133)versus 59 months(range=9-117);median progression free survival was 7.5[95%confidence interval(CI)6.552-8.381]months versus 8.5(95%CI 6.091-10.976)months,p=0.424;median overall survival(OS)was 25.6(95%CI 18.888-32.379)months versus 48.6(95%CI 35.619-61.581)months,p=0.017,respectively.Multivariable analysis established treatment group(CT versus NTZ+CT)as an independent prognostic factor for OS(hazard ratio,0.5;95%CI 0.255-0.979;p=0.043).No significant statistical difference between the two groups with regard to adverse effects.Among them,a subgroup analysis was performed in 53(75.7%)patients who received TP with or without NTZ,which showed similar results.Conclusion:Our findings suggested that NTZ+CT provides a novel treatment option and prolongs survival significantly for R/M-NPC.Background: Advanced head and neck cancer(HNC)is a type of malignancy with a poor prognosis.Patients have limited treatment options and poor efficacy.In recent years,a number of clinical studies have shown that immunotherapy can improve the survival and prognosis of patients with advanced HNC,which is a promising clinical treatment option.Due to the impact of tumor heterogeneity,different individuals have different efficacy for immunotherapy,so it is very important to select the potential benefit population of immunotherapy.It is difficult for HNC patients to obtain tissue specimens due to advanced disease.Liquid biopsy based on cell-free DNA(cfDNA)has shown good results in molecular diagnosis,monitoring treatment outcome and predicting recurrence of a variety of tumors.But so far,the research and application of cfDNA for HNC in immunotherapy are few.This study aims to monitor immunotherapy response and predict the prognosis based on non-invasive biopsy of cfDNA in HNC patients.Methods: Baseline blood samples of 26 advanced HNC patients undergoing immunotherapy at the Cancer Hospital of the Chinese Academy of Medical Sciences and50 healthy control blood samples were collected.Of these,15 patients were dynamically monitored for plasma cfDNA during treatment.Computed tomography(CT)scans were carried out to assess the condition before treatment and the effect post-treatment.Shallow whole genome sequencing(sWGS)of cfDNA was used to identify copy number variations(CNV),and a new metric was developed—IS score—to describe the genome instability(chromosomal instability).The primary aim of this study was the association between biomarker with treatment efficacy including disease control rate(DCR)and progressionfree survival(PFS)in these patients.Results: CNV reproducibility analysis showed that chromosomal arm alterations included copy number losses in 2lp、17p、22q、19q and 3p,and gains of 21 p and 8q.The most frequent CNVs were losses in 17p(harbouring the TP53 and NCOR1 genes)and 22q(harbouring the NF2 and EP300 genes).Compared with the baseline plasma cfDNA sequencing results,patients with progressive disease(PD)after immunotherapy have observed more obvious genomic instability events.The copy number losses in 17p/22q(7.4 vs.17.3 months;P=0.0170)and the IS-score-high group(7.4 vs.19.9 months;P=0.0026)had poorer PFS.The median IS-score of patients with PD was significantly higher than those with disease control(P=0.0089),however,there was no significant difference in cfDNA concentration between the two groups.The IS-score was not significantly correlated with the cfDNA concentration(P=0.48).In the multivariable analyses,the IS-score remained an independent prognostic factor for PFS(P=0.037).Conclusion: sWGS offers a highthroughput,cost-effective and non-invasive way to investigate the cfDNA of patients with HNC.Pre-treatment genome-wide CNA in cfDNA is a potential biomarker predicting the prognosis of advanced HNC patients receiving inmnmotherapy,help identify high-risk patients,and guide clinical decision-making.