| Background Hypopharyngeal squamous cell carcinoma usually accompanied by lymph node metastasis.Even with curative surgery,the prognosis remains poor.The number of positive lymph nodes(PLNN)and positive lymph node ratio(PLNR)are important indicators for assessing the risk of tumor metastasis and prognosis.The purpose of this study was to explore the risk factors and prognosis of lymph node metastasis in hypopharyngeal squamous cell carcinoma after surgery and to establish prognostic models and risk stratification systems to guide clinical practice.Methods Clinical data of patients with hypopharyngeal squamous cell carcinoma after surgery were extracted from the Surveillance,Epidemiology,and End Results(SEER)database from 2004 to 2019.The X-tile software was used to determine the optimal cutoff point,and the Kaplan-Meier method was adopted to calculate overall survival(OS)and disease-specific survival(DSS).Independent prognostic factors affecting OS and DSS were determined by univariate and multivariate Cox analyses,and corresponding nomograms were constructed.The performance of the nomograms was evaluated by the area under the curve(AUC),calibration plots,and decision curves.Results A total of 394 patients with hypopharyngeal squamous cell carcinoma after surgery were included in this study,with a lymph node metastasis rate of up to 80.96%.Patients with age ≤60 years old(P=0.033),T3-T4 staging(P=0.025),and primary tumor diameter greater than 2cm(P=0.041)were more likely to have lymph node metastasis,and lymph node-positive patients were more inclined to receive postoperative chemoradiotherapy.Compared with patients without lymph node metastasis,those with lymph node metastasis had significantly lower 5-year OS and DSS rates(P<0.001).The study further found that PLNN and PLNR were significantly negatively correlated with OS and DSS in patients with lymph node metastasis.In univariate and multivariate Cox analyses,age at diagnosis,race,anatomical site,T stage,PLNN,PLNR,and treatment modality were prognostic factors affecting OS,while race,T stage,PLNN,PLNR,and treatment modality were independent factors affecting DSS.Based on these findings,nomograms were constructed for predicting OS and DSS in patients with lymph nodepositive hypopharyngeal squamous cell carcinoma after surgery,and the AUC of the nomograms was higher than that of the TNM and SEER staging,indicating better predictive ability.Additionally,the calibration plots showed good consistency,indicating that the nomogram models’ predictive results were consistent with actual observations.Furthermore,postoperative patients with hypopharyngeal squamous cell carcinoma with lymph node metastasis were stratified into low,medium,and high-risk subgroups according to the scores calculated by the nomogram model.Survival analysis results showed that compared with patients in the medium-and low-risk subgroups,patients in the high-risk subgroup had significantly lower OS and DSS rates(P<0.001).Conclusion In this study,based on PLNN and PLNR,nomogram models were established for postoperative patients with lymph node metastatic hypopharyngeal squamous cell carcinoma.These models perform well in prognosis prediction and risk stratification of postoperative patients with hypopharyngeal squamous cell carcinoma,and has important clinical application value.Background Hypopharyngeal squamous cell carcinoma is one of the most lethal head and neck carcinomas due to its high rate of local metastasis.However,the genomic landscape of nodal metastatic hypopharyngeal carcinoma remains unclear,and the mechanisms of action leading to nodal metastases remain unclear.The study aimed to identify the genetic alterations in primary and lymph node metastases of hypopharyngeal squamous cell carcinoma,and to explore key genes and regulatory pathways that potentially drive lymph node metastasis.Methods In this study,whole exome sequencing(WES)was performed on postoperative samples from 39 patients with metastatic subpharyngeal squamous cell carcinoma in our center.Of these,30 cases had triple samples including matched primary tumors,metastatic tumors in lymph nodes and normal lymph nodes.The overall gene mutation profile,mutation spectrum,mutation signature,paired sample mutation consistency,copy number variation,tumor mutation burden(TMB),microsatellite instability,clone and subclone,and differential genes were analyzed.Chi-square tests or Fisher exact tests were used to compare the mutation frequency between the primaty and lymph node metastases.KaplanMeier method was adopted for survival analysis,and log-rank test was adopted for comparison between different groups.Results Hypopharyngeal squamous cell carcinoma is a malignancy with a high mutation burden.TTN,TP53,CSMD3,and MUC16 all showed high mutation frequency in both primary site and lymph node metastases.Besides,missense mutations were dominant in both samples,C>T conversion was significantly enriched,and their mutation signature were similar.However,the gene profiles of perfectly matched patients were less consistent(mean: 0.030).There were more mutations in lymph node metastases than in the primary(7371 vs.8586),and there were also specific mutated genes(including unique single nucleotide and copy number variants)in both groups.A total of 119 potential driver metastatic genes were screened by clonal and sub-clonal analysis as well as lymph node unique mutant gene analysis.Pathway enrichment analysis showed that these genes may be involved in the regulation of several signaling pathways,including cancer-related pathways,MAPK signaling pathway,actin cytoskeleton regulation,adhesion plaque,T cell receptor signaling pathway,Jak-stat signaling pathway,B cell receptor signaling pathway,mTOR signaling pathway and TGF-beta signaling pathway.More importantly,PIK3 CB and CREBBP were identified as the key genes driving lymph node metastasis by clonal evolution analysis and lymph node xmique gene variation(P=0.034).Compared with patients with wild type PIK3 CB gene,patients with PIK3 CB gene mutation showed a significant decrease in OS(P=0.009).In addition,in the primary site samples,TMB score was significantly negatively correlated with pT stage,and patients with high TMB(TMB>3.74)had significantly poor DFS(P=0.034)and OS(P=0.026)than patients with low TMB(TMB≤3.74).Conclusions This study presented the somatic mutation profile,copy number variation spectrum,TMB,microsatellite instability,and clone analysis of primary and paired lymph node metastases in patients with metastatic hypopharyngeal squamous cell carcinoma,and made comparison between the metastasis and matched primary tumor.We preliminarily revealed the key driver genes and regulatory pathways of lymph node metastasis,providing an important tiieoretical basis for further exploration of the mechanism of lymph node metastasis of hypopharyngeal carcinoma.Background Adenoid cystic carcinoma of the head and neck is a rare type of head and neck tumor with a relatively good prognosis.Hie optimal treatment for patients with distant metastases has not yet been determined.This study was aimed to investigate the clinical characteristics,treatment modalities,survival outcome,and prognostic factors of patients with metastatic head and neck adenoid cystic carcinoma(HNACC).Methods The clinical data of metastatic HNACC from 1999 to 2020 at the National Cancer Center of China were retrospectively collected.Univariate analysis was adopted using the Kaplan-Meier method.The difference in survival curves between the two groups was estimated using the log-rank test.Multivariate survival analysis was performed with a Cox proportional hazards regression model to evaluate independent prognostic factors associated with improved survival.Results Overall,one hundred seventy-four patients with metastatic HNACC were enrolled.The median overall sxirvival(OS)of metastatic HNACC was 45.6 months,the 1-,3-,5-,and 8-years OS rates were 87.0%,56.6%,38.4%,and 26.0%,respectively.Univariate analysis indicated that smoking history,disease-free interval(DFI),number and sites of metastases,and systemic therapy were associated with OS of patients with metastatic HNACC(all P<0.05).In the multivariate Cox analysis,non-smoking history(HR 2.747,P=0.025),DFI≥3 years(HR L827,P=0.013),and lung metastasis alone(HR 2.270,P=0.007;HR 8.2334,P<0.001)were prognostic factors associated with OS for patients with metastatic HNACC.Nevertheless,sex,age at metastatic HNACC diagnosis,drinking status,primary tumor site,local recurrence,and number of organs involved were not significantly related to OS(all P>0.05).No significant survival difference was found between patients who received systemic therapy and those who did not.Furthermore,local therapy for metastases was not an independent prognostic factor for OS(all P>0.05).Nevertheless,sex,age at metastatic HNACC diagnosis,drinking status,primary tumor site,local recurrence,and number of organs involved were not significantly related to OS(all P>0.05).No significant survival difference was found between patients who received systemic therapy and those who did not(P=0.095).Furthermore,local therapy for metastases was not an independent prognostic factor for OS(P=0.534).Additionally,further subgroup analysis found that local therapy for localized disease could prolong survival in patients with both recurrent and metastatic disease(83.2 months vs.31.2 months,x2=9.816,P=0.002).Conclusion No smoking history,DFI>3years,and lung metastasis alone were favorable prognostic factors affecting OS.For patients with metastatic HNACC,local therapy for metastases could not provide survival benefits,but local therapy for localized disease may prolong survival.Whether initial systemic tiierapy could improve patient prognosis needs further exploration.Objective To investigate the clinicopathological features,survival outcome,and prognostic factors in patients with major salivary acinar cell carcinoma(MSACC)after surgery.Furthermore,this study aimed to develop a prognostic model for predicting overall survival(OS)to provide guidmice for clinical management.Methods Data of patients with MSACC were extracted from the Surveillance,Epidemiology,and End Results database(1975-2019).OS was evaluated using the Kaplan-Meier method and log-rank test.Univariate and multivariate Cox analyses were performed to explore independent prognostic factors affecting OS.The above selected variables were applied to construct a prognostic nomogram model,and the total score was calculated to predict the 5-year and 10-year OS rates of patients.The concordance index,area under the curve,calibration cxirve,and decision-making curve analysis were used to assess the performance of the nomogram.Besides,X-tile software was used to determine the optimal cut-off value of the total score to distinguish patients with different risks.In addition,a web calculator was used to further improve the practicality of the model.Results A steady upward trend in the incidence of MSACC was observed over the past four decades,with an annual percentage change of 1.177%.A total of 1398 patients were enrolled in the analysis,including 970 in the training cohort and 420 in the validation cohort.The 5-and 10-year OS rates were 97.7% and 81.6%,respectively.Age,marital status,sex,histological grade,T stage,and lymph node status were identified as prognostic factors for OS in patients with postoperative MSACC.In this study,a novel nomogram model was developed and verified to have good discriminative ability and clinical applicability,and a web calculator was designed to dynamically predict patient survival.Based on the nomogram-based score,a risk stratification system was further constructed to distinguish patients witii different risks.The OS of high-risk patients was significantly decreased than that of low-risk subgroup.Conclusion The incidence of MSACC was low,but showed a steady increase.Long-term survival of this rare malignancy was influenced by age,marital status,sex,historical grade,T stage,and lymph node status.A robust OS-nomogram was developed and validated to accurately predict individual survival and classify patients at different risk.An aggressive subgroup with poor prognosis in postoperative MSACC was identified,prompting us to be vigilant and consider timely adjustment of subsequent treatment. |
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