| BackgroundDue to the lack of natural biological barriers in the submucosal tissues of the hypopharynx and the abundant lymphatic drainage of the hypopharynx,hypopharyngeal cancer is more incline to local spread and cervical lymph node metastasis.The presence of cervical lymph node metastasis is an significant independent prognostic predictor impairing the therapeutic effect of hypopharyngeal cancer.Compared with patients without cervical lymph node metastasis,the 5-year survival rate of hypopharyngeal cancer patients with cervical lymph node metastasis is almost reduced by half.In addition to the treatment of the primary tumor,therefore,the the metastatic neck lymph nodes dissection is also playing an irreplaceable role in the treatment of hypopharyngeal cancer.Regarding the scope of cervical lymph node dissection in patients with early stage(T1-T2)primary hypopharyngeal cancer,there have been different clinical opinions for many years.In addition,research on predictive models integrating risk factors related to lymph node metastasis in hypopharyngeal cancer has not been reported yet.ObjectiveThis study intends to retrospectively summarize the distribution of metastatic cervical lymph node in T1-T2 stages of hypopharyngeal carcinoma to interpret the reasonable range of cervical lymph node dissection.Meanwhile,by exploring the risk factors related to lymph node metastasis,the author aims to construct an individualized model for predicting the risk of cervical lymph node metastasis in patients.And to provide a theoretical reference for the preoperative clinical decision-making.MethodsThe clinical pathological characteristics of T1-T2 hypopharyngeal carcinoma treated by surgery in our hospital were retrospectively analyzed.Firstly,the distribution of cervical lymph node metastasis of hypopharyngeal carcinoma was summarized.The primary endpoint of this study was cervical lymph node resected was positive,and a total of ten potential risk factors selected,including age,sex,heavy smoking,heavy drinking,tumor location(piriform sinus,posterior pharyngeal wall,postcricoid region),tumor differentiation grade(including highly differentiated,moderately differentiated and poorly differentiated),clinical T stage(T1 and T2),tumor type(exogenous and ulcer),tumor size(≤2,2-3 cm,3-4cm)and perineural/lympho-vascular invasion.The independent risk factors affecting cervical lymph node metastasis of hypopharyngeal carcinoma were screened by univariate and multivariate analysis.Based on the identified risk factors,an individualized model for predicting the risk of cervical lymph node metastasis in patients was initially constructed.The area under the receiver operating characteristic(ROC)curve is used to predict the discrimination ability of the nomogram.By using 500 bootstrap methods,the model was internally validated and the calibration curve was used to assess the calibration of the model.Decision curve analysis(DCA)was performed to indicated the clinical usefulness of the model by calculating the net benefits at different threshold probabilities(0%-100%)in the primary cohort.A two-tailed P<0.05 was considered to be statistically significant.ResultsA total of 349 patients with T1-T2 hypopharyngeal cancer were enrolled,including 282 cases(80.8%)of piriform sinus,46 cases(13.2%)of posterior pharyngeal wall,and 21 cases(6%)of postcricoid region;T2 stage cases accounted for 86.5%.There were 321 males and 28 females,with a male-female ratio of 11.5:1.The average age was 60.4±6.2 years,and the peak incidence of age was among 55 to 70 years.Most patients have a history of heavy smoking(73.4%)and drinking(84.0%).The general type of tumor was mainly ulcerative(67.9%),and 103(29.5%)patients presented perineural/lympho-vascular invasion.The proportion of female patients with posterior ring cancer was 23.8%,which was much higher than that of other subsites(P<0.01).The average age of pyriform sinus cancer patients is lower,and the proportion of heavy smoking and heavy drinking is higher than that of posterior hypopharyngeal wall cancer and posterior ring cancer.The types of tumor tissue differentiation are mainly moderate(45.6%)and poorly differentiated(46.7%).Piriform sinus carcinoma is more prone to poorly differentiated,while tumors of posterior pharyngeal wall and postcricoid region are more likely to be moderately differentiated(P=0.04).A total of 207 patients had cervical lymph nodes positive,and the total metastasis rate was 59.3%.The main levels of metastatic lymph nodes in the ipsilateral neck are areas Ⅱ,Ⅲ,and Ⅳ,and the lymph node metastasis rates are 43.6%,32.4%and 10.0%,respectively;while level I and level V metastasis are rare,and their lymph node metastasis rates are less than 3.7%,respectively.There were 25 cases of bilateral cervical lymph node metastasis,with a metastasis rate of 12.1%,which were mainly located in levels of II,III,and Ⅳ region.The rates of lymph node metastasis were 12.5%,10.2%and 5.6%,respectively.The results of univariate analysis showed that the sex,heavy drinking,tumor location,tumor differentiation grade,clinical Tumor(T)stage,tumor size,perineural/lympho-vascular invasion had a significant impact on cervical lymph node metastasis in T1-T2 hypopharyngeal carcinoma(All P value<0.05).The risk of cervical lymph node metastasis is higher in male patients with a history of heavy drinking,the lower the grade of tumor differentiation,and the larger the tumor size(all OR values>1).Tumors of piriform sinus are more likely to metastasize to lymph nodes,followed by posterior pharyngeal and postcricoid region.Multivariate analysis by using stepwise model selection method identified independent risk factors.All variables except sex were identified.The primary tumor subsite,tumor differentiation grade,tumor diameter,and perineural/lympho-vascular invasion were significantly associated with cervical lymph node metastasis(all P values<0.05),while the effect of risk effect of heavy drinking and clinical T stage is not significant(all P values>0.05).Six predictive variables,including heavy drinking,tumor location,tumor differentiation grade,clinical T stage,tumor size,perineural/lympho-vascular invasion,were integrated into the predictive model,and the results are illustrated in the form of a nomogram.The area under the ROC curve of the model is equal to 0.773,and the internally validated AUC=0.774,indicating that the established prediction model has a high degree of discrimination.The curve fitting line in the calibration curve is relatively close to the reference line,and the two lines roughly overlap,which indicates that the prediction results of the model are reliable.The clinical decision curve shows that when the prediction model is within the threshold probability range of 10-85%,the net benefit is higher than the extreme curve,indicating that the prediction model has a higher clinical application value.ConclusionsThis study showed that hypopharyngeal cancer is more likely to occur in elderly men;most patients have a history of heavy smoking and drinking.The proportion of female patients in postcricoid region cancer is higher than that of pyriform sinus cancer and posterior pharyngeal wall cancer.This study recommends that patients with T1-T2 hypopharyngeal carcinoma should routinely received lymph node dissection of levels of Ⅱ-Ⅳ.And for T2 stage patients,it should be utterly combined with the results of imaging and other examinations,then the contralateral neck should be selectively dissected of level of Ⅱ-Ⅳ area.Primary tumor location,tumor differentiation grade,tumor size,and perineural/lympho-vascular invasion are independently influencing for cervical lymph node metastasis in T1-T2 stages of hypopharyngeal carcinoma.The evaluation of discrimination,calibration and clinical applicability indicates that risk predictive model has high clinical application value. |
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