| Oral cancer which is the most common head and neck cancer,accounts for 3% of malignant tumor,with more than 45,000 newly diagnosed cases each year.TSCC(tongue squamous cell carcinoma)accounts for 25%-40% of oral cancer.TSCC usually causes malfunction of mastication,speech and deglutition,in addition,because of its rapid local invasion and early lymph metastasis features,making tongue cancer patients with poor survival and quality of life.In the case of the prognosis of TSCC,the independent prognostic factors of disease can be screened according to the traditional Kaplan-Meier method and cox proportional hazards model,which can not be used to predict the survival of a single individual.There is currently no available nomogram that can predict the prognosis of tongue squamous cell carcinoma.PYM(Pingyangmycin)and HCPT(Hydroxycamptothecin)are unique drugs in China,with low price,reliable,less toxic side effects,but there is no report of PYM and HCPT combined with radiotherapy used for head and neck cancer which first put forward by our study group.In recent years,the incidence of oropharyngeal cancer has gradually increased,because of the particularity of the location of the oropharyngeal carcinoma,surgery is difficult and has large damage.Chemoradiotherapy is often used to treat advanced oropharyngeal cancer,the study of oropharyngeal cancer chemotherapy drugs is necessary.Purposes:1.To study the effect of HCPT and PYM combined with radiotherapy on the prognosis of patients with advanced oral squamous cell carcinoma.2.To establish the first comprehensive and practical TSCC nomograms that predict OS and tongue cancer-specific survival(TCSS)for patients undergoing surgical treatment as well as those not surgically treated.3.To investigate the relationship of the proliferation,apoptosis,migration and distribution of the cell cycle in FaDu after exposed to HCPT.Methods:1.Collected clinical data of the patients in our hospital with advanced oral squamous cell carcinoma from 2006 to 2015.The prognosis of patients with advanced oral squamous cell carcinoma was analyzed by Kaplan-Meier method and Cox's proportional hazards regression model.2.Clinical,tumor,and treatment characteristics of 12,674 patients diagnosed with TSCC between 2004 and 2013 were collected from the Surveillance,Epidemiology,and End Results database.These patients were then divided into surgery and nonsurgery cohorts,and nomograms were developed for each of these groups.The step-down method and cumulative incidence function were used for model selection to determine the significant prognostic factors associated with OS and TCSS.These prognostic variables were incorporated into nomograms.An external cohort was used to validate the surgery nomograms.3.The growth inhibition was evaluated by MTT assay and the migration were measured by Transwell migration assay.The apoptosis and the cell cycle distribution were detected by flow cytometry after treatment with HCPT.Results:1.Gender(HR=2.091,P=0.009),N stage of clinical TNM classification(HR=1.612,P=0.006)and Chemotherapy(HR=2.253,P=0.018)have significant effect on the prognosis and survival rate of patients with advanced oral squamous cell carcinoma.HCPT and PYM combined with radiotherapy have a better survival rate.2.In the surgery cohort,seven variables were chosen for analysis in the final model based on clinical importance as well as statistical significance for OS probability after univariate and multivariate analyses.These variables were age,race,marital status,TNM status,and tumor grade.The main factors significantly related to TCSS were age,race,marital status,TNM status,and tumor grade.Briefly,age,race,sex,tumor grade,marital status,TNM status,and radiotherapy were independent risk factors of OS and TCSS in the nonsurgery cohort.These independent risk factors were used to develop nomograms for predicting 5-and 8-year OS and TCSS for patients with nonsurgical treatment.the c-indexes of the OS and TCSS nomograms in the internal validation cohort(surgery cohort)were 0.709(95% confidence interval [CI],0.700–0.719)and 0.728(95% CI,0.717–0.739),respectively.In the external validation cohort,the c-indexes were 0.691(95% CI,0.677–0.738)and 0.711(95% CI,0.662–0.760),respectively.The nonsurgery nomograms showed excellent performance,with c-indexes of 0.750(95% CI,0.739–0.761)and 0.754(95% CI,0.742–0.766)for OS and TCSS.3.Various concentration of HCPT could effectively inhibit the growth and migration of cell line FaDu.According to the results of flow cytometry,the cell cycle was arrested in S phase and apoptosis were obviously induced after treated with HCPT(80ng/ml).Conclusion:1.Among patients with advanced oral squamous cell carcinoma,the overall survival rate of patients with male,noninvasive lymph node metastasis and PYM and HCPT combined with radiotherapy was higher than that of female,patients with lymph node metastasis and radiotherapy alone.PYM and HCPT combined with radiotherapy used for the treatment of head and neck cancer is an optional plan;2.we used a large population-based cohort to create a series of nomograms that estimated 5-and 8-year OS and TCSS for patients with TSCC for the first time.These nomograms demonstrated an accurate and powerful predictive ability as shown by internal and external validation;3.HCPT could inhibit the growth and migration of cell line FaDu.HCPT induced apoptosis of the cell cycle in FaDu probably connected with distribution of the cell cycle. |
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