Study On Factors Influencing Prognosis Of Nasopharyngeal Carcinoma

Backgrounds: Nasopharyngeal carcinoma(NPC)remains endemic in southern China,with a peak annual incidence approaching 30 per 100,000 persons.The majority of patients diagnosed with NPC present with advanced-stage disease.Today,concurrent chemoradiotherapy remains the main treatment modality for these patients.Intensity-modulated RT(IMRT)is the current standard of treatment for NPC,with excellent locoregional control achieved by most expert centers.Despite its known limitations,TNM staging system,which is based on anatomic location and cranial nerve involvement,remains the most important prognostic factor in NPC.Primary gross tumor volume(GTVp)has been demonstrated to significantly correlate with prognosis of advanced NPC and some researchers have proposed to add GTVp to the current TNM staging system.However,more prospective studies need to be conducted to evaluate the prognostic value of GTVp for NPC.The frequency of nasopharyngeal carcinoma(NPC)varies with age.Elderly NPC patients(age≥ 60 years)constitutes about 13.8 % of all NPC.Todate,the treatment for geriatric NPC patients generally follows guidelines tailored for non-elderly patients.Patients with locoregionally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by concurrent chemoradiotherapy has shown to further improve progression-free survival(PFS)and overall survival(OS)versus concurrent chemotherapy alone.However,the efficacy and toxicity of elderly patients with locoregionally advanced NPC have not been demonstrated.To delineate the prognostic value of primary gross tumor volume(GTVp)for patients with locoregionally advanced nasopharyngeal carcinoma(NPC)treated with concurrent chemoradiotherapy and compare survival and toxicity between induction chemotherapy followed by concurrent chemoradiotherapy(IC+CCRT)and concurrent chemoradiotherapy(CCRT)alone in elderly patients with advanced nasopharyngeal carcinoma(NPC),we designed these studies.Methods: 1.The CT and MRI images of 249 patients recruited at 6 centers in Guangxi Zhuang Autonomous Region were evaluated by 2 radiologists specializing in NPC.Receiver operating characteristic(ROC)curve analysis was used to evaluate different cutoff points of tumor size.Univariate analysis and multivariate analyses were performed to explore different associations and interactions.2.With the use of propensity-score matching,a total numbers of 190 patients received induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone were appropriately matched.The rates of overall survival(OS),cancer-specific survival(CSS),locoregional recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),and grade 3 to 4 toxicity between two groups were compared.Results: ROC curve analysis was performed to determine the cutoff point,which was 33 mL.The 5-year OS rates for patients with a GTVp <33 vs ≥33 mL was 86.1% vs 70.5%(P= 0.006),the 5-year locoregional recurrence–free rates for patients with a GTVp <33 vs ≥33 mL were 88.5% vs 72%(P= 0.002),the5-year distant metastasis–free rate for patients with a GTVp <33 vs ≥33 mL was85.1% vs 70.5%(P= 0.009),and the complete response rate for patients with a GTVp <33 vs ≥33 mL was 79.9% vs 63.8%(P=.007).In univariate analysis,GTVp significantly correlated with OS(hazard ratio [HR],1.012;P= 0.002),locoregional control(HR,1.014;P < 0.001),and distant metastasis(HR,1.009;P= 0.011).N classification significantly correlated with OS(HR,2.516;P=0.012),locoregional control(HR,3.856;P= 0.005),and distant metastasis(HR,3.398;P= 0.003)as well,while T classification,age,and sex did not.In multivariate analysis,GTVp significantly correlated with OS(HR,1.011;P=0.004),locoregional control(HR,1.012;P= 0.001),and distant metastasis(HR,1.008;P= 0.026).N classification also significantly correlated with OS(HR,2.322;P= 0.02),locoregional control(HR,3.856;P= 0.005),and distant metastasis(HR,3.222;P= 0.004).2.After log-rank test,there were not elevations of FFS(71.1% v 65.3%,P=0.415),LRFFS(81.4% v 76.7%,P= 0.55),DFFS(79.9% v 74.4%,P= 0.524),OS(73.3% v 62.8%,P= 0.281),and CSS(77.9% v 68.6%,P= 0.179)in the combination of induction chemotherapy and concurrent chemoradiotherapy.The cumulative incidence of all grade 3 to 4 toxicity after IC+CCRT(31.1%)was significantly higher than that after CCRT(18.7%,P= 5.59×10-6),especially anemia(9.3% v 1.2%,P= 0.034),leukocytopenia(31.4% v 14%,P= 0.011),and stomatitis(54.7% v 37.2%,P= 0.032).Conclusion: 1.For patients with locoregionally advanced nasopharyngeal carcinoma,GTVp and N staging significantly correlated with overall survival,locoregional control,and distant metastasis.2.33 mL for GTVp with the optimal sensitivity and specificity should be used for clinical practice.3.Incorporation of GTVp into the TNM classification for NPC would help enable more exact prediction of prognosis.4.The therapy of Induction chemotherapy followed by concurrent chemoradiotherapy had no improvements of 5-years LRFFS rate,5-years DFFS rate,5-years OS rate,and 5-years CSS rate in elderly patients with advanced NPC.5.Induction chemotherapy followed by concurrent chemoradiotherapy had high incidence of grade 3 to 4 toxicity in those patients.