Clinical Significance Analysis Of Nasopharyngeal Carcinoma - Related Drug - Resistant Protein And Local Recurrence Of Nasopharyngeal Carcinoma

Purpose:To retrospectively detect the expression of four types of resistance proteins (GST-π, P-gp, MRP1, TOPO-II) and analysis the correlation between clinical outcomes and biomarkers in patients with locally advanced nasopharyngeal carcinoma.Material and methods:Between October2006and October2010,89patients diagnosed with nasopharyngeal carcinoma were enrolled into the database analysis, including54with clinical staging III,35with staging IV according to the AJCC/UICC stage classification. All the patients were diagonosed by pathological biopsy. There were19females and70males. All patients received chemoradiotherapy, which were classified into three approaches:TPF induction chemotherapy plus adjuvant chemo combined IMRT, GP induction chemotherapy plus adjuvant chemo combined IMRT, TPF induction chemotherapy plus concurrent chemoradiotherapy. All of the biopsy tissues were detected with ICH for four types of resistance proteins (P-gp, GST-π,MRP1, TOPO-II). These valuable results were valued by correlated standard for IHC and then enrolled into the final analysis. SPSS19.0were used to analyze the statistics.Results:Up to the March2011, the median following up time was21months (range,6-55months). The three year progression free survival rate, recurrence free survival rate and metastases free survival rate for the89patients were86.1%,91.9%and90.1%。7patients induced neck recurrences,13patients induced metastases, and no one died. The statistical analyse reported that the age (》55) and N stage (N>2) were the bad prognostic factors for the PFS. The positive expression rates for GST-π, TOPO-II, MRP1and P-gp were61.8%,62.9%,33.7%and58.4%o The positive expression of TOPO-II was the highest, which meant the nasopharyngeal carcinoma were drug susceptibility. In patients with N2-3or T3-4the positive results were higher. The positive expression of MRP1and P-gp was districted by statistical analysis between T1-2and T3-4, and also between NO-1and N2-3. Multivariate analyses revealed that MRP1was a prognostic factor for recurrence free survival, the positive expression of P-gp was related with toxicity of marrow depression (P<0.05). The coexpression of TOPO-II and P-gp was correlated with the toxicities including the mucus damage and marrow depression. In the TPF induction plus adjuvant chemo team, the expression of GST-n and MRP1were related with marrow depression while in the GP induction plus adjuvant chemo team, the coexpression of GM、TP、GT were related to the recession of nasopharyngeal tumors while GM、 TM were correlated with recession of neck sites.Conclusions:This present study indicated that the age (》55) and N stage (N>2) were the bad prognostic factors for the PFS. GST-π, TOPO-II, MRP1and P-gp proteins all expressed positively in advanced nasopharyngeal carcinoma, TOPO-II was the highest, which meant the nasopharyngeal carcinoma were drug susceptibility. According to the statistical analyses, the solo expression of these proteins was not the prognostic factors. The effects and toxicities of chemoradiotherapy were affected with coexpression of these biomarkers. This present study proposes reference and foundation for the following up research for resistance proteins in NPC, and also for finding out the molecular biological prognosis factors hence guiding clinic intervention tragedies. Purpose:To study for the treatment outcome, radiation toxicity and the prognostic factors in patients with locally recurrent nasopharyngeal carcinoma (NPC)treated with intensity-modulated radiation therapy (IMRT) in our cancer center.Materials and methods:From Jun2006to October2010,97patients with locally recurrent NPC received re-irradiation using IMRT.12patients were diagnosed by the pathology of biopsy, the others were diagnosed by consulting pathological results or CT/MRI image evidence combing with the previous histories. According to the AJCC/UICC(2002) staging, the number of patients with Stage Ⅰ、Ⅱ、Ⅲ、Ⅳ disease were28,10,32and27respectively. The median age of patients was52years old (range,30-89). There were67males and30females. The median time from the initial radiotherapy to the nasopharyngeal recurrence was51months (range,8-276). All patients were treated with6MV photon with7-9fields using IMRT. The gross tumor volume (GTV) in the nasopharynx received a median prescription dose of6720cGy (range,5600-7200cGy),with median fractionation of2Gy(range,1.9-2.2Gy).67patients received cisplatin-based induction or concurrent or adjuvant chemotherapy. The toxicities were evaluated by CTC3.0.The resistance proteins in PART I were detected with ICH in12biopsy tissues.Results:Up to the March2011, the median follow-up time was20months (range,2-59months).4patients were lost. After re-irradiation,60.8%patients had complete response of primary tumor. Three years overall survival, progression-free survival rate and local-regional progression free survival rate was74.7%、71.9%and79.9%respectively.30patients died,14patients died of nasopharynx hemorrhea, and the others died of metastasis or exhaustion.2patients needed hospitalizations.2patients developed the third recurrence in the nasopharynx and neck respectively. Grade3-4toxicities were reported in15patients. Severe late complications such as eyeball damage/blindness and loss of hearing were observed in7patients.98.1%of GTV received95%of the prescribed dose (V95-GTV). The dose encompassing95%of GTV (D95-GTV) was66.9Gy. The average dose covered of GTV was66.7Gy. The doses of surrounding critical structures were lower than the tolerable thresholds. On statistical analysis, T stage was the independent prognostic factor for endpoints, and the nasopharynx remission situations were related to the PFS endpoint. As to the IHC results, the positive expression of GST-π and TOPO-II were higher than primary nasopharyngeal carcinoma. Statistical analyses didn’t show any correlation between prognosis and the IHC results.Conclusions:Our results showed that IMRT is feasible for patients with recurrent NPC. High dose prescription may result in radio-necrosis of nasopharyngeal mucosa and bleeding. The hemorrhea was the main death cause. The incidence of serious toxicities was also serious; some affected the quality of life. As to the IHC results, the positive expression of GST-π and TOPO-II were higher than primary nasopharyngeal carcinoma. Statistical analyses didn’t show any correlation between prognoses and the IHC results. More patients and longer term follow-up are warranted to evaluate late toxicities, treatment outcome and prognostic factors.