1、 Introduction of nasopharynx Introduction of nasopharyngeal carcinoma (NPC) Related articles of EBV DNA and NPC prognosis - EBV DNA level and NPC recurrence - EBV DNA level and distant metastasis - EBV DNA level and survival - EBV DNA level and treatment response The nasopharynx (nasal part of the p
2、harynx) is the uppermost part of the pharynx It extends from the base of the skull to the upper surface of the soft palate NasopharynxNasopharynxExamination of NasopharynxNasopharyngoscopeFossa of RosenmullerNasopharyngeal Carcinoma (NPC) Epidemiology -Epidemiology - Common in southern regions of Ch
3、ina, Common in southern regions of China, particularly in Guangdong, Fujian, particularly in Guangdong, Fujian, Hong-kong and Taiwan Hong-kong and Taiwan 150 cases per 100,000 people in 150 cases per 100,000 people in Guangdong, 7.7 cases per 100,000 Guangdong, 7.7 cases per 100,000 people in Taiwan
4、, and 0.11.7 per people in Taiwan, and 0.11.7 per 100,000 people in USA100,000 people in USA NPC is seen primarily in middle-NPC is seen primarily in middle-aged (4555 y/o) persons in Asia, a aged (4555 y/o) persons in Asia, a high proportion of African cases high proportion of African cases appear
5、in childrenappear in children Etiology - Etiology - Cause ? Not clearCause ? Not clear EB virus - related to EB virus - related to undifferentiated typeundifferentiated type Gene - (HLA-A2, Aw19, BSin 2, B17, Gene - (HLA-A2, Aw19, BSin 2, B17, BW16)BW16) Diet (salted vegetables, fish and Diet (salte
6、d vegetables, fish and meat - dimethylnitrosamines)meat - dimethylnitrosamines) Environment smoking, nickel Environment smoking, nickel exposure, formaldehyde(exposure, formaldehyde(甲醛甲醛) )Nasopharyngeal Carcinoma (NPC) Symptoms and Signs Neck mass Ear fullness and hearing impairment (middle ear eff
7、usion) Blood tingled sputum Nasal obstruction Headache DiplopiaDiagnosis and Treatment Related Articles of Related Articles of EBV DNA and NPC prognosis EBV DNA and NPC prognosis EBV DNA level and NPC recurrenceEBV DNA level and NPC recurrence Plasma /serum cell-free EBV DNA may be a valuable tool f
8、or the monitor of NPC patients for the early detection of tumor recurrence Lo YM. et al. Cancer Res. 1999 Circulating EBV DNA has been found not only to correlate with disease staging, but also to provide useful information for the monitoring for tumor recurrence Lo YM. et al. Biomed Pharmacother. 2
9、001. Review The failure of complete and rapid elimination of EBV DNA from the circulation predicts disease recurrence To EW. et al. Clin Cancer Res. 2003 This study provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC a well as for monitor
10、ing recurrence and metastasis of this tumor Shao JY. et al. Cancer. 2004 The usefulness of EBV DNA as a useful tool in monitoring NPC by its ability to detect early recurrence and excellent correlation with treatment response Chan SL et al. BMC Cancer. 2006 The plasma EBV DNA assay correctly predict
11、ed all NPC recurrences, and PET had high capacity to localize potential lesion sites Wang WY et al. Cancer. 2011EBV DNA level and NPC recurrence The risks of loco-regional failure were not significantly different between patients with high and those with low EBV DNA levels Leung SF. et al. Cancer. 2
12、003 Plasma EBV DNA load measurement appears to be useful in a low tumor risk area(western Europe). However, development of local recurrences may not always coincide with raised level of EBV DNA Kalpoe JS. et al. J Clin Pathol. 2006 EBV DNA level and NPC recurrenceConclusion -NPC recurrence was highl
13、y related to EBV DNA level, but not always coincidedWith an asymptomatic rise in the plasma EBV DNA level, tumor recurrence should be consideredEBV DNA level and NPC recurrenceEBV DNA level and distant metastasis EBV DNA level and distant metastasis Patients with distant failure had significantly hi
14、gher pre-therapy EBV DNA levels than those without failure Leung SF. et al. Cancer 2003Kaplan Meier plot of freedom from distant failure for patient subgroups with high versus low pretherapy Epstein Barr virus (EBV) DNA levels The time to the first detection of circulating EBV DNA was significantly
15、shorter among patients with distant metastasis. Monitoring plasma EBV DNA level surpassed traditional methods for the early detection of distant failure in patients with NPC Hong RL. et al. Cancer. 2004 The use of plasma EBV DNA measurements for the early diagnosis and staging of NPC a well as for m
16、onitoring recurrence and metastasis of this tumor Shao JY. et al. Cancer 2004EBV DNA level and distant metastasis Conclusion -EBV DNA level was highly related to distant metastasisClose monitoring EBV DNA level could early detect distant failure in NPC patientsEBV DNA level and distant metastasis EB
17、V DNA level and survival Levels of post-treatment plasma EBV DNA in patients with NPC appear to strongly predict progression-free and overall survival and to accurately reflect the post-treatment residual tumor load Chan AT. et al. J Natl Cancer inst. 2002 Pre-therapy circulating EBV DNA load is an
18、independent prognostic factor for overall survival in NPC Leung SF. et al. J Clin Oncol. 2006EBV DNA level and survival Survival probabilities of patient groups according to Epstein-Barr virus (EBV) DNA levels. Low DNA denotes low EBV DNA levels of less than 4000 copies/ml, and high DNA denotes high
19、 EBV DNA levels of 4000 copies/ml Leung SF. et al. J Clin Oncol. 2006 EBV DNA status remains a strong predictor for overall survival in NPC Kenneth WY. et al. Clin Cancer Res. 2006 Metastatic/recurrent NPC patients with low pre-treatment plasma EBV DNA level and undetectable post-treatment plasma EB
20、V DNA showed a favorable prognosis and survival An X. et al. Cancer. 2011EBV DNA level and survival The 5-year overall survival rate in low pre-treatment plasma EBV DNA level and undetectable post-treatment plasma EBV DNA subgroup was 50.6%. However, no patients in the other 3 subgroups survived 5 y
21、ears An X. et al. Cancer. 2011Conclusion -EBV DNA level was highly related to survival rateLower pre-treatment plasma EBV DNA level and undetectable post-treatment plasma EBV DNA showed the best prognosisEBV DNA level and survivalEBV DNA level and treatment responseEBV DNA level and treatment respon
22、se Rapid clearance of plasma Epstein-Barr virus DNA after surgical treatment of nasopharyngeal carcinoma To EW. et al. Clin Caner Res. 2003 The in vivo elimination of EBV DNA is very rapid after surgical resection of NPC The failure of complete and rapid elimination of EBV DNA from the circulation p
23、redicts disease recurrence Plasma EBV DNA clearance rate as a novel prognostic marker for metastatic/recurrent nasopharyngeal carcinoma Wang WY. et al. Clin Cancer Res. 2010 Patients with a short t1/2 of plasma EBV DNA clearance have significantly higher complete response rate and overall survival t
24、han those with long t1/2 The plasma EBV DNA concentrations have no significant effects on outcome predictionEBV DNA level and treatment response The plasma EBV DNA concentrations have no significant effects on outcome prediction The t1/2 of plasma EBV DNA clearance shows significant effects on tumor
25、 response The clearance rates of plasma EBV DNA during the first month of chemotherapy can predict tumor response and patient survival Early change of chemotherapy regimen may be considered for patients with slow plasma EBV DNA clearance rate Wang WY. et al. Clin Cancer Res. 2010EBV DNA level and tr
26、eatment responseConclusion -EBV DNA level was a useful tool to monitor tumor response after therapyThe clearance rates of plasma EBV DNA seemed better than the concentration of plasma EBV DNA in predicting tumor responseEBV DNA level and treatment responseConclusion EBV DNA level was a useful tool in monitoring tumor recurrence, distant metastasis, survival and treatment response in nasopharyngeal carcinoma