**4. Chemotherapy**

Systemic chemotherapy (CT) in NPC is indicated because disease is confined to nasopharynx in < 10% of cases (Lee et al; 1992), while parapharyngeal extension, skull base and intracranial involvement are reported in 80% and 25 to 35% and pathologic cervical nodes are present in 75 to 90% of patients, increasing the risk of initial metastases in advanced stages (Lee et al;1992; Sham et al,1991; Teo et al,1992). CT have been used since the eighties in palliative intent with few devoted phase II trials and the most active agents are cisplatin, 5-fluorouracil (5-FU), doxorubicin, epirubicin, bleomycin, mitoxantrone, methotrexate and vinca alkaloids or more recently ifosfamide or gemcitabine(Bensouda et al,2011;Boussen et al,2010;You et al,2011). CT have been used from the nineties as adjuvant then primary CT(PCT) in NPC(Bachouchi et al,1990) confirming the chemosensitivity of NPC with a high rate of radiologic/endoscopic objective responses to PCT (Bachouchi et al,1990; Ekenel et al,2011).

#### **5. Radiotherapy**

180 Carcinogenesis, Diagnosis, and Molecular Targeted Treatment for Nasopharyngeal Carcinoma

(Sun et al,2005) from 1992 to 2002 for the incidence Rates of NPC among Chinese Americans Living in Los Angeles County and the San Francisco Metropolitan Area with a decrease of 37% for men by 37% and only 1% in women(7). Conversely, male and female NPC world age-standardized incidence reported to be 27.5/105 and 11.3/105 respectively, seems to be stable from 1970-2007 in the Chinese endemic area of Zhongshan (Wei et al, 2010). In Tunisia (Ben Abdallah M,2010), we are observing, like in Singapore, a decreasing incidence of NPC and a projection from the North Tunisia cancer registry for 2024 suggests a significant drop

During the last 20 years, NPC natural history became more known in term of loco-regional extension as well as metastatic disease with technical improvements of flexible nasofibroscopes and modern imagery, such as magnetic resonance imagery and Petscan(Chan et al,2011). This better definition of loco-regional disease extension leads to successive actualizations (1997, 2002 then 2009), of the more used TNM UICC anatomoclinical classification, more adapted to discriminate between the different T and N prognostic stages and eventually to adjust therapeutic protocols according to risk group

T1 Nasopharynx, oropharynx or nasal cavity (**was T2a\***) without parapharyngeal extension

T2a Tumour extends to oropharynx and/or nasal cavity without parapharyngeal extension

T4 Intracranial, cranial nerves, hypopharynx, orbit, infratemporal fossa/masticator space

N1 Unilateral **cervical**, unilateral or bilateral retropharyngeal lymph nodes, above

N3 Metastasis in lymph node(s), >6 cm in dimension (N3a) or in the supraclavicular fossa

7th TNM classification of UICC (International Union against Cancer, 2009)-AJCC, American

Systemic chemotherapy (CT) in NPC is indicated because disease is confined to nasopharynx in < 10% of cases (Lee et al; 1992), while parapharyngeal extension, skull base and intracranial involvement are reported in 80% and 25 to 35% and pathologic cervical nodes are present in 75 to 90% of patients, increasing the risk of initial metastases in advanced stages (Lee et al;1992; Sham et al,1991; Teo et al,1992). CT have been used since the eighties in palliative intent with few devoted phase II trials and the most active agents are

of NPC incidence, while breast and colon cancer will clearly increase.

**3. Staging and classification** 

(Union for International Cancer Control,2009).

T2 Parapharyngeal extension (**was T2b\***)

T2b Tumour with parapharyngeal extension

supraclavicular fossa; < 6 cm

(N3b)>6 cm

**4. Chemotherapy** 

T3 Bony structures of skull base and/or paranasal sinuses

N2 Bilateral **cervical** above supraclavicular fossa; < 6 cm

Joint Committee on Cancer. \*Recent modification

RT remains is the mainstay of of NPC treatment due to its radiosensibility (Boussen et al, 2010; Chan et al, 2010; Lee et al, 1992). Loco-regional RT targets primary tumor, its regional extension and both neck sides (levels Ib–V, and retropharyngeal nodes). Consensual dose is around 70 Gy with dose-fractions of 1.8 to 2Gy, indicated for sterilization of bulky tumor volume and 50–60 Gy or 46–60 Gy for areas at high risk (Lee et al, 1992; Chan et al, 2010).
