1. Nasopharyngeal Carcinoma Dr. Krishna Koirala 2019-02-11

2. Introduction Non lymphomatous squamous-cell carcinoma that occurs in the epithelial lining of the nasopharynx Frequently arises from the pharyngeal recess (fossa of Rosenmüller) posteromedial to the medial crura of the eustachian tube opening in the nasopharynx

3. Fossa of Rosenmuller

4. Epidemiology Accounts for 85% adult nasopharyngeal malignancies and 30% pediatric nasopharyngeal malignancies Common in Chinese and North African people Male preponderance of 3:1 Bimodal age presentation with small peak at 15-25 yrs and a large peak at 55-65 yrs

5. Etiology Genetic – –Commonest in Southern Chinese ( Mongoloid race) – –HLA association Viral : Epstein-Barr Virus Environmental – –Exposure to nitrosamines (dry salted fish), polycyclic hydrocarbons (smoke of incense / wood) – –Smoking, chronic nasal infection, poor ventilation of nasopharynx

6. W.H.O. Classification (Histological) Type 1 : − −Keratinizing squamous cell carcinoma (common in the older adult population) Type 2: − −Non-keratinizing (transitional) carcinoma Type 3: − −Undifferentiated carcinoma ( common in childhood and adolescents, associated with high EBV Ab titre)

7. Clinical Features 1. Neck swelling (60%) Lateral retropharyngeal LN of Rouviere B/L, enlarged jugulodigastric, upper & middle deep cervical nodes and posterior triangle nodes 2. Nasal (40%) Blood stained nasal mucus, epistaxis, nose block, foul smelling nasal discharge 3. Otologic (30%) : Conductive deafness, tinnitus

8. 4. Ophthalmologic (20%) Diplopia & ophthalmoplegia (involvement of CN III, IV, VI), Proptosis (orbit invasion) & blindness (involvement of CN II) 5. Neurologic (20 %) Jugular foramen syndrome: CN IX, X, XI involved by lateral retropharyngeal lymph node Horner's syndrome: sympathetic chain involvement

9. 6. Severe Headache Skull base erosion 7. Trotter's triad – –Conductive deafness: Eustachian Tube block – –Ipsilateral temporo -parietal neuralgia: Trigeminal nerve involvement – –Ipsilateral palatal paralysis: Vagus nerve involved 8. Distant metastasis Bone, lungs & liver

11. Investigations 1. Nasopharyngoscopy and Diagnostic Nasal Endoscopy – –Mass seen in nasopharynx at fossa of Rosenmüller 2. Nasopharyngeal tumor biopsy: blind /under vision 3. F.N.A.C. of neck node 4. C.T. scan head and neck : Tumor extent, skull base erosion, Cervical lymph node metastasis

12. 5. M.R.I. head & neck: for intracranial extension 6. Tests for metastases − −C.T. chest and abdomen, bone scan, P.E.T. scan, liver function tests 7. Serologic tests – –Immuno-fluorescence for IgA antibodies to Viral Capsid Antigen, Ig G antibodies to Early Antigen

13. Diagnostic Nasal Endoscopy Gross – –Proliferative – –Ulcerative – –Infiltrative

14. Computerized Tomogram Scan

15. Magnetic Resonance Imaging

16. Endoscopic Biopsy

17. Whole body bone scan

18. Positron Emission Tomography

19. T.N.M. staging T1 : confined to nasopharynx T2 : soft tissue involvement in oropharynx or nasal cavity or Parapharyngeal space T3 : invasion of bony structures or P.N.S. T4 : intracranial, involvement of orbit, cranial nerves, infratemporal fossa, hypopharynx

20. N0 : no evidence of regional lymph node involvement N1 : unilateral N2 : bilateral (above supraclavicular fossa, < 6 cm) N3 : > 6 cm or in supraclavicular fossa M 0 : no evidence of distant metastasis M 1 : distant metastasis present

21. Stage I: T1 N0 M0 Stage II: T2 or N1 M0 Stage III: T3 or N2 M0 Stage IV: T4 or N3 or M1

22. Treatment modalities 1. Teletherapy or External beam radiotherapy 2. Brachytherapy 3. Chemotherapy 4. Surgery 5. Immunotherapy against E.B.V. 6. Vaccination against EBV: experimental

23. External beam irradiation 2 lateral fields: nasopharynx, skull base and upper neck sparing temporal lobe, pituitary and spinal cord 1 anterior field: lower neck; sparing spinal cord & larynx

24. Brachytherapy Treatment of cancer by the insertion of radioactive implants directly into the tissue Treatment of cancer by the insertion of radioactive implants directly into the tissue Used for small tumor, residual or recurrent tumor – –Interstitial: Radioactive source (Radium, Iridium, Iodine, Gold) inserted into tumor tissue – –Intracavitary: Radioactive source placed inside the catheter or moulds & inserted into nasopharynx – –High dose rate (HDR): High intensity radiation delivered with precision under computer guidance

25. Interstitial Brachytherapy

26. Intracavitary Brachytherapy

27. High Dose Rate Brachytherapy

28. Chemotherapy Drugs used − −Cisplatin − −5-Fluorouracil Indications – –Radiation failure – –Palliation in distant metastasis

29. Surgery 1. Nasopharyngectomy, Cryosurgery : for residual or recurrent tumor 2. Radical neck dissection : for radio-resistant neck node metastasis 3. Palliative debulking : for T4 tumors 4. Myringotomy & grommet insertion : for persistent otitis media with effusion

30. Radical neck dissection & Interstitial Brachytherapy

31. Treatment Protocol T1: External Radiotherapy (6500 c Gy) T2: External Radiotherapy (7000 c Gy) T3 / T4: Radiotherapy + Chemotherapy  Brachytherapy / Salvage surgery if required N0: External Radiotherapy (5000 c Gy) N+: External Radiotherapy (6000 c Gy) + Chemotherapy

32. Prognosis W.H.O. Type 2 and 3 carcinomas have good response to radiotherapy and better survival rates Average 5 year survival rates for treated patients Stage I: 95 – 100 % Stage II: 60 – 80 % Stage III: 30 – 60 % Stage IV: 20 – 30 %

33. Follow up protocol for ca nasopharynx Final assessment (2–3 months after the end of treatment) Final assessment (2–3 months after the end of treatment) –Local and regional exam plus nasopharyngeal endoscopy, FDG-PET/CT and/or MRI First two years First two years –Local and regional exam plus nasopharyngeal fibroscopy (every 3 to 4 months) –Chest X-ray, thyroid function test, CT/MRI (yearly) Two to five years Two to five years –Local and regional exam plus nasopharyngeal fibroscopy (every 6 months) –Chest X-ray, thyroid function test, CT/MRI (yearly)