This document discusses cancer of the nasopharynx (NPC). Some key points: - NPC is uncommon globally but more common in certain regions like Southern China. - Risk factors include EBV infection, consumption of salted fish. - Staging involves MRI and biopsy. Treatment depends on stage but often involves chemotherapy and radiation therapy. - Advanced stages may receive neoadjuvant chemo followed by concurrent chemo-radiation. IMRT has improved treatment. - Sequelae can include cranial neuropathy, xerostomia, endocrine issues. Lifelong follow up is needed due to risk of recurrence or second cancers. Outcomes have improved but salvage options after relapse present challenges

1. Cancer Nasopharynx
Dr. Ajay Manickam MS.,DNB.,(ENT)
Fellow, Head and Neck Surgical Oncology
Tata Medical Center , Kolkata

2. Introduction
▪ Uncommon cancer in most parts of world
▪ 84400 new cases and 51,600 deaths annually
▪ Age Adjusted Rate ranges from 0.6 in US to
26.9 in Southern China
▪ Bimodal age distribution(15-25 + 50-59)
▪ Male to female 2-3:1

3. Epidemiology
Nasopharynx : Male - Thirteen north eastern registry
areas had higher AAR, Nagaland PBCR being the
highest . Delhi registry with an AAR of 0.7 stood at
the fourteenth place.
Female - Nine north eastern registry areas had higher
AAR and Nagaland PBCR led the list .
State Males (%) Females(%)
Nagaland 19.3 10.9
Mizoram 2.8 2.3
Sikkim 3.7 NA
Kolkata 0.36 0.2
Proportion among all cancers

4. AAR per 100,000 population

5. Etiology
• Distinct racial and geographical distribution
• Multifactorial cause
Genetic factors
– Strong association with HLA Class 1 genes

6. Etiology
Environmental factor
– High consumption of salted fish – Dimethyl
nitrosamine
• Formaldehyde
• Tobacco smoking
• Wood dust

7. • Epstein Barr Virus (EBV)
– Particularly non-keratinising type

8. Anatomy

9. Natural History

10. Local Spread
Nasal cavity & PNS
Orbital invasion
Base of Skull, Clivus
Sphenoid sinus
Cavernous Sinus
Lateral Parapharyngeal space
Middle ear cavity
Oropharynx (tonsillar pillars)
C1 vertebrae

11. Site Frequency(%)
Adjacent soft tissue
Nasal Cavity
Parapharyngeal space
Pterygoid muscle
Oropharyngeal wall, soft palate
Prevertebral muscle
87
68
48
21
19
Bony erosion/PNS
Clivus
Sphenoid
Pterygoid plate
Petrous bone
Ethmoid
Maxillary antrum
41
38
27
19
6
4
Extensive/Intracranial extn
Cavernous sinus
Infratemporal fossa
Orbit
Cerebrum, meninges, cisterns
Hypopharynx
16
9
4
4
2

12. Lymph metastases
• Vast avalvular lymph capillary
network
• 85 to 90% present with lymph
nodes
• Bilaterality in 50%
• Two lymph collectors – lateral
and posterior

13. Distant metastases
• 3 to 6 % at presentation
• 18 to 50% in the course of disease

14. Clinical presentation
• Neck mass
• Nasopharyngeal mass symptoms(nasal
obstruction, epistaxis, discharge)
• Nerve deficits

15. Workup
• Proper history and clinical examination
– Head and neck examination
– Complete CNS examination
– Mirror examination
• Routine
– Laboratory studies
– Chest Radiograph(PA+lateral)

16. Diagnostic workup
• Biopsy
(direct visualisation/Fiberoptic
endoscopy/exmn anaesthesia)
• FNAC of neck mass
• Absence of visible mass
– Pharyngeal recess(Fossa of
Rosenmuller) on each of the lateral
wall
– Supero posterior wall
• IgG anti-EA and IgA anti-VCA
• Baseline EBV DNA levels

17. • Staging workup
• Locoregional extent – MRI>CT

18. Metastatic workup - if clinically indicated
• PET
• CT Chest and Abdomen
• Bone Scan

19. STAGING SYSTEMS
• AJCC
• UICC
• Ho(1978)
• Fletcher(1967)

20. Ho staging system
T-stage
T1 Confined to nasopharynx
T2 Nasal fossa, oropharynx,
parapharynx, muscle/
nerves below base of
Skull
T3
a. Bone below base of Skull
b. Bone at base of skull
c. Cranial nerve
d. Orbit, infratemporal fossa, laryngopharynx

21. Ho Staging - Lymphnode
N-stage
N0 None
N1 Upper neck
N2 Mid neck
N3 Supraclavicular fossa
Group
I T1N0M0
II T2N0–1M0, T1N1M0
III T3N0-2M0, T1-2N2M0
IV T1-3N3M0
V T1-4N0-3M1

22. AJCC/UICC 2010 7Th
T category
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor confined to the nasopharynx, or tumor extends to nasal cavity and/or oropharynxb without
parapharyngeal extensionc
T2 Tumor with parapharyngeal extension
T3 Tumor involves bony structures of skull base and/or paranasal sinuses
T4 Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with
extension to the infratemporal fossa/masticator space
N category
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Unilateral metastasis in cervical lymph node(s), ≤6 cm in greatest
dimension, above the supraclavicular fossa, and/or unilateral or
bilateral retropharyngeal lymph node(s), ≤6 cm in greatest
dimension
N2 Bilateral metastasis in cervical lymph node(s), ≤6 cm in greatest
dimension, above the supraclavicular fossae,f
N3 Metastasis in lymph node(s)e >6 cm and/or to supraclavicular
fossaf
N3a. >6 cm in dimension
N3b. Extension to the supraclavicular fossaf

23. Pathological classification
WHO 2005
1. Keratinising squamous cell carcinoma

24. 2. Non -
keratinising
squamous cell
carcinoma
a – Differentiated
b - Undifferentiated

25. 3. Basaloid squamous cell carcinoma

26. • Rare histologies
– Lymphoma 5%
– Adenocarcinoma
– Plasmocytoma
– Melanoma
– Sarcoma

27. Prognostic factors
• Locoregional extent of disease
– T stage
– N stage
– Parapharyngeal extension
– Prevertebral space involvement
• GTV-P
• Histology
• Oropharynx involvement, Ethnicity – not
significant

28. Prognostic factors - contd
• Role of EBV - Circulating cell free DNA
– Pre-treatment assay
– Response to treatment
– Follow up(better than FDG PET)
• Other biomarkers associated with poor
prognosis - EGFR, HIF1α, CA IX, VEGF

29. Treatment
• Stage wise management
Radiotherapy alone
• T1N0M0
Concurrent chemoradiotherapy alone
• T1NOMO(Bulky and old T2a)
• T2NOMO

30. Treatment - contd
T2-4 N0-3 M0
• Neoadjuvant chemotherapy 2# + CCRT
• CCRT + adjuvant chemotherapy
• ALSARAF – GAMECHANGER + DRAWBACK

31. Concurrent chemotherapy
• Cisplatin (30 mg/m2 weekly for 05 to 06
Cycles with RT)
• Cisplatin (100 mg/m2 Day 01, 22 and 43 with
RT )
• Non inferiority trial substituting CDDP with
carboplatin in concurrent(weekly) and
adjuvant setting showed no significant
difference

32. Induction/Sequential chemotherapy
Regime (i)
TIP Protocol:Paclitaxel ( 175 mg/m2 Day 01),Cisplatin (20 mg/m2 Day 01 to
Day 05),Ifosfamide (1200 mg/m2 Day 01 to Day 05 ) and Mesna ( 400
mg/m2 at 0, 4, 8 hrs Day 01 to Day 05) X 2 Cycles
Regime (ii)
DCF Protocol:Docetaxel (75 mg/m2 Day 01), Cisplatin (75 mg/m2 Day 01 )
and 5-FU ( 750 mg/m2 /day continuous IV infusion through PICC Day 01 to
Day 05 Total dose in 5 days 3750 mg/m2) X 2 Cycles
Regime (iii)
Cisplatin(33mg / m2 / day x 3 days) + Ifosfamide (2gm/m2 / day x 3
days) + Mesna rescue X 2 Cycles
Regime (iv)
Cisplatin(100 mg/m2 day 01 and 5 FU 1000 mg/m2/day continuous IV
infusion through PICC Day 01 to Day 05) X 2 cycles
Adjuvant Chemotherapy: Cisplatin (100 mg/m2 day 01 and 5 FU 1000
mg/m2/day continuous IV infusion through PICC Day 01 to Day 05) X 3
cycles

33. Metastatic NPC
▪ Platinum based combination chemotherapy
▪ RT to metastatic sites if clinically indicated
– Cisplatin/carboplatin + Taxane
– Cisplatin + 5FU
– Carboplatin + cetuximab
– Cisplatin + gemcitabine
– Gemcitabine + Vinorelbine
▪ If CR after chemotherapy, patient should be
considered for RT/CRT to npx and neck

34. RT dose and fractionation
▪ Conventional fractionation
70 Gy given over 7 weeks
2 Gy# Mon-Fri
▪ High risk subclinical disease – 60 Gy
▪ Elective sites – 50 Gy

35. Conventional technique
SHRINKING FIELD TECHNIQUE
3 phases
Phase I
• RT to the primary tumor
and upper neck nodes in
one volume – 2 lateral
fields
• Lower neck by single AP
field
• Continued upto 40- 44Gy

36. Phase II
• RT to the primary by 2 lateral
fields
• Or by 2 lateral fields and a
matching anterior field

37. Phase III
• Boost to the gross disease

38. 3DCRT
3DCRT
• Better LC and OS
Jen et al
• T4 control (86% vs 47%)
• Xerostomia (69.2% vs 98%)
• No significant improvement in late toxicities

39. IMRT
• Supplanted conventional technique
Typical plans
• 70 Gy to Gross disease
• 59.4 Gy to high risk subclinical disease
• 54 Gy to low risk
• TMC – 66 Gy in 30 #
• <42 days - Tumour Repopulation

40. IMRT - contd
• Acceleration using dose painting/ SMART
• Boost for persistent disease
• Recurrent disease

41. TREATMENT PLANNING - TMC

42. Sequelae to RT
Temporal lobe necrosis
• Late complication
• Classical symptoms - hallucinations, absence
attacks, déjà vu
• Other symptoms – headache, confusion,
convulsions, hemipareisis
• Accounts for up to 65% of radiation related
deaths
• 1-3% with conventional RT
• 12% with hypofractionated IMRT

43. Sequelae - contd
Cranial neuropathy
• Nerves IX to XII
• Slurring of speech, dysphagia, twitching of
neck muscles
• Radiation induced fibrsosis
• Parapharyngeal boost
• Rarely nerve VI, V also

44. Sequelae - contd
Xerostomia
• Accompanied by dental sequelae
• Lower rates with IMRT
Aural toxicity
• Cisplatin based chemotherpay
• SNHL with mean cohclear dose > 48 Gy
• Pharyngotympanic tube damage

45. Sequelae - contd
Endocrine dysfunction
• Hyperprolactinemia
• Hypothyroidism
• Hypoadrenalism
Second malignancy
• Maxillary osteosarcoma and soft tissue
sarcoma
• Surgery – only chance of cure

46. Follow up
History and physical examination
– 1 to 3 months the first year after treatment
– 2 to 6 months the second year
– 4 to 8 months 3 to 5 years
– Every year thereafter
With
✓ Imaging every 6 months
✓ Thyroid function testing every 6 to 12 months
✓ Speech and swallowing evaluation.
✓ Post treatment plasma EBV DNA surveillance if
facilities available

47. • Cranial nerve palsies 6 months post Rx
– The complete recovery rate was 51%
– Partial recovery rate was 19%
– Worst for 7, 12th CN
– Best for 2, 9, 11th CN

48. • Patient usually assessed after 6 weeks
• Residual disease after 8 weeks – persistent
• Persistent disease – boost
– Brachytherapy
– IMRT
– SRT
– EBRT

49. • Persistent nodal disease
– Electron boost
– Neck dissection

50. Results of treatment
• 5 yr local control rate with conventional
radiation
T1 – 76 to 90% N0 – 82 to 100%
T2 – 75 to 85% N1 – 70 to 92%
T3 – 60 to 70% N2 – 42 to 70%
T4 – 40 to 60% N3 – 32 to 52%
• 5 yr distant metastases rates – 10, 20, 30, 50% for
T1,2,3,4 respectively

51. Salvage irradiation
• Local relapse at a median period of 3 years
post RT
• Reirradiation requires atleast 60 Gy
– 2D EBRT ± brachytherapy boost/3DCRT boost
– IMRT
• Late toxicities were high
• Local control better with SRS>IMRT>EBRT+BT

52. Role of brachytherapy
• Intracavitary or interstitial implants
Rotterdam applicator

53. Role of brachytherapy
▪ Routine boost to the primary site in T1-3
lesions after EBRT
– Earlier studies – showed benefit
– Boost post CCRT showed no improvement in local
control
▪ Residual disease
▪ Recurrrent disease

54. Role of SRT
▪ SRT boost 7 to 12 Gy foll 66 Gy by EBRT
- Excellent LC of 98% included T1-4
▪ Persistent disease
▪ Recurrent disease
▪ Increased rates of distant failure
▪ Temporal lobe necrosis
▪ Retinopathy

55. Conclusion
• Management of NPC is of significant
importance in NE India due to high incidence
• Being a systemic disease requires concurrent
chemoradiation along with systemic
chemotherapy either as induction/adjuvant
• EBV associated and could be used for
diagnosis/followup
• Future trends employ EBV association to
develop immunotherapy, adoptive therapy,
epigenetic therapy, vaccines leading to a
better understanding of the disease

56. - Thank you
MANAGEMENT OF NASOPHARYNGEAL CANCER