Nasopharyngeal carcinoma management

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