nasopharyngeal carcinoma short presentation

1. Nasopharyngeal carcinoma
Dr sreelesh
Rcc Trivandrum
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2. Introduction
• Nasopharyngeal carcinoma is the predominant tumour type arising in the
nasopharynx.(85%)
• Less common
• Lymphoma ~10 %
• Plasmacytoma
• Rare types
– Sarcoma
– Melanoma
– Minor salivary gland tumours
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3. Unique nature Ca Nasopharynx
• Etiology
• Geographic distribution
• Pathology
• Staging
• Distant metastasis
• Treatment & Prognosis
• Recurrence
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4. Anatomy
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5. Lateral wall
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7. EPIDEMIOLOGY
World wide
• ~80,000 new cases/year
• 50,000 deaths/year.
• Regional differences
– Endemic in southern China, Hong Kong
– Rare in west
– Intermediate in middle east.
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8. Incidence
• Increases after 20 years and decreases after 60 years
• M:F 3:1
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9. ETIOLOGY
• Multifactorial
Endemic
Viral
DietGenetic
Non-
endemic
Tobacco
Alcohol
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10. Viral etiology
• Epstein-Barr virus
– Normal nasopharyngeal epithelia lack EBV
– EBV DNA and EBV gene were found in precursor lesions and tumour cells.
– Expression EBV latent proteins, including EBNA-1 and LMP-1 and LMP-2
– Patients also demonstrate specific serologic responses to various gene
products of EBV (Ig A against EBV VCA)
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11. • Human papilloma virus
• HPV was detected in a small subset of carcinomas
• Considered extension of oropharyngal lesions
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13. Diet
• The cooking of salt-cured food
• volatile nitrosamines.
• Early childhood exposure to salted fish
• High consumption of preserved or fermented foods
• Nitrosamines
• bacterial mutagens
• direct genotoxins
• EBV-reactivating substances.
• The use of Chinese medicinal herbs
• The consumption of rancid butter and sheep's fat
• butyric acid, a potential EBV activator
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14. Heredity
• Increased incidence in families
• NPC has been associated with certain HLA haplotypes.
• Associated with genetic polymorphisms, such as CYP2A6
• nitrosamine metabolizing gene.
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15. Molecular pathogenesis
• Copy number losses on chromosomes 1p, 3p, 9p, 9q, 11q, 13q, 14q and
16q and recurrent gains on chromosome 1q, 3q, 8q, 12p and 12q.
• TP53 and RB1,
• p16
• RASSF1A
• CCND1
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16. CLINICAL PRESENTATION
• Most common site of origin is fossa of Rosenmuller.
• Patients may remain asymptomatic for a prolonged period.
• Most presents with locally advanced disease.
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17. Pattern of spread
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19. Painless neck mass 30-70 % /nodal metastasis
Hearing loss or ear drainage 25 % /ET tube involvement
Nasal bleeding or obstruction Nasal cavity
Cranial nerve deficit
VI and V 2(V2 most commonly)
facial pain
Cavernous sinus involvement
headaches Intracranial extension
Trismus pterygoid muscle invasion
Proptosis Orbit
neck discomfort. Retropharyngeal node involvement
9,10 ,11 CN Para pharyngeal space involvement
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20. Metastatic potential
• Most common site
• Cervical nodes
• Up to 90 %
• Bilateral in 50 % cases.
• DM at diagnosis in 5 to 11 %
Distant metastasis
• The location and extent of cervical lymph node mets predict DM
• Bone (75 percent), lung, liver, and distant nodes.
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22. Multiple paraneoplastic syndromes
• Neutrophilia
• Fever of unknown origin
• Hypertrophic osteoarthropathy
• Dermatomyositis
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23. Histology
WHO classification of carcinoma of Nasopharynx
• Type I – Keratinizing squamous cell carcinoma
• Type II – Non keratinizing carcinoma type
Differentiated carcinoma (type 2.1)
Undifferentiated carcinoma (type 2.2)
• Type III – basaloid squamous cell carcinoma
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24. DIAGNOSTIC EVALUATION
• Clinical evaluation of the size and location of cervical lymph nodes
• Indirect nasopharyngoscopy to assess the primary tumor.
• Neurological examination of cranial nerves.
• Confirmation by biopsy of the primary or metastatic node.
• CT/MRI of base of skull to root of neck
• Chest X ray
• Blood counts,RFT,LFT
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25. • Bone scan
– Clinical symptoms
– Biochemical evidence
– N2/N3 nodal disease
• EBV viral capsid antigen and EBV DNA
• PET-CT if available (N3 nodes )
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26. CT or MRI
• MRI preferred over CT
• Better Identification
– Tumor invasion into soft tissue
– Pharyngobasilar fascia obliteration
– Invasion into the sinus of Morgagni
– Skull base invasion
– Lymph node metastases in the carotid and retropharyngeal spaces
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27. EPSTEIN-BARR VIRUS TESTING
• Pre-treatment levels for its prognostic contribution.
• Non-invasive screening
– The combination of IgA VCA and plasma EBV DNA
– Southern china
– Elevated titer may precede NPC many years
• To predict risk of relapse
• Monitoring for disease recurrence
• Alternative to histopathologic diagnosis of nasopharyngeal carcinoma
• EBV-specific antibody-based assays
• Plasma EBV DNA levels
• BARF1 oncogene mRNA detection from nasopharyngeal brushings
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28. STAGING
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38. Prognostic factors
• T stage
• N stage
• Pretreatment EBV levels
• Post treatment EBV levels
• Young females –better
• EGF receptor expression-poor prognosis
• Treatment related factros
• Refinement In RT
• Chemotherapy
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39. Treatment
• Better RT technique
• Better chemotherapy
• Monitoring
• Improvement in Imaging
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40. • Radiotherapy
• Chemotherapy
• Surgery
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41. • Role of surgery
• Not indicated as a primary treatment
• To obtain biopsy
• Neck dissection
– Residual neck nodes following RT
– Isolated neck recurrence
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42. Radiotherapy
• Megavoltage RT is the standard treatment
Rx of choice due to:
1. Early bilateral LN mets
2. Involvement of retropharyngeal node of Rouvier which cannot be
surgically removed
3. Deep seated location and proximity to vital structures
4. Highly radiosensitive nature
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43. Dose of RT
• Primary should receive 70Gy/35# over 7 weeks.
• Involved nodes should receive 66-70Gy/33-35# over 6 to 7 weeks
• Uninvolved nodes receive 50Gy/25# over 5 weeks
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44. Dose alternation ??
• Dose less than 60 Gy : Less local control
• No role of dose escalation with brachy or SRS boost >70 Gy
• Dose > 80 Gy : Temporal lobe necrosis
: Torrential epistaxis
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45. Time and Fractionation
• Prolongation of treatment significantly jeopardizes local control
• Hyper fractionation : no improvement in LC
significant toxicities.
• Dose >2 Gy is associated with TLN
1.8-2 Gy # is the recommended dose
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46. Radiation Technique
Until 1990
• 2D –CRT
• High toxicities
• Higher chance of LR
• Permanent parotid damage
• Worse for locally advanced disease
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47. IMRT
• Advanced form of 3-D RT
• Improve dose conformity
• Better protection of the adjacent organs
• Better local control for locally advanced disease.
• Lower incidence of xerostomia
• pre-serves middle ear function
• Better quality of life
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48. Disadvantages
• Cost
• Marginal miss
• Expertise
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49. • 2003 -2008
• 616 patients
• non-metastatic
• stage I to IVb NPC
• 2D-CRT vs. IMRT
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50. Results
IMRT 2D-RT
5 year local control rate 90.5 84.7
T3 91% 80%
T4 81.5% 62.2%
nodal relapse-free
survival
92.4% 92.9%
5-year overall survival 79.6% 67.1%
Toxicities Less More
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51. Role of Chemotherapy
• Induction
• Concurrent
• Adjuvant
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52. Induction
Theoretical advantages
• Will be better tolerated
• Eradicating micro metastases early.
• Shrinking of the primary tumour to give a wider margin for irradiation
• Better DFS no OS benefit
• NCCN considers induction chemotherapy as cat 3 recommendation
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53. NACT
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54. Concurrent
• Most studied
• More EFS and OS
• Sensitize tumour to the effects of RT
• Better LC rates compared to RT alone
• Improvement in distant failure-free rate
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56. U.S. Intergroup 0099
CRT RT
3 year PFS 69% 24%
3 year OS 78% 47%
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57. U.S. Intergroup 0099
• Issues
– Flawed study design
• Are the benefits from chemo due to concurrent administration,
adjuvant, or both?
– Terminated early after interim analysis showed survival benefit
– RT alone arm performed worse than expected
– Old RT techniques
– Many patients enrolled had WHO type I NPC (not EBV-associated)
– Adjuvant PF chemotherapy only feasible in some patients
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59. Adjuvant chemotherapy
• Intergroup Study 0099 trial
• Cisplatin +5 FU for 3 cycles
• Indicated in
• Patients in good PS
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60. Chinese phase III trial
• 508 patients
• Nonmetastatic advanced NPC
• Adjuvant chemo no advantage
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61. Meta-analysis in NPC
• 8 trials, 1753 pts
 6% absolute survival benefit at 5 years
 Greatest benefit from concurrent chemo
HR=0.60 (concurrent)
HR=0.97 (adjuvant)
HR=0.99 (induction)
Baujat, IJROBP, 20068/15/2015 61

62. Chemoradiation-metaanalysis
• Induction chemo Radiotherapy ? DFS
• Radiotherapy Adjuvant chemo (NS)
• Concurrent ChemoRT (OS,DFS,DM)
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63. Metastatic disease at presentation
• 5- 10 % cases
• Bone Mets –poor prognosis
Favorable group
• Chemo with (CDDP+5FU ) X 2-3 cycles reassess CR CRT
• Otherwise palliation
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64. Treatment
• T1 N0 M0
» RT alone
• T2,T3,T4 or N+,M0
» ChemoRT
» Cisplatin based 3 weekly
• Metastatic
» Platinum based combination CR radical RT
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66. POSTTREATMENT FOLLOW-UP
Documentation of remission
• Clinical
• Endoscopic
• Imaging
3 months
• MRI scan of the skull base and neck
• CT head &neck
• PET-CT
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67. Follow up
• 3 monthly follow up for 2 years
• 4-6 monthly for 3-5 years
• Annually after 5 years
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68. Management of relapse
• Local relapse
– Brach therapy with Au 198 (small lesions)
– Salvage surgery
• No intracranial extension
• No bone erosion
• Nodal relapse
– Salvage neck dissection
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69. Thank you
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