Nasopharyngeal Carcinoma

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Nasopharyngeal Carcinoma

• Peter Ross SpR (LAT)
• East of Scotland
• Perth, November 2005

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Topics

• Role of viral titres in nasopharyngeal cancer
  diagnosis/monitoring
• Treatment strategies for nasopharyngeal carcinoma

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Introduction

• NPC differs from other H N cancer
• Epidemiology
• Pathology
• Diagnostic approach
• Treatment
• Outcome

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Introduction

• NPC differs from other H N cancer
• Epidemiology
• Rare in Europe and North America
• Endemic in the Far East
• Pathology
• Diagnostic approach
• Treatment
• Outcome

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Introduction

• NPC differs from other H N cancer
• Epidemiology
• Pathology
• 3 histological types (W.H.O.)
• Type I Keratinizing SCC
• Type II Nonkeratinizing Differentiated
  Carcinoma
• Type III Nonkeratinizing Undifferentiated
  Carcinoma
• Proven role of EBV (1966) /- HPC
• Diagnostic approach
• Treatment Outcome

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Role Of EBV

• Latent Infection
• Occurs in early life
• Definite role in types II III
• Full EBV genome present in all NPC epithelial
  cells
• Variable role in type I
• Associated in endemic regions, but not others
• Tobacco, Alcohol HPV implicated

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Serological Markers

• EBV in epithelial and B Lymphocyte cells
• Humoral immune response
• multiple anti-EBV serology, includes
• IgG IgA against VCA EA
• Anti-EBNA IgG
• Antibodies against EBV replicator protein ZEBRA
• Circulating EBV DNA (by PCR)
• Oncogenes under investigation

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What is the role of EBV Titres

• Potential uses of
• VCA, EA EBV DNA
• Diagnosis
• VCA EA
• Diagnosis Monitoring
• EBV DNA

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Detection Of NPC

• No one titre suitable
• Variable methods of measuring
• Great variations in results
• However combining 2 titres has had promising
  results

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Detection rate of circulating EBV VCA in NPC
patients and healthy control subjects among
different studies
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Detection rate of circulating EBV EA in NPC
patients and healthy control subjects among
different studies
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Predictive value of EBV serology combinations Low
et al (2000)
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Detection rate of circulating EBV DNA in NPC
patients and healthy control subjects among
different studies
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Predictive value of EBV serology combinations
Leung SF (2004)
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Diagnosis - Summary

• Serology can provide an adjuvant test in the
  diagnosis of NPC
• More than one titre is required
• Biopsy viral detection in biopsy is still the
  gold standard
• There is insufficient evidence for serological
  diagnosis or screening alone

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Indication of Prognosis

• Lo et al Lin et al
• EBV DNA at time of diagnosis
• High DNA levels at diagnosis -
• A poor prognostic indicator,
• Even more so than current staging systems.

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Post Diagnosis Monitoring

• Response To Treatment
• Lo et al, Ngan et al, Hsiao et al Shotelerusk
  et al
• Serial DNA measurements
• Drop in DNA levels after radiotherapy
• Once in remission, those in remission maintained
  low or undetectable levels of EBV DNA.
• Recurrence or distant metastases led to an
  increase in DNA levels.
• Levels at time of diagnosis of recurrence were
  comparable to pre-treatment levels

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Treatment strategies for nasopharyngeal carcinoma

• Radiotherapy
• Historical standard treatment for NPC, inc Neck
• Difficult to protect dose-limiting organs such as
  brain, spinal cord etc
• Improvement in complications since 3D Conformal
  (3DCRT) or Intensity-modulated RT (IMRT)
• Shown to be better than surgery for controlling
  primary neck disease
• Surgery used for radioresistant disease

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5 Year survival after radiation alone for Early
(Stage I-II)(UICC/AJCC 1997)
(Av 86)
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5 Year survival after radiation alone for
Advanced (stage III-IV)
(Average 55)
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Chemo-Radiotherapy

• Locally advanced disease (stage III and IV)
• local recurrence systemic spread are
  significant problems.
• Chemotherapy has been used with radiation in an
  attempt to achieve better local and systemic
  control
• 10 phase III RCTs in advanced disease
• RT vs- CT-RT
• Little evidence for early stage disease

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RCTs using chemotherapy in combination with
radiotherapy in the treatment on advanced staged
NPC
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RCTs using chemotherapy in combination with
radiotherapy in the treatment on advanced staged
NPC
( Av RT 56, CT-RT 66)
From Al-Sarraf M Cancer Control 9387, 2002.
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Combination Chemotherapy

• Meta-analysis of six of the randomized trials
  (Huncharek et al 2003)
• gt 1500 patients
• Comparing combination CT_RT with RT
• Progression-free survival increased 34
• Overall survival increased by 21, at 4 years for
  the chemotherapy arm
• Further studies ongoing

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Recurrent Disease

• Radical external beam radiation,
• Brachytherapy,
• Surgical resection.
• Chemotherapy
• Combinations of the above
• Whole new debate!

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Average Survival 29.8 (not adjusted for patient
numbers)
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(No Transcript)
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Treatment Summary

• Because the results of radiation alone in stages
  I and II are good, radiotherapy continues to be
  the mainstay of treatment for early stage NPC
• Combined Chemotherapy provides improved survival
  in advanced disease, however timing still remains
  unclear.

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Treatment Summary

• The treatment for recurrent disease should be
  tailored to the patient
• Surgery, radiotherapy, brachytherapy and
  chemotherapy can be used
• Immunotherapy Gene therapy may in the future
  also assist in treatment

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• Thank you
• Any Questions?