Patients with histologically confirmed previously untreated NPC are be recruited to join tis
study. The study has obtained approval from local institutional review board.
After written informed consent, baseline investigations including blood tests for routine
hematology, biochemistry and plasma EBV DNA will be taken. Only 3ml of EDTA blood will be
taken for plasma EBV DNA and other potential biomarkers. They will also undergo baseline
imaging investigations including positron-emission tomography with integrated computed
tomography (PET-CT) and magnetic resonance imaging (MRI) of the head and neck regions. An
routine nasoendoscopy and nasopharyngeal biopsies will be obtained to confirm and delineate
the mucosal extent of the disease.
If confirmed non-metastatic, patients will be treated with IMRT using 7-9 radiation beams. A
total dose of 70Gy in 33-35 fractions over 6.5 to 7 weeks will be given. For advanced stage
III to IVB diseases, concurrent chemoradiation using cisplatin 100mg/m2 on Day 1, 22 and 43
of IMRT followed by 3 cycles of adjuvant chemotherapy with cisplatin 80mg/m2 on Day 1 and
5-FU 1000mg/m2 from Day 1 to Day 4 every 4 weeks for 3 more cycles starting 4 weeks after
completion of IMRT will also be given. Some patients will also receive induction chemotherapy
with either (1) cisplatin 100mg/m2 on Day 1 and 5-FU 1000mg/m2 on Day 1 to 5, or cisplatin
100mg/m2 on Day 1 and gemcitabine 1000mg/m2 on Day 1 and Day 8, administered every 3 weeks
for 3 cycles before commencement of chemoradiation, at the discretion of treating oncologists
if their primary tumours are close to critical organs e.g. brainstem, optic chiasm or optic
nerves.
After treatment patients will undergo nasopharyngeal biopsies, patients will undergo
nasopharyngeal biopsies again at 8 weeks after completion of IMRT to confirm histological
complete local remission. Blood will be taken again on the same day for plasma EBV DNA and
other potential biomarkers. Additional biopsies and salvage local treatment e.g.
brachytherapy, stereotactic or IMRT boost will be offered to patients who have persistent
local disease at 12 weeks after completion of IMRT. If complete local remission is confirmed,
patient will have regular follow up every 3 to 4 months for surveillance and survival
outcomes. Regular imaging with MRI and CT scans every 3 to 4 months will also be arranged as
well. Plasma EBV DNA will be measured again at 6 months and 1 year after completion of IMRT
and then as clinically indicated afterwards.
For those with metastatic diseases at diagnosis, systemic chemotherapy (platinum-based
chemotherapy with cisplatin and gemcitabine) will be offered. Blood taking for plasma EBV DNA
and other potential biomarkers at baseline before chemotherapy commencement and then after
every 3 cycles will be arranged. Plasma EBV DNA measurement and imaging examinations with CT
and MRI scans will be arranged at baseline and then after 3-4 cycles of chemotherapy for
tumour response evaluation. If the disease does not show progression according to RECIST 1.1,
patients will receive up to 6 cycles of chemotherapy followed by consolidation IMRT to the
nasopharynx and the neck with 60-70Gy in 33-35 fractions over 6-7 weeks. Additional
stereotactic body radiation therapy (SBRT) will be offered to patients who have
oligo-progression/oligo-metastasis (up to 3 lesions). Patients will have regular follow up
every 3-4 months afterwards. Further salvage palliative chemotherapy or radiation therapy or
best supportive care depending on the patients' wish and performance status will be offered
to those who develop further relapse after first-line chemotherapy and/or consolidation IMRT.
The trend of baseline and serial plasma EBV DNA and other potential biomarkers will be
monitored prospectively.
