Nasopharyngeal Carcinoma: Prospects of Chemo radiation and Changing Trends in Epidemiology
Pradip Kumar Tiwari1* and Nabajyoti Saikia2
1Department of Otolaryngology and Head and Neck Surgery, Assam Medical College, India
2Department of Otolaryngology and Head and Neck Surgery, India
Submission: April 06, 2017; Published: July 27, 2017
*Corresponding author: Pradip Kumar Tiwari, Resident, Department of Otolaryngology and Head and Neck Surgery, Assam Medical College, Dibrugarh, Assam, India, Tel:+91 9864988808/ +91 9435238702; Email: firstname.lastname@example.org
How to cite this article: Pradip K T, Nasopharyngeal Carcinoma: Prospects of Chemo radiation and Changing Trends in Epidemiology. Early Intervention of Cleft Lip and Palate: Current Issues Practices and Protocol. J Head Neck Spine Surg. 2017; 1(2): 555559.
Aim: Study the changing trend basically in the Upper - Assam region of India and its prospects.
Case setting and design: Retrospective study of patients presenting with Nasopharyngeal Carcinoma between the study period of one and a half year (Jan 2014 – Jun 2015) in the, Department of Otolaryngology and Head and Neck Surgery, Assam Medical College, Dibrugarh, Assam, India.
Materials and methods: Fourteen patients were treated in the study period. Different approaches were used.
Results: Nasopharyngeal carcinoma is not confined to any specific ethnic community or age, however bimodal peak was again proved and concurrent chemo-radiation therapy was better than other treatment modalities.
Conclusion: Bimodal peak occurrence of the disease should be emphasized and chemo radiation should be the treatment of choice.
Nasopharyngeal carcinoma is a rare disease all over the world. It has often been less evaluated, misdiagnosed, partially treated, most commonly recurred and prognostically poor carcinoma. It has a bimodal peak with occurrence in the late second decades and in the fifth decades. Presently the incidence of nasopharyngeal carcinoma is low in most parts of the world. The rates are twice as high in males as in females . There has been higher incidence of disease in certain parts of the world mainly south East Asia and southern China. Highest incidence has been reported among people of Guangdong province and Guangxi region of China where the incidence is around 50 or more per 100000 people per year . There has been an increase in the incidence in the upper- Assam region of India. There has been an upsurge in the number of cases reporting to our department, Department of Otolaryngology and Head and Neck Surgery, Assam Medical College, Dibrugarh, Assam, India. Since the department caters to the need of most of the people residing in the Upper - Assam region of India, it can be well said that a changing trend has been seen in the incidence of the disease in recent times. Most of patients present with mass in the neck, nasal obstruction, hearing disorders, bleeding
from nose. The most common presenting symptoms are severe, recurrent epistaxis with persistent nasal obstruction. As the disease progresses, facial pain and deformities, and cranial nerve palsies may occur. The diagnosis of nasopharyngeal carcinoma is essentially based on a careful history and nasal endoscopic examination, supplemented by imaging studies using computed tomogram (CT) and Magnetic Resonance Imaging (MRI). Aspiration cytology to establish histological diagnosis can be carried out. An increase in the reporting of cases was seen during the last year. Although the disease is more in southern Asia it has less relation with ethnicity rather than food habits and environmental set-up. The Naga people with an incidence of 4.3per 100000 people in the upper-Assam and nearby region has been the main concern of the various studies . However other communities having the same cultural practices are now having a rise in the incidence of the disease. This is mainly due to the increase in the populated households and ill-ventilated houses, practicing of salted food- habits and the risk of EBV which is still in research. The present treatment is primarily radiation therapy followed by chemotherapy with cisplatin and other chemotherapy groups mainly docetaxel and 5FU.
The study is a retrospective study. The main objective being to
highlight the changing trend in the epidemiology, pathogenesis,
diagnosis, medical management. Although the study period is
short but it is important and a note should be taken about the
actual scenario that is trending. In a span of one and a half year
(Jan 14’- Jun 15’) there has been alarming reporting of fourteen
cases. Out of fourteen patients two were of age group 16- 19
years and others were of age group 40-75 years.
Out of 585 diagnosed cases of head and neck neoplasms 14
cases were of nasopharyngeal carcinoma. It was a study of 14
patients in a period of one and a half year. There was a bimodal
peak of occurrence mainly 2nd and 5th decades.
Region wise distribution:
Dibrugarh- 6 no’s of cases, 1 Female and 5 Males (6 Hindu ) (Gupta, Lachoom, Sawasi, Madrasi, Kalita, Priya).
Tinsukia-3 no’s of cases, 2 Females and 1 Male (2 Hindu and1Muslim) (Sharma, Shah and Hussain).
Sivasagar-2 no’s of cases, 1 Female and 1 Male (2 Hindu) (Gogoi and Mohan).
Golaghat -1 no. of cases, 1 Male (1 Hindu) (Sahani).
Dhemaji -1 no. of cases, 1 Male (1 Muslim) (Raja).
Jorhat -1 no. of cases, 1 Male (1 Muslim) (Hussain).
4.1.2. Environment: All the above mentioned districts are
generally same as far as environment is concerned and all have
a specific period of dry, hot and dusty weather during similar
period of a year. Communities having the same cultural practices
are now having a rise in the incidence of the disease. This is
mainly due to the increase in the populated households and illventilated
houses and practicing of salted food- habits.
Nasopharyngeal carcinoma is the most common malignant
tumour of the nasopharynx. Microscopically, it is of three types
Keratinising squamous cell carcinoma.
Non-keratinising differentiated carcinoma.
Non-keratinising undifferentiated carcinoma.
Many nasopharyngeal carcinoma also contain lots of
immune system cells, especially lymphocytes. The nonkeratinising
undifferentiated carcinoma may contain many
lymphocytes among the cancer cells and hence also known
as lymphoepithelioma. It may be due to body’s own immune
mechanism. There is generally no change in the treatment
protocol for the different types of carcinoma however the stage
is more important than its type for predicting the prognosis.
All the cases were diagnosed first by diagnostic nasal
endoscopies and then by radiological investigations mainly
CT and MRI. In Figure 1-4 we can see that an ill defined soft
tissue density growth showing heterogenous post-contrast
enhancement is noted in the posterior nasopharynx involving
the torus tubaris, fossa of Rosenmuller, prevertebral muscles.
Superiorly the lesion is eroding the posterior aspect of left
greater wing of sphenoid, left clinoid process, left petrous
apex and infiltrating into the left cavernous sinus. Laterally
the lesion is involving the pterygoid muscles and infiltrating
into left infratemporal fossa and causing widening of the left
stylomandibular foramen. Left cavernous sinus is bulky and
heterogeneously enhancing. Decreased pneumatisation and
increased sclerosis of left mastoid air cells is noted. Collection is
noted in left mastoid air cells and left middle ear cavity. Routine
blood examinations and other systemic laboratory examinations for the chemotherapy and radiotherapy were also performed
in every case. In Figure 5 & 6 we can see histopathologically
that the malignant cells are arranged in small groups and
syncytial sheets. Large numbers of lymphocytes and eosinophils
leukocytes are also present. Large an a plastic epithelial cells
with a considerable amount of cytoplasm and large vesicular
nuclei in which there are one or more very prominent central
nucleoli can be seen. Some of the tumor cells are binucleated.
All the cases were treated by chemo-radiation primarily
radiation in 8 cases followed by chemotherapy and chemotherapy
first followed by radiation in other 6 cases. Cisplatin based
chemotherapy in a dose of 100mg/m2 IV in 1 hour and Docetaxel
in a dose of 100mg/m2 IV in 1 hour on day 1 followed by Cisplatin
chemotherapy in a dose of 100mg/m2 IV in 1 hour on day 2 was
given. Radiation in a dose of 66Gy -72Gy on weekdays for six
weeks was given. Only one patient was treated by surgery and
post-operative radiotherapy was used.
Evaluation of the treatment outcome was done at the end
of the induction chemotherapy and then after 6 weeks for
concurrent chemo radiation. Complete tumor disappearance by
shrinkage as investigated by CT scan was defined as complete
response and tumour shrinkage by 50% or more but less than
complete was taken as partial response. Patients were followed
up clinically at 6 weeks after completion of treatment, then at 3
Radiation alone arm 1: External-beam RT (ERT) was
administered according to the techniques described. The
nasopharynx, adjacent muscles and bones were treated to 66Gy
in 33 fractions-2Gy per fraction, 5 days a week, in bilateral fields
(two lateral faciocervical fields). The total duration of treatment
lasted upto 6 weeks.
Concurrent Chemo radiotherapy arm-2: Patients randomized
to the chemotherapy-radiotherapy arm were planned to receive
Cisplatin 50mg infusion over 2 hours on a weekly basis during
external radiotherapy, starting on the first day of radiotherapy.
The complete blood picture was checked weekly before
Evaluation: Tumor response was evaluated at the end of
Induction Chemotherapy with a CT scan of Nasopharynx
(including the retropharyngeal nodes) to assess the primary
tumor, in addition to clinical measurement of neck lymph nodes.
Toxicity was also evaluated. The same evaluation was carried out
again at 6 weeks after completion of Cisplatin-RT as well as RT
Observations and results: (Figure 7) fourteen patients with
locally advanced Nasopharyngeal Carcinoma were included in
this study. Of the 14 patients, 10 were male (71%) and 4 females
(29%), with 7 patients in arm 1 and 7 patients in arm 2. Mean
age was 46 years (18-75 years).
Assessment of Locoregional response to Induction CT
revealed that complete response was seen in 57% of the
patients. Partial response was seen in 43% of patients.
Assessment of Loco regional response to Concurrent CT and
RT revealed that complete response was seen in 64% of the
patients. Partial response was seen in 36% of patients. No case
showed progressive disease. Most common toxicity was anaemia followed by granulocytopenias, mucositis, stomatitis, vomiting
and diarrhea. In two cases pre-existing chronic suppurative otitis
media gave rise to post-auricular fistula formation. Patients of
Arm 2 had higher percentage of toxicities. In Figure 8 we can see
images of patients showing the metastatic tumour and results of
post concurrent chemo radiation.
Nasopharyngeal carcinoma is a malignant tumor with
unique features that make it pathologically, epidemiologically,
and clinically distinct from other head and neck cancers. There
is no clear association with tobacco or alcohol use in most cases
of nasopharyngeal cancer (World Health Organization [WHO]
grades II and III). Patients with nasopharyngeal carcinoma
have a higher incidence of nodal involvement and bilateral
nodal disease at presentation, and overall (80% to 90%) nodal
metastasis, as compared with patients with other malignancies
of the head and neck. In addition, patients with nasopharyngeal
carcinoma have a higher overall incidence of systemic metastasis
than patients with tumors in other head and neck sites . In
some areas of the world, namely, southern China, Southeast
Asia, North Africa, the Middle East, Alaska, and Greenland,
nasopharyngeal cancer is more common. In these areas,
incidence may be as high as 25 to 50 per 100,000 people .
Radiotherapy has been the traditional, standard form of therapy
for all patients with local and loco regional disease. Marcial et
al.  reported complete local clearance of nasopharyngeal
carcinoma in 96% of patients with T1 disease treated with
radiotherapy, 88% of those with T2, 81% of those with T3, and
74% of those with T4. Complete clearance rates in patients with
N1-3 disease who received irradiation ranged from 93% to 71%.
The 5-year survival rate of these patients with nodal involvement
was only 40%; overall 5-year survival rates of patients with all
stages of nasopharyngeal carcinoma treated with radiotherapy,
reported by various investigators from all over the world,
have ranged from 24% to 62% . Qin et al.  reviewed the
survival rates of 1,379 patients with advanced nasopharyngeal
carcinoma treated with radiotherapy. The majority of patients
had either stage III (n =417) or stage IV cancer (n =647). These
investigators reported that the 5, 10-, and 20-year survival rates
of patients with stage III cancers treated with radiotherapy alone
were 46%, 29%, and 17%, respectively. The 5-, 10-, and 20-year
survival rates of stage IV patients treated with irradiation were
29%, 21%, and 8%, respectively. Overall, the 5-year survival
rate of nasopharyngeal carcinoma patients with stage IV disease
treated with radiotherapy alone was less than 30%, regardless
of country of origin or histopathology. Loco regional recurrences
occur in 40% to 80% of patients, and distant recurrences in 15%
to 50% of patients. The usual radiation dose is 65 to 75Gy in
1.8- to 2.0-Gy fractions, 5 days a week. This dose is crucial for
achieving complete loco regional control and 5-year survival .
Nasopharyngeal carcinomas are highly sensitive to
chemotherapy. Single agents identified as being active in this disease include methotrexate, bleomycin (Blenoxane),
doxorubicin, cisplatin (Platinol), carboplatin (Paraplatin),
and, more recently, paclitaxel (Taxol), and to a lesser extent,
fluorouracil (5-FU) and the vinca alkaloids. For patients with
head and neck cancers in general, and especially for those with
nasopharyngeal carcinoma, combination chemotherapeutic
regimens are more active than single drugs, and cisplatinbased
combinations are more active than non cisplatin-based
Many phase II trials of concurrent chemo radiotherapy
in patients with locally advanced nasopharyngeal carcinoma
have been reported [10-20]. Several chemotherapeutic agents,
especially cisplatin [21-23], produce synergistic and/or additive
effects when used with radiotherapy. One possible advantage
of using concomitant cisplatin and radiotherapy in patients
with head and neck cancers, as opposed to other agents, such
as methotrexate, bleomycin, or 5-FU, is the lack of increased
local side effects (especially mucositis). Most investigators gave
standard one-fraction-per-day irradiation. The radiation dose
was the same as without chemotherapy, i.e., >6,400cGy in most
cases. When the results of concomitant chemo radiotherapy were
compared with those of historical matched control patients,
most investigators reported improvements in local control,
disease-free survival, and overall survival with the combined
treatment. In an early study published by the Radiation Therapy
Oncology Group (RTOG), Haythem et al. reported the results
of concomitant treatment with single-agent cisplatin and
radiotherapy in 124 patients with locally advanced, inoperable
or unrespectable stage III (n = 24) or stage IV (n = 100) head
and neck cancers; this study population included 28 patients
with nasopharyngeal cancers, 27 of whom had stage IV disease.
The cisplatin dose was 100mg/m2, given intravenously with
hydration and mannitol diuresis, once every 3 weeks, concurrent
with standard radiation therapy to a total dose of up to 7,380cGy.
Complete response rates were 70% for all patients and 89% for
those with nasopharyngeal cancers [19,20,24].
When the survival of patients with nasopharyngeal cancer
was compared with survival of those with tumors of other
head and neck sites (all were treated with the same chemo
radiotherapy), a significantly higher survival rate was observed
in the nasopharyngeal carcinoma patients. In addition, the
survival of the nasopharyngeal carcinoma patients treated with
concurrent cisplatin and radiotherapy was significantly better
than the survival of historical matched controls treated with the
same dose of radiotherapy alone [19,20,24].
Nasopharyngeal carcinoma although rare, should not be
misdiagnosed as the available treatment is rewarding and there
should not be any predetermined relation of the disease with
any specific ethnic race or community as we have found in our
study that it is associated with different types of ethnic race or
community. There is also no point in waiting for individual line
of treatment and concurrent chemo-radiation is better than any
line of treatment.