This document summarizes a study on nasopharyngeal cancer patients treated between 1995-2000 in Benghazi, Libya. It found that 59% of patients received neoadjuvant chemotherapy and radiotherapy, while 30% received radiotherapy alone. Patients who received chemotherapy had a better mean survival rate (37.8 months vs 16.2 months) and less metastasis. The study concluded that chemotherapy improves survival outcomes for nasopharyngeal cancer patients.

1. Technical Editor
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2. 391Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3
Introduction
The nasopharynx is a cuboidal shape structure located below
the base of skull and behind the nasal cavity communicating
through posterior choanae. Posterior wall is made up of
clivus and the first two cervical vertebrae and continues
with the roof, which is made of basisphenoid, basioccipital
and anterior arch of atlas the soft palate and nasopharynx
lies inferiorly. The eustachian tube opens in the lateral wall.
The foramen lacerum lies with the boundaries of oropharynx
hence it is an important route of spread in middle cranial
fossa. The cranial nerves, second, third, fourth, sixth and
gasserian ganglion are in close relation to it [Figure 1].
Cancer of nasopharynx is uncommon in most countries
of world, but its highest incidence is seen in South China
followed by Kenya and Hong Kong in North Africa in
Maghreb populations of Tunisia and other Mediterranean
countries. Its incidence is 2‑10/100,000 populations/year.
Environmental factors are associated in the etio‑pathogenesis
of cancer nasopharynx; salted fish, smoke from wood ruff,
etc., are some of them. The relationship of Epstein‑Barr
virus (EBV) has been extensively studied by Ho and his
associates.[1,2]
The elevated levels of serum EBV antibody
are present in patients of nasopharyngeal cancers (NPCs)
Henle and Henle.[3]
Recently, Ji et al.[4]
showed after screening for 15 years,
a subset of population with significant elevated EBV
antibodies has period of sustained elevation of 2‑10 years
before the clinical onset of disease.
The NPC is usually seen between the age group of 30 and
60 years and male female ratio is 3:1.[5]
Cancer of nasopharynx presents with unilateral or bilateral
lymphadenopathy in 75% of cases. Nasal obstruction, epistaxis,
headache, diminished hearing, orbital symptoms, change in
voice difficulty in swallowing and cranial nerve involvement
(I, VI, XI and X)[6]
are common symptoms [Figure 2].
The most common site of distant metastases is
bone (48.5%) followed by lung (30.3%) and
liver (29.3%).[7,8]
Gender, age, lymph node involvement
size, number, tumor extent cranial nerve involvement and
ear symptoms were significant factors affecting survival rates
in nasopharyngeal carcinoma.
Materials and Methods
The record files of 1757 patients referred to our department,
Benghazi radiotherapy and Diagnostic Centre between the
years 1995 and 2000 were scanned. A total of 75 patients
of cancer of nasopharynx were found. We excluded
17 patients who were either defaulters or were recurrent or
met static presentations for our survival analysis.
The Kaplan Meier method of Statistical Package for the
Social Sciences version 10.0 was used to analysis the data.
Follow‑up has been poor and we took the data as per the
record files. The record of the ear/nose/throat (ENT) and
Medical Oncology were also scanned for follow‑up.
Results
The age distribution of 59 patients revealed that majority of the
patients were in two age groups either 25‑49 years (31) (52%)
or 50‑60 years (17) (28.8%) patients [Table 1].
The overall male female ratio was 37 males for
22 females (1.7:1) [Table 2]. The neck swelling either
unilateral or bilateral was the presenting complaint in
44/59 (74%) of our patients and it was also the presenting
symptom in them, followed by the nasal symptoms
obstruction or epistaxis 24/59 (40.6%) patients. Headache
was present in 19/59 (32%) patients. The other symptoms
were change in voice, otologic, neurological and orbital are
according to [Table 3].
Most of the patients 44/59 (74.4%) presented with
undifferentiated histology, 10/59 (16.9%) were differentiated
squamous cell carcinoma, 5/59 (7%) had Anaplastic or
poorly differentiated presentation.
Nasopharyngeal cancers: A retrospective comparative
analysis of radiotherapy alone versus chemo‑radiation
(Benghazi experience)
Pakkirmasthan A, Kurakula S1
Departments of Oncology and 1
Gynecology, Specialist, Sekgoma Memorial Hospital, Serowe, Botswana, Africa
Correspondence to: Dr. Sowjanya Kurakula, E‑mail: drksowjanya@gmail.com
Abstract
INTRODUCTION: Cancer of Nasopharynx is an important disease in Maghreb region. 75 patients (4.3%) of cancer nasopharynx between the years
1995 to 2000 were referred to our centre in Benghazi out of total 1757 patients. This study was done to analyze the clinical presentations and
to study response to the treatment practiced. MATERIALS AND METHODS: 59 patients were available with full records excluding the recurrent
and metastatic presentation. 37 were males with 22 females (1.7:1), (31/59) 52% patients were from 25‑49 years, (17/59) 28.8% were from
50‑60 years. 44/59 (74%) patients presented with Lymphadenopathy either unilateral or bilateral. 46/59 (78%) of patients were in clinical stage II or
III. 44/59 (74%) of patients were of undifferentiated histology. RESULTS: The pattern of clinical response and trend of follow up those that received
neoadjuvant chemotherapy and radiotherapy and radiotherapy alone are discussed. DISCUSSION: In our analysis, we also found that the patients
who had received chemotherapy by and large had a less trend to towards developing metastatic disease and local recurrence and faired better.
CONCLUSION: We are now following the protocol of Neoadjuvant chemotherapy followed by chemo‑radiotherapy and followed by chemotherapy
and results will mature in the years to come.
Key Words: Clinical presentation, nasopharyngeal cancers, response
Original
Article
Access this article online
Quick Response Code: Website:
www.indianjcancer.com
DOI:
10.4103/0019-509X.176718
PMID:
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3. Pakkirmasthan and Kurakula: Nasopharyngeal cancer‑ chemoradiation
Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3392
Table 1: The number of patients in various age
groups
Age groups No. patients %
<15 year 1 1.65
15-24 4 6.7
25-49 31 52.5
50-59 12 20.3
60-69 5 8.4
70-79 4 6.7
This table shows the number of patients in various age groups
Table 2: Tumour, nodes, metastasis status of
patients
Nodal status Tumor status
T1
T2
T3
T4
N0
- 5 1 -
N1
- 13 7 3
N2
- 8 13 3
N3
- 2 1 3
This table shows the tumor and nodal status of the patients
Table 3: Frequency of presenting symptoms in
cancer of nasopharynx (most of patients present
with multiple symptoms)
Symptoms No. %
Neck swelling 44 74
Nasal obstruction 8 13
Epistaxis 16 27
Headache 19 32
Change in voice 4 6.5
Sixth nerve palsy 3 5
Dysphagia 1 1.65
Ear pain 2 3.5
Decreased vision 1 1.65
Decreased hearing 1 1.65
Frequency of presenting symptoms in cancer of nasopharynx (most of patients
present with multiple symptoms)
Most of our patients were in clinical Stage II (AJCC/
UICC1992) 18/59 (30.5%). 28/59 (47.5%) of patients were
in clinical Stage III and 13/59 (22%) were in advanced
Stage IV. Most of our patients were in clinical Stage II or
III 46/59 (78%) [Figure 3].
35/59 (59%) patients were given combined treatment, i.e.
neoadjuvant chemotherapy and radiotherapy and quite a
large number 18/59 (30%) of patients were treated with
radiotherapy alone. The status of six patients regarding
chemotherapy could not be ascertained [Figure 4].
Majority of the patients were given Cisplatin and 5 Flouro
Uracil infusion.
The patients were given chemotherapy (2‑3 cycles) prior to
radiotherapy and then 2 cycles after radiotherapy. Majority
of the patients completed 2‑3 cycles (85%) [Figure 5].
The patients were on monthly follow‑up after treatment
either in radiotherapy or medical oncology clinic and were
assessed clinically including ENT examination and computed
tomography scan.
25/59 (42.3%) achieved complete response, i.e. complete
regression of disease clinical and on ENT examination after the
II, III follow‑up.
10/59 (16.9%) patients achieved partial response while
10/59 (17%) patients could not achieve any response.
Figure 1: The anatomy of nasopharynx
Figure 2: The computed tomography films shows the extent of disease with
regard to treatment planning

4. Pakkirmasthan and Kurakula: Nasopharyngeal cancer‑ chemoradiation
393Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3
Figure 3: The dimensions of the tumor identified in each slice of the
computed tomography scan were mapped on a conventional simulation
film. By courtesy. (Memorial sloan Kettering cancer center)
Figure 4:ComparisonofIMRT,3‑Dconformalandtraditionalparallel‑opposed
field plans, by courtesy. Treatment of primary head and neck cancer
at (Memorial sloan Kettering cancer center). Distribution of cases in relation
to sex, age and stages of various presentations. Statistical Package for the
Social Sciences version 10 is used
Radiotherapy dose of 66/70 Gray for 7‑8 weeks, 1.8 Gray/2
Gray fraction/day was given to most of the patients. It was
given in 5 fractions/week with dose prescribed to mid plane
with all the fields treated in every sitting. It was a three
phase shrinking field technique. The radiation fields included
two opposing lateral fields to treat the primary site and
upper cervical nodes and single anterior field to treat the
lower cervical and supraclavicular nodal sites.
Most of the patients tolerated the treatment well; with (15%)
developing Grade III reaction rest Grade II reactions (85%).
The follow‑up of the patients was poor about 43% patients
were lost to follow‑up. The Kaplan Meier (Statistical
Package for Social Science version 10) software could only
analyze 35 patients. However, still this retrospective analysis
gives some insight into the trend [Figure 6].
The patients who had received neoadjuvant chemotherapy
(2‑3 cycles) followed by radiotherapy showed a favorable
trend of mean survival as compared with these who had not
received chemotherapy (t = 1.992, P < 0.056). The same
trend was seen in clinical Stage II and IV, but clinical Stage
III did not have a marked difference. It was better for males
than for females [Table 4] age wise the younger patients had
better survival pattern as compared to older patients.
The patients who had received chemotherapy had also
a less trend toward metastatic disease as seen in our
data. The patients who were given chemotherapy by
and large did not develop metastatic disease except one
case of T3
N1
M0
(undifferentiated Ca) developed bone
metastases and another T4
N1
M0
(Anaplastic Cancer)
developed brain metastases.
However, one case of T3
N0
M0
which had not received any
chemotherapy developed spinal metastases after a period of
96 months.
The patients who had received neoadjuvant chemotherapy
with radiotherapy also developed local recurrence after
a period of 84 months. The patients who responded to
neoadjuvant chemotherapy followed by radiotherapy or
radiotherapy alone showed a better trend of survival.
The total sample a large proportion is males (63%).
Males have lower survival rates. More than one‑third
survived beyond 2 years, but less than 4 years. Females,
in comparison with males, have a longer survival. Nearly,
one‑fifth of females survived beyond 4 years.
Age is realized as a more important variable associated with
survival. With increase in age, the duration of survival has
found to be decreasing.
As the main independent variable is chemotherapy, which
is a variable associated with duration of survival. The mean
duration of survival has found to vary between those who
Figure 5: The pie diagram shows the response rate. Complete response
is greater than other partial and no response. Statistical package for the
Social Sciences version 10 statistical analysis
Table 4: Mean survival chemo-radiation and
radiation alone
Clinical
stage
Mean survival
chemo-radiation
(months)
Radiation alone
(months)
II 43.0 7.8
III 39.5 24.8
IV 30.2 11.5
Total 37.8 16.2
This table showed the mean survival of the patients who received
neo-adjuvant chemotherapy and radical radiotherapy alone

5. Pakkirmasthan and Kurakula: Nasopharyngeal cancer‑ chemoradiation
Indian Journal of Cancer | July-September 2015 | Volume 52 | Issue 3394
have been given chemotherapy and those who have not
been given chemotherapy (t = 1.992, P = 0.056). This
means that chemotherapy makes a difference in the survival
chances of patients. While a patient who has undergone
chemotherapy survives, on an average, up to 37.9 months,
those who have not undergone chemotherapy survive only
up to 16.2 months [Figure 6].
The cumulative survival in months is shown. The number
one curve is for patients treated on chemo radiotherapy and
the curve number two for patients on radical radiotherapy.
The curve number nine is for those patients, in which the
data was not known.
Discussion
In Libya the incidence is as low as two new cases/100,000
populations/year.
Most of the patients have cancer of nasopharynx between
40 and 60 years similar to what seen in our study
25‑49 (31 patients‑52%) 50‑60 years (17). The male female
ratio in usually 3:1[5]
but in our study is (1.7:1).
Most of the patients were undifferentiated carcinoma (74%)
rest were differentiated and 5/59 (7%) were poorly
differentiated anaplastic carcinoma.
The neck node involvement is seen in 60‑85% of patients at
the time of diagnosis and is the presenting symptom ranges
between 20% and 40%[6,9,10]
and it is comparable with our
data of lymph node involvement 74% patients also is the
presenting symptom in all of them.
NPC patients usually present with symptoms when disease
has spread to the adjacent structures. In our analysis, also
we have seen that clinical Stage II and III account for about
78% of patients.
The use of neoadjuvant and adjuvant chemotherapy with
radiotherapy has reported improvements in disease free
survival.[11‑13]
The intergroup study in USA[14]
reported
80% disease free survival at 2 years with concurrent
chemotherapy and 55% with radiotherapy alone. The
Nasopharynx International Study reported 43% disease
free survival at 4 years chemo‑radiotherapy and 30% with
radiotherapy alone. Chemo‑radiotherapy is now considered
as a standard practice by some authorities.[14]
In our
analysis, we also found that the patients who had received
chemotherapy by and large had a less trend to towards
developing metastatic disease and local recurrence and fared
better. The association of (EBV antibody) and it’s sustained
rise in 2‑10 years before the clinical onset of disease should
help in screening and early diagnosis of disease.
Conclusion
This retrospective analysis gives us the insight into the pattern
of clinical presentation of the patients of cancer of nasopharynx
and the clinical response and pattern of response in the patients
treated with neoadjuvant chemotherapy followed by radical
radiotherapy and radical radiotherapy alone.
This analysis is the first of its type done in our department
Benghazi radiotherapy and diagnostic center an only
important center of referral of radiotherapy for Eastern
part of Libya. The follow‑up of the patients have been
limited, but still this study has clinical response at par with
world literature, encourages us to have more comprehensive
treatment of patients of cancer nasopharynx. We are now
following the protocol of neoadjuvant chemotherapy
followed by chemo‑radiotherapy and followed by
chemotherapy and results will mature in the years to come.
Acknowledgement
I am grateful to several of our colleagues for valuable assistance
during the various stages of preparing this research: Dr. Jemal
khedir ali, Asharaf Abdul Salam and Dr. Faisal Shembesh for
providing a cordial and productive atmosphere. Appreciation is here
expressed to all who have contributed in any way to this study.
References
1. Ho HC, Ng MH, Kwan HC, Chau JC. Epstein‑Barr‑virus‑specific IgA and IgG
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2. Huang DP, Ho JH, Henle W, Henle G. Demonstration of Epstein‑Barr
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3. Henle W, Henle G. Evidence for an etiologic relation of the Epstein‑Barr
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4. Ji MF, Wang DK, Yu YL, Guo YQ, Liang JS, Cheng WM, et al. Sustained
elevation of Epstein‑Barr virus antibody levels preceding clinical onset
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carcinoma. A review of 759 patients. Br J Radiol 1990;63:51‑8.
6. Al‑Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, et al.
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8. Lederman M. Cancer of Nasopharynx: Its Natural History and Treatment.
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9. Chatani M, Teshima T, Inoue T, Azuma I, Yoshimura H, Oshitani T, et al.
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of 105 patients based on a survey of Kansai Cancer Therapist Group.
Cancer 1986;57:2267‑71.
10. Rossi A, Molinari R, Boracchi P, Del Vecchio M, Marubini E, Nava M, et al.
Adjuvantchemotherapywithvincristine,cyclophosphamide,anddoxorubicin
after radiotherapy in local‑regional nasopharyngeal cancer: Results of a
4‑year multicenter randomized study. J Clin Oncol 1988;6:1401‑10.
11. Preliminary results of a randomized trial comparing neoadjuvant
chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy
vs. radiotherapy alone in stage IV (> or=N2, M0) undifferentiated
nasopharyngeal carcinoma: A positive effect on progression‑free survival.
Figure 6: The survival curve shows the survival benefit for chemo‑radiation
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6. Pakkirmasthan and Kurakula: Nasopharyngeal cancer‑ chemoradiation
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International Nasopharynx Cancer Study Group. VUMCAI trial. Int J Radiat
Oncol Biol Phys 1996;35:463‑9.
12. Oh JL, Vokes EE, Kies MS, Mittal BB, Witt ME, Weichselbaum RR, et al.
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14. Licitra L, Bossi P, Palazzi M et al. Chemoradiotherapy in locally advanced
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How to cite this article: Pakkirmasthan A, Kurakula S.
Nasopharyngeal cancers: A retrospective comparative analysis of
radiotherapy alone versus chemo-radiation (Benghazi experience).
Indian J Cancer 2015;52:391-5.
Source of Support: Nil, Conflict of Interest: None declared.
Letters to the Editor
Prolonged survival of a patient with inoperable,
locally advanced adenocarcinoma of pancreas after
autologous immune enhancement therapy with
chemotherapy
Sir,
Life expectancy in advanced pancreatic cancers is only about
nine to ten months with the current treatments including
Chemotherapy.[1]
Herein we report a 26 month survival of
a pancreatic cancer patient treated with Autologous Immune
Enhancement Therapy (AIET) and chemotherapy.
A 40 year old male patient with no family history of
cancer presented with symptoms of Obstructive jaundice,
loss of weight and appetite, pale stools and new onset
Diabetes Mellitus in January 2007. Examination showed
a palpable gallbladder without lymphadenopathy. The
Haemoglobin level was 10.5 g/dl; Tumour marker
CA‑125 was 4.0 U/ml and CA 19‑9 was 3900 U/
ml. Further investigations revealed Carcinoma of the
pancreatic head involving uncinate process with the
tumour measuring 4.2 × 3.2 cm and the Common Bile
Duct (CBD) measuring 1.9 cm without involvement
of the Superior mesenteric vein. Endoscopic retrograde
cholangiopancreatography showed it to be a moderately
differentiated Grade III Adenocarcinoma. CBD stenting
was done in February 2007. Palliative surgery of
Cholecystectomy, hepatico‑jejunostomy using Roux‑n‑Y
loop of jejunum, Gastrojejunostomy and jejuno‑jejunostomy
were done. Subsequently, he was administered six cycles
of adjuvant chemotherapy (Gemcitabine, Leucovorin
and 5‑FU) and three cycles of AIET, as AIET has a
proven record of safety for more than two decades with
randomised clinical trials establishing its efficacy.[2]
After
informed consent, 60 mL of Peripheral Blood (PB) was
collected for each cycle of AIET. The Natural Killer (NK)
Cells and Cytotoxic T lymphocytes were isolated and
expanded following GMP compliant protocols using
the patients’ autologous plasma as earlier reported[3,4]
without using any feeder layers or animal products or
allogeneic serum. The cells multiplied were subjected to
flow cytometry for CD3, CD56, CD16, CD34, CD45 and
HLADR markers which showed an increased activation
of expanded lymphocytes [Figure 1a, b]. Activated and
expanded cells were infused intravenously.
The first AIET infusion was given between the second
and third chemotherapy cycles in April 2007 and the
second infusion after the completion of six cycles of
chemotherapy in December 2007. The tumour marker
CA 19‑9 decreased to 1000 U/ml. Surgical removal
of the tumour was attempted after the second AIET
but in vain. In March 2008, the third AIET was
administered. The average count of lymphocytes infused
was 61.3 millions. The CA 19‑9 decreased further to
600 U/ml after the third AIET [Figure 1c]. The patient
had subjective improvements in appetite and quality of
life. He survived for 26 months after the initial diagnosis
while the expected survival in these patients as per
reported literatures is less than 10 months.[1]
This is in
line or even longer than that reported by Kaneko et al.
in which the survival time of immunotherapy combined
with chemotherapy was 15.8 months in 28 patients
with advanced pancreatic cancers.[5]
The patient did
not have any kind of adverse reactions after the AIET
transfusions. With our experience in this case, where AIET
given in combination with chemotherapy has resulted
in prolonged survival of 26 months in an inoperable
advanced pancreatic carcinoma patient, we recommend that
this option be considered for similar cases.
Figure 1: (a) Flow cytometry image of CD3 + lymphocytes from the peripheral
blood before expansion and activation; (b) The same after in vitro expansion
and activation; (c) The gradual decrease of CA 19‑9 levels during the course
of treatment
c
a