Ayman Reffai1, Mohamed Mesmoudi1,2, Touria Derkaoui1, Naima Ghailani Nourouti1, Amina Barakat1, Nabila Sellal2, Parag Mallick3, Mohcine Bennani Mechita1. 1. Biomedical Genomics and Oncogenetics Research Laboratory, Faculty of Science and Technology of Tangier (FSTT), 531748Abdelmalek Essaadi University (UAE), Tangier, Morocco. 2. Ahmed Ben Zayed Al Nahyan Center of Cancer Treatment, Tangier, Morocco. 3. Canary Center for Cancer Early Detection, School of Medicine, 10624Stanford University, Stanford, CA, USA.
Abstract
BACKGROUND: Nasopharyngeal carcinoma is a multifactorial disease mainly affecting the Asian and North African populations including Morocco. This study aimed to determine the epidemiological profile of nasopharyngeal carcinoma in Northern Morocco as well as its clinicopathological, therapeutic, and prognostic characteristics. METHODS: 129 patients with nasopharyngeal carcinoma followed at the regional center of oncology of Tangier in the period between April 2017 and July 2019, and diagnosed elsewhere from March 2000 to February 2019, were included in this study. Statistical analysis of the data was realized using Statistical Package for the Social Sciences (SPSS) software. RESULTS: Nasopharyngeal carcinoma (NPC) represented 5% of all cases with a median age of 50. The most affected age group was 40-54 years (41.1%). Of all patients, 65.9% were men and 34.1% were women with a sex ratio of 1.93 (Male/Female). Undifferentiated nasopharyngeal carcinomas were the most common histological type affecting 96.12% of patients. At diagnosis, the majority of patients (82.2%) had an advanced stage of NPC (III, VIa, b, c) including 5.4% of metastatic cases (IVc). Most cases (86%) had lymph node involvement with cervical mass being the most common clinical presentation. 81.4% of patients received radiotherapy combined with chemotherapy. Among these patients, 54.3% had concurrent radiochemotherapy preceded by induction chemotherapy. The 5-year overall survival (OS) was 86.8% for all patients. It represented 91.3% for early stages, 87.9% for locally advanced stages, and 57.1% for the metastatic stage significantly. The disease-free survival (DFS) at 5 years was 87.6% knowing that relapse occurred in 16 cases. CONCLUSIONS: Nasopharyngeal carcinoma is a particular disease with a late declaration. It is common in Morocco as is the case in other endemic areas with a high prevalence. Patients' survival is significantly influenced by disease staging.
BACKGROUND: Nasopharyngeal carcinoma is a multifactorial disease mainly affecting the Asian and North African populations including Morocco. This study aimed to determine the epidemiological profile of nasopharyngeal carcinoma in Northern Morocco as well as its clinicopathological, therapeutic, and prognostic characteristics. METHODS: 129 patients with nasopharyngeal carcinoma followed at the regional center of oncology of Tangier in the period between April 2017 and July 2019, and diagnosed elsewhere from March 2000 to February 2019, were included in this study. Statistical analysis of the data was realized using Statistical Package for the Social Sciences (SPSS) software. RESULTS: Nasopharyngeal carcinoma (NPC) represented 5% of all cases with a median age of 50. The most affected age group was 40-54 years (41.1%). Of all patients, 65.9% were men and 34.1% were women with a sex ratio of 1.93 (Male/Female). Undifferentiated nasopharyngeal carcinomas were the most common histological type affecting 96.12% of patients. At diagnosis, the majority of patients (82.2%) had an advanced stage of NPC (III, VIa, b, c) including 5.4% of metastatic cases (IVc). Most cases (86%) had lymph node involvement with cervical mass being the most common clinical presentation. 81.4% of patients received radiotherapy combined with chemotherapy. Among these patients, 54.3% had concurrent radiochemotherapy preceded by induction chemotherapy. The 5-year overall survival (OS) was 86.8% for all patients. It represented 91.3% for early stages, 87.9% for locally advanced stages, and 57.1% for the metastatic stage significantly. The disease-free survival (DFS) at 5 years was 87.6% knowing that relapse occurred in 16 cases. CONCLUSIONS: Nasopharyngeal carcinoma is a particular disease with a late declaration. It is common in Morocco as is the case in other endemic areas with a high prevalence. Patients' survival is significantly influenced by disease staging.
Nasopharyngeal carcinoma (NPC) is a multifactorial disease resulting from a complex
interaction between genetic and environmental factors. It occurs most often in the
epithelial cells lining the interior of the nasopharynx which is the highest part of
the pharynx where the nasal fossae and the Eustachian tube open.According to the most recent WHO classification of head and neck tumors published in
2017 (4th edition), the histological types of nasopharyngeal carcinomas
are defined as keratinizing squamous-cell carcinomas or non-keratinizing carcinomas.
The second type is subdivided into differentiated and undifferentiated carcinomas (UCNT).
UCNT is by far the most common histological type of NPC in endemic areas (>90%).
Nasopharyngeal tumors show a high frequency of metastasis, compared with
other cancers of the head and neck, varying between 5% and 41%.
The regional and distant lymph nodes, the bone, the lungs, and the liver
represent the most common sites of metastasis in this type of cancer.[1,5]This complex malignancy is distinguished from other cancers of the head and neck by
its geographic distribution and its etiology. Although rare in North America and
Europe, with age-standardized incidence rates (ASRs) of less than 1 per 100 000
person-year, nasopharyngeal carcinoma is one of the most common cancers in Southern
China, Southeast Asia, and North Africa with ASRs of 2–10/100 000-year.
NPC has a remarkable sex disparity with a higher risk in males. The sex ratio
is 2–3 men per woman.[7,8]
In North Africa, nasopharyngeal carcinoma generally affects 2 peaks of age. The
first peak is between 10 and 20 years old and the second, the major one, is between
45 and 55 years old. For Chinese and Eskimos, the peak incidence is between 45 and
55 years old.[9,10]In addition to genetic predisposition and environmental factors such as dietary and
toxic substances, the carcinogenesis of the nasopharynx depends on genetic and
epigenetic alterations whose effect is added to the activation of oncogenes and
signaling pathways following the expression of Epstein Barr virus’s (EBV) latent genes.Nasopharyngeal tumors are radiosensitive and rarely accessible for surgery which
makes radiotherapy (RT) the basic therapeutic modality, although the standard
curative treatment of this type of cancer is concurrent radiochemotherapy (CRT). The
latter has shown several benefits like improving clinical outcomes and patients’ survival.
CRT can be followed by adjuvant chemotherapy or preceded by induction
chemotherapy to treat advanced stages of NPC.Another particularity of nasopharyngeal carcinoma is that the majority of patients
are diagnosed at an advanced stage.
The complex anatomy of the nasopharynx and the nonspecific nature of the
symptoms such as cervical masses, rhinological signs, and otological signs make this
cancer with a late declaration causing a major health problem.In Morocco, as is the case in other endemic countries, the incidence and prevalence
of nasopharyngeal carcinoma are high. However, very few studies have been done in
this regard. We note the absence of epidemiological studies and cancer registries in
Northern Morocco. This study aimed to determine the epidemiological profile and the
clinicopathological, therapeutic, and prognostic characteristics of nasopharyngeal
carcinoma in Northern Morocco in order to better understand this complex
disease.
Materials and Methods
Study Population
This epidemiological and clinical study was conducted on patients diagnosed with
nasopharyngeal carcinoma in Northern Morocco. All NPC patients followed and/or
treated at the regional center of oncology of Tangier (Ahmed Ben Zayed Al Nahyan
center of cancer treatment), since its opening, during the period between April
2017 and July 2019 were included in this study. Patients in our cohort were
either treated, followed after relapse, or continued their treatment at the
regional center of oncology of Tangier during the follow-up time.It is a retrospective descriptive study of 129 NPC patients diagnosed elsewhere
from March 2000 to February 2019. Patients’ diagnosis was confirmed by a
nasopharynx or a neck lymph node biopsy. The extent of NPC was determined by
imaging techniques such as magnetic resonance imaging (MRI) and computerized
tomography (CT).
Data Collection
Data were collected from medical records of NPC patients in the regional center
of oncology of Tangier, which is the only public center for cancer treatment in
the Tangier-Tetouan region (North), using detailed technical sheets. The
collection of epidemiological, clinicopathological, therapeutic, and prognostic
data was then classified and managed in a database of Statistical Package for
the Social Sciences (SPSS) software. Patients lost to follow up were afterward
contacted by phone to find out the evolution of the disease. Among the 39 lost
to follow-up patients, only 24 were reachable.
Statistical Analysis
All statistical analysis was performed using SPSS software version 23 designed
for analysis of scientific projects (SPSS, RRID: SCR_002865). Descriptive
analysis of our cohort was carried out to represent the results significantly
for good interpretation. Quantitative variables were presented as central
tendency indicators, like the mean and the median, or/and dispersion indicators
such as the standard deviation. Ordinal and nominal qualitative variables were
presented as frequencies or percentages. In this case, we only calculate the
mode. T-test for independent samples was used for statistical significance. The
survival rate was analyzed with the Kaplan–Meier method.
During this analysis, overall survival (OS) was calculated from the date
of diagnosis until the date of last news or the date of death. Live and lost to
follow-up patients represented censored data while deceased patients represented
uncensored data. Disease-free survival (DFS) was calculated from the date of
diagnosis until the date of last news or the date of relapse. In this case,
uncensored data were relapse cases. Overall survival was compared afterward to
patients’ age, sex, and stage of nasopharyngeal carcinoma using the Log Rank
test, the most popular non-parametric test for comparing two or more survival
curves. The level of significance was set at P-value ≤
0.05.The missing values of this study were treated using 10% as the threshold.
Variables with less than 10% missing data were replaced by the mode for
qualitative variables and by the mean or the median for quantitative variables.
Variables with more than 10% missing data were excluded from the study.
Variables Definition
In this study, a wide range of variables were collected and analyzed. Prevalence,
patients’ age (divided into categories), sex, and origin were grouped into
epidemiological data. The clinicopathological data included symptoms,
histological types, TNM classification (7th edition), and cancer
stages. Treatment data included treatment types (radiotherapy, chemotherapy, and
surgery). For chemotherapy (neoadjuvant, concurrent, and palliative) and
radiotherapy (curative and palliative), variables including chemotherapy
regimens, and radiotherapy total dose, fractions, and duration were studied.
Relapse data included variables such as relapse types (locoregional and
metastatic), common sites, treatment-relapse interval, and treatment after
relapse. The date of diagnosis and last news as well as the evolution data
divided to under control, in treatment, death, and lost to follow-up were used
in survival analysis.
Ethical Aspects
This retrospective study was approved by the regional health directorate and the
regional center of oncology of Tangier in Morocco although it did not require
ethical board approval. All patients included in this study gave their informed
verbal consent prior to their inclusion as instructed by these committees. In
addition, the confidentiality of information collected and the anonymity of
patients were ensured.
Results
Epidemiological Profile
Regarding the prevalence, nasopharyngeal carcinoma represented 5% of all cases
recorded between 2017 and 2019 at the regional center of oncology of Tangier.
During this period, 2583 cases of all cancers were recorded, including 129 cases
of nasopharyngeal cancer.In our cohort, patients’ age ranged from 10 to 88 years, with a pic incidence at
40–54 years old. The mean age was 47 ± 14.9 years with 47.7 for men and 45.7 for
women. The median age of patients was 50 years (50 for men and 51 for women).
Forty-one and one tenth percent (41.1%), 25.6%, and 11.6% of NPC patients were
aged between 40 and 54, 55 and 69, and 10 and 24 years, respectively. Only 3.9%
were aged 70 years or more. In this study, the gender difference was remarkable.
Of the 129 patients, 85 were men (65.9%) and 44 were women (34.1%) with a sex
ratio of 1.93 (Male/Female). The majority of patients lived in urban areas (86%)
compared to rural areas (14%) as shown in Table 1.
Table 1.
Epidemiological Profile and Clinicopathological Characteristics of
NPC Patients in Our Cohort.
Patient characteristics
N = 129 (%)
Age distribution
10–24
15 (11.6)
25–39
23 (17.8)
40–54
53 (41.1)
55–69
33 (25.6)
≥70
5 (3.9)
Sex
Male
85 (65.9)
Female
44 (34.1)
Origin
Urban
111 (86)
Rural
18 (14)
Histological types
Undifferentiated carcinomas
124 (96.12)
Non-keratinizing squamous
3 (2.33)
Keratinizing squamous
2 (1.55)
cTNM classification
T1
6 (4.7)
T2
45 (34.8)
T3
46 (35.7)
T4
32 (24.8)
N0
18 (13.9)
N1
37 (28.7)
N2
60 (46.5)
N3
14 (10.9)
M0
122 (94.6)
M1
7 (5.4)
Cancer stage
I
0 (0)
II
23 (17.8)
III
60 (46.5)
Iva
26 (20.2)
IVb
13 (10.1)
IVc
7 (5.4)
Epidemiological Profile and Clinicopathological Characteristics of
NPC Patients in Our Cohort.
Clinicopathology
Patients in our cohort had several clinical signs at the time of diagnosis; the
most common were cervical mass (65.1%), rhinological signs (64.3%), otological
signs (59.7%), and headaches (27.1%), respectively.Table 1 shows the
other clinicopathological characteristics of NPC patients. Undifferentiated
carcinoma nasopharyngeal type (UCNT) was the most common histological type in
our cohort, representing 96.12%. Differentiated non-keratinizing squamous and
keratinizing squamous were rare, representing 2.33% and 1.55%, respectively.
Regarding cTNM classification, analysis of the size and extension of the tumor
(T) in patients showed that 35.7%, 34.8%, 24.8%, and 4.7% of tumors were
classified T3, T2, T4, and T1, respectively. Among all patients, 86% had lymph
node involvement (N1, N2, and N3). 5.4% of patients were metastatic (M1) at the
time of diagnosis. The most common sites of metastasis were bone, liver, lymph
nodes, and lung. By grouping this data into stages, 82.2% of patients had an
advanced stage (III, IVa, IVb, IVc) of nasopharyngeal carcinoma at the time of
diagnosis, while 17.8% had an early stage (II). None of these were classified as
stage I. Regarding sex, 68.2% of female patients had locoregional advanced NPC
(III, IVa, IVb) at diagnosis, whereas 81.2% of males had locoregional advanced
stage. NPC stages compared to males and females had a p-value
(P = .001 < .05) statistically significant.
Initial Treatment
In this study, the majority of patients (81.4%, 105 individuals) received
radiotherapy combined with chemotherapy (CT), whereas 14.7% (19 individuals)
received chemotherapy alone and 1.6% (2 individuals) received radiotherapy
alone. 2.3% (3 individuals) of patients did not receive any treatment during the
follow-up time. Regarding surgery, only 2 patients have been operated during
their treatment with palliative surgery.Among the patients treated with radiotherapy combined with chemotherapy, 54.3%
(57 patients) received induction chemotherapy before the CRT, while 44.7% (47
patients) had CRT directly. All metastatic patients (5.4%) received a palliative
treatment including 6 with palliative chemotherapy and 1 with palliative
chemotherapy and radiotherapy as shown in Table 2.
Table 2.
Initial Treatment of NPC Patients During the Follow-Up Time.
Treatment type
Frequency
Percentage %
Radiotherapy and chemotherapy
Concurrent
47
44.7
Neoadjuvant and concurrent
57
54.3
Palliative
1
1.0
Total
105
100.0
Chemotherapy alone
Neoadjuvant alone
13
68.4
Palliative
6
31.6
Total
19
100.0
Radiotherapy alone
Total
2
100.0
No treatment
Total
3
100.0
Initial Treatment of NPC Patients During the Follow-Up Time.The most widely used drugs in neoadjuvant (induction) and palliative chemotherapy
were platinum-based combinations including cisplatin–anthracycline. Single drug
protocols such as gemcitabine and taxanes were also used in palliative
chemotherapy. Regarding concurrent chemotherapy, cisplatin was the most used
drug in our study.Radiotherapy was delivered using Volumetric Modulated Arc Therapy (VMAT), an
arc-based approach of Intensity Modulated Radiotherapy (IMRT). The majority of
patients in our cohort received a total dose of 70 Gy in 35 fractions of
curative radiotherapy. The period of radiation varied from 2 to 88 days with a
mean of 54.54 days during the follow-up time.
Relapse
In our cohort, nasopharyngeal cancer relapse occurred in 16 cases (12.4%)
including 7 cases (5.4%) with metastatic relapse, 5 cases (3.9%) with
locoregional and metastatic relapses, and 4 cases (3.1%) with locoregional
relapse. The bone was the most common metastatic site after relapse (66.6%). 15
patients of the 16 cases with relapse (93.8%) had an advanced stage of
nasopharyngeal carcinoma at diagnosis. The period between the end of treatment
and cancer relapse varied between 11 and 1825 days with a mean of 588.27 and a
median of 310.50 days. Among these patients, 10 received after relapse treatment
by the follow-up time, including 6 cases treated with palliative chemotherapy
and radiotherapy, 3 cases treated with palliative chemotherapy, and one case
treated with palliative radiotherapy.
Survival
The mean of patients’ follow-up from diagnosis was 28.6 months with extremes
between 1 and 220 months. The mean of non-metastatic patients’ follow-up was
29.7 months, while the mean of metastatic patients was 9.8 months. The 5-year
overall survival (OS) was 86.8% knowing that the event (death) occurred 17 times
(14 men and 3 women). The OS at 5 years was 91.3% for early stages (I, II),
87.9% for locally advanced stages (III, IVa, IVb), and 57.1% for the metastatic
stage (IVc) with a P-value of .002 (<.05)
statistically significant. Regarding sex, the 5-year OS was 83.5% for males and
93.2% for females with a p-value = .053 (≥.05)
weakly significant. Regarding the age groups 10–24, 25–39, 40–54, 55–69 and ≥
70, the OS at 5 years was 93.3%, 91.1%, 83%, 87.9%, and 80%, respectively, with
a p-value = .71 (>.05) not statistically significant (Figures 1–4). The 5-year DFS was 87.6% knowing
that the event (relapse) occurred in 16 cases (Figure 5).
Figure 1.
Overall survival at 5 years.
Figure 2.
Overall survival at 5 years regarding NPC stages. NPC: Nasopharyngeal
carcinoma.
Figure 3.
Overall survival at 5 years regarding sex.
Figure 4.
Overall survival at 5 years regarding age groups.
Figure 5.
Disease-free survival at 5 years.
Overall survival at 5 years.Overall survival at 5 years regarding NPC stages. NPC: Nasopharyngeal
carcinoma.Overall survival at 5 years regarding sex.Overall survival at 5 years regarding age groups.Disease-free survival at 5 years.
Discussion
Knowing that this is the first epidemiological and clinical study of nasopharyngeal
carcinoma in Northern Morocco with the absence of a cancer registry, these results
give an idea of the epidemiological profile and the clinical characteristics of this
type of cancer in Morocco and particularly in Northern Morocco.In Morocco, as is the case in other endemic areas, nasopharyngeal carcinoma is
one of the most common cancers with a high prevalence. In this study, NPC
represented 5% of all cases reported between 2017 and 2019. This result gives an
idea about the prevalence although it included all patients recorded at the
regional center of oncology of Tangier during that period even if some of them
were diagnosed way before.Our prevalence is higher than that found in Casablanca (1.8%) during the period
from 2008 to 2012 (Cancer registry of Casablanca 2008–2012) and almost similar
to that found by Arfaoui et al (4.9%) in Rabat between 1994 and 2004.[17,18]
Internationally, the prevalence of nasopharyngeal carcinoma was 3.2% (3-year
period) according to the International Agency for Research on Cancer (IARC)
which is lower than the prevalence of this study.
These results confirm that Morocco is one of the regions at risk for this
type of cancer.In our cohort, patient’s ages ranged from 10 to 88 years with a median of
50 years old. Abdullah et al found a median age of 51 years in a study of 266
NPC patients, whereas Alami et al found a median age of 47 years in a study of
163 NPC patients.[19,20] The most common age group in this study was
40–54 years. These results converge at the national level with Arfaoui et al.’s
study and internationally with the results of IARC.[9,17] Unlike the majority of
cancers, nasopharyngeal carcinoma also affects young people.[21,22] 11.6% of
patients in our cohort were between 10 and 24 years old at diagnosis, knowing
that children under 15 are normally treated in pediatric centers except for some
rare cases. Without this condition, the percentage of young NPC patients could
be greater. These results are similar to what Daoud et al. found.
This might be explained by the genetic predisposition which contributes
to the development of NPC at a younger age.The sex disparity was remarkable in this study with a higher risk for males and a
sex ratio of 1.93 (M/F). These results are consistent with the literature
data.[24,25] The sex difference may be due to the great exposure of
men to NPC risk factors including toxic substances and occupational factors such
as wood dust and chemical fumes.[26,27] Further studies on this
level should be done.Our results showed a predominance of urban origins (86%) over rural origins (14%)
which converge with the results of Wei et al. in China.
This could be explained by the difficulty of access to diagnosis and
treatment in rural areas and the urbanization of Moroccan people.In the early stages of the disease, nasopharyngeal cancer may not cause any
symptoms. Clinical signs of NPC appear as the tumor grows in nearby tissue.
Cervical mass caused by lymphadenopathy was the most common symptom in this
cohort, followed by rhinological signs, including nasal congestion and
epistaxis, otological signs such as hearing loss and tinnitus, and headaches.
Other symptoms such as eye signs, neurological signs, and weight loss have been
reported less frequently. These results converge with the literature
data.[15,24] The non-specificity of the symptoms and the complex
anatomy of the nasopharynx make the diagnosis of NPC difficult which could
explain why most patients are diagnosed at an advanced stage.In this study, undifferentiated carcinoma (UCNT) was the most common histological
type of nasopharyngeal cancer with 96.12% of cases. These results are consistent
with all studies like Bahannan A et al and Wided BA et al confirming that UCNT
is the predominant type of NPC in endemic areas.[29,30] Several studies showed
that UCNT and non-keratinizing squamous have better prognosis and are more
responsive to radiation than keratinizing squamous-cell carcinoma although the
latter is more common in non-endemic areas such as the United States of
America.[31,32]Thirty-five and seven tenth percent (35.7%), 34.8%, 24.8%, and 4.7% of tumors in
our cohort were classified T3, T2, T4, and T1, respectively. Of the 129
patients, 86% had lymph node involvement. In a study of 83 NPC patients in
Taiwan, Liu et al found that 42% of patients had T2 tumors, 28% had T4, 23% had
T1, and 7% had T3. Of the 83 patients, 77% had lymph node involvement.
Bahannan et al and Raissouni et al found cervical nodal metastasis in
78.9% and 80% of patients, respectively.[25,30] T-stage and N-stage were
shown to be significant prognostic factors in NPC.[33,34] In this study, 5.4% were
metastatic at the time of diagnosis with bone, liver, lymph node, and lung being
the most common sites of metastasis. These results are similar to the literature
data.[1,35]One of the particularities of NPC is that the majority of patients are diagnosed
at an advanced stage. In this study, 82.2% of patients had an advanced stage
(III, IVa, IVb, IVc) of nasopharyngeal carcinoma including the metastatic stage
(5.4% IVc). Marnouche et al and Mak et al also found a high percentage of
patients with an advanced stage of NPC (85.5% and 66.1%,
respectively).[14,36] These results confirm that NPC is a late declaration
cancer. The detection of anti-EBV antibodies and other serological markers such
as Cyfra 21 can predict this type of cancer, hence their usefulness in early
diagnosis.[37,38] More studies at this level should be done. In this
study, only 68.2% of females had locoregional advanced NPC, compared to 81.2% of
males who had locoregional advanced disease. This difference in NPC stages
between men and women was statistically significant which might result in a
better prognosis for female patients compared to males.
Treatment Modalities
Nasopharyngeal carcinoma is a radiosensitive tumor which makes radiotherapy the
first choice for treating early stages. Many studies have shown that the
addition of chemotherapy to radiotherapy has several benefits including improved
clinical outcomes and survival in patients with locally advanced stages of
NPC.[12,39] In this study, 81.4% of patients received an initial
treatment of radiotherapy (RT) combined with chemotherapy (CT). Among these
patients, 54.3% received induction chemotherapy before the CRT. Wang et al and
Tan et al performed a meta-analysis in which they confirmed that the addition of
induction chemotherapy to CRT to treat advanced stages of NPC improves overall
and progression-free survival.[13,40]In our cohort, patients without treatment (2.3%) and patients treated with
chemotherapy (14.7%) or radiotherapy alone (1.6%) are either lost to follow-up
or have not yet started or completed their treatment by the follow-up time.According to several studies, palliative chemotherapy and radiotherapy as well as
surgery in some cases play an important role in controlling the disease and
prolonging the survival of patients with recurrence or metastasis.[15,41] In this
study, 17 patients (13.18%) including 7 metastatic cases and 10 relapse cases
received palliative treatment, mainly CT and RT. Only 2 patients have been
operated during their treatment (palliative surgery).The most used CT protocols in this study were platinum-based drugs such as
cisplatin combined with anthracycline for neoadjuvant and palliative CT and
cisplatin alone for concurrent CT. Zhou et al. found that docetaxel, cisplatin,
and fluorouracil (TPF)–based induction CT plus CRT results in better survival
outcomes with manageable toxicities compared with CRT alone or double-drug based
induction CT.
Zhang et al. showed that the addition of gemcitabine and cisplatin
induction CT to cisplatin CRT improves patients’ survival.Radiotherapy dose is usually 2 Gy per fraction, 5 days per week with a total dose
of 70 Gy in 49 to 50 days. In our series, the majority of patients received a
total dose of 70 Gy in curative RT (VMAT-IMRT). The treatment period varied from
2 to 88 days with a mean of 54.54 days by the follow-up time. Interruption
during RT treatment has been reported to reduce local control and survival of
patients.[44,45] These delays can be due to the treatment tolerance
and/or logistic issues.The use of IMRT to target the tumor more precisely by increasing the radiation
dose seems to be more promising than conventional RT in treating nasopharyngeal
carcinoma. Several studies have shown that it contributed to an absolute
improvement in locoregional control and survival as well as lower incidence of toxicities.
Recent studies and clinical trials focus nowadays on new treatment
modalities such as immunotherapy, gene, and targeted therapies. Regarding this
latter, monoclonal anti-EGFR antibodies such as cetuximab and nimotuzumab are
among the most studied targeted therapy. Adoptive transfer of autologous
EBV-specific cytotoxic T cells and inhibition of checkpoints such as PD-1 and
CTL-4 to activate the immune system are used as immunotherapy
strategies.[47-49]
Significant cytotoxicity mediated by apoptosis was obtained using a technique of
gene therapy that consists of introducing a viral vector (adenovirus) containing
a transgene which, its expression, is under the transcriptional regulation of
the latent origin of the replication of repeated sequences (oriP) of the Epstein
Barr virus.
Recurrence
Among all patients, 12.4% presented NPC recurrence with a higher rate of
metastatic relapses compared to locoregional relapses. Like other studies, the
most common site of metastatic recurrence in our cohort was the bone. These
results are similar to the literature data.[51,52] In this study, the median
interval between the end of treatment and NPC relapse was 310.50 days. When this
period is less than 90 days (1 case), the tumor is said to be resistant to
treatment. Therapeutic failure and NPC recurrence may be due to the presence of
hypoxic tumors which are known to be radioresistant.
Survival Functions
With a mean follow-up of 28.6 months, the overall survival (OS) of all patients
at 5 years was 86.8%. Marnouche et al. found a 5-year OS of 68%.
Internationally, Mak et al found a 5-year OS of 70.7% in Singapore,
whereas Anne lee et al reported a 5-year OS of 75% in Hong Kong.[36,54] In our
cohort, the DFS at 5 years was 87.6%. Marnouche et al. reported a 5-year DFS of
81.1% in Rabat Morocco.
In Malaysia, Phua et al found a poor DFS of 48.4%.
According to several studies, the OS and DFS improve when patients are
treated with IMRT instead of conventional RT and with concurrent
radiochemotherapy instead of RT alone.[12,56]The five-year overall survival in our cohort for early stages, locally advanced,
and metastatic stages was 91.3%, 87.9%, and 57.1%, respectively, which confirm
that NPC stages influence significantly patients’ survival. These results were
consistent with those of several studies showing that the NPC stage is the most
important prognostic factor for NPC.[20,54,55] Regarding sex, the 5-year
overall survival was higher in women (93.2%) compared to men (83.5%) with
p-value weakly significant. These results were similar to the literature data
showing a female advantage with a higher survival.[57,58] Lu et al and OuYang et al
suggest that the favorable prognosis of female NPC patients is not only
attributed to the early diagnosis and treatment but might also be attributed to
some intrinsic biologic factors of female patients such as the hormonal
differences.[57,58]In this study, OS at 5 years was lower for patients aged 70 years or more (80%)
and for the age group 40–54 years (83%) which is the most affected age category.
The age groups 10–24, 25–39, and 55–69 had an OS of 93.3%, 91.1%, and 87.9%,
respectively, with p-value not statistically significant. In an Indonesian
study, Hutajulu et al. showed that age was an independent predictor for the OS.The limited data accessibility and the study size are considered as the
limitations of the study although the latter represents the first study of its
kind in Northern Morocco. It relates to the national plan for the prevention and
control of cancer.
Conclusion
It is becoming more and more difficult to ignore the role of nasopharyngeal cancer in
Morocco, as is the case in other endemic areas, hence the importance of carrying out
epidemiological studies and establishing cancer registries. NPC remains a complex
malignancy with a late declaration, representing one of the most frequent cancers in
Morocco and particularly in Northern Morocco. It is characterized by its
epidemiological profile and its clinicopathological, therapeutic, and prognostic
factors. Being the first of its kind in Northern Morocco, this study will contribute
to the understanding of this type of cancer by improving the prevention and
patients’ follow-up. It will also allow us to study the molecular and genetic part
of nasopharyngeal carcinoma to subsequently improve therapeutic pathways and early
diagnosis of this disease.
Authors: Shao-Hua Xie; Ignatius Tak-Sun Yu; Lap Ah Tse; Joseph Siu Kie Au; June Sze Man Lau Journal: Int Arch Occup Environ Health Date: 2017-03-02 Impact factor: 3.015
Authors: F Perri; G Della Vittoria Scarpati; F Caponigro; F Ionna; F Longo; S Buonopane; P Muto; M Di Marzo; S Pisconti; R Solla Journal: Onco Targets Ther Date: 2019-02-26 Impact factor: 4.147