Aim of Work: The aim of this work was to study the clinico-epidemiological characteristics of the patients with nasopharyngeal carcinoma (NPC), analyse the prognostic factors of the disease and to analyse the results of different treatment modalities and their effect on loco-regional, distal metastatic disease control and both overall survival (OS) and disease free survival (DFS) rates. Patients and Methods: This is a retrospective study reviewing all adult nasopharyngeal carcinoma (NPC) patients who presented to the radiotherapy department—National Cancer Institute Cairo University in the period from (2000-2010). Results: In this study, it was found that the mean age was 45 years; most of the patients were of locally advanced stages. Multivariate cox proportional hazards regression identified T-stage, radiotherapy course completion & addition of chemotherapy as independent prognostic factors for local control (LC), DFS, & OS. The 5-year LC, DFS and OS rates for all studied patients were 38.2%, 33.5% & 37.2% respectively. The median DFS was 26 months and median OS was 36.5 months. Conclusion: This study matches the published data that support that radical concurrent chemoradiation is the mainstay of treatment of locally advanced NPC, & that T-stage, M-stage, prescribed dose completion, response to initial treatment are independent prognostic factors for survival. All measures should be taken to improve the local response during primary treatment as this will improve survival rates of patients with NPC.
Worldwide, there are 80,000 incident cases of nasopharyngeal carcinoma and 50,000 deaths annually [
The tumor-node-metastasis (TNM) staging system for malignancies is used to evaluate prognosis, aid treatment planning, and facilitate the stratification of treatment. At present, the seventh edition of the American Joint Committee on Cancer (AJCC) staging system is widely used [
Nasopharyngeal carcinoma (NPC) commonly demonstrates extensive invasion of adjacent tissues with poorly defined and large tumors in close proximity to critical structures, such as the brain stem, spinal cord, and optic chiasm. These features of NPC can complicate adequate surgical resection [
Nasopharyngeal carcinoma is highly sensitive to radiotherapy or chemotherapy [
Because of the improved treatment outcome and toxicity profile, IMRT (intensity modulated radiotherapy) is now recommended for definitive treatment for all patients with nasopharyngeal cancer [
This study was conducted to evaluate the clinical and epidemiological characteristics of the patients with NPC who were treated at radiotherapy department, NCI, in the last 10 years. And to study patient management and its outcomes, in addition to analyze potential prognostic factors influencing local control, disease free survival as well as overall survival of the disease
This is a retrospective study of adult nasopharyngeal cancer patients who were treated at the radiotherapy department of the National cancer institute of-Cairo university, in the period between 2000 and 2010.
The study included 158 patients; all of them were with pathologically confirmed nasopharyngeal carcinoma, 18 years of age and above, and with complete data files.
The patients were divided into 5 groups according to the type of treatment they received: 1-Radical RT 2-Radical concurrent chemoradiation (CCRT) 3-CCRT + adjuvant chemotherapy (CTH) (only 2 patients) 4-In- duction CTH + CCRT 5-Palliative RT (Best supportive care).
Regarding radiotherapy, all patients who were treated by radical radiotherapy were treated in supine position using isocentric technique and all of them had proper fixation by a head and neck mask. Radical radiotherapy dose to the target volume ranged from 66 to 72 Gy with a spinal cord shield after 40 Gy while palliative dose was limited to 30 Gy to the target volume.
Statistical AnalysisData was analyzed using IBM SPSS advanced statistics version 20 (SPSS Inc., Chicago, IL). Survival analysis was done using Kaplan-Meier method and comparison between two survival curves was done using log-rank test. All tests were two-tailed. A p-value < 0.05 was considered significant [
The study included 158 patients who were properly staged (
The most frequently used treatment modality in this study was induction chemotherapy plus concurrent chemo-radiotherapy (34.1%), followed by the treatment modality of concurrent chemo-radiotherapy (32.9%) (Ta- ble 2).
Out of the 149 patients who received radical radiotherapy, twenty three patients (15.4%) were treated using 3D conformal radiotherapy (3D CRT) technique, while 2D technique was used for 121patients (81.2%) (
Range | Mean and median | |
---|---|---|
Age | 18 - 77 years | 45 y |
Gender | Number of Patients | Percent |
Male | 111 | 70.3% |
Female | 47 | 29.7% |
Smoking | Number of patients | Percent |
Yes | 93 | 58.9% |
No | 65 | 41.1% |
Clinical presentation | Patients No | Percent |
Neck swelling | 112 | 70.9% |
Headache | 38 | 24% |
Nasal tone | 32 | 20.6% |
Nasal obstruction | 25 | 15.8% |
Epistaxis | 22 | 14% |
CN palsy | 21 | 13.3% |
Dysphagia | 5 | 3.2% |
Performance | Number of patients | Percent |
I | 122 | 77.2% |
II | 24 | 15.2% |
III | 12 | 7.6% |
Pathological types | Number of patients | Percent |
Undifferentiated carcinoma | 121 | 76.6% |
Squamous cell carcinoma | 29 | 18.3% |
Others: | 8 | 5.1% |
Anaplastic carcinoma | 2 | 1.3% |
Adenocarcinoma | 2 | 1.3% |
Adenoid Cystic carcinoma | 4 | |
Stage group | Number of patients | |
I | 6 | 3.8% |
II | 16 | 10.1% |
III | 64 | 40.5% |
IVA | 35 | 22.2% |
IVB | 28 | 17.7% |
IVC | 9 | 5.7% |
158 | 100% |
The patients’ performance at presentation was classified according to the ECOG PER- FORMANCE STATUS (Oken et al., 1982) [
Treatment | Number of patients | Percent |
---|---|---|
Radical radiotherapy | 41 | 26% |
CCRT + adjuvant CTH | 2 | 1.3% |
CCRT | 52 | 32.9% |
Induction CTH + CCRT | 54 | 34.1% |
Best supportive care | 9 | 5.7% |
Total | 158 | 100% |
Course completion | Yes | No | Total |
---|---|---|---|
Radical Radiotherapy | 36 (87.8%) | 5 (12.2%) | 41 (100%) |
CCRT | 47 (87%) | 7 (13%) | 54* (100%) |
Induction CTH + CCRT | 42 (77.8%) | 12 (22.2%) | 54 (100%) |
Total | 125 (3.9%) | 24 (16.1%) | 149 (100%) |
*Including 2 patients who received Adjuvant CTH after the CCRT.
Eighty four percent of total number of included patients continued there radiotherapy course, course discontinuation was attributed to acute side effects in 37.5% of patients, socioeconomic factors in 12.5% of patients.
Acute side effects of radiotherapy were properly reported for 104 patients. Mucositis was by far the most frequently encountered acute side effect in 98.1% of cases, followed by xerostomia in 93.3% of cases with grade 2 being the most frequent.
Patients who received radiotherapy by 2D technique exhibited higher incidence of acute toxicities compared to their counterparts who received 3DCRT, this was highly statistically significant for xerostomia with a p-value > 0.001.
The most frequently encountered late side effects were xerostomia & dysphagia in 80% & 44% of cases respectively.
The incidence of xerostomia, dysphagia, visual affection, hearing affection & neck fibrosis was higher in patients treated with the 2D technique, with xerostomia being significantly lower in patients treated with 3D CRT.
The local response was evaluated in 125 patients who completed the radiotherapy course; evaluation was done 2 - 4 months after treatment by either local imaging or nasopharyngeal endoscopy or both (
The local control among all 149 patients was 48.3% at 3 years and 38.2% at 5 years (
Among all prognostic factors studied, only T-stage (T1-2 vs T3-4), RTH alone vs. RTH + CTH, and RTH course completion had statistically significant difference on both univariate & multivariate analyses.
The DFS among all 149 patients was 42% at 3 years and 33.5% at 5 years.
Local response to treatment | ||
---|---|---|
Local response | Number of patients | Total |
Complete response (CR) | 50 | 40% |
Partial response (PR) | 46 | 36.8% |
Progressive disease (PD) | 10 | 8% |
Not assessed | 19 | 15.2% |
Total | 125 | 100% |
The performance status, T-Stage, the addition of chemotherapy, patients who succeeded to achieve a complete remission and radiotherapy course completion significantly influenced the DFS rates. Multivariate analysis showed them as independent indicators of DFS (
The OS among all 158 patients was 50.9% at 3 years and 37.2% at 5 years (
Patients who were 50 years of age or younger, with performance status I, T1-2 tumor, non-metastatic disease, with stage groups I-III, and those who received chemotherapy in addition to radiotherapy, and those who completed radiotherapy course, and patients who succeeded to achieve a complete remission, had more favorable 3-year & 5-year OS & achieved significantly higher 3-year and 5-year OS rates on univariate analysis .on multivariate analysis performance status and stage group were not persistently significant.
In this retrospective study, 158 patients with nasopharyngeal carcinoma presenting to the radiotherapy department at NCI Cairo from the year 2000 to 2010 were reviewed.
While nasopharyngeal carcinoma can occur in any age, Ferlay et al. 2010 [
The incidence of NPC is higher in males than that in females, and the ratio is 2 - 3:1 [
Most of the patients in our study presented with WHO type III which constituted about 76.6% of all histological type. This came close to the study by Chee et al. (2013) [
The vast majority of patients in our study presented at an advanced stage, as 86% of patients were diagnosed at stage III & IV. Recently, a study from Malaysia analyzing the five-year survival of 134 NPC patients, reported similar findings, where 80% of patients presented at stage III & IV [
With regards to clinical presentation, it was found that 71% of cases presented with a neck swelling. This was entirely consistent with what was reported by Skinner et al. 1991 [
Acute toxicities were recorded during radiotherapy sessions. In the current study, we found that mucositis & xerostomia are the most frequently encountered acute side effects, occurring in 98% & 93.3% respectively. This was nearly similar to what was reported by Lee et al. 2002 [
Most of the studies analyzing the prognostic impact of age in NPC indicate that younger patients have a higher overall survival [
Previous studies have reported slightly better, though not significant, long-term survival rates in women with NPC than in men [
Xiao et al. 2013 [
In a study, retrospectively, reviewed clinical outcome of 905 NPC patients treated by radiation alone during 1990 to 1999 from Mainland China, Karnofsky performance status showed no significant effect on overall and disease-free survival by multivariate analysis [
Many studies have confirmed a clear association between long-term survival and NPC clinical stage [
The efficacy of primary treatment was also found to be an independent prognostic factor affecting long-term survival by univariate & multivariate analyses. The 5-year OS and DFS rates were significantly higher in patients with CR than those with PR (p < 0.001). This was consistent with what was reported by Dou et al. 2014 that the initial treatment modality and its therapeutic efficacy are the major factors affecting the prognosis of patients in all stages of NPC [
Many studies have shown that adding chemotherapy to radiotherapy can improve treatment efficacy and prolong OS in patients with intermediate or advanced stage NPC [
In a meta-analysis by Langendijk et al. 2004, it was shown that the most efficacious way to introduce chemotherapy was concurrently with radiotherapy and this approach resulted in an absolute 5-year survival benefit of 20% [
Several randomized controlled trials compared induction chemotherapy followed by concurrent chemoradiation versus chemoradiation with or without adjuvant chemotherapy in advanced NPC; [
In the treatment of nasopharyngeal carcinoma with radiotherapy, completed planned prescription dose and regular radiotherapy are vital [
The LC as well as the DFS & OS rates in this study were very poor. This may be attributed to a number of reasons. First, over 86% of patients were locally advanced. Second, the 2D technique was used for the vast majority of patients in this study, which may have led to higher acute toxicities that would result in treatment interruptions & radiotherapy course discontinuation [
This study matches the published data that support that radical concurrent chemoradiation is the mainstay of treatment of locally advanced NPC, & that T-stage, M-stage, prescribed dose completion, response to initial treatment are independent prognostic factors for survival.
All measures should be taken to improve the local response during primary treatment as this will improve survival rates of patients with NPC.
Large and multicenteric randomized controlled trials are required to assess whether induction chemotherapy followed by concurrent chemoradiotherapy is superior to chemoradiotherapy for locoregionally advanced NPC.
New techniques like IMRT should be the standard of care for treatment of NPC.
Hebatallah K.Ibrahim,TarekShouman,Azza NiazyTaher,Azza M.Nasr,HeshamAtef, (2015) A Retrospective Study of Clinicoepidemiological Aspects of Nasopharyngeal Cancer at NCI-Cairo (2000-2010). Journal of Cancer Therapy,06,971-980. doi: 10.4236/jct.2015.611105