|Year : 2015 | Volume
| Issue : 3 | Page : 391-395
Nasopharyngeal cancers: A retrospective comparative analysis of radiotherapy alone versus chemo-radiation (Benghazi experience)
A Pakkirmasthan1, S Kurakula2
1 Department of Oncology, Specialist, Sekgoma Memorial Hospital, Serowe, Botswana, Africa
2 Department of Gynecology, Specialist, Sekgoma Memorial Hospital, Serowe, Botswana, Africa
|Date of Web Publication||18-Feb-2016|
Department of Gynecology, Specialist, Sekgoma Memorial Hospital, Serowe, Botswana
Source of Support: None, Conflict of Interest: None
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.
Keywords: Clinical presentation, nasopharyngeal cancers, response
|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
|How to cite this URL:|
Pakkirmasthan A, Kurakula S. Nasopharyngeal cancers: A retrospective comparative analysis of radiotherapy alone versus chemo-radiation (Benghazi experience). Indian J Cancer [serial online] 2015 [cited 2019 Nov 15];52:391-5. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/391/176718
| » 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., The elevated levels of serum EBV antibody are present in patients of nasopharyngeal cancers (NPCs) Henle and Henle.
Recently, Ji et al. 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.
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) are common symptoms [Figure 2].
|Figure 2: The computed tomography films shows the extent of disease with regard to treatment planning|
Click here to view
The most common site of distant metastases is bone (48.5%) followed by lung (30.3%) and liver (29.3%)., 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].
|Table 3: Frequency of presenting symptoms in cancer of nasopharynx (most of patients present with multiple symptoms)|
Click here to view
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.
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].
|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)|
Click here to view
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].
|Figure 4: Comparison of IMRT, 3-D conformal and traditional parallel-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|
Click here to view
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].
|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|
Click here to view
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.
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].
|Figure 6: The survival curve shows the survival benefit for chemo-radiation groups. Statistical Package for the Social Sciences version 10 is used|
Click here to view
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 T3N1M0 (undifferentiated Ca) developed bone metastases and another T4N1M0 (Anaplastic Cancer) developed brain metastases.
However, one case of T3N0M0 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 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 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%,, 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.,, The intergroup study in USA  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. 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|| |
Ho HC, Ng MH, Kwan HC, Chau JC. Epstein-Barr-virus-specific IgA and IgG serum antibodies in nasopharyngeal carcinoma. Br J Cancer 1976;34:655-60.
Huang DP, Ho JH, Henle W, Henle G. Demonstration of Epstein-Barr virus-associated nuclear antigen in nasopharyngeal carcinoma cells from fresh biopsies. Int J Cancer 1974;14:580-8.
Henle W, Henle G. Evidence for an etiologic relation of the Epstein-Barr virus to human malignancies. Laryngoscope 1977;87:467-73.
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 of nasopharyngeal carcinoma. Br J Cancer 2007;96:623-30.
Khor TH, Tan BC, Chia KB. Distant metastasis in nasopharyngeal carcinoma. A review of 759 patients. Br J Radiol 1990;63:51-8.
Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, et al
. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized Intergroup study 0099. J Clin Oncol 1998;16:1310-7.
Hoppe RT, Williams J, Warnke R, Goffinet DR, Bagshaw MA. Carcinoma of the nasopharynx – The significance of histology. Int J Radiat Oncol Biol Phys 1978;4:199-205.
Lederman M. Cancer of Nasopharynx: Its Natural History and Treatment. Spring Field, IL: Charles C Thomas; 1961.
Chatani M, Teshima T, Inoue T, Azuma I, Yoshimura H, Oshitani T, et al
. Radiation therapy for nasopharyngeal carcinoma. Retrospective review of 105 patients based on a survey of Kansai Cancer Therapist Group. Cancer 1986;57:2267-71.
Rossi A, Molinari R, Boracchi P, Del Vecchio M, Marubini E, Nava M, et al
. Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: Results of a 4-year multicenter randomized study. J Clin Oncol 1988;6:1401-10.
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. International Nasopharynx Cancer Study Group. VUMCAI trial. Int J Radiat Oncol Biol Phys 1996;35:463-9.
Oh JL, Vokes EE, Kies MS, Mittal BB, Witt ME, Weichselbaum RR, et al
. Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer. Ann Oncol 2003;14:564-9.
Rischin D, Corry J, Smith J, Stewart J, Hughes P, Peters L. Excellent disease control and survival in patients with advanced nasopharyngeal cancer treated with chemoradiation. J Clin Oncol 2002;20:1845-52.
Licitra L, Bossi P, Palazzi M et al
. Chemoradiotherapy in locally advanced nasopharyngeal cancer (NPC): Results of two consecutive studies. Ann Oncol 2002, 13 Suppl 3:19.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4]