A Retrospective Study of Nasopharyngeal Carcinoma: Clinical and Treatment Outcome

Abstract Background  Nasopharyngeal carcinoma is an uncommon disease endemic to Southern China, Southeast Asia, North Africa, and the Arctic. It is uncommon in southern India, and hence its treatment outcome and prognosis are not widely studied in these areas. In this study, our primary objective was to document the clinical presentation of patients with nasopharyngeal carcinoma in southern India and to analyze the response to treatment and follow-up. Materials and Methods  The study is an institutional-based retrospective study including 26 patients with histology-proven nasopharyngeal carcinoma from January 2011 to December 2017. All patients were treated with standard protocol of intensity modulated radiotherapy with concurrent chemotherapy. Data on patient demographics, clinical presentation, treatment, and follow-up were analyzed. Results  The median age at presentation in our study was 53.5 years. The most common histopathology subtype was nonkeratinizing undifferentiated carcinoma (65%). Nodal metastasis was the most common clinical presentation seen in 88% of the patients. Post-treatment, distant metastasis to the iliac bone, lung, liver, and spleen was seen in two patients. Complete remission was achieved in 65%, whereas three patients developed recurrence after the completion of treatment. Five-year progression-free survival was 69%. Conclusion  Nasopharyngeal carcinoma has a good response to concurrent chemoradiation. Long-term follow-up and planning surveillance strategies are essential post-treatment. Disease awareness to aid in early diagnosis and optimize management is imperative as observed from the delayed presentations in southern India.


Introduction
Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. 1It is an undifferentiated form of squamous cell carcinoma arising from the epithelium of the nasopharynx.The interplay of genetic susceptibility, Epstein-Barr virus (EBV) infection, and environmental factors are the causative factors leading to the development of NPC. 2 The studies on the outcome and prognostic factors are from endemic high-risk regions, and there is limited data on its epidemiology and outcomes reported from southern India. 3n this study, our aim was to document the clinical presentation of patients with NPC in our tertiary care center and to analyze the response to treatment and follow-up.

Methodology
The study is an institutional-based retrospective study from January 2011 to December 2017.The approval of the Institutional Review Board was taken to look into the medical records of patients (IEC dated 6/5/22, reg no.EC/NEW/INST/ 2020/834).The data was retrieved from the Medical Records Department using the International Classification of Diseases code (code number C 11.9).Twenty-six patients with histology-proven NPC and treated with intensity modulated radiotherapy (IMRT) with concurrent chemotherapy were included in the study.All the patients were from southern India.The data of the pre-treatment evaluation collected included a complete history, physical examination, diagnostic nasal endoscopy, complete blood cell counts, blood biochemistry, chest radiographs, and magnetic resonance imaging (MRI) of the head and neck was collected.The staging of the disease according to the 8th edition of the American Joint Committee on Cancer classification was documented.
All patients underwent IMRT with concurrent chemotherapy weekly with 30 mg/m 2 of cisplatin for 6 weeks.Three patients also received adjuvant chemotherapy due to the advanced stage of the disease (stage IV).
The patients were evaluated daily in the hospital for the assessment and management of acute radiation-related toxicities during the course of chemoradiation.After the completion of radiotherapy, follow-up was done after 1 month, followed by 3 monthly for 5 years and every 6 months thereafter.Evaluation at each follow-up visit included evaluation by the otorhinolaryngologist and the oncologist.A clinical history, ear, nose and throat examination, and diagnostic nasal endoscopy were performed at each visit.An MRI of the head and neck was done when any signs of recurrence were suspected, like complaints of ear block, nasal bleeds, anosmia, and neck nodes.Distant metastases were diagnosed by physical examination and suitable imaging studies (positron emission tomography, computed tomography [CT] scan, or MRI).
Nodal metastasis to levels Ib, II, III, and V was seen in 88% (23 patients) of the cases, of which 18 patients had bilateral nodal metastasis to levels Ib, II, III, and V. Post-treatment distant metastases were seen in two patients; one patient had metastasis to the iliac bone and cranial nerve II, III, IV, and V palsy.The other patient had metastasis to the temporal lobe, lung, liver, and spleen, and cranial nerve III, V, VI, VII, VIII, IX, and X palsies (►Table 2).
The majority of the patients belonged to stage III (42%), followed by stage IV (30%), stage II (15%), and stage I (11%).Complete remission was achieved in 65% (17 patients), whereas three patients developed recurrence after the completion of treatment.One, three, and five-year survival rates were analyzed.The 5-year overall survival rate was 69% (18 patients).Two patients expired during the course of the study.The disease-free survival rate was 65% (17 patients) at the end of 5 years.Three patients developed local recurrence, which was detected on diagnostic nasal endoscopy.The nasopharynx examination showed proliferative mass that bled on touch.Three patients developed recurrence to lymph nodes in level II, III, and V lymph nodes during the follow-up period.Six patients were lost to follow-up.
Radiation-induced adverse effects such as xerostomia, oral mucositis, and dry and moist desquamation were seen in all patients.Two patients developed dyspnea due to lung consolidation, of which one developed sepsis, pleural effusion, and metastasis to the skeletal system.Both patients also developed multiple cranial nerve palsies.Both patients had expired during the course of the study.

Discussion
NPC deserves special consideration because of its many distinctive features that set it apart from other carcinomas in the head and neck region, such as the primary location, which can be missed initially, the late presentation of the disease, varying symptoms, and its rarity in southern India.The area with the highest incidence is in southern China, among the Cantonese population of Guangdong Province.The high incidence in these regions is due to combined genetic and environmental factors.It was observed that migrants from high-risk populations who settle in lowincidence areas have higher incidences than the native population, though the incidence reduces in later generations, like Southern Chinese emigrants to North America. 6n endemic locations, it is mostly linked to EBV infection, while genetic and dietary factors, such as preserved smoked foods, may also play a role in its genesis.Well-differentiated variants may also be linked to smoking. 1 EBV titers could not be measured because our study was retrospective.
The tumor can affect pediatric to geriatric age groups.In low-risk regions, the disease incidence is found to increase with age, while in high-incidence areas, there is a bimodal distribution noted with a small peak in adolescent and young adults and a larger later peak at around 50 to 55 years of age. 1 The median age in our population was 53.5 years, which is similar compared with other parts of the world.A review of several large screening studies conducted in high-incidence areas of China was done by Cao et al. 7 It was observed that NPC incidence among high-risk Cantonese of both sexes increased with age until it peaks between 40 and 59 years.In a study done in southern India by Haleshappa et al, 1 the median age at presentation was 35 years.
The disease is two to three times more frequently seen in males than in females. 8The male-female ratio found in our series was 4.2:1, which is similar to studies by Cao et al 7 (2-3:1) and Haleshappa et al 1 (2.8:1).
Awareness of the disease is crucial.A lot of patients present at a later stage due to ignorance.Our study shows that NPC needs to be considered as a differential diagnosis for a patient with epistaxis.
EBV titers could not be measured as our study was retrospective.The study population was small, owing to nonendemic regions of study.Lack of follow-up for all patients is a drawback of our study.Patients should be counseled about the need for post-treatment surveillance and regular for better treatment outcomes.

Table 1
Clinical presentation of NPC Abbreviation: NPC, nasopharyngeal carcinoma.

Table 2
Sites of post-treatment distant metastases