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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 2  |  Page : 909-914

Prognostic significance of residual or recurrent lymph nodes in the neck for patients with nasopharyngeal carcinoma after radiotherapy


1 Department of Otorhinolaryngology, Fuzhou General Hospital of Nanjing Command Zone of PLA, Fuzhou 350025, China
2 Department of Otorhinolaryngology, Fuzong Clinical College of Fujian Medical University, Fuzhou General Hospital of Nanjing Command Zone of PLA, Fuzhou 350025, China

Date of Web Publication25-Jul-2016

Correspondence Address:
Hui Chen
Department of Otorhinolaryngology, Fuzong Clinical College of Fujian Medical University, Fuzhou General Hospital of Nanjing Command Zone of PLA, No. 156 Xihuanbei Road, Fuzhou 350025, Fujian
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.168969

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 > Abstract 


Background: Nasopharyngeal carcinoma is the most frequently diagnosed primary tumor originating from the nasopharynx, and the preferred treatment modality is radiotherapy.
Aims: To identify nasopharyngeal carcinoma prognostic factors in patients with residual or recurrent cervical lymph node metastases after radiotherapy.
Patients and Methods: The clinicopathologic characteristics and prognoses of 67 nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases who were diagnosed and treated were analyzed retrospectively. The Chi-squared test and Cox proportional hazard regression model were used to investigate associations between survival and clinicopathological features. Cumulative survival plots were obtained using the Kaplan–Meier method.
Results: Data analysis using the Cox proportional hazard regression model revealed that the size of residual or recurrent lymph node metastases, level V lymph node involvement, number of involved levels, surgical procedure performed, and distant metastases were significantly associated with overall survival. Chi-squared analysis only determined a significant correlation between distant metastases and patient survival. Furthermore, the Kaplan–Meier analysis demonstrated that the 1-, 3-, and 5-year survival rates for patients were 86.6%, 52.2%, and 38.6%, respectively. Radical neck dissection resulted in substantially longer overall survival than modified neck dissection.
Conclusion: The size of residual or recurrent lymph node metastases, level V lymph node involvement, number of involved levels, surgical procedure performed, and presence of distant metastases were prognostic factors for nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases after radiotherapy, with distant metastases being the most important determinant. Classical radical neck dissection is recommended for treating recurrent nodal disease in nasopharyngeal carcinoma.

Keywords: Nasopharyngeal carcinoma, prognosis, radiotherapy, residual or recurrent lymph node metastases


How to cite this article:
Wang M, Xu Y, Chen X, Chen H, Gong H, Chen S. Prognostic significance of residual or recurrent lymph nodes in the neck for patients with nasopharyngeal carcinoma after radiotherapy. J Can Res Ther 2016;12:909-14

How to cite this URL:
Wang M, Xu Y, Chen X, Chen H, Gong H, Chen S. Prognostic significance of residual or recurrent lymph nodes in the neck for patients with nasopharyngeal carcinoma after radiotherapy. J Can Res Ther [serial online] 2016 [cited 2019 Sep 17];12:909-14. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/909/168969




 > Introduction Top


Nasopharyngeal carcinoma is the most frequently diagnosed primary tumor originating from the nasopharynx, accounting for approximately 70% of all malignancies of the nasopharynx. Although rarely found in the Western countries, nasopharyngeal carcinoma is one of the most common malignant tumors in the Asian populations, particularly in the southern China and Southeast Asia.[1],[2] Currently, the preferred treatment modality is radiotherapy. The overall survival rate for nasopharyngeal carcinoma patients has improved dramatically in recent decades, largely due to advances in radiotherapy techniques and systemic chemotherapy.[3],[4],[5] However, the predominant causes of therapeutic failure for nasopharyngeal carcinoma include residual or recurrent primary tumors and metastases to cervical lymph nodes and distant sites, thus leading to a reduction in the overall survival rate.[6]

Nasopharyngeal carcinoma frequently metastasizes to the lymph nodes in the neck.[7],[8],[9] Even so, the significance of lymph node involvement in nasopharyngeal carcinoma remains controversial. For example, patients with retropharyngeal lymph node involvement were previously staged as N0 using the 2002 American Joint Committee on Cancer staging system but are now staged as N1 using the 2010 guidelines.[10] To date, there are no detailed clinical investigations describing the appropriate therapy and prognosis for nasopharyngeal carcinoma patients with residual or recurrent cervical nodal disease after radiotherapy. In the present study, the clinicopathological features and outcomes of 67 nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases were retrospectively analyzed.


 > Patients and Methods Top


Patients

A retrospective analysis of a total of 67 nasopharyngeal carcinoma cases with residual or recurrent lymph node metastases in the neck was performed. Patients were diagnosed and treated between January 2004 and December 2007. The study cohort was comprised of 49 men and 18 women with a mean age of 47.3 years (range, 19–76 years). The eligibility criteria included pathologically confirmed, nonkeratinizing differentiated or undifferentiated carcinoma, treatment with radiotherapy or concurrent radiotherapy plus chemotherapy, presence of residual or recurrent lymph node metastases in the neck, absence of a residual or recurrent primary tumor, and postoperatively confirmed malignancies. The exclusion criteria included pathologically confirmed adenocarcinoma of other types, failure to complete the full course of treatment, presence of residual or recurrent primary tumor, and the absence of tumor cells in surgical tissues. This study was reviewed and approved by the Ethics Committee of Fuzhou General Hospital.

Diagnostic criteria

Residual lymph node metastases in the neck were defined as malignant masses that remained in the lymph node 3 months after treatment. In contrast, recurrent cervical lymph node metastases were defined as masses that completely regressed within 3 months following treatment but then reappeared again 3 months after treatment. The recurrent lymph node metastases were staged using magnetic resonance imaging and computed tomography.

Clinicopathological characteristics

Patient sex, age, histological type of primary tumors, size of residual or recurrent lymph nodes, bilateral or unilateral lymph node involvement, extent (level) of lymph node involvement, number of levels of lymph node involvement, surgical procedure performed for recurrent lymph nodes, carotid artery invasion, serious postoperative complications, repeated postoperative adjuvant radiotherapy, postoperative recurrence, and presence of distant metastases were extracted from hospital records [Table 1]. Residual or recurrent lymph nodes were confirmed by magnetic resonance imaging and pathological findings. Furthermore, the size of residual or recurrent lymph nodes, extent of lymph node involvement, and presence of distant metastases were also examined with magnetic resonance imaging. The surgical procedures performed for recurrent lymph node metastases included modified neck dissection for rN1 and rN2 patients or patients with a lymph node diameter <1 cm and radical neck dissection for rN3 patients or rN1 and rN2 patients with extracapsular invasion. Patients with residual lymph node metastases after surgery received postoperative radiotherapy with a dosage totaling 35–50 Gy.
Table 1: Clinicopathologic parameters and overall survival of 67 nasopharyngeal carcinoma patients

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Follow-up

Follow-up data were obtained by phone, letter, or hospital referral. Of the 67 patients, 12 (17.9%) received postoperative adjuvant radiotherapy and nine (13.4%) showed recurrence after surgery. By the end of follow-up, 7 (10.4%) patients were deceased and their data were censored in the analysis.

Statistical analysis

The Chi-squared (χ2) test and Cox proportional hazard regression model were used to investigate the associations between survival and various clinicopathological features. Cumulative survival plots were created using the Kaplan–Meier method. A P < 0.05 indicated statistical significance. All statistical analyses were performed using SPSS, version 18.0 for Windows (SPSS Inc., Chicago, IL, USA).


 > Results Top


Among the 67 patients, 9 (13.4%) had residual disease in the neck after surgery, but only two received additional surgical treatment due to the high cost of surgical procedures. Eight patients developed distant metastases 2 years after surgery with recurrent sites including the liver (n = 3), lung (n = 2), bone (n = 1), liver and bone (n = 1), and lung and bone (n = 1).

A Chi-squared test was performed to evaluate the associations between survival and clinicopathological features. The analysis demonstrated that the presence of distant metastases was significantly correlated with patient survival (P < 0.05). However, there were no statistical associations between patient survival rates and other parameters including sex, age, histology of primary tumors, size of residual or recurrent lymph nodes, bilateral or unilateral lymph node involvement, extent of lymph node involvement, number of involved levels, surgical procedure performed for recurrent lymph node metastases, carotid artery invasion, serious postoperative complications, postoperative adjuvant radiotherapy, or postoperative recurrence [Table 1]. Analysis of data using the Cox proportional hazard regression model revealed that the size of residual or recurrent lymph node metastases, level V (accessory nerve) lymph node involvement, number of involved lymph node levels, surgical procedure performed, and presence of distant metastases were significantly associated with overall survival in these patients [Table 2].
Table 2: Multivariate analysis of various prognostic factors in 67 nasopharyngeal carcinoma patients

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A Kaplan–Meier analysis demonstrated that the 1-, 3-, and 5-year survival rates for patients were 86.6%, 52.2%, and 38.6%, respectively, with a mean survival of 42.8 ± 2.6 months [Figure 1]. All the patients didn't receive additional therapy. The 1-, 3-, and 5-year survival rates for patients who received modified neck dissection were 86.9%, 47.8%, and 26.1%, respectively, with a mean survival of 33.0 ± 4.3 months. In contrast, the 1-, 3-, and 5-year survival rates for patients who received radical neck dissection were 86.4%, 63.6%, and 45.1%, respectively, with a mean survival of 47.4 ± 3.3 months. These data indicate that patients receiving radical neck dissection had substantially longer overall survival than those patients who received modified neck dissection [Figure 2].
Figure 1: Kaplan–Meier analysis of the overall survival of 67 nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases

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Figure 2: Kaplan–Meier analysis of the overall survival of 67 nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases with data stratified by radical neck dissection and modified neck dissection

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 > Discussion Top


Many factors contribute to the presence of residual or recurrent cervical lymph node metastases in patients with nasopharyngeal carcinoma after radiotherapy, such as clinicopathological characteristics, tumor angiogenesis, cancer stem cells, and immune response. Treatment of nasopharyngeal carcinoma relies on an evaluation of tumor size, site and extent of residual or recurrent lymph node metastases, histology of the primary tumor, carotid artery invasion, surgical treatment approach, and postoperative adjuvant radiotherapy. Although, there are some reports describing the influence of local recurrence on the prognosis of nasopharyngeal carcinoma patients,[11],[12] the prognostic significance of residual or recurrent cervical lymph node metastases in patients with nasopharyngeal carcinoma required further investigation.

Various nasopharyngeal carcinoma prognostic factors have been reported previously. In the present retrospective study, analysis of nasopharyngeal carcinoma cases showed that the presence of distant metastases was significantly associated with overall survival. The relative risk in patients with distant metastases was 17 times greater than that of patients without distant metastases. These results imply that the presence of distant metastases was a negative prognostic indicator for patients with residual or recurrent lymph node metastases. Although other factors, including the size of residual or recurrent lymph nodes, level V lymph node involvement, number of involved levels, and type of surgical procedure performed also correlated with prognosis, the relative risk of local lymph node metastases was much lower than that of distant metastases. Notably, analysis using the Cox proportional hazard regression model indicated that many factors were associated with patient survival. The prognostic factors observed in this study have also been reported by others.

Previous studies have reported that additional therapy for residual or recurrent lymph node metastases in the neck prolong patient survival.[13],[14] Consistent with previous findings, this analysis also showed excellent 1-, 3-, and 5-year survival rates for patients who underwent neck dissection, indicating that surgery is an effective therapy for patients. Other studies have shown that salvage surgery was also effective in the management of nasopharyngeal carcinoma cases with residual or recurrent cervical lymph node metastases after primary treatment.[15],[16],[17] Furthermore, this analysis also indicated that patients who received radical neck dissection had much longer survival times than those who received modified neck dissection.

Several studies have reported residual or recurrent primary sites in nasopharyngeal carcinoma. However, the prognostic significance for residual or recurrent cervical lymph node metastases remains controversial. In previous studies, re-irradiation of residual or recurrent primary sites provided an acceptable local control rate, but was also associated with several toxicities, such as mucosal necrosis and massive hemorrhage,[18],[19] late-onset pneumonia,[20] temporal lobe injury,[21] and brachial plexus injury.[22] Concurrent chemoradiotherapy was an independent negative prognostic factor for local progression free survival.[23] Chemotherapy alone also has a poor effect and a moderate toxicity.[24],[25] Re-irradiation is an alternative treatment for only selected head and neck cancer patients who are not suitable for salvage surgery. The effectiveness of re-irradiation can be potentiated by chemotherapy or targeted therapy.[26] In our study, however, irradiation after surgery did not improve the survival rate compared to salvage surgery alone. In Addition, radiotherapy can cause cervical fibrosis in patients with nasopharyngeal carcinoma, which can lead to difficulties in diagnosis of residual or recurrent lymph node metastases.[27],[28] Given the difficulties of radiotherapy, classical radical neck dissection, which has a good outcome without major complications, remains the recommended treatment for recurrent nodal disease in nasopharyngeal carcinoma and other head and neck cancers.[29],[30],[31]

These results, together with our observations, strongly suggest that salvage surgery, the preferred classical radical neck dissection technique, is necessary for nasopharyngeal carcinoma patients with residual or recurrent cervical nodal metastases after primary treatment.


 > Conclusion Top


The data demonstrates that the size of residual or recurrent lymph node metastases, level V lymph node involvement, number of involved levels, surgical procedure performed, and distant metastases were prognostic factors for nasopharyngeal carcinoma patients with residual or recurrent cervical nodal metastases after radiotherapy, with the presence of distant metastases being the most important determinant. Furthermore, classical radical neck dissection is recommended for treating recurrent nodal disease in nasopharyngeal carcinoma. We speculate that some of the observed variability in this study is likely due to variable survival data used in these analyses and a relatively small study population. A larger cohort of patients should be analyzed to confirm the findings observed here.

Financial support and sponsorship

This study was supported by grants from the Science and Technology Project (Key Project) of Fujian Province, China (No: 2012y5007), and the Natural Science Foundation of Fujian Province, China (No: 3013J01396, 2015J01485).

Conflicts of interest

There are no conflicts of interest.

 
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