Prognosticators and Risk Grouping in Patients with Lung Metastasis from Nasopharyngeal Carcinoma: A more accurate and appropriate assessment of prognosis
- Xun Cao†1, 2,
- Rong-Zhen Luo†1, 3,
- Li-Ru He1, 4,
- Yong Li1, 2,
- Wen-Qian Lin1, 5,
- You-Fang Chen1, 2 and
- Zhe-Sheng Wen1, 2Email author
© Cao et al; licensee BioMed Central Ltd. 2011
Received: 13 April 2011
Accepted: 26 August 2011
Published: 26 August 2011
Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC.
A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves.
The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%.
In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.
Nasopharyngeal carcinoma (NPC) is a common epithelial malignancy in southern China [1–3]. The highest incidence has been reported in Guangdong province, where the rate is approximately 20 per 100,000 people per year [1, 2]. According to World Health Organisation (WHO) classification based on histological type, most endemic NPCs are type II (non-keratinising carcinoma) and type III (undifferentiated carcinoma), with a high incidence of lymphatic and circulatory metastasis [3, 4]. With improvements in the control of local disease due to advanced diagnostic methods, radiotherapeutic techniques and chemotherapy regimens, distant metastasis (DM) is increasingly becoming the major cause of mortality in NPCs [5, 6]. The survival period after DM is variable, and long-term survival is improved in patients who receive aggressive multimodality therapy [7–11].
Lung metastasis commonly occurs in NPC [9, 12, 13]. Some studies have reported that patients with lung metastasis belong to a distinct group with a good prognosis and better survival [8, 9, 13–15]. Nevertheless, no systematic study has specifically addressed the factors that are associated with lung metastasis in NPC patients. Hence, our retrospective study was designed to examine the relationship between clinical factors and lung metastasis survival (LMS) and overall survival (OS), as well as to identify low-, intermediate- and high-risk subsets that may help in the development of patient-tailored medical support and treatment.
Patient and disease characteristics of 198 NPC patients with lung metastasis
No. of Patients
Site of metastases
Number of metastases
Size of metastases †
Mediastinal nodal metastases ‡
Radiation therapy was the mainstay of treatment. All patients had planning computerized tomography of the head and neck performed with patient in the treatment position. Computerized tomography-assisted radiation treatment planning was obtained before the initiation of radiotherapy. A 4-MV or 6-MV linear accelerator was used for treatment. The radiation dose ranged from 64 to 70 Gy, according to the tumor stage. Advanced-stage patients (65.2%, n = 129) received 4 to 6 cycles of combination chemotherapy (cisplatin/5-fluorouracil) before, during, and/or after radiotherapy. At a clinical examination six weeks later, all patients were in complete remission (CR), as confirmed by endoscopic examination with or without biopsy and a CT or MRI scan of the head and neck.
After the primary treatment, patients were regularly followed up until death or the last follow-up (follow-up visits occurred every 4-6 months in the first 3 years and every 12 months thereafter). The last follow-up was performed in December 2010. To identify local recurrence or distant metastasis, patients were evaluated with periodic examinations of the nasopharynx. Evaluation of systemic complaints included chest X-rays and abdominal ultrasounds. A CT scan of the chest or abdomen and a bone scan were performed if the initial examination showed abnormal findings that were suggestive of metastasis. If the results of the CT scan were suspicious, lung metastasis was confirmed by biopsy.
Pulmonary metastasis was defined by CT imaging and clinical characteristics on basis of at least two of the following criteria: (1) a soft tissue opacity > 5 mm in the short-axis diameter; (2) peripheral location; (3) multiple lung lesions; (4) patients with advanced stage of the primary NPC; (5) patients with DFI≤ 24 months. These criteria and characteristics have been described and used by some previous literatures and reports[13, 16–22].
When lung metastasis(es) was diagnosed, the patient was offered cisplatin-based chemotherapy. Fifty-seven cases (chemotherapy group) received palliative resection or radiotherapy in addition to chemotherapy. One hundred and forty-one patients (chemoradiotherapy group), especially the patients with multiple lung metastases (n = 133), received only chemotherapy. The treatment distribution of patient with solitary lung metastasis were 32 chemotherapy-only patients, 12 chemoradiotherapy patients and 21 chemotherapy plus palliative resection patients. The treatment distribution of patients with multiple lung metastases were 109 chemotherapy-only patients, 17 chemoradiotherapy patients and 7 chemotherapy plus palliative resection. The patients with local recurrence received a second course of external radiotherapy (n = 23).
The survival status was verified using the best available methods, including verifying the clinical attendance records and with direct telecommunication with the patient or their family.
Disease-free interval (DFI) was defined as the interval between the onset of the primary treatment and the time of the first diagnosis of lung metastasis(es). Overall survival (OS) was defined as the time from the date of primary treatment to the date of death or the final clinical follow-up. Lung metastatic survival (LMS) was defined as the interval between the date of first diagnosis of lung metastasis(es) and the date of death or final follow-up. The factor analysis for OS and LMS included gender, age, VCA-IgA titre, EA-IgA titre, T classification, N classification, site of metastases (location of pulmonary metastasis, unilateral or bilateral), number of metastases, size of metastases, mediastinal nodal metastases, local recurrence, secondary metastases [subsequent metastases, any distant organ metastasis(es) just presented after lung metastasis(es)], and DFI. The actuarial OS and LMS were estimated using the Kaplan-Meier method, and the differences between the survival curves were compared using the log-rank test. The Cox proportional hazards regression model was used to assess the prognostic significance of the different factors. Statistical significance was defined as P < 0.05. The statistical analyses were performed using the SPSS 13.0 software package (SPSS, Inc., Chicago, IL).
Patients and Disease Characteristics
A total of 198 patients (156 male and 42 female) were included in this study. The median age was 44.5 years (range, 20 to 80 years). Increased titres of VCA-IgA and EA-IgA were detected in 39.9% (n = 79) and 35.4% (n = 70) patients, respectively. The histological types of 98.5% of the patients were non-keratinising or undifferentiated carcinoma (WHO type II or III). The distribution of patients within the T classifications were 83 T1-T2 patients (41.9%) and 115 T3-T4 patients (58.1%). The distributions in the N classifications were 115 N0-N1 patients (58.1%) and 83 N2-N3 patients (41.9%). Approximately half of the patients had bilateral metastases (52.5%). DFI≤ 24 months occurred in 108 patients (54.5%), compared with DFI > 24 months in 90 patients (45.5%). Most cases had lung metastasis(es) without local recurrence (88.4%) and/or secondary metastases (75.3%). In total, 133 patients (67.2%) had multiple lung metastases, and 61.1% (n = 121) of those patients did not have mediastinal node metastases. Metastases ≥3 cm in diameter was present in 56 cases (28.3%). The details are listed in Table 1.
All the patients were followed up regularly and the last follow-up was carried out in December 2010, 143 cases developed cancer-related deaths (lung metastasis or secondary metastasis).
Univariate Analysis of Clinical Variables
Univariate analysis of clinical variables for LMS and OS
P value *
P value *
0.739 to 1.591
0.726 to 1.563
1.132 to 2.202
1.241 to 2.414
VCA-IgA (≤1:320 vs. >1:320)
1.067 to 2.383
0.909 to 2.028
EA-IgA (≤1:40 vs. >1:40)
0.687 to 1.566
0.762 to 1.743
AJCC T classification
0.939 to 1.845
1.139 to 2.276
AJCC N classification
0.972 to 1.889
1.050 to 2.056
Site of metastases 1
1.127 to 2.205
1.433 to 2.840
Number of metastases 2
1.155 to 2.413
1.404 to 2.971
Size of metastases 3 †
0.710 to 1.504
0.981 to 2.079
Mediastinal node metastases 4 ‡
0.753 to 1.496
0.875 to 1.740
Locoregional recurrence 5
0.787 to 2.071
0.650 to 1.719
Secondary metastases 6
2.116 to 4.541
1.263 to 2.652
DFI (months, ≤24 vs. >24)
0.950 to 1.860
2.923 to 6.060
Multivariate Analysis of Clinical Variables
Multivariate analysis of clinical variables for LMS and OS
P value *
1.107 to 2.484
1.012 to 2.277
Site of metastases 1
0.606 to 1.757
Number of metastases 2
1.013 to 2.481
Secondary metastases 3
1.948 to 5.036
1.355 to 2.682
AJCC T classification
1.074 to 2.177
AJCC N classification
1.149 to 2.289
Site of metastases 1
1.023 to 2.095
Number of metastases 2
0.630 to 1.848
Secondary metastases 3
1.585 to 3.462
3.356 to 7.576
Identification of Low-, Intermediate-, and High-risk Subsets
Based on the univariate and multivariate analyses of the clinical variables, we were able to classify the 198 cases into three subsets according to the presence of independently significant, negative prognostic factors (age, VCA-IgA, T classification, N classification, site of metastases, secondary metastases, number of metastases and DFI) for survival.
Identification of low-, intermediate-, high-risk subsets
No. of patients (%)
90.7 (63.7 to 117.6)
48.2 (36.3 to 60.0)
40.2 (35.6 to 44.8)
Unlike other head and neck squamous cell carcinomas, NPC is a highly chemo- and radiosensitive tumor . An intergroup study compared concurrent chemoradiotherapy (CCRT) with radiotherapy alone and found a significant improvement in survival [23–27]. However, the cases of long-term survivors were anecdotal. Most patients succumbed to DM [5, 6]. Of the patients with metastases, those with lung metastases comprised a distinct group with a better prognosis and length of survival [8, 9, 13–15]. Kwan and associates reported that an 18-year-old patient with NPC and intrathoracic metastases survived disease-free for 5 and a half years after primary therapy . Despite the many reports and the literature on prognostic factors and survival rates in patients with NPC [29–34], the present study is novel because the cohorts were limited to a specific site of metastasis(es), the lungs. Based on the unique aetiology, patient characteristics, uniform therapies and long follow-up after the primary treatment, our study demonstrated several clinical factors that are associated not only with LMS but also with OS. Moreover, three risk subsets have been defined, based on the prognostic factors. These subgroups may aid clinicians in selecting the appropriate treatment strategies for patients.
Compared with previous reports, we examined both LMS and OS. We believe that the disease has an integral course that cannot be divided into several parts. Only considered LMS was contrasted to the point that DM originated from occult dissemination at the first diagnosis of NPC and/or at the onset of primary therapies . In addition, the definition of LMS was influenced by the time of diagnosis of DM, which was in turn influenced by the regularity of follow-up. As a consequence, we also examined OS, which is a more informative and appropriate interval. The impact of DFI on LMS and OS was not ignored in our analysis. We found that the use of DFI, LMS and OS as the outcome measures identified the more comprehensive and credible prognostic factors and minimised potential biases.
Consistent with the findings reported by the previous studies, we confirmed that the independently significant negative predictive factors for survival included advanced increased age, T classification, N classification and VCA-IgA titre [3, 33, 36–38].
Despite some earlier studies that suggested that the number of metastasis(es) and the site of metastasis(es) were not related to survival [13, 39, 40], we found a statistically significantly different survival rate between patients with solitary and multiple metastases and between unilateral and bilateral pulmonary metastases. The discrepancies between the findings in the literature and our study are likely the result of the different methods that were used to assess the survival outcome in various cohorts of patients. However, this conclusion merits additional research. However, our study failed to demonstrate the correlations between size of lung metastasis(es) and survival by either a univariate or multivariate analysis (P > 0.05). Furthermore, we investigated the impact of mediastinal node metastases on survival. Regardless of the status of mediastinal lymph nodes, there was no significant difference in survival. Adenopathy was defined by CT imaging as a lymph node > 1 cm in size in the short-axis diameter. We postulated that the use of node size to predict involvement by the tumor had some limitations. For example, some patients with micrometastases may not be detected, and enlarged lymph nodes from other causes may be wrongly diagnosed. Moreover, the various mediastinal node metastases might lead to various prognoses. For example, metastases in mediastinal and/or subcarinal lymph nodes may present more extensive spread than peribronchial and/or hilar and intrapulmonary lymph nodes. Local recurrence has been widely recognised as an independent prognostic factor [9, 30]. Notably, local recurrence did not predict survival in our study. Although there was a trend that the patients with lung metastasis(es) that were concurrent with local recurrence had a shorter median OS than patients without local recurrence (46.7 vs. 52.8 months), a statistical difference was not observed between the two groups. This may be due to lack of uniform assessment of local recurrence and histological evidence. Additionally, we cannot detect the micro-recurrence of nasopharynx and regional neck lymph nodes. We have shown that in the current study, for the first time, secondary metastases correlated negatively with survival. Future study should focus on adequate and meticulous collection and analysis of the complaints suggesting micrometastases in the course of managing the NPC patient which may improve the usefulness of this predictive factor. The impact of the DFI on survival has been well documented and discussed. Various investigators chose different cut-off points for the DFI[12, 13, 41]. In this study, we found a statistically significant correlation between the DFI (≤24 months vs. >24 months) and survival.
In the design of this study, we hoped to identify prognostic factors for lung metastatic NPC patients and to stratify patients into different risk categories. The survival outcomes of the low-, intermediate- and high-risk subsets were significantly different. We thought those subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports. The outcome of low-risk patients is excellent. The 3-, 5- and 10-year survival rates of the low-risk subset were 77.3%, 60%, and 59%, respectively. We should focus on bringing long-term survival and reducing treatment associated toxicities and complications. Intermediate-risk patients have a modest outcome. The natural history and management of metastatic NPC patients has been long an area of controversy. Our results shown that The 3-, 5- and 10-year survival rates of the intermediate-risk subset were 52.3%, 30%, and 27.8%, respectively. Thus, among those patients, future trials should reevaluate the benefit of sequentially aggressive treatments, such as concurrent chemoradiotherapy and palliative operation. Patients in high-risk subset have poorer prognosis with 3-, 5- and 10-year survival rates as follow: 20.5%, 7%, and 0%. Future studies should focus on relieving clinical symptoms and improving quality of life. We think that these predictive factors and risk groupings could facilitate the establishment of patient-tailored medical strategies and supports.
We acknowledged the limitations of our retrospective analyses. Firstly, not all patients had CT scan of thorax and/or abdomen at the time of diagnosis of NPC, and it is possible that some patients had micrometastasis at the time of diagnosis of NPC which cannot be detected by Chest X-ray and/or ultrasound. Secondly, follow-up CT scan of thorax was not standardized and typically only performed in the patients with abnormal chest X-ray findings. This would, underestimate the true risk of developing lung metastasis(es). If the CT scan of chest and/or PET/CT were used as the standardized follow-up, some micrometastasis in lung missed by X-ray might be detected. However, the clinical and radiographic picture was consistent with lung metastasis(es) from NPC. The primary strength of our study was unique aetiology, patient characteristics, uniform therapies and long follow-up analyzed, which facilitated identifying multiple clinicopathological risk parameters in lung metastatic NPC patients.
Our study is the first to focus on the prognostic factors and outcomes in NPC patients with pulmonary metastasis(es). We illustrated that age > 45 years, advanced T classification and N classification, elevated VCA-IgA titre, bilateral lung metastases, multiple lung metastases, secondary metastases and a DFI≤24 months were independent, significant and negative factors affecting OS or LMS. The prognosis of the low-, intermediate- and high-risk subsets based on these prognostic factors were significantly different. Thus, we would obtain a more accurate and appropriate assessment of the prognosis of a lung metastatic NPC patient and could facilitate the establishment of patient-tailored medical strategies and supports.
This study was supported by grants from the Science and Technology Project of Guangzhou, China (2009Y-C011-2).
- Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61: 69-90. 10.3322/caac.20107View ArticlePubMedGoogle Scholar
- Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005, 55: 74-108. 10.3322/canjclin.55.2.74View ArticlePubMedGoogle Scholar
- Wei WI, Sham JS: Nasopharyngeal carcinoma. Lancet 2005, 365: 2041-2054. 10.1016/S0140-6736(05)66698-6View ArticlePubMedGoogle Scholar
- Marks JE, Phillips JL, Menck HR: The National Cancer Data Base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer 1998, 83: 582-588. 10.1002/(SICI)1097-0142(19980801)83:3<582::AID-CNCR29>3.0.CO;2-RView ArticlePubMedGoogle Scholar
- Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, Zee BC, Law SC, Teo PM, Tung SY, et al.: Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2005, 61: 1107-1116. 10.1016/j.ijrobp.2004.07.702View ArticlePubMedGoogle Scholar
- Ng WT, Lee MC, Hung WM, Choi CW, Lee KC, Chan OS, Lee AW: Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2011, 79: 420-428. 10.1016/j.ijrobp.2009.11.024View ArticlePubMedGoogle Scholar
- Fandi A, Bachouchi M, Azli N, Taamma A, Boussen H, Wibault P, Eschwege F, Armand JP, Simon J, Cvitkovic E: Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type. J Clin Oncol 2000, 18: 1324-1330.PubMedGoogle Scholar
- Hui EP, Leung SF, Au JS, Zee B, Tung S, Chua D, Sze WM, Law CK, Leung TW, Chan AT: Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Cancer 2004, 101: 300-306. 10.1002/cncr.20358View ArticlePubMedGoogle Scholar
- Teo PM, Kwan WH, Lee WY, Leung SF, Johnson PJ: Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma. Cancer 1996, 77: 2423-2431. 10.1002/(SICI)1097-0142(19960615)77:12<2423::AID-CNCR2>3.0.CO;2-NView ArticlePubMedGoogle Scholar
- Wolff HA, Rodel RM, Gunawan B, Overbeck T, Herrmann MK, Hennies S, Hille A, Vorwerk H, Matthias C, Hess CF, Christiansen H: Nasopharyngeal carcinoma in adults: treatment results after long-term follow-up with special reference to adjuvant interferon-beta in undifferentiated carcinomas. J Cancer Res Clin Oncol 2010, 136: 89-97. 10.1007/s00432-009-0640-2PubMed CentralView ArticlePubMedGoogle Scholar
- Khanfir A, Frikha M, Ghorbel A, Karray H, Drira MM, Daoud J: [Metastatic nasopharyngeal carcinoma: clinical study and therapeutic results of 95 cases]. Cancer Radiother 2006, 10: 545-549.View ArticlePubMedGoogle Scholar
- Ong YK, Heng DM, Chung B, Leong SS, Wee J, Fong KW, Tan T, Tan EH: Design of a prognostic index score for metastatic nasopharyngeal carcinoma. Eur J Cancer 2003, 39: 1535-1541. 10.1016/S0959-8049(03)00310-1View ArticlePubMedGoogle Scholar
- Winter H, Meimarakis G, Hoffmann G, Hummel M, Ruttinger D, Zilbauer A, Stelter K, Spelsberg F, Jauch KW, Hatz R, Lohe F: Does surgical resection of pulmonary metastases of head and neck cancer improve survival? Ann Surg Oncol 2008, 15: 2915-2926. 10.1245/s10434-008-0001-4View ArticlePubMedGoogle Scholar
- Cheng LC, Sham JS, Chiu CS, Fu KH, Lee JW, Mok CK: Surgical resection of pulmonary metastases from nasopharyngeal carcinoma. Aust N Z J Surg 1996, 66: 71-73. 10.1111/j.1445-2197.1996.tb01114.xView ArticlePubMedGoogle Scholar
- Ma J, Wen ZS, Lin P, Wang X, Xie FY: [The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma: a retrospective study of 105 cases]. Chin J Cancer 2010, 29: 787-795.View ArticlePubMedGoogle Scholar
- Leong PP, Rezai B, Koch WM, Reed A, Eisele D, Lee DJ, Sidransky D, Jen J, Westra WH: Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma. J Natl Cancer Inst 1998, 90: 972-977. 10.1093/jnci/90.13.972View ArticlePubMedGoogle Scholar
- Shepherd MP: Thoracic metastases. Thorax 1982, 37: 366-370. 10.1136/thx.37.5.366PubMed CentralView ArticlePubMedGoogle Scholar
- Askin FB: Something old? Something new? Second primary or pulmonary metastasis in the patient with known extrathoracic carcinoma. Am J Clin Pathol 1993, 100: 4-5.PubMedGoogle Scholar
- Vyas JJ, Desai PB, Rao ND: Exploratory thoracotomy on a patient with previous malignancy--"metastasis" or "new primary" or "unrelated lesion". J Surg Oncol 1981, 18: 281-286. 10.1002/jso.2930180310View ArticlePubMedGoogle Scholar
- Adkins PC, Wesselhoeft CW Jr, Newman W, Blades B: Thoracotomy on the patient with previous malignancy: metastasis or new primary? J Thorac Cardiovasc Surg 1968, 56: 351-361.PubMedGoogle Scholar
- Husband JE, Reznek RH: Imaging in oncology. 2nd edition. London: Taylor & Francis; 2004.Google Scholar
- Buthiau D, Khayat D: CT and MRI in oncology. Berlin; London: Springer; 1998.View ArticleGoogle Scholar
- Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY: Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol 2003, 21: 631-637. 10.1200/JCO.2003.06.158View ArticlePubMedGoogle Scholar
- Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, et al.: Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2005, 97: 536-539. 10.1093/jnci/dji084View ArticlePubMedGoogle Scholar
- Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, et al.: Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 2002, 20: 2038-2044. 10.1200/JCO.2002.08.149View ArticlePubMedGoogle Scholar
- Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R, Tung R, Siu L, Ng WT, Sze WK, Au GK, et al.: Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2010, 102: 1188-1198. 10.1093/jnci/djq258View ArticlePubMedGoogle Scholar
- Lee N, Harris J, Garden AS, Straube W, Glisson B, Xia P, Bosch W, Morrison WH, Quivey J, Thorstad W, et al.: Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol 2009, 27: 3684-3690. 10.1200/JCO.2008.19.9109PubMed CentralView ArticlePubMedGoogle Scholar
- Kwan WH, Teo PM, Chow LT, Choi PH, Johnson PJ: Nasopharyngeal carcinoma with metastatic disease to mediastinal and hilar lymph nodes: an indication for more aggressive treatment. Clin Oncol (R Coll Radiol) 1996, 8: 55-58.View ArticleGoogle Scholar
- Perez CA, Devineni VR, Marcial-Vega V, Marks JE, Simpson JR, Kucik N: Carcinoma of the nasopharynx: factors affecting prognosis. Int J Radiat Oncol Biol Phys 1992, 23: 271-280. 10.1016/0360-3016(92)90741-YView ArticlePubMedGoogle Scholar
- Kwong D, Sham J, Choy D: The effect of loco-regional control on distant metastatic dissemination in carcinoma of the nasopharynx: an analysis of 1301 patients. Int J Radiat Oncol Biol Phys 1994, 30: 1029-1036.View ArticlePubMedGoogle Scholar
- Chua DT, Sham JS, Kwong DL, Choy DT, Au GK, Wu PM: Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma. A significant factor in local control and distant metastasis. Cancer 1996, 78: 202-210. 10.1002/(SICI)1097-0142(19960715)78:2<202::AID-CNCR3>3.0.CO;2-NView ArticlePubMedGoogle Scholar
- Geara FB, Sanguineti G, Tucker SL, Garden AS, Ang KK, Morrison WH, Peters LJ: Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of distant metastasis and survival. Radiother Oncol 1997, 43: 53-61. 10.1016/S0167-8140(97)01914-2View ArticlePubMedGoogle Scholar
- Cheng SH, Yen KL, Jian JJ, Tsai SY, Chu NM, Leu SY, Chan KY, Tan TD, Cheng JC, Hsieh CY, Huang AT: Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: impact on future clinical trials. Int J Radiat Oncol Biol Phys 2001, 50: 717-726. 10.1016/S0360-3016(01)01509-7View ArticlePubMedGoogle Scholar
- Khanfir A, Frikha M, Ghorbel A, Drira MM, Daoud J: Prognostic factors in metastatic nasopharyngeal carcinoma. Cancer Radiother 2007, 11: 461-464.View ArticlePubMedGoogle Scholar
- Leibel SA, Scott CB, Mohiuddin M, Marcial VA, Coia LR, Davis LW, Fuks Z: The effect of local-regional control on distant metastatic dissemination in carcinoma of the head and neck: results of an analysis from the RTOG head and neck database. Int J Radiat Oncol Biol Phys 1991, 21: 549-556. 10.1016/0360-3016(91)90669-UView ArticlePubMedGoogle Scholar
- Razak AR, Siu LL, Liu FF, Ito E, O'Sullivan B, Chan K: Nasopharyngeal carcinoma: the next challenges. Eur J Cancer 2010, 46: 1967-1978. 10.1016/j.ejca.2010.04.004View ArticlePubMedGoogle Scholar
- Chien YC, Chen JY, Liu MY, Yang HI, Hsu MM, Chen CJ, Yang CS: Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med 2001, 345: 1877-1882. 10.1056/NEJMoa011610View ArticlePubMedGoogle Scholar
- Liu MT, Yeh CY: Prognostic value of anti-Epstein-Barr virus antibodies in nasopharyngeal carcinoma (NPC). Radiat Med 1998, 16: 113-117.PubMedGoogle Scholar
- Mountain CF, McMurtrey MJ, Hermes KE: Surgery for pulmonary metastasis: a 20-year experience. Ann Thorac Surg 1984, 38: 323-330. 10.1016/S0003-4975(10)62280-1View ArticlePubMedGoogle Scholar
- Morrow CE, Vassilopoulos PP, Grage TB: Surgical resection for metastatic neoplasms of the lung: experience at the University of Minnesota Hospitals. Cancer 1980, 45: 2981-2985. 10.1002/1097-0142(19800615)45:12<2981::AID-CNCR2820451216>3.0.CO;2-NView ArticlePubMedGoogle Scholar
- Nibu K, Nakagawa K, Kamata S, Kawabata K, Nakamizo M, Nigauri T, Hoki K: Surgical treatment for pulmonary metastases of squamous cell carcinoma of the head and neck. Am J Otolaryngol 1997, 18: 391-395. 10.1016/S0196-0709(97)90059-4View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.