Skip to main content
Download PDF
Download ePub

Prognostic value of cervical nodal necrosis on staging imaging of nasopharyngeal carcinoma in era of intensity-modulated radiotherapy: a systematic review and meta-analysis

Cancer Imaging volume 22, Article number: 24 (2022) Cite this article

Abstract

Purposes

To systematically review and perform meta-analysis to evaluate the prognostic value of cervical nodal necrosis (CNN) on the staging computed tomography/magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) in era of intensity-modulated radiotherapy.

Methods

Literature search through PubMed, EMBASE, and Cochrane Library was conducted. The hazard ratios (HRs) with 95% confidence intervals (CIs) of CNN for distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were extracted from the eligible studies and meta-analysis was performed to evaluate the pooled HRs with 95%CI.

Results

Nine studies, which investigated the prognostic values of 6 CNN patterns on MRI were included. Six/9 studies were eligible for meta-analysis, which investigated the CNN presence/absence in any nodal group among 4359 patients. The pooled unadjusted HRs showed that the CNN presence predicted poor DMFS (HR =1.89, 95%CI =1.72-2.08), DFS (HR =1.57, 95%CI =1.08-2.26), and OS (HR =1.87, 95%CI =1.69-2.06). The pooled adjusted HRs also showed the consistent results for DMFS (HR =1.34, 95%CI =1.17-1.54), DFS (HR =1.30, 95%CI =1.08-1.56), and OS (HR =1.61, 95%CI =1.27-2.04). Results shown in the other studies analysing different CNN patterns indicated the high grade of CNN predicted poor outcome, but meta-analysis was unable to perform because of the heterogeneity of the analysed CNN patterns.

Conclusion

The CNN observed on the staging MRI is a negative factor for NPC outcome, suggesting that the inclusion of CNN is important in the future survival analysis. However, whether and how should CNN be included in the staging system warrant further evaluation.

Keypoints

  1. 1.

    Cervical nodal necrosis (CNN) is frequently observed in pre-treatment nasopharyngeal carcinoma (NPC);

  2. 2.

    CNN on pre-treatment imaging of NPC is a negative prognosticator of outcome.

  3. 3.

    Inclusion of CNN is critical in the future survival analysis in NPC;

  4. 4.

    It remains unclear whether/how should CNN be included in the staging system.

Introduction

Nasopharyngeal carcinoma (NPC) is a cancer that derives from the epithelial tissues at the back of the nose and prone to spread outside to the adjacent cervical lymph nodes. About 70% of patients have metastatic lymph nodes at presentation [1], often at multiple levels in one or both sides of the neck, and these nodes are an important determinant of survival outcome. Imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has advantages over clinical examinations in depicting this disease, and has been widely used to evaluate the regional metastatic nodes at presentation [2, 3]. Cervical nodal necrosis (CNN) is one of the nodal characteristics frequently observed in metastatic nodes by CT and MRI [4,5,6]. Necrosis is usually associated with tissue hypoxia, which is a strong negative factor for outcome [7, 8] , and so the CNN may have potential to predict outcome. Indeed, some previous studies showed the presence of CNN predicted poor outcome in NPC, but conflicting results also have reported [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27].

To better understand the prognostic value of the CNN in patients with NPC, this review systematically evaluated and summarised the existing literature on the prognostic value of CNN observed on the staging CT/MRI in patients with NPC treated with intensity-modulated radiotherapy (IMRT). Meta-analysis was performed for the data extracted from the eligible studies. This information may clarify the prognostic value of CNN and help to identify the role of CNN in the cancer staging system.

Methods

Search strategy

Methods of the analysis and inclusion criteria were defined in advance, documented, and the proposal was registered at PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42021286561). This study followed the Meta-analyses of Observational Studies in Epidemiology Guidelines [28]. Studies published from the onset of electronic databases up to September 2021 in the PubMed, EMBASE, and Cochrane Library databases were searched with the keywords of “nasopharyngeal AND (carcinoma OR cancer) AND (necrotic OR necrosis) AND (Magnetic Resonance Imaging OR mri OR computed tomography OR CT)”. Records were collated EndnoteTM (Version: X7, Clarivate Analytics, New York, NY, USA), and the titles were screened for duplicates. An Institutional Review Board approval or patient written consent was waived as we only used data from the previously published studies.

Selection criteria

The inclusion criteria were as follows:

(1) Original articles published in English;

(2) Participants: studies with patients with biopsy-proven NPC without distant metastasis and patients who underwent the pre-treatment head and neck staging CT or MR imaging scans;

(3) Comparison: studies that evaluated CNN using CT or MRI;

(4) Outcome: distant metastases-free survival (DMFS) and disease-free survival (DFS) or overall survival (OS).

The exclusion criteria were as follows:

(1) Articles in conference abstracts, case reports, review, and letter to editor formats;

(2) Studies with patients who underwent other than IMRT;

(3) Studies not reporting unadjusted or adjusted HR and 95%CI HR of CNN for DMFS; and

(4) Studies with the patient population overlapped with the previous studies conducted in the same investigated institution for assessing the same CNN pattern.

The records were independently selected by two observers (QYHA and TYS) by assessing the title and then abstracts for the full-text evaluation. Any discrepancy at these steps was resolved by discussion. An additional manual search was performed in the reference lists of the included studies.

Data extraction

Data extraction was performed independently by two observers (QYHA and KFH), and the following data were retrieved: first author, journal name, year of publication, city, hospital/institution, patient recruitment period, number of patients, patient treated with chemotherapy, patients with nodes, patients with CNN, age, sex, follow-up time, and edition of the AJCC staging system for NPC, histological type, CNN patterns, group of patients for survival analysis, unadjusted and adjusted HRs with 95% CI of CNN for the survival endpoints. When HRs with 95% CIs for outcome endpoints were not provided, we used the methods described by Tierney et al. [29] to estimate them from the data extracted from the respective Kaplan–Meier survival curves using the WebPlotDigitizer [30]. Necrosis was identified as a focal area of high signal intensity on T2-weighted MRI, as an area of non-enhancement on contrast-enhanced T1-weighted MRI, or as an area of low attenuation with or without a surrounding rim of enhancement on contrast-enhanced CT [4, 5].

Survival endpoints

DMFS was set as the primary survival endpoint for the analysis as the distant metastases is the main causes of mortality in NPC. DFS and OS were also included as the additional survival endpoints for the analysis if information was provided. DMFS, DFS and OS were calculated from the date of the diagnosis/start of treatment/end of the treatment to the date of distant metastases, date of any disease recurrence, and date of death, respectively.

Quality assessment

The Newcastle-Ottawa-Scale (NOS) [31] for cohort studies to assess the quality of the included studies. The NOS evaluated each study in three parts. The NOS score ranges from 0 to 9, of which 9 indicates the highest quality. The quality assessment was performed by two observers (QYHA and KFH) and discrepancies were solved by discussion with a third observer (TYS).

Statistical analysis

The inter-observer agreements for the article selection by the titles and abstracts were calculated, respectively, and the Cohen’s kappa coefficients were obtained. The meta-analysis was performed for the unadjusted and adjusted HRs of CNN for the survival endpoint(s), respectively. The HRs with 95%CI were pooled with a random- or fixed- effects models. Heterogeneity between studies was assessed using the Cochran Q-statistic and I2 tests. The analysis with an I2 value larger than 50% was considered as substantial heterogeneity. The fixed-effects model was used if the heterogeneity was not significant (I2 < 50% and p-value > 0.05); otherwise, a random-effects model was applied. To test whether a single study affected the combined HR, a sensitivity analysis was performed. All statistical tests were two-sided, and a p-value of less than 0.05 was considered to indicate a statistically significant difference. Publication bias was tested by Begg’s test and Egger’s test. For the interpretation of Egger’s test, statistical significance was defined as p-value of less than 0.1. The meta-analysis was performed using Stata IC (Version 16.0, StataCorp LLC, TX, USA).

Results

Study selection

Figure 1 shows the flowchart for study selection. A total of 668 potential records were initially identified by searching the electronic databases (Fig. 1). After the initial exclusion of the duplicates, reviews, conference abstracts, and letters (n = 421), and further exclusion of 214 and 6 records after assessing the titles and abstracts, respectively, 27 studies remained for full-text reading. No additional articles were identified through manual search from the reference list of the included studies. The kappa coefficients for the study selection by assessing the titles and abstracts were 0.81 and 0.83, respectively. Eighteen studies were subsequently excluded due to the specific reasons (Table 1) [9,10,11,12,13,14,15,16,17,18, 32,33,34,35,36,37,38,39], leaving 9 studies for the further systematic review and analysis [19,20,21,22,23,24,25,26,27].

Fig. 1
figure 1

Flowchart for study selection

Full size image
Table 1 Numbers and reasons for the excluded articles after full-text review
Full size table

Characteristics of the eligible studies

Characteristics of the included studies are shown in Table 2. The included studies were conducted by 5 institutions and the CNN were all evaluated on MRI. Three conducted by the same institution were included because these studies performed analysis to evaluate prognostic values of different CNN patterns [25,26,27]. Analysis was performed to evaluate prognostic values of 6 CNN patterns, which included (1) CNN presence/absence in any nodal group (n =6) [19,20,21,22,23,24], (2) CNN presence/absence in retropharyngeal nodes (RPNs) (n =1) [25], (3) CNN grades (n =1) [26], (4) CNN laterality (n =1) [27], (5) total CNN volume [23], and (6) maximum percentage of nodal necrotic volume of one single node (necrosis%) [23]. According to the NOS criteria, the quality of the eligible studies ranged from 7 to 9 with a median score of 8 (Table 3).

Table 2 Characteristics of the eligible articles
Full size table
Table 3 The Newcastle-Ottawa Scale (NOS) quality assessment of the eligible studies in the meta-analysis
Full size table

Three studies were excluded from the meta-analysis due to the great heterogeneity of the analysed CNN patterns or the limited studies for evaluating each of the CNN patterns. Meta-analysis therefore was only eligible to perform in 6 studies which evaluated the prognostic value of CNN presence/absence in any nodal group [19,20,21,22,23,24]. The eligible studies for meta-analysis were published over 9 years (2013 [19]– 2021 [24]) (Table 2). Patient recruitment ranged from 2003 to 2018 with the follow-up periods ranged from 1.3 to 150 months (Table 2). The total patient number extracted from these studies was 4359 (range 354 –1302) with ages ranging from 12 to 90 years, of which 3216 (73.8%) were male and 1143 (26.2%) were female. Metastatic cervical nodes were observed in 3894 patients, of which CNN was observed in 1622/3894 (41.7%) patients (Table 2). Over 99% of patients had undifferentiated carcinoma or non-keratinising carcinoma (Table 2).

Prognostic value of the CNN presence/absence

Of the 6 studies that are eligible for meta-analysis, 4 studies performed the survival analysis in patients with metastatic nodes (N+ group), and 2 in all patients (Table 2). The unadjusted and adjusted HRs of CNN were reported for DMFS in 5 and 5 studies respectively, for DFS in 3 and 4 studies, respectively, and for OS in 3 and 4 studies, respectively (Figs. 2,3,4).

Fig. 2
figure 2

Forest plots of the meta-analysis showing the pooled hazard ratios (HRs) of CNN presence in any nodal group for distant metastases free survival (DMFS). Meta-analysis was performed for the unadjusted HRs (a) and adjusted HRs (b), respectively

Full size image

The pooled unadjusted HRs showed that the presence of CNN predicted poor DMFS (HR = 1.89, 95%CI = 1.72 – 2.08, I2 = 44.8%, p = 0.123) (Fig. 2), DFS (HR = 1.57, 95%CI = 1.08 – 2.26, I2 = 71.1%, p = 0.063) (Fig. 3), and OS (HR = 1.87, 95%CI = 1.69 – 2.06, I2 = 9.1%, p = 0.333) (Fig. 4). The pooled adjusted HRs also showed the consistent results for DMFS (HR = 1.34, 95%CI = 1.17 – 1.54, I2 = 0.0%, p = 0.426) (Fig. 2), DFS (HR = 1.30, 95%CI = 1.08 – 1.56, I2 = 12.7%, p = 0.318) (Fig. 3), and OS (HR = 1.61, 95%CI = 1.27 – 2.04, I2 = 0.4%, p = 0.390) (Fig. 4). The sensitivity tests of the unadjusted and adjusted HRs for the survival endpoints in the meta-analysis are shown in Fig. 5. Subgroup meta-analysis was performed for the adjusted HRs to further evaluate the prognostic value of CNN presence/absence in patients with metastatic nodes (N+ group). Results showed that the presence of CNN predicted poor DMFS (HR = 1.56, 95%CI = 1.25 – 1.95, I2 = 0.0%, p = 0.837) (Fig. 2), DFS (HR = 1.43, 95%CI = 1.05 – 1.95, I2 = 40.1%, p = 0.196) (Fig. 3), and OS (HR = 1.55, 95%CI = 1.21 – 2.00, I2 = 12.3%, p = 0.320) (Fig. 4).

Fig. 3
figure 3

Forest plots of the meta-analysis showing the pooled hazard ratios (HRs) of CNN presence in any nodal group for disease free survival (DFS). Meta-analysis was performed for the unadjusted HRs (a) and adjusted HRs (b), respectively

Full size image
Fig. 4
figure 4

Forest plots of the meta-analysis showing the pooled hazard ratios (HRs) of CNN presence in any nodal group for overall survival (OS). Meta-analysis was performed for the unadjusted HRs (a) and adjusted HRs (b), respectively

Full size image
Fig. 5
figure 5

Sensitivity analysis showing the association between the adjusted hazard ratios (HRs) of CNN presence in any nodal group and the distant metastases-free survival (a), disease-free survival (b) and overall survival (c)

Full size image

The Begg’s and Egger’s tests showed that no potential publication bias were observed in the meta-analysis (Begg’s, p = 0.211 to >0.999; Egger’s test, p =0.132 to 0.905) except for that of the unadjusted HRs for DMFS (Egger’s test, p = 0.014).

Prognostic values of other CNN patterns

Tang et al [25] evaluated the prognostic value of the presence of CNN in the retropharyngeal nodes (RPNs) in patients with metastatic nodes (N+ group) showing the presence of CNN independently predicted poor DMFS (HR = 1.75, 95%CI =1.10 – 2.79), and DFS (HR = 1.80, 95%CI =1.21 – 2.65). Zhang et al [26] classified patients with nodes into 3 grades of necrosis (grade 0: no necrotic area; grade 1: any node with necrotic area of ≤33%; and grade 2: any node with necrotic area of > 33%) and added the necrosis grades as the continuous variable to the survival analysis. Results showed that patients with higher necrosis grades independently predicted poorer DMFS (HR = 1.36, 95%CI =1.14 – 1.63), DFS (HR = 1.38, 95%CI =1.21 – 1.59), and OS (HR = 1.36, 95%CI =1.13 – 2.45). Xie et al [27] reported patients with bilateral CNN independently predicted poorer DMFS (HR = 2.10, 95%CI =1.10 – 2.40) compared to those with unilateral CNN or without CNN. The study conducted by Ai et al. [23] also quantitatively evaluated the total CNN volume and necrosis% showing necrosis%, but not the total CNN volume, was a factor for predicting DMFS (HR = 3.03, 95%CI =1.242–7.397) and OS (HR = 3.09, 95%CI =1.482–6.431); while necrosis% was not an independent factor to predict outcome when other confounding factors were added to the multivariate analysis.

Discussion

The current review article systematically investigated the studies that evaluated the prognostic values of CNN in patients with NPC, and performed meta-analysis to assess the pooled HRs of CNN presence in any nodal group for DMFS, DFS and OS in 4359 patients. Although over 20 studies have investigated the prognostic value of CNN in patients with NPC, more than half of these studies were excluded for meta-analysis due to insufficient information reported. According the NOS assessment, all eligible studies were scored from 7-9, indicating the data extracted from the studies are reliable. Results from the meta-analysis in 6 studies showed that the CNN presence in any nodal group predicted poor DMFS, DFS, and OS with the pooled adjusted HRs ranging from 1.34 to 1.61 when analysis included all patients, and from 1.43 to 1.56 when analysis only included patients with metastatic nodes (N+ group). Four eligible studies evaluated the prognostic values of five different CNN patterns, which also showed the CNN is a negative factor for outcome.

With the introduction of IMRT to NPC, primary tumour has been well controlled with a local relapse rate of less than 10%, but distant metastases remain problematic and are now the main cause of mortality [40, 41]. More and more studies have found that the presence of nodal metastases is one of the key factors that predict patients at risk of distant metastases. These studies have gone further to investigate the prognostic values of nodal characteristics in detail [42,43,44,45,46]. Necrosis is easily observed in metastatic nodes from NPC but very rarely in primary tumour (about 2%) on the pre-treatment staging MRI [34]. Tang et al [25] reported that CNN was observed in 13% patients with metastatic retropharyngeal nodes, and the current study showed that the incidence of CNN rate was about 42% in patients with metastatic nodes. In the current study, meta-analysis was firstly performed for the unadjusted HRs of CNN, and the results showed that the presence of CNN in any nodal group indeed was a factor to predict poor outcome endpoints. This is expected because necrosis in the pre-treatment malignant tissues commonly indicates the hypoxia of the tissues, and previous studies have also shown that hypoxic malignant tissues are resistant to the treatment [7, 8]. Additionally, meta-analysis was further performed for the adjusted HRs of CNN, and the results indicated that the presence of CNN in any nodal group remained strong to independently predict outcome endpoints after adjusting the other confounding factors.

It is worthy to note that we included five studies conducted by the same institution [19, 20, 25,26,27]. Two of them evaluated the prognostic value of the presence of CNN in any nodal groups in two separate populations and included in the meta-analysis; and three further evaluated prognostic values of three different CNN patterns, respectively, in the overlapped population. Tang [25] showed patients with CNN observed in the metastatic retropharyngeal nodes had worse outcome compared to those with metastatic retropharyngeal nodes but no CNN. Two studies further qualitatively evaluated the role of CNN burden showing that patients who had grade 2 CNN (with a necrotic area over 33% in any node) [26] or with bilateral CNN [27] had poor outcome. Furthermore, a quantitative analysis [23] showed that necrosis% was a factor that predicted poor outcome. These results indicated the high CNN burden in the nodes may reflect the severe hypoxia in the tumour, thus predicting the high risk of disease recurrence. However, whether the grade of CNN burden was an independent predictor for outcome is still unclear as the multivariate analysis in these studies showed conflicting results while meta-analysis was unlikely to be performed due to the great heterogeneity in the CNN patterns analysed in these studies.

Some studies have proposed their modified criteria by incorporating the CNN to the current staging system showing the improvement in the prognostic performance [10, 21, 22]. However, the differences in the pooled HRs of the CNN and extranodal extension (ENE) reported in a previous meta-analysis (the pooled HRs of the ambiguous ENE ranged from 2.62-3.14) [46]indicate that the modification for the cancer staging system should take into account the role of other nodal characteristics. Although the present study could not answer the question whether and how CNN should be included in the current staging system, our results indicate that the inclusion of CNN is critical in the future studies aiming to investigate the prognostic values of nodal characteristics in NPC.

This study has some limitations that may result in the inherent heterogeneity and the publication bias. First, all studies included in this systematic review were retrospective studies. Due to the retrospective nature, the concerns regarding the risk of bias in the included studies could not be avoid. Second, the unadjusted HR and 95%CI of HRs in one study was extracted and calculated from the survival curves [20]; Third, the potential reasons that resulted in the heterogeneity of the meta-analysis was not able to be analysed due to the limited numbers of the eligible studies; Fourth, the publication bias could not be excluded as studies with positive results were more likely to be accepted for publication; Furthermore, this review article did not include studies that evaluated the prognostic value of CNN showing on the pre-treatment PET/CT. However, PET/CT is routinely performed to evaluate distant metastases rather than CNN in patients with NPC in clinical practice.

Conclusion

Results from the current study showed that the presence of CNN in any nodal group observed on the pre-treatment staging MRI is a negative factor for DMFS, DFS, and OS in patients with NPC. Although it remains to be defined whether and how CNN should be included in the staging system, the inclusion of CNN is critical in the future survival analysis in NPC.

Availability of data and materials

Not applicable.

Abbreviations

95%CI:

95% Confidence interval

CNN:

Cervical nodal necrosis

CT:

Computed tomography

DFS:

Disease free survival

DMFS:

Distant metastases free survival

HR:

Hazard ratio

MRI:

Magnetic resonance imaging

NPC:

Nasopharyngeal carcinoma

NOS:

Newcastle-Ottawa-Scale

OS:

Overall survival

References

  1. Ho FC, Tham IW, Earnest A, et al. Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence. BMC Cancer. 2012;12:98.

    Article  PubMed  PubMed Central  Google Scholar 

  2. King AD, Bhatia KSS. Magnetic resonance imaging staging of nasopharyngeal carcinoma in the head and neck. World J Radiol. 2010;2:159.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Razek AKA, A, King A,. MRI and CT of nasopharyngeal carcinoma. AJR Am J Roentgenol. 2012;198:11–8.

    Article  Google Scholar 

  4. Chong VF, Fan YF, Khoo JB. MRI features of cervical nodal necrosis in metastatic disease. Clin Radiol. 1996;51:103–9.

    Article  CAS  PubMed  Google Scholar 

  5. King AD, Tse GMK, Ahuja AT, et al. Head and neck imaging radiology necrosis in metastatic neck nodes : diagnostic accuracy of CT, MR Imaging, and US. Radiology. 2004;230:720–6.

    Article  PubMed  Google Scholar 

  6. Anzai Y, Brunberg JA, Lufkin RB. Imaging of nodal metastases in the head and neck. J Magn Reson Imaging. 1997;7:774–83.

    Article  CAS  PubMed  Google Scholar 

  7. Hui EP, Chan ATC, Pezzella F, et al. Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival. Clin Cancer Res. 2002;8:2595–604.

    CAS  PubMed  Google Scholar 

  8. Hong B, Lui VWY, Hashiguchi M, et al. Targeting tumor hypoxia in nasopharyngeal carcinoma. Head Neck. 2013;35:133–45.

    Article  PubMed  Google Scholar 

  9. Chua DT, Sham JS, Kwong DL, et al. Evaluation of cervical nodal necrosis in nasopharyngeal carcinoma by computed tomography: incidence and prognostic significance. Head Neck. 1997;19:266–75.

    Article  CAS  PubMed  Google Scholar 

  10. Lan M, Huang Y, Chen CY, et al. prognostic value of cervical nodal necrosis in nasopharyngeal carcinoma: analysis of 1800 patients with positive cervical nodal metastasis at MR Imaging. Radiology. 2015;276:536–44.

    Article  PubMed  Google Scholar 

  11. Lu L, Wei X, Li YH, Li WB. Sentinel node necrosis is a negative prognostic factor in patients with nasopharyngeal carcinoma: A magnetic resonance imaging study of 252 patients. Curr Oncol. 2017;24:e220–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen B, Zhan Z, Pan J, et al. (2021) Re-evaluation of the prognostic significance of retropharyngeal node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy. Asia Pac J Clin Oncol. 2022;18(2):e173–81.

  13. Guo Q, Pan J, Zong J, et al. Suggestions for Lymph Node Classification of UICC/AJCC Staging System. Medicine. 2015;94: e808.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chen FP, Zhou GQ, Qi ZY, et al. Prognostic value of cervical nodal tumor volume in nasopharyngeal carcinoma: analysis of 1230 patients with positive cervical nodal metastasis. PLoS ONE. 2017;12:1–13.

    Google Scholar 

  15. Mao YP, Liang SB, Liu LZ, et al. The N staging system in nasopharyngeal carcinoma with radiation therapy oncology group guidelines for lymph node levels based on magnetic resonance imaging. Clin Cancer Res. 2008;14:7497–503.

    Article  CAS  PubMed  Google Scholar 

  16. Ou X, Miao Y, Wang X, et al. The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels. Radiat Oncol. 2017;12:137.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Luo Y, Ren J, Zhou P, et al. Cervical nodal necrosis is an independent survival predictor in nasopharyngeal carcinoma : an observational cohort study. Onco Targets and Therapy. 2016;9:6775–83.

    Article  CAS  Google Scholar 

  18. Ting Y, Chee J, Charn TC, et al. Prognostic significance of cystic lymph nodal metastasis in nasopharyngeal carcinoma. Head Neck. 2017;39:1832–9.

    Article  PubMed  Google Scholar 

  19. Li W-F, Sun Y, Mao Y-P, et al. Proposed lymph node staging system using the International Consensus Guidelines for lymph node levels is predictive for nasopharyngeal carcinoma patients from endemic areas treated with intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86:249–56.

    Article  PubMed  Google Scholar 

  20. Zhang LL, Zhou GQ, Li YY, et al. Combined prognostic value of pretreatment anemia and cervical node necrosis in patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a large-scale retrospective study. Cancer Med. 2017;6:2822–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhou X, Ou X, Yang Y, et al. Quantitative metastatic lymph node regions on magnetic resonance imaging are superior to AJCC N classification for the prognosis of nasopharyngeal carcinoma. J Oncol. 2018;2018:9172585.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Feng Y, Cao C, Hu Q, Chen X. Prognostic value and staging classification of lymph nodal necrosis in nasopharyngeal carcinoma after intensity-modulated radiotherapy. Cancer Res Treat. 2019;51:1222–30.

    Article  CAS  PubMed  Google Scholar 

  23. Ai QY, King AD, Poon DMC, et al. Extranodal extension is a criterion for poor outcome in patients with metastatic nodes from cancer of the nasopharynx. Oral Oncol. 2019;88:124–30.

    Article  PubMed  Google Scholar 

  24. Xu M, Zang J, Luo S, et al. Long-term survival outcomes and adverse effects of nasopharyngeal carcinoma patients treated with IMRT in a non-endemic region: a population-based retrospective study. BMJ Open. 2021;11:1–11.

    Article  Google Scholar 

  25. Tang LL, Guo R, Zhou G, et al. Prognostic value and staging classification of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy. PLoS ONE. 2014;9:1–8.

    Article  Google Scholar 

  26. Zhang L-L, Li J-X, Zhou G-Q, et al. Influence of cervical node necrosis of different grades on the prognosis of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy. J Cancer. 2017;8:959–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Xie C, Li H, Yan Y, et al. a nomogram for predicting distant metastasis using nodal-related features among patients with nasopharyngeal carcinoma. Front Oncol. 2020;10:616.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA. 2000;283:2008–12.

    Article  CAS  PubMed  Google Scholar 

  29. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rohatgi A (2021) WebPlotDigitizer: Version 4.5. In: https://automeris.io/WebPlotDigitizer

  31. Wells G, Shea B, O’Connell D, et al The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. In: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  32. Lan M, Chen C, Huang Y, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients with cervical nodal necrosis. Sci Rep. 2017;7:42624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yeh SA, Tang Y, Lui CC, et al. Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys. 2005;62:672–9.

    Article  PubMed  Google Scholar 

  34. Liang SB, Chen LS, Yang XL, et al. Influence of tumor necrosis on treatment sensitivity and long-term survival in nasopharyngeal carcinoma. Radiother Oncol. 2021;155:219–25.

    Article  CAS  PubMed  Google Scholar 

  35. Du YY, Luo DH, Sun XS, et al. Combining pretreatment plasma Epstein-Barr virus DNA level and cervical node necrosis improves prognostic stratification in patients with nasopharyngeal carcinoma: A cohort study. Cancer Med. 2019;8:6841–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen X, Cao X, Jing B, et al. Prognostic and Treatment Guiding Significance of MRI-Based Tumor Burden Features and Nodal Necrosis in Nasopharyngeal Carcinoma. Front Oncol. 2020;10:1–11.

    Google Scholar 

  37. Liu K, Lin S, Ke L, et al. Prognostic value and the potential role of treatment options for cervical lymph node necrosis in nasopharyngeal carcinoma. Oral Oncol. 2020;109: 104864.

    Article  PubMed  Google Scholar 

  38. Tian Y-M, Zeng L, Lan Y-H, et al. The Value of Cervical Node Features in Predicting Long-Term Survival of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era. Cancer Manag Res. 2021;13:4899–909.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Niu X, Xue F, Liu P, et al. Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease. Transl Oncol. 2021;14(12): 101216.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma. The Lancet. 2019;394:64–80.

    Article  Google Scholar 

  41. Wong KCW, Hui EP, Lo KW, et al. Nasopharyngeal carcinoma: an evolving paradigm. Nat Rev Clin Oncol. 2021;18:679–95.

    Article  CAS  PubMed  Google Scholar 

  42. Ma H, Qiu Y, Li H, et al. Prognostic Value of Nodal Matting on MRI in Nasopharyngeal Carcinoma Patients. J Magn Reson Imaging. 2021;53:152–64.

    Article  PubMed  Google Scholar 

  43. Setakornnukul J, Thephamongkhol K, Chaysiri P. Added value of metastatic cervical lymph node group V in nodal staging of nasopharyngeal cancer. Head Neck. 2020;42:2801–10.

    Article  PubMed  Google Scholar 

  44. Ai QY, King AD, Mo FKF, et al. Staging nodal metastases in nasopharyngeal carcinoma: which method should be used to measure nodal dimension on MRI? Clin Radiol. 2018;73:640–6.

    Article  PubMed  Google Scholar 

  45. Ai Q-Y, King AD, Mo FKF, et al. Prediction of distant metastases from nasopharyngeal carcinoma: Improved diagnostic performance of MRI using nodal volume in N1 and N2 stage disease. Oral Oncol. 2017;69:74–9.

    Article  PubMed  Google Scholar 

  46. Tsai TY, Chou YC, Lu YA, et al. The prognostic value of radiologic extranodal extension in nasopharyngeal carcinoma: Systematic review and meta-analysis. Oral Oncol. 2021;122: 105518.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was partially supported by the Seed Fund for External Research Grant Applications funded by the Department of Health Technology and Informatics, The Hong Kong Polytechnic University. (ref. no. SF2122-HA)

Author information

Author notes

  1. Qi-Yong H. Ai and Kuo Feng Hung contributed equally to this work.

Authors and Affiliations

  1. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong S.A.R., P.R. China

    Qi-Yong H. Ai & Michael Ying

  2. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong S.A.R., P.R. China

    Qi-Yong H. Ai, Tiffany Y. So & Ann D. King

  3. Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, Hong Kong S.A.R., P.R. China

    Kuo Feng Hung

  4. Department of Clinical Oncology, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Prince of Wales Hospital, Sir Y.K. Pao Centre for Cancer, New Territories, Hong Kong S.A.R., P.R. China

    Frankie K. F. Mo, Edwin P. Hui & Brigette B. Y. Ma

  5. Department of Radiology and Organ Imaging, United Christian Hospital, Kowloon, Hong Kong S.A.R., P.R. China

    Wing Tsung Anthony Chin

Authors
  1. Qi-Yong H. Ai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kuo Feng Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiffany Y. So
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frankie K. F. Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wing Tsung Anthony Chin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Edwin P. Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brigette B. Y. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ann D. King
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception: QYHA and ADK; study design: QYHA and KFH; data collection: QYHA and KFH; data analysis: QYHA, KFH, TYS, and FKFM; data interpretation: QYHA, KFH, FKFM, WTAC, EPH, BBYM, MY, and ADK; manuscript writing: QYHA and KFH; manuscript editing: All authors. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Qi-Yong H. Ai.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

All authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ai, QY.H., Hung, K.F., So, T.Y. et al. Prognostic value of cervical nodal necrosis on staging imaging of nasopharyngeal carcinoma in era of intensity-modulated radiotherapy: a systematic review and meta-analysis. Cancer Imaging 22, 24 (2022). https://doi.org/10.1186/s40644-022-00462-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40644-022-00462-6

Keywords

Cancer Imaging

ISSN: 1470-7330

Contact us