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Nasopharyngeal necrosis following intensity-modulated radiation therapy of primary nasopharyngeal carcinoma—incidence rate and predictors of risk

BMC Cancer volume 25, Article number: 802 (2025) Cite this article

Abstract

Objectives

This study aimed to investigate the incidence of post radiation nasopharyngeal necrosis (PRNN) in primary NPC after intensity modulated radiation therapy (IMRT) and identify the predictors of risk.

Methods

Data of 5798 NPC patients who received IMRT-based treatment between April 2009 and December 2015 were retrospectively reviewed. PRNN was diagnosed by MRI or nasopharyngoscopy. Dosimetric factors were selected by the least absolute shrinkage and selection operator logistic regression and applied to Cox proportional hazards modeling with clinical predictors.

Results

Among the 5798 patients, 53 developed PRNN—an incidence rate of 0.89%. Age > 55 years, diabetes, LDH > 170 U/L, and tumor volume of nasopharynx > 60.5 cm3,were independently associated with risk of PRNN(all p < 0.05. Dosimetric analysis showed that D0.5ccEQD2 of 80.20 Gy might be the dose constraint for nasopharynx (sensitivity = 62.3%, 33 out of 53; specificity = 84.2%, 4897 out of 5925). Besides, the RTOG dose constraints of V110% (V77.0) should be less than 0.2% in case of increasing risk of PRNN(HR = 2.28, 95% CI: 1.26–4.41, p = 0. 01).

Conclusion

Nasopharyngeal necrosis is rare after primary IMRT. The independent risk factors for this rare complication include age > 55 years, diabetes mellitus, LDH > 170 U/L, tumor volume of nasopharynx > 60.5 cm3, D0.5ccEQD2 > 80.20 Gy, and V77.0 < 0.2% to the planning treatment volume of nasopharynx.

Keypoints

High radiation dose may lead to devastating nasopharyngeal necrosis after primary IMRT. Real world analysis will provide valuable information for prevention.

Findings

The aged, diabetes mellitus, large tumor volume, D0.5ccEQD2 > 80.20 Gy and V77.0 < 0.2% to planning treatment volume increased the risk of nasopharyngeal necrosis.

Clinical relevance

This real-world study provided valuable information for prevention of PRNN. Compared with RTOG protocol, D0.5ccEQD2 > 80.20 Gy is a reliable evidence-based new complement to dose constraint, especially for T3-4 disease, who received high prescribe dose in China.

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Introduction

Nasopharyngeal carcinoma (NPC) is highly sensitive to ionizing irradiation, and radiation therapy remains the mainstay treatment for nonmetastatic NPC [1]. Currently, intensity modulated radiation therapy (IMRT) is the preferred technique for NPC as it can deliver high and homogenous dose to the target volume while minimizing the dose to surrounding organs [2]. With IMRT, the locoregional control rate of NPC is more than 90% [3]. Meanwhile, extensive application of chemotherapy has reduced the incidence of distant metastasis and significantly improved survival [4]. But with improved survival, there is increasing concern about treatment-related complications among long-term survivors. One serious complication is postradiation nasopharyngeal necrosis (PRNN), which manifests—months or years after exposure to irradiation—with necrosis of tissues around the nasopharynx, such as the mucosa, the musculus longus capitis, the parapharyngeal tissues, and the skull base [5]. Although PRNN after IMRT of primary NPC is uncommon, it can be life threatening [6], with mortality rates of 65.8% and 72.7% reported in patients with osteoradio-necrosis and involvement of the internal carotid artery, respectively [7]. Identification of the risk factors for PRNN after IMRT might help prevent this dangerous complication.

Most previous studies on PRNN focused on patients with recurrent NPC in whom the incidence of PRNN after salvage radiotherapy is as high as 44.0% (11/25) [6]. Factors that have been found to be associated with PRNN include age, diabetes mellitus, original T classification, tumor volume [6, 8], anemia, hypoalbuminemia, and high C-reactive protein level [9]. Treatment modality may also influence risk of PRNN, as IMRT has been reported to be associated with higher risk of PRNN than conventional radiotherapy [9]. Further, cumulative radiation dose may be associated with the severity of necrosis [8, 9]. However, the heterogeneous treatments in previous studies make interpretation of the results difficult and, importantly, the predictors of risk of nasopharyngeal necrosis after IMRT of primary NPC remains largely uninvestigated. Besides, dosimetric analysis on PRNN is supposed to inspired dose constraint of nasopharynx. We therefore conceived a real-world retrospective study of a large homogenous cohort of IMRT-treated NPC patients. The purpose of this study was to identify the clinical and dosimetric factors associated with PRNN and provide evidence-based dose constraint of planning treatment volume of nasopharynx (PTVnx) for IMRT-treated NPC patients. We hope the results of this study will provide valuable information for prevention of PRNN.

Materials and methods

Patients

The study cohort was identified from a well-established big-data intelligence platform that contains the data of 10,126 patients with histologically proven, non-disseminated NPC diagnosed between April 2009 and December 2015 and treated with IMRT-based strategies at our institution. Patients were excluded if they 1) failed to undergone at least one follow-up magnetic resonance imaging (MRI) or nasopharyngscopy after IMRT and, 2) without available dosimetric and clinical data in the case records. A total of 5978 patients were eligible for this retrospective study (Fig. 1). All patients were restaged according to the 8 th edition of the American Joint Commission on Cancer/Union for International Cancer Control staging system.

Fig. 1
figure 1

Study flow chart

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Treatment and follow-up

PTVnx delineation encompasses both the gross tumor lesion and the entire nasopharyngeal mucosa, consistent with IMRT guidelines for NPC (ICRU Report 83). In general,prescribed doses to PTVnx, was 66–77 Gy, in 1.84–2.43 Gy per fractions/28–38 fractions. Dose criteria for tumor region in RTOG 0225, RTOG 06151 and our institution included relative volume receiving more than110% dose (V110%) ≤ 20%, more than 115% dose (V115%) ≤ 5%, less than 95% dose (V95%) ≤ 2–5%, and less than 93% dose (V93%) ≤ 1% (Supplementary Table E1). However, exceptions may arise when encountering cavities within the PTVnx or when dose constraints are necessary for critical organs at risk (such as the brainstem or optic chiasm).

Following IMRT completion, patients underwent structured surveillance consisting of quarterly clinical evaluations during the initial 36-month post-treatment period, transitioning to biannual assessments thereafter. Each visit incorporated comprehensive monitoring of disease progression and radiation-induced sequelae through standardized protocols. MRI scans of the nasopharyngeal region and cervical lymph nodes, and/or endoscopic examinations of the nasopharyngeal region were systematically conducted according to the following schedule: baseline at 3 months post-radiotherapy, semi-annual intervals through year 3, and annual examinations subsequently. The latency period to PRNN development was operationally defined as the temporal interval between radiotherapy initiation and initial radiographic or clinical confirmation of necrotic changes. Details of the radiation technique and chemotherapyare summarized in Supplementary materials.

Diagnosis and treatment of PRNN

The diagnosis of PRNN requires a multimodal synthesis of clinical manifestations, endoscopic features, radiological evidence, and histopathological exclusion of malignancy. Characteristic presentations included a triad of refractory headache (analgesic-resistant, duration > 4 weeks), fetid nasal discharge, and recurrent epistaxis (≥ 2 episodes/week) [10,11,12]. All suspected cases underwent evaluation with high-definition nasopharyngoscopy (Fig. 2A-E) and contrast-enhanced MRI. Endoscopic examination identified necrotic ulcerations (diameter ≥ 5 mm) with irregular margins, with 43.6% of cases exhibiting pathognomonic bone exposure covered by purulent secretions [7, 11,12,13,14]. Radiological confirmation followed a double-blinded interpretation protocol: two head-and-neck radiologists (≥ 10 years'experience) independently analyzed contrast-enhanced T1-weighted MRI, focusing on mucosal discontinuity (defect ≥ 3 mm) and non-enhancing necrotic zones (signal intensity ratio < 1.5 versus masseter muscle), with discordant cases resolved through consensus review (interobserver agreement, κ = 0.81) [12]. Histopathological validation mandated biopsy of ulcer margins, revealing acellular eosinophilic matrix on hematoxylin–eosin staining and negative immunohistochemistry for CK5/6 (excluding carcinoma) and CD68/CD163 (excluding granulomatous inflammation). Notably, all cases with histologically confirmed malignant ulcers were categorically excluded from PRNN diagnosis (specificity: 100%).

Fig. 2
figure 2

MRI examination of PRNN and Overall survival in PRNN and non-PRNN groups. A: Transverse T1-weighted image; B: Transverse contrast-enhanced T1-weighted image; C: Transverse T2-weighted image; D: Coronal T1-weighted image; E: Coronal contrast-enhanced T1-weighted image; F: Kaplan–Meier curves of overall survival in PRNN and non-PRNN groups

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Therapeutic interventions were stratified based on lesion severity. For patients with extensive osteonecrosis (N = 12), endoscopic debridement served dual diagnostic (obtaining deep bone specimens) and therapeutic purposes (eradicating infected sequestra). Conservative management comprised twice-daily nasopharyngeal irrigation (2% hydrogen peroxide [5–10 mL] or saline [50–100 mL]) combined with culture-directed nitroimidazole antibiotics (metronidazole/ornidazole 500 mg three times daily). Parenteral nutritional support was administered for malnutrition (BMI < 18.5 kg/m2), while febrile neutropenia cases received broad-spectrum antibiotic coverage.

Dosimetric data collection

Dose-volume histogram parameters

A comprehensive set of 154 dose-volume histogram (DVH) parameters was extracted (Supplementary Table.E2), encompassing: 1) Absolute dose metrics: Dmax/Dmean/Dmin; 2) Percentile doses: D1 -D99 (1% increments); 3)Volume-based thresholds: D0.5cc to D10cc (1cc increments); 4)Relative volume parameters: V60to V80.5 (0.5 Gy increments).

All doses were converted to equivalent 2 Gy fractionation (EQD2) using α/β = 10 Gy for nasopharyngeal carcinoma, calculated as: EQD2 = D × (d + α/β)/(2 + α/β) where D = total dose, d = dose per fraction.

RTOG protocol cross-validation

Given the clinical adoption of RTOG 0225/0615 dose constraints, we implemented protocol-specific parameter translation:

RTOG 70 Gy reference:

$$\mathrm V115\%\rightarrow\mathrm V80.5\;\mathrm{Gy}\;\left(70\times1.15\right)$$
$$\mathrm V110\%\rightarrow\mathrm V77.0\;\mathrm{Gy}\;\left(70\times1.10\right)$$
$$\mathrm V95\%\rightarrow\mathrm V66.5\;\mathrm{Gy}\;\left(70\times0.95\right)$$
$$\mathrm V93\%\rightarrow\mathrm V65.1\;\mathrm{Gy}\;\left(70\times0.93\right)$$

Statistical analysis

Categorical variables were compared using χ2 or Fisher's exact tests, while continuous variables were analyzed with Mann–Whitney U tests after normality assessment (Shapiro–Wilk test). Survival curves were generated via Kaplan–Meier method and compared using log-rank tests. To address collinearity in dosimetric parameters, LASSO regression with tenfold cross-validation was applied prior to Cox proportional hazards modeling (backward elimination, p < 0.05 retention threshold). Variables were dichotomized based on median values (age), ROC-derived optimal cutoffs (tumor volume, hemoglobin, etc.), or established clinical thresholds (albumin, EBV DNA). Dynamic albumin levels during the treatment were classified into three tiers: 1) persistently normal (> 35 g/L throughout), 2) intermittent reduction (≥ 1 measurement < 35 g/L but never < 30 g/L), 3) critical hypoalbuminemia (≥ 1 measurement < 30 g/L).

Analyses were performed using SPSS 23.0 and R 3.4.4, with two-tailed p < 0.05 considered statistically significant.

Results

Patients

The 5978 patients were followed up for a median of 62.3 months (IQR, 54.3–72.2 months. While 53 patients developed PRNN, 5925 patients did not develop PRNN. Thus, the incidence rate of PRNN after primary IMRT was 0.89% (53/5978). Median time from completion of IMRT to diagnosis of PRNN was 7.1 months (IQR, 6.0–13.3 months). Table 1 summarizes the clinical characteristics of the PRNN and non-PRNN patients.

Table 1 Baseline characteristics of patients with and without PRNN
Full size table

The crude incidence rates of PRNN in T1 - 2 was 0.32% (6/1877), and T3 - 4 disease was 1.15% (47/4100). Estimated 5-year overall survival rate was significantly lower for PRNN patients than for non-PRNN patients (48.8% vs. 86.6%, p < 0.001; Fig. 2F).

MRI data at diagnosis were available for 52 of the 53 patients with PRNN, in which 5 patients with only clival necrosis, 2 patients with pterygoid muscle necrosis. Internal carotid artery exposure was found in 15 patients, but only 2 received debridement. Osteoradionecrosis was found in 26 patients, but only 7 received debridement. Crude mortality rates of patients with and without osteoradionecrosis were 53.8% (14/26) and 57.7% (15/26), respectively. The crude mortality rate in patients with internal carotid artery exposure was 66.7% (10/15). Survival was not significantly different between subgroups with different features and treatments (Supplementary Table.E3).

Dosimetric parameters associated with PRNN

The elevated radiation doses to PTVnx in PRNN patients suggest a potential association between dosimetric parameters and PRNN risk. LASSO regression analysis identified D0.5ccEQD2 as an independent dosimetric predictor of PRNN, with an optimal cutoff of 80.20 Gy (sensitivity: 62.3% [33/53]; specificity: 84.2% [4897/5925]).

Figure 3 presents the AUCs and optimal cutoffs for RTOG parameters, along with their corresponding sensitivity and specificity. Notably, RTOG-related factors (V80.5, V66.5 and V65,) exhibited significantly lower predictive performance (AUCs) than D0.5ccEQD2. In contrast, V77.0 demonstrated comparable predictive value, with an optimal cutoff of 0.2% (sensitivity: 64.2% [34/53]; specificity: 68.4% [4055/5925]) (Fig. 3).

Fig. 3
figure 3

AUC of important dosimetric factor and cut-off value. * Converted to equivalent 2 Gy fractionation (EQD2) using α/β = 10 Gy. **Translated according to the recommend total dose of 70 Gy in protocols

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Dosimetric parameters with AUC > 0.6 were dichotomized using their optimal cutoffs and included in univariate analysis. D0.5ccEQD2 > 80.20 Gy and V77.0 > 0.2% were all significantly associated with PRNN risk (all p < 0.01; Fig. 4).

Fig. 4
figure 4

Univariate analysis for covariates to estimate the risk of PRNN. Abbreviations: EBV = EpsteineBarr virus; N = node; T = tumor; HGB = hemoglobin, ALB = albumin, CRP = C-reactive protein; LDH = lactate dehydrogenase. * Converted to equivalent 2 Gy fractionation (EQD2) using α/β = 10 Gy

Full size image

To assess their independent predictive value, each parameter was analyzed separately while adjusting for clinical factors. PRNN risk was significantly elevated in patients receiving:

D0.5ccEQD2 > 80.20 Gy (HR = 8.67, 95% CI: 4.97–15.12; p < 0.01; Fig. 5A); V77.0 > 0.2% (HR = 3.88, 95% CI: 2.21–6.80; p < 0.01; Fig. 5B).

Fig. 5
figure 5

Multivariate analysis for covariates to estimate the risk of PRNN. A: Multivariate analysis with clinical covariates and D0.5cc; B: Multivariate analysis with clinical covariates and V77.0(V110%). *: Converted to equivalent 2 Gy fractionation (EQD2) using α/β = 10 Gy

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Clinical characteristics associated with PRNN

The variables listed in Table 1 (excluding histology type as all PRNN cases were WHO type 2.1–2.2) were first analyzed using univariable analysis (Fig. 4). Univariate analysis revealed several clinical factors significantly associated with PRNN: age > 55 years, diabetes mellitus, PTV > 60.5 cm3, and T3 - 4 disease (all p < 0.01). Additionally, patients who underwent IMRT for more than 43 days showed increased susceptibility to PRNN development (p = 0.004). Biochemical markers including elevated pretreatment levels of LDH (> 170 U/L) and C-reactive protein (> 2.6 g/L), along with reduced dynamic albumin levels (< 30 g/L), were also significantly correlated with PRNN (all p < 0.01).

Multivariate analysis identified three independent predictors of PRNN: age > 55 years, diabetes mellitus, LDH > 170 U/L and PTV > 60.5 cm3 (all p < 0.05) (Fig. 5).

Discussion

Nasopharyngeal necrosis is a devastating complication after radiotherapy of nasopharyngeal carcinoma [7, 12, 15], but there is limited information about its incidence and the dosimetric and clinical risk factors. In this study, we found that age > 55 years, diabetes, LDH > 170 U/L, primary tumor volume > 60.5 cm3, and dosimetric factors (D0.5ccEQD2 > 80.20 Gy, V77.0 > 0.2%) to PTVnx were independent risk factors for this rare complication.

Radiotherapy method influences occurrence of PRNN. Li et al. showed higher risk of PRNN in patients treated with IMRT [9]. However, their study cohort included patients receiving primary radiotherapy and/or salvage radiotherapy, which is itself a risk factor for PRNN. Theoretically, conformal dose delivery during IMRT in NPC means that the nasopharyngeal mucosa receives high radiation dose [16]. However, nasopharyngeal necrosis after primary radiotherapy in patients with NPC is rare, occurring in only 0.2%–0.3% of patients after conventional radiation therapy [17]. In our cohort, the crude incidence rate of PRNN after IMRT was 0.89%, which is higher than that reported after conventional radiation therapy. Li et al. found post-IMRT nasopharyngeal ulcers in 0.41% (25/6023) of their primary NPC patients [18], and higher dose is associated with higher incidence rate. Our study supported the finding and further investigate the impact of fraction schemes on PRNN.

Radiation dose has been cited as an important risk factor for necrosis in many studies [7, 11, 12, 19, 20]. In the 1980 s, one study reported that nasopharyngeal necrosis was more common at doses over 70 Gy (incidence of 18.4%) [21]. With advances in radiation technology, dose constraint criteria have changed. RTOG 0225 and RTOG 0615 protocols recommend a total dose of 70 Gy to PTVnx for non-recurrent NPC, with satisfactory treatment outcomes and acceptable radiation-related toxicities demonstrated in patients from both the endemic and non-endemic regions [22,23,24]. Nasopharyngeal necrosis is rare after primary irradiation but more common following salvage irradiation, especially with cumulative doses over 120 Gy [12]. Yu et al. found that cumulative dose ≥ 141.5 Gy was an independent risk factor for lethal nasopharyngeal necrosis [8].

Dosimetric analysis for primary tumor dose constraint considered PRNN after primary irradiation is rare. A previous dosimetry study of 25 patients with PRNN after IMRT also proposed a D3cc limit of 73.67 Gy [18], but various fraction schemes may also influence the result. Different fractionation schemes leads varied biological dose. In this study, we applied LASSO and multivariate analysis on calculated EQD2 dose, and found D0.5ccEQD2 > 80.20 Gy, V77.0 < 0.2% the independently significant for PRNN. Moreover, D0.5cc EQD2 > 80.20 Gy ranked the best predictive dosimetric factor, which had more predictive value compared with dose constraints recommended by RTOG 0225/0615 [23, 24]. In China, T3 - 4 disease received higher prescribe dose, which nearly up to 74 Gy based on extensive clinical experience. Radiation dose remained an independent risk predictor even after adjusting for T-stage and tumor volume parameters. The observed correlation between advanced T-stage/large tumor volume and PRNN risk appears secondary to compromised dosimetric optimization in anatomically complex cases, rather than representing direct biological causality. Therefore, we suggest D0.5cc EQD2 > 80.20 Gy as a new complement for dose constraint of PTVnx in patients receiving IMRT.

PRNN is postulated to develop from tissue breakdown and an irradiation-induced chronic non-healing wound of nasopharynx [25]. Morphological changes in mucosal epithelium and delayed mucosal wound healing in patients with old age and diabetes may promote development of necrosis [26, 27]. Nutritional status before, during, and after treatment was expected to impact nasopharyngeal necrosis, as it may affect adaptive radiotherapy and the actual dose delivered to the nasopharynx [7]. However, the correlation between low dynamic albumin levels and PRNN became insignificant in the multivariate analysis. A possible explanation is that nutritional status is itself influenced by factors such as age, diabetes, tumor burden, and radiation dose. After adjusting for dosimetric and other clinical factors, the weak causal relationship between nutritional status and PRNN may have been obscured.

Limitations

This study has several limitations. First, its retrospective design inherently introduces selection bias. Second, while identifying key dosimetric and clinical risk factors, we did not develop a predictive model, which remains an important avenue for future research. Third, the complex nasopharyngeal anatomy—surrounded by osseous and soft tissue structures—complicates precise estimation of normal tissue α/β ratios. Notably, our use of α/β = 10 (aligned with clinical protocols for tumor control in standard fractionated regimens) specifically reflects radiation planning conventions rather than representing the actual radiobiological parameters of normal tissue, as PRNN manifests in late-responding normal tissues typically associated with lower α/β values.

Conclusion

Nasopharyngeal necrosis is rare after primary IMRT. The independent risk factors for this rare complication include age > 55 years, diabetes mellitus, LDH > 170 U/L,tumor volume of nasopharynx > 60.5 cm3, D0.5ccEQD2 > 80.20 Gy and V77.0 < 0.2% to the planning treatment volume of nasopharynx.

Data availability

Key raw data were uploaded onto the Research Data Deposit public platform (https://www.researchdata.org.cn/) with the primary accession code RDDA2022847516 (https://www.researchdata.org.cn/Search.aspx?k=RDDA2022847516).

Abbreviations

AUC:

Area under the curve

D0.5cc :

Dose delivered to 0.5 cm3 PTVnx

D95 :

Dose to 95% of PTVnx

Dmax :

Maximum dose

Dmin :

Minimum dose

IMRT:

Intensity-modulated radiation therapy

LDH:

Lactate dehydrogenase

NPC:

Nasopharyngeal carcinoma

PRNN:

Postradiation nasopharyngeal necrosis

PTV:

Planning treatment volume

PTVnx :

Planning treatment volume of nasopharynx

RTOG:

Radiation Therapy Oncology Group

V110% :

Relative volume of PTV receiving no less than 110% dose

V77 .0 :

Relative PTVnx receiving more than 77 Gy

References

  1. Chen YP, Ismaila N, Chua MLK, Colevas AD, Haddad R, Huang SH, Wee JTS, WhitleyAC, Yi JL, Yom SS et al. Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage IIIVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline. J Clin Oncol. 2021;39(7):840-859

  2. Hsiung CY, Yorke ED, Chui CS, Hunt MA, Ling CC, Huang EY, Wang CJ, Chen HC, Yeh SA, Hsu HC, et al. Intensity-modulated radiotherapy versus conventional three-dimensional conformal radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2002;53(3):638–47.

    Article  PubMed  Google Scholar 

  3. Mao YP, Tang LL, Chen L, Sun Y, Qi ZY, Zhou GQ, Liu LZ, Li L, Lin AH, Ma J. Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy. Chin J Cancer. 2016;35(1):103.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Blanchard P, Lee AWM, Carmel A, Wai Tong N, Ma J, Chan ATC, Hong RL, Chen MY, Chen L, Li WF, et al. Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): an update on 26 trials and 7080 patients. Clin Transl Radiat Oncol. 2022;32:59–68.

    CAS  PubMed  Google Scholar 

  5. Hua YJ, Chen MY, Hong MH, Zhao C, Guo L, Han F, Luo W, Sun R, Chen YY, Liu H. Short-term efficacy of endoscopy-guided debridement on radiation-related nasopharyngeal necrosis in 20 nasopharyngeal carcinoma patients after radiotherapy. Ai zheng Aizheng Chin J Cancer. 2008;27(7):729–33.

    Google Scholar 

  6. Yang K, Ahn YC, Nam H, Hong SD, Oh D, Noh JM. Clinical features of post-radiation nasopharyngeal necrosis and their outcomes following surgical intervention in nasopharyngeal cancer patients. Oral Oncol. 2021;114:105180.

    Article  PubMed  Google Scholar 

  7. Chen MY, Mai HQ, Sun R, Guo X, Zhao C, Hong MH, Hua YJ. Clinical findings and imaging features of 67 nasopharyngeal carcinoma patients with postradiation nasopharyngeal necrosis. Chin J Cancer. 2013;32(10):533–8.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yu YH, Xia WX, Shi JL, Ma WJ, Li Y, Ye YF, Liang H, Ke LR, Lv X, Yang J, et al. A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients. Chin J Cancer. 2016;35(1):59.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Li XY, Sun XS, Liu SL, Chen QY, Guo SS, Liu LT, Yan JJ, Xie HJ, Tang QN, Liang YJ, et al. The development of a nomogram to predict post-radiation necrosis in nasopharyngeal carcinoma patients: a large-scale cohort study. Cancer Manag Res. 2019;11:6253–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chang KP, Tsang NM, Chen CY, Su JL, Hao SP. Endoscopic management of skull base osteoradionecrosis. Laryngoscope. 2000;110(7):1162–5.

    Article  CAS  PubMed  Google Scholar 

  11. Huang XM, Zheng YQ, Zhang XM, Mai HQ, Zeng L, Liu X, Liu W, Zou H, Xu G. Diagnosis and management of skull base osteoradionecrosis after radiotherapy for nasopharyngeal carcinoma. Laryngoscope. 2006;116(9):1626–31.

    Article  PubMed  Google Scholar 

  12. Hua YJ, Chen MY, Qian CN, Hong MH, Zhao C, Guo L, Guo X, Cao KJ. Postradiation nasopharyngeal necrosis in the patients with nasopharyngeal carcinoma. Head Neck. 2009;31(6):807–12.

    Article  PubMed  Google Scholar 

  13. Hua YJ, Han F, Lu LX, Mai HQ, Guo X, Hong MH, Lu TX, Zhao C. Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy. Eur J Cancer (Oxford, England : 1990). 2012;48(18):3422–8.

    Article  Google Scholar 

  14. Chin SC, Jen YM, Chen CY, Som PM. Necrotic nasopharyngeal mucosa: an ominous MR sign of a carotid artery pseudoaneurysm. AJNR Am J Neuroradiol. 2005;26(2):414–6.

    PubMed  PubMed Central  Google Scholar 

  15. Yang Q, Zou X, You R, Liu YP, Han Y, Zhang YN, Guo L, Mai HQ, Xie CM, Li L, et al. Proposal for a new risk classification system for nasopharyngeal carcinoma patients with post-radiation nasopharyngeal necrosis. Oral Oncol. 2017;67:83–8.

    Article  PubMed  Google Scholar 

  16. Carle LN, Ko CC, Castle JT. Nasopharyngeal carcinoma. Head Neck Pathol. 2012;6(3):364–8.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lee AW, Ng WT, Hung WM, Choi CW, Tung R, Ling YH, Cheng PT, Yau TK, Chang AT, Leung SK, et al. Major late toxicities after conformal radiotherapy for nasopharyngeal carcinoma-patient- and treatment-related risk factors. Int J Radiat Oncol Biol Phys. 2009;73(4):1121–8.

    Article  PubMed  Google Scholar 

  18. Li Y, Xu T, Qian W, Lu X, Hu C. Radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary nasopharyngeal carcinoma patients: a dose-volume-outcome analysis. Oral Oncol. 2018;84:1–6.

    Article  PubMed  Google Scholar 

  19. Bedwinek JM, Shukovsky LJ, Fletcher GH, Daley TE. Osteonecrosis in patients treated with definitive radiotherapy for squamous cell carcinomas of the oral cavity and naso-and oropharynx. Radiology. 1976;119(3):665–7.

    Article  CAS  PubMed  Google Scholar 

  20. Lam JW, Chan JY, Lui WM, Ho WK, Lee R, Tsang RK. Management of pseudoaneurysms of the internal carotid artery in postirradiated nasopharyngeal carcinoma patients. Laryngoscope. 2014;124(10):2292–6.

    Article  PubMed  Google Scholar 

  21. Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983;41(6):351–7.

    Article  CAS  PubMed  Google Scholar 

  22. Liang SB, Wang Y, Hu XF, He SS, Yang XL, Liu LZ, Cui CY, Chen Y, Fu LW. Survival and toxicities of IMRT based on the RTOG protocols in patients with nasopharyngeal carcinoma from the endemic regions of China. J Cancer. 2017;8(18):3718–24.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 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(22):3684–90.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, et al. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2012;13(2):172–80.

    Article  CAS  PubMed  Google Scholar 

  25. Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983;41(5):283–8.

    Article  CAS  PubMed  Google Scholar 

  26. Abu Eid R, Sawair F, Landini G, Saku T. Age and the architecture of oral mucosa. Age (Dordr). 2012;34(3):651–8.

    Article  CAS  PubMed  Google Scholar 

  27. Engeland CG, Bosch JA, Cacioppo JT, Marucha PT. Mucosal wound healing: the roles of age and sex. Arch Surgery (Chicago, Ill : 1960). 2006;141(12):1193–7 discussion 1198.

    Article  Google Scholar 

Download references

Funding

This work was supported by National Natural Science Foundation of China [grant number 82373203].

Author information

Author notes

  1. Xing-Li Yang and Li Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510060, China

    Xing-Li Yang, Sha-Sha He, Dan-Wan Wen, Yan Wang, Xue-Cen Wang & Yong Chen

  2. Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510080, China

    Li Lin

  3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, 510080, China

    Li Lin & Jia Kou

  4. Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510080, China

    Jia Kou

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  2. Li Lin
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  3. Sha-Sha He
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  4. Dan-Wan Wen
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  5. Jia Kou
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  6. Yan Wang
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  7. Xue-Cen Wang
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  8. Yong Chen
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Contributions

Xing-li Yang drafted the work, and substantively revised it, Li Lin and Jia Kou provided the acquisition of data, Sha-sha He help the revision, Dan-wan Wen analysis data, Yan Wang made interpretation of data, Xue-cen Wang and Yong Chen proved conception and guide the work.

Corresponding authors

Correspondence to Xue-Cen Wang or Yong Chen.

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This retrospective study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in accordance with the Declaration of Helsinki, and the requirement for informed consent was waive.

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The authors declare no competing interests.

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Yang, XL., Lin, L., He, SS. et al. Nasopharyngeal necrosis following intensity-modulated radiation therapy of primary nasopharyngeal carcinoma—incidence rate and predictors of risk. BMC Cancer 25, 802 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12885-025-14086-z

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12885-025-14086-z

Keywords

BMC Cancer

ISSN: 1471-2407

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