Sage Journals: Discover world-class research

Abstract

Background:

Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited.

Objectives:

To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC.

Design:

In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed.

Methods:

The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan–Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model.

Results:

The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone.

Conclusion:

SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

Keywords

distant metastasis induction chemotherapy lymph node to primary tumor ratio nasopharyngeal carcinoma positron emission tomography standardized uptake value

Introduction

In the era of intensity-modulated radiotherapy (IMRT), locoregional control has been dramatically improved, and distant metastasis has become the primary failure pattern after treatment for nasopharyngeal carcinoma (NPC).^1–3 This highlights the need for effective biomarkers that can accurately predict distant metastasis and guide individualized treatment and disease surveillance.

¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) combines functional metabolic imaging with anatomical structure imaging, which can reflect intratumoral heterogeneity.^4–6 It has been widely used in the diagnosing and staging of NPC.^5–10 Recently, several studies showed that the lymph node-to-primary tumor ratio (NTR) of PET standardized uptake value (SUV) had potential predictive value in some cancers, such as cervical, esophageal cancer, and breast cancer.^4,11,12 However, in NPC, relevant data were limited and the studies were mainly based on the concurrent chemoradiotherapy (CCRT) mode.^13–16 Nowadays, induction chemotherapy (IC) combined with CCRT has become the standard treatment for locoregionally advanced NPC (LA-NPC) since IC can significantly reduce distant metastasis and improve the overall survival (OS) rate.^17–20 For non-endemic NPC, IC + CCRT can significantly reduce grade 3–4 late radiation toxicities, and the response to IC may provide additional prognostic information.²¹ In this context, it was necessary to discuss the prognostic value of SUV NTR for patients treated with IC. However, relevant data on large samples were limited.

This study focused on patients with LA-NPC treated with IC and aimed to (i) evaluate the prognostic value of SUV NTR and (ii) establish a risk stratification model based on SUV NTR to predict distant metastasis.

Patients and methods

Patient selection

From September 2017 to November 2020, 467 patients with pretreatment PET/CT scans were retrospectively reviewed. Inclusion criteria were as follows: (1) pathologically confirmed NPC; (2) underwent ¹⁸F-FDG PET/CT scans before treatment; (3) treated with IC and IMRT; (4) no evidence of distant metastasis; and (5) without previous or concomitant malignant diseases. Patients who participated in the randomized, phase III clinical trial to compare the efficacy and safety of sequential chemoradiotherapy [IC + radiotherapy (RT) + adjuvant chemotherapy (AC)] with IC plus CCRT (IC + CCRT) in patients with LA-NPC (NCT03366415) were also included in the present study. The study was carried out following the Good Clinical Practice guidelines and the Declaration of Helsinki.

Except for PET/CT, patients underwent pretreatment evaluations, including a detailed history and physical examination, magnetic resonance imaging (MRI) (preferred) or CT of the head and neck, fiberoptic nasopharyngoscopy or indirect nasopharyngoscopy, electrocardiogram, and complete blood sampling. All patients were staged based on the eighth edition of the International Union Against Cancer/American Joint Committee on Cancer staging system. The study was approved by the Institutional Review Board of our cancer center (No. 2009224-1).

¹⁸F-FDG PET/CT imaging

Patients were required to fast for at least 6 h before PET/CT scan. ¹⁸F-FDG was given intravenously at a dose of 7.4 MBq/kg. After resting for 1 h, the PET/CT scan was performed using a Siemens Biograph 16HR PET/CT Scanner (Knoxville, TN, USA). The patient kept a supine position with elbows on the forehead in a full carbon flatbed. The scanning range was from the proximal thighs to the head. CT scanning was performed before PET acquisition. The parameters of CT scanning were as follows: 120 kV, 110 mA, slice thickness of 5 mm, rotation time of 0.5 s, and pitch of 1 mm. The PET scan duration was 2–3 min per bed for 6–8 beds. The PET images were reconstructed using the ordered subset maximum expectation iteration method after attenuation correction using CT images. More details have been described previously.²²

SUV-T was defined as the maximum SUV (SUVmax) of the primary tumor, SUV-N was defined as SUVmax of the lymph nodes, and SUV NTR was defined as the lymph NTR of SUVmax. For multiple lymph nodes, SUVmax is defined as the highest SUVmax of the neck lymph nodes, regardless of the size of the lymph nodes.

Treatment, follow-up, and endpoints

All patients received IC and intensity-modulated radiation therapy. In all, 219 (46.9%) patients received concurrent chemotherapy (CCT), and 175 (37.5%) patients received AC. In total, 92 (19.7%) patients received RT alone after IC mainly due to patient rejection, abnormal liver and kidney function, abnormal myocardial enzymes, intolerance, and the impact of COVID-19. The commonly used induction and AC regimens were TP (docetaxel 60–75 mg/m² on day 1, cisplatin 75 mg/m² on day 1 or 25 mg/m²/day on days 1–3) and GP (gemcitabine 1 g/m² on day 1 and day 8, cisplatin 75 mg/m² on day 1 or 25 mg/m²/day on days 1–3). CCT consisted of cisplatin 30–40 mg/m² weekly or 75–80 mg/m² every 3 weeks during IMRT. The radiation (RT) dose was 66–70.4 Gy in 30–32 fractions. The technique of IMRT has been described in a previous study.³

Patients were assessed weekly during IMRT. After treatment, the assessment was done every 3 months for the first 2 years, every 6 months for years 3–5, and yearly after that. Each follow-up included a physical examination of the head and neck and complete blood sampling [including Epstein–Barr virus (EBV) DNA levels, and thyroid and pituitary function]. MRI of the nasopharynx, chest CT, and abdominal ultrasound were performed every 6–12 months. Other tests were recommended according to clinical needs.

The primary endpoint of this study was distant metastasis-free survival (DMFS), which was defined as the time from the first treatment to the first occurrence of distant metastasis. The secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), progression-free survival (PFS), and OS, which were defined as the time from the first treatment to the first occurrence of local recurrence, regional recurrence, progression, or death from any cause, respectively.

Statistical methods

The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of SUV-T, SUV-N, and SUV NTR. Spearman’s tests were used to assess the correlations between variables. The Kaplan–Meier method was used to evaluate LRFS, RRFS, DMFS, OS, and PFS rates. The survival rates were calculated from the day of the first treatment to the date each event happened or the last follow-up. Univariate and multivariate analyses were performed to evaluate potential prognostic factors. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. All the statistical analysis was performed using the Statistical Package for Social Sciences (SPSS version 27.0, IBM Corporation, Chicago, IL, USA) and R (version 4.2, the R Foundation for Statistical Computing, Vienna, Austria). A p value of <0.05 (two-tailed) was considered statistically significant.

Results

Patient characteristics

The baseline and treatment characteristics for 467 enrolled patients are shown in Table 1. The median age at diagnosis was 50 years (range of 13–76, with a mean value of 48.6). The male-to-female ratio was 2.7:1. The median value of SUV-T, SUV-N, and SUV NTR was 11.2 (range of 3–37), 9.6 (1.7–43.5), and 0.94 (0.1–6.6). Positive (⩾500 copies/mL) EBV DNA pre-IC was observed in 352 (75.4%) of the patients.

Table 1.

Patient characteristics (N = 467).

Characteristics	No. (%)
Gender
Male	341 (73.0)
Female	126 (27.0)
Age (year)
Median (range)	50 (13–76)
WHO history type
Non-keratinizing SCC	452 (96.8)
Keratinizing SCC	2 (0.4)
Others	13 (2.8)
T category
T1–2	132 (28.3)
T3–4	335 (71.7)
N category
N1–2	292 (62.5)
N3	175 (37.5)
Overall stage
III	214 (45.8)
IVa	253 (54.2)
Pre-IC EBV DNA
<500 copies/mL	115 (24.6)
⩾500 copies/mL	352 (75.4)
Therapeutic schedule
IC + CCRT	200 (42.8)
IC + RT + AC	156 (33.4)
IC + RT	92 (19.7)
IC + CCRT + AC	19 (4.1)
SUV-T, median (range)	11.2 (3–37)
SUV-N, median (range)	9.6 (1.7–43.5)
SUV NTR, median (range)	0.94 (0.1–6.6)

AC, adjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; EBV DNA, Epstein–Barr virus DNA; IC, induction chemotherapy; NTR, lymph node-to-primary tumor ratio; RT, radiotherapy; SCC, squamous cell carcinoma; SUV-N, maximal standardized uptake value of lymph nodes; SUV-T, maximal standardized uptake value of the primary tumor; WHO, World Health Organization.

Survival outcome

With a median follow-up time of 37 months (interquartile range: 30–44 months), the 3-year LRFS, RRFS, DMFS, OS, and PFS rates were 93.6%, 94.3%, 90.9%, 93.7%, and 81.4%. By the time of the last follow-up, a total of 32 patients died. Treatment failure was observed in 78 patients, including 36 patients with locoregional recurrences alone, 30 with distant metastasis alone, and 12 with both locoregional recurrence and distant metastasis.

Determination of optimal cutoff values and correlation analysis

According to the ROC analysis, the optimal cutoff value of SUV NTR was 0.74 for the prediction of distant metastasis. The area under the curve (AUC) was 0.619 [95% confidence interval (CI): 0.541–0.697, p = 0.011]. The sensitivity, specificity, positive predictive value, and negative predictive value at this value were 90.5%, 35.4%, 58.3%, and 78.8%, respectively. The correlation analysis showed that SUV NTR was weakly correlated with gender, T category, N category, overall stage, and pre-IC EBV DNA. There was a moderate correlation between SUV NTR and SUV-T or SUV-N. Details are shown in Supplemental Table S1.

Prognostic value of SUV NTR on survivals

Univariable analysis showed that N category, overall stage, pre-IC EBV DNA, SUV-N, and SUV NTR were prognostic factors for DMFS. N category, overall stage, SUV-N, and SUV NTR were prognostic factors for RRFS. After controlling for potential confounders, SUV NTR, and overall stage remained independent predictors for DMFS [SUV NTR: hazard ratio (HR): 3.75, 95% CI: 1.33–10.61, p = 0.01; overall stage: HR: 2.11, 95% CI: 1.02–4.35, p = 0.04] and RRFS (SUV NTR: HR: 5.42, 95% CI: 1.28–23.07, p = 0.02; overall stage: HR: 2.64, 95% CI: 1.06–6.56, p = 0.04). Details are shown in Table 2. Patients with high SUV NTR (⩾0.74) had significantly lower DMFS (3-year rates of 87.5% versus 97.4%, p < 0.001) and RRFS (3-year rates of 92% versus 98.7%, p = 0.003) rates compared to those with low SUV NTR. Patients with stage IVa disease had significantly lower DMFS (3-year rates of 87% versus 95.3%, p = 0.002) and RRFS (3-year rates of 91.6% versus 97.3%, p = 0.007) rates compared to those with stage III disease (Supplemental Figure S1).

Table 2.

Analyses of clinical variables for DMFS by Cox proportional hazard regression.

Variables	Test for DMFS	Univariable analysis	p Value	Multivariable analysis	p Value
Variables	Test for DMFS	HR (95% CI)	p Value	HR (95% CI)	p Value
Gender	Female versus Male	0.42 (0.18–1.01)	0.05	0.46 (0.19–1.09)	0.08
Age	⩾60 versus <60	1.07 (0.53–2.18)	0.85	–
T category	T3–4 versus T1–2	0.74 (0.40–1.34)	0.36	–
N category	N3 versus N1–2	2.56 (1.38–4.75)	<0.01	–
Overall stage	IVa versus III	2.89 (1.42–5.89)	<0.01	2.11 (1.02–4.35)	0.04
Pre-IC EBV DNA	⩾500 versus <500	4.76 (1.46–15.50)	0.01	3.16 (0.95–10.45)	0.06
SUV-T	⩾7.95 versus <7.95	0.98 (0.50–1.92)	0.96	–
SUV-N	⩾7.25 versus <7.25	3.25 (1.37–7.71)	0.01	–
SUV NTR	⩾0.74 versus <0.74	5.11 (1.82–14.31)	<0.01	3.75 (1.33–10.61)	0.01

CI, confidence interval; DMFS, distant metastasis-free survival; EBV DNA, Epstein–Barr virus DNA; HR, hazard ratio; IC, induction chemotherapy; NTR, lymph node-to-primary tumor ratio; SUV-N, maximal standardized uptake value of lymph nodes; SUV-T, maximal standardized uptake value of the primary tumor.

RPA risk stratification model based on SUV NTR and the overall stage

Given the independent prognostic value of SUV NTR and overall stage, we established an RPA risk stratification model based on the endpoint of DMFS by combining these two indicators: RPA I (low-risk group): SUV NTR < 0.74 and stage III; (2) RPA II (medium-risk group): SUV NTR ⩾ 0.74 and stage III, or SUV NTR < 0.74 and stage IVa; (3) RPA III (high-risk group): SUV NTR ⩾ 0.74 and stage IVa (Figure 1). The 3-year DMFS rates of patients in the low, medium, and high-risk groups were 98.9%, 93.4%, and 84.2%, respectively (p < 0.001). The corresponding 3-year RRFS rates were 100%, 95.8%, and 89.9%, respectively (p = 0.001). Survival curves are shown in Figure 2.

Figure 1.

Development of an RPA risk stratiﬁcation model based on SUV NTR and overall stage for patients with LA-NPC treated with induction chemotherapy.

Figure 2.

Kaplan–Meier curves for (a) DMFS and (b) RRFS stratiﬁed by the RPA risk stratiﬁcation model.

The ROC analysis and DCA indicated that the RPA model has the best predictive efficiency for DMFS and RRFS compared to SUV NTR or the overall stage alone. The AUC for predicting DMFS was 0.685 versus 0.619–0.621 and 0.692 versus 0.626–0.655 for RRFS (Figure 3 and Supplemental Table S2).

Figure 3.

ROC curves comparing the accuracy of the RPA model with SUV NTR and the TNM stage for predicting (a) DMFS and (b) RRFS.

Therapeutic schedule within each RPA group

We further analyzed the effect of different treatment schedules (IC + RT, IC + CCRT, IC + RT + AC) in each RPA group. The results showed no significant difference in DMFS among patients treated with different treatment schedules in the low- and high-risk groups (RPA I and RPA III). In the medium-risk group (RPA II), the DMFS of patients treated with IC + CCRT was higher than those treated with IC + RT (3-year rates of 95.7% versus 86.9%, p = 0.059). However, the difference did not reach statistical significance. For RRFS, there was no significant difference among patients with different treatment schedules in the low- and medium-risk groups (RPA I and RPA II). However, in the high-risk group (RPA III), patients treated with IC + CCRT had a significantly higher RRFS rate than those treated with IC + RT + AC (3-year rates of 98.4% versus 80.5%, p = 0.02). Survival curves are shown in Supplemental Figure S2.

Discussion

In this study, we analyzed the prognostic value of pretreatment SUV NTR in 467 patients with LA-NPC. We found that SUV NTR was an independent prognostic factor for DMFS and RRFS. Then we established an RPA model based on SUV NTR and the TNM stage, which could effectively predict distant metastasis and regional recurrence. ROC analysis showed that the RPA model had improved prediction efficiency than SUV NTR or the TNM stage alone. Our data are important since it is the first study with a large cohort to show the prognostic value of SUV NTR combined with the eighth edition of the TNM staging system in patients with LA-NPC treated with IC.

SUVmax may be affected by many factors, including blood glucose, liver and kidney function, injection dose, injection-to-scanning time, scanning speed, and partial volume effect.²³ By contrast, SUV NTR was relatively stable and conducive to comparing different patients. In addition, SUV NTR could reflect the heterogeneity between metastatic lymph nodes and primary tumors.¹³ Several retrospective studies^13–16 showed that SUV NTR was an independent predictor of distant metastasis for NPC. However, these studies were mainly based on the CCRT treatment mode. Our study aimed to explore the prognostic value of SUV NTR under the new treatment pattern of IC combined with IMRT. The results showed that SUV NTR remained an effective predictor for distant metastasis and regional recurrence. In addition, the RPA risk stratification model based on SUV NTR displayed improved predictive efficiency in distant metastasis and regional recurrence. The RPA model may help to guide individualized treatment of NPC.

In the subgroup analysis, we found that the DMFS of patients treated with IC + CCRT was higher than those treated with IC + RT (3-year rates of 95.7% versus 86.9%, p = 0.059). However, the difference did not reach statistical significance. No significant difference was found in the high-risk group. Possible reasons included the following: (1) The number of cases in each treatment group was relatively small and (2) the current treatment intensity was still insufficient to improve the DMFS for high-risk patients, and more effective systemic treatment was needed. In addition, we found that the RRFS of high-risk patients was significantly higher in the IC + CCRT group than in the IC + RT + AC group. We attributed this to the radiosensitization of CCT. Since the results were subgroup analysis and the number of cases in each subgroup was relatively small, no conclusion could be reached from the present study. Prospective studies were needed.

Many studies have shown that pretreatment of EBV DNA was an effective predictor of DMFS for NPC.^24–26 In our research, the univariable analysis showed that pre-IC EBV DNA was a potential predictor of DMFS. However, the predictive role disappeared in multivariable analysis. We attributed that to the change of treatment mode since previous studies were mostly based on the CCRT mode, while all patients in our study received IC-based treatment. We speculated that the function of clearing micrometastasis and improving DMFS of IC might reduce the predictive effect of pre-IC EBV DNA. Recently, several studies showed that post-IC EBV DNA was an effective biomarker for LA-NPC.^27–30 There might be an improved performance with the combination of SUV NTR and post-IC EBV DNA for LA-NPC. Further investigations were warranted.

Limitations of our study included its retrospective nature, conducted in a single institution, lack of validation cohort, utilization of multiple strategies, and short follow-up time, which may have the results underpowered. Further research was warranted to validate our results. Despite these limitations, our study is still important since it is the first study with a large cohort to show the prognostic value of SUV NTR combined with TNM stage in patients with LA-NPC treated with IC.

Conclusion

In conclusion, our study demonstrated that SUV NTR was a prognostic biomarker for patients with LA-NPC treated with IC. We developed an RPA risk stratification model based on SUV NTR, which provided improved predictive efficiency for DMFS and RRFS over the eighth edition of the TNM staging system. Studies on optimal individualized treatment and disease surveillance for patients within different risk groups are needed.

Supplemental Material

sj-docx-1-tam-10.1177_17588359241233235 – Supplemental material for Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis

Supplemental material, sj-docx-1-tam-10.1177_17588359241233235 for Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis by Fang-Fang Kong, Guang-Sen Pan, Meng-Shan Ni, Cheng-Run Du, Chao-Su Hu and Hong-Mei Ying in Therapeutic Advances in Medical Oncology

Footnotes

Acknowledgements

We thank Yu Gao and Miao Mo for their help in data acquisition and statistical analysis.

Declarations

ORCID iD

Hong-Mei Ying

Supplemental material

Supplemental material for this article is available online.

References

Lee

, et al. Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol 2015; 33: 3356–3364.

Sun

Chen

, et al. Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol 2014; 110: 398–403.

Zhou

Shi

, et al. Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost. Oncotarget 2015; 6: 38381–38397.

Kim

Yoon

Kim

, et al. Axillary lymph node-to-primary tumor standard uptake value ratio on preoperative (18)F-FDG PET/CT: a prognostic factor for invasive ductal breast cancer. J Breast Cancer 2015; 18: 173–180.

Salamon

Derlin

Bannas

, et al. Evaluation of intratumoural heterogeneity on ¹⁸F-FDG PET/CT for characterization of peripheral nerve sheath tumours in neurofibromatosis type 1. Eur J Nucl Med Mol Imaging 2013; 40: 685–692.

Lee

Park

Lee

, et al. Preoperative [¹⁸F]FDG PET/CT tumour heterogeneity index in patients with uterine leiomyosarcoma: a multicentre retrospective study. Eur J Nucl Med Mol Imaging 2018; 45: 1309–1316.

Liu

Lin

Chang

, et al. ¹⁸F-FDG PET can replace conventional work-up in primary M staging of nonkeratinizing nasopharyngeal carcinoma. J Nucl Med 2007; 48: 1614–1619.

Chan

Yen

, et al. Staging of untreated nasopharyngeal carcinoma with PET/CT: comparison with conventional imaging work-up. Eur J Nucl Med Mol Imaging 2009; 36: 12–22.

Chang

Chan

Yen

, et al. Nasopharyngeal carcinoma staging by (18)F-fluorodeoxyglucose positron emission tomography. Int J Radiat Oncol Biol Phys 2005; 62: 501–507.

10.

Kim

Paeng

, et al. Heterogeneity index evaluated by slope of linear regression on ¹⁸F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging 2017; 44: 1995–2003.

11.

Chung

Cheon

Kim

, et al. Prognostic importance of lymph node-to-primary tumor standardized uptake value ratio in invasive squamous cell carcinoma of uterine cervix. Eur J Nucl Med Mol Imaging 2017; 44: 1862–1869.

12.

Lin

Hung

Chang

, et al. Prognostic value of lymph node-to-primary tumor standardized uptake value ratio in esophageal squamous cell carcinoma treated with definitive chemoradiotherapy. Cancers (Basel) 2020; 12: 607.

13.

Qiu

, et al. Reflecting on the utility of standardized uptake values on ¹⁸F-FDG PET in nasopharyngeal carcinoma. BMC Cancer 2022; 22: 495.

14.

Lou

Chen

Lin

, et al. The prognostic value of the ratio of standard uptake value of lymph node to primary tumor before treatment of locally advanced nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 2023; 280: 347–356.

15.

Hung

Fan

Kang

, et al. Lymph node-to-primary tumor standardized uptake value ratio on PET predicts distant metastasis in nasopharyngeal carcinoma. Oral Oncol 2020; 110: 104756.

16.

Shen

Hung

Tsan

, et al. Utilization of the lymph node-to-primary tumor ratio of PET standardized uptake value and circulating Epstein–Barr virus DNA to predict distant metastasis in nasopharyngeal carcinoma. Radiother Oncol 2022; 177: 1–8.

17.

David

Sharon Spencer Andrew

, et al. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: head and neck cancers, version 2. 2022.

18.

Tang

Chen

, et al. The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma. Cancer Commun (Lond) 2021; 41: 1195–1227.

19.

Zhang

Chen

, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med 2019; 381: 1124–1135.

20.

Chen

Zhang

, et al. Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: long-term results of phase 3 randomized controlled trial. Int J Cancer 2019; 145: 295–305.

21.

Blanchard

El Khoury

, et al. Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by concurrent chemoradiotherapy or chemoradiotherapy alone in locally advanced non-endemic nasopharyngeal carcinoma. Oral Oncol 2016; 62: 114–121.

22.

Zhang

, et al. Establishment and validation of a nomogram with intratumoral heterogeneity derived from ¹⁸F-FDG PET/CT for predicting individual conditional risk of 5-year recurrence before initial treatment of nasopharyngeal carcinoma. BMC Cancer 2020; 20: 37.

23.

Schirmer

Calamia

Wenger

, et al. ¹⁸F-fluorodeoxyglucose-positron emission tomography: a new explorative perspective. Exp Gerontol 2003; 38: 463–470.

24.

Lin

Wang

Chen

, et al. Quantification of plasma Epstein–Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 2004; 350: 2461–2470.

25.

Hou

Zhao

Guo

, et al. Different clinical significance of pre- and post-treatment plasma Epstein–Barr virus DNA load in nasopharyngeal carcinoma treated with radiotherapy. Clin Oncol (R Coll Radiol) 2011; 23: 128–133.

26.

Lee

Kwong

Leung

, et al. The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification. Int J Cancer 2019; 144: 1713–1722.

27.

Chen

Zhou

, et al. Liquid biopsy tracking during sequential chemo-radiotherapy identifies distinct prognostic phenotypes in nasopharyngeal carcinoma. Nat Commun 2019; 10: 3941.

28.

Zhu

Ouyang

Xiong

, et al. Prognostic value of plasma Epstein–Barr virus DNA levels pre- and post-neoadjuvant chemotherapy in patients with nasopharyngeal carcinoma. Front Oncol 2021; 11: 714433.

29.

Huang

Sun

Guo

, et al. Plasma Epstein–Barr virus DNA load after induction chemotherapy predicts outcome in locoregionally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2019; 104: 355–361.

30.

Chen

Luo

Chen

, et al. Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma. Eur J Cancer 2021; 151: 63–71.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB

Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis

Abstract

Background:

Objectives:

Design:

Methods:

Results:

Conclusion:

Keywords

Introduction

Patients and methods

Patient selection

18F-FDG PET/CT imaging

Treatment, follow-up, and endpoints

Statistical methods

Results

Patient characteristics

Survival outcome

Determination of optimal cutoff values and correlation analysis

Prognostic value of SUV NTR on survivals

RPA risk stratification model based on SUV NTR and the overall stage

Therapeutic schedule within each RPA group

Discussion

Conclusion

Supplemental Material

sj-docx-1-tam-10.1177_17588359241233235 – Supplemental material for Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis

Footnotes

Acknowledgements

Declarations

ORCID iD

Supplemental material

References

Supplementary Material

¹⁸F-FDG PET/CT imaging