Age is a significant biomarker for the selection of neoadjuvant chemotherapy plus radiotherapy versus concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma

Abstract

BACKGROUND:

The optimal timing of combined chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma (LA-NPC) is undetermined.

OBJECTIVE:

This study aimed to compare the therapeutic efficacy of neoadjuvant chemotherapy (NACT) followed by radiotherapy (RT) and concurrent chemoradiotherapy (CCRT).

METHODS:

Five hundred and thirty-eight patients diagnosed with LA-NPC and treated with NACT $+$ RT or CCRT alone were enrolled in the study. Restricted cubic spline regression (RCS) was used to determine the relationship between age and the hazard Ratio of death. A Kaplan-Meier analysis was performed to evaluate overall survival (OS) related to NACT $+$ RT or CCRT alone. Cox proportional hazards models were used to adjust for potential confounding factors.

RESULTS:

Compared with the CCRT alone regimen, the NACT + RT regimen showed a significantly better OS rate with a 62% decreased risk of death in a subgroup of patients aged $\geqslant$ 45 years (hazard ratio, HR: 0.38; 95% confidence interval, CI: 0.24–0.61). In patients aged $<$ 45 years, the risk of death was significantly increased when NACT $+$ RT was chosen compared with CCRT (HR: 4.10; 95% CI: 2.09–8.07).

CONCLUSIONS:

Age is a significant biomarker when selecting NACT $+$ RT or CCRT alone in patients with locally advanced NPC.

Keywords

Nasopharyngeal carcinoma neoadjuvant chemotherapy radiotherapy concurrent chemoradiotherapy age

1. Introduction

Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer that originates from epithelial cells of the head and neck. NPC demonstrates an unbalanced endemic distribution and is associated with the Epstein-Barr virus (EBV) [1, 2]. Globally, China has one of the highest incidence and mortality rates for NPC, especially in the southern region [3]. More than 70% of patients with NPC are initially diagnosed with locally advanced disease [4].

Radiotherapy (RT) is the main treatment for NPC as it is suited to the complex anatomy of NPC and its high sensitivity to radiation [5, 6]. With the introduction of intensity-modulated radiation therapy (IMRT) and the use of chemotherapy in patients with advanced diseases, rates of successful local control have improved, and the risk of distant metastasis has also improved greatly [7, 8, 9]. RT is the main treatment for early-stage disease, and the 5-year overall survival (OS) rates in patients with stage I–II NPC can reach 95–100%. However, the 5-year OS rate of patients with stage III–IVA NPC remains unsatisfactory [10], with approximately 30% of patients at high risk of disease recurrence and metastasis. Distant metastasis represents the main mode of failure [11, 12], which may be related to metastatic cancer with a relatively long natural history. For locally advanced NPC (LA-NPC), concurrent chemoradiotherapy (CCRT) can prolong OS. CCRT is considered the standard treatment for LA-NPC [13]. A meta-analysis by Langendijk et al. reported that the most effective way to introduce chemotherapy is to perform it simultaneously with RT, which increases the 5-year survival rate by 20% [14].

In recent decades, numerous trials have studied the value of adding chemotherapy to RT for NPC [15, 16, 17]. Compared with adjuvant chemotherapy (ACT), neoadjuvant chemotherapy (NACT) has the advantages of increasing radiosensitivity, killing micro-metastasis, and reducing tumor stage, as well as better tolerance [18]. There is increasing evidence that patients with LA-NPC can benefit from NACT [19, 20]. Furthermore, compared with CCRT, the incidence of acute side effects of RT after sequential NACT is significantly reduced, and patient compliance is improved [21, 22].

At present, NACT or CCRT are considered superior to RT alone [16], but a long-term follow-up study has shown that there is no significant difference in the survival rate between the two regimens [23]. Therefore, the optimal time to combine chemotherapy with RT remains undetermined. Therefore, this study aimed to compare the relative survival benefits of CCRT and NACT $+$ RT and to identify a better treatment scheme to obtain maximum patient benefits.

2. Materials and methods

2.1 Patient characteristics

This was a secondary retrospective study, and data were collected from patients who received treatment at Sun Yat-Sen University Cancer Center between October 2009 and February 2012. A total of 538 patients satisfied the inclusion criteria and were included in the analysis. Tumor characteristics, histology, age, sex, tumor (T) stage, nodal (N) stage, OS, and treatment regimen (NACT followed by RT and CCRT alone) were recorded.

2.2 Inclusion criteria

Patients were enrolled in the study if they satisfied all the following criteria:

1.
Proven nasopharyngeal carcinoma.
2.
No evidence of distant metastasis.
3.
Treatment modality: Treatment with NACT $+$ IMRT or CCRT alone, patients who received adjuvant chemotherapy (ACT) or surgical treatment were excluded.
4.
Complete follow-up data.

As this was a retrospective analysis, the requirement for informed consent was waived.
2.3 Definitions

Treatment regimens: Patients were treated with neoadjuvant chemotherapy followed by radical IMRT or concurrent chemoradiotherapy alone. The specific regimes of each treatment were as follows: (1) NACT: including paclitaxel in combination with cisplatin (TP) or cisplatin in combination with 5-fluorouracil (PF); (2) CCRT: chemotherapy of cisplatin combined with intensity-modulated radiotherapy – two cycles of each treatment regime should be accomplished (Supplement 1).

The 7 ${}^{\text{th}}$ edition of the International Union against Cancer/American Joint Committee on Cancer staging system was used to classify tumor stages of patients with NPC. A consensus on the histological type was achieved using the 2005 World Health Organization (WHO) classification: (1) WHO grade I was defined as a microscopic morphology type of keratinizing squamous cell carcinoma; (2) WHO grade II was defined as a microscopic morphology type of non-keratinizing differentiated carcinoma; and (3) WHO grade III was defined as a microscopic morphology type of non-keratinizing undifferentiated carcinoma.

The endpoint was OS, which was defined as the time from diagnosis to death for NPC or the last outpatient visit.

2.4 Follow-up and measurement

Patients were required to return for a general physical condition assessment every 3 months in the first 2 years, every 6 months in years 2–5, and annually thereafter. If patients failed to return to the clinic, we obtained their review data by contacting the patient or their families. The follow-up period was defined as the time of first diagnosis or first treatment to death or the last outpatient visit.

Routine tests, including serum tumor markers, electronic nasopharyngoscopy, chest computed tomography, transabdominal color Doppler scan, brain magnetic resonance imaging, bone scan, and positron emission tomography-computed tomography, were performed to evaluate the systemic tumor load.

2.5 Endpoint and statistical analysis

The primary objective of the analysis was to compare the OS of patients with LA-NPC after treatment with NACT followed by RT or CCRT.

Baseline characteristics were compared using the Fisher’s test for categorical variables. Restricted cubic spline regression (RCS) was used to determine the relationship between age and the hazard ratio of death. To explore the association between different treatment regimens with clinical outcome benefits in patients with LA-NPC, the survival rate was estimated using the Kaplan-Meier method; univariate comparisons were performed using the log-rank test. Cox proportional hazards models were used to adjust for potential confounders. The subgroup analysis was performed on five covariates to evaluate the prognosis for NACT followed by RT vs. CCRT, including age, sex, histology, clinical T stage, and clinical N stage; hazard ratios (HRs) and 95% confidence interval (CI) were used to present the results.

All statistical tests were two-sided. $P<$ 0.05 was considered statistically significant. All analyses were performed using SPSS 24.0 (IBM Corp., Armonk, NY, USA) and R 3.1.2 (R-Foundation, Vienna, Austria). The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

3. Results

3.1 Clinical characteristics of NPC patients

The data for this analysis was published in PLOS One in 2016 and included 538 patients who were newly diagnosed with LA-NPC at SYSUCC from October 2009 to February 2012. Among them, 236 (43.9%) received CCRT and 302 (56.1%) received NACT $+$ RT. Univariate analysis showed that age ( $P=$ 0.002) and T stage ( $P=$ 0.01) were significantly different in the NACT $+$ RT and CCRT groups ( $P<$ 0.05) (Table 1).

Table 1
Basic characteristics of the patients in the NACT $+$ RT vs. CCRT groups

Treatment	CCRT	NACT $+$ RT	$P$ -value
No.	236	302
Age (years)	45.8 $\pm$ 11.7	49.0 $\pm$ 11.8	0.002
Age (years)			0.008
$<$ 45	116 (49.2%)	114 (37.7%)
$\geqslant$ 45	120 (50.8%)	188 (62.3%)
Sex			0.083
Male	180 (76.3%)	210 (69.5%)
Female	56 (23.7%)	92 (30.5%)
Histology			0.058
WHO I	0 (0.0%)	4 (1.3%)
WHO II	5 (2.1%)	14 (4.6%)
WHO III	231 (97.9%)	284 (94.0%)
T stage			0.01
1	19 (8.1%)	12 (4.0%)
2	12 (5.1%)	30 (9.9%)
3	59 (25.0%)	96 (31.8%)
4	146 (61.9%)	164 (54.3%)
N stage			0.252
0	30 (12.7%)	32 (10.6%)
1	116 (49.2%)	132 (43.7%)
2	16 (6.8%)	18 (6.0%)
3	74 (31.4%)	120 (39.7%)

Data are presented as numbers (percentage). NACT, neoadjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; RT, radiotherapy; WHO, World Health Organization.

The median follow-up time of this study was 48.0 months (5.0–73.0 months). A total 22.49% (121/538) of the patients died until the final follow-up.

Figure 1.

Kaplan-Meier curves of overall survival in patients with NPC treated with NACT $+$ RT versus CCRT. NACT, neoadjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; RT, radiotherapy; NPC, nasopharyngeal carcinoma.

Figure 2.

Kaplan-Meier curves of overall survival in patients with NPC stratified by age. NACT, neoadjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; RT, radiotherapy; NPC, nasopharyngeal carcinoma.

3.2 OS rate of different treatment regimens

Survival analysis showed that there was no difference between the 5-year survival rate between patients who received NACT $+$ RT and those who received CCRT ( $P=$ 0.75) (Fig. 1). To evaluate the relationship between age and OS, patients were divided into two subgroups based on the median age of 45 years ( $<$ 45 years and $\geqslant$ 45 years) in both the NACT $+$ RT or CCRT alone groups. Subgroup analysis showed that in patients $<$ 45 years, OS was significantly higher in the CCRT group than in the NACT $+$ RT group ( $P<$ 0.0001). In patients aged $\geqslant$ 45 years, OS was significantly higher in the NACT $+$ RT group than in the CCRT group ( $P<$ 0.0001) (Fig. 2).

Table 2
NACT $+$ RT treatment (vs. CCRT) and multivariate HR of overall survival with 95% CIs in NPC

	Death/patient	Non-adjusted model	Adjusted model ${}^{\text{a}}$
All patients	121/538	0.94 (0.66–1.35)	0.85 (0.59–1.22) ${}^{\#}$
Patients aged $\geqslant$ 45 years	74/308	0.38 (0.24–0.61)	0.40 (0.25–0.65) ${}^{\ast}$
Patients aged $<$ 45 years	47/230	4.10 (2.09–8.07)	3.89 (1.95–7.76) ${}^{\ast}$

Data are presented as numbers or hazard ratios (95% confidence interval). ${}^{\text{a}}$ This model is adjusted for age ( $<$ 45 and $\geqslant$ 45 years), sex (male, female), histology (I/II, III), T stage (1/2, 3, 4), and N stage (0/1, 2/3). ${}^{\ast}$ This model is adjusted for sex (male, female), histology (I/II, III), T stage (1/2, 3, 4), and N stage (0/1, 2/3). NACT, neoadjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; RT, radiotherapy; HR, hazard ratio; CI, confidence interval; NPC, nasopharyngeal carcinoma.

Figure 3.

Stratified analysis for unadjusted HR in the subgroups of age, sex, histology, T stage, and N stage HR (vs. continued) $=$ hazard ratio. NACT, neoadjuvant chemotherapy; CCRT, concurrent chemoradiotherapy; RT, radiotherapy; HR, hazard ratio; WHO, World Health Organization.

3.3 Prognostic factors for OS

Compared with the CCRT alone regimen, the NACT $+$ RT regimen was associated with a significantly better OS, with a 62% decrease in risk of death in patients aged $\geqslant$ 45 years at diagnosis (HR: 0.38; 95% CI: 0.24–0.61). In contrast, in patients aged $<$ 45 years at diagnosis, the risk of death was significantly increased with NACT $+$ RT compared to CCRT (HR: 4.10; 95% CI: 2.09–8.07). The results for the T stage (T1/2) (HR: 1.72; 95% CI: 0.65–4.60) and N stage (N2/3) (HR: 1.35; 95% CI: 0.80–2.29) indicated that if a patient with T1N3 underwent the CCRT regimen, they might have better outcomes, although the difference was not statistically significant. The HR of the T stage (T4) was 0.61, and the 95% CI was 0.36–1.02, while that of the N stage (N1/2) was 0.61, and the 95% CI was 0.36–1.02, indicating that the prognosis following the NACT $+$ RT regimen was better; however, it did not reach statistical significance either.

Table 3
The number of death patients in NACT $+$ RT and CCRT

	Death/patient
	All patients	NACT $+$ RT	CCRT
Patients aged $<$ 45 years	47/230	36/114	11/116
Patients aged $\geqslant$ 45, $<$ 57 years	35/162	14/98	21/64
Patients aged $\geqslant$ 57 years	39/146	16/90	23/56

Figure 4.

The relationship between age and the HR of overall mortality.

Finally, multivariate analysis was performed to explore the association between different treatment regimens and overall survival (NACT $+$ RT vs. CCRT) after adjustment for age ( $<$ 45 and $\geqslant$ 45 years), sex (male or female), histology (I/II, III), T stage (1/2, 3, 4), and N stage (0/1, 2/3). At the end of the follow-up, 124 patients had died of NPC (unadjusted HR: 0.94; 95% CI: 0.66–1.35 and adjusted HR: 0.85; 95% CI: 0.59–1.22). (Fig. 3) However, after adjusting for sex, histology (I/II, III), T stage (1/2, 3, 4), and N stage (0/1, 2/3) in patients aged $\geqslant$ 45 years, the unadjusted HR was 0.38, and the 95% CI was 0.24–0.61, while the adjusted HR was 0.40, and the 95% CI was 0.25–0.65. On the other hand, in patients aged $<$ 45 years, the unadjusted HR was 4.10, and the 95% CI was 2.09–8.07, while the adjusted HR was 3.89, and the 95%CI was 1.95–7.76 (Table 2). After exclusion of confounding factors, age was found to be a significant biomarker for patients with advanced NPC treated with NACT $+$ RT vs. CCRT.

3.4 The relationship between age and OS

RCS indicated that the HR of overall mortality increased with age, and was highest at the age of 57, then decreased gradually (Fig. 4). To further explore the relationship between age and the survival of patients with LA-NPC, the study patients were divided into three groups according to the median age and the highest HR of overall mortality ( age $<$ 45 years, 45–57 years, and $\geqslant$ 57 years). We found that among those aged $<$ 45 years, 36 patients treated with the NACT $+$ RT regimen died, and only 11 patients treated with the CCRT regimen died. On the contrary, for patients aged 45–57 years and $\geqslant$ 57 years, there were fewer deaths among those treated with the NACT $+$ RT regimen than with the CCRT regimen (14/98 vs. 21/64, and 16/90 vs. 23/56, respectively) (Table 3). Moreover, the survival difference is statistically significant for patients in the 45–57 years and $\geqslant$ 57 years age groups. The Kaplan-Meier survival curve showed that the CCRT regimen had a much worse OS than the NACT $+$ RT regimen ( $P=$ 0.0086, and $P=$ 0.0011, respectively) (Fig. 5).

Figure 5.

Kaplan-Meier curves of overall survival in patients with NPC stratified by age a: the survival of patients with 45–57 years; b:the survival of patients with $\geqslant$ 57 years.

4. Discussion

In our study, we reported the results of 538 newly diagnosed patients with LA-NPC who received CCRT or NACT $+$ RT between 2009 and 2012. Survival analysis showed no significant difference in the 5-year survival between patients who received NACT $+$ RT and those who received CCRT ( $P=$ 0.75); this finding is consistent with previous studies [24]. However, our univariate analysis indicated that age might have an effect on survival in groups of patients treated with different treatment regimens ( $P=$ 0.002). People aged $\geqslant$ 45 years had better survival with NACT $+$ RT than with CCRT ( $P<$ 0.0001), and this was consistent with the summary analysis of Chua et al. [25] which showed that the 4-year distant metastasis-free survival (DMFS) was 90.2% for NACT $+$ RT vs. 78.1% for CCRT, ( $P=$ 0.004), and the NACT $+$ RT also improved and progression-free survival (PFS) when compared with CCRT (78.1% vs. 67.1%, $P=$ 0.040).

A prospective observational study by Chang et al. [26] showed that CCRT could not provide 5-year estimated OS, disease-free survival (DFS), recurrence-free survival (RFS), or metastasis-free survival (MFS) benefits for patients with locally advanced NPC based on a large number of patients treated with NACT $+$ RT. Furthermore, CCRT may potentially increase the risk of acute poisoning, especially severe myelosuppression and oral mucositis, which is consistent with the INT-0099 in which 37% of patients in the chemoradiotherapy group terminated treatment early because of excessive toxicity [27]. In contrast, the prognosis of patients aged $<$ 45 years who received CCRT was significantly better than that of patients who received NACT $+$ RT ( $P<$ 0.0001). Song et al. reported that patients who received CCRT showed lower local failure than those who received NACT (12% vs. 19%, respectively), suggesting that CCRT can provide better local control [28]. Furthermore, Wu et al. reported that in the first 2 years after completion of treatment, patients receiving NACT had worse regional control than those receiving CCRT [23]. However, previous studies did not analyze the influence of age on the survival prognosis of patients with LA-NPC and analyzed only survival prognosis in the general NPC population. Therefore, we speculated that because age was not considered a confounder, previous studies concluded that there was no statistical difference between NACT $+$ RT and CCRT in LA-NPC. Our study emphasized the importance of age when choosing between diverse treatment options to produce improved survival benefits in LA-NPC patients and drew a satisfactory conclusion. Our results provide a clearer direction for patients with LA-NPC who are diagnosed for the first time.

Moreover, through the subgroup analysis (NACT $+$ RT vs. CCRT), we found that patients with T4 stage and N1-2 stage might achieve better survival with NACT $+$ RT, although the difference did not reach statistical significance, which might be because age was not considered a confounding factor. Thus, our study included a total of 310 patients with staging at T4N0-1 of whom 188 patients were aged $\geqslant$ 45 years old (60.6%) and 122 patients were aged $<$ 45 years old (39.4%). This finding suggests that patients $\geqslant$ 45 years of age account for a high proportion of those at the T4N0-1 stage, indicating that NACT $+$ RT has increasing superiority to CCRT at higher patient stages (T4N1-2) (76.7% vs. 85.4%) and in patients aged $>$ 45 years. The results were consistent with the conclusion of Yao’s report [29], which showed that the 4-year OS in a CCRT group, NACT $+$ RT group, and NACT $+$ CCRT group were 76.7%, 85.4%, and 84.4%, respectively ( $P<$ 0.05). Furthermore, compared with CCRT alone, the OS rate for the NACT $+$ RT group was significantly higher, and NACT $+$ CCRT did not provide any significant advantage over NACT $+$ RT. However, as reported by Xu et al., the 3-year MFS rates were 80.1% and 94.9% in the NACT and CCRT arms, respectively, in patients with T3-4N0-1 ( $P=$ 0.034) [30]. An appropriate explanation is that for patients with T4N0-1 LA-NPC, the local tumor load is the main factor, and the risk of distant metastasis is much lower. In addition, previous studies have shown that NACT can reduce the tumor load and effectively control the subclinical distant metastasis at the same time, which increases the safety margin between tumor volume and radiation volume, and can reduce radiation-related side effects and improve patient compliance. Therefore, we concluded that for patients with a high primary tumor burden and a low potential risk of distant metastasis (T4N0-1), the NACT $+$ RT regimen probably produced satisfactory results.

For patients in the T1/2 stage and N 2/3 stage, the efficacy of CCRT was better than that of NACT $+$ RT, but the difference did not reach statistical significance. Other studies have shown that CCRT improves the survival rate. For patients with advanced N-type and a high risk of metastasis, CCRT is needed regardless of whether ACT is used, and the benefit in terms of OS may be mainly attributed to the CCRT [14, 31, 32]. A subgroup analysis reported by Xu et al. showed that among patients at N 2/3 stage, there was no significant difference in OS, RFS, and DFS between the patients who received CCRT $+$ ACT and those who received NACT $+$ RT $+$ ACT ( $P=$ 0.704) [30]. Combined with the results of this study, for patients at T1-2/N3, the primary tumor focus is small, but lymph node metastasis occurs in the early stage with a high potential risk of distant metastasis. Therefore, CCRT can achieve the greatest coverage in LA-NPC by killing the tumor cells, which can reduce the risk of recurrence and distant metastasis. Therefore, we speculated that CCRT might be a better option for LA-NPC patients with small primary lesions but early lymph node metastasis (T4/N0-1). Therefore, analysis of a large number of retrospective clinical data and prospective studies are needed to confirm our conclusions.

Our study had some limitations. First, this was a retrospective study with a relatively small sample size from a single institution. The use of data from randomized trials performed at different centers could produce more persuasive results. Second, previous studies have shown that the difference in NACT regimens has an impact on the survival rate of patients, and regimens of docetaxel, cisplatin, and fluorouracil can bring greater benefits in local control and distant metastasis than TP [33, 34]. Third, in terms of EBV detection, a previous study found that maintaining a level of EBV deoxyribonucleic acid (DNA) after NACT was a predictor of poor prognosis for patients with LA-NPC [35, 36]. However, our retrospective study did not consider the status of EBV expression, which may have an impact on the evaluation of disease progression and therapeutic effects. Therefore, further studies on EBV expression and EBV DNA replication in tumor tissues are needed. Finally, there was no further analysis of adverse reactions in the two groups. According to previous research [26, 37], compared with CCRT groups, non-CCRT groups have a lower proportion of patients with nausea, vomiting, and oral mucositis, and the incidence of grade 3/4 acute toxicity with CCRT was much higher and more serious. Therefore, the incidence of toxicity may also be a factor influencing the choice of the treatment plan for patients. NACT $+$ RT may be a good choice when patients are older and cannot tolerate the toxicity of CCRT. Analysis of more comprehensive, retrospective clinical data and prospective studies with longer follow-up times are needed to confirm our results.

5. Conclusions

Age has predictive value for the prognosis of patients with LA-NPC; so the age should be considered when selecting NACT $+$ RT or CCRT alone in patients with LA-NPC.

Funding

This work was supported by the Natural Science Foundation of China (Nos 81302067 and 81502360); The Natural Science Foundation of Fujian Province (Nos 2016J01576 and 2020J011147); The Science and Technology Innovation Joint Foundation of Fujian Province (No 2017Y9125).

Authors’ contributions

All authors made a significant contribution to data collection, study design, statistical analysis, the interpretation of results, writing of the manuscript.

Conception: The idea were conceived by the Yihong lin and Xiongbin Yu.

Interpretation Or Analysis Of Date: The interpretation or analysis of data was analyzed by Linbin Lu, Yihong Lin, Junxian Wu.

Preparation Of The Manuscript: The manuscript was written by Yihong Lin.

Revision For Important Intellectual Content: The revision of important intelligence content was completed by Hong Chen, Xuewen Wang, Yayin Chen, Qin Lin.

Supervision: The manuscript was completed under the supervision of Xiong Chen, Xi Chen.

Than, all the uthors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethics approval

Ethical approval was obtained from the Department of Ethics Committee of SYSUCC.

Availability of data and material

The data for this analysis was published in PLOS One with a title that “Neoadjuvant and Concurrent Chemotherapy Have Varied Impacts on the Prognosis of Patients with the Ascending and Descending Types of Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy” in 2016.

Publication ethics

This study was a retrospective analysis, not a particular case study, the ethical approval was obtained from the Department of Ethics Committee of SYSUCC. All authors read and approved the final manuscript and consent for publication.

Consent to participate

This study was a retrospective analysis, so the requirement for informed consent was waived.

Consent for publication

All authors read and approved the final manuscript and consent for publication.

Supplementary data

The supplementary files are available to download from https://dx-doi-org.web.bisu.edu.cn/10.3233/CBM-210357.

sj-docx-1-cbm-10.3233_CBM-210357.docx - Supplemental material

Supplemental material, sj-docx-1-cbm-10.3233_CBM-210357.docx

Footnotes

Acknowledgments

We are grateful for the raw data collected by Professor Jijin Yao at Sun Yat-Sen University Cancer Center. We are also thankful for the statistical analyses of the study supported by the Empower U team of the Department of Epidemiology and Biostatistics, X & Y Solutions Inc., Boston. Last, we would like to thank Editage (www.editage.cn) for English language editing.

Conflict of interest

All authors declare no conflict of interest.

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Age is a significant biomarker for the selection of neoadjuvant chemotherapy plus radiotherapy versus concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSIONS:

Keywords

1. Introduction

2. Materials and methods

2.1 Patient characteristics

2.2 Inclusion criteria

2.4 Follow-up and measurement

2.5 Endpoint and statistical analysis

3. Results

3.1 Clinical characteristics of NPC patients

Table 1 Basic characteristics of the patients in the NACT + RT vs. CCRT groups

Table 2 NACT + RT treatment (vs. CCRT) and multivariate HR of overall survival with 95% CIs in NPC

Table 3 The number of death patients in NACT + RT and CCRT

5. Conclusions

Funding

Authors’ contributions

Ethics approval

Availability of data and material

Publication ethics

Consent to participate

Consent for publication

Supplementary data

sj-docx-1-cbm-10.3233_CBM-210357.docx - Supplemental material

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Basic characteristics of the patients in the NACT $+$ RT vs. CCRT groups

Table 2
NACT $+$ RT treatment (vs. CCRT) and multivariate HR of overall survival with 95% CIs in NPC

Table 3
The number of death patients in NACT $+$ RT and CCRT