 predict DFS in the SYSUCC-A cohort. Age, sex, smoking history, T category, and N category were associated with DFS (p < 0.05 for all) (Table 3). A nomogram based on the above five significant covariates was further constructed in the SYSUCC-A cohort (S4A Fig.). The calibration plots for the three-year DFS predicted well in SYSUCC-A (C-index, 0.713; 95% CI, 0.677 to 0.752) (S4B Fig.), SYSUCC-B (C-index, 0.695; 95% CI, 0.667 to 0.727) (S4C Fig.), and WZRCH (C-index, 0.656; 95% CI, 0.532 to 0.774) (S4D Fig.) cohorts. In addition, the nomogram for DFS had a significantly higher C-index (0.713; 95% CI, 0.677 to 0.752) than the T category (C-index, 0.587; 95% CI, 0.557 to 0.616; p < 0.001), N category (C-index, 0.616; 95% CI, 0.586 to 0.646; p < 0.001), and clinical stage (C-index, 0.618; 95% CI, 0.590 to 0.647; p < 0.001).
Six hundred twenty-seven patients (6%) experienced a local failure event in the Guangzhou cohort. The 1-, 3-, and 5-year LRFS rates were 99.2%, 95.4%, and 93.4%, respectively (Fig. 1D). Five-year LRFS rates for T1, T2, and T3 disease were 98.7%, 94.9%, and 93.7% (p < 0.05), respectively, and all significantly greater when compared with T4 disease (87.4%, p < 0.001 for all) (Fig. 3A). Most likely due to the difficultly of differentiating T2 and T3 disease, the LRFS curves for T2 and T3 disease almost overlapped in the first 6 years after treatment (p=0.047) (Fig. 3A). Additionally, in the SYSUCC-A cohort we performed multivariable analysis for LRFS to generate a nomogram to predict LRFS. The predictors included smoking history, T category, and N category (Table. 3). We further built a nomogram (S5A Fig.) based on weighting of the three significant covariates in the SYSUCC-A cohort, yielding for LRFS a Harrell’s C-index of 0.697 (95% CI, 0.647 to 0.746) (S5B Fig.). The calibration plots for the 3-year LRFS predicted well in the SYSUCC-B (C-index, 0.684; 95% CI, 0.634 to 0.735) (S5C Fig.) and the WZRCH (C-index, 0.652; 95% CI, 0.501 to 0.831) (S5D Fig.) cohorts. In addition, the nomogram for LRFS had a higher C-index (0.697; 95% CI, 0.647 to 0.746) than T category (C-index, 0.650; 95% CI, 0.597 to 0.703), though narrowly statistically significant (p=0.053).
Kaplan-Meier curves for 10,126 nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy: local relapse-free survival (A) stratified by T category and regional relapse-free survival (B) stratified by N category.
Five hundred twenty-six of the 10,126 patients (5%) suffered regional recurrence in the overall Guangzhou cohort, and the 1-, 3-, and 5-year RRFS rates were 99.1%, 96.0%, and 94.3%, respectively (Fig. 1E). The 1-, 3-, and 5-year rates for RRFS stratified by N category was detailed in Fig. 3B. As the N category increased from N0 to N3, risk of suffering regional recurrence was also associated with an increase accordingly (p < 0.05 for all) (Fig. 3B). This is most likely due to the difficultly in differentiating between N2 and N3 disease. The RRFS curves for N2 and N3 disease were not clearly separated following 6 years after treatment (p=0.031) (Fig. 3B). Among the SYSUCC-A cohort, multivariable analysis for RRFS was conducted to generate a nomogram to predict RRFS. Significant predictors of RRFS were T category and N category (Table 3). A nomogram that was based on weighting of the two significant covariates were constructed in the SYSUCC-B (S6A Fig.). In the SYSUCC-A cohort, calibration plots for 3-year RRFS were well predicted (C-index, 0.672; 95% CI, 0.593 to 0.751) (S6B Fig.). This was also observed in the SYSUCC-B cohort (C-index, 0.650; 95% CI, 0.594 to 0.705) (S6C Fig.) and WZRCH cohort (C-index, 0.616; 95% CI, 0.431 to 0.785) (S6D Fig.). In addition, the nomogram for RRFS had a higher C-index (0.672; 95% CI, 0.593 to 0.751) than N category (C-index, 0.643; 95% CI, 0.581 to 0.705), with a potential trend towards statistical significance (p=0.054).
To create user-friendly access, the underlying statistical formulas were implemented in the web-based nomograms. Web-based nomogram users will be able to estimate the individual 1-, 3-, and 5-year OS, DMFS, DFS, LRFS, and RRFS by entering the sex, age, history of smoking status, T category, and N category. S7 Fig. presents a screenshot of the web-based nomograms which are available on https://modelstore.yiducloud.com.cn/#/?lang=en. For example, a male patient that was 46 years of age with T3N2M0 NPC enters the clinic. This patient had no prior history of smoking. The estimated 1-, 3-, and 5-year for OS were 99.14%, 90.61%, and 86.35%, DMFS were 94.07%, 84.05%, and 82.81%, DFS were 92.61%, 77.97%, and 72.48%, LRFS were 99.02%, 95.27%, and 92.95%, and RRFS were 98.55%, 93.19%, and 90.32%.
Although various studies have built nomograms for predicting survival outcomes after RT for NPC, a web-based prediction model is still needed for clinical assessment and patient counseling. To the best of our knowledge, this is the first study to include external validation to characterize patterns of disease recurrence, and establish web-based nomograms derived from large series of patients with NPC who underwent radical IMRT. These user-friendly web-based models may serve as a useful tool for providing patient counseling and helping physicians to make individual follow-up plans.
The current study showed that patients with stage I disease had an excellent survival rate of 99.5%. In contrast, stage IVA disease patients were most challenging to treat, with 25% of patients dying within 5 years. A similar trend was also observed in patients with N3 category. With the use of IMRT, local relapse rate in NPC improved greatly and more than 70% of the deaths are attributed to distant metastasis [14]. For this reason, prognostic value for T category has potentially become weaker compared with N category because of great local control. Consistent with the conclusion, N category has comparable prognostic accuracy in OS compared with clinical stage in our study. This observation was the result of weakening impact for the T category on clinical stage, which would reduce the prediction efficiency of clinical stage for OS [15]. Although prognostic models could provide a more accurate and precise prediction than the TNM staging system, there are few prognostic models related to OS for NPC. Recently, Liang et al. [16] developed a nomogram for predicting OS based on 1520 non-metastatic patients diagnosed with NPC that underwent curative IMRT with the Harrel’s C-index of 0.69 (95% CI, 0.67 to 0.71). In the current series, a prognostic nomogram to predict OS was built and our nomogram provided a higher C-index 0.736 (95% CI, 0.690 to 0.783) than the study reported by Liang et al. [16]. Moreover, the nomogram performance was verified in all validation cohorts. Therefore, our nomogram potentially provides a more accurate method for predicting OS among NPC patients.
With the improvement of locoregional control in the modern era, distant metastasis is now the primary failure pattern for NPC. The result from the present study was found to be in line with previous studies [17]. Our study showed that the actual 5-year DMFS was 86.9%, which is comparable to results by Sun et al. [18] and Lai et al. [19], though slightly higher than a study by Wu et al. (5-year DMFS, 81.8%) [20]. We postulate that the utilization rate of chemotherapy might partly be attributed to the inconsistency. It is well recognized that distant control could be improved by using chemotherapy, especially