Patient characteristics and prognosis
Of the 605 patients with pathologically confirmed NPC, 433 were males and 172 were females. The median age of the patients was 48 years old (12-81 years old), 97.52% of the pathological types were WHO II-III, and 2.47% of the pathological types were WHO type I. The counts and percentages of patients with T1, T2, T3, and T4 NPC were 156 (25.78%), 120 (19.83%), 161 (26.61%), and 168 (27.76%), respectively; and the counts and percentages of patients with N0, N1, N2, and N3 NPC were 48 (7.93%) and 165 (27.27%), 303 (50.08%), 89 (14.71%), respectively. The number and percentages of patients in stages I, II, III, IVa and IVb were 22 (3.63%), 86 (14.21%), 250 (41.32%), 237 (39.17%) and 10 (1.65%), respectively (Table 1). In all patients, 10 patients were in stage IVb, and 4 patients gave up treatment during radiotherapy. A total of 591 patients were followed up for 8-81 months with a median of 37 months, and the 5-year OS, PFS, LRFS, and DMFS were 80.1%, 69.4%, 88.4%, and 83.9%, respectively. Seventy-four patients died, and the main cause of death was distant metastasis, followed by local recurrence and hemorrhage of the nasopharynx. Forty-two cases had local recurrence, mainly in the nasopharyngeal cavity, skull base bone, carotid sheath area, intracranial cavernous sinus area, etc. Seventy-five cases had distant metastasis, most commonly in the liver, lungs and bones. Patients with a single metastasis site were rare, and most patients had two or three sites with simultaneous metastasis.
Cervical lymph node metastasis
In the 605 patients, 557 patients (92.06%) had cervical lymph node metastasis (Supplementary table 1). The top four levels with the highest probability of lymph node metastasis were IIb (77.85%), VIIa (73.05%), IIa (60.0%), and III (41.48%). The levels with less than a 5% probability of the lymph node metastasis was IVb (1.98%), Vc (1.48%), VIIb (0.82%), and VIII (0.49%), and no lymph node metastasis was found in levels Ia, VI, IX and X. There were 12 patients with lymph node metastasis in level IVb, and these patients also had lymph node metastasis in the level IVa. Nine patients had lymph node metastasis in level Vc, and these patients were also accompanied by lymph node metastasis in level Vb. Three patients with lymph node metastasis in level VIII were associated with lymph node metastasis in levels Ib, II, and III, and one patient with lymph node metastasis in level II showed local necrosis and lymph node fusion.
Distribution characteristics of metastatic lymph nodes in the PLV region
In the whole group of 605 patients, 30 patients (4.95%) showed lymph node metastasis in the PLV region (Supplementary table 2). There was a total of 49 metastatic lymph nodes, including 25 metastatic lymph nodes in the left neck and 24 metastatic lymph nodes in the right neck. In one patient, lymph node metastasis in the PLV region occurred simultaneously on both sides of the neck. There were 23 metastatic lymph nodes with a short diameter of less than 10 mm, 22 metastatic lymph nodes with a short diameter of 11-20 mm, and 4 metastatic lymph nodes with a short diameter of 21-30 mm. The median vertical distance of the center point of each metastatic lymph node from the anterior surface of the trapezius muscle in the standard NPC patient was 14 mm (3-37 mm). There were 25 lymph nodes with a vertical distance of less than 10 mm, 14 lymph nodes with a vertical distance between 11 and 20 mm, 7 lymph nodes with a vertical distance between 21 and 30 mm, and 3 lymph nodes with a vertical distance of more than 31 mm. The centers of 93.87% (46/49) of the metastatic lymph nodes in the PLV region were located less than 25 mm from the anterior surface of the trapezius muscle. The distribution of the metastatic lymph nodes in the PLV region is shown in Supplementary table 3. The location of the corresponding CT layer of the standard NPC patient is shown in Figure 2.
Correlation analysis of lymph node metastasis in the PLV region
To analyze the relationship between lymph node metastasis in the PLV region and other cervical lymph node metastasis, linear regression analysis was used. The lymph node metastasis in the PLV region was used as the dependent variable, and the remaining lymph node regions were included as independent variables in the analysis. The results showed that the lymph node metastasis of the PLV region was associated with the ipsilateral IVa (P = 0.018), Va, Vb and Vc levels (all P < 0.001), and no correlations were found for the other variables (Table 2).
Prognosis of patients with lymph node metastasis in the PLV region
The number of patients with lymph node metastasis in PLV region was 30, but 1 patient with stage IVB was excluded and we followed up 29 patients. A total of 29 patients with lymph node metastasis in PLV were followed up for a median of 21 (4 to 60) months. Fourteen patients had distant metastasis, 11 patients died during the follow-up period (death overlapped with distant metastasis), and 2 patients relapsed. The 5-year OS, PFS, LRFS, and DMFS were 41.6%, 27.7%, 89.1%, and 47.3%, respectively.
Prognosis of patients with N3 NPC with or without lymph node metastasis in the PLV region
The number of patients with N3 was 89, but 3 patients with N3 in stage IVB were excluded, so the cases of patients with N3 NPC with or without lymph node metastasis in the PLV region were 26 and 60, respectively. The 5-year OS, PFS, LRFS, and DMFS of the two groups were 41.8% and 67.3% (P = 0.007), 27.8% and 48.5% (P = 0.005), 92.3% and 80.5% (P = 0.521), and 40.6% and 78.4% (P < 0.001), respectively (Table 3, Figure 3).
Univariate and multivariate analysis
The univariate results showed gender and age were prognostic factors for 5-year OS(all P < 0.05), T-stage was a prognostic factor for 5-year LRFS(P = 0.003), The N-stage and TNM stage were prognostic factors for 5-year OS, PFS, LRFS, and DMFS(all P < 0.05), Involvement of lower neck was a prognostic factor for 5-year OS, PFS, and DMFS(all P < 0.001) (Table 4). Involvement of lower neck was refined into levels IVa, IVb, Vb, and Vc and the PLV region in multivariate analysis, and the parameters were designed as two categorical variables (Table 5). Analysis showed that lymph node metastasis in the PLV region was an independent prognostic factor for DMFS (P=0.044) rather than for OS and PFS (Table 5, Supplementary table 4 and 5).