Overall, 1608 patients were in the database. Out of these, 661 patients met inclusion criteria. Average age at time of diagnosis was 56.8 ± 10.1 years, with 558 (84.4%) being male and 103 (15.6%) being female. Mean follow-up time was 78.9 ± 106.4 months. Out of the 661 patients that were included, 67 patients (10.1%) eventually had lymphatic recurrence of the tumor. 135 (20.4) patients had their primary tumor site in the oral cavity, 179 (27.1%) in the oropharynx, 118 (17.8%) in the hypopharynx and 229 (34.6%) in the larynx. In terms of sides, 158 (23.9%) were situated bilaterally, 23 (3.5%) in the midline, 255 (38.6%) on the right and 225 (34.0%) on the left side. In terms of clinical lymph node category, 261 (39.4%) patients were classified as inapparent/cN0, 111 (16.8%) as N1, 246 (37.2%) as N2 and 5 (0.8%) as N3; in 38 (5.7%) patients, there was no information on clinical lymph node status (cNx). After pathological examination, 302 (45.7%) were classified as pN0, 119 (18.0%) were classified as pN1, and 240 (36.3%) as pN2. 105 (15.6%) patients developed systemic metastasis during follow up, while 558 (84.4%) did not. 291 (44.1%) patients underwent adjuvant radio-(chemo-)therapy after initial surgical tumor therapy, while 370 (55.9%) did not. (Table 1) Respective Kaplan-Meier-diagrams can be found in Fig. 1.
Table 1
– Basic patient, tumor and surgery characteristics of all patients included in the study
Characteristic | No. of Patients (n = 661) |
Age (years) | 56.8 ± 10.1 [15.7–91.6] |
Gender (male/female) | 558 (84.4%) / 103 (15.6%) |
Follow up (months) | 78,9 ± 106.4 [0.3–263.3] |
Origin |
Tumor Origin: Oral cavity | 135 (20.4%) |
Tumor Origin: Oropharynx | 179 (27.1%) |
Tumor Origin: Hypopharynx | 118 (17.8%) |
Tumor Origin: Larynx | 229 (34.6%) |
Side |
Tumor side: bilateral | 158 (23.9%) |
Tumor side: midline | 23 (3.5%) |
Tumor side: right | 255 (38.6%) |
Tumor side: left | 225 (34.0%) |
Tumor Stage |
pT1 | 86 (13.0%) |
pT2 | 208 (31.5%) |
pT3 | 239 (36.2%) |
pT4 | 128 (19.4%) |
Lymph Node Status |
cN0 | 261 (39.4%) |
cN1 | 111 (16.8%) |
cN2 | 246 (37.2%) |
cN3 | 5 (0.8%) |
cNx | 38 (5.7%) |
pN0 | 302 (45.7%) |
pN1 | 119 (18.0%) |
pN2 | 240 (36.3%) |
Development of distant metastasis during follow-up |
M0 | 558 (84.4%) |
M1 | 103 (15.6%) |
Postoperative (chemo-)radiotherapy |
No adjuvant therapy | 370 (55.9%) |
Postoperative (chemo-)radiotherapy | 291 (44.1%) |
Levels Treated in Neck Dissection |
Ipsilateral ND | 644 (97.4%) |
Level I ispilateral | 120 (18.2%) |
Level II ispilateral | 613 (92.7%) |
Level III ispilateral | 605 (91.5%) |
Level IV ispilateral | 140 (21.2%) |
Level V ispilateral | 26 (3.9%) |
Contralateral ND | 319 (48.3%) |
Level I contralateral | 54 (8.2%) |
Level II contralateral | 313 (47.4%) |
Level III contralateral | 309 (46.7%) |
Level IV contralateral | 55 (8.3%) |
Level V contralateral | 7 (1.1%) |
Out of these patients, 644 (97.4%) underwent ispiateral and 319 (48.3%) underwent contralateral neck dissection. On the ipsilateral side, Level I was operated on in 120 (18.2%) patients, Level II in 613 (92.7%), Level III in 605 (91.5%), Level IV in 140 (21.2%) and Level V in 26 (3.9%) patients. On the contralateral side, Level I was operated in 54 (8.2%) patients, Level II in 313 (47.4%), Level III in 398 (46.7%), Level IV in 55 (8.3%) and Level V in 7 (1.1%) patients (Table 1).
The exact comparisons between the groups in terms of OS and RCR can be found in Table 2. Univariate testing found significant differences in RCR between hypopharynx and larynx as well as hypopharynx and oropharynx, showing lower hazard of regional recurrence for primaries located in the oropharynx (HR 0.6 [0.4–1.0]) and larynx (HR 0.4 [0.2–0.7]). In terms of OS, only the difference between larynx and hypopharynx was significant, demonstrating a better prognosis for laryngeal cancer (HR 0.4 [0.2–0.7]). However, multivariate testing showed a significant influence of the tumor site on both RCR and OS. In terms of pathological tumor category, there was no uni- or multivariate influence on RCR. In terms of OS, pT4a compared to all other categories showed significant differences in univariate testing. Multivariate testing showed a significant influence of pathological tumor category on OS.
Table 2
– Univariate and multivariate testing of tumor and surgery characteristics and their respecitve influence on OS and RCR
Stage | Hazard Ratio | p (univariate) | p (multiple) | Hazard Ratio | p (univariate) | p (multiple) |
| Regional Control Rate | Overall Survival |
Tumor Origin | | < 0.01 | < 0.01 | | 0.02 | 0.01 |
Larynx vs. Hypopharynx | 0.4 [0.2–0.7] | < 0.01 | 0.4 [0.2–0.7] | < 0.01 |
Oral Cavity vs. Hypopharynx | 0.6 [0.4–1.1] | 0.12 | 0.6 [0.4–1.1] | 0.12 |
Oropharynx vs. Hypopharynx | 0.6 [0.4–1.0] | 0.05 | 0.7 [0.4–1.2] | 0.16 |
Oral Cavity vs. Larynx | 1.7 [1.0–3.1] | 0.06 | 1.5 [0.9–2.8] | 0.15 |
Oropharynx vs. Oral Cavity | 0.9 [0.5–1.6] | 0.78 | 1.1 [0.6–1.9] | 0.80 |
Oropharynx vs. Larynx | 1.5 [0.6–1.5] | 0.12 | 1.6 [0.9–2.8] | 0.08 |
Pathological Tumor Category | | 0.13 | 0.07 | | < 0.01 | < 0.01 |
pT2 vs. pT1 | 1.6 [0.8–3.2] | 1.7 [0.8–3.6] | 0.16 |
pT3 vs. pT1 | 1.1 [0.5–2.1] | 1.2 [0.6–2.7] | 0.57 |
pT4 vs. pT1 | 1.7 [0.8–3.4] | 3.1 [1.5–6.5] | < 0.01 |
pT3 vs. pT2 | 0.6 [0.4–1.0] | 0.7 [0.4–1.2] | 0.25 |
pT4 vs. pT3 | 0.6 [0.4–1.0] | 2.5 [1.5–4.2] | < 0.01 |
pT4 vs. pT2 | 1.0 [0.6–1.7] | 1.8 [1.1–3.0] | 0.01 |
Clinical Lymph Node Category | | < 0.01 | < 0.01 | | < 0.01 | < 0.01 |
cN1 vs. cN0 | 1.9 [1.1–3.4] | 0.03 | 1.8 [1.0–3.4] | 0.06 |
cN2 vs. cN0 | 2.4 [1.5–3.8] | < 0.01 | 3.0 [1.8–4.9] | < 0.01 |
cN3 vs. cN0 | 5.4 [1.3–22.7] | 0.02 | 9.4 [2.2–40.0] | < 0.01 |
cN2 vs. cN1 | 1.3 [0.7–2.1] | 0.40 | 1.6 [0.9–2.8] | 0.09 |
cN3 vs. cN1 | 2.6 [0.6–11.2] | 0.20 | 4.9 [1.1–22.2] | 0.04 |
cN3 vs. cN2 | 2.3 [0.6–9.6] | 0.24 | 3.0 [0.7–12.3] | 0.13 |
Pathological Lymph Node Category | | < 0.01 | < 0.01 | | < 0.01 | < 0.01 |
pN1 vs. pN0 | 1.9 [1.0–3.5] | 0.05 | 2.6 [1.4–5.0] | < 0.01 |
pN2 vs. pN0 | 4.0 [2.5–6.4] | < 0.01 | 5.2 [3.1–8.7] | < 0.01 |
pN2 vs. pN1 | 2.1 [1.3–3.7] | < 0.01 | 2.0 [1.2–3.3] | 0.01 |
Development of distant metastasis | 6.6, [4.5–9.6] | < 0.01 | 0.25 | 9.8 [6.5–14.6] | < 0.01 | < 0.01 |
Postoperative (Chemo-) radiation | 0.9, [0.6–1.3] | 0.51 | < 0.01 | 0.5 [0.3–0.8] | < 0.01 | 0.13 |
Neck Dissection ipsilateral | 0.7 [0.3–2.0] | 0.56 | 0.37 | 0.9 [0.3–3.0] | 0.93 | 0.64 |
Level I ipsilateral | 1.3 [0.8–2.0] | 0.30 | 0.25 | 1.0 [0.6–1.7] | 0.96 | 0.68 |
Level II ipsilateral | 0.5 [0.3–0.9] | 0.01 | 0.72 | 0.5 [0.3–0.9] | 0.02 | 0.83 |
Level III ipsilateral | 0.6 [0.3–1.1] | 0.07 | 0.18 | 0.6 [0.3–1.0] | 0.05 | 0.96 |
Level IV ipsilateral | 1.1 [0.7–1.8] | 0.62 | 0.44 | 1.2 [0.8–1.9] | 0.42 | 0.61 |
Level V ipsilateral | 0.8 [0.2–2.5] | 0.68 | 0.44 | 0.7 [0.2–2.9] | 0.63 | 0.27 |
Neck Dissection contralateral | 1.0 [0.7–1.4] | 0.93 | 0.40 | 1.3 [0.9–2.0] | 0.14 | 0.79 |
Level I contralateral | 1.6 [0.9–2.9] | 0.10 | 0.17 | 1.8 [ 1.0–3.3] | 0.04 | 0.07 |
Level II contralateral | 1.0 [0.7–1.4] | 0.89 | 0.88 | 1.3 [0.9–1.9] | 0.23 | 0.21 |
Level III contralateral | 1.0 [0.7–1.4] | 0.96 | 0.70 | 1.3 [0.9–1.9] | 0.20 | 0.83 |
Level IV contralateral | 1.2 [0.7–2.4] | 0.50 | 0.48 | 1.6 [0.8–2.9] | 0.16 | 0.86 |
Level V contralateral | 0.0 [0.0 - ∞] | 0.15 | 0.23 | 0.0 [0 - ∞] | 0.20 | 0.30 |
Clinical lymph node status showed a significant effect on RCR in any stage compared with cN0 in univariate analysis, demonstrating a higher hazard ratio of regional recurrence in cN + disease. For overall survival this was only the case for cN2 and compared to cN1. Multivariate testing showed a significant influence both for RCR and OS (Table 2).
Pathological lymph node status showed a significant influence on RCR and OS both in univariate and multivariate testing. Development of distant metastasis showed a significant influence on OS both in uni- and multivariate testing and a significant influence on RCR in univariate testing. Adjuvant (chemo)radiotherapy showed a significant impact on RCR in multivariate and a significant impact on OS in univariate testing. Treated levels during SND showed a significant influence on RCR if ipsilateral Level II was treated in univariate testing. In terms of OS, ipsilateral regions II and III as well as contralateral level I showed a significant influence in univariate testing.
To test whether the observed impact on OS and RCR was dependent on the tumor origin, COX-regression models were fitted that considered the interactions of the tumor origin. These models found a significant influence of surgical treatment of levels I and V ipsilateral and level III contralateral on OS. None of the fitted models revealed a significant influence of any level treated on RCR. (Table 3) Significant findings in these levels indicated that treatment or omission of treatment of these regions may influence overall survival dependent of tumor origin.
Table 3
– COX-Regression Models of Operated Regions dependent and independent of tumor origin
| Overall Survival p (multiple) | Regional Control Rates p (multiple) |
Region | 0.02 | < 0.01 |
Level I Ipsilateral | 0.93 | 0.36 |
Level II Ipsilateral | 0.08 | 0.04 |
Level III Ipsilateral | 0.69 | 0.10 |
Level IV Ipsilateral | 0.58 | 0.79 |
Level V Ipsilateral | 0.54 | 0.68 |
Level I Contralateral | 0.02 | 0.25 |
Level II Contralateral | 0.39 | 0.80 |
Level III Contralateral | 0.65 | 0.87 |
Level IV Contralateral | 0.45 | 0.50 |
Level V Contralateral | 0.20 | 0.16 |
Models with Tumor Origin Interaction |
Level I Ipsilateral | 0.03 | 0.81 |
Level II Ipsilateral | 0.19 | 0.07 |
Level III Ipsilateral | 0.43 | 1.00 |
Level IV Ipsilateral | 0.47 | 0.95 |
Level V Ipsilateral | 0.02 | 0.16 |
Level I Contralateral | 0.66 | 0.14 |
Level II Contralateral | 0.98 | 0.99 |
Level III Contralateral | < 0.01 | 0.13 |
Level IV Contralateral | 0.60 | 0.68 |
Level V Contralateral | 1.00 | 1.00 |
Subsequently, we fitted COX-regression models for each tumor region. (Table 4) Treatment of level V ipsilateral or level III contralateral showed no significant influence on OS in any tumor origin. Treatment of level I ipsilateral showed a significant influence on OS when the tumor originated in the oral cavity. The hazard ratio calculated was 0.4 with a confidence interval of 0.2–0.9. This indicated a favorable effect of SND in level I in HNSCC of the oral cavity.
Table 4
– Influence of Neck Dissection Levels for each Tumor Origin
Parameter | Region |
Hypopharynx | Larynx | Oral Cavity | Oropharynx |
Level I Ispilateral | 4.0 [0.9–17.2] p = 0.06 | 3.7 [0.5–27.3] p = 0.21 | 0.4 [0.2–0.9] p = 0.02 | 1.9 [0.8–4.7] p = 0.17 |
Level V Ipsilateral | 0.0 [0.0 - ∞] p = 0.16 | 0.0 [0.0 - ∞] p = 0.24 | 0.0 [0.0 - ∞] p = 0.26 | 3.0 [0.7–13.1] p = 0.14 |
Level III Contralateral | 1.7 [0.7–3.7] p = 0.22 | 1.2 [0.5–2.8] p = 0.68 | 1.7 [0.7–4.0] p = 0.21 | 1.4 [0.7–2.9] p = 0.38 |