The median age was 52 years (range 44-60 years). Seventy-four patients (69.2%) were male, and 87 (81.3%) of them had WHO type III histology. Of the 107 patients, 14 (13.1%), 36 (33.6%), 21 (19.6%), and 36 (33.6%) had T1, T2, T3, and T4 tumors, respectively. Fourteen (13.1%), 13 (12.1%), 55 (51.4%), and 25 (23.4%) had N0, N1, N2, and N3 nodal involvement, respectively. Three (2.8%), 13 (12.1%), 40 (37.4%), and 51 (47.7%) of them showed stage 1, 2, 3, and 4a, respectively. The median follow-up time was 50.0 months (range 21.5-84.5 months). At the date of the last follow-up day, 39 (36.4%) patients had a loco-regional recurrence, 44 (41.1%) patients had distant metastasis, and 46 (43%) of them died (Table 1).
Treatment types and response assessment:
One hundred seven patients were treated; 9 (8.4%) of them with RT only, 48 (44.9%) with CCRT, 37 (34.6%) with induction chemotherapy followed by CCRT, and 13 (12.1%) with CCRT followed by adjuvant chemotherapy. Fifty-two (48.6%), 36 (33.6%), 5 (4.6%), and 14 (13.1%) had complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) according to RECIST criteria, respectively (Table 1).
Cut-off values of parameters and comparison of groups:
The median value for pre-treatment lymphocyte count, serum albumin concentration, and PNI were 1800 per mm3 (range 1320 - 2400 per mm3), 41 gr/L (range 38 - 44 gr/L), and 51 (range 44.5 - 54.5), respectively. And for post-treatment, the values were 1090 per mm3 (range 700-1370 per mm3), 40 gr/L (range 34 - 42 gr/L), and 45 (40.5 - 49.5), respectively (Table 1).
According to ROC analyses done for finding statistically significant PNI cut-off values, 50.65 (area under the curve (AUC):0.317, P=0.001) for pre-treatment PNI, and 44.75 (AUC:0.155, P<0.001) for post-treatment PNI.
Two groups were created based on high or low PNI values. When we compared the groups according to their clinical and demographic features, for pre-treatment PNI, only age was statistically significantly higher in PNI≤50.65 group (p<0.01). There were no differences between other parameters. However, for post-treatment PNI, N3 nodal involvement and disease stage 4a were more common in PNI≤44.75 group (p=0.04 and 0.02, respectively). According to the treatment response assessment between PNI groups, there were no differences between pre-treatment PNI groups. For post-treatment PNI groups, CR was much more than non-CR in PNI>44.75 group, and this was statistically significant (p<0.01) (Table 2).
The 5-year LRRFS, DMFS, and OS rates were 80.4%, 82.6%, and 78.2%, respectively. Ten-year LRRFS, DMFS, and OS rates were 68.2%, 76.2%, and 56.4%, respectively. For the whole treatment population, median LRRFS was 15.3 months (95% CI: 8.9-21.7 months), median DMFS was 11.8 months (95% CI: 5.2-18.4 months), and median OS was 121 months (95% CI: 56.2-185.9 months).
Of the pre-treatment PNI analysis, median LRRFS was 8.9 months (95% CI: 6.4-11.5 months) in PNI≤50.65 group while it was 28.3 months (95% CI: 16.1-40.5 months) in PNI>50.65 group (p<0.01). Median DMFS was 8.9 months (95% CI: 6.3-11.6 months) in PNI≤50.65 group while it was 19.2 months (95% CI: 6.8-31.5 months) in PNI>50.65 group (p<0.01). Median OS was 46.9 months (95% CI: 26.4-67.5 months) in PNI≤50.65 group, while it was not assessed (NA) in PNI>50.65 group (p<0.01) (Figure 1).
Of the post-treatment PNI analysis, median LRRFS was 11.5 months (95% CI: 5.4-17.6 months) in PNI≤44.75 group while it was 28.3 months (95% CI: 9.0-47.6 months) in PNI>44.75 group (p=0.04). Median DMFS was 11.5 months (95% CI: 1.7-21.3 months) in PNI≤44.75 group while it was 12.0 months (95% CI: 0.9-26.2 months in PNI>44.75 group (p>0.05). Median OS was 49.9 months (95% CI: 26.8-67.0 months) in PNI≤44.75 group, while it was not assessed (NA) in PNI>44.75 group (p<0.01) (Figure 1).
Univariate and multivariate analyses:
In the univariate analysis, N category, TNM stage, treatment type, treatment response, and pre-treatment PNI were associated with LRRFS. In contrast, only pre-treatment PNI was associated with DMFS. In the multivariate analyses for LRRFS and DMFS, only pre-treatment PNI was statistically significant (p<0.01 and p=0.04, respectively) (Table 3).
In the univariate analysis of OS, age, histologic subtype, T category, N category, TNM stage, treatment response, pre-treatment PNI, and post-treatment PNI were both associated with survival. The multivariate analysis for OS, T category, N category, treatment response, pre-treatment PNI, and post-treatment PNI was statistically significant (Table 4).
As seen in whole multivariate analyses pre-treatment, PNI was an independent prognostic factor for worse LRRFS, DMFS, and OS. In contrast, post-treatment PNI was the only independent prognostic factor for OS (Table 4).
Combined prognostic analysis of PNI values:
The patients were examined by dividing into four groups for the combined prognostic value of pre-and post-treatment PNI: patients with high pre-treatment and high post-treatment PNI were defined as group 1, low pre-treatment and high post-treatment PNI as group 2, high pre-treatment and low post-treatment PNI as group 3, and low pre-treatment and low post-treatment PNI as group 4. Differences between the groups were statistically significant (p<0.01). When the univariate analysis was done to find the prognostic effect of groups according to select group 4 as an indicator, group 1,2 and 3 had an HR of 0.12 (95% CI 0.05-0.30, p<0.01), 0.18 (95% CI 0.06-0.52, p<0.01), and 0.48 (95% CI 0.23-0.99, p=0.047), respectively. As in the analysis, group 2 had a statistically significant effect on prognosis like group 1 (Figure 2).