2.1 Patients’ characteristics.
397 patients fulfilled the inclusion criteria and were evaluable for the biomarkers of interest.
Characteristics of evaluated patients are described in Table 1. The mean age at diagnosis was 60.2 years (range 27-89); 271 (68.3%) were BRCA wild-type (BRCA-WT), with 17 (4.3%) having a BRCA variant of uncertain significance (BRCA-VUS), and 127 (31.7%) had a BRCA 1/2 pathogenetic variants (BRCA-PVs). Among the latter, 79 (19.9%) patients presented with BRCA1 mutation, and 47 (11.8%) presented with BRCA2.
The association between the preoperative NLR score and clinicopathologic characteristics of EOC patients are also shown in Table 1.
Regarding the BRCA status, no significant differences were found with regard of NLR values (p-value: 0.97). The majority of patients presented as stage III of disease (282, 71.8%), without differences related to NLR value. We found a significant correlation of NLR with disease distribution, with more patients with low tumor load in Group 1 (NLR <4) versus Group 2 (NLR > 4) (44.6% vs 67.3%) (p<0.0001).
Moreover, patients in group 1 (110, 55.6%) underwent PDS more frequently than patient in group 2 (76, 38.2%) (p-value 0.001), with no statistically significant difference of complete/optimal cytoreduction in the overall population. Among patients undergoing PDS, those with lower NLR had also lower surgical complexity score (59, 54.1%) compared with those in group 2 (23, 30.7%) (p-value 0.002).
2.2 Impact of NLR on survival
The median follow-up was 24 months (range 4-47). At the time of final analysis, 210 (52.9%) of patient have recurred in the overall population, with more recurrences among group 2 (57.8%) versus group 1 (48%) respectively, p=0.03). Similarly, 105 (24.2%) patients were dead, 64 (32.2%) in group 2 and 41 (20.7%) in group 1 (p=0.007).
In the overall population, median progression free survival (mPFS) was 21 months; those with NLR < 4 had a significant 7-month increase in mPFS, compared with patients with NLR >4 (26 months vs 19 months, p=0.009, Figure. 1).
Focusing on the BRCA status, among BRCAmut patients, those with lower NLR had a significantly prolonged mPFS (35 months vs 23 months, p= 0.03, Figure 2a); similarly, among BRCA wild type patients, those with lower NLR had a slightly significant 3-month increase in mPFS, compared with patients in group 2 (19 months vs 16 months, p=0.05, Figure 2b). At multivariate analysis for PFS, independent factors of prolonged PFS were BRCA mutational status (HR 0.50, CI 95% 0.35-0.71), having received complete cytoreduction (HR 0.51, CI 95% 0.35-0.75) and NLR < 4 (HR 0.69, CI 95% 0.51-0.95) (Table 2).
Median overall survival (mOS) at 60 months was still not reached and 3 years OS was 72% in group 1 and 60% in group 2 (p=0.007). Statistically significant differences related to NLR were found in the BRCAmut (mOS not reached in both groups, p=0.05), and BRCA wild-type (mOS not reached in both groups, p=0.027) populations (Figure 3). In the multivariate analysis, the strongest predictors of longer OS were BRCA mutational status (HR 0.47, CI 95% 0.26-0.85) having received complete cytoreduction (HR 0.42, CI 95% 0.25-0.72), NLR < 4 (HR 0.58, CI 95% 0.36-0.95) and younger age (HR 1.03, CI 95% 1.01-1.06) (Table 3).