Patients

Between October 2017 and January 2022, 76 and 85 LA NSCLC patients who received durvalumab were included in the training and test sets, respectively (Table 1). Median age was 62 and 65 years, respectively, and 74% of patients were male. Most patients were active or wean smokers, and presented adenocarcinoma (55,2% and 44,7% in training and test set, respectively) and stage IIIB disease (51,3% and 56,4%). In training set PD-L1 positivity was mainly upper than 49% while the PD-L1 status was mainly between 1 and 49% in the test set. The mean time between the last RT session and the first course of durvalumab was 29 days (3–67) and 35 days (3–88). Many adenocarcinomas (61,9% and 47,3%) presented with a driver mutation, including 4,8% and 7,9% of EGFR mutation.

Table 1 Baseline clinicopathologic characteristics

In training set, 8 patients (10,5%) received 50 to 54 Gy in 3 to 5 fractions using an exclusive stereotactic technique on the tumor volume and normofractionated radiotherapy (RT) on the lymph node volume. In test set, 21 patients (24,4%) received 70 Gy on tumor and lymph node volumes. The most common dose received was 66 Gy (60,5% and 68,6%).

The median NLR was nearby between training set (3,87 [2,36 − 5,61]) and test set (4,1 [2,76 − 5,41]), as was the median LyC (0,850 [0,613-1,10] and 0,885 [0,590-1,09]).

Median (interquartile) follow up was 35,39 (19,97, 49,23) months in training set and 35,74 (24,47, 45,87) months in test set.

In overall population, median OS was 59,4 months (95% CI: 42,4-NR) (Fig. 1A) and median PFS was 32,6 months (95%CI: 20-NR) (Fig. 1B).

Fig. 1

Survival of the entire population. (A) OS. (B) PFS

Cut off determination

For OS, with an area under the curve (AUC) of 0,603 (95%CI 0,4674-0,7385) the best NLR cut off was 2,94 (appendix A. 1). For Lyc the more significant cut off was 0,61 G/L with an AUC of 0,582 (95%IC 0,4366-0,727) (appendix A. 2).

Overall survival according to NLR

In training set, in univariate analysis, patients with NLR > 2,94 did not present a worse OS (median 36,7 months vs. not reached (NR); HR: 2,42, 95% CI: 0,94 − 6,2, p = 0,066) (Fig. 2A, Table 2A). In the test set, NLR > 2,94 was also not associated with a significant reduction in OS (HR: 1,86, 95% CI: 0,77 ; 3,76, p = 0,12) (Fig. 2B, Table 2C).

Fig. 2

OS according to pre durvalumab NLR. (A) Training set. (B) Test set

Table 2 Prognostic factors for OSOverall survival according to lymphocytes count

In training set, in univariate analysis, patients with LyC > 0,61 G/L had better OS (median NR vs. 28 months; HR: 0,39, 95% CI: 0,17, 0,91, p = 0,030) (Fig. 3A, Table 2A). In multivariate analysis, this OS improvement for patients with LyC > 0,61 G/L was not found (HR: 0,41, 95% CI: 0,17, 1,00, p = 0,057) while PS 2 was significantly associated with shorter OS (HR: 4,02, IC95%: 1,60, 10,1, p = 0,002) (Table 2B). In test set patients with LyC > 0,61 G/L had higher OS in univariate (HR: 0,68, IC95% : 0,18 ; 0,78, p = 0,0062) (Fig. 3B, Table 2C) and multivariate analysis (HR: 0,46, IC95%: 0,22, 0,96, p = 0,039) (Table 2D).

Fig. 3

OS according to pre durvalumab lymphocytes count (G/L). (A) Training set. (B) Test set

Progression free survival according to NLR

In training set, patients with NLR > 2,94 did not have shorter PFS (HR = 1,68, p = 0,15) with median of 18 months (95% CI: 12, NR) vs. not reached (95% CI: 23, NR) (Fig. 4A).

The same results was observed in test set (HR: 1,25, p = 0,51) with a median PFS of 25,1 months (95% CI: 17, NR) vs. 39 months (95% CI: 19, NR), (Fig. 4B).

Fig. 4

PFS according to pre durvalumab NLR. (A) Training set. (B) Test set

Progression free survival according to lymphocytes count and type of recurrence

In training set, patients with LyC > 0,61 G/L did not have longer PFS (HR 0,66, p = 0,28) with a median PFS NR (95% CI: 18, NR) vs. 18 months (95% CI: 8, NR), (Fig. 5A).

Fig. 5

PFS according to pre durvalumab lymphocytes count (G/L). (A) Training set. (B) Test set

In test set patients with LyC > 0,61 had better PFS (HR: 0,5 p = 0,042), with a median PFS of 43 months (95% CI: 25,NR) vs. 12 months (95% CI: 10, NR), (Fig. 5B).

In training set, 21 patients (27,6%) had local relapse, mainly in lymph nodes. Twenty-two patients (28,9%) had distant metastasis, 11 extracranial (14,5%), 13 intracranial (17,1%) including 2 (2,6%) patients with synchrone intra and extracranial recurrence (appendix B). In comparison in test set, 43 patients (50,5%) had local relapse, mainly in lymph nodes. Thirty-one (36,4%) had distant metastasis, 17 extracranial (20%), 19 intracranial (22,4%) including 2 (2.4%) patients with synchrone intra and extracranial recurrence (appendix B).