Lung Cancer br similar pattern was observed
Lung Cancer 133 (2019) 69–74
similar pattern was observed in the PFS analyses (Suppl. Fig. 2).
The univariate survival analysis for the whole study population, presented in Table 3, showed that younger age at diagnosis, female gender, lower stage and better PS were associated with prolonged OS, whereas the remaining variables showed a trend towards statistical significance in a varying manner. We observed no significant impact on OS for the 25- and 75- c-MET H-score quartiles (data not shown).
The three diﬀerent quartiles of c-MET H-score were examined se-parately with Cox-regression multivariate analyses (adjuvant treatment not initially included because of 209 patients with missing data, see Table 2). All other variables were included in these analyses. We ob-served no statistical significant impact on OS for the 25- and the 75-quartile (data not shown), but the 50-quartile (c-MET H-score 20) was an independent prognostic variable in the whole study Ferrostatin 1 with
a HR = 0.79 (95%CI: 0.64−0.97, p value = 0.022), together with gender, histology, stage and PS (Table 3). There was a larger number of missing data regarding the delivery of adjuvant treatment (see Table 2), compared to all other variables; therefore we performed two additional Cox-regression multivariate analyses, one including adjuvant therapy as a co-variate and one in the subgroup of patients who received adjuvant therapy. In the first ana-lysis, c-MET H-score ≥20 was an independent prognostic factor with a HR = 0.73 (95% CI: 0.57−0.94, p-value = 0.016), together with his-tology and stage with adjuvant treatment showing a strong trend in favour of longer OS (HR = 0.77 with 95% CI: 0.59–1.03, p-value = 0.081) (Table 3). In the multivariate subgroup analysis including only patients who received adjuvant therapy, we observed a stronger prog-nostic eﬀect of c-MET H-score ≥20 with a HR = 0.61 (95% CI: 0.40−0.93, p-value = 0.022), with histology and stage retaining their independent prognostic value (Table 3). In all the above mentioned multivariate models, higher c-MET H-score as a continuous variable was an independent positive prognostic factor (Suppl. Table 1).
Univariate and multivariate Cox-regression PFS analyses were un-dertaken in a similar manner to the OS analyses mentioned above. Although these analyses failed to show any statistically significant re-sult for c-MET as an independent prognostic variable, we observed a trend towards better PFS in patients with H-score ≥20. This trend was more profound in the multivariate analysis, including adjuvant treat-ment as a covariate (HR = 0.77, 95 %CI: 0.69–1.04, p-value = 0.085), and in the subgroup of patients who received adjuvant treatment (HR = 0.65, 95% CI: 0.41–1.04, p-value = 0.075) (Suppl. Table 1).
3.3. Subgroup OS analysis in lung adenocarcinoma and squamous cell carcinoma patients with stage IIA-IIIB
Descriptive analysis for the whole study population showed that 20.4% of stage IA and 40.6% of stage IB patients received adjuvant chemotherapy, whereas the majority of patients with stage IIA-IIIB re-ceived adjuvant therapy (Suppl. Table 2). This discrepancy between existing evidence regarding adjuvant therapy and the real life data in our cohort resulted in the subgroup analysis of patients with stage IIA
–IIIB disease (n = 202). We included only patients with adenocarci-noma and squamous cell carcinoma in this analysis due to low/no re-presentation of the remaining histological subtypes in patients with stage IIA-IIIB disease (Suppl. Table 2).
Univariate OS analysis showed a significant OS impact of c-MET H-score ≥20 in this subgroup (HR = 0.60, 95% CI: 0.43−0.83, p-value = 0.002). Multivariate Cox regression OS analyses done as pre-viously described, showed that c-MET H-score ≥20 was a strong in-dependent positive prognostic factor (Suppl. Table 4) in all three mul-tivariate models. Univariate PFS analysis failed to show any significant eﬀect of c-MET H- score, but the multivariate PFS analyses in the whole study population (adjuvant treatment not included) and in the analysis with adjuvant treatment included as a co-variate, showed a positive correlation between H-score ≥20 and longer PFS (Suppl. Table 1).
Fig. 1. Overall Survival curves. 1a: Whole study population, 1b: Patients who received adjuvant treatment, 1c: Patients who did not receive any adjuvant treatment.
Univariate and multivariate Cox regression models (cMET < 20, ≥20 score).
Multivariate incl. Treatment
Multivariate, only treated patients
Adenocarcinoma 1.00 ref.
Performance status (PS)
Current smoker 1.00 ref.
No treatment 1.00